Gabapentin

Gabapentin, which is used to treat epilepsy and neuropathic pain, was licensed in the United Kingdom in May 1993 and approved by the US FDA in December 1993. Gabapentin is an anticonvulsant medicine that prevents or treats seizures and convulsions by regulating electrical activity in the brain. Gabapentin was originally intended to relax muscles and prevent spasms. It is also used to treat nerve pain by blocking pain signals as they travel via injured nerves in the brain.

BRAND NAMES:

Gralise – These are available in the form of Gralise gabapentin tablets used in neuropathic pains.

Neurontin – Gabapentin is the active ingredient present in this, which is marketed as Neurontin gabapentin capsules 100mg and 300mg.

Horizant – It is available as Horizant gabapentin enacarbil extended-release tablets 300 & 500mg.

MECHANISM OF ACTION:

Gabapentin's exact mechanism of action for nerve pain or seizures remains uncertain. It may impede certain nerve signals. Seizures occur due to abnormal electrical activity in the brain. It may interfere with aberrant electrical activity in the brain. Some biochemical events in the central nervous system that may explain its anti-epileptic effect include increased extracellular GABA concentrations in some regions of the brain due to increased activity of glutamic acid decarboxylase, which produces GABA, and decreased breakdown by GABA decarboxylase. Magnetic resonance imaging spectroscopy revealed a worldwide rise in GABA levels in the brain following gabapentin administration.

PHARMACOKINETICS:

Absorption: The variable bioavailability of gabapentin at clinical dosages could be due to transporter saturation. The creation of prodrugs overcame the limitations of oral absorption. Increased gabapentin dose reduces bioavailability. Gabapentin's plasma concentration peaks within 2 to 4 hours.

Distribution: The distribution has an average apparent volume of 58±6L. Gabapentin has a plasma protein binding rate of less than 3%.

Metabolism: It is not metabolized in humans and is eliminated solely in the urine as an unchanged drug.

Gabapentin does not induce or inhibit CYP enzymes. Gabapentin encarbil undergoes substantial first-pass hydrolysis through nonspecific carboxylesterase activity within enterocytes and to a lesser degree in hepatocytes.

Excretion: Elimination of gabapentin is mainly through renal excretion. It undergoes first-order kinetic elimination and renal impairment will linearly decrease gabapentin elimination with a good correlation with creatine clearance. The elimination half-life of gabapentin is between 4.8 to 8.7. It does not induce or inhibit hepatic microsomal enzymes.

PHARMACODYNAMICS:

It is an anti-convulsant medication that inhibits the release of excitatory neurotransmitters, making it suitable for treating pathologic neurotransmission disorders such as neuropathic pain and seizures. Gabapentin is available in two forms: gabapentin immediate release and the prodrug gabapentin enacarbil. Gabapentin is available in tablets of 600 mg and 800 mg, capsules of 100 mg, 300 mg, and 400 mg, and an oral solution of 250 mg/5 mL. Gabapentin enacarbil is available as 300 mg extended-release tablets. It is ineffective in the absence of seizures and should be used with caution in patients with mixed seizure disorders that include absent seizures. Gabapentin has been linked to drug reactions, including eosinophilia and systemic symptoms known as multiorgan hypersensitivity.

DOSAGE AND ADMINISTRATION:

Gabapentin is available in two forms as gabapentine extended release and gabapentin encarbil. These are available in tablet form with strengths of 600mg and 800mg, and capsules in strengths of 100mg,300mg, and 400mg as well as an oral solution of 259mg/5ml. Gabapentin enacarbil is available in 300mg extended-release tablets.

Primarily the treatment of gabapentin starts with a dosage of 300mg/d and gradually increases to 3 times daily. The effects of gabapentin can be noticeable in the first week of medication and simultaneously we can observe improvement in some cases. If we want to discontinue the therapeutic it is possible to taper the dose over more than 7 days.

300 to 1200mg dosage of gabapentin is recommended orally thrice a day for patients suffering from partial seizures. 300 to 600mg dosage of gabapentin is recommended three times a day for patients suffering from post-herpetic neuralgia. 400 and 800mg of gabapentin should be taken thrice a day orally in patients with fibromyalgia. For neuropathic pain relief, the recommended dosage is gabapentin encarbil 600mg once a day with a maximum daily dosage of 1800mg.

CONTRAINDICATIONS:

Gabapentin is not recommended for those who are hypersensitive to the medicine or its components. Sudden withdrawal of gabapentin in epilepsy patients can result in a high frequency of epilepsy.

DRUG INTERACTIONS:

• Ask your doctor about any previous medications you may be taking before starting a new one. It has been known to interact with certain drugs, including

• Products with antihistamines for colds, coughs, and allergies

• Medications used for anxiety, sleep, and depression, including amitriptyline, fluoxetine, and sertraline.

• Medications for seizures include phenobarbital and primidone.

• Before taking gabapentin, wait at least two hours after taking aluminum or magnesium-containing antacids.

• Before surgery, patients are given general, local, or muscle relaxants.

FOOD INTERACTIONS:

Alcohol should be avoided because gabapentin has CNS depressant properties that may be enhanced by co-administration with alcohol. Gabapentin may be taken with or without food.

ADVERSE REACTIONS: