Levemir

Levemir is an antidiabetic drug that is an analogue of human insulin and has a prolonged effect.

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Indications Levemir

It is used in basal treatment of people with diabetes. The medicine can be prescribed for the treatment of diabetes in addition to adults and children aged 2 years and older.

Release form

The drug is released in the form of a parenteral medicinal solution, in special 3 ml syringe pens. Inside the box there are 1 or 5 such syringes.

Pharmacodynamics

Levemir is a soluble form of basal human insulin. It has a powerful prolonged effect and is used for basal treatment of people diagnosed with type 1 diabetes.

The drug has a noticeable predictability of the expression and nature of the effect (if compared with insulin glargine, as well as NPH insulin). Its long-term therapeutic effect is associated with a significant relationship between the structures of the insulin detemir element, and also with the synthesis of the active element of the drug with albumin (binding occurs with the participation of side chains of fatty acids).

At the same time, the prolonged effect of the drug is ensured by the ability of insulin detemir to distribute significantly more slowly (if these indicators are compared with NPH insulin) within target tissues. The complex mechanism of prolonged effect helps to ensure a well-predictable mechanism of drug effect.

The antidiabetic effect of the drug is due to the improvement of the ability of target tissues to absorb glucose (after the synthesis of insulin with specific endings of muscle and also adipose tissues), and in addition to this, a decrease in the ability of the liver to release glucose.

The drug's action lasts for a maximum of 24 hours (the exact duration depends on the size of the dosage used), which allows the solution to be administered either once or twice a day. On average, 2-3 medicinal injections are required to achieve the required glycemic control with a two-time administration.

During tests, the use of the drug in a dose of 0.2-0.4 U/kg caused the development of 50% of the maximum effect in the 3-4th hour after injection (in general, the effect lasted a maximum of 14 hours).

The solution has linear parameters of action - the overall and peak effects, as well as the duration of action of the drug are proportional to the dosage sizes.

Long-term use of the drug during clinical trials showed a small (compared to the indicators with the introduction of NPH insulin) basal variation in the level of glucose within the serum.

However, long-term clinical trials found smaller changes in weight in people who received Levemir (compared to people who used other forms of insulin).

In people with type 2 diabetes who were taking insulin in addition to oral antidiabetic therapy, a reduction in the incidence of nocturnal hypoglycemia was observed after taking Levemir.

In some groups of patients treated with insulin detemir, the development of antibodies was observed after long-term use, but this effect did not affect the therapeutic efficacy of glycemic control.

Pharmacokinetics

Peak values of the active element of the drug are observed in the serum after 6-8 hours after subcutaneous injection. In case of administration of the solution twice a day, suitable glycemic control is observed after the 2-3rd injection. In different groups of patients, there is a significantly smaller individual difference in the rate of absorption of the active component (compared to the use of other main insulin agents).

The absolute bioavailability values of the drug are approximately 60% (after subcutaneous administration of the solution).

The main part of the applied dose of the drug circulates within the vascular bed – this fact is demonstrated by the distribution volume indicator, which is approximately 0.1 l/kg.

In vivo and in vitro tests have not revealed any clinically significant interactions between insulin detemir in combination with fatty acids or other drugs synthesized with protein.

The metabolic processes of the active substance Levemir are similar to those carried out with endogenous insulin. All derivatives of the drug have no medicinal activity.

The final half-life after subcutaneous administration of a drug depends on the absorption rate inside the subcutaneous layer and, taking into account the quantity, reaches a range of 5-7 hours.

The solution has linear pharmacokinetic parameters.

Dosing and administration

The drug is administered subcutaneously through a special syringe pen. The drug helps to develop a long-term antidiabetic effect (maximum 24 hours), due to which it can be used as a basal form of insulin, administered once or twice a day. It is allowed to use the drug for monotherapy or in combination with a bolus form of insulin, liraglutide or antidiabetic oral drugs.

The dose size of the drug is determined individually; small daily variability in basal glucose levels within the serum allows for the most accurate selection of the insulin dosage for glycemic control.

The average recommended initial dose for people taking oral antidiabetic medications is 10 U or 0.1-0.2 U/kg once a day. Serum glucose levels should be closely monitored at the initial stage of treatment to ensure the correct dose is chosen.

If the glucose values after self-measurement on an empty stomach in the morning are greater than 10 mmol/l, the dose of the drug is increased by 8 U, and if these values are in the range of 9.1-10, as well as 8.1-9 and 6.1-8, the doses should be increased by 6, 4 or 2 U, respectively. If the glucose values measured under the above conditions are 3.1-4 mmol/l, the dose of insulin detemir should be reduced by 2 U, and if the value is less than 3.1 mmol/l, it should be reduced by 4 U.

The frequency of injections is prescribed by the doctor, taking into account the adjuvant treatment and the patient's body's need for insulin.

People who need to inject insulin twice a day are advised to perform the 2nd procedure before the evening meal or before bedtime.

It is necessary to take into account that correction of physical activity and nutrition, as well as severe stress or the development of concomitant pathology may cause the need to change the dosage of the drug.

Use of Levemir in certain categories of patients.

It is important to remember that changes in liver/kidney function may require adjustment of drug dosages (as the patient's need for insulin changes). The condition of people in this group should be closely monitored and portion sizes should be adjusted if deterioration in glycemic control is detected.

During the tests, the safety and therapeutic efficacy of the drug in patients aged 2 years and older were noted. Children requiring insulin therapy require careful monitoring of serum glucose values. It is necessary to carefully select the sizes of insulin doses for children.

Scheme for switching to Levemir from other insulin forms.

People previously using long-acting or moderate-acting insulins should carefully titrate their doses when switching to Levemir. Very careful monitoring of serum glucose levels is necessary during this process.

Conducting combination treatment for diabetes requires a revision of the regimen and dosages of all medications used when switching to a different type of insulin.

Scheme for administration of medicinal solution.

Injections must be administered subcutaneously only. Intravenous injections and intramuscular injections are prohibited. With intravenous administration of insulin, hypoglycemia may develop in a pronounced form (even fatal).

It is not possible to administer the medication using insulin pumps that have a continuous injection function; the medication can only be administered using a syringe pen.

For subcutaneous injections, the site should be chosen in the area of the anterior femoral surface, on the shoulder or in the anterior part of the peritoneum. All injections are recommended to be performed in different areas of the body (even within one small area), otherwise it may provoke the development of lipodystrophy.

The duration of action and the degree of expression of the antidiabetic effect of the drug may vary depending on the rate of blood circulation, temperature, the size of the portion of the drug, the injection site, as well as indicators of physical activity (due to the rate of metabolism and absorption of the active element of the drug).

Injections should be performed at the same time of day, most convenient for the patient.

The syringe is used in combination with disposable needles (NovoTwist or NovoFine), which are 8 mm long. The syringe is capable of injecting 1-60 units of insulin, also having a step of 1 unit.

Scheme of using a syringe pen when administering an injection.

The pen is intended exclusively for the administration of Levemir insulin injections.

Injection procedure:

• Before starting the administration, it is necessary to check the insulin type;
• remove the protective cap from the syringe;
• remove the packaging label from the single-use needle and then attach it tightly to the syringe;
• remove the outer cap from the needle (it must be kept until the end of the injection procedure);
• remove the inner protective cap from the needle and dispose of it immediately;
• set the portion size, after which you can begin the injection. To set the dosage, you need to use a special selector;
• insert the needle into the selected location and then press the button on the syringe;
• you need to hold the button down without removing the needle for at least 6 seconds (to inject the entire dose);
• remove the needle and remove it from the syringe using the outer protective cap;
• close the syringe with the protective cap.

A new needle must be inserted for each injection. If the needle is damaged or bent before the procedure, it should be disposed of and a new one should be used. To prevent accidental needle sticks, the inner protective cap must not be re-attached to the needle after it has been removed.

