Gabapen

Approved Indications:

• Neuropathic Pain: Treatment of peripheral neuropathic pain, including postherpetic neuralgia (PHN).
• Epilepsy: Adjunctive therapy for partial seizures, with or without secondary generalization, in adults and pediatric patients aged 3 years and older.
• Restless Legs Syndrome (RLS): Treatment of moderate to severe primary Restless Legs Syndrome.

Off-label Uses (Clinically Accepted):

• Diabetic peripheral neuropathy
• Central neuropathic pain (e.g., pain due to spinal cord injury)
• Fibromyalgia
• Migraine prophylaxis
• Anxiety disorders (e.g., generalized anxiety disorder)
• Bipolar disorder adjunct therapy
• Alcohol dependence and withdrawal management

Adults:

• Neuropathic Pain and Postherpetic Neuralgia:
  Initial dose: 300 mg on Day 1
  Titrate to 300 mg twice daily on Day 2
  Then 300 mg three times daily on Day 3
  Maintenance dose: 900–1800 mg/day in divided doses
  Maximum dose: up to 3600 mg/day based on tolerance and response.
• Partial Seizures (Adjunctive Therapy):
  Start at 300 mg three times daily; titrate as needed up to 1800 mg/day in divided doses; max 3600 mg/day.
• Restless Legs Syndrome:
  Typical dose is 600 mg once daily at approximately 5 PM; dose may be adjusted up to 2400 mg daily.

Pediatric Patients (≥3 years):

• For epilepsy, initial dose 10–15 mg/kg/day divided into three doses; titrate gradually up to 25–35 mg/kg/day.

Elderly:

• Dose adjustment recommended due to decreased renal function; start with lower doses and titrate carefully.

Renal Impairment:

• Dose adjustment required based on creatinine clearance; dosing interval or amount should be reduced accordingly.

Administration:

• Oral administration only.
• Can be taken with or without food.
• Capsules/tablets should be swallowed whole.
• Oral solution should be measured accurately and shaken well before use.

Gabapentin is a structural analogue of gamma-aminobutyric acid (GABA), but it does not bind directly to GABA_A or GABA_B receptors. Its primary mechanism involves binding selectively to the α2δ subunit of voltage-gated calcium channels in the central nervous system. This binding decreases calcium influx into presynaptic neurons, which reduces the release of excitatory neurotransmitters such as glutamate, norepinephrine, and substance P. This modulation reduces neuronal excitability and helps control seizures and neuropathic pain.

• Absorption: Gabapentin is absorbed in the small intestine via a saturable L-amino acid transport system, resulting in dose-dependent bioavailability (approximately 60% at 300 mg dose, decreasing with higher doses).
• Onset of Action: Effects typically begin 1 to 3 hours after oral administration.
• Distribution: Widely distributed throughout body tissues; does not bind significantly to plasma proteins.
• Metabolism: Not appreciably metabolized in humans.
• Elimination: Excreted unchanged primarily by the kidneys.
• Half-life: Approximately 5 to 7 hours in healthy adults; prolonged in renal impairment.

• Pregnancy: Classified as Category C by the FDA. Animal studies have shown adverse effects on the fetus, but adequate and well-controlled studies in pregnant women are lacking. Gabapentin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
• Lactation: Gabapentin is excreted in human breast milk in small amounts. Caution is advised when administered to breastfeeding mothers, and infants should be monitored for sedation or other adverse effects.

• Primary Class: Anticonvulsant / Neuropathic Pain Agent
• Subclass: GABA analogue (although it does not act directly on GABA receptors)

• Known hypersensitivity to gabapentin or any of its excipients.
• History of hypersensitivity reactions such as angioedema or anaphylaxis to gabapentin.

• Renal Impairment: Requires dose adjustment to avoid toxicity.
• Suicidal Thoughts and Behavior: Increased risk observed with antiepileptic drugs including gabapentin; patients should be monitored for worsening depression or suicidal ideation.
• Respiratory Depression: Risk increased when used with CNS depressants, especially in patients with respiratory disease or the elderly.
• Dizziness and Somnolence: Common side effects; may increase fall risk, especially in elderly patients.
• Abrupt Discontinuation: Can precipitate seizures; dose tapering is recommended when discontinuing.
• Hypersensitivity Reactions: Rare but potentially serious; discontinue if symptoms develop.

Common Adverse Effects (≥10%):

• Dizziness
• Somnolence
• Fatigue
• Ataxia
• Peripheral edema
• Nystagmus
• Tremor

Less Common and Serious Side Effects:

• Stevens-Johnson syndrome (rare)
• Anaphylaxis
• Angioedema
• Suicidal ideation
• Respiratory depression (especially with other CNS depressants)

Onset: Side effects generally appear early in therapy or during dose escalation; many improve with continued treatment.

• Antacids: May reduce gabapentin absorption; separate administration by at least 2 hours.
• CNS Depressants (e.g., opioids, benzodiazepines): Additive sedation and respiratory depression possible.
• No significant CYP450 interactions: Low potential for metabolic drug interactions.
• Alcohol: Enhances CNS depressant effects; use caution.

• Approval expanded for treatment of Restless Legs Syndrome.
• Increased emphasis on dose adjustments in renal impairment and caution in elderly patients.
• Updated warnings regarding respiratory depression when combined with opioids or other CNS depressants.
• Continued monitoring for suicidal ideation as with all antiepileptic drugs.

• Store at controlled room temperature between 20°C and 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep capsules and tablets in their original container, tightly closed.
• Oral solution should be refrigerated at 2°C to 8°C (36°F to 46°F); do not freeze.
• Shake oral solution well before use.
• Keep out of reach of children.