Gabapentin Tablets USP 600mg Taj Pharma

1. Name of the medicinal product

Gabapentin Tablets USP 600mg Taj Pharma
Gabapentin Tablets USP 800mg Taj Pharma

2. Qualitative and quantitative composition

a) Gabapentin Tablets USP 600mg Taj Pharma
Each film-coated tablet contains:
Gabapentin USP 600mg
Excipients: Q.S.

b) Gabapentin Tablets USP 800mg Taj Pharma
Each film-coated tablet contains:
Gabapentin USP 800mg
Excipients: Q.S.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Film-coated tablets

White to off-white, Oval shaped, film coated tablets.

4. Clinical particulars

Therapeutic indications

Epilepsy

Gabapentin Taj Pharma 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 (see section 5.1).

Gabapentin Taj Pharma 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 Taj Pharma is indicated for the treatment of peripheral neuropathic pain such as painful diabetic neuropathy and post-herpetic neuralgia in adults.

Posology and method of administration

Posology

For all indications a titration scheme for the initiation of therapy is described in Table 1, 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.

Discontinuation of Gabapentin Taj Pharma

In accordance with current clinical practice, if Gabapentin Taj Pharma has to be discontinued it is recommended this should be done gradually over a minimum of 1 week independent of the indication.

Epilepsy

Epilepsy typically requires long-term therapy. Dosage is determined by the treating physician according to individual tolerance and efficacy.

Adults and adolescents:

In clinical trials, the effective dosing range was 900 to 3600mg/day. Therapy may be initiated by titrating the dose as described in Table 1 or by administering 300mg three times a day (TID) on Day 1. Thereafter, based on individual patient response and tolerability, the dose can be further increased in 300mg/day increments every 2-3 days up to a maximum dose of 3600mg/day. Slower titration of Gabapentin Taj Pharma dosage may be appropriate for individual patients. The minimum time to reach a dose of 1800mg/day is one week, to reach 2400mg/day is a total of 2 weeks, and to reach 3600mg/day is a total of 3 weeks. Dosages up to 4800mg/day have been well tolerated in long-term open-label clinical studies. The total daily dose should be divided in three single doses, the maximum time interval between the doses should not exceed 12 hours to prevent breakthrough convulsions.

Children aged 6 years and above:

The starting dose should range from 10 to 15mg/kg/day and the effective dose is reached by upward titration over a period of approximately three days. The effective dose of Gabapentin Taj Pharma in children aged 6 years and older is 25 to 35mg/kg/day. Dosages up to 50mg/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 Taj Pharma plasma concentrations to optimize Gabapentin Taj Pharma therapy. Further, Gabapentin Taj Pharma may be used in combination with other antiepileptic medicinal products without concern for alteration of the plasma concentrations of Gabapentin Taj Pharma or serum concentrations of other antiepileptic medicinal products.

Peripheral neuropathic pain

Adults

The therapy may be initiated by titrating the dose as described in Table 1. Alternatively, the starting dose is 900mg/day given as three equally divided doses. Thereafter, based on individual patient response and tolerability, the dose can be further increased in 300mg/day increments every 2-3 days up to a maximum dose of 3600mg/day. Slower titration of Gabapentin Taj Pharma dosage may be appropriate for individual patients. The minimum time to reach a dose of 1800mg/day is one week, to reach 2400mg/day is a total of 2 weeks, and to reach 3600mg/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 therapy.

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.

Elderly (over 65 years of age)

Elderly patients may require dosage adjustment because of declining renal function with age (see Table 2). Somnolence, peripheral oedema and asthenia may be more frequent in elderly patients.

Renal impairment

Dosage adjustment is recommended in patients with compromised renal function as described in Table 2 and/or those undergoing haemodialysis. Gabapentin Taj Pharma 100mg capsules can be used to follow dosing recommendations for patients with renal insufficiency.

Total daily dose should be administered as three divided doses. Reduced dosages are for patients with renal impairment (creatinine clearance < 79 ml/min).

The 150mg daily dose to be administered as 300mg every other day.

For patients with creatinine clearance <15 ml/min, the daily dose should be reduced in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7.5 ml/min should receive one-half the daily dose that patients with a creatinine clearance of 15 ml/min receive).

Use in patients undergoing haemodialysis

For anuric patients undergoing haemodialysis who have never received Gabapentin Taj Pharma, a loading dose of 300 to 400mg, then 200 to 300mg of Gabapentin Taj Pharma following each 4 hours of haemodialysis, is recommended. On dialysis-free days, there should be no treatment with Gabapentin Taj Pharma.

For renally impaired patients undergoing haemodialysis, the maintenance dose of Gabapentin Taj Pharma should be based on the dosing recommendations found in Table 2. In addition to the maintenance dose, an additional 200 to 300mg dose following each 4-hour haemodialysis treatment is recommended.

Method of administration

For oral use.

Gabapentin Taj Pharma can be given with or without food and should be swallowed whole with sufficient fluid-intake (e.g. a glass of water).

