Postherpetic Neuralgia
The most commonly observed adverse events associated with the use of gabapentin in adults, not seen at an equivalent frequency among placebo-treated patients, were dizziness, somnolence, and peripheral edema.
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In the 2 controlled studies in postherpetic neuralgia, 16% of the 336 patients who received gabapentin and 9% of the 227 patients who received placebo discontinued treatment because of an adverse event. The adverse events that most frequently led to withdrawal in gabapentin-treated patients were dizziness, somnolence, and nausea.
Incidence in Controlled Clinical Trials
Table 3 uls treatment-emergent signs and symptoms that occurred in at least 1% of gabapentin-treated patients with postherpetic neuralgia participating in placebo-controlled trials and that were numerically more frequent in the gabapentin group than in the placebo group. Adverse events were usually mild to moderate in intensity.
| a Reported as blurred vision | ||
| Body System/Preferred Term | Gabapentin N=336 % | Placebo N=227 % |
| ÂÂÂBody as a Whole | ||
| ÂÂÂÂÂÂAsthenia | 5.7 | 4.8 |
| ÂÂÂÂÂÂInfection | 5.1 | 3.5 |
| ÂÂÂÂÂÂHeadache | 3.3 | 3.1 |
| ÂÂÂÂÂÂAccidental injury | 3.3 | 1.3 |
| ÂÂÂÂÂÂAbdominal pain | 2.7 | 2.6 |
| ÂÂÂDigestive System | ||
| ÂÂÂÂÂÂDiarrhea | 5.7 | 3.1 |
| ÂÂÂÂÂÂDry mouth | 4.8 | 1.3 |
| ÂÂÂÂÂÂConstipation | 3.9 | 1.8 |
| ÂÂÂÂÂÂNausea | 3.9 | 3.1 |
| ÂÂÂÂÂÂVomiting | 3.3 | 1.8 |
| ÂÂÂÂÂÂFlatulence | 2.1 | 1.8 |
| ÂÂÂMetabolic and Nutritional Disorders | ||
| ÂÂÂÂÂÂPeripheral edema | 8.3 | 2.2 |
| ÂÂÂÂÂÂWeight gain | 1.8 | 0 |
| ÂÂÂÂÂÂHyperglycemia | 1.2 | 0.4 |
| ÂÂÂNervous System | ||
| ÂÂÂÂÂÂDizziness | 28 | 7.5 |
| ÂÂÂÂÂÂSomnolence | 21.4 | 5.3 |
| ÂÂÂÂÂÂAtaxia | 3.3 | 0 |
| ÂÂÂÂÂÂThinking abnormal | 2.7 | 0 |
| ÂÂÂÂÂÂAbnormal gait | 1.5 | 0 |
| ÂÂÂÂÂÂIncoordination | 1.5 | 0 |
| ÂÂÂÂÂÂAmnesia | 1.2 | 0.9 |
| ÂÂÂÂÂÂHypesthesia | 1.2 | 0.9 |
| ÂÂÂRespiratory System | ||
| ÂÂÂÂÂÂPharyngitis | 1.2 | 0.4 |
| ÂÂÂSkin and Appendages | ||
| ÂÂÂÂÂÂRash | 1.2 | 0.9 |
| ÂÂÂSpecial Senses | ||
| ÂÂÂÂÂÂAmblyopiaa | 2.7 | 0.9 |
| ÂÂÂÂÂÂConjunctivitis | 1.2 | 0 |
| ÂÂÂÂÂÂDiplopia | 1.2 | 0 |
| ÂÂÂÂÂÂOtitis media | 1.2 | 0 |
Other events in more than 1% of patients but equally or more frequent in the placebo group included pain, tremor, neuralgia, back pain, dyspepsia, dyspnea, and flu syndrome.
There were no clinically important differences between men and women in the types and incidence of adverse events. Because there were few patients whose race was reported as other than white, there are insufficient data to support a statement regarding the distribution of adverse events by race.
