Gabapentin

Pharmacodynamics
Pharmacological action - analgesic, anticonvulsant.It prevents the occurrence of epileptic seizures during the induction of seizures by maximum electroshock and pentylenetetrazole in mice and rats, as well as in other preclinical models (for example, lines with genetically determined epilepsy, etc.). The relevance of these models in epilepsy in humans has not been established. Gabapentin is structurally similar to the GABA neurotransmitter, but does not alter the radioligand binding of GABA to GABA or GABAA receptors, is not metabolized to a GABA or GABA receptor agonist, and does not inhibit the capture or destruction of GABA. In studies using the radioligand binding method, gabapentin at concentrations up to 100 μM did not show affinity for a number of other receptors, including benzodiazepine, glutamate, N-methyl-D-aspartate, quisqualate, kainate, glycine (strychnine-insensitive and strychnine-sensitive), alpha1 -, alpha2- and beta-adrenergic, adenosine A1 and A2, muscarinic and nicotinic cholinergic, dopamine D1 and D2, H1-histamine, serotonin 5-HT1 and 5-HT2, opiate mu-, delta and kappa, cannabinoid 1, as well as to the binding sites of voltage-sensitive calcium channels labeled with nitrendipine or diltiazem) or voltage-sensitive sodium channels (labeled with 20-alpha-benzoate-batrachotoxinin A). In addition, gabapentin did not affect the cellular uptake of dopamine, norepinephrine and serotonin. In vitro studies using radiolabeled gabapentin, gabapentin binding sites were found in rat brain tissue, including the neocortex and hippocampus. The protein in the brain tissues of animals with a high affinity for gabapentin has been identified as an additional subunit of the voltage-activated calcium channel. The clinical significance of this binding fact has not yet been established. In experimental studies, gabapentin prevents allodynia and hyperalgesia, and especially the pain response in various models of neuropathic pain in rats and mice (models of streptozocin-induced diabetes, spinal cord injuries, etc.). In addition, it reduces the pain response in peripheral inflammation models, but does not affect the direct behavior due to pain. The relevance of these models for pain in humans has not been established. The efficacy of gabapentin as an adjuvant antiepileptic therapy in adults and children (3 years of age and older) with refractory partial seizures was established in multicenter, placebo-controlled, double-blind, clinical trials with parallel groups. Evidence of effectiveness was obtained in three studies involving 705 patients (aged 12 years and older) and in one study involving 247 children (aged 3 to 12 years). All patients included in these studies had a history of at least 4 partial seizures per month, despite the use of one or more antiepileptic drugs in therapeutic doses, and in the regimen of the antiepileptic therapy established by him, seizures were observed within a 12-week baseline - within 6 weeks). For patients with ongoing epileptic seizures (at least 2, and in some studies, 4 seizures per month), gabapentin or placebo was added to the therapy for 12 weeks. Efficiency was evaluated by the number of patients whose seizure frequency decreased by 50% or more compared to the initial level, and the “response coefficient” was calculated by the formula (T-B) / (T + B), where B is the base frequency of epileptic seizures and T is the frequency of epileptic seizures in the patient during treatment. The response rate ranged from 1 to +1. A value of zero indicates no change; the complete disappearance of seizures gives a value of 1, an increase in the frequency of seizures gives a positive response coefficient. A 50% decrease in the frequency of epileptic seizures corresponds to a response coefficient of 0.33. In the first study, gabapentin at a dose of 1200 mg / day, divided into 3 doses, was compared with placebo. The response rate was 23% (14/61) in the gabapentin group and 9% (6/66) in the placebo group; differences between groups were statistically significant. The response rate was also higher in the gabapentin group (−0.199) than in the placebo group (−0.044); the differences also reached a degree of statistical significance. In the second study, gabapentin (1200 mg / day in 3 divided doses, n = 101) was compared with placebo (n = 98), but to determine the dependence of the effect on the dose, two smaller groups in the number of patients who were prescribed gabapentin at a dose of 600 were additionally included in the study mg / day (n = 53) and 1800 mg / day (n = 54). The degree of response in the group taking gabapentin at a dose of 1200 mg / day (16%) was higher than in the