Gabapentin - instructions for use, dose, side effects, contraindications

Pharmacodynamics:The exact mechanism of action of gabapentin is still unknown. Having structural similarity with gamma-aminobutyric acid, without binding to GABA receptors and GABA agonists, it interacts with new binding receptors in cortical neurons (possibly associated with the L-system of amino acid transport through their cell membranes). The drug exhibits anticonvulsant and anti-neurological properties.Not metabolized to gamma-aminobutyric acid or agonist of its receptors and does not inhibit the capture or degradation of gamma-aminobutyric acid.

Pharmacokinetics:Gabapentin quickly absorbed, food intake slightly increases absorption and maximum plasma concentration in the plasma by 14%. Virtually not metabolized in the human body. The "apparent" volume of distribution after administration of 150 mg of the drug is 50-60 l / kg. Passes through the blood-brain barrier. The concentration in the cerebrospinal fluid reaches 20% of that in the plasma. The bioavailability of gabapentin decreases with increasing dose. When you take 900 mg per day - 60%, at 3600 mg per day - 33%. Binding to plasma proteins is less than 3%. Not metabolized by enzymes of the liver, is excreted by renal excretion. The half-life is 5-7 hours and does not depend on the dose of the drug, with the creatinine clearance less than 30 ml / min increased to 52 hours. The time to reach the maximum concentration is 2-4 hours. The therapeutic concentration of gabapentin in the blood plasma is not known. The frequency of seizures significantly decreases only at a concentration of 2 mg / l (11.7 μmol / l). The clearance of gabapentin is directly proportional to the creatinine clearance. Higher ground clearance - in children under the age of five; in children of the first year of life, the variability is unstable.In elderly people and in patients with impaired renal function, clearance of gabapentin is reduced. Elimination by the kidneys (up to 100% unchanged). Removed from the body during hemodialysis.

Indications:For monotherapy of partial epileptic seizures with or without secondary generalization in adults and children over 12 years of age;

Second-line drug for partial epileptic seizures in children 3-12 years of age;

Treatment of neuropathic pain (including postherpetic neuralgia and diabetic neuropathy) in patients older than 18 years.

The effectiveness of prescribing with diabetic neuropathy at a dose of 900-1800 mg per day is comparable to that with amitriptyline at a dose of 25-75 mg per day, but gabapentin better tolerate patients.

ICD-10

VI.G40-G47.G40.0 Localized (focal) (partial) idiopathic epilepsy and epileptic syndromes with convulsive seizures with a focal start

VI.G40-G47.G40.2 Localized (focal) (partial) symptomatic epilepsy and epileptic syndromes with complex partial seizures

VI.G40-G47.G40.1 Localized (focal) (partial) symptomatic epilepsy and epileptic syndromes with simple partial seizures

VI.G50-G59.G53.0 * Neuralgia after shingles (B02.2 +)

Contraindications:Hypersensitivity to the drug; children under 3 years old (safety and efficacy not studied).

Carefully:Pregnancy, breast-feeding.

Impaired renal function (elimination is prolonged in patients who are not receiving hemodialysis, and shortened in patients receiving him a dosage adjustment based on creatinine clearance).

When taking gabapentin, do not drive vehicles and use sophisticated techniques that require increased concentration.

Pregnancy and lactation:The action category for the fetus by the FDA is C. There have not been well-controlled studies on humans. In animal experiments, the drug did not affect fertility, showed moderate teratogenicity and embryotoxicity.

Lactation: the drug penetrates into breast milk, its effects on breastfed infants are not studied. Pregnant and lactating mothers should be gabapentin, only if the potential benefit exceeds the potential risk.

Dosing and Administration:The maximum daily dose is 3600 mg (in 3 doses). There is evidence of a good tolerability of patients at a dose of 4800 mg. The maximum single dose to 1200 mg.The standard scheme of application is 300 mg 3 times a day inside. Titrate the dose should be, focusing on the clinical response, rather than the concentration of gabapentin in the blood plasma. Children are prescribed 10 mg / kg once a day inside. Then gradually increase to a maintenance dose of 20 mg / kg 3 times a day.