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Special warnings and precautions for use

Anaphylaxis

Gabapentin Taj Pharma can cause anaphylaxis. Signs and symptoms in reported cases have included difficulty breathing, swelling of the lips, throat, and tongue, and hypotension requiring emergency treatment. Patients should be instructed to discontinue Gabapentin Taj Pharma and seek immediate medical care should they experience signs or symptoms of anaphylaxis (see section 4.8).

Suicidal ideation and behavior

Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomised placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for Gabapentin Taj Pharma.

Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

Acute pancreatitis

If a patient develops acute pancreatitis under treatment with Gabapentin Taj Pharma, discontinuation of Gabapentin Taj Pharma should be considered (see section 4.8).

Seizures

Although there is no evidence of rebound seizures with Gabapentin Taj Pharma, abrupt withdrawal of anticonvulsant agents in epileptic patients may precipitate status epilepticus (see section 4.2).

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 Taj Pharma.

As with other anti-epileptics, attempts to withdraw concomitant anti-epileptics in treatment refractory patients on more than one anti-epileptic, in order to reach Gabapentin Taj Pharma monotherapy have a low success rate.

Gabapentin Taj Pharma is not considered effective against primary generalized seizures such as absences and may aggravate these seizures in some patients. Therefore, Gabapentin Taj Pharma should be used with caution in patients with mixed seizures including absences.

Gabapentin Taj Pharma treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall). There have also been post marketing reports of loss of consciousness, confusion and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medicinal product.

Concomitant use with opioids

Patients who require concomitant treatment with opioids should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence, sedation and respiratory depression. Patients who use Gabapentin Taj Pharma and morphine concomitantly may experience increases in Gabapentin Taj Pharma concentrations. The dose of Gabapentin Taj Pharma or opioids should be reduced approximately (see section 4.5).

Respiratory depression

Gabapentin Taj Pharma has been associated with severe respiratory depression. Patients with compromised respiratory function, respiratory or neurological disease, renal impairment, concomitant use of CNS depressants and the elderly might be at higher risk of experiencing this severe adverse reaction. Dose adjustments might be necessary in these patients.

Elderly (over 65 years of age)

No systematic studies in patients 65 years or older have been conducted with Gabapentin Taj Pharma. In one double blind study in patients with neuropathic pain, somnolence, peripheral oedema 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.

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 Taj Pharma abuse e.g. drug-seeking behavior, dose escalation, development of tolerance.

Paediatric population

The effects of long-term (greater than 36 weeks) Gabapentin Taj Pharma 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.

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 Taj Pharma (see section 4.8).

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 Taj Pharma 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.

Interaction with other medicinal products and other forms of interaction

There are spontaneous and literature case reports of respiratory depression and/or sedation associated with Gabapentin Taj Pharma and opioid use. In some of these reports, the authors considered this a particular concern with the combination of Gabapentin Taj Pharma and opioids, especially in elderly patients

In a study involving healthy volunteers (N=12), when a 60mg controlled-release morphine capsule was administered 2 hours prior to a 600mg Gabapentin Taj Pharma capsule, mean Gabapentin Taj Pharma AUC increased by 44% compared to Gabapentin Taj Pharma administered without morphine. Therefore, patients who require concomitant treatment with opioids should be carefully observed for signs of CNS depression, such as somnolence, sedation and respiratory depression and the dose of Gabapentin Taj Pharma or opioid should be reduced appropriately.

No interaction between Gabapentin Taj Pharma and phenobarbital, phenytoin, valproic acid, or carbamazepine has been observed.

Gabapentin Taj Pharma steady-state pharmacokinetics are similar for healthy subjects and patients with epilepsy receiving these anti-epileptic agents.

Coadministration of Gabapentin Taj Pharma with oral contraceptives containing norethindrone and/or ethinyl estradiol, does not influence the steady-state pharmacokinetics of either component.

Coadministration of Gabapentin Taj Pharma with antacids containing aluminium and magnesium, reduces Gabapentin Taj Pharma bioavailability up to 24%. It is recommended that Gabapentin Taj Pharma be taken at the earliest two hours following antacid administration.

Renal excretion of Gabapentin Taj Pharma is unaltered by probenecid.

A slight decrease in renal excretion of Gabapentin Taj Pharma that is observed when it is coadministered with cimetidine is not expected to be of clinical importance.

Fertility, pregnancy and 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 practised 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 Taj Pharma:

Gabapentin Taj Pharma crosses the human placenta

There are no or limited amount ofdata from the use of Gabapentin Taj Pharma in pregnant women.

Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Gabapentin Taj Pharma should not be used during pregnancy unless the potential benefit to the mother clearly outweighs the potential risk to the foetus.

No definite conclusion can be made as to whether Gabapentin Taj Pharma is causally 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 Taj Pharma is excreted in human milk. Because the effect on the breast-fed infant is unknown, caution should be exercised when Gabapentin Taj Pharma is administered to a breast-feeding mother. Gabapentin Taj Pharma should be used in breast-feeding mothers only if the benefits clearly outweigh the risks.

