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Valproic side effects: Valproic Acid (Oral Route) Side Effects

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Valproic Acid (Oral Route) Side Effects

Side Effects

Drug information provided by: IBM Micromedex

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

  1. Black, tarry stools

  2. bleeding gums

  3. bloating or swelling of the face, arms, hands, lower legs, or feet

  4. blood in the urine or stools

  5. confusion

  6. cough

  7. crying

  8. delusions of persecution, mistrust, suspiciousness, or combativeness

  9. diarrhea

  10. difficult or labored breathing

  11. dysphoria

  12. false beliefs that cannot be changed by facts

  13. false or unusual sense of well-being

  14. feeling of unreality

  15. fever

  16. general feeling of discomfort or illness

  17. headache

  18. hoarseness

  19. joint pain

  20. loss of appetite

  21. lower back or side pain

  22. mental depression

  23. muscle aches and pains

  24. nausea

  25. nervousness

  26. painful or difficult urination

  27. pinpoint red spots on the skin

  28. poor insight and judgment

  29. problems with memory or speech

  30. quick to react or overreact emotionally

  31. rapid weight gain

  32. rapidly changing moods

  33. runny nose

  34. sense of detachment from self or body

  35. shakiness in the legs, arms, hands, or feet

  36. shivering

  37. sleepiness or unusual drowsiness

  38. sore throat

  39. sweating

  40. tightness in the chest

  41. tingling of the hands or feet

  42. trembling or shaking of the hands or feet

  43. trouble recognizing objects

  44. trouble sleeping

  45. trouble thinking and planning

  46. trouble walking

  47. unusual bleeding or bruising

  48. unusual tiredness or weakness

  49. unusual weight gain or loss

  50. vomiting
Less common

  1. Abnormal dreams

  2. absence of or decrease in body movement

  3. anxiety

  4. bloody nose

  5. bloody or cloudy urine

  6. blurred vision

  7. burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings

  8. change in personality

  9. change in walking and balance

  10. changes in patterns and rhythms of speech

  11. chest pain

  12. clumsiness or unsteadiness

  13. cold sweats

  14. constipation

  15. dark urine

  16. deep or fast breathing with dizziness

  17. degenerative disease of the joint

  18. difficulty with moving

  19. discouragement

  20. dizziness

  21. dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position

  22. dry mouth

  23. excessive muscle tone

  24. fast, irregular, pounding, or racing heartbeat or pulse

  25. fear

  26. feeling of warmth or heat

  27. feeling sad or empty

  28. flushing or redness of the skin, especially on the face and neck

  29. frequent urge to urinate

  30. heavy non-menstrual vaginal bleeding

  31. increased need to urinate

  32. indigestion

  33. irritability

  34. lack of appetite

  35. lack of coordination

  36. large, flat, blue or purplish patches in the skin

  37. leg cramps

  38. lip smacking or puckering

  39. loss of bladder control

  40. loss of interest or pleasure

  41. loss of strength or energy

  42. multiple swollen and inflamed skin lesions

  43. muscle pain or stiffness

  44. muscle tension or tightness

  45. normal menstrual bleeding occurring earlier, possibly lasting longer than expected

  46. numbness of the feet, hands and around mouth

  47. pains in the stomach, side, or abdomen, possibly radiating to the back

  48. passing urine more often

  49. pounding in the ears

  50. puffing of the cheeks

  51. rapid or worm-like movements of the tongue

  52. rapid weight gain

  53. restlessness

  54. seeing, hearing, or feeling things that are not there

  55. shakiness and unsteady walk

  56. slurred speech

  57. small red or purple spots on the skin

  58. sweating

  59. swollen joints

  60. tiredness

  61. trouble with concentrating

  62. trouble with speaking

  63. twitching

  64. uncontrolled chewing movements

  65. uncontrolled movements of the arms and legs

  66. unsteadiness, trembling, or other problems with muscle control or coordination

  67. vomiting of blood or material that looks like coffee grounds

  68. yellow eyes or skin
Incidence not known

  1. Aggression

  2. bladder pain

  3. blistering, peeling, loosening of the skin

  4. blisters on the skin

  5. bone pain, tenderness, or aching

  6. chest discomfort

  7. cloudy urine

  8. decrease in height

  9. decreased urine output

  10. difficulty swallowing

  11. feeling that others are watching you or controlling your behavior

  12. feeling that others can hear your thoughts

  13. feeling, seeing, or hearing things that are not there

  14. hives, itching, skin rash

  15. increased sensitivity of the skin to sunlight

  16. increased thirst

  17. irritability

  18. joint or muscle pain

  19. loss of balance control

  20. loss of consciousness

  21. mask-like face

  22. pain in the back, ribs, arms, or legs

  23. pain or swelling in the arms or legs without any injury

  24. puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue

  25. red skin lesions, often with a purple center

  26. red, irritated eyes

  27. redness or other discoloration of the skin

  28. seizures

  29. severe mood or mental changes

  30. severe sunburn

  31. shuffling walk

  32. slow heartbeat

  33. slowed movements

  34. slurred speech

  35. sores, ulcers, or white spots in the mouth or on the lips

  36. stiffness of the arms and legs

  37. swelling of the face, ankles, or hands

  38. swollen or painful glands

  39. tic-like (jerky) movements of the head, face, mouth, and neck

  40. unusual behavior

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

  1. Change in consciousness

  2. fainting

  3. loss of consciousness

  4. slow or irregular heartbeat

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  1. Belching

  2. body aches or pain

  3. change in vision

  4. congestion

  5. continuing ringing or buzzing or other unexplained noise in the ears

  6. hair loss or thinning of the hair

  7. hearing loss

  8. heartburn

  9. impaired vision

  10. lack or loss of strength

  11. loss of memory

  12. problems with memory

  13. seeing double

  14. tender, swollen glands in the neck

  15. uncontrolled eye movements

  16. voice changes

  17. weight gain

  18. weight loss
Less common

  1. Absent, missed, or irregular menstrual periods

  2. burning, dry, or itching eyes

  3. change in taste or bad unusual or unpleasant (after) taste

  4. coin-shaped lesions on the skin

  5. cough producing mucus

  6. cramps

  7. dandruff

  8. discharge or excessive tearing

  9. dry skin

  10. earache

  11. excess air or gas in the stomach or bowels

  12. eye pain

  13. feeling of constant movement of self or surroundings

  14. full feeling

  15. heavy bleeding

  16. increased appetite

  17. itching of the vagina or genital area

  18. loss of bowel control

  19. neck pain

  20. oily skin

  21. pain

  22. pain during sexual intercourse

  23. pain or tenderness around the eyes and cheekbones

  24. passing gas

  25. rash with flat lesions or small raised lesions on the skin

  26. redness or swelling in the ear

  27. redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid

  28. redness, swelling, or soreness of the tongue

  29. sensation of spinning

  30. sneezing

  31. stiff neck

  32. stopping of menstrual bleeding

  33. thick, white vaginal discharge with no odor or with a mild odor
Incidence not known

  1. Breast enlargement

  2. changes in hair color or texture

  3. discoloration of the fingernails or toenails

  4. increased hair growth, especially on the face

  5. unexpected or excess milk flow from the breasts

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Portions of this document last updated: July 01, 2021

Copyright © 2021 IBM Watson Health. All rights reserved. Information is for End User’s use only and may not be sold, redistributed or otherwise used for commercial purposes.


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Valproic acid: medicine used for bipolar disorder, epilepsy and migraine

Valproic acid is a prescription medicine. It’s important to take it as your doctor tells you.

Dosage

The usual dose for treating bipolar disorder for:

  • adults – 750mg to 2,000mg a day, split into 2 or 3 doses
  • children – the doctor will work out the right dose for your child

The usual dose for preventing migraine for:

  • adults – 500mg to 1,000mg a day, split into 2 or 3 doses

The usual dose for treating epilepsy for:

  • adults and older children (aged 12 years and over) – 600mg to 2,000mg a day, split into 2 to 4 doses
  • younger children (weighing more than 20kg) – the doctor will use your child’s weight to work out the right dose for them

If you need to take your medicine more than once a day, you’ll take equal doses that add up to your daily total. Ask your doctor or a pharmacist if you’re unsure how much to take each time.

If you’re taking valproic acid and have kidney problems, your doctor may prescribe a lower dose.

How and when take it

Valproic acid comes as gastro resistant tablets and capsules. These release the valproic acid into your body as soon as they pass through your stomach.

Swallow the tablets or capsules whole with a drink of water or juice. Do not chew them.

You can take valproic acid with or without food, but it’s best to do the same each time.

If you’re taking valproic acid twice a day, try to leave a gap of 10 to 12 hours between doses. For example you could take your first dose in the morning (between 7am and 8am) and your second dose in the evening (between 7pm and 8pm).

If you take it 3 to 4 times a day, try to space your doses evenly throughout the day. If you need to take 3 doses, for example, you could take a dose first thing in the morning, early afternoon and bedtime.

Will my dose go up or down?

To reduce the chance of side effects, your doctor will start you off on a low dose of valproic acid. They will increase it gradually over a few days or weeks.

Once you find a dose that suits you, it will usually stay the same, unless your condition changes, or your doctor starts you on a new medicine that may interfere with valproic acid.

What if I forget to take it?

If you forget a dose, take it as soon as you remember, unless it’s less than 2 hours to your next dose. In this case, skip the missed dose and take your next one at the usual time.

Never take 2 doses at the same time. Never take an extra dose to make up for a forgotten one.

If you have epilepsy, it’s important to take this medicine regularly. Missing doses can trigger a seizure.

If you often forget doses, it may help to set an alarm to remind you. You could also ask your pharmacist for advice on other ways to help you remember to take your medicine.

What if I take too much?

Taking too much valproic acid can lead to symptoms such as:

  • feeling or being sick (nausea or vomiting)
  • headaches, or feeling dizzy
  • muscle weakness
  • breathing problems
  • feeling confused, or changes to your normal behaviour
  • passing out

If you need to go to A&E, take the valproic acid packet or the leaflet inside it, plus any remaining medicine, with you.

Valproic Acid Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

See also Warning section.

Diarrhea, dizziness, drowsiness, hair loss, blurred/double vision, change in menstrual periods, ringing in the ears, shakiness (tremor), unsteadiness, weight changes may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Parts of a capsule may appear in your stool. Tell your doctor right away if this occurs.

A small number of people who take anticonvulsants for any condition (such as seizure, bipolar disorder, pain) may experience depression, suicidal thoughts/attempts, or other mental/mood problems. Tell your doctor right away if you or your family/caregiver notice any unusual/sudden changes in your mood, thoughts, or behavior including signs of depression, suicidal thoughts/attempts, thoughts about harming yourself.

Severe (sometimes fatal) brain disorder (encephalopathy) has rarely occurred, particularly in patients with certain metabolic disorders (urea cycle disorders). Tell your doctor right away if you develop unexplained weakness, vomiting, or sudden mental/mood changes (such as confusion).

Get medical help right away if you have any very serious side effects, including: chest pain, easy bruising/unexplained bleeding, fast/slow/irregular heartbeat, swelling of hands/feet, uncontrolled eye movement (nystagmus), feeling cold/shivering, rapid breathing, loss of consciousness.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: fever, swollen lymph nodes, rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US –

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Valproic Acid Side Effects

Valproic acid is a useful medication that is indicated for several health conditions but may lead to significant side effects in some individuals. There are a large number of possible adverse effects that have an impact on many different organs and systems in the body.

Image Credit: Saiful52/Shutterstock.com

Severe Effects

In some cases, individuals may be allergic to valproic acid, leading to a potentially dangerous situation when an allergic reaction occurs. If patients notice signs of hypersensitivity, they should seek medical advice as soon as possible to prevent unfavorable outcomes.

Valproic acid has the potential to cause life-threatening damage to the liver, particularly for young children taking multiple medications in the first six months of therapy.

It can also cause serious damage to the pancreas that has fatal potential. Pain in the stomach area and back, accompanied by nausea, vomiting, or loss of appetite may be indicative of pancreatitis and warrants further investigation and possible treatment.

Pregnant women and women who are planning to become pregnant in the near future should be advised against taking valproic acid, as there is a high risk of birth defects. It is recommended that all women of childbearing age take appropriate contraceptive precautions to avoid conceiving whilst being treated with valproic acid.

