Gabapentin

When ATH:
N03AX12

White or off-white crystalline solid, easily soluble in water and in acidic and basic aqueous solutions. Molecular weight 171,24.

Pharmacological action.
Anticonvulsant, analgesic.

Application.

According to Physicians Desk Reference (2003), gabapentin shown in partsialynыh эpilepticheskih pripadkah with or without generalization in secondness vzroslыh and children aged 12 years (as an additional means), partial seizures in children 3-12 years (as an additional means), and for the treatment of post-herpetic neuralgia in adults.

Hypersensitivity, Children up to age 3 years with partial seizures (effectiveness as an adjunct in the treatment is not installed) and to 12 years of post-herpetic neuralgia (studies on the efficacy and safety have not been conducted).

Perhaps during pregnancy, only if the effect of therapy outweighs the risk to the fetus (adequate and well-controlled studies in pregnant women has not been). At the time of treatment should stop breastfeeding (Gabapentin passes into breast milk when taken orally).

The most commonly observed adverse events, associated with the use of gabapentin in adults, whose frequency is different from that in patients, placebo treatment, were dizziness, drowsiness, and peripheral edema.

In two controlled clinical trials 16% from 336 patients, receiving gabapentin, and 9% from 227 patients, placebo, discontinued treatment because of side effects. The most common side effects, lead to the cancellation of gabapentin, were dizziness, drowsiness and nausea.

In the table 1 The symptoms of the disease and symptoms, were observed in at least 1% patients with post-herpetic neuralgia, treated with gabapentin, participated in placebo-controlled trials, and the incidence of which was higher, than placebo. The intensity of adverse events were mild to moderate.

Table 1

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Other side effects, observed in more than 1% patients, But there are equally or even more frequently in the group, placebo, were pain, tremor, neuralgia, backache, dyspepsia, dyspnoea, flu-like symptoms.

No significant clinical differences between men and women according to the type and frequency of adverse events. Because the study included only a few patients nonwhite race, data, to support a statement regarding the distribution of adverse events by race, insufficiently.

The most commonly observed adverse events, associated with the use of gabapentin in combination with other antiepileptic drugs in patients over 12 years, not seen at the same frequency band, placebo treatment, were somnolence, dizziness, ataxia, fatigue, and nystagmus. The most commonly observed adverse events, associated with the use of gabapentin in combination with other antiepileptic drugs in children from 3 to 12 years, not seen at the same frequency band, placebo treatment, It was viral infection, fever, nausea and / or vomiting, somnolence, and hostility.

About 7% from 2074 patients aged 12 years and about 7% from 449 children aged 3 to 12 years, treated with gabapentin in pre-marketing clinical trials, discontinued treatment because of side effects. The most common side effects, leads to the elimination of the drug in patients over 12 years, were somnolence (1,2%), ataxia (0,8%), fatigue (0,6%), nausea and / or vomiting (0,6%) and dizziness (0,6%). The most common side effects, lead to the abolition of the drug in children, It was emotional lability (1,6%), hostility (1,3%) and hyperkinesia (1,1%).

In the table 2 The symptoms of the disease and symptoms, were observed in at least 1% older patients 12 years with epilepsy, treated with gabapentin, participated in placebo-controlled trials, and the incidence of which was higher in the group, prynymavshey gabapentin. The intensity of adverse events were mild to moderate.

Table 2

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* In addition to the ongoing antiepileptic treatment
** Amblyopia is often described as blurred vision

When prescribing the medicine should be kept in mind, These data, obtained by the addition of gabapentin to the ongoing antiepileptic treatment, They can not be used to predict the frequency of adverse events in general medical practice, where the characteristics of the patient and other factors may differ from those, that prevailed in the clinical trials. Similarly,, said frequency of side effects can not be directly compared to rates, obtained in other clinical studies, involving different treatment regimens, other subjects or researchers. However, these data can serve as a basis for estimating the relative contribution of the drug and "non-drug factors" in the occurrence of adverse events in the study population.

Other side effects, observed in more than 1% older patients 12 years, But there are equally or even more frequently in the group, placebo, were headache, viral infection, fever, nausea and / or vomiting, abdominal pain, diarrhea, convulsions, insomnia, emotional lability, rash, acne.

Among the side effects, related to treatment with gabapentin and occur with a frequency of at least 10%, drowsiness and ataxia were, presumably, dose-dependent.

The overall incidence and type of adverse events were similar in men and women, treated with gabapentin. The frequency of adverse events increased slightly with increasing age of the patient as a group, gabapentin-treated, and placebo. Because the study involved only 3% (28/921) patients nonwhite race, data, to support a statement regarding the distribution of adverse events by race, insufficiently.

