Gabavex 100/Gabavex 300

Gabavex 100/Gabavex 300

gabapentin

Manufacturer:

Vexxa Lifesciences

Distributor:

VE Pharma
Full Prescribing Info
Contents
Gabapentin.
Description
Each capsule contains: Gabapentin USP 100 mg or 300 mg.
Gabapentin is Cyclohexaneacetic acid. 1-(amonimethyl)-1 (Aminomethyl) cyclohexaneacitic acid. It's Molecule formula weight is 171.24. Gabapentin is white to off-white, crystalline solid, Freely soluble in water and in alkaline and acidic solutions.
Excipients/Inactive ingredient: Approved colours used in capsule shell.
Action
Pharmacological Classification: Antiepileptic.
Pharmacology: Pharmacodynamics: Mechanism of Action: The precise mechanism of action of gabapentin is not known.
Gabapentin is structurally related to the neurotransmitter GABA (gamma-aminobutyric acid) but its mechanism of action is different from that of several other active substances that interact with GABA synapses, including valproate, barbiturates, benzodiazepines, GABA transaminase inhibitors, GABA uptake inhibitors, GABA agonists, and GABA prodrugs. In vitro studies with radiolabeled gabapentin have characterized a novel peptide binding site in rat brain tissues including neocortex and hippocampus that may relate to anticonvulsant and analgesic activity of gabapentin and its structural derivatives. The binding site for gabapentin has been identified as the alpha2-delta subunit of voltage-gated calcium channels.
Gabapentin at relevant clinical concentrations does not bind to other common drug or neurotransmitter receptors of the brain including GABAA, GABAB, benzodiazepine, glutamate, glycine or N-methyl-d-aspartate receptors.
Gabapentin does not interact with sodium channels in vitro and so differs from phenytoin and carbamazepine. Gabapentin partially reduces responses to the glutamate agonist N-methyl-D-aspartate (NMDA) in some test systems in vitro, but only at concentrations greater than 100 µM, which are not achieved in vivo. Gabapentin slightly reduces the release of monoamine neurotransmitters in vitro. Gabapentin administration to rats increases GABA turnover in several brain regions in a manner similar to valproate sodium, although in different regions of brain. The relevance of these various actions of gabapentin to the anticonvulsant effects remains to be established. In animals, gabapentin readily enters the brain and prevents seizures from maximal electroshock, from chemical convulsants including inhibitors of GABA synthesis, and in genetic models of seizures.
Pharmacokinetics: Absorption: Following oral administration, peak plasma gabapentin concentrations are observed within 2 to 3 hours. Gabapentin bioavailability (fraction of dose absorbed) tends to decrease with increasing dose. Absolute bioavailability of a 300 mg capsule is approximately 60%. Food, including a high-fat diet, has no clinically significant effect on gabapentin pharmacokinetics.
Gabapentin pharmacokinetics are not affected by repeated administration. Although plasma gabapentin concentrations were generally between 2 µg/mL and 20 µg/mL in clinical studies, such concentrations were not predictive of safety or efficacy. Pharmacokinetic parameters are given in Table 1. (See Table 1.)

Click on icon to see table/diagram/image

Distribution: Gabapentin is not bound to plasma proteins and has a volume of distribution equal to 57.7 Iitres. In patients with epilepsy, gabapentin concentrations in cerebrospinal fluid (CSF) are approximately 20% of corresponding steady-state trough plasma concentrations. Gabapentin is present in the breast milk of breast-feeding women.
Biotransformation: There is no evidence of gabapentin metabolism in humans. Gabapentin does not induce hepatic mixed function oxidase enzymes responsible for drug metabolism.
Elimination: Gabapentin is eliminated unchanged solely by renal excretion. The elimination half-life of gabapentin is independent of dose and averages 5 to 7 hours.
In elderly patients, and in patients with impaired renal function, gabapentin plasma clearance is reduced. Gabapentin elimination-rate constant, plasma clearance, and renal clearance are directly proportional to creatinine clearance.
Gabapentin is removed from plasma by hemodialysis. Dosage adjustment in patients with compromised renal function or undergoing hemodialysis is recommended.
Gabapentin pharmacokinetics in children were determined in 50 healthy subjects between the ages of 1 month and 12 years. In general, plasma gabapentin concentrations in children > 5 years of age are similar to those in adults when dosed on a mg/kg basis.
In a pharmacokinetic study in 24 healthy pediatric subjects aged between 1 month and 48 months, an approximately 30% lower exposure (AUC), lower C max and higher clearance per body weight have been observed in comparison to available reported data in children older than 5 years.
Linearity/Non-linearity: Gabapentin bioavailability (fraction of dose absorbed) decreases with increasing dose which imparts non-linearity to pharmacokinetic parameters which include the bioavailability parameter (F) e.g. E%, CL/F, Vd/F. Elimination pharmacokinetics (pharmacokinetic parameters which do not include F such as CLr and T 1/2), are best described by linear pharmacokinetics. Steady state plasma gabapentin concentrations are predictable from single-dose data.
Indications/Uses
Epilepsy: Gabapentin is indicated as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in adults and children aged 6 years and above.
Gabapentin is indicated as monotherapy in the treatment of partial seizures with and without secondary generalization in adults and adolescents aged 12 years and above.
Treatment of peripheral neuropathic pain: Gabapentin is indicated for the treatment of peripheral neuropathic pain such as painful diabetic neuropathy and post-herpetic neuralgia in adults.
Dosage/Direction for Use
For oral use.
Gabapentin can be given with or without food and should be swallowed whole with sufficient fluid-intake (e.g. a glass of water).
For all indications a titration scheme for the initiation of therapy is described in Table 2. Which is recommended for adults and adolescents aged 12 years and above. Dosing instructions for children under 12 years of age are provided under a separate sub-heading later in this section. (See Table 2.)