Before starting the administration of the drug, you need to check the insulin flow. This is done as follows:

• it is necessary to set the 2 U mark on the selector;
• holding the syringe in a vertical position, with the needle pointing up, you should gently tap it in the area where the cartridge is located;
• still holding the syringe in a vertical position, you need to press the button. As a result, the dosage selector should return to the 0 mark, and a drop of medicine should appear on the tip of the needle;
• if after carrying out the above manipulations a drop of solution does not appear, it is necessary to replace the needle and repeat the procedure described above;
• It is forbidden to repeat this manipulation more than 6 times - if there is no result after such a number of attempts, it can be concluded that the syringe is faulty, and therefore it can no longer be used.

The dose set on the selector can be changed both downwards and upwards by turning the selector in the required direction. When setting the dose, be careful not to press the start button (as this may cause insulin to leak out).

It is important to remember that the syringe selector cannot be set to a dosage that exceeds the amount of medication remaining in the cartridge. The insulin residue scale cannot be used to select the dose.

It is essential to remove the needle from the syringe after each procedure, because leaving it in place can cause the drug to leak out.

When performing injection procedures, general aseptic rules must be observed.

It is also important to remember that the syringe is intended for individual use only.

Cleaning and subsequent storage of the syringe pen.

It is not recommended to use the syringe if it has been dropped or deformed (as this may cause the medicine to leak out).

The outer part of the syringe used must be cleaned with cotton wool, which is pre-soaked in ethanol. The syringe must not be held under running water, completely immersed in alcohol, or lubricated with various agents.

Refilling the syringe is prohibited.

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Use Levemir during pregnancy

Pregnant women who use insulin detemir should closely monitor serum glucose levels. During pregnancy, the body's need for insulin changes, and the dose of the drug should be adjusted accordingly. In the first trimester, the need for insulin decreases, but in the second and third trimesters, it increases significantly. After childbirth, the need for insulin quickly returns to the pre-pregnancy level.

Levemir does not have a negative impact on the course of pregnancy or the healthy development of the fetus, and no increase in the likelihood of abnormalities in the fetus was found during tests.

Tests conducted on animals did not demonstrate any toxic effects of the drug on reproductive activity.

There is no information about the penetration of the drug into breast milk. The likelihood of its active component affecting breastfed infants is not very high, because inside the gastrointestinal tract the element is broken down, acquiring the form of amino acids.

During lactation, more careful selection of the insulin dose size and diet regimen may be required.

Contraindications

The use of the drug is contraindicated if the patient has hypersensitivity to insulin detemir or auxiliary medicinal elements.

Side effects Levemir

Most of the negative signs found during testing of the solution were either the result of the antidiabetic effect of insulin or a consequence of the underlying disease.

Often, when using the drug, patients developed hypoglycemia.

During the use of the syringe for subcutaneous injection, local reactions may develop - for example, the appearance of tissue edema, itching, skin hyperemia, and hematomas at the injection site have been noted. In addition, generalized signs of hypersensitivity may appear on the skin, including itching, urticaria, and rashes.

Local symptoms often disappear on their own, without requiring special therapy. These manifestations are most pronounced at the initial stage of drug use, the intensity gradually decreases during the course of therapy.

At the initial stage of insulin therapy, people undergoing treatment may develop refractory disorders, as well as tissue edema, which disappear on their own during the course of treatment.

With the development of significant positive dynamics of glycemic control in people with diabetes, painful neuropathy in the acute stage may develop (it is treatable and occurs due to strong changes in serum glucose levels).

At the first stage of treatment, along with a significant improvement in the effectiveness of glycemic control, patients may experience transient negative dynamics in the course of diabetic retinopathy (in this case, long-term and effective glycemic control reduces the risk of development and progression of this pathology).

