Side effects of oxcarbazepine 150 mg. Oxcarbazepine 150 mg: Comprehensive Guide to Side Effects, Uses, and Dosage
What are the common side effects of oxcarbazepine 150 mg. How does oxcarbazepine work for treating seizures. What precautions should be taken when using oxcarbazepine. What are the serious side effects to watch out for with oxcarbazepine.
Understanding Oxcarbazepine: An Antiepileptic Medication
Oxcarbazepine is a prescription medication belonging to the class of antiepileptic drugs. It is primarily used to treat partial seizures in individuals with epilepsy. Available in various forms, including oral extended-release tablets, immediate-release tablets, and suspension, oxcarbazepine is marketed under brand names such as Trileptal and Oxtellar XR, as well as in generic form.
The exact mechanism of action for oxcarbazepine is not fully understood. However, it is believed to work by blocking sodium channels in the brain, which helps prevent seizures from spreading. Additionally, it may influence potassium and calcium levels in the brain to control seizure activity.
Common Side Effects of Oxcarbazepine 150 mg
While oxcarbazepine can be an effective treatment for partial seizures, it’s important to be aware of potential side effects. The most common side effects associated with oxcarbazepine 150 mg include:
- Dizziness
- Drowsiness
- Nausea
- Vomiting
- Vision problems (double vision, blurred vision)
- Trembling
- Coordination issues
For immediate-release tablets, additional side effects may include:
- Skin rash
- Increased risk of infections (especially in children)
- Stomach pain
- Upset stomach
Extended-release tablets may also cause:
- Headaches
- Weakness
Serious Side Effects and Precautions
While less common, oxcarbazepine can cause serious side effects that require immediate medical attention. These include:
Low Sodium Levels
How can you recognize low sodium levels caused by oxcarbazepine? Symptoms may include nausea, tiredness, lack of energy, headache, confusion, and an increase in seizure frequency or severity. If you experience these symptoms, contact your healthcare provider promptly.
Allergic Reactions and Multi-Organ Hypersensitivity
In rare cases, oxcarbazepine can cause severe allergic reactions or multi-organ hypersensitivity. Signs to watch for include:
- Persistent fever, swollen glands, or sore throat
- Skin rash
- Swelling of the face, eyes, lips, or tongue
- Difficulty swallowing or breathing
- Hives
- Painful sores in the mouth or around the eyes
- Yellowing of the skin or eyes
Serious Skin Reactions
Oxcarbazepine may cause life-threatening allergic reactions known as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These conditions can cause severe damage to the skin and internal organs. Individuals of Asian ancestry with a specific genetic risk factor (HLA-B*1502 allele) may be at higher risk for these reactions.
Dosage and Administration of Oxcarbazepine
The dosage of oxcarbazepine 150 mg will vary depending on individual factors such as age, weight, and the severity of the condition being treated. It’s crucial to follow your doctor’s instructions carefully when taking this medication.
Immediate-Release vs. Extended-Release Formulations
How do immediate-release and extended-release tablets differ in their use? Immediate-release tablets may be used alone or in combination with other medications to treat seizures. Extended-release tablets, on the other hand, are always used as part of a combination therapy with other anti-seizure medications.
Gradual Dosage Adjustments
Can you stop taking oxcarbazepine suddenly? It’s important not to abruptly discontinue oxcarbazepine unless instructed by your doctor. Sudden cessation can lead to more severe seizures. If your doctor decides to stop your treatment, they will gradually reduce your dosage to minimize the risk of increased seizure activity.
Drug Interactions and Precautions
Oxcarbazepine can interact with other medications, potentially affecting their efficacy or increasing the risk of side effects. It’s crucial to inform your healthcare provider about all medications, supplements, and herbal products you are taking.
Potential Drug Interactions
Which medications may interact with oxcarbazepine? Some common interactions include:
- Other antiepileptic drugs
- Oral contraceptives
- Calcium channel blockers
- Certain antidepressants
Special Precautions
Are there specific groups that should exercise caution when using oxcarbazepine? Particular care should be taken in the following cases:
- Pregnancy and breastfeeding
- Elderly patients
- Individuals with kidney or liver problems
- Those with a history of allergic reactions to carbamazepine
Monitoring and Follow-up Care
Regular monitoring is essential when taking oxcarbazepine to ensure its effectiveness and minimize potential side effects. Your healthcare provider may recommend periodic blood tests to check sodium levels and liver function.
Seizure Diary
How can you help your doctor assess the effectiveness of oxcarbazepine? Keeping a seizure diary can be invaluable. Record the frequency, duration, and intensity of seizures, as well as any side effects you experience. This information can help your doctor make informed decisions about your treatment plan.
Regular Check-ups
Attending scheduled follow-up appointments is crucial for managing your epilepsy effectively. These visits allow your doctor to assess your response to the medication, adjust dosages if necessary, and address any concerns you may have.
Lifestyle Considerations While Taking Oxcarbazepine
Taking oxcarbazepine may require some lifestyle adjustments to ensure your safety and optimize treatment outcomes.
Driving and Operating Machinery
Oxcarbazepine can cause drowsiness and slow down your thinking and reaction time. It’s advisable to avoid driving, using machinery, or engaging in activities that require alertness until you know how the medication affects you.
Alcohol Consumption
Is it safe to drink alcohol while taking oxcarbazepine? Alcohol can increase the sedative effects of oxcarbazepine and may also increase the risk of seizures. It’s best to avoid alcohol or consult your doctor about safe limits.
Sun Protection
Oxcarbazepine may increase your skin’s sensitivity to sunlight. Take precautions such as wearing protective clothing and using sunscreen when outdoors.
Patient Education and Support
Education plays a crucial role in managing epilepsy effectively. Understanding your condition, treatment options, and potential side effects can empower you to take an active role in your healthcare.
Support Groups
Joining epilepsy support groups can provide valuable emotional support and practical advice. These groups offer opportunities to connect with others facing similar challenges and share experiences and coping strategies.
Epilepsy Action Plans
Working with your healthcare provider to develop an epilepsy action plan can be beneficial. This plan should outline steps to take during a seizure, emergency contact information, and any specific instructions related to your treatment.
