Pregabalin

LYRICA is indicated for: • Management of neuropathic pain associated with diabetic peripheral neuropathy • Management of postherpetic neuralgia • Adjunctive therapy for the treatment of partial‑onset seizures in patients 1 month of age and older • Management of fibromyalgia • Management of neuropathic pain associated with spinal cord injury LYRICA is indicated for: • Neuropathic pain associated with diabetic peripheral neuropathy (DPN). • Postherpetic neuralgia (PHN). • Adjunctive therapy for the treatment of partial‑onset seizures in patients 1 month of age and older. • Fibromyalgia. • Neuropathic pain associated with spinal cord injury

LYRICA (pregabalin) binds with high affinity to the alpha 2 -delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues. Although the mechanism of action of pregabalin has not been fully elucidated, results with genetically modified mice and with compounds structurally related to pregabalin (such as gabapentin) suggest that binding to the alpha 2 -delta subunit may be involved in pregabalin’s anti-nociceptive and antiseizure effects in animals. In animal models of nerve damage, pregabalin has been shown to reduce calcium-dependent release of pro-nociceptive neurotransmitters in the spinal cord, possibly by disrupting alpha 2 -delta containing-calcium channel trafficking and/or reducing calcium currents.

• For adult indications, begin dosing at 150 mg/day. For partial‑onset seizure dosing in pediatric patients 1 month of age and older, refer to section 2.4. • Dosing recommendations: INDICATION Dosing Regimen Maximum Dose DPN Pain 3 divided doses per day 300 mg/day within 1 week. PHN 2 or 3 divided doses per day 300 mg/day within 1 week. Maximum dose of 600 mg/day. Adjunctive Therapy for Partial‑Onset Seizures in Pediatric and Adult Patients Weighing 30 kg or More 2 or 3 divided doses per day Maximum dose of 600 mg/day. Adjunctive Therapy for Partial‑Onset Seizures in Pediatric Patients Weighing Less than 30 kg 1 month to less than 4 years: 3 divided doses per day 4 years and older: 2 or 3 divided doses per day 14 mg/kg/day. Fibromyalgia 2 divided doses per day 300 mg/day within 1 week. Maximum dose of 450 mg/day.

LYRICA is contraindicated in patients with known hypersensitivity to pregabalin or any of its components. Angioedema and hypersensitivity reactions have occurred in patients receiving pregabalin therapy. • Known hypersensitivity to pregabalin or any of its components.

• Angioedema (e.g., swelling of the throat, head, and neck) can occur, and may be associated with life-threatening respiratory compromise requiring emergency treatment. Discontinue LYRICA immediately in these cases. • Hypersensitivity reactions (e.g., hives, dyspnea, and wheezing) can occur. Discontinue LYRICA immediately in these patients. • Antiepileptic drugs, including pregabalin, the active ingredient in LYRICA, increase the risk of suicidal thoughts or behavior. • Abrupt or rapid discontinuation may increase the risk for seizures. Withdrawal symptoms or suicidal behavior and ideation have been observed after discontinuation. Taper LYRICA gradually over a minimum of 1 week. • Respiratory depression: May occur with LYRICA, when used with concomitant CNS depressants or in the setting of underlying respiratory impairment. Monitor patients and adjust dosage as appropriate.

The following serious adverse reactions are described elsewhere in the labeling: • Angioedema • Hypersensitivity • Suicidal Behavior and Ideation • Increased Risk of Adverse Reactions with Abrupt or Rapid Discontinuation • Respiratory Depression • Dizziness and Somnolence • Peripheral Edema • Weight Gain • Tumorigenic Potential • Ophthalmological Effects • Creatine Kinase Elevations • Decreased Platelet Count • PR Interval Prolongation Most common adverse reactions (greater than or equal to 5% and twice placebo) in adults are dizziness, somnolence, dry mouth, edema, blurred vision, weight gain, and thinking abnormal (primarily difficulty with concentration/attention). Most common adverse reactions (greater than or equal to 5% and twice placebo) in pediatric patients for the treatment of partial‑onset seizures are increased weight and increased appetite.

Since LYRICA is predominantly excreted unchanged in the urine, undergoes negligible metabolism in humans (less than 2% of a dose recovered in urine as metabolites), and does not bind to plasma proteins, its pharmacokinetics are unlikely to be affected by other agents through metabolic interactions or protein binding displacement. In vitro and in vivo studies showed that LYRICA is unlikely to be involved in significant pharmacokinetic drug interactions. Specifically, there are no pharmacokinetic interactions between pregabalin and the following antiepileptic drugs: carbamazepine, valproic acid, lamotrigine, phenytoin, phenobarbital, and topiramate. Important pharmacokinetic interactions would also not be expected to occur between LYRICA and commonly used antiepileptic drugs. Pharmacodynamics Multiple oral doses of LYRICA were co-administered with oxycodone, lorazepam, or ethanol.

Store at 25°C (77°F), excursions permitted to 15°C to 30°C (59°F to 86°F).