A Review of the Combination of Phentermine and Topiramate Extended-Release for Weight Loss

Abstract

The Food and Drug Administration recently approved the combination of phentermine and extended-release topiramate (PHN/TPM) for weight loss. This is one of only two weight-loss agents to arrive on the US market in the last decade. This product combines the anorexigenic agent, phentermine, which is approved for the short-term treatment of weight loss, with a carbonic anhydrase inhibitor, topiramate, which is approved for non-weight loss indications, including seizure disorders and migraine headache. Although the combination is believed to be synergistic, no clinical trial data currently address this. The PHN/TPM combination is a once-daily formulation. Mean weight loss among participants who completed 1 year of PHN/TPM treatment in research trials, in combination with lifestyle modification, has ranged from approximately 7% (lower doses) to over 14% (higher doses), relative to approximately 2% with placebo. In addition to weight loss, PHN/TPM resulted in improved comorbidities and quality of life, although it has not been shown to improve mental/psychosocial issues. Among the common adverse events observed in clinical trials are paresthesia, dry mouth, constipation, and headache. Other noteworthy adverse events that occurred more commonly with PHN/TPM versus placebo included dysgeusia, insomnia, irritability, and alopecia. Laboratory abnormalities in serum bicarbonate and potassium were also observed in a subset of patients. Due to the teratogenic potential of topiramate, women of child-bearing potential are required to have a negative pregnancy test at baseline and are instructed to take monthly pregnancy tests. As part of a risk-management approach, only pharmacies certified by the manufacturer will be allowed to dispense PHN/TPM and will be required to provide information on birth defects. Like phentermine, the combination drug will be designated as a schedule IV medication. In comparison with other agents currently on the market, the combination of PHN/TPM appears to provide significant advantages for weight loss, while improving comorbid conditions and quality of life. Monitoring for laboratory abnormalities, adverse events, and changes in psychiatric status should occur during therapy. © 2012 The Author(s).