Gastrointestinal Effects

Gastrointestinal complications are the most common side effects associated with the use of valproic acid. These effects may include:

  • Abdominal pain
  • Diarrhea
  • Dyspepsia
  • Gingival disorder
  • Nausea
  • Vomiting
  • Constipation
  • Dry mouth
  • Fecal incontinence
  • Flatulence
  • Gastralgia
  • Gastroenteritis
  • Pancreatitis

Most of these effects are transient and subside with continued use or upon removal of the medication.

Hepatic Effects

It is common for liver enzymes such as bilirubin to increase as a result of therapy with valproic acid, particularly in the initial stages of treatment. This can lead to injury and damage to the liver and possible hepatic failure.

If signs of hepatic dysfunction become evident, such as elevation of transaminases and amylase in the blood, it is recommended to reduce the dose to manage this.

Nervous System

Side effects related to the nervous system that commonly occur to people taking valproic acid treatments include:

  • Dizziness
  • Headache
  • Tremor
  • Abnormal gait
  • Convulsion
  • Incoordination
  • Enhanced reflexes
  • Memory impairment
  • Dyskinesia

Cardiovascular

Common cardiovascular adverse effects include:

  • Edema
  • Hypertension
  • Hypotension
  • Tachycardia
  • Peripheral edema

Dermatological

Common dermatological adverse effects that occur include:

  • Alopecia
  • Dry skin
  • Rash
  • Itch
  • Seborrhea

Changes in hair growth and increased sweating may also occur but are less commonly reported.

Genitourinary

Common adverse effects to the genitourinary system include:

  • Amenorrhea
  • Cystitis
  • Dysmenorrhea
  • Dysuria
  • Urinary incontinence
  • Increased frequency of urination
  • Vaginitis

Psychiatric Effects

Common psychiatric side effects include:

  • Nervousness
  • Abnormal dreams
  • Aggression
  • Agitation
  • Confusion
  • Depression
  • Hallucinations
  • Insomnia
  • Attention disorders
  • Behavior abnormalities
  • Hyperactivity
  • Learning disorders

Children taking valproate treatment are particularly prone to learning and attention disorders, hyperactivity, and abnormalities in behavior.

Other Effects

There are several other effects to other areas of the body, such as:

  • Hematological: thrombocytopenia, anemia, hemorrhage
  • Musculoskeletal: arthralgia, arthrosis, cramping, myalgia, twitching
  • Ocular: blurred vision, diplopia, abnormal vision, conjunctivitis, dry eyes, eye pain
  • Respiratory: Respiratory infection, dyspnea, cough
  • Gastrointestinal: increased appetite, weight loss or gain, anorexia

Other side effects such as back pain, chills, edema, fever, malaise and other infections may also occur.

This is not a complete list of all the possible side effects of valproic acid and a patient may report other signs as a result of taking the medication. These should be managed appropriately to ensure the optimal health of the individual and reported to regulating bodies to alert future patients that may need to use valproic acid.

References

Further Reading

Short-Term Side Effects of Low Dose Valproate Monotherapy in Epileptic Children: A Prospective Study

Iran J Child Neurol. 2019 Spring; 13(2): 37–46.

, MD,1, MD,2, MD,1,2 and , MD2

Parisa Nasr ESFAHANI

1Students’ Research Center, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Jafar NASIRI

2Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

Shervin BADIHIAN

1Students’ Research Center, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

Omid YAGHINI

2Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

1Students’ Research Center, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

2Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

Corresponding Author: Yaghini O. MD, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran . Email: [email protected]

Received 2017 Apr 1; Revised 2017 Jul 9; Accepted 2018 Apr 21.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objectives

Considering the common use of valproate among children, we investigated the short-term side-effects of low dose valproate monotherapy in epileptic children.

Materials & Methods

In this prospective study, 209 epileptic children (48.3% male, mean age: 7.02 ± 3.13 yr) on low therapeutic dose of valproate monotherapy (20-30 mg/kg/d) were enrolled during 2014-2015 in Isfahan Pediatric Neurology Clinic, Isfahan University of Medical Sciences, Isfahan, Iran and side-effects were evaluated through frequent clinical visits and laboratory tests during 6 months of valproate therapy.

Results

Weight gain was reported in 53.1% of patients. Decreased appetite was seen in 11% of patients, more frequent in younger cases (P=0.006). Abdominal pain, nausea/vomiting, diarrhea, and constipation were reported in 16.3%, 2.4%, 1.4%, and 1% of patients, respectively. Headache, tremor, dizziness, abnormal color vision, myoclonus, and bruxism were seen in 5.7%, 1.4%, 1%, 1%, 1%, and 0.5% of patients, respectively. Enuresis, hair loss, and skin rash were reported in 8.1%, 6.7%, and 0.5% of patients, respectively. Thrombocytopenia, impaired liver function tests, and leukopenia occurred in 1%, 1%, and 0.5% of patients, respectively.

Conclusion

Low dose valproate monotherapy may cause numerous side-effects, mostly not life-threatening and requiring no action. Besides more reported complications, we observed decreased appetite (among younger patients), enuresis, and abnormal color vision which are onlybriefly discussed in the literature and need to be addressed more.

Key Words: Adverse drug reactions, Epilepsy, Pediatrics, Valproate monotherapy

Introduction

Valproate (VPA) is a broad-spectrum antiepileptic drug, used for treatment of certain types of seizures since 1970 (1). It can also be used in other conditions including some psychiatric disorders and prophylaxis of migraine (1). Epilepsy is a common disease among children and adolescents. Approximately 10.5 million children under 15 yr (about 0.8%) suffer from active epilepsy, of whom more than 80% live in developing countries (2). Although VPA is an old antiepileptic drug, it is still widely administered for epileptic patients, since it is favorably safe and inexpensive (3).

VPA may cause transient and non-hazardous side effects as well as serious and life-threatening side effects. Transient and non-hazardous side effects include weight gain, drowsiness, transient hair loss, tremor, increased gamma-glutamyl transferase, nausea, headache, and other complications (1, 4). Serious side effects include hepatotoxicity, encephalopathy, coagulation disorders, pancreatitis, and bone marrow suppression (1, 5, 6). Complications of VPA are also classified as gastrointestinal, neurological, metabolic and endocrine, hematologic, pulmonary, renal, dermatologic, mitochondrial, and hepatic adverse events (1). These complications may be associated with factors such as age and dose (1).

Although several studies were conducted on the subject, no study was designed to evaluate these complications in a pediatric population on low dose VPA as monotherapy. We aimed to investigate the short-term complications of low dose VPA in a pediatric population through frequent interviews, clinical visits, and lab tests during a 6-month period of therapy.

Materials and Methods

This cross-sectional prospective study performed during 2014-2015 in Isfahan Pediatric Neurology Clinic, Isfahan University of Medical Sciences, Isfahan, Iran. Patients ranging from 2 to 15 yr old, with diagnosis of epilepsy supposed to start low therapeutic dose of VPA (20-30 mg/kg/d) as monotherapy were included in the study. The exclusion criteria were defined as any other comorbid disease or medical condition including chronic hepatic disease, chronic renal disease, metabolic syndromes, diabetes, progressive neurological diseases, diseases of digestive system, and coagulation disorders; experiencing worsened seizures after starting VPA; needing higher doses of VPA; taking any other medication affecting body weight.

The study was approved by the regional bioethics committee of Isfahan University of Medical Sciences and informed consent was obtained from all patients or their parents.

VPA was started for patients with the decision of pediatric neurologists and based on the recent guidelines on treatment of epilepsy (7). After recruitment, a thorough history was taken from patients and they underwent complete physical and neurological examination. We designed a data collection questionnaire which included patients’ characteristics and demographic data, initial weight, seizure type, prescribed dose of VPA, and possible side effects of the drug (based on previous studies), including weight gain, change in appetite (according to parents’ evaluation), abdominal pain, nausea/vomiting, headache, enuresis, hair loss (diffuse reduction of hair defined as losing more than 100 hairs daily, evaluated by parents), diarrhea, constipation, tremor, skin rash, dizziness, abnormal color vision (sensible changes in the color vision or dominance of certain colors stated by the patient), bruxism, and myoclonus. To evaluate weight gain, we weighed patients at two time-points: before taking VPA, and after 6 months of taking VPA. As we expected no considerable changes in the children’s height and in turn, their body mass index, we calculated weight-for-age Z-score for each subject in these two time-points, using national z-score tables for boys and girls. Two amounts were compared to each other then, and increased z-score for ≥1 unit was considered as weight gain (8).

Blood samples were also taken to evaluate complete blood count with differentials (CBC-diff), serum glutamic oxaloacetic transaminase (SGOT), and serum glutamic pyruvic transaminase (SGPT) at four time-points: before starting the medication, 1 month, 3 months, and 6 months after starting the medication. Blood samples were obtained between 8 and 9 in the morning, after an overnight fast and before breakfast. Platelet count <150,000 /µL was considered as thrombocytopenia, WBC <4000 /µL was considered as leukopenia and increased SGOT and SGPT for more than two times were considered as increased liver enzymes. In patients with serious side effects, drug intolerance, and impaired lab tests, VPA was discontinued and was replaced with another drug. All the observed adverse drug reactions were rated using Naranjo scale (9) into one of the categories of highly probable, probable, possible, and doubtful. Naranjo scale determines whether an adverse drug reaction is actually due to the medication or it is caused by other factors. This scale evaluates the probability of a complication through 10 questions (9).

We reported data using descriptive statistics for frequencies and analytical statistics (Mann-Whitney test) for analysis of possible differences, using SPSS 19 (Chicago, IL, USA). A P-value less than 0.05 was considered as significant.

Results

Overall, 229 patients were included initially and 20 of them were excluded (13 patients with worsened seizures and 7 cases who needed higher doses of VPA). Of the remained cases, 101 patients (48.3%) were male and the mean age (standard deviation [SD]) was 7. 02 (3.13). Most patients had generalized seizures (75.6%) followed by absence seizures (9.6%), partial seizures (8.6%), and myoclonic seizures (6.2%).

Adverse drug reactions and their association with age are summarized in . Weight gain was seen in 111 patients (53.1%) while 33% of patients reported increased appetite and 11% of them reported decreased appetite. Older patients experienced increased appetite more frequently (P=0.006). Abdominal pain was reported in 16.3% of patients. It was mostly transient and lead to VPA discontinuation in none of the cases.

Table 1

Complications of valproate and their association with patients’ age

Category Subcategory Frequency (%) Age (Mean ± SD) P-value Naranjo scale
Weight gain Yes 111 (53.1) 7.29 ± 3.03 0.121 Probable ADR
No 98 (46.9) 6.79 ± 3.19
Appetite Increased 69 (33) 8 ± 3.28 0.006 Probable ADR
Decreased 23 (11) 6.72 ± 2.08 Possible ADR
No change 117 (56) 6.51 ± 3.10
Abdominal pain Yes 34 (16.3) 7.75 ± 2.73 0.54 Probable ADR
No 175 (83.7) 6.88 ± 3.20
Nausea/vomiting Yes 5 (2.4) 9.20 ± 4.09 0.160 Probable ADR
No 204 (97.6) 6.97 ± 3.10
Headache Yes 12 (5.7) 10.50 ± 3.15 <0.001 Probable ADR
No 197 (94.3) 6.81 ± 3.01
Enuresis Yes 17 (8.1) 7 ± 3.15 0.895 Possible ADR
No 192 (91.9) 7.03 ± 3.14
Hair loss Yes 14 (6.7) 8.25 ± 3.31 0.142 Probable ADR
No 195 (93.3) 6.94 ± 3.11
Diarrhea Yes 3 (1.4) 6.67 ± 1.53 0.912 Probable ADR
No 206 (98.6) 7.03 ± 3.15
Tremor Yes 3 (1.4) 12 ± 2 0.017 Probable ADR
No 206 (98.6) 6.95 ± 3.09
Skin rash Yes 1 (0.5) 2 0.029 Probable ADR
No 208 (99.5) 7.05 ± 3.12
Dizziness Yes 2 (1) 7.50 ± 0.71 0.540 Probable ADR
No 207 (99) 7.02 ± 3.15
Constipation Yes 2 (1) 5 0.340 Probable ADR
No 207 (99) 7.04 ± 3.14
Bruxism Yes 1 (0.5) 7 0.871 Possible ADR
No 208 (99.5) 7.02 ± 3.14
Myoclonus Yes 2 (1) 8.50 ± 4.95 0.596 Possible ADR
No 207 (99) 7.01 ± 3.13
Abnormal color vision Yes 2 (1) 6.5 ± 2.12 0.981 Possible ADR
No 207 (99) 7.03 ± 3.15
Thrombocytopenia Yes 2 (1) 5.5 ± 0.71 0.520 Probable ADR
No 207 (99) 7.04 ± 3.15
Leukopenia Yes 1 (0.5) 15 0.029 Probable ADR
No 208 (99.5) 6.99 ± 3.09
Increased liver enzymes Yes 2 (1) 4.5 ± 0.71 0.199 Probable ADR
No 207 (99) 7.05 ± 3.14

Twelve patients (5.7%) complained of headache, seen more in older ages (P<0.001). Enuresis and hair loss were reported in 17 (8.1%) and 14 (6.7%) patients respectively. Tremor and diarrhea were seen in 3 (1.4%) patients, and tremor was seen more in older ages (P=0.017). Only 2 patients (0.1%) presented one of the symptoms of dizziness, constipation, abnormal color vision, and myoclonus and one patient (0.5%) experienced skin rash or bruxism. Abnormal color vision was reversed by drug discontinuation.

