Gabapentin Capsules USP 100mg Taj Pharma

1. Name of the medicinal product

Gabapentin Capsules USP 100mg Taj Pharma
Gabapentin Capsules USP 300mg Taj Pharma
Gabapentin Capsules USP 400mg Taj Pharma

2. Qualitative and quantitative composition

a) Gabapentin Capsules USP 100mg Taj Pharma
Each hard gelatin capsule contains:
Gabapentin 100mg
Excipients: Q.S.

b) Gabapentin Capsules USP 300mg Taj Pharma
Each hard gelatin capsule contains:
Gabapentin 300mg
Excipients: Q.S.

c) Gabapentin Capsules USP 400mg Taj Pharma
Each hard gelatin capsule contains:
Gabapentin 400mg
Excipients: Q.S.

Each 100mg capsule contains 16.83mg lactose (as monohydrate).

For a full list of excipients, see section 6.1.

3. Pharmaceutical form

Hard capsules (capsules):

White hard capsule, imprinted “100/30/400” and containing a white crystalline powder.

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

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 longterm 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 patients (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.

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

b To be administered as 300mg every other day.

c 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

Suicidal ideation and behaviour

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 pancreatits

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

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 appropriately (see section 4.5).

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 refractive 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.

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.

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.

Dizziness, somnolence, loss of consciousness, confusion, and mental impairment

Gabapentin Taj Pharma treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall) in the elderly population. 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.

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).

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.

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 behaviour, dose escalation, development of tolerance.

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.

Gabapentin Taj Pharma capsules contain lactose

Gabapentin Taj Pharma capsules contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take Gabapentin Taj Pharma capsules.

• 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

There are no adequate data 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 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 ( 1/10000 to < 1/1000); 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.

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 grams.

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

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

Gabapentin Taj Pharma 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 Taj Pharma 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 Taj Pharma and its structural derivatives.

The binding site for Gabapentin Taj Pharma has been identified as the alpha2-delta subunit of voltage-gated calcium channels.

Gabapentin Taj Pharma 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-daspartate receptors.

Gabapentin Taj Pharma does not interact with sodium channels in vitro and so differs from phenytoin and carbamazepine. Gabapentin Taj Pharma 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 Taj Pharma slightly reduces the release of monoamine neurotransmitters in vitro.

Gabapentin Taj Pharma 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 Taj Pharma to the anticonvulsant effects remains to be established. In animals, Gabapentin Taj Pharma readily enters the brain and prevents seizures from maximal electroshock, from chemical convulsants including inhibitors of GABA synthesis, and in genetic models of seizures.

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 nonlinearity 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 tumours was found only in male rats at the highest dose. Peak plasma drug concentrations in rats at 2000mg/kg are 10 times higher than plasma concentrations in humans given 3600mg/day. The pancreatic acinar cell tumours 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 tumours 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 doses given 60, 300, and 1500mg/kg/day during organogenesis. These doses are approximately 1/4 to 8 times the daily human dose of 3600mg on amg/m2 basis.

6. Pharmaceutical particulars
   • List of excipients

Capsules fill:

Lactose Monohydrate;

Maize Starch;

Talc.

Capsule shell:

Gelatin;

Titanium Dioxide

Printing ink:

Shellac;

Iron oxide black;

Propylene glycol.

• Incompatibilities

Not applicable

• Shelf life

Three years

• Special precautions for storage

Do not store above 30°C.

• Nature and contents of container

PVC/aluminium foil blister packs

Each blister pack and box contain: 10, 20, 30, 40, 50, 60, 100, 120, 240, 360 and 500 hard gelatin capsules.

Not all pack size 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 Taj Pharma capsules USP 100mg Taj Pharma

Package leaflet: Information for the user

Gabapentin capsules USP 100mg 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 or pharmacist.
• 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 or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Gabapentin Taj Pharma is and what it is used for
2. What you need to know before you take Gabapentin Taj Pharma
3. How to take Gabapentin Taj Pharma
4. Possible side effects
5. How to store Gabapentin Taj Pharma
6. Contents of the pack and other information

1. WHAT Gabapentin Taj Pharma IS AND WHAT IT IS USED FOR

This medicine is called Gabapentin Taj Pharma and it contains the active substance Gabapentin Taj Pharma (called Gabapentin Taj Pharma throughout this leaflet).

