Usage
- Gabapentin is prescribed for the treatment of neuropathic pain (e.g., postherpetic neuralgia, diabetic neuropathy) and as adjunctive therapy for partial seizures with and without secondary generalization in adults and children aged 6 years and above. In adolescents aged 12 years and above, and adults, it is also indicated as monotherapy for partial seizures. It’s also used off-label for restless legs syndrome, hot flashes, and other conditions.
- Pharmacological Classification: Anticonvulsant, analgesic (for neuropathic pain), GABA analogue.
- Mechanism of Action: Gabapentin’s precise mechanism of action is not fully understood, but it is believed to involve binding to the α2δ-1 subunit of voltage-gated calcium channels. Although structurally related to GABA, it does not bind to GABA receptors or affect GABA metabolism. This binding may reduce the release of excitatory neurotransmitters, thereby decreasing neuronal excitability and pain signal transmission.
Alternate Names
How It Works
- Pharmacodynamics: Gabapentin decreases neuronal excitability by binding to the α2δ-1 subunit of voltage-gated calcium channels. This binding reduces calcium influx into presynaptic nerve terminals, and in turn reduces the release of excitatory neurotransmitters, such as glutamate, norepinephrine, and substance P. Its action on pain pathways explains its analgesic effects in neuropathic pain. Anticonvulsant effects are thought to be a consequence of its action on calcium channels in central nervous system regions involved with seizures.
- Pharmacokinetics:
- Absorption: Gabapentin is absorbed from the gastrointestinal tract via a saturable transport system, meaning increasing doses result in proportionally less absorption (decreasing bioavailability). Peak plasma concentrations are reached in 2-3 hours after oral administration. Food does not significantly affect absorption.
- Metabolism: Gabapentin undergoes minimal metabolism in the liver.
- Elimination: Gabapentin is primarily eliminated unchanged by renal excretion. The elimination half-life is 5-7 hours in individuals with normal renal function and increases significantly with renal impairment.
Dosage
Standard Dosage
Adults:
- Epilepsy (Adjunctive): Starting dose: 300 mg three times a day (900 mg/day). Titrate as needed up to a maximum of 3600 mg/day, divided into three doses.
- Epilepsy (Monotherapy; Adults and Adolescents 12+): As per adjunctive therapy dosing.
- Neuropathic Pain: Starting dose: 300 mg once a day, titrated up as tolerated to 3600 mg/day. Alternatively, start with 300 mg three times a day. Slower titration is recommended in special populations.
- Restless Leg Syndrome: Gabapentin enacarbil (extended-release): 600 mg orally twice a day.
Children (6-11 years):
- Epilepsy (Adjunctive): Starting dose: 10-15 mg/kg/day divided into three doses. Titrate upwards over three days to an effective dose of 25-35 mg/kg/day, maximum 50 mg/kg/day.
Special Cases:
- Elderly Patients: Dosage adjustments based on renal function.
- Patients with Renal Impairment: Dose reduction is necessary. Refer to dosing tables in package inserts for specifics, which factor in creatinine clearance.
- Patients with Hepatic Dysfunction: No dosage adjustment usually needed.
- Patients with Comorbid Conditions: Monitor carefully for drug interactions and adjust as needed.
Clinical Use Cases
- Intubation: A single preoperative dose of 800 mg may attenuate cardiovascular responses.
- Surgical Procedures: Preoperative doses ranging from 300-1200 mg may be used to reduce postoperative pain.
- Mechanical Ventilation: 300 mg every 8 hours as an adjunct to standard sedation.
- Intensive Care Unit (ICU) Use: For pain and agitation in neonates and infants: starting dose around 10 mg/kg/day titrated up to 25 mg/kg/day. Adult ICU use similar to mechanical ventilation dosing.
- Emergency Situations: No specific emergency uses.
Dosage Adjustments
- Dose adjustments required in patients with renal dysfunction based on creatinine clearance.
Side Effects
Common Side Effects:
- Somnolence, dizziness, ataxia, fatigue, nystagmus, tremor, peripheral edema, nausea, vomiting, dry mouth.
Rare but Serious Side Effects:
- Angioedema, anaphylaxis, multiorgan hypersensitivity reactions, suicidal ideation, rhabdomyolysis, respiratory depression (particularly in patients with respiratory compromise).
Long-Term Effects:
- Cognitive impairment, weight gain.
Adverse Drug Reactions (ADR):
- Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome has been reported.
Contraindications
- Hypersensitivity to gabapentin.
Drug Interactions
- Antacids: Reduced gabapentin absorption.
- CNS Depressants (e.g., alcohol, opioids, benzodiazepines): Additive CNS depression.
- Hydrocodone: Increased gabapentin AUC.
- Morphine: Increased morphine AUC with gabapentin.
- No significant CYP450 enzyme interactions.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (FDA classification).
- Fetal Risks: Potential risks, but insufficient data for definitive conclusions. Use only if clearly needed.
- Breastfeeding: Gabapentin is excreted in breast milk. Potential for adverse effects in the infant. Monitor the infant if gabapentin use is necessary during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Binds to α2δ-1 subunit of voltage-gated calcium channels, reducing neurotransmitter release.
- Side Effects: Somnolence, dizziness, ataxia, fatigue. Rarely, serious reactions like anaphylaxis.
- Contraindications: Hypersensitivity to gabapentin.
- Drug Interactions: Antacids, CNS depressants, hydrocodone, morphine.
- Pregnancy & Breastfeeding: Potential risks; use with caution.
- Dosage: Varies by condition and patient factors; up to 3600 mg/day for adults.
- Monitoring Parameters: Renal function, adverse effects.
Popular Combinations
- Gabapentin is often combined with other anticonvulsants for seizure control or with other analgesics for neuropathic pain.
Precautions
- Monitor for suicidal ideation, especially in patients with a history of depression or psychiatric illness.
- Assess renal function before and during treatment, especially in elderly patients.
- Caution in patients with respiratory compromise due to the risk of respiratory depression.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Gabapentin?
A: The dosage varies depending on indication and patient factors. For adults with epilepsy or neuropathic pain, the starting dose is usually 300 mg three times daily, titrated up to a maximum of 3600 mg/day. Children’s dosages are weight-based.
Q2: What are the most common side effects of Gabapentin?
A: The most common side effects include somnolence, dizziness, ataxia, fatigue, and peripheral edema.
Q3: How should Gabapentin be administered?
A: Gabapentin can be administered orally with or without food. Capsules and tablets should be swallowed whole.
Q4: Does Gabapentin interact with other medications?
A: Yes, Gabapentin can interact with antacids, CNS depressants, hydrocodone, morphine, and possibly other medications.
Q5: Can Gabapentin be used during pregnancy or breastfeeding?
A: Gabapentin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It’s excreted in breast milk, so caution is advised while breastfeeding.
Q6: Is Gabapentin effective for all types of pain?
A: Gabapentin is primarily indicated for neuropathic pain. Its efficacy for other types of pain may vary.
Q7: How long does it take for Gabapentin to start working?
A: The effects of Gabapentin are usually noticeable within the first week, although optimal benefit may take several weeks.
Q8: Are there any contraindications for Gabapentin?
A: The primary contraindication is hypersensitivity to gabapentin.
A: Gabapentin undergoes minimal metabolism and is primarily eliminated unchanged by the kidneys.
Q10: Does Gabapentin require dose adjustments for patients with renal impairment?
A: Yes, dose adjustments are needed for patients with impaired renal function based on creatinine clearance.
Please note that this information is current as of February 16, 2025, and may be subject to change. Always refer to the latest prescribing information and clinical guidelines for the most up-to-date information.
