Vivus Inc's Qsymia

In an FDA press release dated July 17, 2012, the agency announced approval of Qsymia (phentermine and topiramate extended-release) capsules as an adjunct to diet and exercise for weight reduction in patients with obesity, defined by a body mass index (BMI) of 30 kg/m² or greater, or for weight reduction in patients with a BMI of 27 kg/m² or greater (overweight) with 1 or more comorbidities related to excess weight, including hypertension, type 2 diabetes mellitus (T2DM), or dyslipidemia.^1,2 Qsymia has some potential for causing dependence, qualifying Qsymia as a schedule IV medication. The Risk Evaluation and Mitigation Strategy (REMS) for Qsymia requires special certification of prescribers and dispensing pharmacies.³

Pharmacology and Pharmacokinetics

Qsymia is an extended-release combination of 2 medications: the anorexigenic sympathomimetic amine, phentermine, and the appetite-suppressing satiety-enhancing medication, topiramate. The exact mechanism of action of each medication is unknown.²

In healthy individuals, the mean half-life of phentermine is about 20 hours and the mean half-life of topiramate is about 65 hours.²

The manufacturer recommends dose adjustment of Qsymia to half the usual recommended dose in patients with moderate to severe renal impairment and in patients with moderate hepatic impairment. No dose adjustment is required in patients with mild renal impairment or in patients with mild to moderate hepatic impairment. Qsymia has not been studied in patients with end-stage renal disease receiving dialysis or in patients with severe hepatic impairment.²

Dosage and Administration

Patients may take each once-daily dose of Qsymia in the morning without regard to food. Patients starting Qsymia should begin with 14 days of 3.75 mg/23 mg daily, followed by 10 weeks of 7.5 mg/46 mg daily and a 12-week follow-up appointment to evaluate weight-loss progress. If the patient has lost less than 3% of initial body weight by 12 weeks, the physician should either discontinue the medication or increase the dose. The second dose escalation begins with a titration dose of 11.25 mg/69 mg daily for 14 days followed by 10 weeks of treatment with the highest dose, 15 mg/92 mg. If the highest dose does not result in loss of at least 5% of initial body weight at the 12-week follow-up appointment, the patient should discontinue Qsymia. To minimize the chance of seizure, patients discontinuing Qsymia should take 1 tablet of the remaining medication every other day for at least 1 week before stopping altogether.²

Clinical Trials

In the first phase 3 study, investigators evaluated Qsymia versus placebo, along with diet and exercise, in 514 patients with obesity or BMI-defined overweight status with 2 or more weight-related comorbidities. This trial excluded patients with T2DM. After 4 weeks of dose titration and 52 weeks of treatment, investigators evaluated the percentage of weight lost from baseline (10.9% with 15 mg/92 mg vs 1.6% with placebo; P <.0001), the percentage of patients achieving a 5% or greater reduction in weight from baseline (67% with 15 mg/92 mg versus 17% with placebo; P <.0001), and the percentage of patients achieving a 5% or greater reduction in weight from baseline (47% with 15 mg/92 mg vs 7% with placebo; P <.0001).²

A second phase 3 study evaluated use in patients with T2DM. In this trial, investigators measured weight reductions as well as modest reductions in blood pressure, blood lipids, and fasting blood glucose with use of Qsymia.²

Contraindications, Warnings, and Precautions

Qsymia is contraindicated in pregnant patients (category X), patients with hyperthyroidism, patients with past idiosyncratic or hypersensitivity reactions to sympathomimetic amines, and patients who are taking or recently stopped using a monoamine oxidase inhibitor.²

Important warnings related to Qsymia include potential increases in heart rate, worsening of mood disorders, exacerbation of sleep disorders, acute myopia, secondary angle closure glaucoma, cognitive impairment (especially with other medications or alcohol), and metabolic acidosis. In patients with T2DM, use of Qsymia may necessitate dosage adjustments of antidiabetic agents.²

Use of Qsymia in patients taking oral contraceptives may result in changes in menstrual bleeding patterns due to increased exposure to norethindrone and decreased exposure to ethinyl estradiol. Monitoring for hypokalemia is recommended in patients taking potassium-depleting diuretics.²

Common adverse events with Qsymia, occurring in 5% or more of patients in trials, and at least 50% more frequently in active-treatment groups than in patients treated with placebo, included paraesthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth. For a complete discussion of potential adverse events and drug interactions, please consult the product package insert.²

Michael R. Page earned his PharmD from the Ernest Mario School of Pharmacy at Rutgers University. He has worked as a community pharmacist at CVS Pharmacy and is currently clinical editor in clinical and scientific affairs at Pharmacy Times.

References

• FDA. FDA approves weight-management drug Qsymia [press release]. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm312468.htm. Accessed October 2013.
• QSYMIA (phentermine and topiramate extended-release) capsules [package insert]. Mountain View, CA: VIVUS, Inc; 2013.
• FDA. Qsymia (phentermine and topiramate extended-release) capsules risk evaluation and mitigation strategy. www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM312598.pdf. Accessed October 2013.