Protect the Platelets

New Warnings

A new safety warning has been posted by the Food and Drug Administration (FDA) for the bisphosphonates class, which includes the following agents:

• Alendronate (Fosamax, Fosamax plus D);
• Etidronate (Didronel);
• Ibandronate (Boniva);
• Pamidronate (Aredia);
• Risedronate (Actonel, Actonel plus Ca);
• Tiludronate (Skelid); and
• Zoledronic acid (Reclast, Zometa).

The warning notes the possibility of severe with sometimes-incapacitating bone, joint, and/or musculoskeletal pain when patients receive bisphosphonate therapy. This pain can arise days, months, or years after beginning bisphosphonate therapy. 

Upon discontinuation of bisphosphonate treatment, some patients have reported complete symptom relief; others have reported slow or partial resolution. The risk factors associated with this effect are unknown.

Because this symptom is included in the prescribing information for all bisphosphonates, the association between bisphosphonates and severe musculoskeletapain may be disregarded by healthcare professionals, delaying diagnosis, prolonging pain and/or impairment, and necessitating the use of additional therapies for improvement.

This severe musculoskeletal pain is in contrast to the acute phase response (e.g., fever, chills, bone pain, myalgias, and arthralgias) that may accompany initial administration of intravenous bisphosphonates, which may occur with initial exposure to once-weekly or once-monthly doses of oral bisphosphonates. These symptoms usually resolve within a few days with continued drug use.

Healthcare professionals should consider whether bisphosphonate use might be responsible for severe musculoskeletal pain in patients who have these symptoms and consider temporary or permanent bisphosphonate discontinuation.

Chantix tablets (varenicline, Pfizer) have received a labeling change including language about depression and suicidal behavior, following patient reports of mood disorders and erratic behavior cited by the FDA (which is reviewing the drug’s safety). Patients should be observed for serious neuropsychiatric symptoms, including behavior changes, agitation, depressed mood, suicidal ideation, and suicidal behavior. This new language is more prominent in the product labeling and stresses that patients should be monitored for these changes. To date, no causal relationship has been identified.—MK

Off the Market

Bidil immediate-release tablets (combination isosorbide dinitrate/hydralazine HCl, NitroMed)has been discontinued by its manufacturer. The company is developing a once-daily extended-release formulation for treatment of heart failure in self-identified black patients. A filing of the New Drug Application is planned for 2010.

Roferon-A prefilled syringes (interferon alfa-2a recombinant, Roche) will no longer be available when the existing supplies are depleted (estimated early to mid-2008). Discontinuation is related to the life cycle of the product and not safety or efficacy. The last distribution for Roferon-A was in late 2007. These formulations still can be obtainable through wholesalers or retail pharmacies until their supplies are exhausted. Alternative therapies are available for all Roferon-A indications. For additional information, call the Roche Pharmaceuticals Service Center at (800) 526-6367.