When should you take your medicines. How does timing affect drug efficacy. Why is it important to consider your body’s natural rhythms when taking medication. What role does the circadian clock play in drug metabolism.

The Importance of Medication Timing in Healthcare

For many people, taking medication is a routine part of daily life. Whether it’s antibiotics for an infection, cholesterol-lowering drugs, or treatments for conditions like high blood pressure, depression, or acid reflux, proper medication administration is crucial for optimal health outcomes. While dosage instructions are typically clear, the timing of when to take certain medicines can significantly impact their effectiveness and potential side effects.

Understanding the relationship between medication timing and the body’s natural rhythms is key to maximizing therapeutic benefits and minimizing unwanted effects. This article explores the science behind chronotherapy – the practice of synchronizing medication administration with the body’s circadian rhythms – and provides practical guidance on optimizing medication schedules.

The Body’s Circadian Clock and Its Impact on Drug Efficacy

Our bodies operate on a 24-hour cycle known as the circadian rhythm, controlled by an internal biological clock. This clock regulates various physiological processes, including hormone production, metabolism, and even gene expression. These rhythmic changes throughout the day can significantly influence how our bodies respond to medications.

How does the circadian rhythm affect drug efficacy? The body’s internal clock can impact:

• Drug absorption rates
• Metabolism and elimination of medications
• Receptor sensitivity to drugs
• The intensity of drug effects

By aligning medication timing with these natural rhythms, healthcare providers can potentially enhance treatment outcomes and reduce side effects.

Chronotherapy: Tailoring Medication Schedules to Biological Rhythms

Chronotherapy is an emerging field in medicine that focuses on optimizing treatment efficacy by considering the body’s natural rhythms. This approach recognizes that the timing of drug administration can be just as important as the dosage itself.

What are some examples of chronotherapy in practice?

• Administering blood pressure medications in the evening to coincide with the natural rise in blood pressure that occurs before waking
• Timing chemotherapy drugs to target cancer cells when they’re most vulnerable
• Scheduling anti-inflammatory medications to align with peak inflammation periods in conditions like rheumatoid arthritis

By leveraging the body’s natural rhythms, chronotherapy aims to enhance drug efficacy while potentially reducing dosages and minimizing side effects.

Optimizing Medication Timing for Common Health Conditions

Different health conditions and medications may benefit from specific timing strategies. Here are some examples of how chronotherapy can be applied to common health issues:

Cholesterol Management

Why should short-acting statins be taken at night? Cholesterol production in the liver peaks during sleep, typically between midnight and 3 am. By taking short-acting statins before bedtime, you can maximize their cholesterol-lowering effects when they’re most needed.

Diabetes Management

When is the best time to take long-acting insulin? Long-acting insulin, such as Levemir, is often recommended to be taken with the last meal of the day or at bedtime. This timing helps provide better blood glucose control throughout the night and into the early morning hours.

Cardiovascular Health

Why take certain anticoagulants with the evening meal? Some anticoagulants are more effectively absorbed when taken with food. Administering these medications with the evening meal ensures they reach peak effectiveness in the morning hours when the risk of cardiovascular events is highest.

Acid Reflux Treatment

What’s the optimal time to take acid reflux medication? Drugs that treat acid reflux are most effective when taken before the first meal of the day. This timing coincides with the highest activity of stomach acid pumps, allowing the medication to block acid secretion most efficiently.

Managing Side Effects Through Strategic Medication Timing

In addition to enhancing efficacy, proper medication timing can help mitigate unwanted side effects. Here are some examples:

• ADHD medications: Taking these in the morning can help avoid insomnia, a common side effect
• Hepatitis B treatments: Administering these at bedtime can minimize daytime drowsiness and dizziness
• Corticosteroids: Morning dosing can help reduce sleep disturbances and mimic the body’s natural cortisol rhythm

By aligning medication timing with the body’s natural rhythms and daily activities, patients can often experience improved tolerability and adherence to their treatment regimens.

