Meditan

Meditan is a drug from the anticonvulsant category.

Indications Meditana

It is used to treat epilepsy - as an additional agent for the treatment of partial seizures (also in cases with complications in the form of secondary generalization) in children over 6 years of age and adults. In addition, the drug is used in monotherapy of the above-mentioned disorder in adolescents from 12 years of age and adults.

The medication is also prescribed for the treatment of neuropathic pain (peripheral type) - for example, with neuropathy of diabetic origin or post-acute neuralgia (in adults).

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Release form

The drug is released in capsules, in the amount of 10 pieces inside a blister pack. Capsules with a volume of 0.1 and 0.4 g are released in 3 blister packs in a box, and capsules with a volume of 0.3 g are sold in 3 or 6 plates inside a box.

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Pharmacodynamics

There are no precise data regarding the mechanism of therapeutic effect exerted by gabapentin.

The structure of gabapentin is in many ways similar to the neurotransmitter GABA, but the mechanism of its medicinal effect is different from the effect of other elements that interact with GABA endings (including barbiturates, substances that slow down the activity of GABA transferase, valproates, agents that inhibit the process of GABA uptake, and also GABA precursors and agonists of GABA elements).

Therapeutic doses of gabapentin do not result in synthesis with the terminals of other common drugs or with neurotransmitter terminals in the brain (including the terminals of GABA and GABAB, glutamate with benzodiazepines, glycine or NMDA).

The element gabapentin did not interact (in vitro tests) with Na channels, which distinguishes it from carbamazepine and phenytoin. Separate in vitro test systems showed that gabapentin partially reduced the intensity of the action of the glutamate agonist NMDA. This effect can only be achieved at drug levels exceeding 100 μmol, and this is not possible in vivo. Gabapentin also slightly reduces the secretion of monoamine neurotransmitters in vitro.

Gabapentin increases GABA metabolism in certain areas of the rat brain; sodium valproate also has this effect, but in other areas of the brain. What significance these effects of gabapentin have in relation to its anticonvulsant effect is unknown.

In animals, the active element of the drug passes through the blood-brain barrier and stops the maximum tolerable seizures caused by electric shock, as well as seizures induced by chemical convulsants (including substances that slow down the binding of GABA), and those provoked by the influence of genetic factors.

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Pharmacokinetics

Absorption.

After oral administration of gabapentin, plasma Cmax values are noted after 2-3 hours. With an increase in the dose of the drug, a tendency to a decrease in the level of bioavailability of the substance (its absorbed part) can be seen. The absolute bioavailability values after taking a 0.3 g capsule are approximately 60%. Eating food (including fatty foods) has no clinical significance for the pharmacokinetic parameters of gabapentin.

The pharmacokinetics of the drug is not affected by repeated administration of the drug. Although the plasma parameters of the drug during clinical tests fluctuated within 2-20 mcg/ml, these values do not determine the degree of safety and effectiveness of the drug.

Distribution processes.

The medicinal element is not subject to protein synthesis in the blood plasma. The distribution volume of the drug is 57.7 liters. The level of the substance in the cerebrospinal fluid in people with epilepsy is approximately 20% of the minimum equilibrium values in the plasma. Gabapentin can pass into breast milk.

Excretion.

Gabapentin is excreted unchanged only through the kidneys. The half-life of the element is not tied to the dosage size and is on average 5-7 hours.

In adults with impaired renal function, decreased plasma drug clearance values are observed. The elimination rate constant, as well as the clearance in the kidneys and plasma, are directly proportional to the CC values.

The substance is excreted from plasma during hemodialysis sessions. Therefore, people with renal dysfunction undergoing hemodialysis should adjust the dose of Meditan.

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Dosing and administration

The capsules are taken orally, without regard to food intake. The medicine should be washed down with a large amount of liquid (1 glass of plain water).

The mode of use during the initial selection of dosage for adolescents from 12 years of age and adults: on the 1st day, take 0.3 g per day (once); on the 2nd day - 2 times a day 0.3 g of the drug; on the 3rd day - 3 times a day 0.3 g of the drug.