Fertility

There is no effect on fertility in animal studies (see section 5.3).

Effects on ability to drive and use machines

Gabapentin Taj Pharma may have minor or moderate influence on the ability to drive and use machines. Gabapentin Taj Pharma 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.

Undesirable effects

The adverse reactions observed during clinical studies conducted in epilepsy (adjunctive and monotherapy) and neuropathic pain have been provided in a single list below by class and frequency:

very common (≥ 1/10); common (≥1/100 to <1/10), uncommon (≥ 1/1000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (< 1/10000) . Where an adverse reaction was seen at different frequencies in clinical studies, it was assigned to the highest frequency reported.

Additional reactions reported from post-marketing experience are included as frequency Not known (cannot be estimated from the available data) in italics in the list below.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Infections and infestations

Very Common: Viral infection

Common: Pneumonia, respiratory infection, urinary tract infection, infection, otitis media

Blood and the lymphatic system disorders

Common: leucopenia

Not known: thrombocytopenia

Immune system disorders

Uncommon: allergic reactions (e.g. urticaria)

Not known: hypersensitivity syndrome, a systemic reaction with a variable presentation that can include fever, rash, hepatitis, lymphadenopathy, eosinophilia, and sometimes other signs and symptoms , anaphylaxis (see section 4.4)

Metabolism and Nutrition Disorders

Common: anorexia, increased appetite

Uncommon: hyperglycaemia (most often observed in patients with diabetes)

Rare: hypoglycaemia (most often observed in patients with diabetes)

Not known: hyponatraemia

Psychiatric disorders

Common: hostility, confusion and emotional lability, depression, anxiety, nervousness, thinking abnormal

Unknown: agitation

Not known: hallucinations

Nervous system disorders

Very Common: somnolence, dizziness, ataxia

Common: convulsions, hyperkinesias, dysarthria, amnesia, tremor, insomnia, headache, sensations such as paresthesia, hypaesthesia, coordination abnormal, nystagmus, increased, decreased, or absent reflexes

Uncommon: hypokinesia, mental impairment

Rare: loss of consciousness

Not known: other movement disorders (e.g. choreoathetosis, dyskinesia, dystonia)

Eye disorders

Common: visual disturbances such as amblyopia, diplopia

Ear and Labyrinth disorders

Common: vertigo

Not known: tinnitus

Cardiac disorders

Uncommon: palpitations

Vascular disorders

Common: hypertension, vasodilatation

Respiratory, thoracic and mediastinal disorders

Common: dyspnoea, bronchitis, pharyngitis, cough, rhinitis

Rare: Respiratory depression

Gastrointestinal disorders

Common: vomiting, nausea, dental abnormalities, gingivitis, diarrhea, abdominal pain, dyspepsia, constipation, dry mouth or throat, flatulence

Uncommon: dysphagia

Not known: pancreatitis

Hepatobiliary disorders

Not known: hepatitis, jaundice

Skin and subcutaneous tissue disorders

Common: facial oedema, purpura most often described as bruises resulting from physical trauma, rash, pruritus, acne

Not known: Stevens-Johnson syndrome, angioedema, erythema multiforme, alopecia, drug rash with eosinophilia and systemic symptoms (see section 4.4)

Musculoskeletal and connective tissue disorders

Common: arthralgia, myalgia, back pain, twitching

Not known: myoclonus, rhabdomyolysis

Renal and urinary disorders

Not known: acute renal failure, incontinence

Reproductive system and breast disorders

Common: impotence

Not known: breast hypertrophy, gynaecomastia ,sexual dysfunction (including changes in libido, ejaculation disorders and anorgasmia)

General disorders and administration site conditions

Very Common: fatigue, fever

Common: peripheral oedema, abnormal gait, asthenia, pain, malaise, flu syndrome

Uncommon: generalized oedema

Not known: withdrawal reactions (mostly anxiety, insomnia, nausea, pains, sweating), chest pain. Sudden unexplained deaths have been reported where a causal relationship to treatment with Gabapentin Taj Pharma has not been established.

Investigations

Common: WBC (white blood cell count) decreased, weight gain

Uncommon: elevated liver function tests SGOT (AST), SGPT (ALT) and bilirubin

Not known: blood creatine phosphokinase increased

Injury, poisoning and procedural complications

Common: accidental injury, fracture, abrasion

Uncommon : fall

Under treatment with Gabapentin Taj Pharma cases of acute pancreatitis were reported. Causality with Gabapentin Taj Pharma is unclear (see section 4.4).

In patients on haemodialysis due to end-stage renal failure, myopathy with elevated creatine kinase levels has been reported

Respiratory tract infections, otitis media, convulsions and bronchitis were reported only in clinical studies in children. Additionally, in clinical studies in children, aggressive behaviour and hyperkinesias were reported commonly.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

Overdose

Acute, life-threatening toxicity has not been observed with Gabapentin Taj Pharma overdoses of up to 49 g. Symptoms of the overdoses included dizziness, double vision, slurred speech, drowsiness, loss of consciousness,lethargy and mild diarrhoea. All patients recovered fully with supportive care. Reduced absorption of Gabapentin Taj Pharma at higher doses may limit drug absorption at the time of overdosing and, hence, minimise toxicity from overdoses.