Individual Variations in Circadian Rhythms: The “Morning Lark” vs. “Night Owl” Phenomenon

While general guidelines for medication timing can be helpful, it’s important to recognize that individual circadian rhythms can vary significantly. Some people naturally tend to wake early and feel most alert in the morning (“morning larks”), while others are more active and alert in the evening (“night owls”).

How do these individual differences impact medication timing? The optimal time to take a medication may vary depending on a person’s unique sleep-wake cycle. For example, what constitutes “morning” for a night owl may be several hours later than for a morning lark.

Factors that can influence individual circadian rhythms include:

• Genetics
• Age
• Lifestyle factors (e.g., work schedules, social habits)
• Environmental cues (e.g., light exposure)

As research in chronotherapy advances, healthcare providers may increasingly consider these individual variations when prescribing medication regimens.

The Future of Personalized Chronotherapy

Advancements in chronobiology and personalized medicine are paving the way for more tailored approaches to medication timing. Researchers are developing methods to precisely measure an individual’s internal body time, which could allow for highly customized dosing schedules.

What technologies are being explored for personalized chronotherapy?

• Wearable devices that track sleep-wake cycles and other physiological markers
• Genetic testing to identify circadian rhythm gene variants
• Machine learning algorithms to predict optimal dosing times based on individual data

As these technologies evolve, we may see a shift towards more precise, individualized medication schedules that maximize efficacy while minimizing side effects.

Practical Tips for Optimizing Your Medication Schedule

While the field of chronotherapy continues to advance, there are steps you can take now to optimize your medication timing:

1. Read medication labels carefully and follow timing instructions
2. Consult with your pharmacist or healthcare provider about the best time to take each medication
3. Be consistent with your medication schedule to maintain steady drug levels
4. Consider your personal sleep-wake cycle when planning medication times
5. Use medication reminder apps or alarms to help you stay on schedule
6. Keep a medication diary to track any side effects or changes in efficacy

Remember, any changes to your medication regimen should always be discussed with your healthcare provider first.

The timing of medication administration is a critical yet often overlooked aspect of treatment. By understanding the relationship between our body’s natural rhythms and drug efficacy, we can work towards more effective and personalized treatment approaches. As research in chronotherapy continues to evolve, we may see increasingly sophisticated methods for tailoring medication schedules to individual needs, ultimately leading to improved health outcomes and quality of life for patients.

In the meantime, being mindful of medication timing and working closely with healthcare providers can help optimize current treatment regimens. Whether you’re a morning lark or a night owl, understanding your body’s rhythms and how they interact with your medications is a valuable step towards more effective healthcare management.

When Should You Take Your Medicines?

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J Biol Rhythms. Author manuscript; available in PMC 2021 Mar 11.

Published in final edited form as:

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Almost everyone has experience taking medicine—antibiotics for an infection or drugs to treat high cholesterol, high blood pressure, depression, or acid reflux. The label instructs us on how many to take and when to take them. We know not to take more than the label says to prevent an overdose. But does when we take medicine matter?

The simple answer is: yes! Our lives have rhythm—before we wake, our heart rate and blood pressure rise to prepare us to go from the sleep to the wake state. These changes happen because of the body’s internal (circadian) clock, which controls most bodily functions according to a 24-h day-night cycle. Because our bodies function differently in the morning than in the evening, taking medicines at a specific time can improve how they work and/or minimize side effects.

The more complicated answer is: it depends on how the drug works. Taking a drug in the morning or at night can help improve its therapeutic effect. Sleep aids are obvious; you take them before you want to go to sleep. Most drugs are less obvious. Short-acting statins used to treat high cholesterol should be taken prior to bedtime, as cholesterol levels increase during sleep. Short-acting statins are cleared from the body quickly; taking them before bed maximizes their efficacy. Long-acting insulin should be taken with the last meal of the day or at bedtime to provide better blood glucose control while sleeping. Some anticoagulants should be taken with an evening meal to aid with absorption so that the drug is effective in the morning when you are at the highest risk for a cardiovascular event. Drugs that treat acid reflux are most effective when taken before the first meal when the number of stomach pumps is highest; the drug blocks pumps in the stomach lining from secreting acid.