group taking placebo (8%), but the differences were not statistically significant. The degree of response in the group taking 600 mg / day of gabapentin (17%) was also not significantly higher than in the group taking placebo, however, in the group taking 1800 mg / day, the degree of response (26%) was statistically higher than that in the group taking a placebo. The response coefficient in patients taking gabapentin at a dose of 1200 mg / day (−0.103) was higher than in the placebo group (−0.022), but this difference also had no statistical significance (p = 0.224). The best response was observed in the group taking gabapentin at a dose of 600 mg / day (−0.105) and at a dose of 1800 mg / day (−0.222) than in patients taking 1200 mg / day, while in the group taking gabapentin at a dose of 1800 mg / day, a statistically significant difference was achieved compared with placebo.In the third study, gabapentin (900 mg / day in 3 divided doses, n = 111) was compared with placebo (n = 109), and to study the dose-dependence of the effect, a group of patients (n = 52) who were prescribed 1200 mg / day were additionally included in the study gabapentin. There were statistically significant differences in the degree of response in the group taking gabapentin at a dose of 900 mg / day (22%), compared with placebo (10%). Response coefficients in the groups taking gabapentin at a dose of 900 mg / day (−0.119) and at a dose of 1200 mg / day (−0.184) were statistically significantly higher than that in the placebo group (−0.027). In all three of the above studies, the study of the effect of gabapentin in the prevention of secondary generalized tonic-clonic seizures showed statistically significant results and positive trends in almost all patients included in these studies.Analysis of the degree of response in the combined data of all three studies at all doses used (gabapentin - n = 162, placebo - n = 89) also indicates significant advantages of gabapentin over placebo in reducing the frequency of secondary generalized tonic-clonic seizures. Two of the three controlled trials used more than one dose of gabapentin. In each of these studies, no significant increase in dose-dependent response was found. However, there is an obvious general tendency to increase the effectiveness of gabapentin with increasing dose. In a fourth study involving pediatric patients (3 to 12 years old), gabapentin at a dose of 25–35 mg / kg / day (n = 118) was compared with placebo (n = 127). The response coefficient in all patients with partial seizures was significantly higher with gabapentin (−0.146) than in the placebo group (−0.079). Studies in children aged 1 month to 3 years who received 40 mg / kg / day of gabapentin (N = 38) compared with placebo (N = 38) did not reveal statistically significant differences in the degree of response and in the response rate in the studied patients . The efficacy of gabapentin for the control of postherpetic neuralgia was evaluated in two randomized, double-blind, placebo-controlled, multicenter trials in 563 patients. The criterion for the selection of patients was the preservation of pain for more than 3 months after the healing of skin rashes caused by shingles. Gabapentin was prescribed in a dose of 1800 to 3600 mg / day in 3 divided doses. In both studies, significant differences from placebo were found in the range of doses used. Typically, significant pain relief was observed during the first week of treatment and persisted until its end. In studies in mice and rats given orally gabapentin at a dose of more than 8000 mg / kg, a lethal dose has not been established. The following symptoms of acute toxicity were observed in animals: ataxia, shortness of breath, ptosis, sedation, decreased activity, or agitation. In experiments on mice and rats, to which gabapentin was mixed into food for 2 years, a statistically significant increase in the number of cases of acinar cell adenoma and pancreatic carcinoma in male rats was detected when receiving a high dose of 2000 mg / kg / day. At this dose, the peak plasma concentration of gabapentin in rats was 10 times higher than that in humans who received gabapentin at a dose of 3600 mg / day. Pancreatic acinar cell carcinoma did not affect survival, did not metastasize, and did not show local invasion. The relevance of these data to carcinogenic risk in humans has not been established. In standard in vitro and in vivo tests, gabapentin did not show mutagenic or genotoxic properties. No effect on fertility and reproduction was found in rats treated with gabapentin at a dose of up to 2000 mg / kg (approximately 5 times the maximum recommended dose for humans in terms of mg / m2).
