Side Effects of Gabapentin
Most Common Side Effects
Gabapentin most commonly causes dizziness (17-28%), somnolence (14-21%), and peripheral edema (8%), with most side effects being mild to moderate and improving significantly after the first week of treatment. 1, 2
Central Nervous System Effects
- Dizziness occurs in 17-28% of patients and is the most frequent CNS side effect 2
- Somnolence/drowsiness affects 14-21% of patients 1, 2
- Ataxia (unsteadiness/coordination problems) occurs in 13% of patients taking gabapentin for epilepsy and 3% for postherpetic neuralgia 1, 2
- Fatigue affects approximately 11% of patients 2
- Cognitive effects including thinking abnormalities (3%), amnesia (2%), and confusion occur less frequently 2
Other Physical Side Effects
- Peripheral edema (leg/ankle swelling) occurs in 8% of patients with postherpetic neuralgia and 2% with epilepsy 2
- Weight gain affects 2-3% of patients 1, 2
- Visual disturbances including diplopia (double vision, 6%), nystagmus (8%), and blurred vision (3-4%) 2
- Gastrointestinal effects such as nausea/vomiting (4%), diarrhea (6%), dry mouth (5%), and constipation (4%) 2
Serious but Rare Side Effects
Psychiatric and Behavioral Effects
- Suicidal thoughts or behavior occur in approximately 1 in 500 patients (0.2%) 1, 2
- In pediatric patients (3-12 years), gabapentin can cause emotional lability, aggressive behavior, hostility (8%), hyperactivity, problems with concentration, restlessness, and changes in school performance 2
Severe Allergic Reactions
- Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and life-threatening allergic reactions can occur, presenting with skin rash, hives, difficulty breathing, fever, swollen glands, facial/throat swelling, jaundice, unusual bruising/bleeding, or severe fatigue 2
- Anaphylaxis and angioedema have been reported in postmarketing surveillance 2
Other Serious Effects
- Altered mental status requiring hospitalization occurs in approximately 1.27% of older adults (mean age 76) on high doses (>600 mg/day) within 30 days of initiation 3
- Rhabdomyolysis (muscle breakdown) with elevated creatine kinase has been reported 2
- Sudden unexplained death in epilepsy patients is a known risk 2
Time Course and Management of Side Effects
Most side effects improve markedly after the first week of treatment and are largely resolved by week 4. 1
- Side effects are typically dose-related, with higher incidence at doses above 1800 mg/day 1
- Approximately 10% of patients discontinue gabapentin due to side effects in clinical trials 1
- Slow titration starting at 300 mg/day can minimize side effects 1
- Unlike opioids, tolerance does not develop to most gabapentin side effects 1
Special Population Considerations
Renal Impairment
- Dose adjustment is mandatory in patients with kidney problems or on hemodialysis due to reduced clearance 1, 2
Elderly Patients
- Older adults have increased risk of altered mental status, falls, confusion, and sedation 3
- High doses (>600 mg/day) in older adults carry a 1.29-fold increased risk of hospitalization with altered mental status compared to low doses 3
Pregnancy and Breastfeeding
- Safety in pregnancy is unknown; patients should be enrolled in the North American Antiepileptic Drug Pregnancy Registry 2
- Gabapentin passes into breast milk 2
Critical Safety Warnings
Withdrawal Risk
- Never stop gabapentin suddenly as this can cause seizures (status epilepticus) in epilepsy patients or serious withdrawal problems 2
- Gradual tapering over at least 1 week is required when discontinuing 1
Drug Interactions
- Gabapentin has no significant drug interactions and does not inhibit liver enzymes 1, 4
- However, antacids containing aluminum and magnesium reduce absorption; wait at least 2 hours between antacid and gabapentin doses 2
- Combining with opioids, benzodiazepines, or other CNS depressants increases risk of serious breathing problems 2