Overdoses of Gabapentin Taj Pharma, particularly in combination with other CNS depressant medications, may result in coma

Although Gabapentin Taj Pharma can be removed by haemodialysis, based on prior experience it is not usually required. However, in patients with severe renal impairment, haemodialysis may be indicated.

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

5. Pharmacological properties

Pharmacodynamic properties

Pharmacotherapeutic groups: Other antiepileptics,

Mechanism of action

The precise mechanism of action of Gabapentin Taj Pharma is not known.

Gabapentin Taj Pharma readily enters the brain and prevents seizures in a number of animal models of epilepsy. Gabapentin Taj Pharma does not possess affinity for either GABAA or GABAB receptor nor does it alter the metabolism of GABA. It does not bind to other neurotransmitter receptors of the brain and does not interact with sodium channels. Gabapentin Taj Pharma binds with high affinity to the α2δ (alpha-2-delta) subunit of voltage-gated calcium channels and it is proposed that binding to the α2δ subunit may be involved in Gabapentin Taj Pharma’s antiseizure effects in animals. Broad panel screening does not suggest any other drug targets other than α2δ.

Evidence from several preclinical models inform that the pharmacological activity of Gabapentin Taj Pharma may be mediated via binding to α2δ through a reduction in release of excitatory neurotransmitters in regions of the central nervous system. Such activity may underlie Gabapentin Taj Pharma’s anti-seizure activity. The relevance of these actions of Gabapentin Taj Pharma to the anticonvulsant effects in humans remains to be established.

Gabapentin Taj Pharma also displays efficacy in several preclinical animal pain models. Specific binding of Gabapentin Taj Pharma to the α2δ subunit is proposed to result in several different actions that may be responsible for analgesic activity in animal models. The analgesic activities of Gabapentin Taj Pharma may occur in the spinal cord as well as at higher brain centers through interactions with descending pain inhibitory pathways. The relevance of these pre-clinical properties to clinical action in humans is unknown.

Clinical efficacy and safety

A clinical trial of adjunctive treatment of partial seizures in paediatric subjects, ranging in age from 3 to 12 years, showed a numerical but not statistically significant difference in the 50% responder rate in favour of the Gabapentin Taj Pharma group compared to placebo. Additional post-hoc analyses of the responder rates by age did not reveal a statistically significant effect of age, either as a continuous or dichotomous variable (age groups 3-5 and 6-12 years).

The data from this additional post-hoc analysis are summarised in the table below:

*The modified intent to treat population was defined as all patients randomised to study medication who also had evaluable seizure diaries available for 28 days during both the baseline and double-blind phases.

• Pharmacokinetic properties

Absorption

Following oral administration, peak plasma Gabapentin Taj Pharma concentrations are observed within 2 to 3 hours. Gabapentin Taj Pharma bioavailability (fraction of dose absorbed) tends to decrease with increasing dose. Absolute bioavailability of a 300mg capsule is approximately 60%. Food, including a high-fat diet, has no clinically significant effect on Gabapentin Taj Pharma pharmacokinetics.

Gabapentin Taj Pharma pharmacokinetics are not affected by repeated administration. Although plasma Gabapentin Taj Pharma 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 3.

Table 3

Summary of Gabapentin Taj Pharma mean (%CV) steady-state pharmacokinetic parameters following every eight hours administration

Distribution

Gabapentin Taj Pharma is not bound to plasma proteins and has a volume of distribution equal to 57.7 litres. In patients with epilepsy, Gabapentin Taj Pharma concentrations in cerebrospinal fluid (CSF) are approximately 20% of corresponding steady-state trough plasma concentrations. Gabapentin Taj Pharma is present in the breast milk of breast-feeding women.

Biotransformation

There is no evidence of Gabapentin Taj Pharma metabolism in humans. Gabapentin Taj Pharma does not induce hepatic mixed function oxidase enzymes responsible for drug metabolism.

Elimination

Gabapentin Taj Pharma is eliminated unchanged solely by renal excretion. The elimination half-life of Gabapentin Taj Pharma is independent of dose and averages 5 to 7 hours.

In elderly patients, and in patients with impaired renal function, Gabapentin Taj Pharma plasma clearance is reduced. Gabapentin Taj Pharma elimination-rate constant, plasma clearance, and renal clearance are directly proportional to creatinine clearance.

Gabapentin Taj Pharma is removed from plasma by haemodialysis. Dosage adjustment in patients with compromised renal function or undergoing haemodialysis is recommended (see section 4.2).