Regarding patients’ lab tests, 2 cases (1%) developed thrombocytopenia, one patient (0.5%) had leukopenia, and in 2 patients had (1%) impaired liver function tests. In general, side effects lead to drug discontinuation in 12 patients, including 2 patients with thrombocytopenia, 1 patient with leukopenia, 7 patients with drug intolerance, and 2 patients with abnormal color vision.

Regarding all the side effects (except appetite change), 101 patients (48.3%) experienced one side effect, 29 patients (13.9%) experienced two side effects, 13 patients (6.2%) experienced three side effects and 3 patients (1.5%) experienced four or five side effects. Therefore, only 30.1% of patients experienced no side effects.

Discussion

Weight gain is one of the common complications of VPA seen in 53.1% of our patients, without any association with age. A study on Iranian children showed weight gain due to VPA in 40% of patients (10), however, another study reported weight gain in 58% of their cases (11). A negative correlation between weight gain and duration of treatment was reported before (12). weight gain is seen more in epileptic patients over 10 yr old (13). In contrast, no association was found between weight gain and age, gender, and drug dose in another study (14), which is also consistent with our findings.

In a clinical trial on epileptic children, increased appetite was reported in all of their subjects with marked weight gain (15). Increased and decreased appetite were seen in 33% and 11% of our patients, respectively. We found that patients with increased appetite are older than those with decreased or unchanged appetite. Based on our results, decreased appetite may be a complication of low dose VPA particularly in younger ages, however, we believe that evaluation of appetite may not be precise enough in our study since it was evaluated by parents. Decreased appetite has not been reported in previous studies and needs to be investigated more in the future, especially in younger patients.

Other gastrointestinal side effects in our study included abdominal pain (16.3%), nausea/vomiting (2.4%), constipation (1%), and diarrhea (1.4%). Gastrointestinal complications are known as common side effects of VPA occurring in up to 50% of patients (1, 4, 16). These symptoms are usually transient and require no intervention (4). Sudden onset of abdominal pain may be due to acute pancreatitis, which is an uncommon but serious side effect of VPA (1). We had no report of pancreatitis among our cases.

Neurological adverse effects reported among our cases were as follows: Dizziness (1%), headache (5.7%), tremor (1.4%), abnormal color vision (1%), myoclonus (0.5%), and bruxism (0.5%). We found headache more in older patients. Older patients are more capable of expressing their headache and this may be a factor affecting our results. Dizziness and headache are suggested as VPA side effects in previous studies (17). Tremor is commonly reported as a side effect of VPA (17) occurring in 1%-6% of patients (4) and is known to be dose dependent (18). Bruxism and myoclonus are rarely reported in the literature as side effects of VPA (1, 19).

We found enuresis in 8.1% of our patients. Enuresis due to VPA intake is less being addressed in the literature (18). In a study, 72 epileptic patients ranging from 2 to 15 yr were on long-term VPA therapy and reported enuresis in 17 of them (24%), which stopped after discontinuation of the drug. Age was the only factor introduced as the predicting factor for enuresis in this study (18). Moreover, Egger and Brett reported enuresis in 7% of their study group (100 subjects) (20). We confirm previous findings on the frequency of enuresis after VPA therapy, but after a short-term period, however, we found no association between enuresis and age. Enuresis was a new finding in our patients and they did not have history of enuresis due to seizures.

Hair loss was reported by 6.7% of our patients. Several studies have addressed the possible effects of VPA on hair growth, such as alopecia, thinning hair, and color change (4, 21). The occurrence of this condition has been reported from 3.5% to 11% in previous studies (21). Hair loss due to VPA is usually scattered, without any scars, occurring 3 to 6 months after starting VPA, and is suggested to be associated with higher doses of the medication in a few studies (21). Only one case (0.5%) complained of skin rash in our study. Skin rash is a rarely reported complication of VPA, mostly seen in combination therapies and is disappeared after drug discontinuation (4, 22).

VPA might impair color perception significantly (23). A study on adolescents on VPA monotherapy showed that VPA can significantly affect central and para-central color vision after a short-term period (24). Ophthalmologic examination of these patients is recommended in case ophthalmic symptoms develop (24). Two of our patients (1%) complained of abnormal color vision during their treatment. The complication was reversed by VPA discontinuation. Our patients described their condition as seeing objects with abnormal colors or dominancy of certain colors. Considering the reversibility of these symptoms, it seems not to be a serious complication of VPA.

We found thrombocytopenia in 1% of our patients. Thrombocytopenia is a dose-dependent complication of VPA (1, 4). This condition has been reported in a wide range of 1% to 32% in patients with different age groups and is known as the most common hematologic side effect of VPA (1, 18, 25, 26). Thrombocytopenia is reported more frequently due to multiple drug treatment, being female, and initial thrombocytopenia (27). Children are more prone to thrombocytopenia because of using higher doses of the drug compared to adults. Reduction or discontinuation of VPA results in increasing platelet counts in the next few days in these patients (25).

One of our patients (0.5%) developed leukopenia during the study. Leukopenia is rarely reported as a complication of VPA and is reversible by drug discontinuation and happens more in combination therapies (28). Bone marrow suppression and production of antibodies against thrombocytes may be responsible for decrease in blood cell lines (1). Increased liver enzymes were observed in 1% of our patients. Elevation of serum transaminases is a common and mainly reversible side effect of VPA, although it may develop to more severe and irreversible conditions such as severe hepatotoxicity (1, 4, 5, 29). Hepatotoxicity is reported to happen more in younger ages (30) and higher administered doses of VPA (29).

In this study, we had some limitations that should be noted. First, this study was open and uncontrolled. Therefore, we could not compare the frequency of complications with the normal population which makes it hard to distinguish adverse events from adverse effects. Second, some complications, such as hair loss and color vision, were evaluated based on parents’ or patients’ evaluation, while measuring them with more objective tools (for example dermatologic or ophthalmologic examination) might change the results. These results may be underestimated or overestimated in our study, based on parents’ precision and their obsession with their children. Third, we studied subjects who were on low dose VPA monotherapy, while VPA may develop more side effects on polytherapy and higher doses. Forth, there are some other side effects of VPA including oligomenorrhea in female adolescents and decreased serum levels of vitamin D not measured in this study. Despite these limitations, this is the first study that evaluates side effects of low dose VPA monotherapy in epileptic children in a prospective design.

In conclusion, low dose VPA monotherapy may cause numerous side effects, however, most of them are not dangerous and life-threatening. We reported decreased appetite especially in patients with younger ages which needs to be investigated more in future studies. Moreover, we addressed enuresis and abnormal color vision briefly discussed in the literature and need to be studied more. Further studies with larger study population and longer follow up period are recommended to evaluate our findings.

Acknowledgment

This project was conducted as a thesis under grant number 393359 funded by Vice-Chancellor for Research and Technology of Isfahan University of Medical Sciences. The funder had no role in study design, data collection, analysis and interpretation of data, writing the report, and making decision to submit the manuscript.

Authors’ contribution

Dr. Yaghini and Dr. Nasiri conceptualized the study, designed the study, cooperated in implementation of study, cooperated in data collection, analysis, and interpretation, and approved the final manuscript as submitted. Dr. Nasr and Dr. Badihian helped in designing the study, implemented the study, collected data, analyzed and interpreted data, prepared the first draft of the manuscript, and approved the final manuscript as submitted.

All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Conflict of interest

The authors declare that they have no conflict of interest.

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Depakene, Stavzor (valproic acid) dosing, indications, interactions, adverse effects, and more

  • acetaminophen

    Minor (1)valproic acid decreases levels of acetaminophen by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

  • acetaminophen IV

    Minor (1)valproic acid decreases levels of acetaminophen IV by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

  • acetaminophen rectal

    Minor (1)valproic acid decreases levels of acetaminophen rectal by increasing metabolism. Minor/Significance Unknown. Enhanced metabolism incr levels of hepatotoxic metabolites.

  • alosetron

    Minor (1)valproic acid will increase the level or effect of alosetron by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

  • aspirin

    Monitor Closely (1)aspirin increases levels of valproic acid by plasma protein binding competition. Use Caution/Monitor.

  • aspirin rectal

    Monitor Closely (1)aspirin rectal increases levels of valproic acid by plasma protein binding competition. Use Caution/Monitor.

  • aspirin/citric acid/sodium bicarbonate

    Monitor Closely (1)aspirin/citric acid/sodium bicarbonate increases levels of valproic acid by plasma protein binding competition. Use Caution/Monitor.

  • atracurium

    Minor (1)valproic acid decreases effects of atracurium by pharmacodynamic antagonism. Minor/Significance Unknown.

  • avapritinib

    Monitor Closely (1)valproic acid will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

  • axitinib

    Monitor Closely (1)valproic acid increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

  • biotin

    Minor (1)valproic acid decreases levels of biotin by unspecified interaction mechanism. Minor/Significance Unknown. Biotin supplementation may be necessary.

  • blinatumomab

    Monitor Closely (1)blinatumomab increases levels of valproic acid by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

  • bosentan

    Minor (1)valproic acid will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

  • bremelanotide

    Serious – Use Alternative (1)bremelanotide will decrease the level or effect of valproic acid by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

  • brodalumab

    Monitor Closely (1)brodalumab, valproic acid. Other (see comment). Use Caution/Monitor.
    Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, brodalumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of brodalumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

  • calcium/magnesium/potassium/sodium oxybates

    Serious – Use Alternative (1)valproic acid increases levels of calcium/magnesium/potassium/sodium oxybates by Other (see comment). Avoid or Use Alternate Drug.
    Comment: If stabilized on calcium/magnesium/potassium/sodium oxybates, decrease nightly dose by at least 20% when starting valproic acid; if already taking valproic acid, use a lower starting calcium/magnesium/potassium/sodium oxybates dose; monitor dose and adjust dose accordingly.

  • carbamazepine

    Monitor Closely (2)valproic acid will increase the level or effect of carbamazepine by Mechanism: decreasing metabolism. Use Caution/Monitor. Valproic acid may increase or decrease carbamazepine levels.

    carbamazepine decreases levels of valproic acid by increasing metabolism. Use Caution/Monitor.

  • carvedilol

    Monitor Closely (1)valproic acid will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

  • celecoxib

    Minor (1)valproic acid will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

  • cholestyramine

    Monitor Closely (1)cholestyramine decreases levels of valproic acid by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

  • cisatracurium

    Minor (1)valproic acid decreases effects of cisatracurium by pharmacodynamic antagonism. Minor/Significance Unknown.

  • clarithromycin

    Minor (1)clarithromycin increases levels of valproic acid by decreasing metabolism. Minor/Significance Unknown.

  • clonazepam

    Minor (1)clonazepam, valproic acid. Mechanism: unknown. Minor/Significance Unknown. Possible risk of absence seizure.

  • clozapine

    Minor (1)valproic acid decreases levels of clozapine by plasma protein binding competition. Minor/Significance Unknown.

  • colestipol

    Minor (1)colestipol decreases levels of valproic acid by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

  • conjugated estrogens

    Monitor Closely (1)conjugated estrogens will decrease the level or effect of valproic acid by increasing elimination. Modify Therapy/Monitor Closely. May lead to increased seizure frequency

  • cyanocobalamin

    Minor (1)valproic acid decreases levels of cyanocobalamin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

  • deutetrabenazine

    Monitor Closely (1)valproic acid and deutetrabenazine both increase sedation. Use Caution/Monitor.

