Description:

Indiga (Gabapentin) is a new antiepileptic drug that is structurally similar to the neurotransmitter gamma aminobutyric acid (GABA) and the endogenous amino acidآ  L-leucin e. Chemically Gabapentin is 1-(amino methyl) cyclohexaneacetic acid. Its empirical formula is C9H17NO2.

Mechanism of Action

Gabapentin has proven affinity for special site in brain tissues such as neocortex and hippocampus. Though exact mechanism of its CNS depressant and anticonvulsant activity is not fully understood, it is thought to be activated through peptide binding sites (receptor).

Pharmacokinetics:

1.    Absorption

Gabapentin is absorbed from the gastrointestinal tract by means of saturable mechanism. Gabapentin bioavailability is not dose proportional i.e. as dose is increased bioavailability is decreased. Absolute bioavailability of 300mg oral dose is approximately 60%. At doses of 300mg and 400mg, Gabapentin bioavailability was unchanged following multiple-dose administration. Food has no effect on the rate and extent of absorption.

2.    Distribution

Gabapentin circulates largely unbound (آ•آ 3%) to plasma proteins. Gabapentin i distributed into breast milk.

3.    Metabolism and Elimination

Gabapentin is not appreciably metabolized and is eliminated from the systemic circulation by renal excretion as unchanged drug. Elimination half-life (T1/2) ranges from 5 to 7 hours and is unaltered by dose or following multiple dosing. Gabapentin elimination rate constant, plasma clearance and renal clearance are directly proportional to creatinine clearance.

Special Populations

Ø   Renal insufficiency

The mean Gabapentin half-life ranged from about 6.5 hours (patients with creatinine clearance (CLcr) >60mL/min) to 52 hours (CLcr <30mL/min) and Gabapentin renal clearance ranged from 90mL/min (CLcr >60mL/min) to about 10mL/min (CLcr <30mL/min). Gabapentin dosage should be adjusted in patients with compromised renal function.

Ø   Patients on Haemodialysis

Gabapentin dosage should be adjusted in patients undergoing haemodialysis.

Ø   Elderly Patients

Reduction of Gabapentin dose may be required in patients who have age related compromised renal function.

Indications and Usage

There are many evolving indications of Gabapentin under trial. Its main indications are for the treatment of neuropathic pain and epilepsy.

1) Neuropathic Pain

Indiga (Gabapentin) is indicated

For various types of neuropathic pain in adults:

a.     Post herpetic neuralgia (PHN).

b.     Peripheral diabetic neuropathies.

c.     Trigeminal neuralgia.

2) Epilepsy

Indiga (Gabapentin) is indicated as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in patients over 12 years of age with epilepsy. Indiga is also indicated as adjunctive therapy in the treatment of partial seizures in pediatric patients, age 3 to 12 years.

Dosage & Administration:

Indiga (Gabapentin) is given in titrations that lead to an effective dose. Treatment progresses rapidly and can be accomplished over a few days. The total dose should be divided into three doses given at intervals not exceeding 12 hours. Indiga (Gabapentin) may be given orally with or without food.

Ø   Neuropathic Pain:

(Adults-over the age of 18)

The initial daily dose of Indiga (Gabapentin) can be titrated as given in the table below.

Effectiveness as an adjunct therapy of neuropathic pain in pediatric patients has not been established.

Ø   Epilepsy:

Adults and children over 12 years of age:

Therapy may be initiated by administering 300mg three times a day on day 1 or by titrating the dose as described in the following table.

Thereafter the dose maybe increased in increments of 300mg daily until effective epileptic control is achieved, which is usually within the range of 900-1200mg daily. Higher doses up to a maximum of 2400mg daily may be required in some patients.

Ø   Children aged 6 to 12 years:

The initial recommended dose of Indiga (Gabapentin) is 25-35mg/kg/day given in divided doses (3 times a day). Titration to an effective dose can take place over 3 days by giving 10mg/kg/day on day 1, 20mg/kg/day on day 2 and 25-35mg/kg/day on day 3.