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

Gabapentin Taj Pharma is 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 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 in addition to the current treatment unless told otherwise. Gabapentin Taj Pharma 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

Do not take Gabapentin Taj Pharma

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

Warnings and precautions

Talk to your doctor or pharmacist before taking Gabapentin Taj Pharma:

• 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

Gabapentin Taj Pharma treatment has been associated with dizziness and sleepiness, which could increase the likelihood of falls in older people. There have also been reports of loss of consciousness and confusion (see section 4).

Cases of abuse and dependence have been reported for Gabapentin Taj Pharma. 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 ‘Tell your doctor straight away’.

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 discolouration 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.

Children and adolescents

There is limited data available on the effects of long-term Gabapentin Taj Pharma therapy (> 36 weeks); therefore the benefits must be weighed against the potential risks.

Gabapentin Taj Pharma is not recommended for use in children under 6 years old.

Other medicines and Gabapentin Taj Pharma

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without prescription. 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. In addition, combination of Gabapentin Taj Pharma with opioids may cause symptoms like sleepiness and/or decrease in breathing.

Antacids for indigestion

The absorption of Gabapentin Taj Pharma from the stomach may be reduced if you are taking any medicines used to treat ulcer (antacids containing aluminium and magnesium) at the same time. It is therefore recommended that Gabapentin Taj Pharma is taken at the earliest two hours after taking an antacid.

Gabapentin Taj Pharma is not expected to interact with other drugs against epilepsy or your oral contraceptive pill.

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

Gabapentin Taj Pharma with food

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

No specific studies in pregnant women have been done with this medicine. However 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. Do not suddenly discontinue taking this medicine. The seizures may reappear, which could have serious consequences for you and your baby.

Breast-feeding

Gabapentin Taj Pharma 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.

Fertility

There is no effect on fertility in animal studies.

Driving and using machines

Gabapentin Taj Pharma 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 medicine affects your ability to perform these activities.

Gabapentin Taj Pharma Capsules contains lactose

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

3. HOW TO TAKE Gabapentin Taj Pharma

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

Your doctor will determine what dose is appropriate for you.

If you take Gabapentin Taj Pharma to treat epilepsy the recommended dose is

Adults and adolescents

Take the number of capsules 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 progressively up to a maximum of 3600mg each day. Your doctor will tell you to take the dose in 3 divided 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 25-35 mg/kg/day.

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

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

If you take Gabapentin Taj Pharma to relieve peripheral neuropathic pain the recommended dose is

Adults

Take the number of capsules 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 progressively up to a maximum of 3600mg each day. Your doctor will tell you to take the dose in 3 divided 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 problem with your kidneys or are undergoing haemodialysis.

If you are an elderly patient (over 65 years old), you should take Gabapentin Taj Pharma as indicated unless if 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 is too strong or too weak, talk to your doctor or pharmacist as soon as possible.

Method of administration

Gabapentin Taj Pharma is for oral use. Always swallow the capsules with plenty of water.

Continue taking Gabapentin Taj Pharma until your doctor tells you to stop. You should not stop taking this medicine without medical advice.

If you take more Gabapentin Taj Pharma 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 than your doctor prescribed. Take along any capsules 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

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

Do not stop taking Gabapentin Taj Pharma 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 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.

Stop taking this medicine and see a doctor straight away if you experience any of the following symptoms 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).
• blistering, peeling or bleeding of the skin around the lip, eyes, mouth, nose and genitals. You may also have flu-like symptoms and a high temperature. These could be symptoms of Stevens-Johnson syndrome.
• yellowing of your skin or whites of your eyes, tiredness and fever. This may be due to inflammation of the liver or changes in the way your liver is working.
• persistent stomach pain, feeling sick and being sick. These may be symptoms of acute pancreatitis (an inflamed pancreas).
• frequent infections such as fever, severe chills, sore throat or mouth ulcers. This may be due to a lower than normal white blood cell count (shown by a blood test).
• decreased platelets (blood clotting cells).
• bruising more easily than usual. This could be because of a blood problem (thrombocytopenia).
• seeing or hearing things which are not there (hallucinations).
• problems with abnormal movements such as writhing, jerking movements and stiffness.
• ringing in the ears (tinnitus).
• serious kidney disease (acute kidney failure). Symptoms may include an increase in the need to pass water, passing of very small amounts of water, feeling tired, swelling of the hands and feet and a shortness of breath.
• difficulty breathing, swelling of the lips, throat and tongue or dizziness, lightheadedness or fainting (due to low blood pressure) requiring emergency treatment. These may be signs of a serious, possibly life threatening allergic reaction (anaphylaxis)
• 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 pans 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 hospitalized 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 d you develop muscle pain and/or weakness