Some drugs lead to unwanted side effects. Taking a drug in the morning or at night could help control side effects. For example, drugs that treat attention-deficit hyperactivity disorder (ADHD) can cause insomnia and should be taken in the morning. Medicine used to treat hepatitis B makes some people dizzy and tired and should be taken at bedtime. Therefore, day-dependent dosing can improve how drugs work, improve how they are absorbed and metabolized, or help avoid undesirable side effects.

“Morning” can be at different times for different people. The time on a wall clock is the same for all of us, but our body’s clock can have wildly different timing. Some of us are “morning larks,” while others are “night owls.” Shift work, jet lag, or even staying out too late on the weekends (social jetlag) can cause our body clock to shift out of phase with the clock on the wall. Therefore, we can’t always rely on the clock on the wall or the standard definition of “morning” to tell us when to take medicine. We should take medicines according to our individual sleep-wake cycle. In fact, scientists are improving methods to precisely measure each person’s individualized internal body time, which will allow clinicians to provide better dosing instructions based on each patient’s body clock.

Knowing when to take medicine can be confusing. If you don’t know when to take your medicine, read the label and ask your pharmacist and doctor.

Ambien

Sanofi-Aventis US LLC (2008, February) Ambien. Official FDA label https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/019908s027lbl.pdf.

This one is obvious, you take before you want to sleep.

Atripla

Bristol-Myers Squibb and Gilead Sciences, LLC (2015, November) Atripla. Bristol-Myers Squibb and Gilead Sciences, LLC. Official FDA label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021937s037lbl.pdf.

Atripla has a time-of-day (bedtime) recommendation, as it can make people dizzy and tired.

Levemir

Novo Nordisk Inc. (2012, January) Levemir. Official FDA label. https://www.accessdata.fda.gov/drug-satfda_docs/label/2012/021536s037lbl.pdf.

When taken once a day, Levemir, a long-acting insulin, is supposed to be taken with your last meal or at bedtime. This serves to provide better blood glucose control while sleeping.

Nexium

Astrazeneca Pharmaceuticals LP (2014, December) Nexium. Official FDA label. https://www.access-data.fda.gov/drugsatfda_docs/label/2014/022101s014021957s017021153s050lbl. pdf.

The best time for administration is before a meal after a period of fasting (once a day before your first meal) when the highest number of proton pumps are localized to the wall of the stomach.

Ritalin

Novartis Pharmaceuticals Corp. (2010) Ritalin. Official FDA label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021284s018lbl.pdf.

Drugs used to treat ADHD can cause insomnia. Consequently, once-a-day ADHD drugs such as Ritalin LA are supposed to be taken daily in the morning.

Xarelto

Janssen Pharmaceuticals Inc. (2011, December) Xarelto. Official FDA label. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202439s001lbl.pdf.

This drug should be taken with your last meal, as this aids in absorption and allows the drug to be on board when you wake up and are at highest risk for a cardiovascular event.

Zocor

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (2012, February) Zocor. Official FDA label. https://www.accessdata.fda.gov/drug-satfda_docs/label/2012/019766s085lbl.pdf.

Your body synthesizes cholesterol while you sleep. Zocor inhibits the rate-limiting enzyme in cholesterol biosynthesis. As Zocor is short acting, the FDA label recommends it be taken prior to bedtime in concert with the peak in cholesterol biosynthesis.

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Levemir side effects and how to avoid them

Levemir is a brand-name FDA (Food and Drug Administration) approved medication manufactured by Novo Nordisk Inc. It is classified as a long-lasting insulin and is used to treat diabetes. While Levemir is generally well tolerated, there are some potential side effects that people should be aware of. The most common side effects of Levemir include injection site reactions. Less common but more serious side effects can include serious allergic reactions.

Learn more about the side effects of Levemir and what you can do to avoid them.

What is Levemir?

Levemir is a prescription medication used to lower high blood sugar levels (hyperglycemia) in adults and children with type 1 diabetes and type 2 diabetes mellitus. It’s a type of insulin that works in the same way as the insulin your body produces. A key difference, however, is the fact it’s long-lasting.

