New FDA Actions: Vivus Inc's Qsymia

Qsymia (phentermine and topiramate extended-release capsules; CIV) is approved with lifestyle interventions for chronic weight management in adults.

Qsymia (phentermine and topiramate extended-release capsules; CIV) is one of the first anti-obesity medications to gain FDA approval and enter the US market since 1999. It is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index of:

• 30 kg/m² or greater (obese) or
• 27 kg/m² or greater (overweight) in the presence of at least 1 weight-related comorbidity (eg, hypertension, type 2 diabetes mellitus, dyslipidemia)¹

Qsymia is accompanied by a Risk Evaluation and Mitigation Strategy related to its contraindicated use in pregnancy.^1,2

Pharmacology and Pharmacokinetics

Phentermine is a sympathomimetic amine thought to reduce weight by causing release of catecholamines in the hypothalamus, resulting in reduced appetite and decreased food consumption. Topiramate’s impact on weight may be due to its effects on both appetite suppression and satiety enhancement, induced by combined pharmacologic effects (eg, augmentation of gamma-aminobutyrate, inhibition of AMPA/kainate excitatory glutamate receptors).¹

Pharmacokinetics of both phentermine and topiramate are affected in patients with varying degrees of renal and hepatic impairment; as such, associated dosing adjustments are in place.¹

Dosage and Administration

Qsymia is initiated at 3.75/23 mg daily for 14 days, after which the dose is increased to 7.5/46 mg daily. Further dose escalations (or treatment discontinuation) are recommended if weight is not reduced by at least 3% at 12 weeks.¹

Qsymia is taken once daily in the morning with or without food; it is avoided in the evening because of the possibility of insomnia. Due to the possibility of precipitating seizures, Qsymia should be gradually discontinued by taking a dose every other day for at least 1 week prior to stopping treatment.

Clinical Trials

The safety and efficacy of Qsymia were evaluated in 2 multicenter, phase 3 trials that included severely obese patients (EQUIP study) and overweight or obese patients with at least 2 weight-related comorbidities (eg, hypertension, hypertriglyceridemia, type 2 diabetes, central adiposity [CONQUER study]). The average weight loss in EQUIP was 10.9% for Qsymia 15/92 mg and 1.6% for placebo. The average weight loss in CONQUER was 9.8% for Qsymia 15/92 mg, 7.8% for Qsymia 7.5/46 mg, and 1.2% for placebo.²

The most commonly observed side effects (5% or greater) in clinical studies include paresthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth.

Contraindications, Warnings, and Precautions

Qsymia is contraindicated in pregnancy, because it is classified as Pregnancy Category X due to its associated risk of fetal orofacial clefts with first trimester exposure. Women of reproductive potential should have a negative pregnancy test before treatment and monthly thereafter and use effective contraception consistently during therapy. Qsymia is also contraindicated in patients with glaucoma or hyperthyroidism; patients actively receiving treatment or within 14 days following treatment with monoamine oxidase inhibitors; and patients with hypersensitivity to sympathomimetic amines, topiramate, or any of the inactive ingredients in Qsymia.¹

Qsymia may increase resting heart rate (HR); therefore, regular measurement of resting HR is recommended for all patients, especially those with cardiac or cerebrovascular disease or when initiating or increasing the dose. Qsymia is not recommended in patients with recent or unstable cardiac or cerebrovascular disease.¹

Topiramate increases the risk of suicidal thoughts or behavior. As such, patients should be monitored for emergence or worsening of depression, suicidal thoughts/behavior, and/or any unusual changes in mood or behavior. Qsymia is not recommended in patients with a history of suicidal attempts or active suicidal ideation, and should be discontinued in patients experiencing these complications.¹

Qsymia may cause mood disorders (ie, depression, anxiety), insomnia, and cognitive dysfunction. Patients should be cautioned accordingly regarding operating automobiles and other hazardous machinery.¹

Acute angle closure glaucoma has been reported in patients treated with topiramate. Symptoms, which commonly occur within 1 month of initiating treatment, include acute onset of decreased visual acuity and/or eye pain. Qsymia should be discontinued immediately if symptoms occur.

Increases in serum creatinine and hyperchloremic, nonanion gap, metabolic acidosis have been reported in patients treated with Qsymia; in these cases, dose reduction or therapy discontinuing should be considered.¹

Dr. Beyzarov is scientific director for the Pharmacy Times Office of Continuing Professional Education

References

1. Ioannides-Demos LL, Piccenna L, McNeil JJ. Pharmacotherapies for obesity: past, current, and future therapies. J Obes. 2011;2011:179674.

2. Qsymia complete prescribing information. www.qsymia.com/pdf/full-prescribing-information.pdf. Accessed July 25, 2012 .

3. Vivus announces FDA approval of once daily Qsymia™ (Phentermine and Topiramate Extended-release) Capsules. CIV. http://ir.vivus.com/releasedetail.cfm?ReleaseID=692685. Accessed July 25, 2012.