Epilepsy
The most commonly observed adverse events associated with the use of gabapentin in combination with other antiepileptic drugs in patients >12 years of age, not seen at an equivalent frequency among placebo-treated patients, were somnolence, dizziness, ataxia, fatigue, and nystagmus. The most commonly observed adverse events reported with the use of gabapentin in combination with other antiepileptic drugs in pediatric patients 3 to 12 years of age, not seen at an equal frequency among placebo-treated patients, were viral infection, fever, nausea and/or vomiting, somnolence, and hostility (see
WARNINGS, Neuropsychiatric Adverse Events
).
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Approximately 7% of the 2074 patients >12 years of age and approximately 7% of the 449 pediatric patients 3 to 12 years of age who received gabapentin in premarketing clinical trials discontinued treatment because of an adverse event. The adverse events most commonly associated with withdrawal in patients >12 years of age were somnolence (1.2%), ataxia (0.8%), fatigue (0.6%), nausea and/or vomiting (0.6%), and dizziness (0.6%). The adverse events most commonly associated with withdrawal in pediatric patients were emotional lability (1.6%), hostility (1.3%), and hyperkinesia (1.1%).
Incidence in Controlled Clinical Trials
Table 4 uls treatment-emergent signs and symptoms that occurred in at least 1% of gabapentin-Âtreated patients >12 years of age with epilepsy participating in placebo-controlled trials and were numerically more common in the gabapentin group. In these studies, either gabapentin or placebo was added to the patientâs current antiepileptic drug therapy. Adverse events were usually mild to moderate in intensity.
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The prescriber should be aware that these figures, obtained when gabapentin was added to concurrent antiepileptic drug therapy, cannot be used to predict the frequency of adverse events in the course of usual medical practice where patient characteristics and other factors may differ from those prevailing during clinical studies. Similarly, the cited frequencies cannot be directly compared with figures obtained from other clinical investigations involving different treatments, uses, or investigators. An inspection of these frequencies, however, does provide the prescribing physician with one basis to estimate the relative contribution of drug and nondrug factors to the adverse event incidences in the population studied.
| Body System/Adverse Event | Gabapentina N=543 % | Placeboa N=378 % |
| a Plus background antiepileptic drug therapy b Amblyopia was often described as blurred vision. | ||
| ÂÂÂBody As A Whole | ||
| ÂÂÂÂÂÂFatigue | 11 | 5 |
| ÂÂÂÂÂÂWeight Increase | 2.9 | 1.6 |
| ÂÂÂÂÂÂBack Pain | 1.8 | 0.5 |
| ÂÂÂÂÂÂPeripheral Edema | 1.7 | 0.5 |
| ÂÂÂCardiovascular | ||
| ÂÂÂÂÂÂVasodilatation | 1.1 | 0.3 |
| ÂÂÂDigestive System | ||
| ÂÂÂÂÂÂDyspepsia | 2.2 | 0.5 |
| ÂÂÂÂÂÂMouth or Throat Dry | 1.7 | 0.5 |
| ÂÂÂÂÂÂConstipation | 1.5 | 0.8 |
| ÂÂÂÂÂÂDental Abnormalities | 1.5 | 0.3 |
| ÂÂÂÂÂÂIncreased Appetite | 1.1 | 0.8 |
| ÂÂÂHematologic and Lymphatic Systems | ||
| ÂÂÂÂÂÂLeukopenia | 1.1 | 0.5 |
| ÂÂÂMusculoskeletal System | ||