The active ingredient in Levemir is called insulin detemir, a type of synthetic (man-made) insulin that works in the same way as the insulin your body makes naturally. The only key difference is that insulin detemir has been designed to be longer acting than natural insulin, so it works over a longer time period.

When you inject Levemir under your skin, the insulin detemir is released into your bloodstream. It travels around your body in your blood and helps your cells absorb sugar. It can be active for up to 24 hours, so it can cover your insulin needs over the course of a full day.

Levemir dosage

Levemir is available in injection form as 3 mL Levemir FlexTouch prefilled insulin pens and 10 mL multiple dose vials.

Levemir is taken by injecting it under your skin (subcutaneous injection) into the thigh, upper arm, or abdomen using either a syringe or a pre-filled FlexTouch self-injecting pen. You typically inject Levemir once every 24 hours at the same time each day. Allow Levemir to reach room temperature before injecting a dose.

You are advised to read the medication guide provided with this medicine for the drug information and patient information, and always speak with your healthcare provider for medical advice about any changes to your dose so they can monitor and evaluate your condition.

Levemir side effects

The most common possible side effects of Levemir in clinical trials include:

• Injection site reactions such as itching, rashes, skin thickening, or pits forming in your skin (lipodystrophy)
• Weight gain
• Allergic reactions that can cause swelling of your face, tongue, or throat
• Difficult or painful urination
• Swelling (edema) of your hands and feet

Levemir can cause more serious side effects, including:

• Serious allergic reactions to the medication that may be life-threatening and can cause anaphylaxis – skin rash, trouble breathing, fast heartbeats, feeling faint, or swollen face, tongue, or throat
• Your blood sugar falls too low to dangerous levels (severe hypoglycemia). Keep a glucagon kit, glucose tablets, or fruit juice available in case of severe low blood sugar
• Hypokalemia (low potassium level)

If you experience any of these serious side effects, stop taking Levemir and seek medical attention immediately. You are encouraged to report the negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Does Levemir affect the kidneys?

Levemir should not affect the kidneys, but kidney problems are common in those with diabetes.

Does Levemir cause hair loss?

Levemir is not associated with hair loss, but insulin resistance, which is associated with diabetes, may cause hair loss.

Does Levemir cause weight gain?

Levemir can cause weight gain, a common side effect of all types of insulin. Levemir causes weight increases in those with type 1 or type 2 diabetes but less than other long-acting insulins.

Does Levemir cause mood swings?

No, Levemir does not cause mood swings. Levemir may cause severe low blood sugar and result in changes in mood, such as anxiety.

Levemir drug interactions

Levemir can interact with other medications, including:

• Antibiotics such as cinoxacin, ciprofloxacin, enoxacin, norfloxacin, and ofloxacin
• Thiazolidinedione medications (TZDs) such as pioglitazone and rosiglitazone, taken to treat diabetes
• Any other diabetes medications – metformin, glipizide, or other insulin products
• Angiotensin II receptor blockers such as candesartan, losartan, and valsartan
• Angiotensin-converting enzymes (ACE) inhibitors such as captopril, enalapril, and perindopril
• Antidepressants, including monoamine oxidase inhibitors and selective serotonin reuptake inhibitors – phenelzine, selegiline, and sertraline
• Beta 2-stimulants taken to treat asthma – salmeterol, formoterol
• Beta-blockers taken to treat high blood pressure – propranolol, sotalol
• Diuretics taken to make you lose water and salt, usually to treat high blood pressure – bumetanide, furosemide
• Estrogen containing drugs, including birth control and hormone replacements
• Fenofibrate taken to lower blood triglyceride levels
• Thyroid hormones taken to treat thyroid gland disorders – levothyroxine, liothyronine

Before taking Levemir, be sure to tell your doctor about all of the medications you are taking to ensure they are safe to take at the same time.

What is the best time of day to take Levemir?

Take Levemir once daily with dinner or at bedtime, or twice a day in the morning, and then with dinner, at bedtime, or 12 hours after your morning dose.

Why do you take Levemir at night?

Levemir is a long-acting insulin that reduces fasting blood glucose levels more effectively with less nighttime hypoglycemia compared to other insulins.

Is Levemir safe during pregnancy?