Other side effects include:

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

• viral infection
• feeling drowsy, dizzy, lack of coordination
• feeling tired, fever

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

• pneumonia, respiratory infections, urinary tract infections, inflammation of the ear or other infections
• anorexia, increase in appetite
• anger towards others, confusion, mood changes, depression, anxiety, nervousness, strange or unusual thoughts
• convulsions, jerky movements, difficulty speaking, loss of memory, tremor, difficulty sleeping, headache, sensitive skin, decreased sensation (numbness), difficulty with coordination, unusual eye movements, increased, decreased or absent reflexes
• blurred vision, double vision
• vertigo
• high blood pressure, flushing or dilation of blood vessels
• difficulty breathing, bronchitis, sore throat, cough, 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 in walking, weakness, pain, feeling unwell, flu-like symptoms
• increase in weight
• accidental injury, fracture, abrasion

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

• decreased movement
• fall,
• mental impairment
• racing heart beat
• swelling that may involve the face, body and limbs
• abnormal blood test results suggesting problems with the liver
• increase in blood glucose levels (most often observed in patients with diabetes)
• agitation (a state of chronic restlessness and unintentional and purposeless motions)
• difficulty swallowing

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

• loss of consciousness
• decrease in blood glucose levels (most often observed in patients with diabetes)
• trouble breathing, shallow breaths (respiratory depression)

Not known cannot be estimated from available data):

• a group of side effects that could include swollen lymph nodes (isolated small raised lumps under skin), fever, rash, and inflammation of liver occurring together,
• incontinence (leakage of urine which you cannot control),
• increased breast tissue, breast enlargement
• side effects following the sudden stopping of Gabapentin Taj Pharma (anxiety, difficulty in sleeping, feeling sick, pain, sweating), chest pain,
• breakdown of muscle fibres (rhabdomyolysis),
• low blood sodium level (hyponatraemia),
• change in blood test results (creatine phosphokinase increased),
• problems with sexualfunctioning including inability to achieve a sexual climax, delayed ejaculation.

Additional side effects in children and adolescents

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

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

Keep out of sight and reach of children.

Do not store above 25°C.

Do not use these capsules after the expiry date which is stated on the carton. The expiry date refers to the last day of that month.

Do not throw away medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

6. CONTENTS OF THE PACK AND OTHER INFORMATION

What Gabapentin Taj Pharma Capsules contain

The active substance is Gabapentin Taj Pharma. Each capsule contains other 100mg, 300mg or 400mg of Gabapentin Taj Pharma.

The other ingredients are:

Gabapentin Taj Pharma 100mg Capsules: Lactose monohydrate, Maize starch, Talc, Titanium Dioxide and Gelatin.

Gabapentin Taj Pharma 300mg Capsules: Lactose monohydrate, Maize starch, Talc, Titanium Dioxide, Yellow Iron Oxide and Gelatin.

Gabapentin Taj Pharma 400mg Capsules: Lactose monohydrate, Maize starch, Talc, Titanium Dioxide, Yellow Iron Oxide, Red Iron Oxide and Gelatin,

The printing ink used on the capsule contains: Shellac, Titanium and FD&C Blue 1/Brilliant blue FCF Lake.

What Gabapentin Taj Pharma Capsules look like and contents of the pack

Gabapentin Taj Pharma 100mg Capsules are white, hard capsules.

Gabapentin Taj Pharma 300mg Capsules are yellow, hard capsules.

Gabapentin Taj Pharma 400mg Capsules are orange-yellow, hard capsules.

Pack size:

PVC/aluminium foil blister packs

Each blister pack and box contain: 10, 20, 30, 40, 50, 60, 100, 120, 240, 360 and 500 hard gelatin capsules.

Not all pack size 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