  • dexmethylphenidate

    Minor (1)dexmethylphenidate increases effects of valproic acid by decreasing metabolism. Minor/Significance Unknown.

  • diclofenac

    Minor (1)valproic acid will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

  • dronabinol

    Monitor Closely (1)dronabinol increases levels of valproic acid by plasma protein binding competition. Modify Therapy/Monitor Closely. Dronabinol is highly bound to plasma proteins and may displace and increase the free fraction of other concomitantly administered highly protein-bound drugs. This has not been confirmed in vivo. Caution with narrow therapeutic index drugs that are highly protein bound when initiating or increasing the dose of dronabinol.

  • dulaglutide

    Monitor Closely (1)dulaglutide, valproic acid. Other (see comment). Use Caution/Monitor.
    Comment: Dulaglutide slows gastric emptying and may impact absorption of concomitantly administered oral medications; be particularly cautious when coadministered with drugs that have a narrow therapeutic index.

  • dupilumab

    Monitor Closely (1)dupilumab, valproic acid. Other (see comment). Use Caution/Monitor.
    Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, dupilumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of dupilumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

  • ertapenem

    Serious – Use Alternative (1)ertapenem decreases levels of valproic acid by unknown mechanism. Avoid or Use Alternate Drug. Risk of seizure. Possible decreased GI absorption and/or increased renal clearance of valproic acid.

  • erythromycin base

    Minor (1)erythromycin base increases levels of valproic acid by decreasing metabolism. Minor/Significance Unknown.

  • erythromycin ethylsuccinate

    Minor (1)erythromycin ethylsuccinate increases levels of valproic acid by decreasing metabolism. Minor/Significance Unknown.

  • erythromycin lactobionate

    Minor (1)erythromycin lactobionate increases levels of valproic acid by decreasing metabolism. Minor/Significance Unknown.

  • erythromycin stearate

    Minor (1)erythromycin stearate increases levels of valproic acid by decreasing metabolism. Minor/Significance Unknown.

  • esketamine intranasal

    Monitor Closely (1)esketamine intranasal, valproic acid.
    Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

  • estradiol

    Monitor Closely (1)estradiol will decrease the level or effect of valproic acid by increasing elimination. Modify Therapy/Monitor Closely. May lead to increased seizure frequency

  • estrogens esterified

    Monitor Closely (1)estrogens esterified will decrease the level or effect of valproic acid by increasing elimination. Modify Therapy/Monitor Closely. May lead to increased seizure frequency

  • ethinylestradiol

    Monitor Closely (1)ethinylestradiol will decrease the level or effect of valproic acid by increasing elimination. Modify Therapy/Monitor Closely. May lead to increased seizure frequency

  • ethotoin

    Monitor Closely (1)valproic acid will increase the level or effect of ethotoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (2)valproic acid, ethotoin. Mechanism: plasma protein binding competition. Minor/Significance Unknown. Valproic acid may increase or decrease phenytoin levels.

    ethotoin decreases levels of valproic acid by increasing metabolism. Minor/Significance Unknown.

  • etravirine

    Monitor Closely (1)valproic acid will increase the level or effect of etravirine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

  • ezogabine

    Minor (1)ezogabine decreases levels of valproic acid by Other (see comment). Minor/Significance Unknown.
    Comment: Ezogabine may induce glucuronidation that results in small decreases of trough levels.

  • fedratinib

    Serious – Use Alternative (1)valproic acid will increase the level or effect of fedratinib by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of fedratinib (a CYP3A4 and CYP2C19 substrate) with dual CYP3A4 and CYP2C19 inhibitor. Effect of coadministration of a dual CYP3A4 and CYP2C19 inhibitor with fedratinib has not been studied.

  • felbamate

    Minor (1)valproic acid increases levels of felbamate by decreasing metabolism. Minor/Significance Unknown.

  • ferric maltol

    Monitor Closely (1)ferric maltol, valproic acid.
    Either increases levels of the other by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of ferric maltol with certain oral medications may decrease the bioavailability of either ferric maltol and some oral drugs. For oral drugs where reductions in bioavailability may cause clinically significant effects on its safety or efficacy, separate administration of ferric maltol from these drugs. Duration of separation may depend on the absorption of the medication concomitantly administered (eg, time to peak concentration, whether the drug is an immediate or extended release product).

  • finerenone

    Monitor Closely (1)valproic acid will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.

  • flibanserin

    Monitor Closely (1)valproic acid will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

  • flurbiprofen

    Minor (1)valproic acid will increase the level or effect of flurbiprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

  • fluvastatin

    Minor (1)valproic acid will increase the level or effect of fluvastatin by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

  • fosphenytoin

    Monitor Closely (1)valproic acid will increase the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (2)valproic acid, fosphenytoin. Mechanism: plasma protein binding competition. Minor/Significance Unknown. Valproic acid may increase or decrease phenytoin levels.

    fosphenytoin decreases levels of valproic acid by increasing metabolism. Minor/Significance Unknown.

  • glycerol phenylbutyrate

    Monitor Closely (1)valproic acid decreases effects of glycerol phenylbutyrate by Other (see comment). Use Caution/Monitor.
    Comment: Valproic acid may induce hyperammonemia; monitor ammonia levels closely when coadministered with glycerol phenylbutyrate.

  • guanfacine

    Monitor Closely (1)guanfacine increases levels of valproic acid by unknown mechanism. Use Caution/Monitor. Both 3-hydroxy guanfacine (metabolite) and valproic acid are metabolized by glucuronidation, possibly resulting in competitive inhibition.

  • guselkumab

    Monitor Closely (1)guselkumab, valproic acid. Other (see comment). Use Caution/Monitor.
    Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of guselkumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

  • ibuprofen

    Minor (1)valproic acid will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

  • ibuprofen IV

    Minor (1)valproic acid will increase the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

  • imipenem/cilastatin

    Serious – Use Alternative (1)imipenem/cilastatin will decrease the level or effect of valproic acid by unknown mechanism. Avoid or Use Alternate Drug. Data from in vitro and animal studies suggest carbapenems may inhibit hydrolysis of the valproic acid glucuronide metabolite (VPA-g) back to valproic acid, thus decreasing the serum concentrations of valproic acid/divalproex sodium.

  • imipenem/cilastatin/relebactam

    Serious – Use Alternative (1)imipenem/cilastatin/relebactam will decrease the level or effect of valproic acid by unknown mechanism. Avoid or Use Alternate Drug. Data from in vitro and animal studies suggest carbapenems may inhibit hydrolysis of the valproic acid glucuronide metabolite (VPA-g) back to valproic acid, thus decreasing the serum concentrations of valproic acid/divalproex sodium.

  • isoniazid

    Minor (1)isoniazid increases levels of valproic acid by decreasing metabolism. Minor/Significance Unknown.

  • ivacaftor

    Monitor Closely (1)valproic acid increases levels of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor when coadministered with weak CYP3A4 inhibitors .

  • ixekizumab

    Monitor Closely (1)ixekizumab, valproic acid. Other (see comment). Use Caution/Monitor.
    Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, ixekizumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of ixekizumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

  • lamotrigine

    Monitor Closely (1)valproic acid increases levels of lamotrigine by decreasing metabolism. Modify Therapy/Monitor Closely.

  • lemborexant

    Monitor Closely (1)valproic acid will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.

  • lesinurad

    Serious – Use Alternative (1)valproic acid, lesinurad. Other (see comment). Avoid or Use Alternate Drug.
    Comment: Avoid coadministration with inhibitors of epoxide hydrolase (valproic acid) which may interfere with metabolism of lesinurad.

  • levocarnitine

    Minor (1)valproic acid decreases levels of levocarnitine by unspecified interaction mechanism. Minor/Significance Unknown.

  • lomitapide

    Monitor Closely (1)valproic acid increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

  • lomustine

    Monitor Closely (1)valproic acid will increase the level or effect of lomustine by decreasing metabolism. Use Caution/Monitor. Coadministration of valproic acid may inhibit metabolism and increase the toxicity of lomustine.

  • lonafarnib

    Serious – Use Alternative (1)valproic acid will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

  • mefloquine

    Minor (1)mefloquine decreases levels of valproic acid by unspecified interaction mechanism. Minor/Significance Unknown.

  • meloxicam

    Minor (1)valproic acid will increase the level or effect of meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

  • meropenem

    Serious – Use Alternative (1)meropenem decreases levels of valproic acid by unknown mechanism. Avoid or Use Alternate Drug. Risk of seizure. Possible decreased GI absorption and/or increased renal clearance of valproic acid.

  • meropenem/vaborbactam

    Serious – Use Alternative (1)meropenem/vaborbactam decreases levels of valproic acid by unknown mechanism. Avoid or Use Alternate Drug. Risk of seizures. If administration of meropenem/vaborbactam is necessary, then supplemental anticonvulsant therapy should be considered .

  • metoclopramide intranasal

    Serious – Use Alternative (1)valproic acid, metoclopramide intranasal.
    Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug.
    Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

  • midazolam intranasal

    Monitor Closely (2)valproic acid will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

    midazolam intranasal, valproic acid.
    Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

  • mipomersen

    Monitor Closely (1)mipomersen, valproic acid.
    Either increases toxicity of the other by Other (see comment). Use Caution/Monitor.
    Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

  • nateglinide

    Monitor Closely (1)valproic acid will increase the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

  • nitazoxanide

    Serious – Use Alternative (1)nitazoxanide, valproic acid.
    Either increases levels of the other by Mechanism: plasma protein binding competition. Avoid or Use Alternate Drug.

  • onabotulinumtoxinA

    Minor (1)valproic acid decreases effects of onabotulinumtoxinA by pharmacodynamic antagonism. Minor/Significance Unknown.

  • oritavancin

    Monitor Closely (1)oritavancin will increase the level or effect of valproic acid by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Oritavancin is a weak CYP2C19 inhibitor; caution if coadministered with CYP2C19 substrates that have a narrow therapeutic index

  • orlistat

    Monitor Closely (1)orlistat decreases levels of valproic acid by inhibition of GI absorption. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Risk of convulsions.

  • osilodrostat

    Monitor Closely (1)osilodrostat will decrease the level or effect of valproic acid by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

  • ospemifene

    Monitor Closely (1)valproic acid, ospemifene.
    Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.

  • pancuronium

    Minor (1)valproic acid decreases effects of pancuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

  • parecoxib

    Monitor Closely (1)valproic acid will increase the level or effect of parecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

  • perampanel

    Minor (1)perampanel increases levels of valproic acid by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

  • pexidartinib

    Serious – Use Alternative (1)valproic acid and pexidartinib both increase Other (see comment). Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

  • phenobarbital

    Minor (1)valproic acid increases levels of phenobarbital by unspecified interaction mechanism. Minor/Significance Unknown.

  • phenytoin

    Monitor Closely (1)valproic acid will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (2)valproic acid, phenytoin. Mechanism: plasma protein binding competition. Minor/Significance Unknown. Valproic acid may increase or decrease phenytoin levels.

    phenytoin decreases levels of valproic acid by increasing metabolism. Minor/Significance Unknown.

  • piroxicam

    Minor (1)valproic acid will increase the level or effect of piroxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

  • pretomanid

    Serious – Use Alternative (1)valproic acid, pretomanid.
    Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug.
    Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

  • primidone

    Minor (1)valproic acid increases effects of primidone by increasing metabolism. Minor/Significance Unknown. Valproic acid enhances the conversion of primidone to phenobarbital.

  • propofol

    Monitor Closely (1)valproic acid increases effects of propofol by pharmacodynamic synergism. Use Caution/Monitor.

  • rapacuronium

    Minor (1)valproic acid decreases effects of rapacuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

  • rocuronium

    Minor (1)valproic acid decreases effects of rocuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

  • rufinamide

    Monitor Closely (1)valproic acid increases levels of rufinamide by decreasing metabolism. Use Caution/Monitor. Initiate rufinamide at a dose

  • ruxolitinib

    Minor (1)valproic acid will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

  • sage

    Minor (1)sage decreases effects of valproic acid by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction; some species of sage may cause convulsions.