Oxcarbazepine 150 mg can be an effective treatment for partial seizures in individuals with epilepsy. However, it’s essential to be aware of potential side effects, follow dosage instructions carefully, and maintain open communication with your healthcare provider. By staying informed and vigilant, you can maximize the benefits of this medication while minimizing risks.
Side Effects, Dosage, Uses, and More
Highlights for oxcarbazepine
- Oxcarbazepine oral tablet is available as brand-name drugs and as a generic drug. Brand names: Trileptal and Oxtellar XR.
- Oxcarbazepine comes as an oral extended-release tablet, immediate-release tablet, and suspension.
- Oxcarbazepine oral tablet is used to treat a type of seizure, called a partial seizure, in people with epilepsy.
- Serious skin reactions: This drug may cause life-threatening allergic reactions. These are called Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These reactions may cause severe damage to your skin or internal organs. Your risk may be higher if you have Asian ancestry with a genetic risk factor. Your doctor may test you to see if you have the HLA-B*1502 allele. If your results from this test are positive, you may be at risk for developing these serious skin reactions. However, you can still have these reactions without the genetic risk factor. Call your doctor right away if you have any of these symptoms while taking this drug:
- skin rash
- hives
- sores in your mouth
- blistering or peeling of your skin
- Suicidal thoughts: This drug may increase your risk of suicidal thoughts. Your risk may be higher if you already have a mood disorder, such as depression or anxiety. Call your doctor right away if you have any of these symptoms, especially if they are new or worse, or if they worry you:
- thoughts about suicide or dying
- attempts to commit suicide
- new or worsened depression
- new or worsened anxiety
- feeling agitated or restless
- panic attacks
- new or worsened irritability
Oxcarbazepine is a prescription drug. It comes as an oral extended-release tablet, immediate-release tablet, and suspension.
Oxcarbazepine oral tablet is available as the brand-name drugs Trileptal and Oxtellar XR. It’s also available as a generic drug. Generic drugs usually cost less than the brand-name version. In some cases, they may not be available in every strength or form as the brand-name drug.
The immediate-release tablet may be used alone or as part of a combination therapy with other medications to treat seizures. The extended-release tablet is always used with other medications.
Why it’s used
Oxcarbazepine is used to treat partial seizures in people with epilepsy.
Don’t suddenly stop this drug
- Don’t suddenly stop taking this drug unless your doctor tells you to. Doing so may cause you to have more severe seizures. If your doctor is stopping your treatment with oxcarbazepine, your dosage will be slowly lowered to reduce your risk of having more seizures.
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How it works
Oxcarbazepine belongs to a class of drugs called antiepileptic medications. A class of drugs is a group of medications that work in a similar way. These drugs are often used to treat similar conditions.
It isn’t known exactly how this drug works to stop seizures. It may block sodium channels to stop seizures from spreading to the rest of the brain. It may also act on potassium and calcium in the brain to stop seizures.
Oxcarbazepine oral tablet may cause drowsiness. It can also slow your thinking and reaction time. You shouldn’t drive, use machinery, or do similar tasks that require alertness until you know how this drug affects you.
This drug can also cause other side effects.
More common side effects
The more common side effects of oxcarbazepine depend on the drug form.
- Side effects for all forms of the drug include:
- dizziness
- sleepiness
- nausea
- vomiting
- eye problems, such as double vision, blurred vision, or cataracts
- trembling
- problems with walking and coordination (unsteadiness)
- Oxcarbazepine immediate-release tablets may also cause the following:
- skin rash
- infections, especially in children
- stomach pain
- upset stomach
- Oxcarbazepine extended-release tablets may also cause the following:
- headache
- weakness
If these effects are mild, they may go away within a few days or a couple of weeks. If they’re more severe or don’t go away, talk to your doctor or pharmacist.
Serious side effects
Call your doctor right away if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency. Serious side effects and their symptoms can include the following:
- Low sodium levels in your blood. Symptoms can include:
- nausea
- tiredness
- lack of energy
- headache
- confusion
- more frequent or more severe seizures
- Allergic reactions or serious problems (multi-organ hypersensitivity) that affect your organs and other parts of your body, such as the liver or blood cells. Symptoms can include:
- fever, swollen glands, or sore throat that don’t go away or that come and go
- skin rash
- swelling of your face, eyes, lips, or tongue
- trouble swallowing or breathing
- hives
- painful sores in your mouth or around your eyes
- yellowing of your skin or the whites of your eyes
- unusual bruising or bleeding
- severe tiredness or weakness
- severe muscle pain
- frequent infections or infections that don’t go away
- Suicidal thoughts or actions. Symptoms can include:
- thoughts about suicide or dying
- attempts to commit suicide
- new or worsened depression
- new or worsened anxiety
- feeling agitated or restless
- panic attacks
- trouble sleeping (insomnia)
- new or worsened irritability
- anger
- acting aggressive or violent
- acting on dangerous impulses
- an extreme increase in activity and talking (mania)
- other unusual changes in behavior or mood
- Serious skin reactions. Oxcarbazepine may cause life-threatening allergic skin reactions. These are called Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These may cause severe damage to your skin and internal organs. Your risk may be higher if you have Asian ancestry with a genetic risk factor. If you’re Asian, your doctor may test you for this genetic factor. You can still have these reactions without the genetic risk factor. Call your doctor right away if you have any of these symptoms:
- skin rash
- hives
- sores in your mouth, nose, or eyes
- blistering or peeling of your skin
- Serious blood disorders. Oxcarbazepine may cause a decrease in all types of blood cells, or just white blood cells. Symptoms can include:
- bruising more easily
- bleeding from your nose, or your gums after brushing your teeth
- blood in your urine
- blood in your stool, which may appear either bright red or dark and tarry
- increased infections
- longer illnesses as compared to normal
- tiredness
Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this information includes all possible side effects. This information is not a substitute for medical advice. Always discuss possible side effects with a healthcare provider who knows your medical history.
Oxcarbazepine oral tablet can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.
To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.
Examples of drugs that can cause interactions with oxcarbazepine are listed below.
