Gaba 300-EZS

Gabapentin capsules are indicated for: Management of postherpetic neuralgia in adults Adjunctive therapy in the treatment of partial onset seizures, with and without secondary generalization, in adults and pediatric patients 3 years and older with epilepsy Gabapentin capsules are indicated for: Postherpetic neuralgia in adults ( 1 ) Adjunctive therapy in the treatment of partial onset seizures, with and without secondary generalization, in adults and pediatric patients 3 years and older with epilepsy ( 1 )

Gabapentin capsules are contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients. Known hypersensitivity to gabapentin or its ingredients ( 4 )

Drug Reaction with Eosinophilia and Systemic Symptoms (Multiorgan hypersensitivity): Discontinue if alternative etiology is not established ( 5.1 ) Anaphylaxis and Angioedema: Discontinue and evaluate patient immediately ( 5.2 ) Driving Impairment; Somnolence/Sedation and Dizziness: Warn patients not to drive until they have gained sufficient experience to assess whether their ability to drive or operate heavy machinery will be impaired ( 5.3 , 5.4 ) Increased seizure frequency may occur in patients with seizure disorders if gabapentin is abruptly discontinued ( 5.5 ) Suicidal Behavior and Ideation: Monitor for suicidal thoughts/behavior ( 5.6 ) Neuropsychiatric Adverse Reactions in Children 3 to 12 Years of Age: Monitor for such events ( 5.7 )

5.1 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity, has occurred with gabapentin. Some of these reactions have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection.

Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Gabapentin should be discontinued if an alternative etiology for the signs or symptoms cannot be established.

5.2Anaphylaxis and Angioedema

Gabapentin can cause anaphylaxis and angioedema after the first dose or at any time during treatment. Signs and symptoms in reported cases have included difficulty breathing, swelling of the lips, throat, and tongue, and hypotension requiring emergency treatment. Patients should be instructed to discontinue gabapentin and seek immediate medical care should they experience signs or symptoms of anaphylaxis or angioedema.

5.3Effects on Driving and Operating Heavy Machinery

Patients taking gabapentin should not drive until they have gained sufficient experience to assess whether gabapentin impairs their ability to drive. Driving performance studies conducted with a prodrug of gabapentin (gabapentin enacarbil tablet, extended-release) indicate that gabapentin may cause significant driving impairment. Prescribers and patients should be aware that patients’ ability to assess their own driving competence, as well as their ability to assess the degree of somnolence caused by gabapentin, can be imperfect.

Concentrations increased by morphine; may need dose adjustment ( 5.4 , 7.2 )

7.1Other Antiepileptic Drugs

Gabapentin is not appreciably metabolized nor does it interfere with the metabolism of commonly coadministered antiepileptic drugs [see Clinical Pharmacology (12.3) ].

7.2Opioids Hydrocodone Coadministration

of gabapentin with hydrocodone decreases hydrocodone exposure [see Clinical Pharmacology (12.3) ]. The potential for alteration in hydrocodone exposure and effect should be considered when gabapentin is started or discontinued in a patient taking hydrocodone. Morphine When gabapentin is administered with morphine, patients should be observed for signs of CNS depression, such as somnolence, sedation and respiratory depression [see Clinical Pharmacology (12.3) ] .

7.3Maalox®

(aluminum hydroxide, magnesium hydroxide) The mean bioavailability of gabapentin was reduced by about 20% with concomitant use of an antacid (Maalox ® ) containing magnesium and aluminum hydroxides. It is recommended that gabapentin be taken at least 2 hours following Maalox administration [see Clinical Pharmacology (12.3) ] .

7.4Drug/Laboratory Test Interactions

Because false positive readings were reported with the Ames N-Multistix SG ® dipstick test for urinary protein when gabapentin was added to other antiepileptic drugs, the more specific sulfosalicylic acid precipitation procedure is recommended to determine the presence of urine protein.

8.1Pregnancy Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as gabapentin, during pregnancy. Encourage women who are taking gabapentin during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling the toll free number 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/ . Risk Summary There are no adequate data on the developmental risks associated with the use of gabapentin in pregnant women.