Animal studies show an increased risk of fetal damage. The importance of this is not fully understood in humans. Further testing is needed to investigate the effects of Levemir during pregnancy.

Levemir warnings & precautions

Don’t take Levemir if you:

• Are allergic to the active ingredient insulin detemir
• Are allergic to any of the other ingredients in Levemir
• Have diabetic ketoacidosis – a condition where high blood sugar causes high levels of ketones to build up in your body

Talk to your doctor before taking Levemir if you:

• Are taking any of the medications that could interact with Levemir
• Have heart failure
• Are pregnant or are planning to become pregnant
• Are breastfeeding or are planning to breastfeed – This medication passes into breast milk

You should always check with your doctor or pharmacist before taking any medication, including Levemir, to ensure it is safe for you.

How to avoid Levemir side effects

The best way to avoid side effects is to take Levemir as directed by your doctor. Follow your doctor’s instructions carefully and do not take more or less than prescribed.

If you experience any side effects, talk to your doctor or pharmacist. They may be able to recommend ways to help reduce or prevent some of the side effects.

1. Stick to the recommended dosage

Take your prescribed dose of Levemir as recommended by your healthcare professional. Do not take more or less than prescribed.

2. Monitor your blood sugar levels

If you have diabetes, it is important to monitor your blood sugar levels closely while taking Levemir. Check your blood sugar levels as directed by your doctor and report any changes to your doctor immediately.

3. Drink plenty of fluids

Drink eight to 10 glasses of water or fluids every day to help prevent dehydration, which can make side effects worse.

4. Avoid alcohol

Avoid drinking alcohol while taking Levemir, as it can increase your risk of hypoglycemia.

5. Don’t skip meals

Eating regular meals and snacks will help to prevent low blood sugar levels (hypoglycemia).

6. Check your feet

If you have diabetes, check your feet for any cuts, sores, or redness regularly. Tell your doctor if you experience any problems with your feet while taking Levemir.

7. Know the signs and symptoms of Levemir side effects

Signs and symptoms of side effects include injection site reactions and allergic reactions. If you experience any of these symptoms, speak to your doctor for medical advice.

8. Tell your doctor about all medications you’re taking

Be sure to tell your doctor about all other medications you’re taking, including over-the-counter drugs, vitamins, and herbal supplements, as they can interact with Levemir.

9. Get regular medical checkups

It is important to get regular medical checkups and monitor your medical conditions. Your doctor will monitor your side effects and may adjust your dose of Levemir as needed.

Medically reviewed

A medical professional has reviewed this article.

Medical Writer & Reviewer

Insulin Levemir® once a day is optimal

Recent studies confirm that the use of Levemir ^® (insulin detemir) once a day in patients with type II diabetes mellitus (DM) who previously did not use insulin is equally effective, as is the use of insulin glargine. Additionally, it was found that when using the drug Levemir ^® in patients, a less pronounced increase in body weight is noted. The results of the study were published in the journal Diabetologia.

It was found that the level of glycosylated hemoglobin (HbA1c) was the same in those who received Levemir ^® 1 time per day and 2 times per day (7.1%). Thus, the use of Levemir 1 time per day is optimal.

This randomized comparative study between Levemir ^® and insulin glargine lasted for 1 year. The patients were divided into 2 groups: in the 1st group, Levemir 9 was added to therapy with oral hypoglycemic drugs0003 ® , in the 2nd – insulin glargine.

According to the results obtained, it was found that the effectiveness of glycemic control is the same in both groups: after 52 weeks, the level of HbA1c decreased by 1.5% in both groups and amounted to 7.2 and 7.1%, respectively. In patients who completed the study with the frequency of administration of Levemir ^® 1 time per day, the level of HbA1c was the same as in those who used insulin glargine (7.1%). The study also found that weight gain was significantly less pronounced in patients treated with Levemir ^® 1 time per day (2.3 kg), compared with patients who received insulin glargine (3.9 kg) or Levemir ^® 2 times a day (3.7 kg). Thus, with the frequency of administration of the drug Levemir ^® 2 times a day, its positive effect on the patient’s body weight decreases. The frequency of episodes of hypoglycemia during this study was low and amounted to 5.8 in the group using Levemir ^® and 6.2 with insulin glargine.