| ÂÂÂÂÂÂMyalgia | 2 | 1.9 |
| ÂÂÂÂÂÂFracture | 1.1 | 0.8 |
| ÂÂÂNervous System | ||
| ÂÂÂÂÂÂSomnolence | 19.3 | 8.7 |
| ÂÂÂÂÂÂDizziness | 17.1 | 6.9 |
| ÂÂÂÂÂÂAtaxia | 12.5 | 5.6 |
| ÂÂÂÂÂÂNystagmus | 8.3 | 4 |
| ÂÂÂÂÂÂTremor | 6.8 | 3.2 |
| ÂÂÂÂÂÂNervousness | 2.4 | 1.9 |
| ÂÂÂÂÂÂDysarthria | 2.4 | 0.5 |
| ÂÂÂÂÂÂAmnesia | 2.2 | 0 |
| ÂÂÂÂÂÂDepression | 1.8 | 1.1 |
| ÂÂÂÂÂÂThinking Abnormal | 1.7 | 1.3 |
| ÂÂÂÂÂÂTwitching | 1.3 | 0.5 |
| ÂÂÂÂÂÂCoordination Abnormal | 1.1 | 0.3 |
| ÂÂÂRespiratory System | ||
| ÂÂÂÂÂÂRhinitis | 4.1 | 3.7 |
| ÂÂÂÂÂÂPharyngitis | 2.8 | 1.6 |
| ÂÂÂÂÂÂCoughing | 1.8 | 1.3 |
| ÂÂÂSkin and Appendages | ||
| ÂÂÂÂÂÂAbrasion | 1.3 | 0 |
| ÂÂÂÂÂÂPruritus | 1.3 | 0.5 |
| ÂÂÂUrogenital System | ||
| ÂÂÂÂÂÂImpotence | 1.5 | 1.1 |
| ÂÂÂSpecial Senses | ||
| ÂÂÂÂÂÂDiplopia | 5.9 | 1.9 |
| ÂÂÂÂÂÂAmblyopiab | 4.2 | 1.1 |
| ÂÂÂLaboratory Deviations | ||
| ÂÂÂÂÂÂWBC Decreased | 1.1 | 0.5 |
Other events in more than 1% of patients >12 years of age but equally or more frequent in the placebo group included: headache, viral infection, fever, nausea and/or vomiting, abdominal pain, diarrhea, convulsions, confusion, insomnia, emotional lability, rash, acne.
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Among the treatment-emergent adverse events occurring at an incidence of at least 10% of gabapentin-treated patients, somnolence and ataxia appeared to exhibit a positive dose-response relationship.
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The overall incidence of adverse events and the types of adverse events seen were similar among men and women treated with gabapentin. The incidence of adverse events increased slightly with increasing age in patients treated with either gabapentin or placebo. Because only 3% of patients (28/921) in placebo-controlled studies were identified as nonwhite (black or other), there are insufficient data to support a statement regarding the distribution of adverse events by race.
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Table 5 uls treatment-emergent signs and symptoms that occurred in at least 2% of gabapentin-Âtreated patients age 3 to 12 years of age with epilepsy participating in placebo-controlled trials and were numerically more common in the gabapentin group. Adverse events were usually mild to moderate in intensity.
| Body System/Adverse Event | Gabapentina N=119 % | Placeboa N=128 % |
| a Plus background antiepileptic drug therapy | ||
| ÂÂÂBody As A Whole | ||
| ÂÂÂÂÂÂViral Infection | 10.9 | 3.1 |
| ÂÂÂÂÂÂFever | 10.1 | 3.1 |
| ÂÂÂÂÂÂWeight Increase | 3.4 | 0.8 |
| ÂÂÂÂÂÂFatigue | 3.4 | 1.6 |
| ÂÂÂDigestive System | ||
| ÂÂÂÂÂÂNausea and/or Vomiting | 8.4 | 7 |
| ÂÂÂNervous System | ||
| ÂÂÂÂÂÂSomnolence | 8.4 | 4.7 |
| ÂÂÂÂÂÂHostility | 7.6 | 2.3 |
| ÂÂÂÂÂÂEmotional Lability | 4.2 | 1.6 |
| ÂÂÂÂÂÂDizziness | 2.5 | 1.6 |
| ÂÂÂÂÂÂHyperkinesia | 2.5 | 0.8 |
| ÂÂÂRespiratory System | ||
| ÂÂÂÂÂÂBronchitis | 3.4 | 0.8 |
| ÂÂÂÂÂÂRespiratory Infection | 2.5 | 0.8 |
Other events in more than 2% of pediatric patients 3 to 12 years of age but equally or more frequent in the placebo group included: pharyngitis, upper respiratory infection, headache, rhinitis, convulsions, diarrhea, anorexia, coughing, and otitis media.
