Neurontin

Neurontin is given orally with or without food.

Coadministration of gabapentin with the oral contraceptive Norlestrin does not influence the steady-state pharmacokinetics of norethindrone or ethinyl estradiol.

For urinary protein determination the sulfosalicylic acid precipitation procedure is recommended, as false positive readings were reported with the Ames N-Multistix SG dipstick test, when gabapentin or placebo was added to other anticonvulsant drugs.

There is no interaction between Neurontin (gabapentin) and phenytoin, valproic acid, carbamazepine, or phenobarbital. Consequently, Neurontin may be used in combination with other commonly used antiepileptic drugs without concern for alteration of the plasma concentrations of gabapentin or the other antiepileptic drugs.

A literature article reported that when a 60 mg controlled release morphine capsule was administered 2 hours prior to a 600 mg gabapentin capsule in healthy volunteers (N=12), mean gabapentin AUC increased by 44% compared to gabapentin administered without morphine. Morphine pharmacokinetic parameter values were not affected by administration of gabapentin 2 hours after morphine in this study. Because this was a single dose study, the magnitude of the interaction at steady state and at higher doses of gabapentin are not known.

Interactions with herbal products have not been established.

The drug interaction data described in this subsection were obtained from studies involving healthy adults and adult patients with epilepsy:

Renal excretion of gabapentin is unaltered by probenecid.

In healthy adult volunteers (N=18), the coadministration of single doses of naproxen sodium capsules (250 mg) and gabapentin (125 mg) increased the amount of gabapentin absorbed by 12% to 15%. Gabapentin did not affect naproxen pharmacokinetic parameters in this study. These doses are lower than the therapeutic doses for both drugs. Therefore, the magnitude of interaction at steady state and within the recommended dose ranges of either drug is not known.

Coadministration of gabapentin with an aluminum and magnesium-based antacid reduces gabapentin bioavailability by up to 20%. Although the clinical significance of this decrease is not known, coadministration of similar antacids and gabapentin is not recommended.

In vitro studies were performed to investigate the potential of gabapentin to inhibit the major cytochrome P450 enzymes (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) that mediate drug and xenobiotic metabolism, using isoform selective marker substrates and human liver microsomal preparations. Only at the highest concentration tested (171 μg/mL; 1 mM) was a slight degree of inhibition (14% to 30%) observed with isoform CYP2A6. No inhibition was observed with any of the other isoforms tested at gabapentin concentrations up to 171 μg/mL (approximately 15 times the C_max at 3600 mg/day). Gabapentin is not an inducer of cytochrome P450 enzymes.

At plasma concentrations associated with doses up to 3600 mg/day (C_max 11.6 μg/mL), the highest recommended daily dose, a metabolically-based interaction between gabapentin and a drug whose clearance is dependent upon the major cytochrome P450 enzymes is unlikely.

Gabapentin is not metabolized to a significant extent in humans and does not interfere with the metabolism of commonly administered antiepileptic drugs. (See Drug Interactions, Drug-Drug Interactions, Antiepileptic Agents). Gabapentin also shows a low level of binding to plasma proteins (approximately 3%) and is eliminated solely by renal excretion as unchanged drug. (See Action and Clinical Pharmacology.) Consequently, there have been few drug interactions described in which the pharmacokinetics of gabapentin or other coadministered drugs were affected to an appreciable extent.

Coadministration of single doses of gabapentin (125 mg to 500 mg; N=48) and hydrocodone (10 mg; N=50) decreased the C_max and AUC values of hydrocodone in a dose-dependent manner relative to administration of hydrocodone alone. The C_max and AUC values for hydrocodone were 2% and 4% lower, respectively, after administration of 125 mg gabapentin and 16% and 22% lower, respectively, after administration of 500 mg gabapentin. The mechanism for this interaction is unknown. Hydrocodone increased gabapentin AUC values by 14%. The magnitude of interaction with higher doses of gabapentin is not known.

A slight decrease in renal excretion of gabapentin observed when it is coadministered with cimetidine is not expected to be of clinical importance. The effect of gabapentin on cimetidine has not been evaluated.

If Neurontin dose is reduced, discontinued or substituted with an alternate anticonvulsant or an alternate anticonvulsant is added to Neurontin therapy, this should be done gradually over a minimum of 1 week (a longer period may be needed at the discretion of the prescriber. (See Warnings and Precautions.)

