RX & OTC Update

Qsymia

Obesity management with pairing of two drugs.

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Rx Update 

Qsymia at a glance

  • Indications

    • Chronic weight management as an adjunct to diet and physical activity

    • Indicated for > 30 kg/m2 or > 27 kg/m2 and having at least one cardiovascular risk factor

  • Contraindications

    • Pregnancy, Category X

    • Hyperthyroidism

    • Glaucoma

    • Use with monoamine oxidase inhibitors

Vivus Inc. has created Qsymia, a controlled-release capsule containing phentermine and topiramate. Phentermine has actions similar to amphetamine and acts in the brain to decrease appetite, reduce food intake and promote weight loss.1 Topiramate has approval for seizure disorders and diabetic neuropathy.2 For obesity, it works at multiple levels within the brain to enhance feelings of satisfaction following a meal.
Obesity management begins with diet and exercise.3 Candidates for drug treatment are those who fail a 6 month trial of lifestyle intervention. Plus, individuals should have a body mass index > 30 kg/m2, or > 27 kg/m2 and having at least one risk factor (e.g., hypertension, dyslipidemia, type 2 diabetes mellitus).4 Alternatives include orlistat (over-the-counter Alli) and prescription (Xenical), phentermine alone, and newly approved, lorcaserin (Belviq), planned for release in 2013.2

The CONQUER trial enrolled more than 2,400 patients in a randomized, double-blind study that lasted 56 weeks.5 The adult subjects weighed between 27 and 45 kg/m2. Subjects were given placebo or randomized to daily low-dose (P/T 7.5 mg/46 mg) or daily high-dose (P/T 15 mg/92 mg) drug. Patients were counseled on a calorie-restricted diet and exercise. The trial enrolled obese and overweight patients who had at least two or more obesity-related conditions. The mean age was 51 years and they were mostly female (70 percent) and Caucasian (86 percent). Subjects had type 2 diabetes or impaired fasting glucose (67-68 percent) and hypertension (52-53 percent) with a mean blood pressure of 128.3/80.6 mm Hg and mean heart rate of 72 bpm.

The primary endpoint (achieving a 5 percent weight loss) was achieved in 70 percent in the high-dose arm and 62 percent in the low-dose arm versus 21 percent in the placebo arm (p < 0.0001). Weight change was significantly greater in those on the high dose (- 10.2 kg) and low dose (-8.1 kg) versus placebo (- 1.4 kg)(p < 0.0001). Secondary endpoints improved such as blood pressure, lipids and blood glucose. The high discontinuation rate due to side effects may be ameliorated with individualized dosing.6 Low dose Qsymia had a favorable effect in individuals with cardiovascular risk factors and may find a niche in management due to fewer dose-related side effects.6

Dosage, Costs, Pharmacokinetics

The adult dosing approach involves slow upward and downward titration.2 To initiate treatment, start at P/T 3.75 mg/23 mg once daily for 2 weeks followed by P/T 7.5 mg/46 mg once daily for 12 weeks. If there is no weight loss (< 3 percent of body weight), then titrate to P/T 11.25 mg/69 mg once daily for 2 weeks followed by P/T 15 mg/92 mg once daily for another 12 week period. If weight loss is < 5 percent of body weight, gradually decrease the dose.

Abrupt withdrawal may precipitate seizures. The capsule should not be chewed or opened, and can be taken with or without food in the morning to reduce insomnia. It is a DEA Schedule IV controlled drug (phenteremine) due to the potential for abuse, and patients must participate in a Risk Evaluation and Mitigation Strategy (REMS) program. The medication is dispensed from a single designated REMS pharmacy (www.QsymiaREMS.com). The average wholesale cost for a 14-week course at the low-dose and high-dose titration phases is $525 to $700, respectively.7

Phentermine is predominantly (70-80 percent) eliminated by the kidneys and the remainder is eliminated by metabolism via the Cytochrome P450 3A4 enzymes.1 The half-life is 20 hours. Topiramate is also extensively cleared by the kidneys, and only 5 percent of the dose is converted to metabolites. The half-life is 65 hours. The maximum dose is reduced in individuals with impaired kidney function (with CrCl < 50 mL/min) and moderate hepatic impairment. It has not been studied in end stage renal disease or severe hepatic impairment.

Drug Interactions

Emerging data describes interactions with drugs to treat diabetes, seizure disorders, diuretics and other conditions.1 Providers should consult with a pharmacist on the latest information available to interpret the impact of these interactions. Plus, there is an interaction with oral hormonal contraceptives. Studies have shown changes in concentrations of estrogen and progestin resulting in irregular bleeding and increased likelihood of pregnancy. Also, delay start until 2 weeks after discontinuing an MAO inhibitor.

Side effects

The most common side effects are dizziness, insomnia and paresthesia.1 Patients also report dysgeusia (metallic taste), dry mouth and constipation. The drug was discontinued due to side effects at a rate of 11-17 percent in clinical trials. The most frequent reason was due to changes in vision and mood (e.g., depression, anxiety). Patients reporting blurred vision or eye pain should be evaluated for acute angle-closure glaucoma. Reports of problems with concentration and memory occurred soon after starting treatment.

Fetal Risk

Women who may become pregnant are at high risk for teratogenicity of the fetus.1 The drug is Pregnancy Category X and the fetus can be affected by cleft lip, possibly cleft palate and other congenital defects. The greatest risk is exposure during the first trimester. There is a Pregnancy Surveillance Program phone line (1-888-998-4887.) A negative pregnancy test should be documented at baseline and monthly, and counsel patients on using contraceptives during treatment if they have the potential to become pregnant.

Monitoring

There is no boxed warning at this time.1 Vital signs should be checked routinely since the drug can increase in heart rate and lower blood pressure. Metabolic acidosis can occur, so order a baseline serum chemistry including serum creatinine, potassium (hypokalemia) and serum bicarbonate at baseline, 4 weeks, and periodically thereafter. Monitor glucose closely in patients who have diabetes due to the potential for hypoglycemia and need to adjust medications associated with weight loss.

References for this article can be accessed here.

Grace Earl is an ambulatory care pharmacist at the University of the Sciences and her practice site is at Hahnemann University Hospital, Philadelphia.


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