Oral birth control pills
Taking oxcarbazepine with oral birth control pills makes the pills less effective. This means you may get pregnant even though you’re taking birth control pills. You should use a second form of birth control while you’re taking oxcarbazepine, such as a condom. Examples of these oral birth control pills include:
- birth control pills that contain ethinylestradiol
- birth control pills that contain levonorgestrel
Parkinson’s disease drugs
Transdermal selegiline can not be taken with oxcarbazepine. Taking them together could lead to side effects that could be life-threatening. These side effects include a high blood pressure crisis, seizures, coma, or heart collapse.
Seizure drugs
Taking oxcarbazepine with phenytoin increases phenytoin levels in your blood. This raises your risk of side effects from phenytoin. Your doctor may decrease your dosage of phenytoin if you take it with oxcarbazepine.
Certain seizure drugs decrease the level of oxcarbazepine in your body. If you take oxcarbazepine with these drugs, oxcarbazepine may not work as well to treat your seizures. Your doctor may increase your dosage of oxcarbazepine if you take it with these drugs. Examples of these drugs include:
- carbamazepine
- phenobarbital
Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.
This drug comes with several warnings.
Allergy warning
Many people who are allergic to carbamazepine are also allergic to this drug. Tell your doctor if you’re allergic to carbamazepine.
Oxcarbazepine may cause allergic reactions. Symptoms can include:
- swelling of your face, eyes, lips, or tongue
- painful sores in the mouth or nose, or around the eyes
- trouble swallowing or breathing
- skin rash
- hives
If you develop these symptoms, call 911 or go to the nearest emergency room.
Don’t take this drug again if you’ve ever had an allergic reaction to it. Taking it again could be fatal (cause death).
Alcohol interaction warning
You shouldn’t drink alcohol while taking oxcarbazepine. Alcohol can worsen certain side effects from the drug, such as sleepiness or dizziness.
Warnings for people with certain health conditions
For people with liver problems: Your doctor won’t need to change your oxcarbazepine dosage if you have mild or moderate liver problems. If you have severe liver problems, your doctor may monitor your oxcarbazepine usage more closely.
For people with kidney problems: This drug is removed from your body by your kidneys. If you have severe kidney damage (creatinine clearance less than 30 mL/minute), your doctor may give you a lower dosage, and increase the dosage slowly. This can help prevent too much of the drug from building up in your body and causing side effects.
Warnings for other groups
For pregnant women: This drug is a category C pregnancy drug. That means two things:
- Research in animals has shown adverse effects to the fetus when the mother takes the drug.
- There haven’t been enough studies done in humans to be certain how the drug might affect the fetus.
Tell your doctor if you’re pregnant or plan to become pregnant. This drug should be used during pregnancy only if the potential benefit justifies the potential risk.
For women who are breastfeeding: This drug passes into breast milk and can cause serious effects in a child who is breastfed. You and your doctor may need to decide if you’ll take this drug or breastfeed.
When to call the doctor
- Call your doctor if your seizures get worse or if you have any new types of seizures while taking this drug.
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For seniors: As you age, your kidneys may not work as well as they once did. Your body may process this drug more slowly. Your doctor may start you on a lowered dosage so that too much of this drug doesn’t build up in your body. Or they may prescribe a different drug to treat your seizures. Too much of the drug in your body can be dangerous. Your kidney function (creatinine clearance) should be checked before you start taking this drug.
All possible dosages and forms may not be included here. Your dose, form, and how often you take it will depend on:
- your age
- the condition being treated
- how severe your condition is
- other medical conditions you have
- how you react to the first dose
Drug forms and strengths
Generic: Oxcarbazepine
- Form: oral immediate-release tablet
- Strengths: 150 mg, 300 mg, 600 mg
Brand: Trileptal
- Form: oral immediate-release tablet
- Strengths: 150 mg, 300 mg, 600 mg
Brand: Oxtellar XR
- Form: oral extended-release tablet
- Strengths: 150 mg, 300 mg, 600 mg
Dosage for seizures (epilepsy)
Immediate-release tablets
Adult dosage (ages 17–64 years)
- When taking oxcarbazepine alone to treat seizures:
- The maximum dosage is 1,200 mg taken by mouth two times per day.
- Your doctor may have you start with 300 mg taken two times per day. Your doctor may then increase your total daily dosage by 300 mg every 3 days to a dosage of 1,200 mg/day (600 mg two times per day).
- When taking oxcarbazepine with other medications to treat seizures:
- The maximum dosage is 600 mg taken by mouth two times per day.
- Start with 300 mg taken two times per day. Each week, your doctor may increase your total daily dosage by no more than 600 mg.
- If you’re taking dosages over 1,200 mg per day, you doctor should monitor you closely for side effects during dosage increases.
- When switching from another seizure medication to oxcarbazepine alone:
- The maximum dosage is 1,200 mg taken by mouth two times per day.
- You may start with 300 mg of oxcarbazepine taken twice per day. At the same time, your doctor may start to reduce the dosage of your other seizure drug(s). It may take three to six weeks to be completely off your other seizure drug(s). Your doctor should monitor you closely during this overlapping time period.
- Each week, your doctor may increase your total daily dosage by no more than 600 mg.
Child dosage (ages 4–16 years)
Your child’s dosage will be based on their weight. It will also be based on whether they’re switching from one seizure medication to another.
Child dosage (ages 2–3 years)
Your child’s dosage will be based on their weight.
Child dosage (ages 0–1 year)
This drug is not recommended for children younger than 2 years.
Senior dosage (ages 65 years and older)
Oxcarbazepine is removed from your body through your kidneys. As you age, your kidneys may not work as well as they used to. If you have kidney problems, your doctor may start you at half of the standard starting dosage (300 mg per day) and increase your dosage slowly.
Extended-release tablets
Adult dosage (ages 18–64 years)
- When taking this drug with other medications to treat seizures:
- The recommended dosage is 1,200–2,400 mg taken by mouth once per day.
- Each week, your doctor may increase your total daily dosage by no more than 600 mg.
Child dosage (ages 6–17 years)
Your child’s dosage will be based on their weight.
Child dosage (ages 0–5 years)
This drug is not recommended for children younger than 6 years.
