Phentermine and Topiramate

Phentermine and topiramate extended-release capsules are indicated in combination with a reduced-calorie diet and increased physical activity to reduce excess body weight and maintain weight reduction long term in: Adults and pediatric patients aged 12 years and older with obesity Adults with overweight in the presence of at least one weight-related comorbid condition Limitations of Use The effect of phentermine and topiramate extended-release capsules on cardiovascular morbidity and mortality has not been established. The safety and effectiveness of phentermine and topiramate extended-release capsules in combination with other products intended for weight loss, including prescription drugs, over-the-counter drugs, and herbal preparations, have not been established.

Phentermine is a sympathomimetic amine with pharmacologic activity similar to the prototype drugs of this class used in obesity, amphetamine (d- and d/l-amphetamine). Drugs of this class used in obesity are commonly known as "anorectics" or "anorexigenics." The effect of phentermine on weight reduction and long-term maintenance of body weight is likely mediated by release of catecholamines in the hypothalamus, resulting in reduced appetite and decreased food consumption, but other metabolic effects may also be involved. The exact mechanism of action is not known. The precise mechanism of action of topiramate on weight reduction and long-term maintenance of body weight is not known.

Take orally once daily in morning. Avoid administration in evening to prevent insomnia. Recommended starting dosage is 3.75 mg/23 mg (phentermine mg/topiramate mg) daily for 14 days, then increase to 7.5 mg/46 mg daily. Escalate dosage based on weight loss in adults or BMI reduction in pediatric patients. See the Full Prescribing Information for details regarding discontinuation or dosage escalation. Gradually discontinue 15 mg/92 mg dosage to prevent possible seizure. Do not exceed 7.5 mg/46 mg dosage for patients with moderate or severe renal impairment or patients with moderate hepatic impairment.

Phentermine and topiramate extended-release capsules are contraindicated in patients: Who are pregnant With glaucoma With hyperthyroidism Taking or within 14 days of stopping a monoamine oxidase inhibitors With known hypersensitivity to phentermine, topiramate or any of the excipients in phentermine and topiramate extended-release capsules, or idiosyncrasy to the sympathomimetic amines. Anaphylaxis and angioedema have occurred with topiramate. Pregnancy. Glaucoma. Hyperthyroidism. Taking or within 14 days of stopping monoamine oxidase inhibitors. Known hypersensitivity to any component of phentermine and topiramate extended-release capsules or idiosyncrasy to sympathomimetic amines

Embryo-Fetal Toxicity: Can cause fetal harm. In patients who can become pregnant, a negative pregnancy test is recommended before initiating phentermine and topiramate extended-release capsules and monthly during therapy, advise use of effective contraception. Phentermine and topiramate extended-release capsules are available through a limited program under a Risk Evaluation and Mitigation Strategy (REMS). Suicidal Behavior and Ideation: Monitor for depression or suicidal thoughts. Discontinue phentermine and topiramate extended-release capsules if symptoms develop. Risk of Ophthalmologic Adverse Reactions: Acute myopia and secondary angle closure glaucoma have been reported. Immediately discontinue phentermine and topiramate extended-release capsules if symptoms develop. Consider phentermine and topiramate extended-release capsules discontinuation if visual field defects occur.

The following clinically significant adverse reactions are described elsewhere in the labeling: Embryo-Fetal Toxicity Suicidal Behavior and Ideation Risk of Ophthalmologic Adverse Reactions Mood and Sleep Disorders Cognitive Impairment Slowing of Linear Growth Metabolic Acidosis Decrease in Renal Function Risk of Seizures with Abrupt Withdrawal of phentermine and topiramate extended-release capsules Kidney Stones Oligohydrosis and Hyperthermia Hypokalemia Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Reactions Serious Skin Reactions Anaphylaxis and Angioedema Allergic Reactions Due to Inactive Ingredients FD&C Yellow No. 5 Most common adverse reactions in: Adults (incidence ≥ 5% and at least 1.5 times placebo) are: paraesthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth.

Table 5 displays clinically significant drug interactions with phentermine and topiramate extended-release capsules. Table 5. Clinically Significant Drug Interactions with Phentermine and Topiramate Extended-Release Capsules Monoamine Oxidase Inhibitors Clinical Impact Concomitant use of phentermine with monoamine oxidase inhibitors (MAOIs) increases the risk of hypertensive crisis. Intervention Concomitant use of phentermine and topiramate extended-release capsules are contraindicated during MAOI treatment and within 14 days of stopping an MAOI.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F). Keep container tightly closed and protect from moisture.