The process of drug withdrawal.

Doctors recommend discontinuing the drug gradually, over a period of at least 7 days, regardless of the treatment regimen used.

Epilepsy.

In case of epilepsy, long-term treatment is often necessary. The dose of the drug is selected by the doctor, taking into account the effect of the drug and the patient's tolerance.

Adolescents over 12 years of age and adults with epilepsy are usually prescribed doses within 0.9-3.6 g per day. Therapy begins with titration of the drug dose or with a dosage of 0.3 g taken three times a day on the first day. Then, taking into account the therapeutic effect and tolerability of the drug, the dose can be increased by 0.3 g every subsequent 2-3 days, reaching a maximum of 3.6 g per day.

Some people require less rapid titration of the drug. The shortest period to reach a dose of 1.8 g per day is 7 days; 2.4 g - 14 days; 3.6 g - 21 days.

In long-term clinical tests, a dose of 4.8 g per day was well tolerated. The daily dosage should be divided into 3 doses. The intervals between doses should not exceed 12 hours – this is necessary to avoid interruption of antiepileptic treatment and to prevent the development of seizures.

For children aged 6-12 years, the initial dosage per day is 10-15 mg/kg. Effective dosage is achieved by titration over approximately 3 days. Children over 6 years of age should take 25-35 mg/kg per day.

The daily therapeutic dose of 50 mg/kg has been shown to be well tolerated (verified in long-term clinical trials). The total daily dose is divided into 3 equal-sized doses. The interval between doses can be a maximum of 12 hours.

There is no need to monitor the serum drug levels. Combined use of Meditan with other anticonvulsants is also allowed, because in this case the plasma gabapentin level or serum levels of other anticonvulsants do not change.

Neuropathic pain of a peripheral nature.

Adults first titrate the dose of the drug or divide the initial daily dosage of 0.9 g into 3 doses. After that, taking into account the effect and tolerance, the dose should be increased to the maximum value of 3.6 g per day according to the scheme described above.

Long-term clinical studies (more than 5 months) of the safety and medicinal effect of the drug in the treatment of neuropathic pain (diabetic form of neuropathy of a painful nature or PGN) have not been conducted. If longer-term therapy is required for neuropathic pain, the doctor must assess the patient's condition before continuing it and determine whether additional treatment is needed.

People with poor general health or some aggravating symptoms (post-transplant condition, low weight) need to titrate more slowly, reduce the step dose, or prolong the intervals between dose increases.

Elderly people (over 65 years of age).

Elderly patients should have their doses adjusted individually, as they may have weakened renal function. Such patients often experience peripheral edema and a feeling of weakness or drowsiness.

People with renal insufficiency.

Individuals with severe forms of the disorder or those undergoing hemodialysis should have their therapy regimen individually selected. They are recommended to use capsules with a volume of 0.1 g.

Serving sizes for kidney problems:

• CC values >80 ml/minute – take a total of 0.9-3.6 g of the drug per day;
• CC level within 50-79 ml/minute – consumption of 0.6-1.8 g of drug;
• CC indicators within 30-49 ml/minute – taking 0.3-0.9 g of medication;
• QC values within 15-29 ml/minute – use of 0.15*-0.3 or 0.15*-0.6 g of the substance.

*use in a 0.1 g portion 3 times a day, with intake every other day.

People on hemodialysis.

People with anuria undergoing hemodialysis and who have never taken Meditan before should take a loading dose of 0.3-0.4 g, followed by 0.2-0.3 g after every 4 hours of the hemodialysis session. The drug should not be taken on days when the procedure is not being performed.

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Use Meditana during pregnancy

Systemic risks of epilepsy and the use of anticonvulsants.

The probability of developing a congenital disease in a child whose mother took anticonvulsants increases two- to three-fold. The appearance of a "hare" lip, as well as defects in the development of the cardiovascular system and defects affecting the neural tube, was often noted. Complex anticonvulsant treatment has an even higher probability of developing anomalies (in comparison with monotherapy), which is why, if it is necessary to use drugs, monotherapy is recommended, if possible.