The results described are also confirmed by data from other studies published earlier, including PREDICTIVE ^® 303 – an extensive randomized clinical trial involving more than 5,000 patients. According to his data, in patients with type II diabetes switched from NPH-insulin or insulin glargine to Levemir ^® , a significant decrease in body weight (more than 0.6 kg in 3 months) was noted over 26 weeks against the background of a significant improvement in control glycemia and reduce the frequency of episodes of hypoglycemia.

“Based on previous clinical and observational studies, as well as data from the latest study, it has been established that the administration of Levemir 9 is optimal.0003 ® 1 time per day, – says Alexander Boyko, General Director of the Novo Nordisk representative office in Ukraine and Moldova. “We believe that in the following studies it is necessary to use the once-daily administration algorithm, and we intend to confirm the effectiveness of the drug with this regimen of administration, which will allow us to make adjustments to the instructions for using this insulin analogue.”

Recall that Levemir ^® is a modern long-acting insulin, which is used to meet the need for basal insulin. Levemir ^® is released gradually, therefore causing a less dramatic change in blood glucose levels compared to conventional long-acting NPH insulins. In combination with oral hypoglycemic drugs, the initial dose of Levemir ^® is 10 U or 0.1-0.2 U / kg. Dose selection for each patient is carried out individually. The drug is administered 1 time per day in the evening, during dinner or at bedtime. Pre-filled pen Levemir ^® Flexpen ^® provides easy drug administration. Levemir FlexPen

💊 Composition of Levemir ^® FlexPen ^®

yourself

Search for analogues

Interaction

Description of the active ingredients of the preparation

Levemir ^® FlexPen ^®
(Levemir ^® FlexPen ^® )

The scientific information provided is general and cannot be used to make decisions.
decisions about the use of a particular drug.

Update date: 2021.01.14

Marketing authorization holder:

NOVO NORDISK A/S
(Denmark)

ATX code:

A10AE05

(Insulin detemir)

Active substance:
insulin detemir
(insulin detemir)

Rec.INN

WHO registered

Dosage form

Release form, packaging and composition
drug Levemir

^® FlexPen ^®

Solution for subcutaneous injection transparent, colorless.

Excipients : glycerol – 16 mg, phenol – 1.8 mg, metacresol – 2.06 mg, zinc acetate – 65.4 mcg, sodium hydrogen phosphate dihydrate – 0.89 mg, sodium chloride – 1.17 mg, hydrochloric acid or sodium hydroxide – q.s., water d / i – up to 1 ml.

3 ml (300 IU) – glass cartridges (1) – multi-dose disposable syringe pens for multiple injections (5) – cardboard packs.

* 1 unit contains 142 mcg of salt-free insulin detemir, which corresponds to 1 unit. human insulin (IU).

Clinical and pharmacological group:

Long-acting human insulin analog

Pharmacotherapeutic group:

Hypoglycemic agent – long-acting insulin analogue

Pharmacological action

Long-acting insulin, a soluble analogue of human insulin. Produced by recombinant DNA biotechnology using a strain of Saccharomyces cerevisiae.

Prolonged action is due to the pronounced self-association of insulin detemir molecules at the injection site and the binding of the drug molecules to albumin through connection with the side chain. Insulin detemir, compared with insulin isophane, reaches peripheral target tissues more slowly. These combined slow distribution mechanisms provide a more reproducible absorption and action profile for insulin detemir compared to insulin isophane.

Interacts with a specific receptor on the outer cytoplasmic membrane of cells and forms an insulin-receptor complex that stimulates intracellular processes, incl. synthesis of a number of key enzymes (hexokinase, pyruvate kinase, glycogen synthetase).

The decrease in blood glucose is due to an increase in its intracellular transport, increased uptake by tissues, stimulation of lipogenesis, glycogenogenesis, and a decrease in the rate of glucose production by the liver.

At doses of 0.2-0.4 U/kg 50%, the maximum effect occurs in the range from 3-4 hours to 14 hours after administration. The duration of action is up to 24 hours, depending on the dose.