In the table 3 The symptoms of the disease and symptoms, were observed in at least 2% patients aged 3 to 12 years with epilepsy, treated with gabapentin, participated in placebo-controlled trials, and the incidence of which was higher in the group, prynymavshey gabapentin. The intensity of adverse events were mild to moderate.

Table 3

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Other side effects, observed in more than 2% Children aged 3-12 years, But there are equally or even more frequently in the group, placebo, were pharyngitis, upper respiratory tract infection, headache, rhinitis, convulsions, diarrhea, anorexia, cough, otitis media.

Other side effects, observed in all clinical trials

Clinical trials in adults and adolescents with epilepsy

In all clinical trials of adjuvant therapy in epilepsy, only some of which were placebo-controlled, Gabapentin was administered 2074 older patients 12 years. During these trials, all adverse effects, clinicians recorded using terminology of their own choosing. In order to provide comparable estimates of the results, similar types of adverse events were grouped into a smaller number of standard category using a modified COSTART dictionary terminological. These categories are used in the list below. Said rate represents the proportion of all 2074 older patients 12 years, in which the side effect mentioned type was observed at least once during gabapentin. Taking into account all cases except for already listed in table 2, as well as formulated in general terms and without an apparent causal connection, with the use of the drug. Side effects on the body systems were distributed and presented in order of decreasing frequency using the following definitions: often the side effects, met at least 1 from 100 patients; infrequently, ranging from 1 from 100 to 1 from 1000; rarely — less than 1 from 1000 patients.

Body as a Whole: often fatigue, malaise, swelling of the face; infrequently-allergies, generalized edema, weight loss; rarely is the unusual sensations, fatiguability, alcohol intolerance, hangover.

Cardiovascular system: often, hypertension; infrequently-hypotension, angina, peripheral circulatory disorders, heartbeat, tachycardia, migraine, murmur; rarely is a fibrilllâciâ flutter, heart failure, tromboflebit, deep vein thrombosis, myocardial infarction, stroke, lehochnыy thrombosis, ventricular or atrial premature beats, bradycardia, pericardial rub, heart block, pulmonary embolism, hyperlipidemia, hypercholesterolemia, pericardial effusion, perikardit.

Digestive system: often — anorexia, flatulence, gingivitis; infrequently-Glossitis, krovotochivosty right, thirst, stomatitis, increased salivation, gastroenteritis, hemorrhoids, hematochezia, scatacratia, gepatomegaliya; rarely is dysphagia, belching, pancreatitis, pepticheskaya ulcer, colitis, blisters in the mouth, discolouration of the teeth, bridou, salivary gland enlargement, bleeding lips, esophagitis, hiatal hernia, hematemesis, proctitis, irritable bowel syndrome, rectal hemorrhage, esophagism.

Endocrine system: rare hyperthyroidism, gipotireoz, goiter, a decrease in estrogen levels, ovarian failure, epididymitis, swelling of the testicles, cushingoid phenomenon.

Blood and lymphatic system: often-purpupa, most often described as a hematoma resulting from physical trauma; infrequently-anemia, thrombocytopenia, lymphadenopathy; rarely, an increase in the number of leukocytes, Lymphocytosis, nehodzhkinskaya lymphoma, increased bleeding.

Musculoskeletal System: often, arthralgia; infrequently - tendonitis, arthritis, joint stiffness, swelling of the joints, positive Romberg test; rarely is a chondrite rib, osteoporosis, ʙursit, contracture.

Nervous system: often Vertigo, giperkineziya, paraesthesia, decreased or absent reflexes, increased reflexes, alarm, hostility; rarely is a tumor of the CENTRAL NERVOUS SYSTEM, synkopэ, unusual dreams, afazija, gipesteziya, intracranial hemorrhage, hypotension, dysesthesia, paresis, dystonia, hemiplegia, Bell's paralysis, stupor, cerebellar dysfunction, Babinski syndrome, violations in locating, subdural hematoma, apathy, hallucinations, reduction or loss of libido, ažitaciâ, paranoia, depersonalization, euphoria, hypersensitivity, a sense of power, feeling of intoxication, suicidal thoughts, psychosis; rarely — horeoatetoz, orofatsialynaya dyskinesia, encephalopathy, nerve palsy, personality change, increased libido, relaxed temperament, apraxia, violation of the control fine movements, meningism, local myoclonus, giperesteziya, gipokineziya, craze, neurosis, vapors, antisocial reaction, suicidal intentions.

Respiratory system: often pneumonia; infrequently — nosebleeds, dyspnoea, apnea; rarely — mucositis, aspiration pneumonia, hyperventilation, Ikotech, laringit, nazalynaya obstruction, snoring, bronchospasm, gipoventilyatsiya, pulmonary edema.