Pharmacokinetics
Gabapentin is not significantly metabolized in humans. The bioavailability of gabapentin decreases with increasing dose and after administration of doses of 900, 1200, 2400, 3600 and 4800 mg / day (divided into 3 doses) is 60, 47, 34, 33 and 27%, respectively. Eating has little effect on the rate and extent of gabapentin absorption (14% increase in area under the AUC and Cmax curve).Binding to plasma proteins is less than 3%, the apparent volume of distribution after iv administration at a dose of 150 mg is 58 ± 6 L. In patients with epilepsy, Cmin in the cerebrospinal fluid was approximately 20% of the corresponding plasma level.Gabapentin is excreted by renal excretion. T1 / 2 - 5-7 hours and does not depend on the dose and subsequent multiple doses. Excretion rate constant, plasma clearance and renal clearance of gabapentin are directly proportional to creatinine clearance. In the elderly and in patients with impaired renal function, the plasma clearance of gabapentin is reduced. Gabapentin can be removed from plasma by hemodialysis.Patients with impaired renal function, the elderly and those on hemodialysis need a dose adjustment. In children with renal failure, gabapentin has not been studied. Patients with age-related impairment of renal function may need a dose reduction.Since gabapentin is not metabolized by the liver, studies in people with impaired liver function have not been conducted.A study of the pharmacokinetics of gabapentin in children with epilepsy showed that for children aged 3 to 4 years, in order to achieve the same average plasma concentration that is observed in children from 5 to 12 years old with a daily dose of 30 mg / kg, a daily dose of 40 mg is required / kg. Special comparative studies of the pharmacokinetics of gabapentin in men and women have not been conducted, however, apparently, there are no significant differences in the pharmacokinetic parameters of gabapentin in men and women.The pharmacokinetic differences in people of different racial groups have not been studied, however, since gabapentin is excreted mainly by the kidneys, and creatinine clearance in people of different races is not significantly different, the existence of such differences is not expected.
Contraindications
Hypersensitivity, children under 3 years old with partial seizures (efficacy as an additional treatment has not been established) and up to 12 years with postherpetic neuralgia (studies on efficacy and safety have not been conducted).
Pregnancy and lactation
It is possible during pregnancy only if the expected effect of therapy exceeds the risk to the fetus (adequate and well-controlled studies in pregnant women have not been conducted).The FDA category of action on the fetus is C. At the time of treatment, breast-feeding should be stopped (gabapentin passes into breast milk when taken orally).