Other Adverse Events Observed During All Clinical Trials
Clinical Trials in Adults and Adolescents (Except Clinical Trials in Neuropathic Pain)
Gabapentin has been administered to 4717 patients >12 years of age during all adjunctive therapy clinical trials (except clinical trials in patients with neuropathic pain), only some of which were placebo-controlled. 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 uling below. The frequencies presented represent the proportion of the 4717 patients >12 years of age 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 uled in Table 4, those too general to be informative, and those not reasonably associated with the use of the drug.
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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 1/1000 patients; rare events are those occurring in fewer than 1/1000 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 System:
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 System:
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, bulers in mouth, tooth discolor, perlèche, salivary gland enlarged, lip hemorrhage, esophagitis, hiatal hernia, hematemesis, proctitis, irritable bowel syndrome, rectal hemorrhage, esophageal spasm.
Endocrine System:
Rare:
hyperthyroid, hypothyroid, goiter, hypoestrogen, ovarian failure, epididymitis, swollen testicl*, cushingoid appearance.
Hematologic and Lymphatic System:
Frequent:
purpura most often described as bruises resulting from physical trauma;
Infrequent:
anemia, thrombocytopenia, lymphadenopathy;
Rare:
WBC count increased, lymphocytosis, non-Hodgkinâs lymphoma, bleeding time increased.
Musculoskeletal System:
Frequent:
arthralgia;
Infrequent:
tendinitis, arthritis, joint stiffness, joint swelling, positive Romberg test;
Rare:
costochondritis, osteoporosis, bursitis, contracture.
Nervous System:
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, 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.
Respiratory System:
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 System:
Infrequent:
hematuria, dysuria, urination frequency, cystitis, urinary retention, urinary incontinence, vagin*l hemorrhage, amenorrhea, dysmenorrhea, menorrhagia, breast cancer, unable to climax, ejacul*tion abnormal;
Rare:
kidney pain, leukorrhea, pruritus genital, renal stone, acute renal failure, anuria, glycosuria, nephrosis, nocturia, pyuria, urination urgency, vagin*l pain, breast pain, testicl* 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.
Clinical trials in Pediatric Patients With Epilepsy
Adverse events occurring during epilepsy clinical trials in 449 pediatric patients 3 to 12 years of age treated with gabapentin that were not reported in adjunctive trials in adults are:
Body as a Whole:
dehydration, infectious mononucleosis
Digestive System:
hepatitis
Hemic and Lymphatic System:
coagulation defect
Nervous System:
aura disappeared, occipital neuralgia
Psychobiologic Function:
sleepwalking
Respiratory System:
pseudocroup, hoarseness
Clinical Trials in Adults With Neuropathic Pain of Various Etiologies
Safety information was obtained in 1173 patients during double-blind and open-label clinical trials including neuropathic pain conditions for which efficacy has not been demonstrated. Adverse events reported by investigators were grouped into standardized categories using modified COSTART IV terminology. Listed below are all reported events except those already uled in Table 3 and those not reasonably associated with the use of the drug.
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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 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients.
Body as a Whole:
Infrequent:
chest pain, cellulitis, malaise, neck pain, face edema, allergic reaction, abscess, chills, chills and fever, mucous membrane disorder;
Rare:
body odor, cyst, fever, hernia, abnormal BUN value, lump in neck, pelvic pain, sepsis, viral infection.
