The prescribing information is now available for weight-loss drugs Belviq and Qsymia. Labeling matters, as both physicians and patients should read it. Many other factors, perhaps more important, will also come into play regarding how these drugs fare in terms of revenue. Marketing will be key. Eisai, a large established pharmaceutical company, is marketing Belviq, which is made by Arena (ARNA). Vivus (VVUS), which makes Qsymia, is building a sales force that will target obesity physicians and clinics initially.
When the drugs will be available is not clear yet. Belviq awaits scheduling by the DEA. Both drugs were approved recently.
There has been much discussion on Seeking Alpha about distribution of Qsymia. Physicians will need to complete an education session online that takes 20 minutes (no fast forwarding; it is a narrated presentation). Apparently the drug will be distributed through select mail order pharmacies.
What follows below is a side-by-side comparison of the highlights of the prescribing information for each category. Labeling matters to the extent physicians and patients should read it carefully. What can we discern from comparison of the highlights of the prescribing information? The full prescribing information follows the highlights in the PDF documents available online (links above).
Also, on the issue of pregnancy, information in this article was pulled from the full prescribing information since it one of the more significant safety issues. The other significant safety issue, cardiovascular safety, for both drugs is not resolved yet. The FDA is requiring clinical trials addressing cardiovascular safety with major adverse cardiovascular events (MACE) as the primary outcome. Contrave, in development by Orexigen (OREX), is currently in cardiovascular safety trials.
Indications seem identical. Both are easily administered oral formulations, but Qysmia could involve dosage escalation. Both drugs are contraindicated in pregnancy (and nursing women), but clearly Qysymia (topiramate) has teratogenic risk -- hence the REMS. Belviq is a serotonergic agonist, so the warnings and drug interactions are similar to other serotonergic drugs (agonists and serotonin selective reuptake inhibitors). Both drugs advise discontinuation after 12 weeks if the patient does not respond.
Below are highlights from the prescribing information, which are linked above. This is obviously an incomplete version of the information contained in the full prescribing information and is meant for investment research purposes only.
Belviq: 30 kg/m2 or greater (obese) (1) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition, (e.g., hypertension, dyslipidemia, type 2 diabetes) (1)
Qsymia: 30 kg/m2 or greater (obese) (1) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbidity such as hypertension, type 2 diabetes mellitus, or dyslipidemia (1)
Dosage and Usage
Belviq: Twice daily, discontinue after 12 weeks if patient does not respond
Qsymia: Take once daily in morning. Avoid evening dose to prevent insomnia (2.1)
- Recommended dose: Qsymia 3.75 mg/23 mg (phentermine 3.75 mg/topiramate 23 mg extended-release) daily for 14 days; then increase to 7.5 mg/46 mg daily (2.1)
- Discontinue or escalate dose (as described) if 3% weight loss is not achieved after 12 weeks on 7.5 mg/46 mg dose (2.1)
- Discontinue Qsymia if 5% weight loss is not achieved after 12 weeks on maximum daily dose of 15 mg/92 mg (2.1)
- Discontinue 15 mg/92 mg dose gradually (as described) to prevent possible seizure (2.1)
- Do not exceed 7.5 mg/46mg dose for patients with moderate or severe renal impairment or patients with moderate hepatic impairment (2.2, 2.3)
From the full prescibing information: BELVIQ is contraindicated during pregnancy, because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm. Maternal exposure to lorcaserin in late pregnancy in rats resulted in lower body weight in offspring which persisted to adulthood. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard of maternal weight loss to the fetus.
Qsymia: Pregnancy (4), Glaucoma (4), Hyperthyroidism (4), During or within 14 days of taking monoamine oxidase inhibitors
From the full prescibing information: Pregnancy Category X Risk Summary Qsymia is contraindicated in pregnant women. The use of Qsymia can cause fetal harm and weight loss offers no potential benefit to a pregnant woman. Available epidemiologic data indicate an increased risk in oral clefts (cleft lip with or without cleft palate) with first trimester exposure to topiramate, a component of Qsymia. When multiple species of pregnant animals received topiramate at clinically relevant doses, structural malformations, including craniofacial defects, and reduced fetal weights occurred in offspring. If this drug is used during pregnancy, or if a patient becomes pregnant while taking this drug, treatment should be discontinued immediately and the patient should be apprised of the potential hazard to a fetus. There is a Qsymia Pregnancy Surveillance Program to monitor maternal-fetal outcomes of pregnancies that occur during Qsymia therapy. Healthcare providers and patients are encouraged to report pregnancies by calling 1-888-998-4887.