Physicians should instruct their patients that if a dose is missed, the next one should be taken as soon as possible. However, if it is within 4 hours of the next dose, the missed dose is not to be taken and the patient should return to the regular dosing schedule. To avoid breakthrough convulsions the maximum time between doses should not exceed 12 hours.

The dose may be increased, depending on the response and tolerance of the patient, using 300 or 400 mg capsules, or 600 or 800 mg tablets 3 times a day up to 1800 mg/ day. In clinical trials, the effective dosage range was 900 to 1800 mg/day, given 3 times a day using 300 mg or 400 mg capsules, or 600 mg or 800 mg tablets. Dosages up to 2400 mg/day have been well tolerated in long-term open-label clinical studies. Doses of 3600 mg/day have also been administered to a small number of patients for a relatively short duration and have been well tolerated.

Although data from clinical trials suggest that doses higher than 1200 mg/day may have increased efficacy in some patients, higher doses may also increase the incidence of adverse events. (See Adverse Reactions.)

Because gabapentin is not metabolized to a significant extent in humans, no studies have been performed in patients with hepatic impairment.

Because Neurontin is eliminated solely by renal excretion, dosage adjustments are recommended for patients with renal impairment (including elderly patients with declining renal function) and patients undergoing hemodialysis. (See Dosage and Administration, Special Patient Populations, Table 2.)

Daily maintenance doses should be given in three equally divided doses, and the maximum time between doses in a three times daily schedule should not exceed 12 hours to prevent breakthrough convulsions. It is not necessary to monitor gabapentin plasma concentrations in order to optimize Neurontin therapy. Further, as there are no drug interactions with commonly used antiepileptic drugs, Neurontin may be used in combination with these drugs without concern for alteration of plasma concentrations of either gabapentin or other antiepileptic drugs.

The starting dose is 300 mg three times a day.

Neurontin is not indicated for use in children under 18 years of age. (See Indications and Clinical Use; Warnings and Precautions, Special Populations.)

Neurontin (gabapentin) is given orally with or without food.

Frequent: anorexia, flatulence, gingivitis; Infrequent: glossitis, gum hemorrhage, thirst, stomatitis, increased salivation, gastroenteritis, hemorrhoids, bloody stools, fecal incontinence, hepatomegaly; Rare: dysphagia, eructation, pancreatitis, peptic ulcer, colitis, blisters in mouth, tooth discolor, perlèche, salivary gland enlarged, lip hemorrhage, esophagitis, hiatal hernia, hematemesis, proctitis, irritable bowel syndrome, rectal hemorrhage, esophageal spasm.

Frequent: abnormal vision; Infrequent: cataract, conjunctivitis, eyes dry, eye pain, visual field defect, photophobia, bilateral or unilateral ptosis, eye hemorrhage, hordeolum, hearing loss, earache, tinnitus, inner ear infection, otitis, taste loss, unusual taste, eye twitching, ear fullness; Rare: eye itching, abnormal accommodation, perforated ear drum, sensitivity to noise, eye focusing problem, watery eyes, retinopathy, glaucoma, iritis, corneal disorders, lacrimal dysfunction, degenerative eye changes, blindness, retinal degeneration, miosis, chorioretinitis, strabismus, eustachian tube dysfunction, labyrinthitis, otitis externa, odd smell.

pulmonary edema.

headache, movement disorders such as choreoathetosis, dyskinesia, dystonia.

Frequent: asthenia, malaise, face edema; Infrequent: allergy, generalized edema, weight decrease, chill; Rare: strange feelings, lassitude, alcohol intolerance, hangover effect.

acne, alopecia, angioedema, erythema muiltiforme, rash, Stevens-Johnson syndrome.

Adverse events following the abrupt discontinuation of gabapentin have also been reported during postmarketing experience. The most frequently reported events were anxiety, insomnia, nausea, pain and sweating.

Infrequent: alopecia, eczema, dry skin, increased sweating, urticaria, hirsutism, seborrhea, cyst, herpes simplex; Rare: herpes zoster, skin discolor, skin papules, photosensitive reaction, leg ulcer, scalp seborrhea, psoriasis, desquamation, maceration, skin nodules, subcutaneous nodule, melanosis, skin necrosis, local swelling.

viral infection.

tinnitus.

breast hypertrophy, gynecomastia.