Gabapentin Taj Pharma pharmacokinetics in children were determined in 50 healthy subjects between the ages of 1 month and 12 years. In general, plasma Gabapentin Taj Pharma concentrations in children> 5 years of age are similar to those in adults when dosed on amg/kg basis. In a pharmacokinetic study in 24 healthy paediatric subjects aged between 1 month and 48 months, an approximately 30% lower exposure (AUC), lower Cmax 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 Taj Pharma bioavailability (fraction of dose absorbed) decreases with increasing dose which imparts non-linearity to pharmacokinetic parameters which include the bioavailability parameter (F) e.g. Ae%, CL/F, Vd/F. Elimination pharmacokinetics (pharmacokinetic parameters which do not include F such as CLr and T1/2), are best described by linear pharmacokinetics. Steady state plasma Gabapentin Taj Pharma concentrations are predictable from single-dose data.

• Preclinical safety data

Carcinogenesis

Gabapentin Taj Pharma was given in the diet to mice at 200, 600, and 2000mg/kg/day and to rats at 250, 1000, and 2000mg/kg/day for two years. A statistically significant increase in the incidence of pancreatic acinar cell tumors was found only in male rats at the highest dose. Peak plasma drug concentrations in rats at 2000mg/kg/day are 10 times higher than plasma concentrations in humans given 3600mg/day. The pancreatic acinar cell tumors in male rats are low-grade malignancies, did not affect survival, did not metastasize or invade surrounding tissue, and were similar to those seen in concurrent controls. The relevance of these pancreatic acinar cell tumors in male rats to carcinogenic risk in humans is unclear.

Mutagenesis

Gabapentin Taj Pharma demonstrated no genotoxic potential. It was not mutagenic in vitro in standard assays using bacterial or mammalian cells. Gabapentin Taj Pharma did not induce structural chromosome aberrations in mammalian cells in vitro or in vivo, and did not induce micronucleus formation in the bone marrow of hamsters.

Impairment of Fertility

No adverse effects on fertility or reproduction were observed in rats at doses up to 2000mg/kg (approximately five times the maximum daily human dose on amg/m2 of body surface area basis).

Teratogenesis

Gabapentin Taj Pharma did not increase the incidence of malformations, compared to controls, in the offspring of mice, rats, or rabbits at doses up to 50, 30 and 25 times respectively, the daily human dose of 3600mg, (four, five or eight times, respectively, the human daily dose on amg/m2 basis).

Gabapentin Taj Pharma induced delayed ossification in the skull, vertebrae, forelimbs, and hindlimbs in rodents, indicative of fetal growth retardation. These effects occurred when pregnant mice received oral doses of 1000 or 3000mg/kg/day during organogenesis and in rats given 2000mg/kg prior to and during mating and throughout gestation. These doses are approximately 1 to 5 times the human dose of 3600mg on amg/m2 basis.

No effects were observed in pregnant mice given 500mg/kg/day (approximately 1/2 of the daily human dose on amg/m2 basis).

An increased incidence of hydroureter and/or hydronephrosis was observed in rats given 2000mg/kg/day in a fertility and general reproduction study, 1500mg/kg/day in a teratology study, and 500, 1000, and 2000mg/kg/day in a perinatal and postnatal study. The significance of these findings is unknown, but they have been associated with delayed development. These doses are also approximately 1 to 5 times the human dose of 3600mg on amg/m2 basis.

In a teratology study in rabbits, an increased incidence of post-implantation fetal loss, occurred in pregnant rabbits given 60, 300, and 1500mg/kg/day during organogenesis. These doses are approximately 0.3 to 8 times the daily human dose of 3600mg on amg/m2 basis. The margins of safety are insufficient to rule out the risk of these effects in humans.

6. Pharmaceutical particulars
   • List of excipients

Core tablet

Maize starch,

Copovidone,

Poloxamer 407,

Hydroxypropyl cellulose

Magnesium stearate

Coating

Hydroxypropyl cellulose

Talc

Printing ink composition

Propylene glycol,

Shellac glaze,

Iron oxide black,

Ammonium hydroxide

• Incompatibilities

Not applicable.

• Shelf life

3 years

• Special precautions for storage

Do not store above 30°C.

• Nature and contents of container

Tablets are in blister pack, the PVC/PVdC-aluminum blisters packed in final carton along with package insert.

Supplied in packs of: 20, 30, 50, 60, 90, 100, 200 and 500 tablets

Not all pack sizes may be marketed.

Special precautions for disposal and other handling

No special requirements.

Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at: Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Gabapentin Tablets USP 600mg Taj Pharma

Package leaflet: Information for the user

Gabapentin 600mg Film-coated tabletsTaj Pharma
Gabapentin 800mg Film-coated tablets Taj Pharma

Gabapentin Taj Pharma

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

 Keep this leaflet. You may need to read it again.

 If you have any further questions, ask your doctor, pharmacist or nurse.

 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

 If you get any side effects,talk to your doctor, pharmacist or nurse.This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Gabapentin Taj Pharma Film-coated tablets are and what they are used for
2. What you need to know before you take Gabapentin Taj Pharma Film-coated tablets
3. How to take Gabapentin Taj Pharma Film-coated tablets
4. Possible side effects
5. How to store Gabapentin Taj Pharma Film-coated tablets
6. Content of the pack and other information

1. What Gabapentin Taj Pharma Film-coated tablets are and what they are used for

Gabapentin Taj Pharma Film-coated tablets belong to a group of medicines used to treat epilepsy and peripheral neuropathic pain (long lasting pain caused by damage to the nerves).