Application in elderly patients

Age-related renal impairment is more likely in elderly patients; the dose is set in accordance with the clearance of creatinine.

Use in children

Children older than 3 years gabapentin mainly used as an additional treatment for partial seizures with secondary generalization or without it. The drug is prescribed in case of ineffectiveness of other antiepileptic drugs.

In children younger than 3 years, the effectiveness of gabapentin with additional treatment of partial seizures is not established. The safety and effectiveness of gabapentin in the treatment of postherpetic neuralgia in children has not been studied.

In controlled studies in children aged 3-12 years, adverse reactions from the CNS were recorded, including emotional lability, aggressiveness, impaired concentration.

In children with kidney failure gabapentin not studied.

Side effects:Slightly pronounced and tend to decrease when discontinuing admission.

From the side of the central nervous system and the peripheral nervous system: amnesia, ataxia, confusion, impaired coordination of movements, depression, dizziness, dysarthria, increased nervous excitability, nystagmus, drowsiness, impaired thinking, tremor, convulsions, amblyopia, diplopia, hyperkinesia, strengthening, weakening or lack of reflexes, paresthesia, anxiety, hostility , violation of gait.

From the digestive tract: changes in tooth color, diarrhea, increased appetite, dry mouth, nausea, vomiting, flatulence, anorexia, gingivitis, abdominal pain, pancreatitis, changes in functional liver tests.

On the part of the hematopoiesis system: leukopenia, a decrease in the number of leukocytes, thrombocytopenic purpura.

From the respiratory system: rhinitis, pharyngitis, cough, pneumonia.

From the musculoskeletal system: myalgia, arthralgia, fractures of bones.

From the cardiovascular system: arterial hypertension, manifestations of vasodilation.

From the urinary system: urinary tract infection, urinary incontinence.

Allergic reactions: erythema multiforme, Stevens-Johnson syndrome.

Dermatological reactions: maceration of the skin, acne, itching, rash.

Other: pain in the back, fatigue, peripheral edema, impotence, asthenia, malaise, facial swelling, weight gain, accidental trauma, asthenia, flu-like syndrome, fluctuations in blood glucose, in children - viral infection, otitis media.

Overdose:These symptoms may indicate an overdose: diarrhea, diplopia, dysarthria, lethargy, drowsiness, lethargy.

There is no specific antidote. Treatment is symptomatic; Hemodialysis (recommended on the basis of clinical status or patients with chronic renal failure) can completely eliminate the drug from the body.

Patients who intentionally exceed the dose are referred to a consultation with a psychiatrist.

Interaction:Alcohol or drugs that depress the central nervous system - an increase in sedation.

Antacids, especially those containing aluminum or magnesium: an antacid agent taken during or within 2 hours after taking gabapentin, inhibits the bioavailability of the latter by 20% (gabapentin should be taken at least 2 hours after taking the antacid drug).

Hydrocodone - simultaneous administration with gabapentin reduces the maximum plasma concentration and area under the hydrocodone concentration-time curve and increases the concentration of gabapentin by 14%.

Morphine - simultaneous use increases the area under the concentration-time curve by 44%, the concentration of gabapentin in the plasma, increasing the sedative effect (a dose reduction of each drug may be required).

Special instructions:Gabapentin does not interact with other, most commonly used antiepileptic drugs.

Antiepileptic drugs can increase folate deficiency during pregnancy (one of the possible causes of fetal development disorders), therefore, during the treatment period an additional intake of folic acid is recommended.

Anticonvulsants are ineffective for the relief of acute pain. The results of the studies do not give grounds for using them as a means of first choice.

Gabapentin is effective in postherpetic neuralgia and diabetic neuropathy, but has no advantages over carbamazepine - a less expensive alternative.

Patients with age-related impairment of renal function are reduced in dose, depending on the creatinine clearance.

In people with reduced liver function, most likely, the drug is prescribed in the usual dosage, since gabapentin not metabolized in the liver.

It is necessary to cancel or replace the drug for an alternative medicine gradually, for a minimum of 1 week. A sharp cessation of treatment with antiepileptic drugs can trigger the development of epileptic status in patients with epilepsy.

Instructions

Gabapentin (Gabapentinum)