Adverse Drug Reaction Overview: Commonly Observed Adverse Events: The most commonly observed adverse events associated with the use of gabapentin in combination with other antiepileptic drugs, not seen at an equivalent frequency in placebo-treated patients, were somnolence, dizziness, ataxia, fatigue, nystagmus and tremor (see Table 6).
Adverse Events Leading to Discontinuation of Treatment: Approximately 6.4% of the 543 patients who received gabapentin in the placebo-controlled studies withdrew due to adverse events. In comparison, approximately 4.5% of the 378 placebo-controlled participants withdrew due to adverse events during these studies. The adverse events most commonly associated with withdrawal were somnolence (1.2%), ataxia (0.8%), fatigue, nausea and/or vomiting and dizziness (all at 0.6%).
Clinical Trial Adverse Drug Reactions: Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.
Incidence in Controlled Clinical Trials: Adults: Multiple doses of gabapentin were administered to 543 subjects with partial seizures in placebo-controlled clinical trials of 12 weeks duration. In these studies, either gabapentin (at doses of 600, 900, 1,200 or 1,800 mg/day) or placebo was added to the patient's current antiepileptic drug therapy. Treatment-emergent signs and symptoms that occurred in at least 1% of patients participating in these studies are listed in Table 6. (See Table 6.)
Click on icon to see table/diagram/image
Dose-Related Treatment Emergent Adverse Events: Among the treatment-emergent adverse events occurring in gabapentin-treated patients, somnolence and ataxia appeared to exhibit a positive dose-response relationship. Patients treated with 1,800 mg/day (n = 54, from one controlled study) experienced approximately a two-fold increase, as compared to patients on lower doses of 600 to 1,200 mg/day (n = 489, from several controlled studies), in the incidence of nystagmus (20.4%), tremor (14.8%), rhinitis (13%), peripheral edema (7.4%), coordination abnormal, depression and myalgia (all at 5.6%). Adverse events were usually mild to moderate in intensity, with a median time to resolution of 2 weeks. Data from long-term, open, uncontrolled studies shows that gabapentin treatment does not result in any new or unusual adverse events.
Other Adverse Drug Reactions Observed in All Clinical Trials: Adverse events that occurred in at least 1% of the 2,074 individuals who participated in all clinical trials, only some of which were placebo-controlled, are described as follows. During these trials, all adverse events were recorded by the clinical investigators using terminology of their own choosing. To provide a meaningful estimate of the proportion of individuals having adverse events, similar types of events were grouped into a smaller number of standardized categories using modified COSTART dictionary terminology. These categories are used in the listing as follows. The frequencies presented represent the proportion of the 2,074 patients exposed to gabapentin who experienced an event of the type cited on at least one occasion while receiving gabapentin. All reported events are included except those already listed in Table 6, those too general to be informative, and those not reasonably associated with the use of the drug.
Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are defined as those occurring in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1,000 patients; rare events are those occurring in fewer than 1/1,000 patients.
Body as a Whole: Frequent: asthenia, malaise, face edema.
Infrequent: allergy, generalized edema, weight decrease, chill.
Rare: strange feelings, lassitude, alcohol intolerance, hangover effect.
Cardiovascular: Frequent: hypertension.
Infrequent: hypotension, angina pectoris, peripheral vascular disorder, palpitation, tachycardia, migraine, murmur.
Rare: atrial fibrillation, heart failure, thrombophlebitis, deep thrombophlebitis, myocardial infarction, cerebrovascular accident, pulmonary thrombosis, ventricular extrasystoles, bradycardia, premature atrial contraction, pericardial rub, heart block, pulmonary embolus, hyperlipidemia, hypercholesterolemia, pericardial effusion, pericarditis.
Digestive: Frequent: anorexia, flatulence, gingivitis.
Infrequent: glossitis, gum hemorrhage, thirst, stomatitis, increased salivation, gastroenteritis, hemorrhoids, bloody stools, fecal incontinence, hepatomegaly.
Rare: dysphagia, eructation, pancreatitis, peptic ulcer, colitis, blisters in mouth, tooth discolor, perlèche, salivary gland enlarged, lip hemorrhage, esophagitis, hiatal hernia, hematemesis, proctitis, irritable bowel syndrome, rectal hemorrhage, esophageal spasm.
Endocrine: Rare: hyperthyroid, hypothyroid, goiter, hypoestrogen, ovarian failure, epididymitis, swollen testicle, cushingoid appearance.