Click on icon to see table/diagram/image

Epilepsy: Epilepsy typically requires long-term therapy. Dosage is determined by the threating physician according to individual tolerance and efficacy. When in the judgement of the clinician there is a need dose reduction, discontinuation, or substitution with an alternative medication, this should be done gradually over a minimum of one week.
Children aged 6 years and above: The starting dose should range from 10 to 15 mg/kg/day and the effective dose is reached by upward titration over a period of approximately three days. The effective dose of gabapentin in children aged 6 years and older is 25 to 35 mg/kg/day. Dosage up to 50 mg/kg/day have been well tolerated in a long-term clinical study. The total daily dose should be divided in three single doses. The maximum time interval between doses should not exceed 12 hours.
It is not necessary to monitor gabapentin plasma concentrations of gabapentin or serum concentration of other antiepileptic medicinal products.
Peripheral neuropathic pain: Adults: The therapy may be initiated by titrating the dose as described in Table 2. Alternatively, the starting dose is 900 mg/day given as three equally divided doses. Thereafter, based on individual patient response and tolerability, the dose can be further increased in 300 mg/day increments every 2-3 days up to maximum dose of 3600 mg/day. Slower titration of gabapentin dosage may be appropriate for individual patients. The minimum time to reach dose of 1800 mg/day is one week, to reach 2400 mg/day is a total of 2 weeks, and to reach 3600 mg/day is a total of 3 weeks.
In the treatment of peripheral neuropathic pain such as painful diabetic neuropathy and post-herpetic neuralgia, efficacy and safety have not been examined in clinical studies for treatment periods longer than 5 months. If a patient requires dosing longer than 5 months for the treatment of peripheral neuropathic pain, the treating physician should assess the patient's clinical status and determine the need for additional theraphy.
Instruction for all areas of indication: In patients with poor general health, i.e. low body weight, after organ transplantation etc., the dose should be titrated more slowly, either by using smaller dosage strengths or longer intervals between dosage increases.
Use in elderly patients (over 65 years of age): Elderly patients may require dosage adjustment because of declining renal function with age (see Table 3). Somnolence, peripheral oedema and asthenia may be more frequent in elderly patients.
Use in patients with renal impairment: Dosage adjustment is recommended in patients with compromised renal function as described in Table 3 and/or those undergoing haemodialysis. Gabapentin 100 mg capsules can be used to follow dosing recommendations for patients with renal insufficiency. (See Table 3.)