Side effects
Postherpetic neuralgia The most frequently observed side effects associated with the use of gabapentin in adults, the frequency of which differed from that among patients treated with placebo, were dizziness, drowsiness, and peripheral edema. In two controlled clinical trials, 16% of 336 patients receiving gabapentin and 9% of 227 patients receiving placebo discontinued treatment due to side effects. The most common adverse events leading to the abolition of gabapentin were dizziness, drowsiness, and nausea.Other side effects observed in more than 1% of patients, but occurring equally or even more often in the placebo group, were pain, tremor, neuralgia, back pain, dyspepsia, dyspnea, flu-like syndrome. There were no significant clinical differences between men and women by type and frequency of adverse events. Since only a few patients of the non-white race participated in the studies, there is insufficient data to suggest the distribution of adverse events by race.Epilepsy.The most commonly observed side effects associated with the use of gabapentin in combination with other antiepileptic drugs in patients older than 12 years of age who did not occur with the same frequency in the placebo group were drowsiness, dizziness, ataxia, fatigue and nystagmus. The most frequently observed side effects associated with the use of gabapentin in combination with other antiepileptic drugs in children aged 3 to 12 years who did not occur with the same frequency in the placebo group were viral infection, fever, nausea and / or vomiting, drowsiness and hostility.Approximately 7% of the 2074 patients over the age of 12 years and approximately 7% of the 449 children aged 3 to 12 years who received gabapentin in a home-marketing clinical trial discontinued treatment due to side effects. The most common side effects leading to drug discontinuation in patients over 12 years old were drowsiness (1.2%), ataxia (0.8%), fatigue (0.6%), nausea and / or vomiting (0.6%) ) and dizziness (0.6%). The most common side effects leading to drug discontinuation in children were emotional lability (1.6%), hostility (1.3%) and hyperkinesia (1.1%).When prescribing a medicine, it should be borne in mind that these data obtained by adding gabapentin to ongoing antiepileptic therapy cannot be used to predict the incidence of adverse events in general medical practice, where patient characteristics and other factors may differ from those that prevailed in clinical trials.Similarly, the indicated frequency of side effects cannot be directly compared with indicators obtained in other clinical studies, including various treatment regimens, of other subjects or researchers. However, these data can serve as a basis for assessing the relative contribution of the drug and “non-drug factors” to the occurrence of side effects in the studied population.Other side effects observed in more than 1% of patients over 12 years of age, but occurring equally or even more often in the placebo group, were headache, viral infection, fever, nausea and / or vomiting, abdominal pain, diarrhea, convulsions , insomnia, emotional lability, rash, acne.Among the side effects associated with treatment with gabapentin and occurring with a frequency of at least 10%, drowsiness and ataxia were presumably dose-dependent.The overall frequency and type of adverse events were similar in men and women treated with gabapentin. The incidence of adverse events increased slightly with increasing age of the patient both in the gabapentin-treated group and in the placebo group. Since only 3% (28/921) of non-white race patients participated in the studies, there is insufficient data to suggest assumptions about the distribution of adverse events by race.Other side effects observed in more than 2% of children aged 3-12 years, but occurring equally or even more often in the placebo group were pharyngitis, upper respiratory tract infections, headache, rhinitis, convulsions, diarrhea, anorexia , cough, otitis media.Clinical trials in adults and adolescents with epilepsy. In all clinical trials of adjuvant therapy for epilepsy, among which only a few were placebo-controlled, gabapentin was prescribed to 2074 patients over 12 years of age. During these trials, all side effects were recorded by clinicians using the terminology of their choice. To provide a comparable assessment of results, similar types of adverse events were grouped into fewer standard categories using the modified COSTART terminology dictionary.These categories are used in the lists below. The indicated frequency is a fraction of all 2074 patients over 12 years of age in whom the side effect of the mentioned type was observed at least once during gabapentin administration. All cases are taken into account, with the exception of those already listed in Table 2, as well as those formulated in general terms and not having a visible causal connection with the