Gabarone - Drug Monograph

Introduction

Gabarone (gabapentin) is an anticonvulsant medication originally developed as a structural analog of gamma-aminobutyric acid (GABA). While it was initially approved for the treatment of partial seizures, its therapeutic applications have expanded significantly to include neuropathic pain management and other off-label uses. Gabarone represents one of several branded formulations of gabapentin available in various markets.

Mechanism of Action

Gabarone's exact mechanism of action differs from traditional GABAergic drugs. Despite its structural similarity to GABA, it does not directly act on GABA receptors. Instead, it binds to the α2δ subunit of voltage-gated calcium channels in the central nervous system. This binding modulates calcium influx into neurons, reducing the release of excitatory neurotransmitters such as glutamate, norepinephrine, and substance P. The resulting neuronal hyperexcitability reduction underlies its anticonvulsant and analgesic effects.

Indications

• FDA-approved:

- Partial-onset seizures with and without secondary generalization (adjunctive therapy in patients ≥3 years) - Postherpetic neuralgia (neuropathic pain following shingles) in adults

• Common off-label uses:

- Diabetic neuropathy - Fibromyalgia - Restless legs syndrome - Migraine prophylaxis - Anxiety disorders - Alcohol withdrawal syndrome

Dosage and Administration

• Adults and adolescents (>12 years): Initial dose 300 mg TID, titrate upward to 900-1800 mg/day in three divided doses (maximum 3600 mg/day)
• Children 3-12 years: 10-15 mg/kg/day in three divided doses, titrated over 3 days

• Day 1: 300 mg once
• Day 2: 300 mg BID
• Day 3: 300 mg TID
• May increase to 1800 mg/day (600 mg TID) based on response

• Renal impairment: Dose reduction required based on creatinine clearance
• Elderly: Consider reduced dosing due to decreased renal function
• Hepatic impairment: No dosage adjustment needed (renally excreted)
• Administration: With or without food; capsules should be swallowed whole

Pharmacokinetics

• Absorption: Saturable L-amino acid transport system in small intestine; bioavailability decreases with increasing doses (60% at 300 mg, 33% at 1600 mg)
• Distribution: Volume of distribution ~58 L; not significantly protein bound
• Metabolism: Not significantly metabolized; no hepatic cytochrome P450 involvement
• Elimination: Excreted unchanged primarily renally; elimination half-life 5-7 hours
• Steady-state: Reached within 2 days

Contraindications

• Known hypersensitivity to gabapentin or any component of the formulation
• Acute pancreatitis (relative contraindication)

Warnings and Precautions

• Suicidal Behavior and Ideation: Antiepileptic drugs increase risk of suicidal thoughts/behavior
• CNS Depression: May impair mental and/or physical abilities; caution when operating machinery
• Respiratory Depression: Increased risk when used with CNS depressants, particularly in elderly or patients with respiratory compromise
• Withdrawal Symptoms: Abrupt discontinuation may precipitate seizures or withdrawal symptoms
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Potentially fatal reaction reported
• Tumorigenic Potential: Pancreatic acinar cell tumors observed in rat studies
• Renal Impairment: Requires dosage adjustment

Drug Interactions

• CNS Depressants: Enhanced sedative effects with alcohol, opioids, benzodiazepines
• Antacids: Aluminum/magnesium-containing antacids reduce absorption by 20%; separate administration by至少2 hours
• Opioids: Increased risk of respiratory depression and CNS depression
• Hydrocodone: Gabapentin may increase hydrocodone exposure
• Morphine: Gabapentin AUC increased by morphine coadministration
• MAOIs: Theoretical increased seizure risk

Adverse Effects

• Dizziness (28%)
• Somnolence (21%)
• Peripheral edema (8%)
• Fatigue (11%)
• Ataxia (5%)
• Nystagmus (8%)

• Suicidal behavior and ideation
• Angioedema
• Stevens-Johnson syndrome
• DRESS
• Rhabdomyolysis
• Severe dizziness and coordination problems
• Respiratory depression

Monitoring Parameters

• Efficacy: Seizure frequency/duration, pain scales, functional assessment
• Safety: Mental status changes, mood alterations, suicidal ideation
• Renal Function: Serum creatinine at baseline and periodically
• Neurological: Coordination, dizziness, sedation
• Other: Weight gain, peripheral edema, visual changes
• Therapeutic Drug Monitoring: Not routinely required due to poor correlation between plasma levels and efficacy

Patient Education

• Take exactly as prescribed; do not stop abruptly
• May cause dizziness/drowsiness—avoid driving or hazardous activities until effects known
• Avoid alcohol and other CNS depressants
• Report any mood changes, depression, or suicidal thoughts immediately
• Notify provider if pregnancy is planned or suspected
• Rise slowly from sitting/lying position to minimize dizziness
• Separate antacid administration by至少2 hours if needed
• Report signs of allergic reaction: swelling, rash, difficulty breathing
• Keep all follow-up appointments for monitoring

References

1. FDA Prescribing Information: Gabapentin Capsules 2. Backonja M, et al. Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus. JAMA. 1998;280(21):1831-1836 3. Rowbotham M, et al. Gabapentin for the treatment of postherpetic neuralgia. JAMA. 1998;280(21):1837-1842 4. Patsalos PN, et al. Antiepileptic drugs—best practice guidelines for therapeutic drug monitoring. Ther Drug Monit. 2008;30(1):1-13 5. American Epilepsy Society. Guidelines for seizure management. Epilepsy Currents. 2016;16(1):48-61 6. Toth C. Gabapentin: An update of its pharmacological properties and therapeutic use in epilepsy. Drugs. 2019;79(18):1989-2004 7. Clinical Pharmacology [database online]. Tampa, FL: Elsevier; 2023