Dermatological disorders: Parts - alopecia, eczema, xerosis, increased perspiration, hives, girsutizm, seborrhea, cyst, herpes simplex; rarely, shingles, depigmentation of the skin, papular rash, photosensitivity reaction, Foot ulcers, seborrhea scalp, psoriasis, peeling, maceration, cutaneous and / or subcutaneous nodules, melanosis, skin necrosis, Local swelling.

Genito-urinary system: infrequently-hematuria, dizurija, frequent urination, cystitis, urinary retention, vaginal bleeding, amenorrhea, dysmenorrhoea, menorragija, mammary cancer, abnormal ejaculation; seldom-pain in the kidneys, white, genital itching, stones in the kidneys, acute renal failure, anurija, glycosuria, nephrosis, nocturia, pyuria, uriesthesia, vaginal pain, pain in the breast, pain in the testicle.

Senses: often a violation of Visual acuity; infrequently-cataract, conjunctivitis, dry eyes, eye pain, defect angle, photophobia, bilateral or unilateral ptosis, bleeding in the eye, barley, hearing loss, otalgia, noise in ears, inner ear infection, otitis, loss of taste, unusual taste, eye twitching, feeling of ear congestion; rare is ocular itching, ccomodation, perforated eardrum, sensitivity to noise, problems with focusing of, watery eyes, retionopatiâ, glaucoma, Irit, corneal disease, dysfunction of the lacrimal duct, Degenerative changes in the eye, blindness, degeneration setchatki, mioz, horeoretinit, kosoglazie, eustachian tube dysfunction, laʙirintit, otitis externa, unusual smell.

In 449 children aged 3 to 12 years with epilepsy in clinical trials for the treatment of gabapentin observed following side effects, which there was no adjuvant therapy in adults:

Body as a Whole: degidratatsiya, kissing disease.

Nervous system: the disappearance of the aura, zatыlochnaya neuralgia.

Clinical trials in adults with neuropathic pain of various etiologies

Information about the safety of the obtained during the double-blind and open-controlled clinical trials involving 1173 patients, including patients with neuropathic pain, for which treatment efficacy has not been demonstrated. Reported side effects clinicians are grouped into groups using standard terminology modified COSTART IV. Taking into account all cases except for already listed in table 1 not reasonably associated with the use of the drug.

Side effects on the body systems were distributed and presented in order of decreasing frequency using the following definitions: often the side effects, met at least 1 from 100 patients; infrequently, ranging from 1 from 100 to 1 from 1000; rarely — less than 1 from 1000 patients.

Body as a Whole: infrequently — chest pain, cellulitis, malaise, pain in the neck, swelling of the face, allergic reaction, abscess, cold, cold and fever, blennosis; rarely is the emergence of special body odor, cyst, fever, hernia, deviation of blood urea nitrogen, swelling in the neck, pelvic pain, sepsis, viral infection.

Cardiovascular system: infrequently-hypertension, synkopэ, heartbeat, migraine, gipotenziya, the peripheral blood circulation, cardiovascular disorders, stroke, congestive heart failure, myocardial infarction, vasodilation; seldom-angina, heart failure, increased capillary fragility, phlebitis, tromboflebit, varicose veins.

Digestive system: infrequently-gastroenteritis, increased appetite, gastrointestinal upset, candidiasis of the oral mucosa, gastritis, loss of language and / or teeth, thirst, violation of the chair, anorexia, changes in liver function tests, periodontal abscess; rarely — cholecystitis, cholelithiasis, duodenal ulcer, scatacratia, increase the level of gamma-glutamyl, gingivitis, kishechnaya obstruction, intestinal ulcers, ground, ulcers of the mouth, defeat rectum, rectal bleeding, stomatitis.

Blood and lymphatic system: infrequently-ecchymosis, anemia; rarely — Lymphadenopathy, chyliform reaction, reduction in the level of prothrombin.

Metabolism and nutrition disorders of the: seldom-swelling, gout, gipoglikemiâ, weight loss; rarely is an increase in alkaline phosphatase level, diabetic ketoacidosis, increased levels of lactate dehydrogenase.

Musculoskeletal System: infrequently-arthritis, arthralgia, myalgia, arthrosis, leg cramps, myasthenia; seldom-pain in the tibia, arthronosos, tendon disease.

Nervous system: often is confusion, depression; infrequently-Vertigo, nervousness, paraesthesia, insomnia, neuropathy, decreased libido, alarm, depersonalization, a decrease reflexes, speech disorder, unusual dreams, dysarthria, emotional lability, nistagmo, stupor, euphoria, gipersteziya, gipokineziya; rarely ajitation, hypertension, increase libido, movement disorder, myoclonus, vestibular disorders.

