Qsymia (phentermine and topiramate extended-release capsules)

Qsymia is 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 Qsymia on cardiovascular morbidity and mortality has not been established.

The safety and effectiveness of Qsymia in combination with other products intended for weight loss, including prescription drugs, over-the-counter drugs, and herbal preparations, have not been established.

Qsymia is contraindicated in pregnancy; in patients with glaucoma; in hyperthyroidism; in patients receiving treatment or within 14 days following treatment with monoamine oxidase inhibitors (MAOIs); or in patients with hypersensitivity or idiosyncrasy to sympathomimetic amines, topiramate, or any of the inactive ingredients in Qsymia.

The most commonly observed side effects in controlled clinical studies, 5% or greater and at least 1.5 times placebo, in adults include paraesthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth. Common side effects in pediatric patients aged 12 years and older at ≥4% and greater than placebo include depression, dizziness, arthralgia, pyrexia, influenza, and ligament sprain.

Qsymia can cause fetal harm. Data from a pregnancy registry and epidemiologic studies indicate that a fetus exposed to topiramate, a component of Qsymia, in the first trimester of pregnancy has an increased risk of oral clefts (cleft lip with or without cleft palate). Pregnancy testing is recommended before initiating Qsymia treatment in patients who can become pregnant and monthly during Qsymia therapy. Advise patients who can become pregnant of the potential risk to a fetus and to use effective contraception during Qsymia therapy.

Topiramate, a component of Qsymia, increases the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue Qsymia in patients who experience suicidal thoughts or behaviors. Qsymia is not recommended in patients with a history of suicidal attempts or active suicidal ideation.

Acute angle closure glaucoma has been reported in patients treated with topiramate, a component of Qsymia. Symptoms include acute onset of decreased visual acuity and/or eye pain. Symptoms typically occur within 1 month of initiating treatment with topiramate but may occur at any time during therapy. The primary treatment to reverse symptoms is immediate discontinuation of Qsymia. Elevated intraocular pressure of any etiology, if left untreated, can lead to serious adverse events including permanent loss of vision.

Visual field defects (independent of elevated intraocular pressure) have been reported in clinical trials and in postmarketing experience in patients receiving topiramate. In clinical trials, most of these events were reversible after topiramate discontinuation. If visual problems occur at any time during treatment, consider discontinuing Qsymia.

Qsymia can cause mood disorders, including depression and anxiety, as well as insomnia. Patients with a history of depression may be at increased risk. For clinically significant or persistent symptoms consider dose reduction or withdrawal of Qsymia.

Qsymia can cause cognitive dysfunction (e.g., impairment of concentration/attention, difficulty with memory, and speech or language problems, particularly word-finding difficulties). Since Qsymia has the potential to impair cognitive function, patients should be cautioned about operating hazardous machinery, including automobiles.

Qsymia is associated with a reduction in height velocity (centimeters of height gained per year) in obese pediatric patients 12 to 17 years of age. Monitor height velocity in pediatric patients treated with Qsymia. Consider dosage reduction or discontinuation of Qsymia if pediatric patients are not growing or gaining height as expected.

Hyperchloremic, non-anion gap, metabolic acidosis has been reported in patients treated with Qsymia. Measurement of electrolytes including serum bicarbonate prior to starting Qsymia and during Qsymia treatment is recommended. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing Qsymia.

Qsymia can cause an increase in serum creatinine that reflects a decrease in renal function (glomerular filtration rate). In phase 3 trials, peak increases in serum creatinine were observed after 4 to 8 weeks of treatment. On average, serum creatinine gradually declined but remained elevated over baseline creatinine values. The changes in serum creatinine (and measured GFR) with short-term Qsymia treatment appear reversible with treatment discontinuation, but the effect of chronic treatment on renal function is not known. Therefore, measurement of serum creatinine prior to starting Qsymia and during Qsymia treatment is recommended. If persistent elevations in creatinine occur while taking Qsymia, reduce the dose or discontinue Qsymia.

Serious skin reactions (Stevens-Johnson Syndrome [SJS] and Toxic Epidermal Necrolysis [TEN]) have been reported in patients receiving topiramate. Qsymia should be discontinued at the first sign of a rash, unless the rash is clearly not drug related. If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed, and alternative therapy should be considered. Inform patients about the signs of serious skin reactions.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity has been reported in patients taking topiramate. Qsymia should be discontinued if an alternative etiology for the signs or symptoms cannot be established.

Hypersensitivity reactions, including anaphylaxis and angioedema, have occurred in patients treated with topiramate in the postmarketing setting. If a hypersensitivity reaction occurs, discontinue Qsymia and initiate appropriate therapy.

The concomitant use of alcohol or central nervous system (CNS) depressant drugs (e.g., barbiturates, benzodiazepines, and sleep medications) with phentermine or topiramate may potentiate CNS depression or other centrally mediated effects of these agents. Therefore, avoid concomitant use of alcohol with Qsymia.

In situations where immediate termination of Qsymia is medically required, appropriate monitoring is recommended. Patients discontinuing Qsymia 15 mg/92 mg should be gradually tapered as recommended.

Adjust dose of Qsymia for patients with moderate or severe renal impairment. Qsymia has not been studied in patients with end-stage renal disease on dialysis. Avoid use of Qsymia in this patient population.

Adjust dose of Qsymia for patients with moderate hepatic impairment. Qsymia has not been studied in patients with severe hepatic impairment. Avoid use of Qsymia in this patient population.

Avoid the use of Qsymia with other drugs that inhibit carbonic anhydrase (e.g., zonisamide, acetazolamide or methazolamide). Use of topiramate by patients on a ketogenic diet may also result in a physiological environment that increases the likelihood of kidney stone formation. Increase fluid intake to increase urinary output which can decrease the concentration of substances involved in kidney stone formation.

Patients treated with Qsymia should be advised to monitor for decreased sweating and increased body temperature during physical activity, especially in hot weather. Caution should be used when Qsymia is prescribed with other drugs that predispose patients to heat-related disorders; these drugs include, but are not limited to, other carbonic anhydrase inhibitors and drugs with anticholinergic activity.

When prescribing Qsymia, patients should be monitored for hypokalemia. It is recommended that a blood chemistry profile is obtained at baseline and periodically during treatment.

Phentermine, a component of Qsymia, has known potential for abuse. Qsymia is a schedule IV controlled-substance prescription medication.

To report negative side effects, contact VIVUS LLC at 1-888-998-4887 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see the Important Safety Information, Full Prescribing Information, and Healthcare Provider Counseling Tool for Patients of Reproductive Potential for Qsymia.