The following table shows the recommended maintenance doses according to the respective weight.

Special Populations:

1.    Renal Impaired Patients

A dosage adjustment is recommended in renally impaired patients with neuropathic pain or epilepsy.

* Total daily dose should be administered as a t.i.d regimen. Doses used to treat patients with normal renal function (creatinine clearance >80mL/min) range from 900 to 3600mg/day. Reduced dosages are for patients with renal impairment (creatinine clearance <79mL/min).

** To be administered on every other day.

2.    Patients undergoing Haemodialysis

The recommended loading dose of Indiga (Gabapentin) is 300-400mg then 200-300mg following each 4 hours of haemodialysis.

Contraindications:

Gabapentin is contraindicated in patients with known hypersensitivity to Gabapentin or any of the components of the product.

Precautions:

1.    Gabapentin should not be abruptly discontinued because آ آ آ آ 

2.     Caution is recommended in patients with a history of  psychotic illness.

3.     Gabapentin should not be considered a treatment of absence seizures and may exacerbate these seizures in some patients. Consequently, Gabapentin should be used with caution in patients who have mixed seizure disorders that include absence seizures.

4.     Patients should be advised neither to drive a car nor to operate complex machinery until they have gained sufficient experience on Gabapentin.

Pregnancy:

There are no adequate and well-controlled studies in pregnant women. Gabapentin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing:

Gabapentin is secreted into breast milk following oral administration. The effect on the nursing infant is unknown. Therefore, Gabapentin should be used in nursing women only if the potential benefits clearly outweigh the risks.

Drug Interactions:

Ø   Naproxen

Ø   Hydrocodone

Ø   Morphine

Ø   Antacid

Have drug interaction, when co-administered with Gabapentin.

Adverse Reactions:

Ø   Neuropathic Pain

Common:

 Dizziness, somnolence.

Less Common:

آDiarrhea, dry mouth, peripheral edema, weight gain, abnormal gait, amnesia, ataxia, abnormal thinking, rash and amblyopia.

Rare:

Accidental injury, asthenia, back pain, constipation, flatulence, nausea, confusion, hypesthesia, vertigo, dyspnea and pharyngitis.

Ø   Epilepsy (Adults)

Common:

Dizziness & somnolence.

Less Common:

Ataxia, fatigue, nystagmus, tremor, diplopia, amblyopia, abnormal vision, dysarthria, amnesia, asthenia, paraesthesia, arthralgia, purpura, dyspepsia, anxiety, weight increase, urinary tract infection and pharyngitis.

Uncommon:

Leucopenia, nervousness, rhinitis and male sexual dysfunction (impotence).

Rare:

Urinary incontinence, pancreatitis, elevated liver function tests, erythema multiforme and Stevens Johnson Syndrome, confusion, depression, emotional liability, hostility, abnormal thinking and psychoses/hallucinations, blood glucose fluctuations in patients with diabetes, myalgia, headache, nausea and/or vomiting.

Ø   Epilepsy (Children 3-12 years)

Common:

Emotional liability, nervousness and thinking abnormally, all reports of these events were rated as mild or moderate and discontinuation or dose reduction was infrequent.

Uncommon:

Somnolence, fatigue, weight increase, hostility, emotional liability, dizziness, hyperkinesia, nausea/vomiting, viral infection, fever, bronchitis & respiratory infection are rated as uncommon and rarely observed.

Adverse events associated with both epilepsy and neuropathic pain include:

acute kidney failure, allergic reaction including urticaria, alopecia, angioedema, chest pain, hepatitis, jaundice, movement disorders such as choreoathetosis, dyskinesia and dystonia, palpitation, thrombocytopenia, and tinnitus.

Presentation:

Indiga (Gabapentin) 100mg in alu-alu blister pack of 10 Capsules.

Indiga (Gabapentin) 300mg in alu-alu blister pack of 10 Capsules.

Indiga (Gabapentin) 400mg in alu-alu blister pack of 10 Capsules.