Cardiovascular System:
Infrequent:
hypertension, syncope, palpitation, migraine, hypotension, peripheral vascular disorder, cardiovascular disorder, cerebrovascular accident, congestive heart failure, myocardial infarction, vasodilatation;
Rare:
angina pectoris, heart failure, increased capillary fragility, phlebitis, thrombophlebitis, varicose vein.
Digestive System:
Infrequent:
gastroenteritis, increased appetite, gastrointestinal disorder, oral moniliasis, gastritis, tongue disorder, thirst, tooth disorder, abnormal stools, anorexia, liver function tests abnormal, periodontal abscess;
Rare:
cholecystitis, cholelithiasis, duodenal ulcer, fecal incontinence, gamma glutamyl transpeptidase increased, gingivitis, intestinal obstruction, intestinal ulcer, melena, mouth ulceration, rectal disorder, rectal hemorrhage, stomatitis.
Endocrine System:
Infrequent:
diabetes mellitus.
Hemic and Lymphatic System:
Infrequent:
ecchymosis, anemia;
Rare:
lymphadenopathy, lymphoma-like reaction, prothrombin decreased.
Metabolic and Nutritional:
Infrequent:
edema, gout, hypoglycemia, weight loss;
Rare:
alkaline phosphatase increased, diabetic ketoacidosis, lactic dehydrogenase increased.
Musculoskeletal:
Infrequent:
arthritis, arthralgia, myalgia, arthrosis, leg cramps, myasthenia;
Rare:
shin bone pain, joint disorder, tendon disorder.
Nervous System:
Frequent:
confusion, depression;
Infrequent:
vertigo, nervousness, paresthesia, insomnia, neuropathy, libido decreased, anxiety, depersonalization, reflexes decreased, speech disorder, abnormal dreams, dysarthria, emotional lability, nystagmus, stupor, circumoral paresthesia, euphoria, hyperesthesia, hypokinesia;
Rare:
agitation, hypertonia, libido increased, movement disorder, myoclonus, vestibular disorder.
Respiratory System:
Infrequent:
cough increased, bronchitis, rhinitis, sinusitis, pneumonia, asthma, lung disorder, epistaxis;
Rare:
hemoptysis, voice alteration.
Skin and Appendages:
Infrequent:
pruritus, skin ulcer, dry skin, herpes zoster, skin disorder, fungal dermatitis, furunculosis, herpes simplex, psoriasis, sweating, urticaria, vesiculobullous rash;
Rare:
acne, hair disorder, maculopapular rash, nail disorder, skin carcinoma, skin discoloration, skin hypertrophy.
Special Senses:
Infrequent:
abnormal vision, ear pain, eye disorder, taste perversion, deafness;
Rare:
conjunctival hyperemia, diabetic retinopathy, eye pain, fundi with microhemorrhage, retinal vein thrombosis, taste loss.
Urogenital System:
Infrequent:
urinary tract infection, dysuria, impotence, urinary incontinence, vagin*l moniliasis, breast pain, menstrual disorder, polyuria, urinary retention;
Rare:
cystitis, ejacul*tion abnormal, swollen penis
,
gynecomastia, nocturia, pyelonephritis, swollen scrotum
,
urinary frequency, urinary urgency, urine abnormality.
Postmarketing and Other Experience
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In addition to the adverse experiences reported during clinical testing of gabapentin, the following adverse experiences have been reported in patients receiving marketed gabapentin. These adverse experiences have not been uled above and data are insufficient to support an estimate of their incidence or to establish causation. The uling is alphabetized: angioedema, blood glucose fluctuation, breast hypertrophy, erythema multiforme, elevated liver function tests, fever, hyponatremia, jaundice, movement disorder, Stevens-Johnson syndrome.
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Adverse events following the abrupt discontinuation of gabapentin have also been reported. The most frequently reported events were anxiety, insomnia, nausea, pain and sweating.