Frequent: hypertension; Infrequent: hypotension, angina pectoris, peripheral vascular disorder, palpitation, tachycardia, migraine, murmur; Rare: atrial fibrillation, heart failure, thrombophlebitis, deep thrombophlebitis, myocardial infarction, cerebrovascular accident, pulmonary thrombosis, ventricular extrasystoles, bradycardia, premature atrial contraction, pericardial rub, heart block, pulmonary embolus, hyperlipidemia, hypercholesterolemia, pericardial effusion, pericarditis.

Rare: hyperthyroid, hypothyroid, goiter, hypoestrogen, ovarian failure, epididymitis, swollen testicle, cushingoid appearance.

chest pain, fever, peripheral edema.

blood glucose fluctuations in patients with diabetes.

thrombocytopenia.

Since Neurontin was administered most often in combination with other antiepileptic agents, it was not possible to determine which agent(s) was associated with adverse events.

Frequent: purpura most often described as bruises resulting from physical trauma; Infrequent: anemia, thrombocytopenia, lymphadenopathy; Rare: WBC count increased, lymphocytosis, non-Hodgkin's lymphoma, bleeding time increased.

confusion, emotional lability, hallucinations, insomnia.

abdominal pain, diarrhea, nausea and/or vomiting, pancreatitis.

Adverse events that occurred in at least 1% of the 2074 individuals who participated in all clinical trials, only some of which were placebo-controlled, are described below. During these trials, all adverse events were recorded by the clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals having adverse events, similar types of events were grouped into a smaller number of standardized categories using modified COSTART dictionary terminology. These categories are used in the listing below. The frequencies presented represent the proportion of the 2074 patients exposed to Neurontin who experienced an event of the type cited on at least one occasion while receiving Neurontin. All reported events are included except those already listed in Table 1, those too general to be informative, and those not reasonably associated with the use of the drug.

Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are defined as those occurring in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients.

The most commonly observed adverse events associated with the use of Neurontin (gabapentin) in combination with other antiepileptic drugs, not seen at an equivalent frequency in placebo-treated patients, were somnolence, dizziness, ataxia, fatigue, nystagmus and tremor (see Table 1).

hyponatremia.

Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.

palpitation.

Approximately 6.4% of the 543 patients who received Neurontin in the placebo-controlled studies withdrew due to adverse events. In comparison, approximately 4.5% of the 378 placebo-controlled participants withdrew due to adverse events during these studies. The adverse events most commonly associated with withdrawal were somnolence (1.2%), ataxia (0.8%), fatigue, nausea and/or vomiting and dizziness (all at 0.6%).

Frequent: arthralgia; Infrequent: tendinitis, arthritis, joint stiffness, joint swelling, positive Romberg test; Rare: costochondritis, osteoporosis, bursitis, contracture.

acute kidney failure, urinary incontinence.

Frequent: vertigo, hyperkinesia, paresthesia, decreased or absent reflexes, increased reflexes, anxiety, hostility; Infrequent: CNS tumors, syncope, dreaming abnormal, aphasia, hypesthesia, intracranial hemorrhage, hypotonia, dysesthesia, paresis, dystonia, hemiplegia, facial paralysis, stupor, cerebellar dysfunction, positive Babinski sign, decreased position sense, subdural hematoma, apathy, hallucination, decrease or loss of libido, agitation, paranoia, depersonalization, euphoria, feeling high, doped-up sensation, suicide attempt, psychosis; Rare: choreoathetosis, orofacial dyskinesia, encephalopathy, nerve palsy, personality disorder, increased libido, subdued temperament, apraxia, fine motor control disorder, meningismus, local myoclonus, hyperesthesia, hypokinesia, mania, neurosis, hysteria, antisocial reaction, suicide.

rare or very rare cases of hepatic events including hepatitis sometimes associated with elevated liver function tests (LFTs) and jaundice. Isolated reports have been received for hepatic function abnormal, hepatitis cholestatic, liver failure, and hepatitis fulminant. In most of these reports, patients taking multiple medications, including those known to be potentially hepatotoxic, while being treated with Neurontin.