In nonclinical studies in mice, rats, and rabbits, gabapentin was developmentally toxic (increased fetal skeletal and visceral abnormalities, and increased embryofetal mortality) when administered to pregnant animals at doses similar to or lower than those used clinically [see Data]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal data When pregnant mice received oral doses of gabapentin (500, 1,000, or 3,000 mg/kg/day) during the period of organogenesis, embryofetal toxicity (increased incidences of skeletal variations) was observed at the two highest doses. The no-effect dose for embryofetal developmental toxicity in mice (500 mg/kg/day) is less than the maximum recommended human dose (MRHD) of 3,600 mg/kg on a body surface area (mg/m 2 ) basis.

In studies in which rats received oral doses of gabapentin (500 to 2,000 mg/kg/day) during pregnancy, adverse effect on offspring development (increased incidences of hydroureter and/or hydronephrosis) were observed at all doses. The lowest dose tested is similar to the MRHD on a mg/m 2 basis. When pregnant rabbits were treated with gabapentin during the period of organogenesis, an increase in embryofetal mortality was observed at all doses tested (60, 300, or 1,500 mg/kg).

The lowest dose tested is less than the MRHD on a mg/m 2 basis. In a published study, gabapentin (400 mg/kg/day) was administered by intraperitoneal injection to neonatal mice during the first postnatal week, a period of synaptogenesis in rodents (corresponding to the last trimester of pregnancy in humans). Gabapentin caused a marked decrease in neuronal synapse formation in brains of intact mice and abnormal neuronal synapse formation in a mouse model of synaptic repair.

Gabapentin has been shown in vitro to interfere with activity of the α2δ subunit of voltage-activated calcium channels, a receptor involved in neuronal synaptogenesis. The clinical significance of these findings is unknown.

The following serious adverse reactions are discussed in greater detail in other sections: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity [see Warnings and Precautions (5.1) ] Anaphylaxis and Angioedema [see Warnings and Precautions (5.2) ] Somnolence/Sedation and Dizziness [see Warnings and Precautions (5.4) ] Withdrawal Precipitated Seizure, Status Epilepticus [see Warnings and Precautions (5.5) ] Suicidal Behavior and Ideation [see Warnings and Precautions (5.6) ] Neuropsychiatric Adverse Reactions (Pediatric Patients 3 to 12 Years of Age) [see Warnings and Precautions (5.7) ] Sudden and Unexplained Death in Patients with Epilepsy [see Warnings and Precautions (5.9) ] Most common adverse reactions (incidence greater than or equal to 8% and at least twice that for placebo) were: Postherpetic neuralgia: Dizziness, somnolence, and peripheral edema ( 6.1 ) Epilepsy in patients greater than 12 years of age: Somnolence, dizziness, ataxia, fatigue, and nystagmus ( 6.1 ) Epilepsy in patients 3 to 12 years of age: Viral infection, fever, nausea and/or vomiting, somnolence, and hostility ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Actavis at 1-800-432-8534 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Postherpetic Neuralgia The most common adverse reactions associated with the use of gabapentin in adults, not seen at an equivalent frequency among placebo-treated patients, were dizziness, somnolence, and peripheral edema.

In the 2 controlled trials 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 reaction. The adverse reactions that most frequently led to withdrawal in gabapentin-treated patients were dizziness, somnolence, and nausea. Table 3 lists adverse reactions 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.

TABLE 3. Adverse Reactions in Pooled Placebo-Controlled Trials in Postherpetic Neuralgia Gabapentin N=336 % Placebo N=227 % Body as a Whole Asthenia 6 5 Infection 5 4 Accidental injury 3 1 Digestive System Diarrhea 6 3 Dry mouth 5 1 Constipation 4 2 Nausea 4 3 Vomiting 3 2 Metabolic and Nutritional Disorders Peripheral edema 8 2 Weight gain 2 0 Hyperglycemia 1 0 Nervous System Dizziness 28 8 Somnolence 21 5 Ataxia 3 0 Abnormal thinking 3 0 Abnormal gait 2 0 Incoordination 2 0 Respiratory System Pharyngitis 1 0 Special Senses Amblyopia a 3 1 Conjunctivitis 1 0 Diplopia 1 0 Otitis media 1 0 a Reported as blurred vision Other reactions 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.