After subcutaneous administration, a pharmacodynamic response is observed proportional to the administered dose (maximum effect, duration of action, overall effect).

The nocturnal glucose control profile is flatter and more even with insulin detemir than with insulin isophane, which is reflected in a lower risk of nocturnal hypoglycemia.

Pharmacokinetics

Terminal T _1/2 after s / c injection is determined by the degree of absorption from the subcutaneous tissue and is 5-7 hours depending on the dose.

Indications of the active substances of the drug

Levemir

^® FlexPen ^®

Diabetes.

Open list of ICD-10 codes

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.

Inject s/c into the thigh, anterior abdominal wall or shoulder. It is necessary to change injection sites within the anatomical region to prevent the development of lipodystrophy. Insulin will act faster if it is injected into the anterior abdominal wall.

Administer 1 or 2 times/day based on patient needs. Patients who require twice daily dosing for optimal glycemic control may administer the evening dose either at dinner or at bedtime or 12 hours after the morning dose.

In elderly patients, as well as with impaired liver and kidney function, blood glucose levels should be more closely monitored and insulin doses should be adjusted.

Dosage adjustment may also be required if the patient increases physical activity, changes in their usual diet, or if there is a concomitant disease.

When switching from intermediate-acting and long-acting insulins to insulin detemir, dosage and timing of administration may need to be adjusted. Careful monitoring of blood glucose levels during transfer and during the first weeks of treatment with insulin detemir is recommended. Adjustment of concomitant hypoglycemic therapy (dose and timing of short-acting insulin preparations or dose of oral hypoglycemic drugs) may be required.

Side effects

Adverse reactions related to influence on carbohydrate metabolism: often – hypoglycemia, the symptoms of which usually develop suddenly and may include pallor of the skin, cold sweat, increased fatigue, nervousness, tremor, anxiety, unusual fatigue or weakness, disorientation, impaired concentration, drowsiness, severe hunger, blurred vision, headache, nausea, palpitations. Severe hypoglycemia can lead to loss of consciousness and / or convulsions, temporary or irreversible impairment of brain function, up to death.

Adverse reactions at injection sites: often – local hypersensitivity reactions (redness, swelling and itching at the injection site), as a rule, are temporary, ie. disappear with continued treatment; rarely – lipodystrophy (as a result of non-compliance with the rule of changing the injection site within the same area).

Allergic reactions: rarely – urticaria, skin rash, as well as generalized reactions – skin itching, increased sweating, gastrointestinal disorders, angioedema, difficulty breathing, tachycardia, lowering blood pressure.

On the part of the organ of vision: rarely – refractive error (usually temporary and observed at the beginning of insulin treatment), diabetic retinopathy (long-term improvement in glycemic control reduces the risk of progression of diabetic retinopathy; however, intensification of insulin therapy with a sharp improvement in carbohydrate metabolism control may lead to temporary worsening of diabetic retinopathy).

From the side of the nervous system: in some cases – peripheral neuropathy, which is usually reversible.

Other: rarely – edema.

Contraindications for use

Increased individual sensitivity to insulin detemir.

Use in pregnancy and lactation

There are currently no data on the clinical use of insulin detemir during pregnancy and lactation.

Patients with diabetes mellitus should be carefully monitored during the period of possible onset and throughout the entire duration of pregnancy and the level of glucose in the blood plasma should be monitored. The need for insulin, as a rule, decreases in the first trimester and gradually increases in the second and third trimesters of pregnancy. Shortly after delivery, insulin requirements quickly return to pre-pregnancy levels.

During breastfeeding, it may be necessary to adjust the dose of the drug and diet.

In experimental animal studies no difference was found between the embryotoxic and teratogenic effects of insulin detemir and human insulin.

Use in hepatic impairment

In hepatic impairment, blood glucose levels should be monitored more closely and the insulin dose adjusted.

Use for impaired renal function

In case of impaired renal function, blood glucose levels should be more closely monitored and insulin doses should be adjusted.

Use in children

Insulin detemir is not recommended for use in children under 6 years of age.