Infrequent: hematuria, dysuria, urination frequency, cystitis, urinary retention, urinary incontinence, vaginal hemorrhage, amenorrhea, dysmenorrhea, menorrhagia, breast cancer, unable to climax, ejaculation abnormal; Rare: kidney pain, leukorrhea, pruritus genital, renal stone, acute renal failure, anuria, glycosuria, nephrosis, nocturia, pyuria, urination urgency, vaginal pain, breast pain, testicle pain.

Frequent: pneumonia; Infrequent: epistaxis, dyspnea, apnea; Rare: mucositis, aspiration pneumonia, hyperventilation, hiccup, laryngitis, nasal obstruction, snoring, bronchospasm, hypoventilation, lung edema.

Among the treatment-emergent adverse events occurring in Neurontin-treated patients, somnolence and ataxia appeared to exhibit a positive dose-response relationship. Patients treated with 1800 mg/day (n=54, from one controlled study) experienced approximately a two-fold increase, as compared to patients on lower doses of 600 to 1200 mg/day (n=489, from several controlled studies), in the incidence of nystagmus (20.4%), tremor (14.8%), rhinitis (13%), peripheral edema (7.4%), coordination abnormal, depression and myalgia (all at 5.6%). Adverse events were usually mild to moderate in intensity, with a median time to resolution of 2 weeks.

Data from long-term, open, uncontrolled studies shows that Neurontin treatment does not result in any new or unusual adverse events.

Sudden, unexplained deaths in patients with epilepsy have been reported where a causal relationship to treatment with gabapentin has not been established.

Post-marketing adverse events that have been reported, that may have no causal relationship to gabapentin, include:

allergic reaction including anaphylactic reaction and urticaria.

The safety and efficacy in patients under the age of 18 have not been established. (See Warnings and Precautions, Special Populations.)

Systematic studies in geriatric patients have not been conducted. (See Warnings and Precautions, Special Populations.)

Acute, life-threatening toxicity has not been observed with Neurontin (gabapentin) overdoses of up to 49 g ingested at one time. In these cases, dizziness, double vision, slurred speech, drowsiness, lethargy and mild diarrhea were observed. All patients recovered with supportive care.

An oral lethal dose of gabapentin was not identified in mice and rats given doses as high as 8000 mg/kg. Signs of acute toxicity in animals included ataxia, laboured breathing, ptosis, hypoactivity, or excitation.

Gabapentin can be removed by hemodialysis. Although hemodialysis has not been performed in the few overdose cases reported, it may be indicated by the patient's clinical state or in patients with significant renal impairment.

Reduced absorption of gabapentin at higher doses may limit drug absorption at the time of overdosing and, hence, reduce toxicity from overdoses.

In managing overdosage, consider the possibility of multiple drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of overdosage.

Each hard gelatin CONI-SNAP capsule, with yellow opaque body and cap printed with “PD” on one side and “Neurontin/300 mg” on the other, contains: gabapentin 300 mg. Nonmedicinal ingredients: cornstarch, lactose and talc; capsule shell may contain: FD&C Blue No. 2, gelatin, red iron oxide, silicon dioxide, sodium lauryl sulfate, titanium dioxide and yellow iron oxide. Bottles of 100.

Each white, elliptical, film-coated tablet, with “Neurontin 600” printed on one side contains: gabapentin 600 mg. Nonmedicinal ingredients: ammonium hydroxide, black iron oxide, candelilla wax, copolyvidone, cornstarch, hydroxypropylcellulose, magnesium stearate, poloxamer 407 NF and talc. Bottles of 100.

Each hard gelatin CONI-SNAP capsule, with orange opaque body and cap printed with “PD” on one side and “Neurontin/400 mg” on the other, contains: gabapentin 400 mg. Nonmedicinal ingredients: cornstarch, lactose and talc; capsule shell may contain: FD&C Blue No. 2, gelatin, red iron oxide, silicon dioxide, sodium lauryl sulfate, titanium dioxide and yellow iron oxide. Bottles of 100.