The active ingredient in Gabapentin Taj Pharma Film-coated tablets is Gabapentin Taj Pharma.

Gabapentin Taj Pharma Film-coated tablets are used to treat:

 Various forms of epilepsy (seizures that are initially limited to certain parts of the brain, whether the seizure spreads to other parts of the brain or not). The doctor treating you or your child 6 years of age and older will prescribe Gabapentin Taj Pharma Film-coated tablets for you to help treat epilepsy when the current treatment is not fully controlling the condition. You or your child 6 years of age and older should take Gabapentin Taj Pharma Film-coated tablets in addition to the current treatment unless told otherwise. Gabapentin Taj Pharma Film-coated tablets can also be used on its own to treat adults and children over 12 years of age.

 Peripheral neuropathic pain (long lasting pain caused by damage to the nerves). A variety of different diseases can cause peripheral neuropathic pain (primarily occurring in the legs and/or arms), such as diabetes or shingles. Pain sensations may be described as hot, burning, throbbing, shooting, stabbing, sharp, cramping, aching, tingling, numbness, pins and needles etc.

2. What you need to know before you take Gabapentin Taj Pharma Film-coated tablets

Do not take Gabapentin Taj Pharma Film-coated tablets

if you are allergic to Gabapentin Taj Pharma or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or pharmacist befpre taking Gabapentin Taj Pharma Film-coated tablets:

 if you suffer from kidney problems your doctor may prescribe a different dosing schedule

 if you are on haemodialysis (to remove waste products because of kidney failure), tell your doctor if you develop muscle pain and/or weakness

 if you develop signs such as persistent stomach pain, feeling sick and being sick contact your doctor immediately as these may be symptoms of acute pancreatitis (an inflamed pancreas).

 if you have nervous system disorders, respiratory disorders, or you are more than 65 years old, your doctor may prescribe you a different dosing regimen

Cases of abuse and dependence have been reported for Gabapentin Taj Pharma from the post-marketing experience.

Talk to your doctor if you have a history of abuse or dependence.

A small number of people being treated with anti-epileptics such as Gabapentin Taj Pharma have had thoughts of harming or killing themselves. If at any time you have these thoughts, immediately contact your doctor.

Important information about potentially serious reactions

A small number of people taking Gabapentin Taj Pharma get an allergic reaction or potentially serious skin reaction, which may develop into more serious problems if they are not treated. You need to know the symptoms to look out for while you are taking Gabapentin Taj Pharma.

Read the description of these symptoms in section 4 of this leaflet under ‘Contact your doctor immediately if you experience any of the following symptoms after taking this medicine as they can be serious’

Muscle weakness, tenderness or pain and particularly, if at the same time, you feel unwell or have a high temperature it may be caused by an abnormal muscle breakdown which can be life-threatening and lead to kidney problems. You may also experience discoloration of your urine, and a change in blood test results (notably blood creatine phosphokinase increased). If you experience any of these signs or symptoms, please contact your doctor immediately.

Other medicines and Gabapentin Taj Pharma Film-coated tablets

Tell your doctor or pharmacist if you are taking or have recently taken or might take any other medicines.

In particular, tell your doctor (or pharmacist) if you are taking or have been recently taking any medicines for convulsions, sleeping disorders, depression, anxiety, or any other neurological or psychiatric problems.

Medicines containing opioids such as morphine

If you are taking any medicines containing opioids (such as morphine), please tell your doctor or pharmacist as opioids may increase the effect of Gabapentin Taj Pharma Film-coated tablets. In addition, combination of Gabapentin Taj Pharma film-coated tablets with opioids may cause symptoms like sleepiness and/or decrease in breathing.

Antacids for indigestion

If Gabapentin Taj Pharma Film-coated tablets and antacids containing aluminium and magnesium are taken at the same time, absorption of Gabapentin Taj Pharma Film-coated tablets from the stomach may be reduced. It is therefore recommended that Gabapentin Taj Pharma Film-coated tabletsis taken at the earliest two hours after taking an antacid.

Gabapentin Taj Pharma Film-coated tablets:

 is not expected to interact with other antiepileptic drugs or the oral contraceptive pill.

 may interfere with some laboratory tests, if you require a urine test tell your doctor or hospital what you are taking.

Taking Gabapentin Taj Pharma Film-coated tablets with food and drink

Gabapentin Taj Pharma Film-coated tablets can be taken with or without food.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

Gabapentin Taj Pharma Film-coated tablets should not be taken during pregnancy, unless you are told otherwise by your doctor. Effective contraception must be used by women of child-bearing potential.

There have been no studies specifically looking at the use of Gabapentin Taj Pharma in pregnant women, but other medications used to treat seizures have reported an increased risk of harm to the developing baby, particularly when more than one seizure medication is taken at the same time. Therefore, whenever possible, you should try to take only one seizure medication during pregnancy and only under the advice of your doctor.