Use in the Elderly

In the elderly, blood glucose levels should be more closely monitored and insulin doses should be adjusted.

Special instructions

Insulin detemir is not recommended for use in children under 6 years of age.

Intensive therapy with insulin detemir is not believed to result in weight gain.

The lower risk of nocturnal hypoglycemia compared to other insulins allows more intensive dose titration to achieve blood glucose targets.

Insulin detemir provides better glycemic control (based on fasting plasma glucose) than insulin isophane. Insufficient dose of the drug or discontinuation of treatment, especially in type 1 diabetes mellitus, can lead to the development of hyperglycemia or diabetic ketoacidosis. As a rule, the first symptoms of hyperglycemia appear gradually, over several hours or days. These symptoms include thirst, frequent urination, nausea, vomiting, drowsiness, redness and dryness of the skin, dry mouth, loss of appetite, and the smell of acetone in the exhaled air. In type 1 diabetes, untreated hyperglycemia leads to diabetic ketoacidosis and can be fatal.

Hypoglycemia can develop if the insulin dose is too high in relation to the insulin requirement.

Skipping meals or unplanned strenuous exercise may lead to hypoglycemia.

After compensation of carbohydrate metabolism, for example, with intensified insulin therapy, patients may change their typical symptoms, precursors of hypoglycemia, of which patients should be informed. The usual warning symptoms may disappear with a long course of diabetes mellitus.

Comorbidities, especially infections and fever, usually increase the body’s need for insulin.

The transfer of a patient to a new type or preparation of insulin from another manufacturer should occur under strict medical supervision. If the concentration, manufacturer, type, species (animal, human, human insulin analogs) and / or method of its production (genetically engineered or animal-derived insulin) changes, dose adjustment may be required.

Insulin detemir should not be administered intravenously as this may lead to severe hypoglycemia.

Mixing insulin detemir with a fast-acting insulin analogue such as insulin aspart results in an action profile with a reduced and delayed peak effect compared to their separate administration.

Influence on the ability to drive vehicles and mechanisms

Patients’ ability to concentrate and reaction speed may be impaired during hypoglycemia and hyperglycemia, which can be dangerous in situations where these abilities are especially needed (for example, when driving a car or work with machines and mechanisms). Patients should be advised to take measures to prevent the development of hypoglycemia and hyperglycemia when driving a car and working with mechanisms. This is especially important for patients with no or reduced symptoms of developing hypoglycemia or suffering from frequent episodes of hypoglycemia. In these cases, the feasibility of such work should be considered.

Drug interactions

The hypoglycemic effect of insulin is enhanced by oral hypoglycemic drugs, MAO inhibitors, ACE inhibitors, carbonic anhydrase inhibitors, non-selective beta-blockers, bromocriptine, sulfonamides, anabolic steroids, tetracyclines, clofibrate, ketoconazole, mebendazole, pyridoxine, theophylline, cyclophosphamide, fenfluramine , lithium preparations, preparations containing ethanol. The hypoglycemic effect of insulin is weakened by oral contraceptives, corticosteroids, thyroid hormones, thiazide diuretics, heparin, tricyclic antidepressants, sympathomimetics, danazol, clonidine, slow calcium channel blockers, diazoxide, morphine, phenytoin, nicotine.

Under the influence of reserpine and salicylates, both weakening and strengthening of the action of insulin detemir are possible.

Octreotide/lanreotide can either increase or decrease the body’s need for insulin.

Beta-blockers may mask symptoms of hypoglycemia and delay recovery from hypoglycemia.

Ethanol may enhance and prolong the hypoglycemic effect of insulin.

When insulin preparations are used in combination with drugs of the thiazolidinedione group in patients with type 2 diabetes mellitus, fluid retention in the body may occur, resulting in an increased risk of development and progression of chronic heart failure, especially in patients with diseases of the cardiovascular system and the presence of factors risk of chronic heart failure. Patients receiving such therapy should be monitored regularly for signs of heart failure. If heart failure occurs, therapy should be carried out in accordance with current standards of care.

Pharmaceutical interactions

Some drugs, such as those containing thiol or sulfite, when added to insulin detemir, can cause degradation of insulin detemir.