Each hard gelatin CONI-SNAP capsule, with white opaque body and cap printed with “PD” on one side and “Neurontin/100 mg” on the other, contains: gabapentin 100 mg. Nonmedicinal ingredients: cornstarch, lactose and talc; capsule shell may contain: FD&C Blue No. 2, gelatin, red iron oxide, silicon dioxide, sodium lauryl sulfate, titanium dioxide and yellow iron oxide. Bottles of 100.

Each white, elliptical, film-coated tablet, with “Neurontin 800” printed on one side contains: gabapentin 800 mg. Nonmedicinal ingredients: candelilla wax, copolyvidone, cornstarch, hydroypropylcellulose, hypromellose, magnesium stearate, poloxamer 407 NF, red iron oxide, yellow iron oxide and talc. Bottles of 100.

Systematic studies in geriatric patients have not been conducted. Adverse clinical events reported among 59 patients over the age of 65 years treated with Neurontin did not differ from those reported for younger individuals. The small number of individuals evaluated and the limited duration of exposure limits the strength of any conclusions reached about the influence of age, if any, on the kind and incidence of adverse events associated with the use of Neurontin.

As Neurontin is eliminated primarily by renal excretion, dosage adjustment may be required in elderly patients because of declining renal function. (See Dosage and Administration, Dosing Considerations; Action and Clinical Pharmacology, Special Populations and Conditions.)

The abuse and dependence potential of gabapentin has not been evaluated in human studies. As with any CNS active drug, however, physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of abuse or misuse of Neurontin.

Gabapentin produced an increased incidence of acinar cell adenomas and carcinomas in the pancreas of male rats, but not female rats or in mice, in oncogenic studies with doses of 2000 mg/kg which resulted in plasma concentrations 14 times higher than those occurring in humans at a dose of 2400 mg/day. The relevance of these pancreatic acinar cell tumours in male rats to humans is unknown, particularly since tumours of ductal rather than acinar cell origin are the predominant form of human pancreatic cancer.

Neurontin (gabapentin) is not considered effective in the treatment of absence seizures and should therefore be used with caution in patients who have mixed seizure disorders that include absence seizures.

Clinical trials data do not indicate that routine monitoring of clinical laboratory parameters is necessary for the safe use of Neurontin. Neurontin may be used in combination with other commonly used antiepileptic drugs without concern for alteration of the blood concentrations of gabapentin or other antiepileptic drugs.

Patients who require concomitant treatment with morphine may experience increases in gabapentin concentrations. Patients should be carefully observed for signs and symptoms of CNS depression, such as somnolence, and the dose of gabapentin or morphine should be reduced appropriately. (See Drug Interactions.)

As with other anticonvulsant agents, abrupt withdrawal is not recommended because of the possibility of increased seizure frequency. There have been post-marketing reports of adverse events such as anxiety, insomnia, nausea, pain and sweating following abrupt discontinuation of treatment. (See Adverse Reactions, Post-market Adverse Drug Reactions.) When in the judgement of the clinician there is a need for dose reduction, discontinuation or substitution with an alternative medication, this should be done gradually over a minimum of 1 week (a longer period may be needed at the discretion of the prescriber).

The safety and efficacy in patients under the age of 18 have not been established. Data in 39 patients between the ages of 12 and 18 years included in the double-blind, placebo-controlled trials showed that, at doses of 900 to 1200 mg/day, gabapentin was superior to placebo in reducing seizure frequency. Doses above 1200 mg/day have not been investigated. Safety data showed that the incidence of adverse events in this group of patients was similar to that observed in older individuals.

In controlled clinical trials involving patients, 3 to 12 years of age (N=323), psychiatric adverse events such as emotional lability, hostility, hyperkinesia and thought disorder were reported at a higher frequency in patients treated with gabapentin compared to placebo.

Patients with uncontrolled epilepsy should not drive or handle potentially dangerous machinery. During clinical trials, the most common adverse reactions observed were somnolence, ataxia, fatigue, and nystagmus. Patients should be advised to refrain from activities requiring mental alertness or physical coordination until they are sure that Neurontin does not affect them adversely.

No evidence of impaired fertility or harm to the fetus due to gabapentin administration was revealed in reproduction studies in mice at doses up to 62 times, and in rats and rabbits at doses up to 31 times the human dose of 2400 mg/day.