  • sarilumab

    Monitor Closely (1)sarilumab, valproic acid. Other (see comment). Use Caution/Monitor.
    Comment: Formation of CYP450 enzymes can be altered by increased levels of cytokines such as IL-6. Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA. Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations. Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index.

  • secukinumab

    Monitor Closely (1)secukinumab, valproic acid. Other (see comment). Use Caution/Monitor.
    Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, secukinumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of secukinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

  • sevelamer

    Monitor Closely (1)sevelamer decreases levels of valproic acid by increasing elimination. Use Caution/Monitor.

  • sodium oxybate

    Serious – Use Alternative (1)valproic acid increases levels of sodium oxybate by Other (see comment). Avoid or Use Alternate Drug.
    Comment: If stabilized on sodium oxybate, decrease nightly dose by at least 20% when starting valproic acid; if already taking valproic acid, use a lower starting sodium oxybate dose; monitor dose and adjust dose accordingly.

  • sodium phenylacetate

    Serious – Use Alternative (1)valproic acid decreases effects of sodium phenylacetate by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Valproic acid may exacerbate hyperammonemia in pts. with urea cycle disorders.

  • succinylcholine

    Minor (1)valproic acid decreases effects of succinylcholine by pharmacodynamic antagonism. Minor/Significance Unknown.

  • sulfamethoxazole

    Minor (1)valproic acid will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

  • tazemetostat

    Monitor Closely (1)valproic acid will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

  • teduglutide

    Monitor Closely (1)teduglutide increases levels of valproic acid by sedation. Use Caution/Monitor. Teduglutide may increase absorption of concomitant PO medications; caution with with drugs requiring titration or those with a narrow therapeutic index; dose adjustment may be necessary.

  • temozolomide

    Monitor Closely (1)valproic acid increases levels of temozolomide by decreasing metabolism. Use Caution/Monitor. Cautions is advised.

  • tiagabine

    Minor (1)valproic acid decreases levels of tiagabine by increasing metabolism. Minor/Significance Unknown.

  • tinidazole

    Monitor Closely (1)valproic acid will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

  • tolbutamide

    Minor (1)valproic acid will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

  • topiramate

    Monitor Closely (1)valproic acid, topiramate.
    Either increases toxicity of the other by unknown mechanism. Use Caution/Monitor. Risk of hyperammonemia with or without encephalopathy; pts. with inborn errors of metabolism may be at greater risk. S/S: altered LOC, lethargy, vomiting.Minor (1)topiramate decreases levels of valproic acid by increasing metabolism. Minor/Significance Unknown.

  • ustekinumab

    Monitor Closely (1)ustekinumab, valproic acid. Other (see comment). Use Caution/Monitor.
    Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

  • vecuronium

    Minor (1)valproic acid decreases effects of vecuronium by pharmacodynamic antagonism. Minor/Significance Unknown.

  • voriconazole

    Minor (1)valproic acid will increase the level or effect of voriconazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

  • vorinostat

    Serious – Use Alternative (1)vorinostat, valproic acid. pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of severe thrombocytopenia and GI bleeding. Monitor platelet count q 2 wks for first 2 months.

  • warfarin

    Monitor Closely (1)valproic acid will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

  • zidovudine

    Monitor Closely (1)valproic acid increases levels of zidovudine by decreasing metabolism. Use Caution/Monitor. Potential for increased toxicity. .

  • Apo-Valproic – Uses, Side Effects, Interactions

    How does this medication work? What will it do for me?

    Valproic acid belongs to the class of medications called anticonvulsants. It is used to manage and control certain types of seizures. It works on the central nervous system (CNS) in the brain to reduce the number and severity of seizures.

    This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

    Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

    Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

    What form(s) does this medication come in?

    Capsule 

    Each colourless, liquid-filled, opaque, orange, soft gelatin capsule imprinted “APO 250” in red ink, contains 250 mg of valproic acid. Non-medicinal ingredients: ammonium hydroxide, corn oil, FD&C Yellow No. 6, gelatin, glycerin, isopropyl alcohol, methylparaben, n-butyl alcohol, pharmaceutical glaze, propylene glycol, propylparaben, simethicone, synthetic red iron oxide, and titanium dioxide.

    Oral solution 

    Each 5 mL of bright orange-red liquid with a distinctive strawberry aroma contains the equivalent of 250 mg of valproic acid, as the sodium salt. Non-medicinal ingredients: artificial strawberry flavour, FD&C Red No. 40, glycerin, methylparaben, propylparaben, purified water, sodium hydroxide, sorbitol, and sucrose.

    How should I use this medication?

    The recommended dose of valproic acid is based on body weight. The dose of medication is usually started at a low level (15 mg per kg of body weight per day) to minimize side effects, and increased gradually until seizures are controlled with a minimum of side effects. The maximum recommended dose is 60 mg per kg of body weight per day.

    The capsules should be swallowed whole. Do not chew or puncture the capsules. Use an oral syringe to measure each dose of the liquid, as it gives a more accurate measurement than household teaspoons. Valproic acid may be taken with food or on an empty stomach, however taking this medication with food may help to reduce stomach upset.

    Many things can affect the dose of a medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.

    It is important to take this medication exactly as prescribed by your doctor. If you miss a dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

    Store this medication at room temperature, protect it from light and moisture, and keep it out of the reach of children.

    Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

    Who should NOT take this medication?

    Do not take valproic acid if you:

    • are allergic to valproic acid or any ingredients of the medication
    • have liver disease or significant reduction in liver function
    • have Alpers syndrome or Alpers-Huttenlocher syndrome, conditions caused by nervous system breakdown
    • have porphyria
    • have certain metabolic disorders (urea cycle disorders)

    Valproic acid should not be used by pregnant women if there is a suitable alternative medication.

    What side effects are possible with this medication?

    Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

    The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

    The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

    Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

    • diarrhea
    • dizziness
    • headache
    • indigestion
    • nausea
    • sedation
    • vomiting
    • weakness

    Although most of these side effects listed below don’t happen very often, they could lead to serious problems if you do not seek medical attention.

    Check with your doctor as soon as possible if any of the following side effects occur:

    • abdominal or stomach cramps (severe)
    • changes in hair (hair loss or increased hair on face, chest, and back)
    • hallucinations (seeing or hearing things that aren’t there)
    • increase in seizures
    • decreased level of consciousness, increasing tiredness and weakness with behaviour changes (extreme irritability, combativeness)
    • nausea or vomiting (continuing)
    • signs of bleeding (e.g., unusual nosebleeds, bruising, blood in urine, coughing blood, bleeding gums, cuts that don’t stop bleeding)
    • signs of depression (e.g., poor concentration, changes in weight, changes in sleep, decreased interest in activities, thoughts of suicide)
    • signs of liver problems (e.g., nausea, vomiting, diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools)
    • signs of muscle damage (e.g., muscle pain, tenderness or weakness, or brown or discoloured urine) – especially if you also have a fever or a general feeling of being unwell
    • tremor
    • urinary incontinence

    Seek immediate medical attention if any of the following occur:

    • signs of pancreatitis (e.g., abdominal pain on the upper left side, back pain, nausea, fever, chills, rapid heartbeat, swollen abdomen)
    • symptoms of a serious allergic reaction, including angioedema (e.g., hives; swelling of the face, mouth, hands, or feet; and difficulty breathing)
    • signs of a severe skin reaction such as blistering, peeling, a rash covering a large area of the body, a rash that spreads quickly, or a rash combined with fever or discomfort
    • thoughts of self-harm

    Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

    Are there any other precautions or warnings for this medication?

    Before you begin using a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should use this medication.

    Blood clotting: This medication may make it more difficult for the blood to clot. If you take anticoagulant (blood thinning) medications, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. If you notice any signs of bleeding, such as frequent nosebleeds, unexplained bruising, or black and tarry stools, notify your doctor as soon as possible. Your doctor will order routine blood tests to make sure potential problems are caught early.

    Take appropriate precautions and ensure that all doctors involved in your care are aware of all medication use. Tests for blood clotting should take place before any surgery. Platelet count and coagulant tests should take place before starting treatment with valproic acid.

    Drowsiness/reduced alertness: Valproic acid may affect the mental or physical abilities needed to drive or operate machinery. Avoid driving, operating machinery, or performing other hazardous tasks until you have determined how this medication affects you.

    Hypersensitivity syndrome: A severe allergic reaction called hypersensitivity syndrome has occurred for some people with the use of valproic acid. Stop taking the medication and get immediate medical attention if you have symptoms of a severe allergic reaction, including fever, swollen glands, yellowing of the skin or eyes, or flu-like symptoms with skin rash or blistering.

    Kidney function: Kidney disease or reduced kidney function may cause this medication to build up in the body, causing side effects. If you have reduced kidney function or kidney disease, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

    Liver function: Liver failure has occurred infrequently for people taking valproic acid, usually during the first 6 months of treatment. Children under 2 years of age who take valproic acid together with other epilepsy medications are at greatest risk (nearly 20 times greater) of developing serious liver problems. These children typically have other medical conditions such as congenital metabolic disorders, severe seizure disorders accompanied by mental retardation, or organic brain disease. Liver function tests should take place before starting treatment with valproic acid.

    Symptoms that can occur before serious liver problems include seizure control, malaise, weakness, lethargy, loss of appetite, and vomiting. People who take valproic acid should tell their doctor at once if they experience these symptoms. Increases in the levels of ammonia in the blood, with or without lethargy or coma, have been reported and may be present despite normal liver function tests.

    Pancreatitis: Cases of life-threatening pancreatitis (inflammation of the pancreas) have been reported for both children and adults. This can occur at any time during the use of valproic acid. If you experience signs of pancreatitis such as abdominal pain on the upper left side, back pain, loss of appetite, nausea, fever, chills, rapid heartbeat, or swollen abdomen contact your doctor immediately.

    Sedation: Valproic acid may cause sedation, especially when combined with another sedating drug such as alcohol.

    Seizures: Some people experience an increase in seizures or new types of seizures when taking valproic acid. If you experience a change in your seizures, contact your doctor as soon as possible.

    Stopping the medication: Valproic acid should not be stopped suddenly, as this can cause seizures to increase in frequency and severity. If you need to stop taking this medication, it should be reduced gradually. Talk to your doctor about the best way to stop this medication.

    Suicidal thoughts: There is a small risk that this medication may result in thoughts of suicide. If you experience these symptoms or any other behaviour change while taking this medication, contact your doctor immediately. Family members or caregivers of people who are taking this medication should contact the person’s doctor immediately if they notice unusual behaviour changes.

    Pregnancy: There is an increased risk of serious birth defects for a child whose mother takes valproic acid during pregnancy. Valproic acid may cause a defect of the spine called spina bifida, cleft palate, heart defects, autism, or slowed or reduced mental development. Women of child-bearing age must use effective birth control while taking valproic acid.

    Before becoming pregnant, women with epilepsy should speak to their doctor about other options for seizure medications. If you become pregnant while taking this medication, contact your doctor immediately.

    People who need medications to prevent major seizures should not stop taking them. If it is necessary to stop taking this medication, your doctor will advise you of the best way to reduce or change the medication.

    Breast-feeding: This medication passes into breast milk. If you are a breast-feeding mother and are taking valproic acid it may affect your baby. Talk to your doctor about whether you should continue breast-feeding. As a general rule, women who are taking valproic acid are advised not to breast-feed.

    Children: If valproic acid is given to children 2 years old or younger, it should be used with extreme caution and as a single medication. The benefits of seizure control should be weighed against the risk.

    Seniors: People over the age of 65 may be more at risk of developing side effects from this medication and may require lower dosages.

    What other drugs could interact with this medication?

    There may be an interaction between valproic acid and any of the following:

    • acarbose
    • acetazolamide
    • alcohol
    • aminosalicylic acid
    • antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
    • ASA
    • barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
    • benzodiazepines (e.g., diazepam, lorazepam, clonazepam)
    • birth control pills (estrogens)
    • bismuth subsalicylate
    • carbamazepine
    • cholestyramine
    • ertapenem
    • estrogens (e.g., conjugated estrogen, estradiol, ethinyl estradiol)
    • ethosuximide
    • guanfacine
    • HIV protease inhibitors (e.g., atazanavir, indinavir, ritonavir, saquinavir)
    • imipenem
    • irinotecan
    • isoniazid
    • lamotrigine
    • lomustine
    • lorazepam
    • macrolide antibiotics (e.g., clarithromycin, erythromycin)
    • mefloquine
    • meropenem
    • minoxidil
    • monoamine oxidase inhibitors (MAOIs; e.g., moclobemide, phenelzine, rasagiline, selegiline, tranylcypromine)
    • orlistat
    • oxcarbazepine
    • phenytoin
    • primidone
    • rifampin
    • rufinamide
    • selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine, paroxetine, sertraline)
    • sodium oxybate
    • temozolamide
    • topiramate
    • tricyclic antidepressants (e.g., amitriptyline, nortriptyline)
    • vorinostat
    • warfarin
    • zidovudine

    If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

    • stop taking one of the medications,
    • change one of the medications to another,
    • change how you are taking one or both of the medications, or
    • leave everything as is.

