Pharmacy & Therapeutics - April 2008 - (Page 236) Pharmaceutical Approval Update desvenlafaxine is 50 mg once daily with or without food. In clinical studies, doses of 50 to 400 mg/day were effective, but no additional benefits were observed at doses higher than 50 mg/day; adverse events and discontinuations were more frequent at higher doses. When discontinuing treatment, gradual dose reduction is recommended whenever possible. Tablets should be taken whole and should not be divided, crushed, chewed, or dissolved. Renal impairment: The recommended dose in patients with moderate renal impairment is 50 mg/day. The recommended dose in patients with severe renal impairment and ESRD is 50 mg every other day. The dose should not be escalated in patients with moderate or severe renal impairment or ESRD. Hepatic impairment: Dose escalation above 100 mg/day is not recommended. Desvenlafaxine tablets are available in strengths of 50 and 100 mg. Each tablet contains 76 mg or 152 mg of desvenlafaxine succinate, equivalent to 50 mg or 100 mg of desvenlafaxine. Commentar y: MDD is a common mental disorder, affecting about 121 million people worldwide. In the U.S., MDD affects approximately 15 million adults, or 6.7% of the U.S. population 18 years of age and older in a given year. Depression is among the leading causes of disability and the fourth leading contributor to the global burden of disease. A study estimated that the total economic burden of depression was $83.1 billion in 2000, including direct treatment costs and suicide-related and work-related costs. The controversy among experts is whether desvenlafaxine (Pristiq) is a substantial improvement over existing antidepressants. Although the chemical formula is similar to that of venlafaxine (Effexor), it is unclear whether the new product has advantages over its predecessor. Wyeth claims that desvenlafaxine does not need to be gradually ramped up to an ideal dosage, so that patients can immediately begin taking the full dose and may see faster results. This can be crucial, because patients must often try multiple drugs before they find their way out of their depression, a process that can take many painful weeks. A second purported advantage of desvenlafaxine is that it delivers the main metabolite of Effexor in an already active state without having to pass through the liver. This may prevent many undesirable drug–drug interactions. Time will tell whether desvenlafaxine offers a noticeable improvement over Effexor or at least a way to avoid the terrible withdrawal symptoms. The Food and Drug Administration (FDA) approved desvenlafaxine based on four eightweek double-blind studies, but results of antidepressant trials can be easily manipulated through selective reporting. Having perhaps learned from its past mistakes, the FDA gave a conditional approval, contingent on Wyeth’s promise to continue research into the drug’s efficacy and safety by conducting at least one study each of sexual dysfunction, pediatric reactions, dosing differences, and relapse prevention. Ideally, the results of all of these studies will be open to public scrutiny. Sources: www.wyeth.com; www.treatmentonline.com; http://biz.yahoo.com Rilonacept (Arcalyst) Injection for Subcutaneous Use Manufacturer: Regeneron, Tarrytown, N.Y. Indication: Rilonacept, an orphan drug, is indicated for the treatment of cryopyrin-associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome (FACS) and Muckle–Wells syndrome, in adults and children 12 years of age and older. Drug Class: This product is a targeted inhibitor of interleukin-1 (IL-1), the key driver of inflammation in cryopyrin syndromes. Uniqueness of Product: Rilonacept (IL-1 Trap) is a recombinant biological protein-based product designed to bind the IL-1 cytokine to prevent its interaction with cell–surface receptors. Warnings and Precautions: Infection and immunosuppression. IL-1 blockade may interfere with immune response to infections. Serious, lifethreatening infections have been reported in patients taking rilonacept. Treatment should be discontinued if a serious infection develops. Patients with active or chronic infections should not use rilonacept. Hypersensitivity. Hypersensitivity reactions associated with rilonacept have been rare. If a hypersensitivity reaction occurs, the drug should be discontinued and appropriate therapy should be initiated. Immunization. Live vaccines should not be given concurrently with rilonacept. Before patients begin taking rilonacept, they should receive all recommended vaccinations. Dosage and Administration: Adults. For adults 18 years of age and older, therapy should begin with a loading dose of 320 mg, delivered as two 2-mL, subcutaneous (SQ) injections of 160 mg on the same day at two different sites. Dosing continues with a once-weekly injection of 160 mg, given as a single 2-mL, SQ injection. Rilonacept should not be administered more often than once weekly. Pediatric patients. For pediatric patients 12 to 17 years of age, treatment begins with a loading dose of 4.4 mg/kg, up to a maximum of 320 mg, delivered as one or two SQ injections with a maximum single-injection volume of 2 mL. Dosing is continued with a once-weekly injection of 2.2 mg/kg, up to a maximum of 160 mg, administered as a single subcutaneous injection, up to 2 mL. If the initial dose is given as two injections, both injections should be given on the same day at two different sites. Rilonacept should not be given more often than once weekly. Commentar y: CAPS includes a spectrum of rare inherited inflammatory conditions, including familial cold autoinflammatory syndrome (FCAS), Muckle–Wells syndrome, and neonatal onset multisystem inflammatory disease. These autoinflammatory disorders are characterized by spontaneous systemic inflammation. A novel feature of these conditions is that exposure to mild degrees of cold temperatures can provoke a major inflammatory episode that occurs within hours. The syndromes are caused by a range of mutations in the gene CIAS1 (NALP3), which encodes a protein named cryopyrin (meaning “icy-fire”). In a pivotal development program, patients receiving rilonacept experienced a greater improvement in overall symptom 236 P&T® • April 2008 • Vol. 33 No. 4 http://www.wyeth.com http://www.treatmentonline.com http://biz.yahoo.com
For optimal viewing of this digital publication, please enable JavaScript and then refresh the page. If you would like to try to load the digital publication without using Flash Player detection, please click here.