Hematologic and Lymphatic: Frequent: purpura most often described as bruises resulting from physical trauma.
Infrequent: anemia, thrombocytopenia, lymphadenopathy.
Rare: WBC count increased, lymphocytosis, non-Hodgkin's lymphoma, bleeding time increased.
Musculoskeletal: Frequent: arthralgia.
Infrequent: tendinitis, arthritis, joint stiffness, joint swelling, positive Romberg test.
Rare: costochondritis, osteoporosis, bursitis, contracture.
Nervous: Frequent: vertigo, hyperkinesia, paresthesia, decreased or absent reflexes, increased reflexes, anxiety, hostility.
Infrequent: CNS tumors, syncope, dreaming abnormal, aphasia, hypesthesia, intracranial hemorrhage, hypotonia, dysesthesia, paresis, dystonia, hemiplegia, facial paralysis, stupor, cerebellar dysfunction, positive Babinski sign, decreased position sense, subdural hematoma, apathy, hallucination, decrease or loss of libido, agitation, paranoia, depersonalization, euphoria, feeling high, doped-up sensation, suicide attempt, psychosis.
Rare: choreoathetosis, orofacial dyskinesia, encephalopathy, nerve palsy, personality disorder, increased libido, subdued temperament, apraxia, fine motor control disorder, meningismus, local myoclonus, hyperesthesia, hypokinesia, mania, neurosis, hysteria, antisocial reaction, suicide.
Respiratory: Frequent: pneumonia.
Infrequent: epistaxis, dyspnea, apnea.
Rare: mucositis, aspiration pneumonia, hyperventilation, hiccup, laryngitis, nasal obstruction, snoring, bronchospasm, hypoventilation, lung edema.
Dermatological: Infrequent: alopecia, eczema, dry skin, increased sweating, urticaria, hirsutism, seborrhea, cyst, herpes simplex.
Rare: herpes zoster, skin discolor, skin papules, photosensitive reaction, leg ulcer, scalp seborrhea, psoriasis, desquamation, maceration, skin nodules, subcutaneous nodule, melanosis, skin necrosis, local swelling.
Urogenital: Infrequent: hematuria, dysuria, urination frequency, cystitis, urinary retention, urinary incontinence, vaginal hemorrhage, amenorrhea, dysmenorrhea, menorrhagia, breast cancer, unable to climax, ejaculation abnormal.
Rare: kidney pain, leukorrhea, pruritus genital, renal stone, acute renal failure, anuria, glycosuria, nephrosis, nocturia, pyuria, urination urgency, vaginal pain, breast pain, testicle pain.
Special Senses: Frequent: abnormal vision.
Infrequent: cataract, conjunctivitis, eyes dry, eye pain, visual field defect, photophobia, bilateral or unilateral ptosis, eye hemorrhage, hordeolum, hearing loss, earache, tinnitus, inner ear infection, otitis, taste loss, unusual taste, eye twitching, ear fullness.
Rare: eye itching, abnormal accommodation, perforated ear drum, sensitivity to noise, eye focusing problem, watery eyes, retinopathy, glaucoma, iritis, corneal disorders, lacrimal dysfunction, degenerative eye changes, blindness, retinal degeneration, miosis, chorioretinitis, strabismus, eustachian tube dysfunction, labyrinthitis, otitis externa, odd smell.
Post-Market Adverse Drug Reactions: Sudden, unexplained deaths in patients with epilepsy have been reported where a causal relationship to treatment with gabapentin has not been established.
Post-marketing adverse events that have been reported, which may have no causal relationship to gabapentin are as follows: agitation, anaphylactic reaction, angioedema, blood creatine phosphokinase increased, blood glucose abnormal, drug rash with eosinophilia and systemic symptoms, fall, gynaecomastia, hepatic function abnormal, hepatitis, hepatitis cholestatic, hepatitis fulminant, hyperglycemia, hypoglycemia, hypersensitivity, hyponatremia, jaundice, loss of consciousness, pancreatitis, pulmonary oedema, renal failure acute, rhabdomyolysis, sexual dysfunction (including changes in libido, ejaculation disorders and anorgasmia), Stevens-Johnson syndrome.
Adverse events following the abrupt discontinuation of gabapentin have also been reported during post-marketing experience. The most frequently reported events were anxiety, insomnia, nausea, pain and sweating.