    An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

    Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

    All material copyright MediResource Inc. 1996 – 2021. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Source: www.medbroadcast.com/drug/getdrug/Apo-Valproic

    Valproic acid

    Valproic acid is an anticonvulsant drug. It is widely used for the treatment of various types of epilepsy in adults and children (large and small seizures, myoclonic, tonic-clonic and bipolar forms).

    Russian synonyms

    Apilepsin, Depakin, Orfiril, Konvulex.

    English synonyms

    Acidum valproicum, Valproate, Valproic Acid, Depakote.

    Research method

    Immunochemiluminescence analysis.

    Units

    μg / ml (micrograms per milliliter).

    What biomaterial can be used for research?

    Venous blood.

    How to properly prepare for the study?

    • Do not eat for 2-3 hours before the study, you can drink clean still water.
    • Do not smoke within 30 minutes prior to examination.

    General information about the study

    Valproic acid inhibits the enzyme GABA-transferase and, as a result, increases the content of the inhibitory neurotransmitter – gamma-aminobutyric acid (GABA) – in the nervous system.Under conditions of accumulation of GABA in the central structures of the brain, the threshold of excitability and the level of convulsive readiness decrease.

    Prescribed for patients suffering from epilepsy in all its manifestations (large and small seizures, myoclonic, tonic-clonic and bipolar forms), behavioral changes inherent in epilepsy, affective disorders, as well as in the treatment of manias accompanied by bipolar disorders in children, with febrile seizures , children’s tics. Recently, it has been used for neurological and mental disorders, for the prevention and treatment of migraine, neuropathic pain, for behavioral disorders with panic episodes, aggression, etc.In addition, according to the research results, the antitumor activity of valproic acid, which is used in myelodysplastic syndromes and acute monocytic leukemia, was revealed.

    Valproic acid preparations are rapidly and almost completely absorbed in the gastrointestinal tract, reaching a maximum concentration in the blood after 1.5-4 hours. Moreover, they are characterized by nonlinear (dose-dependent) pharmacokinetics, when the concentration of the drug in the blood increases or decreases faster than the increased or decreased dose.If the upper limit of their average therapeutic level is exceeded, it is necessary to take into account the greater likelihood of side effects, in some cases up to intoxication.

    Valproic acid is mainly metabolized in the liver and can cause liver damage, especially during the first 6 months after starting treatment. Therefore, before therapy with valproic acid, each patient needs to pass a series of tests to study liver function.

    Valproic acid is characterized by low toxicity; severe side effects can occur during prolonged treatment.These include weight gain, nausea, ovarian cysts, tremors, dizziness, depression of consciousness, manifestations of pancreatitis and liver damage (severe abdominal pain and vomiting, lethargy, yellow skin or eyes). Side effects are more common in infants and young children, especially when treated in combination with other antiepileptic drugs. Poisoning with valproic acid preparations is in most cases mild, serious overdose, when the patient’s life is in danger, are extremely rare.Overdoses are most often associated with depression of the central nervous system. A significant excess of the dose of the drug can cause coma and respiratory failure. In this regard, in the course of treatment, it is required to determine the concentration of the drug in the blood of patients in order to assess the level of toxicity and control the elimination of drugs from the body.

    Individual dosage based on therapeutic control of the concentration of the drug in the blood serum, increases the effectiveness and safety of therapy and allows you to achieve success in each case.

    Blood for analysis is taken twice (this is a standard technique): 1st sample – immediately before the drug is taken by the patient (residual concentration after the last dose), 2nd sample – 2-3 hours after administration (reaching the maximum concentration in the blood). At the same time, the procedure for taking blood is determined by the attending physician and may differ significantly from the standard method.

    What is the research used for?

    • To determine the most effective concentration of valproic acid and the mode of its administration in the treatment of certain diseases.
    • To prevent the toxic effects of valproic acid preparations.

    When is the study scheduled?

    • For violations of the liver, kidney or gastrointestinal tract, which affect the pharmacokinetics of valproic acid preparations.
    • In case of doubt about the correctness of the drug intake by the patient.
    • If acute poisoning with valproic acid drugs is suspected (depression of consciousness, disorientation, increased drowsiness, tachycardia, pulmonary edema, manifestations of pancreatitis and liver damage).
    • When prescribing a drug after reaching a stable concentration (at least equal to five half-lives).
    • When the patient is less than a year old – due to rapidly changing body weight (every 1-3 months).
    • With positive dynamics of the disease against the background of ongoing therapy, in general, 1-2 times a year.
    • Upon confirmation of pregnancy, at 8-10 weeks of pregnancy, then once every 2 months, at 34-36 weeks, after childbirth twice within 8 weeks, and with continuing seizures – at each visit to a neurologist (epileptologist) …
    • After the appointment or cancellation of other drugs of combined anticonvulsant therapy.

    What do the results mean?

    Reference values: 50 – 100 μg / ml.

    Reasons for an increase in the level of valproic acid:

    • excess dosage and / or incorrect administration of valproic acid preparations;
    • acute poisoning with valproic acid preparations.

    Reasons for a decrease in the level of valproic acid:

    • Elimination of valproic acid preparations from the body.

    The generally accepted therapeutic range for valproic acid is 50-100 μg / ml. The toxic effect develops at concentrations above 100 μg / ml.

    What can influence the result?

    • Decreased liver function in a number of its diseases can cause an increase in the concentration of valproic acid in the blood serum, even in the absence of an increase in doses of the administered drug.

    Download an example of the result

    Important notes

    • Before starting therapy with valproic acid preparations, each patient must pass a series of tests to study liver function.
    • Doses of drugs are selected by the attending physician for each patient individually, they cannot be changed independently.
    • Concomitant use of other anticonvulsants increases the toxic effect of valproic acid and increases the risk of side effects, therefore, it is necessary to control the concentration in serum of these drugs.

    Also recommended

    Who orders the study?

    Neurologist, psychiatrist, psychotherapist, narcologist, toxicologist, general practitioner.

    Literature

    • Smirnova O. Yu., Sitnikov I. Yu., Savinov SV Drug monitoring as the most important factor in the correct approach in the treatment of epilepsy and convulsive syndromes.
    • Sokolov A. V. Therapeutic drug monitoring. // High-quality clinical practice, 2002, No. 1, p. 78-88.
    • Problems of Forensic Science 2007, LXXll, 416-432: Toxicological analysis of valproic acid in blood by FPIA in comparison to GC-MS.
    • Lacy, Charles F. Drug Information Handbook. Lexi-Comp, Inc. 2002.
    • Hirschfeld, Robert. “Safety and Tolerability of Oral Loading Divalproex Sodium in Acutely Manic Bipolar Patients”. Journal of Clinical Psychiatry. 60 (1999): 815-818.
    • Lagace DC, Obrien WT, Gurvich N, Nachtigal MW, Klein PS. Valproic acid: How it works. Or not. Clin Neurosci Res 2004; 4: 215-225.

    Active substance VALPROIC ACID (ACIDUM VALPROICUM)

    HSDB, RTECS, EINECS: 2-Propylvaleric acid.
    MESH, USPDDN: 2-propylpentanoic acid.

    M m = 144.22 Yes. White fine crystalline powder. Let’s dissolve in water and alcohol. Solubility in water at 20 ° C = 2000 mg / l. log P (octanol-water) = 2.75.

    Release form: tablets, enteric-coated tablets, capsules, syrup, injection solution, extended-release film-coated tablets.

    Medicinal preparations containing the active substance VALPROIC ACID

    antiepileptic drugs

    antiepileptic drugs

    antiepileptic drugs

    antiepileptic drugs

    antiepileptic drugs

    antiepileptic drugs

    antiepileptic drugs

    is an anticonvulsant agent effective in various forms of epilepsy.It is believed that valproate increases the concentration of GABA in the central nervous system by inhibiting the enzyme GABA transferase.

    Well absorbed in the digestive tract. Plasma C max is observed 1–4 hours after ingestion. When choosing a dose, it should be borne in mind that the level of the active substance in the CSF is about 1 / 1 0 its concentration in the blood. It is excreted mainly in the urine in the form of glucuronide; T ½ – 8-15 hours, in patients taking antiepileptic drugs for a long time – 6-10 hours.After oral administration, the active substance penetrates the placental barrier, as well as into breast milk.

    generalized and minor epileptic seizures; focal (partial) seizures with simple and complex symptoms; convulsive syndrome in organic brain diseases; behavioral disorders associated with epilepsy; febrile seizures in children; tick in children.

    adults and adolescents – a daily dose of 20-30 mg / kg of body weight; to achieve a stable clinical effect, the dose can be increased by 200 mg / day with an interval of 3-4 days; the highest daily dose is 50 mg / kg.For newborns and young children, the dose is selected individually: the daily dose is usually 30 mg / kg; the frequency of admission in children under the age of 1 year – 2 times, in older children – 3 times a day.

    hypersensitivity to valproate; dysfunction of the liver and pancreas, hemorrhagic diathesis.

    possible nausea, vomiting, diarrhea, liver and pancreatic dysfunction, isolated stuporous state, ataxia, tremor, skin rash, angioedema, anemia, thrombocytopenia, prolonged bleeding time, leukopenia, rarely – alopecia, increased appetite, weight gain, amenorrhea and menstrual irregularities.

    children under 3 years of age have the highest risk of developing liver dysfunction when using valproate. During the first 6 months of treatment, it is necessary to regularly monitor liver function tests, blood composition and prothrombin level.

    Application during pregnancy – in 1–2% of cases, it can cause malformations of the neural tube in the fetus (meningocele, spina bifida). For women of reproductive age, treatment should not be interrupted; monotherapy is recommended in the minimum effective dose, distributed over several doses per day.

    valproic acid potentiates the action of antipsychotics, antidepressants; increases the concentration of barbiturates in blood plasma; reduces the total concentration of phenytoin, increasing the concentration of its free fraction. Anticonvulsants – inducers of microsomal liver enzymes (phenytoin, phenobarbital, carbamazepine) – reduce the concentration of valproic acid in the blood plasma.

    Clinical manifestations of acute massive overdose usually occur in the form of coma of varying degrees with muscle hypotonia, hyporeflexia, miosis and respiratory depression.Emergency care in a hospital should include gastric lavage (effective within 10-12 hours after taking the pills), osmotic diuresis, constant monitoring of the functions of the cardiovascular and respiratory systems. In severe cases, dialysis or exchange transfusion is indicated. There is only one report of the successful use of naloxone in acute valproic acid poisoning. In the event of a significant overdose, a lethal outcome is possible, however, in general, the prognosis for an overdose is favorable.

    Valproic acid (Acidum valproicum) (quantity): to pass the analysis to “HEMOCHELP”

    Valproic acid is an anticonvulsant drug. By inhibiting GABA-transferase, it increases the content of gamma-aminobutyric acid in the central nervous system, which leads to a decrease in the threshold of excitability and the level of convulsive readiness of the motor zones of the brain. It is used to treat various types of epilepsy in adults and children (large and small seizures, myoclonic, tonic-clonic and bipolar forms).It is prescribed for patients suffering from epilepsy, behavioral changes inherent in epilepsy, affective disorders, as well as in the treatment of manias, with febrile convulsions in children, children’s tics. Recently, the drug has been used for the prevention and treatment of migraine, neuropathic pain, behavior disorders with panic episodes, aggression. The antitumor activity of valproic acid, which is used in myelodysplastic syndromes and acute monocytic leukemia, has been shown.

    Valproic acid remains the gold standard for antiepileptic drugs used in childhood. It is metabolized in the liver and can cause liver damage, especially during the first 6 months after starting treatment. Therefore, before starting treatment with valproic acid, it is necessary to donate blood for laboratory tests to determine the level of liver enzymes, indicators of blood coagulation.