There are no adequate and well-controlled studies to establish the safety of gabapentin in pregnant women. Gabapentin should only be used during pregnancy if the potential benefit to the mother outweighs the potential risk to the fetus.

Gabapentin is excreted in human milk. Because the effect on the nursing infant is unknown, caution should be exercised when gabapentin is administered to a nursing mother. Gabapentin should be used in nursing mothers only if the potential benefit to the mother outweighs the potential risks to the fetus.

Store at controlled room temperature, 15-30°C.

Store at controlled room temperature, 20-25°C.

Because gabapentin is not metabolized to a significant extent in humans, no study was performed in patients with hepatic impairment.

Apparent oral clearance (CL/F) of gabapentin decreased as age increased, from about 225 mL/min in subjects under 30 years of age to about 125 mL/min in subjects over 70 years of age. Renal clearance (CLr) of gabapentin also declined with age; however, this decrease can largely be explained by the decline in renal function. Reduction of gabapentin dose may be required in patients who have age-related compromised renal function. (See Dosage and Administration, Dosing Considerations.)

Less than 3% of gabapentin is bound to plasma proteins. The apparent volume of distribution of gabapentin after 150 mg intravenous administration is 58±6 L (Mean±SD). In patients with epilepsy, gabapentin concentrations in cerebrospinal fluid are approximately 20% of corresponding steady-state trough plasma concentrations.

All pharmacological actions following gabapentin administration are due to the activity of the parent compound; gabapentin is not metabolized to a significant extent in humans.

Plasma gabapentin concentrations are dose-proportional at doses of 300 to 400 mg q8h, ranging between 1 µg/mL and 10 µg/mL, but are less than dose-proportional above the clinical range (>600 mg q8h). There is no correlation between plasma levels and efficacy.

Gabapentin pharmacokinetics are not affected by repeated administration, and steady state plasma concentrations are predictable from single dose data. Gabapentin steady-state pharmacokinetics are similar for healthy subjects and patients with epilepsy receiving antiepileptic agents.

Following oral administration of Neurontin (gabapentin), peak plasma concentrations are observed within 2 to 3 hours. Absolute bioavailability of a 300 mg dose of Neurontin capsules is approximately 59%. At doses of 300 and 400 mg, gabapentin bioavailability is unchanged following multiple dose administration.

Food has no effect on the rate or extent of absorption of gabapentin.

Neurontin (gabapentin) exhibits antiseizure activity in mice and rats both in the maximal electroshock and in the pentylenetetrazol seizure models.

Gabapentin is structurally related to the neurotransmitter GABA (gamma-aminobutyric acid) but does not interact with GABA receptors, it is not metabolized to GABA or to GABA agonists, and it is not an inhibitor of GABA uptake or degradation. Gabapentin at concentrations up to 100 µM did not demonstrate affinity for other receptor sites such as benzodiazepine, glutamate, glycine or N-methyl-D-aspartate receptors nor does it interact with neuronal sodium channels or L-type calcium channels.

The mechanism of action of gabapentin has not yet been established, however, it is unlike that of the commonly used anticonvulsant drugs.

In vitro studies with radiolabelled gabapentin have revealed a gabapentin binding site in rat brain tissues including neocortex and hippocampus. The identity and function of this binding site remain to be elucidated.

In patients with impaired renal function, gabapentin clearance is markedly reduced and dosage adjustment is necessary. (See Dosage and Administration, Dosing Considerations and Special Patient Populations, Table 2.)

Gabapentin is not appreciably metabolized to a significant extent in humans. Gabapentin does not induce or inhibit hepatic mixed function oxidase enzymes responsible for drug metabolism and does not interfere with the metabolism of commonly coadministered antiepileptic drugs.

In a study in anuric subjects (N=11), the apparent elimination half-life of gabapentin on non-dialysis days was about 132 hours; during dialysis the apparent half-life of gabapentin was reduced to 3.8 hours. Hemodialysis thus has a significant effect on gabapentin elimination in anuric subjects.

Dosage adjustment in patients undergoing hemodialysis is necessary. (See Dosage and Administration, Dosing Considerations and Special Patient Populations, Table 2.)

There are no pharmacokinetic data available in children under 18 years of age.

Neurontin (gabapentin) is contraindicated in patients who have demonstrated hypersensitivity to the drug or to any of the components of the formulation.