use of the drug.Side effects were distributed across the body's systems and presented in order of decreasing occurrence frequency using the following definitions: often - side effects that occurred in at least 1 out of 100 patients; infrequently - from 1 in 100 to 1 in 1000; rarely, in less than 1 out of 1000 patients.The body as a whole: often - asthenia, malaise, swelling of the face; infrequently - allergies, generalized edema, weight loss; rarely - unusual sensations, fatigue, intolerance to alcohol, hangover.Cardiovascular system: often - hypertension; infrequently - hypotension, angina pectoris, peripheral circulatory disorders, palpitations, tachycardia, migraine, heart murmur; rarely - atrial fibrillation, heart failure, thrombophlebitis, deep thrombophlebitis, myocardial infarction, stroke, pulmonary thrombosis, ventricular or atrial extrasystole,bradycardia, pericardial friction noise, heart block, pulmonary embolism, hyperlipidemia, hypercholesterolemia, pericardial effusion, pericarditis.Digestive system: often - anorexia, flatulence, gingivitis; infrequently - glossitis, bleeding gums, thirst, stomatitis, increased salivation, gastroenteritis, hemorrhoids, bloody stools, fecal incontinence, hepatomegaly; rarely - dysphagia, belching, pancreatitis, peptic ulcer, colitis, blisters in the mouth, discoloration of teeth, angular stomatitis, enlarged salivary glands, lip bleeding, esophagitis, hiatal hernia, bloody vomiting, proctitis, irritable bowel syndrome, rectal hemorrhage esophagospasm.Endocrine system: rarely - hyperthyroidism, hypothyroidism, goiter, a decrease in estrogen levels, ovarian failure, epididymitis, testicular swelling, cushingoid phenomena.Blood and lymphatic system: often - purpupa, most often described as a hematoma as a result of physical trauma; infrequently - anemia, thrombocytopenia, lymphadenopathy; rarely - an increase in the number of white blood cells, lymphocytosis, non-Hodgkin's lymphoma, increased bleeding.Musculoskeletal system: often - arthralgia; infrequently - tendonitis, arthritis, joint stiffness, joint swelling, a positive Romberg test; rarely - rib chondritis, osteoporosis, bursitis, contracture. Nervous system: often - vertigo, hyperkinesia, paresthesia, a decrease or absence of reflexes, an increase in reflexes, anxiety, hostility; infrequently - CNS tumors, syncope, unusual dreams, aphasia, hypesthesia, intracranial bleeding, hypotension, dysesthesia, paresis, dystonia, hemiplegia, facial paralysis, stupor, cerebellar dysfunction, Babinsky syndrome, locomotion, subdural hematoma, apathy,hallucinations, decrease or loss of libido, agitation, paranoia, depersonalization, euphoria, increased sensitivity, a feeling of strength, a feeling of intoxication, suicidal thoughts, psychosis; rarely - choreoathetosis, orofacial dyskinesia, encephalopathy, nerve palsy, personality change, increased libido, impaired temperament, apraxia, impaired control of fine movements, meningism, local myoclonus, hyperesthesia, hypokinesia, mania, neurosis, hysteria, antisocial intentions. Respiratory system: often - pneumonia; infrequently - nosebleeds, dyspnea, apnea; rarely - mucositis, aspirated pneumonia, hyperventilation, hiccups, laryngitis, nasal obstruction, snoring, bronchospasm, hypoventilation, pulmonary edema. Dermatological disorders: often - alopecia, eczema, dry skin, increased sweating, urticaria, hirsutism, seborrhea, cyst formation, herpes simplex; rarely - shingles, skin depigmentation, papular rashes, photosensitivity reactions, foot ulcers, scalp seborrhea, psoriasis, desquamation, maceration, skin and / or subcutaneous nodules, melanosis, skin necrosis, local swelling. Genitourinary system: infrequently - hematuria, dysuria, rapid urination, cystitis, urinary retention, vaginal bleeding, amenorrhea, dysmenorrhea, menorrhagia, breast cancer, impaired ejaculation; rarely - kidney pain, leucorrhoea, genital itching, kidney stones, acute renal failure, anuria, glucosuria, nephrosis, nocturia, pyuria, urination, vaginal pain, pain in the mammary gland, pain in the testicle.Sense organs: often - violation of visual acuity; infrequently - cataracts, conjunctivitis, dry eyes, eye pain, visual impairment, photophobia, bilateral or unilateral ptosis, eye hemorrhage, barley, hearing loss, otalgia, tinnitus, infection of the inner ear, otitis media, loss of taste, unusual taste sensations, twitching of the eye, a feeling of stuffiness in the ear;rarely - itching, accommodation disturbance, perforation of the eardrum, sensitivity to noise, problems with focusing vision, watery eyes, retionopathy, glaucoma, iritis, corneal disease, lacrimal canal dysfunction, degenerative eye changes, blindness, retinal degeneration, myosis, choreoretinitis, strabismus, dysfunction of the Eustachian tube, labyrinthitis, otitis externa, unusual sense of smell.Clinical trials in children with epilepsy In 449 children aged 3 to 