GABAPENTIN: Package Insert and Label Information (Page 4 of 6)

Incidence in Controlled Clinical Trials

Table 4 lists treatment-emergent signs and symptoms that occurred in at least 1% of gabapentin-treated 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 patient’s current antiepileptic drug therapy. Adverse events were usually mild to moderate in intensity.

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.

Table 4. Treatment-Emergent Adverse Event Incidence in Controlled Add-On Trials in Patients > 12 Years of Age (Events in at Least 1% of Gabapentin Patients and Numerically More Frequent Than in the Placebo Group)

* Plus background antiepileptic drug therapy
Body System/Adverse Event	Gabapentin *	Placebo *
	n = 543	n = 378
	%	%
Body as a Whole
Fatigue	11	5
Weight increase	2.9	1.6
Back pain	1.8	0.5
Peripheral edema	1.7	0.5
Cardiovascular
Vasodilation	1.1	0.3
Digestive System
Dyspepsia	2.2	0.5
Mouth or throat dry	1.7	0.5
Constipation	1.5	0.8
Dental abnormalities	1.5	0.3
Increased appetite	1.1	0.8
Hematologic and Lymphatic Systems
Leukopenia	1.1	0.5
Musculoskeletal System
Myalgia	2	1.9
Fracture	1.1	0.8
Nervous System
Somnolence	19.3	8.7
Dizziness	17.1	6.9
Ataxia	12.5	5.6
Nystagmus	8.3	4
Tremor	6.8	3.2
Nervousness	2.4	1.9
Dysarthria	2.4	0.5
Amnesia	2.2	0
Depression	1.8	1.1
Thinking abnormal	1.7	1.3
Twitching	1.3	0.5
Coordination abnormal	1.1	0.3
Respiratory System
Rhinitis	4.1	3.7
Pharyngitis	2.8	1.6
Coughing	1.8	1.3
Skin and Appendages
Abrasion	1.3	0
Pruritus	1.3	0.5
Urogenital System
Impotence	1.5	1.1
Special Senses
Diplopia	5.9	1.9
Amblyopia	4.2	1.1
Laboratory Deviations
WBC 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.

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.

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.

Table 5 lists treatment-emergent signs and symptoms that occurred in at least 2% of gabapentin-treated 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.

Table 5. Treatment-Emergent Adverse Event Incidence in Pediatric Patients Age 3 to 12 Years in a Controlled Add-On Trial (Events in at Least 2% of Gabapentin Patients and Numerically More Frequent Than in the Placebo Group)

* Plus background antiepileptic drug therapy
Body System/Adverse Event	Gabapentin *	Placebo *
	n = 119	n = 128
	%	%
Body as a Whole
Viral infection	10.9	3.1
Fever	10.1	3.1
Weight increase	3.4	0.8
Fatigue	3.4	1.6
Digestive System
Nausea and/or vomiting	8.4	7
Nervous System
Somnolence	8.4	4.7
Hostility	7.6	2.3
Emotional lability	4.2	1.6
Dizziness	2.5	1.6
Hyperkinesia	2.5	0.8
Respiratory System
Bronchitis	3.4	0.8
Respiratory 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 listing 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 listed in Table 4 , 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 1/1000 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, blisters in mouth, tooth discolor, perleche, 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 testicle, 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-Hodgkin’s lymphoma, bleeding time increased

Musculoskeletal System

Frequent: arthralgia

Infrequent: tendinitis, arthritis, joint stiffness, joint swelling, positive Romberg test

Rare: costochondritis, osteoporosis, bursitis, contracture