Click on icon to see table/diagram/image

Use in patients undergoing haemodialysis: For anuric patients undergoing haemodialysis who have never received gabapentin a loading dose of 300 to 400 mg then 200 to 300 mg of gabapentin following each 4 hours haemodialysis, is recommended. On dialysis-free days, there should be no treatment with gabapentin.
For renally impaired patients undergoing haemodialysis, the maintenance dose of gabapentin should be based on dosing recommendations found in Table 3. In addition to the maintenance dose, an additional 200 to 300 mg dose following each 4-hour haemodialysis treatment recommended.
Overdosage
Acute life-threatening toxicity has not been observed with gabapentin overdoses of up to 49 g.
Symptoms of the overdoses included dizziness. Double vision, slurred speech. Drowsiness. Lethargy and mild diarrhea. All patients recovered fully with supportive care. Reduced absorption of gabapentin at higher doses may limit drug absorption at the time of overdosing and hence. Minimize toxicity from overdoses.
Although gabapentin can be removed by haemodialysis, based on prior experience it is usually not required. However, in patients with severe renal impairment, haemodialysis may be indicated.
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 labored breathing, ptosis. Hypoactivity or excitation.
Contraindications
Gabapentin capsules USP are contraindicated in patients who have demonstrated hypersensitivity to the drug or any of its ingredients.
Special Precautions
Suicidal ideation and behavior: Suicidal ideation and behavior have been reported in patients treated with antiepileptic agents in several indications. A meta-analysis of randomized placebo controlled trials of antiepileptic drugs has also shown a small increased risk of suicidal ideation and behavior. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for gabapentin. Therefore patients should be monitored for signs of suicidal ideation and behaviors and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behavior emerge.
Acute pancreatitis: If a patient develops acute pancreatitis under treatment with gabapentin, discontinuation of gabapentin should be considered.
Seizures: Although there is no evidence of rebound seizures with gabapentin, abrupt withdrawal of anticonvulsants in epileptic patients may precipitate status epilepticus.
As with other antiepileptic medicinal products, some patients may experience an increase in seizure frequency or the onset of new types of seizures with gabapentin.
As with other antiepileptics, attempts to withdraw concomitant antiepileptics in treatment refractive patients on more than one antiepileptic, in order to reach gabapentin monotherapy have a low success rate.
Gabapentin is not considered effective against primary generalized seizures such as absences and may aggravate these seizures in some patients. Therefore, gabapentin should be used with caution in patients with mixed seizures including absences.
Gabapentin treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall). There have also been reports of confusion, loss of consciousness and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medication.
Abuse and Dependence: Cases of abuse and dependence have been reported in the post-marketing database. Carefully evaluate patients for a history of drug abuse and observe them for possible signs of gabapentin abuse e.g. drug-seeking behavior, dose escalation, development of tolerance.
Drug Rash with Eosinophilia and Systemic Symptoms (DRESS): Severe, life-threatening, systemic hypersensitivity reactions such as Drug rash with eosinophilia and systemic symptoms (DRESS) have been reported in patients taking antiepileptic drugs including gabapentin.
It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Gabapentin should be discontinued if an alternative etiology for the signs or symptoms cannot be established.
Laboratory tests: False positive readings may be obtained in the semi-quantitative determination of total urine protein by dipstick tests. It is therefore recommended to verify such a positive dipstick test result by methods based on a different analytical principle such as the Biuret method, turbidimetric or dye-binding methods, or to use these alternative methods from the beginning.
Neurontin hard capsules contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Effects on Ability to Drive and Use Machines: Gabapentin may have minor or moderate influence on the ability to drive and use machines.
Gabapentin acts on the central nervous system and may cause drowsiness, dizziness or other related symptoms. Even, if they were only of mild or moderate degree, these undesirable effects could be potentially dangerous in patients driving or operating machinery. This is especially true at the beginning of the treatment and after increase in dose.
Use in Children: The effects of long-term (greater than 36 weeks) gabapentin therapy on learning, intelligence, and development in children and adolescents have not been adequately studied. The benefits of prolonged therapy must therefore be weighed against the potential risks of such therapy.
Use in Elderly (over 65 years of age): No systematic studies in patients 65 years or older have been conducted with gabapentin. In one double blind study in patients with neuropathic pain, somnolence, peripheral edema and asthenia occurred in a somewhat higher percentage in patients aged 65 years or above, than in younger patients. Apart from these findings, clinical investigations in this age group do not indicate an adverse event profile different from that observed in younger patients.
Use In Pregnancy & Lactation