Senior dosage (ages 65 years and older)
Your doctor may want to start at a lower dosage (300 mg or 450 mg per day). Your doctor may increase your dosage each week by 300–450 mg per day until you’re at a dosage that’s working to control your seizures.
Special dosage considerations
People with kidney problems: If you have severe kidney damage (creatinine clearance less than 30 mL/minute), your doctor may start you at half of the usual starting dosage of the immediate-release tablet (300 mg per day) and increase it slowly.
For the extended-release tablet, your doctor may increase your dosage once per week by 300–450 mg per day until the dosage is working for you.
Dosage warnings
- If you’re using higher doses (higher than 1,200 mg per day) of the immediate-release tablets, your doctor should monitor you closely during dosage increases.
- Your dosage will decrease as you age since your body gets rid of the drug more slowly as you age.
- If your doctor wants to switch you from immediate-release tablets (Trileptal) to the extended-release form (Oxtellar XR), you may need a higher dosage.
Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this list includes all possible dosages. This information is not a substitute for medical advice. Always talk to your doctor or pharmacist about dosages that are right for you.
Oxcarbazepine is used for long-term treatment. It comes with serious risks if you don’t take it as prescribed.
If you stop taking the drug suddenly or don’t take it at all: This may cause serious problems, such as having more seizures, or seizures that don’t stop.
If you miss doses or don’t take the drug on schedule: Your medication may not work as well or may stop working completely. For this drug to work well, a certain amount needs to be in your body at all times.
If you take too much: Your doctor will treat any symptoms you’re having. These could include tremors, lack of coordination, double vision or trouble seeing, drowsiness, slowed heart rate, or coma.
If you think that you’ve taken too much of this drug, call your doctor or local poison control center. If the symptoms are severe, call 911 or go to the nearest emergency room right away.
What to do if you miss a dose: If you forget to take your dose, take it as soon as you remember. If it’s just a few hours until the time for your next dose, wait and only take one dose at that time. Never try to catch up by taking two doses at once. This could cause dangerous side effects.
How to tell this drug is working: You should have fewer seizures.
Keep these considerations in mind if your doctor prescribes oxcarbazepine for you.
General
- Take the extended-release form without food. If you don’t take these tablets on an empty stomach, you may be more likely to have side effects. Food causes higher levels of the medication to build up in your blood.
- The immediate-release tablet can be taken with or without food.
- Take the extended-release form one time per day. Take it at least 1 hour before or 2 hours after a meal.
- Don’t cut, crush, or chew the extended-release tablets.
Storage
- Store oxcarbazepine at room temperature between 59°F and 86°F (15°C and 30°C).
- Don’t freeze oxcarbazepine.
- Keep it away from light.
- Don’t store this medication in moist or damp areas, such as bathrooms.
Travel
When traveling with your medication:
- Always carry your medication with you. When flying, never put it into a checked bag. Keep it in your carry-on bag.
- Don’t worry about airport X-ray machines. They can’t harm your medication.
- You may need to show airport staff the pharmacy label for your medication. Always carry the original prescription-labeled container with you.
- Don’t put this medication in your car’s glove compartment or leave it in the car. Be sure to avoid doing this when the weather is very hot or very cold.
Clinical monitoring
Before starting and during your treatment with oxcarbazepine, your doctor will check your:
- kidney function
- liver function
- sodium levels
- complete blood count
- thyroid function
You and your doctor should also watch for the following:
- seizure frequency
- serious skin reactions
- suicidal thoughts and behaviors
There are other drugs available to treat your condition. Some may be better suited for you than others. Talk to your doctor about other drug options that may work for you.
Disclaimer: Healthline has made every effort to make certain that all information is factually correct, comprehensive, and up-to-date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or other healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses./span>
Oxcarbazepine Oral Tablet 150 mg
Uses
This medicine is used for the following purposes:
- nerve pain
- seizures
Instructions
This medicine may be taken with or without food.
It is very important that you take the medicine at about the same time every day. It will work best if you do this.
Store at room temperature in a dry place. Do not keep in the bathroom.
Keep the medicine away from heat and light.
It is important that you keep taking each dose of this medicine on time even if you are feeling well.
If you forget to take a dose on time, take it as soon as you remember. If it is almost time for the next dose, do not take the missed dose. Return to your normal dosing schedule. Do not take 2 doses of this medicine at one time.
Please tell your doctor and pharmacist about all the medicines you take. Include both prescription and over-the-counter medicines. Also tell them about any vitamins, herbal medicines, or anything else you take for your health.
Do not suddenly stop taking this medicine. Check with your doctor before stopping.
This medicine may decrease the effectiveness of some birth controls which use hormones (such as birth control pills and patches). Use an extra form of birth control, such as condoms, while on this medicine.
It is very important that you follow your doctor’s instructions for all blood tests.
It is very important that you keep all appointments for medical exams and tests while on this medicine.
Cautions
Tell your doctor and pharmacist if you ever had an allergic reaction to a medicine. Symptoms of an allergic reaction can include trouble breathing, skin rash, itching, swelling, or severe dizziness.
Do not use the medication any more than instructed.
Your ability to stay alert or to react quickly may be impaired by this medicine. Do not drive or operate machinery until you know how this medicine will affect you.
Please check with your doctor before drinking alcohol while on this medicine.
Family should check on the patient often. Call the doctor if patient becomes more depressed, has thoughts of suicide, or shows changes in behavior.
Call the doctor if there are any signs of confusion or unusual changes in behavior.
Tell the doctor or pharmacist if you are pregnant, planning to be pregnant, or breastfeeding.
Ask your pharmacist if this medicine can interact with any of your other medicines. Be sure to tell them about all the medicines you take.
Do not start or stop any other medicines without first speaking to your doctor or pharmacist.
Do not share this medicine with anyone who has not been prescribed this medicine.
This medicine is associated with increased risk of death in certain patients. Please speak with your doctor about the benefits and risks of using this medicine.
This medicine can cause serious side effects in some patients. Important information from the U.S. Food and Drug Administration (FDA) is available from your pharmacist. Please review it carefully with your pharmacist to understand the risks associated with this medicine.
Side Effects
The following is a list of some common side effects from this medicine. Please speak with your doctor about what you should do if you experience these or other side effects.