12 years with epilepsy during clinical trials with gabapentin, the following side effects were observed that were not observed with adjuvant therapy in adults:The body as a whole: dehydration, infectious mononucleosis. Digestive system: hepatitis. Blood and lymphatic system: coagulation disorder. Nervous system: disappearance of an aura, occipital neuralgia. Psychobiological function: sleepwalking. Respiratory system: false croup, dysphonia. Clinical trials in adults with neuropathic pain of various etiologies Safety information was obtained in double-blind and openly controlled clinical trials involving 1173 patients, including patients with neuropathic pain, for whom treatment efficacy has not been demonstrated. Side effects noted by clinicians are grouped into standard groups using modified COSTART IV terminology. All cases are taken into account with the exception of those already listed in table 1 and not having a visible causal relationship with the use of the drug. Side effects were distributed across the body's systems and presented in order of decreasing occurrence frequency using the following definitions: often - side effects that occurred in at least 1 out of 100 patients; infrequently - from 1 in 100 to 1 in 1000; rarely, in less than 1 out of 1000 patients.The body as a whole: infrequently - chest pain, cellulitis, malaise, neck pain, facial swelling, allergic reaction, abscess, colds, colds and fevers, mucosal lesions; rarely - the appearance of a special body odor, cyst formation, fever, hernia, deviation of the blood urea nitrogen value, swelling in the neck, pelvic pain, sepsis, viral infection.Cardiovascular system: infrequently - hypertension, syncope, palpitations, migraines, hypotension, impaired peripheral circulation, cardiovascular disorders, stroke, congestive heart failure, myocardial infarction, vasodilation; rarely - angina pectoris, heart failure, increased fragility of capillaries, phlebitis, thrombophlebitis, varicose veins.Digestive system: infrequently - gastroenteritis, increased appetite, gastrointestinal upset, candidiasis of the oral mucosa, gastritis, damage to the tongue and / or teeth, thirst, impaired stool, anorexia, changes in liver function tests, periodontal abscess; rarely - cholecystitis, cholelithiasis, duodenal ulcer, fecal incontinence, increased levels of gamma-glutamyl transpeptidase, gingivitis, intestinal obstruction, intestinal ulcer, melena, oral ulcer, rectal lesion, rectal bleeding, stomatitis.Endocrine system: infrequently - diabetes mellitus. Blood and lymphatic system: infrequently - ecchymosis, anemia; rarely - lymphadenopathy, lymphoid reaction, decrease in prothrombin level. Metabolism and nutritional disorders: infrequently - edema, gout, hypoglycemia, weight loss; rarely - an increase in the level of alkaline phosphatase, diabetic ketoacidosis, an increase in the level of lactate dehydrogenase. Musculoskeletal system: infrequently - arthritis, arthralgia, myalgia, arthrosis, spasms of the calf muscles, myasthenia gravis; rarely - pain in the tibia, joint disease, tendon disease. Nervous system: often - confusion, depression; infrequently - vertigo, nervousness, paresthesia, insomnia, neuropathy, decreased libido, anxiety, depersonalization, decreased reflexes, speech disturbance, unusual dreams, dysarthria, emotional lability, nystagmus, stupor, euphoria, hypersthesia, hypokinesia; rarely - agitation, hypertension, increased libido, impaired movement, myoclonus, vestibular disorders.Respiratory system: infrequently - increased cough, bronchitis, rhinitis, sinusitis, pneumonia, asthma, lung disease, nosebleeds; rarely - hemoptysis, voice change.Skin and skin appendages: infrequently - itching, skin ulcer, dry skin, shingles, skin disease, fungal dermatitis, furunculosis, lichen, psoriasis, excessive sweating, urticaria, rash; rarely, acne, hair disease, maculopapular rash, nail disease, skin carcinoma, skin depigmentation, skin hypertrophy.Sensory organs: infrequently - impaired visual acuity, eye disease, perversion of taste, ear pain, deafness; rarely - conjunctival hyperemia, diabetic retinopathy, eye pain, retinal vein thrombosis, loss of taste.Genitourinary system: infrequently - urinary tract infection, dysuria, impotence, urinary incontinence, vaginal candidiasis, pain in the mammary gland, menstrual irregularities, polyuria, urinary retention; seldom - cystitis, violation of ejaculation, gynecomastia, nocturia, pyelonephritis, swelling of the penis and scrotum, frequent urination, urination, change in urine.In the post-marketing period during the treatment with gabapentin, the following side effects were noted that are not listed above and for which there is insufficient data to assess their frequency or significance: angioedema, fluctuations in blood glucose, erythema multiforme, increased activity of liver enzymes, fever, hyponatremia, jaundice, Stevens-Johnson syndrome.