Women of reproductive age, as well as pregnant women, if they need anticonvulsant treatment, should consult a doctor before starting it. At the stage of planning conception, it is also necessary to reconsider the need for anticonvulsant therapy. It is prohibited to abruptly and suddenly stop using anticonvulsants, because this may result in convulsions, which will significantly worsen the condition of both the woman and the fetus.

Developmental delays in children born to mothers with epilepsy are quite rare. In such cases, it is impossible to differentiate what exactly caused the developmental delay in the child - genetic disorders, maternal epilepsy, social reasons, or the use of anticonvulsants during pregnancy.

Risks of using gabapentin.

There are no relevant data regarding the use of the substance during pregnancy. Animal tests have shown that it has reproductive toxicity, but the risks to the human body are unknown. Meditan should not be used during pregnancy unless the benefit to the woman is much more likely than the risks of complications to the fetus.

Gabapentin can be excreted in breast milk. Since the effect of the drug on infants has not been studied, it should be prescribed during lactation with great caution. The use of gabapentin during this period is justified only in situations where the benefit to the woman is more expected than the possibility of negative consequences for the child.

Contraindications

Contraindicated for use in people with intolerance to the active ingredient or other auxiliary components of the drug.

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Side effects Meditana

Taking capsules may cause some side effects:

• Diseases caused by parasites or infections: viral infections often occur. Infections affecting the urinary or respiratory system, pulmonary inflammation and otitis media are quite common;
• disorders affecting the lymph and hematopoietic processes: leukopenia often occurs. Rarely - thrombocytopenia;
• immune damage: occasionally, allergic symptoms (such as urticaria) may occur. DRESS syndrome or general disorders with various manifestations may occur (including hepatitis, rashes, fever, eosinophilia, lymphadenopathy, etc.);
• nutritional and metabolic disorders: anorexia or increased appetite is often observed. Hyperglycemia sometimes occurs (mainly in diabetics). Hypoglycemia occasionally occurs (also usually in diabetics). Hyponatremia may develop;
• Mental health problems: anxiety, hostility, confusion, abnormal thinking, depression, or emotional instability are common. Hallucinations occasionally occur;
• Disorders of the nervous system: a feeling of drowsiness, dizziness or ataxia are often observed. Quite often, hyperkinesis, headaches, convulsions, tremor, nystagmus are observed, as well as dysarthria, sensory disorders (hypesthesia or paresthesia) or coordination, insomnia, amnesia or memory impairment, as well as potentiation of reflexes, their weakening or complete absence. Rarely, movement disorders appear (including dyskinesia, choreoathetosis or dystonia) or loss of consciousness occurs. Sometimes, a disorder of mental function or hypokinesia may be observed;
• problems with visual function: visual disturbances often occur (for example, diplopia or amblyopia);
• disorders of the auditory system: vertigo often appears. Occasionally, tinnitus occurs;
• symptoms affecting the heart: occasionally there is an increase in heartbeat;
• vascular dysfunction: often there is an increase in blood pressure or vasodilation;
• problems related to respiratory function, the sternum and mediastinum: bronchitis, runny nose, dyspnea, cough or pharyngitis often occur;
• Gastrointestinal manifestations: nausea, diarrhea, gingivitis, vomiting, dental pathology, signs of dyspepsia, abdominal pain, constipation, dry throat or oral mucosa, and flatulence are often observed. Pancreatitis occasionally occurs;
• disorders of the biliary tract and liver: occasionally jaundice or hepatitis develops;
• Lesions affecting the subcutaneous layer and epidermis: purpura (usually appearing as bruises resulting from trauma), itching, facial swelling, rashes, and acne are common. Rarely, angioedema, alopecia, Stevens-Johnson syndrome, erythema multiforme, and drug rash occur, accompanied by systemic symptoms and eosinophilia;
• disorders of connective tissues and skeletal muscles: myalgia, back pain, arthralgia and muscle twitching often occur. Rhabdomyolysis or myoclonic seizures may develop;
• problems with the urinary system or kidneys: urinary incontinence is often observed. Rarely - acute renal failure;
• lesions of the mammary glands and reproductive organs: impotence often develops. Gynecomastia, hypertrophy of the mammary glands or sexual dysfunction (including anorgasmia, ejaculation disorder and changes in libido) may occur;
• Systemic symptoms: most commonly, fever and increased fatigue are observed. Also common are a feeling of weakness or discomfort, pain, generalized or peripheral swelling, gait disturbance, and flu-like symptoms. Withdrawal effects (usually hyperhidrosis, anxiety, nausea, insomnia, and pain) and chest pain occur occasionally. There are reports of sudden death, but in such cases, no clear link to drug use has been established;
• data from various tests: weight gain or a decrease in the number of leukocytes often occurs. Sometimes an increase in liver function values (ALT or AST) and bilirubin are observed. An increase in CPK values and fluctuations in sugar values in diabetics may be observed;
• intoxication or injury: often fractures, injuries or abrasions occur that are accidental in nature.