Contact your doctor immediately if you become pregnant, think you might be pregnant or are planning to become pregnant while taking Gabapentin Taj Pharma Film-coated tablets. Do not suddenly discontinue taking this medicine as this may lead to a breakthrough seizure, which could have serious consequences for you and your baby.

Breast feeding

Gabapentin Taj Pharma, the active substance of Gabapentin Taj Pharma Film-coated tablets, is passed on through human milk. Because the effect on the baby is unknown, it is not recommended to breast-feed while using Gabapentin Taj Pharma Film-coated tablets.

Fertility

There is no effect on fertility in animal studies.

Driving and using machines

Gabapentin Taj Pharma Film-coated tablets may produce dizziness, drowsiness and tiredness. You should not drive, operate complex machinery or take part in other potentially hazardous activities until you know whether this medication affects your ability to perform these activities.

3. How to take Gabapentin Taj Pharma Film-coated tablets

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Your doctor will determine what dose is appropriate for you.

Epilepsy, the recommended dose is:

Adults and adolescents:

Take the number of tablets as instructed. Your doctor will usually build up your dose gradually.

The starting dose will generally be between 300mg and 900mg each day. Thereafter, the dose may be increased as instructed by your doctor up to a maximum of 3600mg each day and your doctor will tell you to take this in 3 separate doses, i.e. once in the morning, once in the afternoon and once in the evening.

Children aged 6 years and above:

The dose to be given to your child will be decided by your doctor as it is calculated against your child’s weight.

The treatment is started with a low initial dose which is gradually increased over a period of approximately 3 days.

The usual dose to control epilepsy is 25-35mg/kg/day.

It is usually given in 3 separate doses, by taking the tablet(s) each day, usually once in the morning, once in the afternoon and once in the evening.

Gabapentin Taj Pharma Film-coated tablets is not recommended for use in children below 6 years of age.

Peripheral Neuropathic Pain, the usual dose is:

Adults:

Take the number of tablets as instructed by your doctor. Your doctor will usually build up your dose gradually.

The starting dose will generally be between 300mg and 900mg each day.

Thereafter, the dose may be increased as instructed by your doctor, up to a maximum of 3600mg each day and your doctor will tell you to take this in 3 separate doses, i.e. once in the morning, once in the afternoon and once in the evening.

If you have kidney problems or are receiving haemodialysis

Your doctor may prescribe a different dosing schedule and/or dose if you have problems with your kidneys or are undergoing haemodialysis.

If you are an elderly patient (over 65 years of age) you should take the normal dose of Gabapentin Taj Pharma Film-coated tablets unless you have problems with your kidneys. Your doctor may prescribe a different dosing schedule and/or dose if you have problems with your kidneys.

If you have the impression that the effect of Gabapentin Taj Pharma Film-coated tablets is too strong or too weak, talk to your doctor or pharmacist as soon as possible.

Method of administration

Gabapentin Taj Pharma Film-coated tablets is for oral use. Always swallow the capsules or tablets with plenty of

water.

Continue taking Gabapentin Taj Pharma Film-coated tablets until your doctor tells you to stop.

If you take more Gabapentin Taj Pharma Film-coated tablets than you should

Higher than recommended doses may result in an increase in side effects including loss of consciousness, dizziness, double vision, slurred speech, drowsiness and diarrhoea. Call your doctor or go to the nearest hospital emergency unit immediately if you take more Gabapentin Taj Pharma Film-coated tablets than your doctor prescribed.

Take along any tablets that you have not taken, together with the container and the label so that the hospital can easily tell what medicine you have taken.

If you forget to take Gabapentin Taj Pharma Film-coated tablets

If you forget to take a dose, take it as soon as you remember unless it is time for your next dose. Do not take a double dose to make up for a forgotten dose.

If you stop taking Gabapentin Taj Pharma Film-coated tablets

Do not stop taking Gabapentin Taj Pharma Film-coated tablets unless your doctor tells you to. If your treatment is stopped it should be done gradually over a minimum of 1 week.

If you stop taking Gabapentin Taj Pharma Film-coated tablets suddenly or before your doctor tells you, there is an increased risk of seizures.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Contact your doctor IMMEDIATELY if you experience any of the following symptoms after taking this medicine as they can be serious:

• severe skin reactions that require immediate attention, swelling of the lips and face, skin rash and redness and/or hair loss (these may be symptoms of a serious allergic reaction) persistant stomach pain, feeling sick and being sick as these may be symptoms of acute pancreatitis (an inflamed pancreas)breathing problems, which if severe you may need emergency and intensive care to continue breathing normally
• Gabapentin Taj Pharma may cause a serious or life-threatening allergic reaction that may affect your skin or other parts of your body such as your liver or blood cells. You may or may not have rash when you get this type of reaction. It may cause you to be hospitalised or to stop Gabapentin Taj Pharma.