Warnings and Precautions
- Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions: The safety of coadministration with other serotonergic or antidopaminergic agents has not been established. Manage with immediate BELVIQ discontinuation and provide supportive treatment (5.1)
- Valvular heart disease: If signs or symptoms develop consider BELVIQ discontinuation and evaluate the patient for possible valvulopathy. (5.2)
- Cognitive Impairment: May cause disturbances in attention or memory. Caution with use of hazardous machinery when starting BELVIQ treatment (5.3)
- Psychiatric Disorders, including euphoria and dissociation: Do not exceed recommended dose of 10 mg twice daily (5.4)
- Monitor for depression or suicidal thoughts. Discontinue if symptoms develop. (5.4)
- Use of Antidiabetic Medications: weight loss may cause hypoglycemia. Monitor blood glucose. BELVIQ has not been studied in patients taking insulin (5.5)
- Priapism: Patients should seek emergency treatment if an erection lasts >4 hours. Use BELVIQ with caution in patients predisposed to priapism. (5.6)
- Fetal Toxicity: Females of reproductive potential: Obtain negative pregnancy test before treatment and monthly thereafter; use effective contraception. Qsymia is available through a limited program under a Risk Evaluation and Mitigation Strategy (REMS) (5.1)
- Increase in Heart Rate: Monitor heart rate in all patients, especially those with cardiac or cerebrovascular disease (5.2)
- Suicidal Behavior and Ideation: Monitor for depression or suicidal thoughts. Discontinue Qysmia if symptoms develop (5.3)
- Acute Myopia and Secondary Angle Closure Glaucoma: Discontinue Qsymia (5.4)
- Mood and Sleep Disorders: Consider dose reduction or withdrawal for clinically significant or persistent symptoms (5.5)
- Cognitive Impairment: May cause disturbances in attention or memory. Caution patients about operating automobiles or hazardous machinery when starting treatment (5.6)
- Metabolic Acidosis: Measure electrolytes before/during treatment (5.7)
- Elevated Creatinine: Measure creatinine before/during treatment (5.8)
- Use of Antidiabetic Medications: Weight loss may cause hypoglycemia. Measure serum glucose before/during treatment (5.9)
Belvic: Most common adverse reactions (greater than 5%) in non-diabetic patients are headache, dizziness, fatigue, nausea, dry mouth, and constipation, and in diabetic patients are hypoglycemia, headache, back pain, cough, and fatigue.
Qysymia: Most common adverse reactions (incidence greater than or equal to 5%) are: paraesthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth (6.1).
Belvic: Serotonergic drugs (selective serotonin reuptake inhibitors (SSRIs),serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), triptans, bupropion, dextromethorphan, St. John's Wort): use with extreme caution due to the risk of serotonin syndrome. (7.1)
Qsymia: Oral contraceptives: Altered exposure may cause irregular bleeding but not increased risk of pregnancy. Advise patients not to discontinue oral contraceptives if spotting occurs (7.2). CNS depressants including alcohol: Potentiate CNS depressant effects. Avoid concomitant use of alcohol (7.3) Non-potassium sparing diuretics: May potentiate hypokalemia. Measure potassium before/during treatment (7.4)
Use in Specific Populations
- Nursing Mothers: Discontinue drug or nursing (8.3)
- Pediatric Use: Safety and effectiveness not established and use not recommended
- Nursing Mothers: Discontinue drug or nursing (8.3)
- Pediatric Use: Safety and effectiveness not established and use not recommended (8.4)
Source: Prescribing information for Belviq and Qsymia.