- agitated feeling or trouble sleeping
- constipation
- dizziness
- drowsiness or sedation
- lack of energy and tiredness
- headaches
- nausea
- stomach upset or abdominal pain
- vomiting
Call your doctor or get medical help right away if you notice any of these more serious side effects:
- loss of balance
- bleeding that is severe or takes longer to stop
- unusual bruising or discoloration on skin
- changes in memory, mood, or thinking
- confusion
- depression or feeling sad
- fainting
- muscle pain
- muscle weakness
- skin irritation such as redness, itching, rash, or burning
- shakiness
- red, peeling or blistering skin
- light colored stool
- suicidal thoughts
- unusual or unexplained tiredness or weakness
- blurring or changes of vision
A few people may have an allergic reaction to this medicine. Symptoms can include difficulty breathing, skin rash, itching, swelling, or severe dizziness. If you notice any of these symptoms, seek medical help quickly.
Extra
Please speak with your doctor, nurse, or pharmacist if you have any questions about this medicine.
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IMPORTANT NOTE: This document tells you briefly how to take your medicine, but it does not tell you all
there is to know about it.Your doctor or pharmacist may give you other documents about your medicine.
Please talk to them if you have any questions.Always follow their advice. There is a more complete
description of this medicine available in English.Scan this code on your smartphone or tablet or use
the web address below. You can also ask your pharmacist for a printout. If you have
any questions, please ask your pharmacist.
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💊 Composition of the drug Oxcarbazepine-native ✅ Use of Oxcarbazepine-native Save Search for analogues Interaction Description of the active ingredients of the preparation Oxcarbazepine native The scientific information provided is general and cannot be used to make decisions. Update date: 2020.05.07 Marketing authorization holder: PHARMCOMPANY LLC Manufactured:NATIVA LLC (Russia) ATX code: N03AF02 (Oxcarbazepine) Active substance: Rec.INN registered by WHO Dosage forms
Release form, packaging and composition |
1 tab. | |
oxcarbazepine | 150 mg |
– 10 mg, hypromellose – 4.2 mg, magnesium stearate – 2.2 mg, microcrystalline cellulose – 32.8 mg.
Shell composition: Opadry pink (hypromellose – 62.5%, titanium dioxide – 30.94%, macrogol – 6.25%, iron dye red oxide – 0.09%, iron dye (II, III) oxide / iron dye black oxide – 0.02%) – 10 mg.
10 pcs. – cellular contour packings (1) – packs of cardboard.
10 pcs. – cellular contour packings (2) – packs of cardboard.
10 pcs. – cellular contour packings (3) – packs of cardboard.
10 pcs. – cellular contour packings (5) – packs of cardboard.
30 pcs. – polyethylene bottles (1) – cardboard packs.
50 pcs. – polyethylene bottles (1) – cardboard packs.
Film-coated tablets grayish brown with a light pink tint, oval, biconvex, scored on one side; at the break – the core is white or almost white.
1 tab. | |
oxcarbazepine | 300 mg |
– 20 mg, hypromellose – 8.4 mg, magnesium stearate – 4.4 mg, microcrystalline cellulose – 65.6 mg.
Shell composition: Opadray purple (hypromellose – 62.5%, titanium dioxide – 28.95%, macrogol 400 – 6.25%, iron dye red oxide – 0.1%, iron dye (II, III) oxide / iron dye black oxide – 0.75 %, iron dye yellow oxide – 3.35%) – 16 mg.
10 pcs. – cellular contour packings (1) – packs of cardboard.
10 pcs. – cellular contour packings (2) – packs of cardboard.
10 pcs. – cellular contour packings (3) – packs of cardboard.
10 pieces. – cellular contour packings (5) – packs of cardboard.
30 pcs. – polyethylene bottles (1) – cardboard packs.
50 pcs. – polyethylene bottles (1) – cardboard packs.
Film-coated tablets pink, oval, biconvex, scored on one side; at the break – the core is white or almost white.
1 tab. | |
oxcarbazepine | 600 mg |
Excipients : colloidal silicon dioxide – 3.2 mg, crospovidone – 40 mg, hypromellose – 16.8 mg, magnesium stearate – 8.8 mg, microcrystalline cellulose – 131.2 mg.
Shell composition: Opadry pink (hypromellose – 62.5%, titanium dioxide – 30.94%, macrogol – 6.25%, iron dye red oxide – 0.2%, iron dye yellow oxide – 0.09%, iron dye (II, III) oxide / iron dye black oxide – 0.02%) – 26 mg.
10 pcs. – cellular contour packings (1) – packs of cardboard.
10 pcs. – cellular contour packings (2) – packs of cardboard.
10 pcs. – cellular contour packings (3) – packs of cardboard.
10 pcs. – cellular contour packings (5) – packs of cardboard.
30 pcs. – polyethylene bottles (1) – cardboard packs.
50 pcs. – polyethylene bottles (1) – cardboard packs.
Clinical and pharmacological group:
Anticonvulsant drug
Pharmacotherapeutic group:
Antiepileptic agent
Pharmacological action
Antiepileptic agent. Pharmacological activity is primarily due to the action of the metabolite – monohydroxy derivative (MHP) oxcarbazepine. The mechanism of action of oxcarbazepine and its metabolite is mainly associated with the blockade of voltage-dependent sodium channels, which leads to stabilization of overexcited neuronal membranes, inhibition of the occurrence of serial neuronal discharges and a decrease in synaptic conduction of impulses.
The implementation of the anticonvulsant action is facilitated by an increase in the conductivity of potassium ions and the modulation of calcium channels activated by a high membrane potential. There was no significant interaction with brain neurotransmitters or receptor binding. Experimental studies have shown that oxcarbazepine and its metabolite have a pronounced anticonvulsant effect.
The efficacy of oxcarbazepine in epileptic seizures has been demonstrated both in monotherapy and in the use of oxcarbazepine as part of combination therapy in children and adults.
Pharmacokinetics
After oral administration, oxcarbazepine is completely absorbed and largely metabolized to form the pharmacologically active metabolite, the 10-monohydroxy derivative. After a single dose of oxcarbazepine, depending on the dosage form used, C max metabolite in plasma is 24.9-34 µmol / l, the average time to reach it is about 4.5-6 hours. Pharmacokinetic studies have shown that 2 % oxcarbazepine and 70% MGP; the rest is accounted for by secondary metabolites, rapidly excreted from the blood plasma.