    Valproic acid is characterized by low toxicity; severe side effects can occur only during prolonged treatment.

    Synonyms of drugs: apilepsin, depakin, orfiril, konvulex.

    Research method: immunochemiluminescent analysis.

    Indication for the start:

    • Selection of the regimen for taking the drug
    • Appointment of valproic acid at a dose of more than 50 mg / kg / day.
    • Change in the dose of the drug (as well as 2 – 3 days after its administration)
    • Prevention of the toxic effect of the drug, the appearance of signs of toxicosis (depression of consciousness, disorientation, increased drowsiness, tachycardia, pulmonary edema, manifestations of pancreatitis and liver damage)
    • Renewal of epileptic seizures
    • Children in the first year of life for the purpose of dose control in connection with rapidly changing body weight
    • Monitoring of treatment in patients with chronic liver and kidney diseases
    • Control of drug concentration after prescribing or discontinuing other drugs of combined anticonvulsant therapy.
    • With a positive dynamics of the disease against the background of ongoing therapy, it is recommended to control the indicators 1-2 times a year.

    Reference values: 50 – 100 μg / ml.

    Reasons for an increase in the level of valproic acid:

    • Excess dosage, incorrect regimen of valproic acid preparation;
    • Acute poisoning with valproic acid preparations.
    • The toxic effect develops at concentrations above 100 μg / ml.

    Not earlier than 4 hours after the last meal. The sampling conditions are determined by the attending physician in accordance with the objectives of the study.

    Reasons for an increase in the level of valproic acid:
    Excess dosage, incorrect regimen of valproic acid preparation; Acute poisoning with valproic acid preparations.The toxic effect develops at concentrations above 100 μg / ml.

    Valproate preparations for the treatment of agitated behavior in people with dementia

    Relevance

    Agitated behavior is very common in advanced dementia. It can include verbal behavior such as yelling and physical behavior such as wandering or physical aggression. It has been shown to exacerbate the stress of caregivers, increase the risk of injury, and increase the need for people with dementia to be hospitalized.

    The type of medication used to treat agitated behavior in people with dementia is valproate, which is available in several different drugs (valproic acid, sodium divalproexate, sodium valproate, and hemi-sodium valproate). These medications are not recommended in these guidelines (for example, from the National Institute of Health and Medical Excellence), but are sometimes still prescribed for people with dementia to treat agitated behavior.

    Purpose of this review

    We wanted to review the evidence of how effective and safe it is to prescribe valproate to people with dementia to treat agitation.

    Studies included in this review

    We searched medical databases up to December 2017 for studies comparing any valproate to a placebo (dummy) for the treatment of agitated behavior in people diagnosed with dementia.

    We included five studies with 479 participants who had different types of dementia and agitated behavior. Most of the studies lasted six weeks, although one only lasted three weeks. The studies were generally well conducted, but the methods were not always fully described, and in one study there was a high risk of bias due to the large number of people dropping out of the valproate group.

    Highlights

    Studies have measured agitated behavior using a variety of scales, and the reliability of the evidence for the different scales ranged from moderate to very low.Overall, we found no evidence that valproate medications improved behavior or, in particular, agitated behavior. We found that valproate medications likely had little or no effect on participants’ ability to perform daily activities. We couldn’t be sure if they influenced cognition (thinking and remembering) because the reliability of the evidence was very low.

    In three studies, we found low reliability evidence that participants taking valproate were more likely to be injured than participants taking placebo.We couldn’t be as certain about the differences in terms of serious harm, such as events such as serious illness or hospitalization, but data from two studies showed that they may be more frequent in participants taking valproate. Some of the side effects associated with valproate were drowsiness, nausea, vomiting, watery stools, and urinary tract infections.

    Conclusions

    We found only five comparatively small studies to be included in this review.They differed in their methods, the type of drugs and their doses, the duration of treatment, and the scales used to measure. This limited the ability to combine data from all studies. However, we can be reasonably confident in the conclusion that valproate medications do not improve agitated behavior in dementia. They can also be associated with harmful effects.

    Depaken (valproic acid) Side effects, images, use, dosage, overdose in RxList

    • Generic Name: Valproic Acid
    • Brand Name: Depakene

    Information for Depakene Patients, Including Side Effects

    Brands: Depakone, Depakene, Sodium Valproate
    Generic Name: Valproic Acid (Oral / Injection)
    • What is Valproic Acid (Depacon, Depaken, Sodium Valproate)?
    • What are the possible side effects of Valproic Acid (Depacon, Depaken, Sodium Valproate)?
    • What is the most important information I should know about Valproic Acid (Depacon, Depaken, Sodium Valproate)?
    • What should I discuss with my doctor before taking valproic acid (Depacon, Depaken, Sodium Valproate)?
    • How do I take valproic acid (Depacon, Depaken, sodium valproate)?
    • What happens if I miss an appointment (Depacon, Depaken, Sodium Valproate)?
    • What happens if I overdose (Depacon, Depaken, Sodium Valproate)?
    • What should I avoid while taking valproic acid (Depacon, Depaken, sodium valproate)?
    • What other drugs will affect valproic acid (Depacon, Depaken, sodium valproate)?
    • Where can I get more information (Depacon, Depaken, Sodium Valproate)?

    What is Valproic Acid (Depacon, Depaken, Sodium Valproate)?

    Valproic acid is used to treat various types of seizure disorders.Valproic acid is sometimes used in conjunction with other anticonvulsants.

    Valproic acid is also used to treat manic episodes associated with bipolar disorder (manic depression) and to prevent migraines.

    Valproic acid may also be used for purposes not listed in this medication guide.

    What are the possible side effects of valproic acid (Depacon, Depaken, sodium valproate)?

    Get emergency medical help if you have signs of an allergic reaction (hives, difficulty breathing, swelling of the face or throat) or a serious skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and scaling).

    Get medical attention if you have a serious drug reaction that can affect many parts of your body. Symptoms may include: skin rash, fever, swollen glands, muscle pain, severe weakness, unusual bruising or yellowing of the skin or eyes.

    Call your doctor right away if someone taking this medicine has signs of liver or pancreas problems. such as: loss of appetite, pain in the upper stomach (which may spread to your back), ongoing nausea or vomiting, dark urine, swelling of the face, or jaundice (yellowing of the skin or eyes).

    Tell your doctor about any new or worsening symptoms. , for example: mood or behavior changes, depression, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), or thoughts of suicide or self-harm … …

    Call your doctor right away if you have any of these side effects:

    • confusion, tiredness, feeling cold, vomiting, mental change;
    • easy bruising, unusual bleeding (from nose, mouth, or gums), purple or red pinpoint spots under the skin;
    • severe drowsiness; or
    • exacerbation of seizures.

    Severe drowsiness is more likely in older people.

    Common side effects may include:

    • nausea, vomiting, abdominal pain, diarrhea;
    • dizziness, drowsiness, weakness;
    • Headache;
    • tremors, problems with walking or coordination;
    • blurred vision, double vision;
    • hair loss; or
    • change in appetite, weight gain.

    This is not a complete list of side effects and they may arise.Ask your doctor about side effects. You can report side effects to the FDA by calling 1-800-FDA-1088.

    What is the most important information I should know about valproic acid (Depacon, Depaken, Sodium Valproate)?

    Valproic acid can cause liver failure, which can be fatal, especially in children under 2 years of age and in people with liver problems caused by certain genetic disorders.

    p 4 yellow tablet street value

    You should not use valproic acid if you have liver disease, a urea cycle disorder, or a genetic disorder such as Alpers disease or Alpers-Hattenlocher syndrome.

    Do not start or stop taking this medication during pregnancy without consulting your doctor. This medicine may harm an unborn baby or cause birth defects, but seizures during pregnancy may harm both mother and baby.

    Do not use valproic acid to prevent migraines if you are pregnant.

    Call your doctor right away if someone taking this medicine has signs of liver or pancreas problems. such as: loss of appetite, pain in the upper stomach (which may spread to your back), ongoing nausea or vomiting, dark urine, swelling of the face, or jaundice (yellowing of the skin or eyes).

    Do not stop taking valproic acid without consulting your doctor. A sudden stop can cause a serious, life-threatening seizure.

    Information for Depakene patients, including how to take

    What should I discuss with my doctor before taking Valproic Acid (Depakone, Depakene, Sodium Valproate)?

    You should not use valproic acid if you are allergic to it or if you have:

    • liver disease;
    • K urea cycle disturbance; or
    • genetic mitochondrial disease (MYE-toe-KON-dree-al), such as Alpers disease or Alpers-Hattenlocher syndrome, especially in children under 2 years of age .

    Valproic acid can cause liver failure, which can be fatal, especially in children under 2 years of age and in people with liver problems caused by genetic mitochondrial disease.

    Tell your doctor if you have ever had:

    • liver problems caused by genetic mitochondrial disease;
    • depression, mental illness, or suicidal thoughts or actions;
    • family history of urea cycle disorder or unknown cause of infant death; or
    • HIV or CMV (cytomegalovirus) infection.

    Some young people have suicidal thoughts when they first take valproic acid. Your doctor should check your progress at regular visits. Your family or other caregivers should also be alert to changes in your mood or symptoms.

    The use of valproic acid during pregnancy may increase the risk of serious birth defects that may develop early in pregnancy. even before you know you are pregnant.Using this medication during pregnancy can also affect cognitive abilities (reasoning, intelligence, problem solving) later in your baby’s life. However, a seizure during pregnancy can harm both the mother and the baby.

    If you are taking valproic acid for seizures or manic episodes: The benefits of preventing these conditions may outweigh any risks associated with this medicine. There may be other medications that are safer to use during pregnancy. Do not start or stop taking valproic acid without the advice of your doctor.

    Can I drive while taking Vicodin?

    Do not use valproic acid to prevent migraines if you are pregnant or may become pregnant.

    If you are not pregnant, use effective contraception to prevent pregnancy while taking valproic acid. Tell your doctor if you start or stop using hormonal contraceptives that contain estrogen (birth control pills, injections, implants, skin patches, and vaginal rings).Estrogen can interact with valproic acid and reduce its effectiveness in preventing seizures.

    It may not be safe to breastfeed while using this medication. Ask your doctor about any risk.

    How do I take valproic acid (Depacon, Depaken, sodium valproate)?

    Follow all directions on the prescription label and read all medication guides or directions. Your doctor may change your dose from time to time. Use the medicine exactly as directed.

    Valproic acid oral is taken orally. Valproic Acid Injection is injected into a vein as an infusion. A healthcare professional will give you this injection if you are unable to take the medicine by mouth.

    Drink plenty of water while you are taking this medicine. You may need to change your dose if you are not getting enough fluids every day.

    Take with food if this medicine causes stomach upset.

    Measure liquid medicine with a special dosage spoon or medicine cup.If you do not have a dose measuring device, ask your pharmacist for one.

    Swallow capsule whole and do not crush, chew, break or open it.

    Tell your doctor if you notice a capsule shell in your stool that has not been absorbed or melted in the body. You may need to check your blood valproic acid levels.

    You may need frequent blood tests.

    If you need surgery, tell the surgeon ahead of time that you are taking valproic acid.

    In emergencies, carry or carry with you a medical ID to inform others that you are taking valproic acid.

    Toprol XL side effects in the long term

    Do not suddenly stop using valproic acid , even if you feel good. A sudden stop can cause a serious, life-threatening seizure. Follow your doctor’s instructions for dose reduction.

    Store at room temperature away from moisture and heat.

    Information for Depakene patients, including the missed dose

    What happens if I miss a dose (Depakone, Depakene, Sodium Valproate)?

    Take your medicine as soon as possible, but skip the missed dose if it is almost time for your next dose. Do not take two doses at a time.

    What happens if I overdose (Depacon, Depaken, Sodium Valproate)?

    Seek emergency medical attention or call the Poison Helpline at 1-800-222-1222.

    What should I avoid while taking valproic acid (Depacon, Depaken, sodium valproate)?

    Drinking alcohol may increase some of the side effects of valproic acid.

    Avoid driving or hazardous activities until you know how this medicine will affect you. Your reactions may be disturbed.

    What other drugs will affect valproic acid (Depacon, Depaken, sodium valproate)?

    It is sometimes unsafe to take certain medications at the same time. Some medicines can affect the blood levels of other medicines you take, which may increase side effects or make medicines less effective.