There are data on the development of acute pancreatitis during therapy using Meditan, but it was not possible to link this fact with the use of gabapentin.

In people with end-stage renal failure undergoing hemodialysis, myopathy with increased CPK levels has been reported.

Otitis media, respiratory tract infections, bronchitis and convulsions were observed only in clinical tests in children. In addition, hyperkinesis and aggressive behavior were often observed in the children tested.

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Overdose

The appearance of life-threatening toxic signs was not observed even when the drug was consumed in doses of up to 49 g per day.

Manifestations of intoxication include: diplopia, dizziness, loss of consciousness, a feeling of lethargy or drowsiness, slurred speech, and mild diarrhea. All symptoms disappeared after maintenance therapy. Decreased absorption of the drug in large doses may limit the absorption of other drugs and reduce the toxic effect in case of overdose.

While gabapentin can be removed from the body through hemodialysis, it is often not necessary, although it may be indicated for people with renal insufficiency.

Tests on rats and mice did not reveal a lethal dose of the drug, although in these cases dosages of up to 8 g/kg were used. Among the signs of acute poisoning in animals were ptosis, ataxia, decreased activity or, on the contrary, increased excitability, as well as difficulty in breathing.

Intoxication with the drug, especially in combination with other CNS depressants, can cause a comatose state.

Interactions with other drugs

Taking it together with antacids (magnesium- or aluminum-containing) reduces the bioavailability of Meditan by a maximum of 24%. The medicine should be taken at least 2 hours after using antacids.

Combination with cimetidine results in a slight decrease in renal excretion of gabapentin, but this effect is not clinically significant.

Tests involving volunteers (N=12) who took morphine capsules (60 mg) with a controlled release type 120 minutes before taking 0.6 g gabapentin showed that there is an increase in the mean AUC values of the latter by 44% compared with schemes in which morphine was not used. Because of this, with such combinations, it is necessary to closely monitor the condition of patients in order to recognize signs of CNS depression (feeling of drowsiness) in time and reduce the dosage of Meditan or morphine.

If other medications that affect the central nervous system are taken incorrectly, or if the drug is combined with alcoholic beverages, the negative effects of gabapentin in the central nervous system (ataxia, drowsiness, etc.) may be potentiated.

When combined with myelotoxic drugs, the hematotoxic effect increases (leukopenia develops).

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Storage conditions

Meditan should be kept in places closed to children. Temperature values are within 25ºС.

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Shelf life

Meditan can be used within 24 months from the date of release of the therapeutic drug.

Application for children

Gabapentin is prescribed in pediatrics for children suffering from epilepsy: as an additional agent during treatment of a child over 6 years of age or as monotherapy for adolescents over 12 years of age.

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Analogues

Analogues of the drug are the medications Gabamax, Gabagama 800, Gabapentin with Gabalept, and in addition Neuralgin with Tebantin, Gabantin 300, Neuropentin and Nupintin.

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