Binding of the metabolite to plasma proteins, mainly albumin, is about 40%. In the therapeutic range, the degree of binding does not depend on the concentration of the drug in the blood serum. Oxcarbazepine and MGP do not bind to α 1 -acid glycoprotein. Apparent V d – 49 l. From ss MHD in blood plasma is achieved on the 2-3rd day when taking oxcarbazepine 2 times / day. In the equilibrium state, the pharmacokinetic parameters of MGP are linear and dose-dependent in the range of daily doses of 300 mg – 2400 mg.
Oxcarbazepine is rapidly metabolized by hepatic cytosolic enzymes to the pharmacologically active MHD metabolite, which undergoes further glucuronidation. Minor amounts of MHP (about 4% of the dose) are oxidized to form an inactive metabolite – 10, 11-dihydroxy derivative (DHP).
Oxcarbazepine is excreted as metabolites mainly by the kidneys (95%), less than 1% is excreted unchanged. Approximately 80% of excreted metabolites are MHD, of which 49% are glucuronides and 27% are unchanged MGP. DGP is excreted unchanged (about 3%), oxcarbazepine conjugates account for 13%. About 4% of the dose is excreted in the feces.
Oxcarbazepine is rapidly excreted from the blood plasma, the apparent T 1/2 is 1.3 – 2.3 hours. GP from creatinine clearance. With CC less than 30 ml / min after a single dose of 300 mg of oxcarbazepine T 1/2 MHL increases to 19 hours, and AUC doubles.
Weight-adjusted clearance of MHD in children decreases with age and body weight, approaching that of adults. Weight-adjusted clearance in children aged 1 month to 4 years is 93% higher than in adults. As a result, it is expected that the AUC of MHD in children of this age group will be 2 times less than that in adults when using the same doses (when adjusted for body weight). Weight-adjusted clearance in children aged 4 to 12 years is 43% higher than in adults. The estimated AUC of MHD in children of this age group is 2/3 of that in adults when using the same doses (when adjusted for body weight). It is assumed that in children aged 13 years and older, due to the increase in body weight, the clearance of MHD, adjusted for body weight, corresponds to the clearance of MHD in adults.
After taking oxcarbazepine at a single dose of 300 mg or multiple doses of 600 mg/day in healthy volunteers aged 60-82 years, plasma C max and AUC values for MHD were 30-60% higher compared with the same indicators in young volunteers (18-32 years old), which is associated with an age-related decrease in CC.
Pregnant women experience a number of physiological changes that can lead to a gradual decrease in plasma levels of MHD during pregnancy.
Indications of the active substances of the drug
Oxcarbazepine native
Simple and complex partial epileptic seizures with or without secondary generalization in adults and children aged 1 month and older.
Generalized tonic-clonic epileptic seizures in adults and children aged 2 years and older.
Open list of ICD-10 codes
G40 | Epilepsy |
Dosage regimen
The method of administration and dosing regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. Compliance of the dosage form of a particular drug with indications for use and dosing regimen should be strictly observed.
Take orally.
Initial dose – 8-10 mg/kg body weight/day. Further, the dose is adjusted depending on the treatment regimen, the age of the patient, the effectiveness of treatment, and kidney function.
For patients with impaired renal function (CC less than 30 ml / min), adjustment of the initial dose and dosing regimen is required.
Side effects
Most common (≥ 10%) : drowsiness, headache, dizziness, diplopia, nausea, vomiting, fatigue.
From the side of the hematopoietic system: sometimes – leukopenia; very rarely – suppression of bone marrow hematopoiesis, agranulocytosis, aplastic anemia, neutropenia, pancytopenia, thrombocytopenia.
From the immune system: very rarely – hypersensitivity reactions accompanied by fever and rash (including multiple organ disorders). With the development of hypersensitivity reactions, damage to the circulatory and lymphatic systems (eosinophilia, thrombocytopenia, lymphadenopathy, splenomegaly), muscles and joints (myalgia, swelling in the joints, arthralgia), nervous system (encephalopathy), kidneys (proteinuria, interstitial nephritis, renal failure) is possible. ), lungs (shortness of breath, pulmonary edema, bronchospasm, interstitial inflammation), abnormal liver function tests, angioedema, anaphylactic reactions.
From the side of metabolism: often – hyponatremia; very rarely – clinically significant hyponatremia (sodium concentration <125 mmol / l - usually during the first 3 months of drug therapy; in some patients - more than 1 g after the start of treatment), leading to the development of such manifestations and symptoms as seizures, confusion, decreased level of consciousness, encephalopathy, visual disturbances (including blurred vision), nausea, vomiting, folic acid deficiency; very rarely - hypothyroidism.
From the side of the central nervous system: very often – drowsiness, headache, dizziness; often – ataxia, tremor, nystagmus, impaired attention, amnesia; confusion, depression, apathy, agitation, emotional lability.
From the senses: very often – diplopia; often – visual impairment, blurred vision, vertigo.
From the side of the cardiovascular system: very rarely – arrhythmias, AV blockade, arterial hypertension.
From the digestive system: very often – nausea, vomiting; often – diarrhea, constipation, abdominal pain; sometimes – an increase in the activity of liver enzymes, an increase in the concentration of alkaline phosphatase in the blood; very rarely – pancreatitis and / or increased levels of lipase and / or amylase, hepatitis.
Dermatological reactions: often – rash, alopecia, acne.
Allergic reactions: sometimes – urticaria; very rarely – angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), erythema multiforme.
Other: very often – feeling tired; often – asthenia; very rarely – systemic lupus erythematosus.
In children under 4 years of age: very often (11%) – drowsiness; often (≥1%–<10%) - ataxia, irritability, vomiting, lethargy, fatigue, nystagmus, tremor, loss of appetite, increased concentration of uric acid in the blood.
Contraindications for use
Children under 3 years of age; hypersensitivity to oxcarbazepine.