In total, the following adverse reactions were observed in patients during post-marketing and clinical trials (this includes reactions that were observed only occasionally):

• immune damage: rashes, allergic symptoms, urticaria and manifestations of anaphylaxis;
• metabolic disorders: development of hypoglycemia;
• disorders in the functioning of the central nervous system: the occurrence of polyneuropathy;
• manifestations from the sense organs: diabetic retinopathy, as well as temporary refractory disorders;
• lesions affecting the subcutaneous layer and skin: development of lipodystrophy (the risk of this disease increases with regular repeated injections of drugs into the same area of the skin without changing the injection site);
• local signs: temporary swelling, itching and hyperemia.

Single use of the drug has resulted in symptoms of anaphylaxis (including potentially fatal cases). If the patient develops signs of anaphylaxis or Quincke's edema during treatment, they should immediately seek emergency medical care.

Hypoglycemia that occurs during the use of Levemir is usually caused by an incorrect selection of the insulin dose, as well as a change in diet or physical activity. In addition, the risk of hypoglycemia increases if the patient has infections that cause hyperthermia.

Severe hypoglycemia can lead to seizures, loss of consciousness, and then to transient and permanent brain damage and death. Among the first signs of pathology: a feeling of weakness, drowsiness and thirst, loss of orientation, development of tremor, tachycardia, headaches, nausea and visual disturbances, as well as pale skin, a feeling of hunger and cold sweat. It is necessary to remember that the early symptoms of the disease can weaken their intensity with long-term treatment using insulin, as well as with combination therapy with other drugs and in people who have long suffered from diabetes.

Overdose

At present, it has not yet been possible to fully formulate the specific concept of insulin intoxication. When administering too high doses of Levemir, the patient may develop hypoglycemia.

If a mild form of the disorder is observed, the patient needs to consume fast carbohydrates (for example, a glucose tablet or a small piece of sugar). People with diabetes should always have something sweet with them.

If hypoglycemia develops in a severe form, when the patient loses consciousness, it is necessary to administer glucagon (intramuscularly or subcutaneously in a dose of 0.5-1 mg). If there is no improvement from the use of glucagon after 10-15 minutes, an infusion of glucose solution should be performed.

After the patient regains consciousness, he must be given carbohydrates to take orally to prevent a relapse.

Interactions with other drugs

When using drugs and other medications in combination, it is necessary to take into account the effect of different drugs on the body's need for insulin, as well as the level of glucose tolerance.

Oral antidiabetic drugs, non-selective β-adrenergic receptor antagonists, MAOIs, ACE inhibitors, salicylates, and in addition, steroid anabolics and sulfonamides can reduce the body's need for insulin.

GCS, oral contraception, thiazide diuretics, sympathomimetics, growth hormones, thyroid hormones and danazol, on the contrary, increase the need for insulin.

The combination of β-adrenergic antagonists with Levemir may result in masking of hypoglycaemic symptoms.

The need for insulin may change when using the substances octreotide or lanreotide.

Ethanol in combination with the drug is able to potentiate the duration and degree of expression of the antidiabetic effect of insulin detemir.

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Storage conditions

The syringe pen used by the patient must be kept in a place out of reach of children at standard temperature marks. If the syringe is not used, it should be kept at a temperature within the range of 2-8 ^o C.

At standard temperature, a syringe of the drug can be stored for a maximum of 1.5 months.

Freezing Levemir solution is prohibited. The syringe should be kept in a dark place, protected from sunlight.

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Shelf life

Levemir can be used for 2.5 years from the date of release of the drug.

Application for children

Levemir should not be given to children under 2 years of age.

Analogues

The following drugs are analogs of the drug: Insulin Lente GPP, Insulong SPP, Aktrafan NM, as well as Insulin Minilente SPP, Iletin II Lente and Insulin Superlente SPP. The list also includes Lymphomyosot, Januvia, Humulin Ultralente, as well as Multisorb, Lymphomyosot, Bagomet, Metamin and Apidra. In addition, Glucobay, Glemaz and Levemir Penfill.

Reviews

Levemir receives good reviews from people suffering from diabetes. Among the advantages, patients note high efficiency, no addiction to the drug, no weight gain, and the ability to use the drug during pregnancy.

Among the disadvantages, most point out the high cost of the medicine. Some also complain about the inconvenience of using medicinal cartridges.