Call your doctor right away if you have any of the following symptoms:

• skin rash
• hives
• fever
• swollen glands that do not go away
• swelling of your lip and tongue
• yellowing of your skin or of the whites of the eyes
• unusual bruising or bleeding
• severe fatigue or weakness
• unexpected muscle pain
• frequent infections

These symptoms may be the first signs of a serious reaction. A doctor should examine you to decide if you should continue taking Gabapentin Taj Pharma. If you are on haemodialysis, tell your doctor if you develop muscle pain and/or weakness

Other side effects include:

Very common (may affect more than 1 in 10 people):

• viral infection
• dizziness
• lack of coordination
• viral infection
• feeling drowsy
• feeling tired
• fever

Common (may affect up to 1 in 10 people):

• convulsions
• jerky movements
• difficulty with speaking
• loss of memory
• tremor
• difficulty sleeping
• headache
• sensitive skin
• decreased sensation (numbness)
• difficulty with coordination
• unusual eye movement
• increased, decreased or absent reflexes
• pneumonia, respiratory infections, urinary tract infection, inflammation of the ear or other infections
• low white blood cell counts
• anorexia
• increased appetite
• anger towards others
• confusion
• mood changes
• depression
• anxiety
• nervousness
• difficulty with thinking
• blurred vision, double vision
• vertigo
• high blood pressure
• flushing or dilation of blood vessels
• difficulty breathing, bronchitis, cough
• sore throat
• dry nose
• vomiting (being sick), nausea (feeling sick)
• problems with teeth, inflamed gums
• diarrhoea
• stomach pain
• indigestion
• constipation
• dry mouth or throat
• flatulence
• facial swelling
• bruises
• rash, itch
• acne
• joint pain, muscle pain, back pain
• twitching
• difficulties with erection (impotence)
• swelling in the legs and arms
• difficulty with walking
• weakness, pain
• feeling unwell
• flu-like symptoms
• decrease in white blood cells
• increase in weight
• accidental injury, fracture, abrasion

Additionally in clinical studies in children, aggressive behaviour and jerky movements were reported.

Uncommon (may affect up to 1 in 100 people):

• agitation (a state of chronic restlessness and unintentional and purposeless motions)
• allergic reactions such as hives
• decreased movement
• racing heartbeat
• swelling that may involve the face, trunk and limbs
• abnormal blood test results suggesting problems with the liver
• mental impairment
• fall
• high blood sugar (most often observed in patients with diabetes)
• Difficulty swallowing

Rare (which may affect up to 1 in 1, 000 people):

• Low blood sugar (most often observed in patients with diabetes)
• Loss of consciousness
• Trouble breathing, shallow breaths (respiratory depression)

Side-effects foe which the frequency cannot be estimated based on the available data:

• hyponatraemia

Since introduction to the market the following side-effects have been reported:

• acute kidney failure, incontinence
• inflammation of the liver, yellowing of the skin and eyes (jaundice),
• hallucinations
• problems with abnormal movements such as writhing, jerking movements and stiffness
• adverse events following the abrupt discontinuation of Gabapentin Taj Pharma (anxiety, difficulty sleeping, feeling sick, pain, sweating), chest pain
• increased breast tissue, breast enlargement
• decreased platelets (blood clotting cells)
• ringing in the ears
• a group of side effects that could include swollen lymph nodes (isolated small raised lumps under the skin), fever, rash, and inflammation of liver occurring together
• blood glucose fluctuations in patients with diabetes
• breakdown of muscle fibers (rhabdomyolosis)
• change in blood rest results (creatine phosphokinase increased)
• problems with sexual functioning including inability to achieve a sexual climax, delayed ejaculation
• low blood sodium level
• anaphylaxis (serious, potentially life threatening allergic reaction including difficulty breathing, swelling of the lips, throat, and tongue, and hypotension requiring emergency treatment)

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Gabapentin Taj Pharma Film-coated tablets

• Keep this medicine out of the sight and reach of children.
• Do not store above 30C.
• Do not use this medicine after the expiry date which is stated on the carton after ‘EXP’. The expiry date refers to the last day of that month.
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Content of the pack and other information

What Gabapentin Taj Pharma Film-coated tablets contain:

The active substance is Gabapentin Taj Pharma. Each film-coated tablet has either 600mg or 800mg Gabapentin Taj Pharma.

The other ingredients are:

Core tablet:

Maize starch, Copovidone, Poloxamer 407, Hydroxypropyl cellulose, Magnesium Stearate

Coating:

Hydroxypropyl cellulose, talc

Printing ink composition

Propylene glycol, Shellac glaze, Iron oxide black, Ammonium hydroxide

What Gabapentin Taj Pharma Film-coated tablets look like and contents of the pack:

600mg Tablets are available as white to off-white, Oval shaped, film coated tablets.

800mg Tablets are available as white to off-white, Capsule shaped, film coated tablets.

Gabapentin Taj Pharma Film-coated tablets are packed in PVC/PVdC -aluminum blister packs of 20, 30, 50, 60, 90, 100, 200 and 500 tablets

Not all pack sizes may be marketed.

Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at: Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com