Pregnancy and lactation
Limited experience with pregnancy. Reports suggest that oxcarbazepine use during pregnancy may be associated with the development of birth defects (eg, cleft palate).
In experimental studies when using oxcarbazepine in toxic doses, there was an increase in embryonic mortality, slowing down and impaired development and growth of the fetus. If the patient plans to become pregnant or becomes pregnant while using oxcarbazepine, and if there is a question about the use of oxcarbazepine during pregnancy, the expected benefits of therapy and the possible risk to the fetus, especially in the first trimester of pregnancy, should be carefully weighed.
Use the lowest effective dose of oxcarbazepine during pregnancy.
When clinically effective in women of childbearing age, oxcarbazepine should be used as monotherapy.
Effective antiepileptic treatment should not be interrupted during pregnancy, as disease progression may adversely affect the mother and fetus.
Folic acid deficiency is known to develop during pregnancy. Antiepileptic drugs can exacerbate this deficiency, which is one of the possible causes of fetal developmental disorders, so additional folic acid supplementation is recommended.
When used during pregnancy, it must be taken into account that physiological changes occurring in the body of a pregnant woman can lead to a gradual decrease in the concentration of the active metabolite in the blood plasma. To achieve maximum control of the symptoms of the disease, it is necessary to regularly evaluate the clinical effect of oxcarbazepine and determine the concentration of the metabolite in the blood plasma. Determination of the concentration of MHD in blood plasma is also recommended in the postpartum period, especially if the dose of oxcarbazepine was increased during pregnancy.
There are reports that the use of antiepileptic drugs during pregnancy can lead to increased bleeding in newborns. As a precautionary measure, vitamin K 1 is recommended during the last few weeks of pregnancy and in newborns whose mothers received oxcarbazepine.
Oxcarbazepine and MHD cross the placental barrier and are excreted in breast milk. The concentration ratio in milk and plasma was 0.5 for both substances. Since the effect on newborns of oxcarbazepine and MHD, received with mother’s milk, is not known, oxcarbazepine should not be used during breastfeeding.
Precautions
Use with caution in patients with known hypersensitivity to carbamazepine, as in this group of patients, approximately 25-30% of cases may develop hypersensitivity reactions to oxcarbazepine. In patients with no history of hypersensitivity to carbamazepine, it is also possible to develop hypersensitivity reactions to oxcarbazepine, including multiple organ disorders. In the event of an immediate type hypersensitivity reaction, oxcarbazepine should be discontinued immediately and alternative therapy instituted.
Use with caution in patients with severe hepatic impairment.
In patients with impaired renal function and low serum sodium levels, or in patients receiving concomitant treatment with drugs that promote sodium excretion from the body (diuretics, drugs that affect the secretion of ADH), the concentration should be determined before starting therapy with oxcarbazepine sodium in blood serum. In the future, the concentration of sodium in the blood serum should be monitored 2 weeks after the start of therapy and then monthly for 3 months or as needed. With particular attention to these risk factors should be treated in elderly patients. If it is necessary to prescribe diuretics and other drugs that reduce the concentration of sodium in the blood serum, patients receiving oxcarbazepine should follow the same recommendations. If clinical symptoms appear that suggest hyponatremia, serum sodium concentration should be measured. For other patients, measurement of serum sodium concentration can be performed during routine blood tests.
If symptoms of severe bone marrow suppression develop, consideration should be given to discontinuing oxcarbazepine.
Patients receiving anticonvulsants rarely experienced episodes of suicidal behavior and thoughts. The mechanism of increased risk of suicide in this category of patients has not been established. Therefore, at all stages of treatment, careful monitoring of patients receiving oxcarbazepine is necessary.
Weight should be monitored in all patients with heart failure to detect fluid retention in a timely manner. With fluid retention or with the progression of symptoms of heart failure, the concentration of sodium in the blood serum should be determined. If hyponatremia occurs, fluid intake should be limited. When using oxcarbazepine, in very rare cases, a violation of cardiac conduction is possible, therefore, during the period of treatment, careful monitoring of patients with previous conduction disorders (AV blockade, arrhythmia) is necessary.
Dermatological reactions have been observed in both children and adults with oxcarbazepine and developed on average 19 days after the start of treatment. There are isolated reports of recurrence of skin reactions when oxcarbazepine is restarted. With the development of skin reactions against the background of the use of oxcarbazepine, consideration should be given to its cancellation and the appointment of another antiepileptic agent.
If hepatitis is suspected, discontinuation of oxcarbazepine should be considered.
As with all antiepileptic drugs, oxcarbazepine should be discontinued gradually due to the risk of increased seizure frequency.
Influence on the ability to drive vehicles and mechanisms
Patients who develop dizziness, drowsiness or other disorders of the central nervous system during the use of oxcarbazepine should not drive vehicles or work with mechanisms during the period of treatment.
Drug interactions
Oxcarbazepine and its pharmacologically active metabolite MHD are inhibitors of cytochrome CYP2C19. Therefore, when using oxcarbazepine in high doses, drug interactions with drugs metabolized by CYP2C19 (phenobarbital, phenytoin) are possible. For some patients, dose reduction of drugs – substrates of CYP2C19 may be required. Oxcarbazepine and MHD have been shown to interact weakly or not at all with the following microsomal isoenzymes: CYP1A2, CYP2A6, CYP2C9, CYP2D9, CYP2E1, CYP4A4 and CYP4C11.
As inducers of CYP3A4 and CYP3A5, oxcarbazepine and MHD reduce plasma concentrations of drugs metabolized by these isoenzymes: dihydropyridine calcium antagonists, oral contraceptives, and antiepileptic drugs (eg, carbamazepine). With simultaneous use with oxcarbazepine, a decrease in plasma concentrations of other drugs that are substrates of CYP3A4 and CYP3A5 enzymes (for example, drugs of the immunosuppressant group – cyclosporine) is also possible.
Because MHD is a weak inducer of UDP-glucuronyl transferase in vitro, it is therefore unlikely that it would interfere in vivo with the metabolism of drugs excreted as glucuronic acid conjugates (eg, valproic acid and lamotrigine). But, taking into account even the weak inducing ability of oxcarbazepine and MHD, it may be necessary to increase the doses of concomitantly used drugs metabolized with the participation of CYP3A4 or UDP-glucuronyl transferase. If oxcarbazepine is discontinued, the dose of these drugs may need to be reduced.