    Many drugs can affect valproic acid. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed here. Tell your doctor about all of your current medicines and any medicines you start or stop using.

    Where can I get more information (Depacon, Depaken, Sodium Valproate)?

    Your pharmacist can provide more information about valproic acid.


    Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medicine only as directed. Every effort has been made to ensure that the information provided by Cerner Multum, Inc. is accurate, up-to-date and complete.(“Multum”), but no guarantees are given. The information contained herein about the drug may vary over time. Multum’s information has been collected for use by medical practitioners and consumers in the United States, and therefore Multum does not warrant that use outside the United States is appropriate unless specifically noted otherwise. Multum’s Medication Information does not recommend medication, patient diagnosis, or recommend therapy.Multum’s Drug Information is an information resource designed to help licensed medical practitioners care for their patients and / or serve consumers who see this service as an addition to the experience, skills, knowledge and judgment of medical practitioners, not a replacement. The absence of a warning for a given drug or drug combination should in no way be construed as an indication that the drug or drug combination is safe, effective, or appropriate for any given patient.Multum assumes no responsibility for any aspect of health care that is governed by the information Multum provides. The information contained in this document is not intended to cover all possible uses, indications, precautions, warnings, drug interactions, allergic reactions or side effects. If you have questions about any medications you are taking, ask your doctor, nurse, or pharmacist.

    Copyright 1996-2019 Cerner Multum, Inc.

    90,000 💊 Depaken (valproic acid) side effects, interactions, uses and medicines

    Trademarks: Depakene

    Generic Name: Valproic Acid

    What is Valproic Acid (Depaken)?

    Valproic acid affects chemicals in the body that can cause seizures.

    Valproic acid is used to treat various types of seizures. Valproic acid is sometimes used in conjunction with other anticonvulsants.

    Valproic acid is also used to treat manic episodes associated with bipolar disorder (manic depression) and to prevent migraines.

    Valproic Acid may also be used for purposes not listed in this medication guide.

    white embossed capsule VALPROIC 250

    white capsule with the inscription US 250

    white, imprinted VALPROIC 250-0364

    capsule white with embossing VALPROIC 250-0364

    white, embossed LOGO 2120

    oval, white, with logo 2120

    What are the possible side effects of valproic acid (Depaken)?

    Seek emergency medical attention if you have signs of an allergic reaction (hives, difficulty breathing, swelling of the face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or a purplish skin rash with blistering and scaling).

    Call your doctor right away if someone taking this medicine has signs of liver or pancreas problems, such as: loss of appetite, pain in the upper abdomen (which may spread to the back), ongoing nausea or vomiting, dark urine, facial swelling, or jaundice (yellowing of the skin or eyes).

    Tell your doctor about any new or worsening symptoms , such as: mood or behavior changes, depression, anxiety, panic attacks, sleep problems, or if you feel impulsivity, irritability, agitation, hostility, aggressiveness, anxiety, hyperactivity (mentally or physically) or thoughts of suicide or self-harm.

    Call your doctor right away if you have any of these other side effects:

    • Confusion, fatigue, feeling cold, vomiting, change in your mental state;
    • easy bruising, unusual bleeding (nose, mouth, or gums), purple or red pinpoint spots under the skin;
    • severe drowsiness;
    • exacerbation of seizures; or
    • signs of inflammation in your body – swollen glands, flu symptoms, severe tingling or numbness, muscle weakness, chest pain, new or worsening cough with fever, trouble breathing.

    Common side effects may include:

    • nausea, vomiting, abdominal pain, diarrhea;
    • dizziness, drowsiness, weakness;
    • Headache;
    • 90,039 tremors, trouble walking or coordination;

    • blurred vision, double vision;
    • hair loss; or
    • appetite changes, weight gain.

    This is not a complete list of side effects and others may occur.Ask your doctor about side effects. You can report side effects to the FDA at 1-800-FDA-1088.

    What is the most important information I should know about valproic acid (Depaken)?

    Valproic acid can cause liver failure, which can be fatal, especially in children under 2 years of age and in people with liver problems caused by certain genetic disorders.

    You should not use valproic acid if you have liver disease, a urea cycle disorder, or a genetic disorder such as Alpers disease or Alpers-Hattenlocher syndrome.

    Follow your doctor’s instructions for taking this medicine if you are pregnant. Valproic acid may harm an unborn baby, but seizures during pregnancy can harm both mother and baby. The benefit of preventing seizures may outweigh any risks to the baby.

    Do not use valproic acid to prevent migraines if you are pregnant.

    Call your doctor right away if someone taking this medicine has signs of liver or pancreas problems, such as: loss of appetite, pain in the upper abdomen (which may spread to the back), ongoing nausea or vomiting, dark urine, facial swelling, or jaundice (yellowing of the skin or eyes).

    Do not stop using valproic acid without consulting your doctor. Sudden stopping can cause severe, life-threatening seizures.

    What should I discuss with my doctor before taking valproic acid (Depaken)?

    You should not use valproic acid if you are allergic to it or if you have:

    • liver disease;
    • violation of the urea cycle; or
    • a genetic mitochondrial (MYE-toe-KON-dree-al) disorder such as Alpers disease or Alpers-Hattenlocher syndrome, especially in a child under 2 years old .

    Valproic acid can cause liver failure, which can be fatal, especially in children under 2 years of age and in people with liver problems caused by a genetic disorder of mitochondria.

    Tell your doctor if you have ever had:

    • liver problems caused by a genetic disorder of mitochondria;
    • depression, mental illness, or suicidal thoughts or actions;
    • family history of urea cycle disorder or infant mortality with unknown cause; or
    • HIV or CMV (cytomegalovirus) infection.

    Some young people have suicidal thoughts when they first take valproic acid. Your doctor should check your progress at regular visits. Your family or other caregivers should also be alert to changes in your mood or symptoms.

    Do not use valproic acid to prevent migraines if you are pregnant.

    If you are taking valproic acid for seizures or manic episodes: This medicine may harm the unborn baby and affect cognitive abilities (reasoning, intelligence, problem solving) later in the baby’s life.However, seizures during pregnancy can harm both the mother and the baby. Do not start or stop taking this medicine during pregnancy without consulting your doctor.

    Use effective birth control while using valproic acid and tell your doctor right away if you become pregnant. Tell your doctor if you start or stop using hormonal contraception that contains estrogen (birth control pills, injections, implants, skin patches, and vaginal rings).Estrogen can interact with valproic acid and make it less effective in preventing seizures.

    Seizure control is very important during pregnancy. The benefit of preventing seizures may outweigh any risks associated with taking valproic acid. There may be other seizure medications that are safer to use during pregnancy. Follow your doctor’s instructions for taking valproic acid while you are pregnant.

    It may not be safe to breastfeed while using this medication.Ask your doctor about any risk.

    How should I take valproic acid (depaken)?

    Follow all directions on the prescription label and read all medication manuals or instructions. Your doctor may occasionally change your dose. Use the medicine exactly as directed.

    Drink plenty of water while you are taking this medicine. Your dose may need to be changed if you are not getting enough fluids every day.

    Take with food if this medicine upsets your stomach.

    Measure out liquid medicine with a special dosage spoon or medicine cup. If you do not have a dispenser, ask your pharmacist for one.

    Swallow Extended-Release Capsule whole and do not crush, chew, break, or open it.

    You may need frequent blood tests.

    When absolutely necessary, wear or carry a medical identification to let others know you are using valproic acid.

    If you need surgery, tell the surgeon ahead of time that you are using valproic acid.

    Do not suddenly stop using valproic acid , even if you feel good. A sudden stop can cause a serious, life-threatening type of seizure. Follow your doctor’s instructions to reduce the dose.

    Store at room temperature away from moisture and heat.

    What happens if I miss a dose (Depaken)?

    Take the medicine as soon as possible, but skip the missed dose if it is almost time for the next dose. Do not take two doses at a time.

    What happens if I overdose (Depaken)?

    Seek emergency medical attention or call the Poison Helpline at 1-800-222-1222.

    What should I avoid while taking valproic acid (Depaken)?

    Drinking alcohol may increase certain side effects of valproic acid.

    Avoid driving or hazardous activities until you know how this medication will affect you.Your reactions may be disturbed.

    Valproic acid can make your sunburn easier. Avoid sun exposure or tanning beds. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

    What other drugs will affect valproic acid (Depaken)?

    Sometimes it is not safe to take certain medications at the same time. Some medicines can affect the blood levels of other medicines you take, which may increase side effects or make medicines less effective.

    Many drugs can affect valproic acid. This includes prescription and over-the-counter medicines, vitamins and herbal products. Not all possible interactions are listed here. Tell your doctor about all of your current medicines and any medicines you start or stop using.

    Your pharmacist can provide more information on valproic acid.

    How to take antiepileptic drugs (AEDs)

    General

    Antiepileptic drugs (AEDs) reduce the excess excitability of brain cells, preventing the development of epileptic seizures.The effect of AEDs depends on their concentration in the blood, so the drug should be taken daily. Most modern AEDs need to be taken 2 times a day (morning and evening) so that their blood concentration remains stable.

    How to increase the dose of the drug?

    The slower the dose is escalated, the lower the risk of side effects. Usually they start with ½ or 1 tablet in the evening, after a few days add ½ or 1 tablet in the morning, and so on, bringing the dose to therapeutic.

    What to do if I miss a dose?

    For such cases, drugs have been developed that must be taken 2 times a day.If you forget to take your morning dose and remember it after a few hours – feel free to take it. If you remembered the forgotten dose only in the evening, do not drink the morning + evening dose. Drink only in the evening and do not forget to take the drug again.

    How do I remember to take the drug?

    It is necessary to “tie” the intake of the drug to regular events in life, for example: after breakfast and after dinner, after morning and evening walks with the dog, after morning and evening washing.You can use reminders on your mobile phone. If the patient suffers from impaired memory and thinking, relatives should monitor the medication intake. We recommend keeping a seizure diary every day and recording each medication intake.

    How to take medication: before or after meals?

    This is not important for modern drugs. However, some of the AEDs can irritate the stomach, so we usually recommend taking it after meals.

    How to exchange one drug for another?

    The most important rule is to do everything gradually.In most cases, at first, the dose of the “new” drug is gradually increased, then the dose of the “old” drug is also gradually reduced.

    How to replace a drug with its analogue of another manufacturer (after all, the active substance is the same there)?

    A universal rule – if the body is accustomed to a certain drug of a certain company, then it is better not to change it. However, if there is no other choice (they stopped giving the drug for free and offer a substitute, but there is no money to buy the old drug), then it is necessary to gradually replace the “old” tablets with “new” ones.If you abruptly quit the “old” ones and start drinking the “new” ones, the risk of developing seizures and side effects is higher.

    How hazardous are AEDs to health?

    Unfortunately, there are no absolutely safe drugs. In the world, 80% of patients taking AEDs report some side effects. The more modern the drug, the more side effects are indicated in its instructions for use (the manufacturer indicates them so that it cannot be sued). Side effects can be divided into 3 groups:

    A) Reactions of idiosyncrasy (individual intolerance).They develop in the first months after starting the medication. Most often – skin rash, jaundice, severe abdominal pain, bleeding, severe vomiting (there may be other manifestations). Idiosyncrasy manifests itself suddenly, it is impossible to predict it in advance. At risk are patients who have previously had severe adverse reactions to any drugs. If, after starting to take the medication, any serious disorders appear, you must immediately stop taking it and consult a doctor.

    B) Dose-related side effects (they are not present at small doses, but they appear at large doses).Typical examples: drowsiness, double vision, unsteadiness when walking, lethargy, trembling hands, etc. It is not necessary to cancel the drug immediately, the tactics depend on the severity of the side effects and the effectiveness of the drug (if the side effects are weak and there are no seizures, you will most likely have to put up with them, if the side effects are strong, but the seizures continue anyway, there is no point in taking the drug). Often, over time, the body “gets used” to such side effects and their severity decreases.

    B) Chronic side effects – occur with prolonged use of AED (thickening of the gingival mucosa, weight gain or decrease, hormonal disorders, hearing or vision loss, etc.)). In some cases, after discontinuation of the drug, these side effects may disappear (for example, weight gain or weight loss), in other cases, these side effects are irreversible.

    However, prescribing AED is the main treatment for epilepsy worldwide, because epileptic seizures in most cases pose a greater health threat than taking AEDs.