Interaction
A clinically significant interaction between gabapentin and other anticonvulsants (phenytoin, valproic acid, phenobarbital, carbamazepine), as well as oral contraceptives containing norethisterone and / or ethinyl estradiol, has not been established. Antacids reduce the bioavailability of gabapentin (in studies when taken with Maalox, the bioavailability of gabapentin was reduced by 20%, when taken 2 hours after taking Maalox, by 5%).Cimetidine slightly reduces the excretion of gabapentin. Naproxen (at a dose of 250 mg), apparently, increases the absorption of gabapentin (at a dose of 125 mg) from 12 to 15%. Gabapentin does not affect the pharmacokinetic parameters of naproxen. Significant interactions of these drugs in recommended doses are not known. Morphine (60 mg) when taken 2 hours after taking gabapentin (600 mg) increased the AUC of gabapentin by 44%.
Dosage and administration
Inside, swallowing whole, regardless of food intake and drinking plenty of fluids. If it is necessary to reduce the dose, cancel the drug or replace it with an alternative agent, this should be done gradually over a period of at least one week. Neuropathic pain in adults The initial daily dose is 900 mg, divided into three doses; if necessary, the dose is gradually increased to a maximum of 3600 mg / day. Treatment can be started immediately with a dose of 900 mg / day (300 mg 3 times a day) or during the first 3 days the dose can be increased gradually to 900 mg per day. according to the following scheme: 1st day: 300 mg 1 time per day .; 2nd day: 300 mg 2 times a day .; 3rd day: 300 mg 3 times a day. Partial cramps Adults and children from 12 years: effective dose - from 900 to 2400 mg / day. Therapy can be started with a dose of 300 mg 3 times a day. on the first day or gradually increase to 900 mg according to the scheme described above. Subsequently, the dose can be increased to a maximum of 3600 mg / day (divided into 3 equal doses). The maximum interval between doses when taking the drug three times should not exceed 12 hours in order to avoid the resumption of seizures. Recommendations for patients on hemodialysis Hemodialysis patients who have not previously taken Gabapentin are recommended to prescribe a drug in a saturating dose of 300-400 mg, and then apply it 200-300 mg every 4 hours of hemodialysis.
Overdose
An acute overdose was reported when taking 49 g. In this case, the following symptoms occurred: diplopia, slurred speech, drowsiness, lethargy, diarrhea. Treatment: maintenance therapy, hemodialysis.
Special instructions
When combined with morphine, it is necessary to strictly control the emerging side effects from the central nervous system. The dose of gabapentin and morphine is reduced gradually. Gabapentin should be taken no earlier than 2 hours after taking antacid. When determining protein in urine using the Ames N-Multistix SG test, false-positive results are possible with the combined use of gabapentin with other anticonvulsants, therefore it is recommended to use more specific methods.