Pregnancy: Risk related to epilepsy and antiepileptic medicinal products in general: The risk of birth defects is increased by a factor of 2–3 in the offspring of mothers treated with an antiepileptic medicinal product. Most frequently reported are cleft lip, cardiovascular malformations and neural tube defects. Multiple antiepileptic drug therapy may be associated with a higher risk of congenital malformations than monotherapy therefore it is important that monotherapy is practiced whenever possible. Specialist advice should be given to women who are likely to become pregnant or who are of childbearing potential and the need for antiepileptic treatment should be reviewed when a woman is planning to become pregnant. No sudden discontinuation of antiepileptic therapy should be undertaken as this may lead to breakthrough seizures, which could have serious consequences for both mother and child. Developmental delay in children of mothers with epilepsy has been observed rarely. It is not possible to differentiate if the developmental delay is caused by genetic, social factors, maternal epilepsy or the antiepileptic therapy.
Risk related to gabapentin: There are no adequate data from the use of gabapentin in pregnant women.
Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown.
Gabapentin should not be used during pregnancy unless the potential benefit to the mother clearly outweighs the potential risk to the fetus.
No definite conclusion can be made as to whether gabapentin is associated with an increased risk of congenital malformations when taken during pregnancy, because of epilepsy itself and the presence of concomitant antiepileptic medicinal products during each reported pregnancy.
Breast-feeding: Gabapentin is excreted in human milk. Because the effect on the breast-fed infant is unknown, caution should be exercised when gabapentin is administered to a breast-feeding mother. Gabapentin should be used in breast-feeding mothers only if the benefits clearly outweigh the risks.
Adverse Reactions
Infections and infestations: Very Common: Viral infection.
Common: Pneumonia, respiratory infection, urinary tract infection, otitis media.
Blood and the lymphatic system disorders: Common: Leucopenia.
Rare: Thrombocytopenia.
Immune system disorders: Rare: Allergic reactions (e.g. urticaria).
Metabolism and nutrition disorders: Common: Anorexia, increased appetite.
Psychiatric disorders: Common: Hostility, confusion and emotional lability, depression, anxiety, nervousness, abnormal thinking.
Rare: Hallucinations.
Nervous system disorders: Very common: Sommolence, dizziness, ataxia.
Common: Convulsions, hyperkinesias, dysarthria, amnesia, tremor, insomnia, headache, sensations such as paresthesia, hypaesthesis. Coordination abnormal, nystagmus, increased, decreased or absent reflexes.
Rare: Movement disorders (e.g. choreoathosis, dyskinesia, dystonia.
Eye disorders: Common: Visual disturbances as amblyopia, diplopia.
Ear and labyrinth disorders: Common: Vertigo.
Rare: Tinnitus.
Cardiac disorders: Rare: Palpitations.
Vascular disorder: Common: Dyspnoea, Bronchitis, pharyngitis, cough, rhinitis.
Gastrointestinal disorders: Common: Vomiting, nausea, dental abnormalities, gingivitis, diarrhea, abnormal pain, dyspepsia, constipation, dry mouth or throat, flatulence.
Rare: Pancreatitis.
Hepatobiliary disorders: Rare: Hepatitis, jaundice.
Skin and subcutaneous tissue disorders: Common: Facial oedema, purpura most as bruises resulting from physical trauma, rash, pruritis, acne.
Rare: Stevens-Johnson syndrome, angioedema, erythema multiforme, alopecia.
Musculoskeletal, connective tissue and bone disorders: Common: Arthralgia, myalgia, back pain, twitching, throat, flatulence.
Renal and urinary disorders: Common: Incontinence.
Rare: Acute renal failure.
Reproductive system and breast disorder: Common: Impotence.
General disorders and administration site conditions: Very Common: Fatigue, fever.
Common: Peripheral or generalized oedema, abnormal gait, asthenia pain, malaise, flu syndrome.
Rare: Withdrawal reactions (mostly anxiety, insomnia nausea, pains, sweating), chest pain. Sudden unexplained deaths have been reported where a causal relationship to treatment with gabapentin has not been established.
Investigations: Common: WBC (white blood cell count) decreased, weight gain.
Rare: Blood glucose fluctuations in patients with diabetes, elevated liver function tests.
Injury and poisoning: Common: Accidental injury fracture, abrasion.
Under treatment with gabapentin cases of acute pancreatics were reported. Causality with gabapentin is unclear.
Respiratory tract infections, otitis media, convulsions and bronchitis were reported only in clinical studies in children. Additional in clinical studies inchildren, aggressive behavior and hyperkinesias were reported commonly.
Drug Interactions
No interaction between gabapentin and phenobarbital, phenytoin, valproic acid or carbamazepine has been observed.
Gabapentin steady-state pharmacokinetics is similar for healthy subjects and patients with epilepsy receiving these antiepileptic agents.
Co-administration of gabapentin with oral contraceptives containing norethindrone and/or ethinyl estradiol does not influence the steady-state pharmacokinetics of either component.
Co-administration of gabapentin with antacids containing aluminum and magnesium reduces gabapentin bioavailability up to 24%. It is recommended that gabapentin be taken at the earliest two hours following antacid administration.
Renal excretion of gabapentin is unaltered by probenecid.
A slight decrease in renal excretion of gabapentin that is observed when it is co-administered with cimetidine is not expected to be of clinical importance.
Storage
Store at temperature not exceeding 30°C.
Shelf-Life: 3 years from the date of manufacturing.
MIMS Class
ATC Classification
N03AX12 - gabapentin ; Belongs to the class of other antiepileptics.
Presentation/Packing
Gabavex 100: Cap 100 mg (caramel/pink colour hard gelatin capsule shell size "2" containing white colour powder) x 100's.
Gabavex 300: Cap 300 mg (red/white colour hard gelatin capsule size "0" containing white colour powder) x 100's.
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