Respiratory system: infrequently — increased cough, bronchitis, rhinitis, sinusitis, pneumonia, asthma, Pulmonary Disease, nose bleed; rarely, hemoptysis, voice alteration.

Skin and skin appendages: seldom-itching, skin ulcer, xerosis, shingles, skin disease, fungal dermatitis, furunculosis, lichen simplex, psoriasis, increased perspiration, hives, rash with blisters; rarely, acne, Hair diseases, maculopapular rash, Nail disease, skin cancer, depigmentation of the skin, skin hypertrophy.

Senses: rarely is a violation of Visual acuity, eye disease, dysgeusia, Ear ache, deafness; rarely is a conjunctival hyperemia, diabeticheskaya retinopathy, eye pain, retinal vein thrombosis, ageusia.

Genito-urinary system: rarely is a urinary tract infection, dizurija, impotence, urinary incontinence, vaginal candidiasis, pain in the breast, menstrual disorders, polyuria, urinary retention; rarely is cystitis, abnormal ejaculation, gynecomastia, nocturia, pyelonephritis, swelling of the penis and scrotum, frequent urination, uriesthesia, changes in urine.

In post-marketing period for the treatment of gabapentin observed the following side effects, not listed above, and for which insufficient data to evaluate their frequency or importance: angioedema, fluctuations in blood glucose level, erythema multiforme, increase in liver enzymes, fever, giponatriemiya, jaundice, Syndrome Stevens - Johnson.

Clinically significant interaction between gabapentin and other anticonvulsants (phenytoin, valproic acid, phenobarbital, Carbamazepine), and oral contraceptives, containing norethisterone and / or ethinyl estradiol, not installed.

Antacids reduce the bioavailability of gabapentin (studies at a joint reception with Maalox bioavailability of gabapentin was reduced by 20%, When administered through 2 h after administration Maaloksa-on 5%).

Naproxen (dose 250 mg), apparently, increases absorption of gabapentin (dose 125 mg) from 12 to 15%. Gabapentin has no effect on the pharmacokinetic parameters of naproxen. Meaningful interactions of these drugs at the recommended doses are not known.

Morphine (60 mg) When administered through 2 h after administration of gabapentin (600 mg) increased the AUC of gabapentin by 44%.

Overdose.

Acute overdose have been reported when taking 49 g. In this case, there were the following symptoms: diplopia, gibberish, drowsiness, lethargy, diarrhea.

Postgerpeticheskaya neuralgia: in 1-day treatment is 300 mg / day one, in 2-nd day 1600 mg / day (in 2 admission), in the 3-rd day 900 mg / day (in 3 admission). If you need to reduce pain in a subsequent dose can be increased up to 1800 mg / day (in 3 admission).

Epilepsy (as an additional means): older patients 12 years-900-1800 mg/day (in 3 admission). The initial dose - 300 mg 3 once a day, if necessary, increase the dose to 1800 mg / day. The daily dose should not exceed 3600 mg. Children 3-12 years-initial dose of 10-15 mg/kg/day (in 3 admission), effective dose is selected within titration 3 days.

Babies 5 years and older — effective dose 25-35 mg/kg/day, children 3-4 years- 40 mg / kg / day (in 3 admission).

Maximum interval between meals should not exceed dose 12 no.

Abolition of gabapentin and / or adding to the treatment of other anticonvulsants carried out gradually over a period of not less than 1 Sun.

Patients (senior 12 years) with impaired renal function (creatinine clearance less than 60 ml / min) or patients, receiving hemodialysis, reduce the dose. When the clearance of not less than 60 mL/min — 900-3600 mg/day, When clearance 30-59 mL/min-400-1400 mg/day, 15-29 ml/min — 200-700 mg/day, less 15 mL/min — 100-300 mg/day. Patients, hemodialysis, additional postgemodializnaâ dose is 125-350 mg after each 4-hour hemodialysis session.

Gabapentin should not be administered to patients 12 years with reduced renal function (studies have not been conducted). Be wary appoint older (more likely to age renal dysfunction; dose set in accordance with a creatinine clearance).

While receiving gabapentin should not drive and use sophisticated technology, which requires high concentration of attention.

When co-administered with morphine is necessary to strictly control the adverse effects arising from the CNS. The dose of gabapentin and morphine reduced gradually.

Gabapentin should be taken no earlier than, than 2 h after administration antacida.

In determining the urine protein test via Ames N-Multistix SG may receive false positive results when used together with other gabapentin anticonvulsants, so it is recommended to use more specific methods.

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