In vitro studies have confirmed the weak inducing ability of oxcarbazepine and MGP in relation to the isoenzymes of the CYP2B and CYP3A4 enzyme subsystems. The inducing effect of oxcarbazepine and MHD on other CYP isoenzymes is unknown.
Plasma concentration of phenytoin increases by up to 40% with simultaneous use of oxcarbazepine at a dose of 1200 mg / day and above. Therefore, when using oxcarbazepine at such doses, a reduction in the dose of phenytoin may be required.
The increase in serum concentrations of phenobarbital with simultaneous use with oxcarbazepine is insignificant (15%).
Simultaneous administration of strong inducers of cytochrome P450 isoenzymes (ie carbamazepine, phenytoin and phenobarbital) reduces plasma concentrations of MHD (by 29-40%).
Oxcarbazepine has been shown to interact with ethinyl estradiol and levonorgestrel. The average AUC values for them decreased by 48-52% and 35-52%, respectively. Interaction studies of oxcarbazepine with other oral or implantable contraceptives have not been conducted. Thus, the simultaneous use of oxcarbazepine and hormonal contraceptives may lead to a decrease in the effectiveness of the latter.
Co-administration of oxcarbazepine and felodipine may result in a 28% decrease in felodipine AUC, although plasma concentrations remain within the therapeutic range.
On the other hand, with simultaneous use with verapamil, a decrease in the concentration of MHD in the blood serum by 20% is possible. This reduction has no clinical significance.
Cimetidine, erythromycin, dextropropoxyphene do not affect the pharmacokinetic parameters of MHD; viloxazine slightly affects the concentration of MHD in plasma (the concentration of MHD increases by 10% after repeated co-administration). There was no interaction with warfarin when taking both single and multiple doses of oxcarbazepine.
Oxcarbazepine may increase the sedative effect of ethanol.
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Oxcarbazepine native . Description of the drug in the reference book Vidal.
Side effects, etc., what helps, overdose
THERE ARE CONTRAINDICATIONS. POSSIBLE SIDE EFFECTS. SPECIALIST CONSULTATION REQUIRED. Epilepsy
The author of the article
Asanova Natalya Gennadievna,
Diploma of pharmaceutical education: 587802
All authors
Content of the article
- Trileptal: mn
- Trileptal 150
- Trileptal 600
- Trileptal: side effects
- Summary
- Ask an expert about the topic of the article
9041 8 Trileptal from what
Epilepsy is the most common neurological disease in the world. According to WHO estimates, about 50 million people suffer from it. For comparison: with a diagnosis of dementia on the planet live 35 million patients.
Epilepsy is accompanied by recurrent episodes of seizures that occur due to high activity of neurons in the brain. Thanks to pharmacology in the 21st century, 70% of those suffering from epilepsy can be prevented or reduced in the frequency of seizures.
Pharmacist Natalya Asanova talks about the anticonvulsant drug Trileptal: what is included in the composition, what are the dosages and side effects.
Trileptal: mn
The active ingredient in Trileptal is oxcarbazepine. This is the “second generation” of the well-known drug carbamazepine. Due to a small change in the structure of the molecule, it has fewer side effects. The anticonvulsant effect of Trileptal is aimed at stabilizing overexcited neuronal membranes and reducing the conduction of impulses. Oxcarbazepine is included in the Federal clinical guidelines for the treatment of epilepsy and status epilepticus in adults and children.
The drug is produced by Novartis Pharma AG (Switzerland) in the form of tablets with three dosages: 150, 300 and 600 mg. The second dosage form – suspension for oral administration – is convenient for dosing and is usually used in pediatric practice. It is also suitable for patients who have difficulty swallowing tablets or in cases where it is not possible to provide a dose with tablets.
All products Trileptal
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Trileptal from what
Trileptal according to the information in the RLS (Register of Medicines) refers to antiepileptic drugs and is used as monotherapy, as well as in combination with other anticonvulsants. Trileptal is prescribed for adults and children over 1 month of age to prevent and reduce the frequency of epileptic seizures.
Indications for use:
- simple (conscious) and complex (with impairment of consciousness) partial epileptic seizures, with or without secondary generalization (loss of consciousness)
- generalized tonic-clonic seizures (change of tension and muscle spasms against the background of loss of consciousness)
Many anticonvulsants, like Trileptal, are mood stabilizers. They have the ability to stabilize mood by reducing abnormal brain activity. They are used for mental disorders to reduce irritability, quarrelsomeness, impulsivity, dysphoria. The effectiveness of Trileptal as a potential mood stabilizer has not been proven. The official instructions do not contain indications for the use of Trileptal in bipolar disorder and depression.
Trileptal 150
Trileptal 150 mg light green oval tablets with T/D and C/G embossed on opposite sides. Due to the double-sided risk, they can be broken to make it easier to swallow. Take the tablets regardless of the meal time. Tablets of 150 mg are contraindicated in children under 3 years of age.
The initial dose for adults is 600 mg per day, divided into 2 doses. If necessary, increase the dose gradually. The dosage is prescribed by the attending physician. You need a prescription to buy Trileptal in a pharmacy.
Trileptal 600
Trileptal 600 mg light pink oval tablets with TF/TF and CG/CG embossed on opposite sides. Also have a risk on both sides. Approved for use by children from 3 years.
Therapeutic maintenance doses are prescribed in the range of 600-2400 mg, in most patients a good clinical effect is achieved at a dose of 900 mg per day. To take the right dosage, the patient can use tablets of 150, 300 and 600 mg.
Trileptal: side effects
The drug has an inhibitory effect on the central nervous system. Therefore, in 10% of patients, Trileptal gives side effects that appear in a moderate form at the beginning of treatment and disappear over time:
- drowsiness
- headache and dizziness
- nausea, vomiting
- fatigue
- double vision (diplopia)
- attention disorder, amnesia
Often while taking Trileptal, patients gain weight, they experience nervousness, emotional instability, confusion, apathy and depression. Another drug reduces the content of sodium in the blood, especially in the elderly (need to be controlled!).