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Update on U.S. Prescribing Information for ZERIT (stavudine)
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Bristol-Myers Squibb is committed to understanding both the efficacy and safety profiles of our medicines. Based on a comprehensive review of post-marketing reports, internal safety databases and published literature, which further characterized the risk benefit profile of ZERIT (stavudine), Bristol-Myers Squibb determined that ZERIT continues to provide benefit for some HIV-infected patients and proactively initiated with the FDA a label update and risk evaluation and mitigation strategy (REMS) for ZERIT which includes a medication guide. The label was updated on December 10, 2010 and can be viewed at http://packageinserts.bms.com/pi/pi_zerit.pdf.
A summary of the sections and information being updated is listed below:
- Entire label reformatted based on FDA guidance to industry (Physician Labeling Rule)
- Additional information added to section on Fat Redistribution
- Addition of lipoatrophy, lipodystrophy, and neutropenia to the section on Postmarketing Experience
- New information on the cross resistance profile of stavudine in section on Microbiology.
- Conversion of Patient Information to a Medication Guide
Bristol-Myers Squibb proposed the REMS in the US to inform patients of the potential serious risks associated with the use of ZERIT capsules or ZERIT oral solution. As part of the REMS, a medication guide will be provided to all patients to be dispensed along with each prescription. Additionally, the capsule container labels and oral solution outer carton and container labels were also changed to make the product dosage strengths easier to distinguish.
As with all our medicines, we work closely with the FDA to monitor safety events that occur with the use of our products.
IMPORTANT INFORMATION about ZERIT (stavudine)
INDICATION:
ZERIT® (stavudine), in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV-1) infection.
IMPORTANT SAFETY INFORMATION:
· Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including stavudine and other antiretrovirals. Permanent discontinuation of ZERIT should be considered for patients with confirmed lactic acidosis.
· Fatal lactic acidosis has been reported in pregnant women who received the combination of stavudine and didanosine with other antiretroviral agents. This combination should be used with caution during pregnancy, and is recommended only if the potential benefit clearly outweighs the potential risk.
· ZERIT is contraindicated in patients with clinically significant hypersensitivity to stavudine or any of the components contained in the formulation.
· Hepatic decompensation (some fatal) has occurred in HIV-1/HCV coinfected patients receiving combination antiretroviral therapy for HIV-1 and interferon and ribavirin. Discontinuation of ZERIT should be considered as medically appropriate.
· Motor weakness has been reported rarely in patients receiving combination antiretroviral therapy. If motor weakness develops, ZERIT should be discontinued.
· Peripheral sensory neuropathy, manifested by numbness, tingling, or pain in the hands or feet, has been reported in patients receiving ZERIT therapy. Peripheral sensory neuropathy, which can be severe, is dose related and occurs more frequently in patients with advanced HIV-1 disease, a history of peripheral sensory neuropathy, or who are receiving other drugs associated with neuropathy, including didanosine. If peripheral sensory neuropathy develops, permanent discontinuation of ZERIT should be considered. In some cases, symptoms may worsen temporarily following discontinuation.
· Fatal and nonfatal pancreatitis have occurred during therapy when ZERIT was part of a combination regimen that included didanosine in both treatment-na•ve and treatment-experienced patients regardless of degree of immunosuppression. Reinstitution of ZERIT after a confirmed diagnosis of pancreatitis should be undertaken with caution and close monitoring; avoid use in combination with didanosine.
· Clinical lipoatrophy or lipodystrophy developed in a higher proportion of patients treated with stavudine compared to tenofovir or abacavir. The severity and incidence of lipoatrophy or lipodystrophy are cumulative over time with stavudine-containing regimes. Patients receiving ZERIT should be monitored for symptoms and questioned about body changes. A benefit-risk assessment for each patient should be made, and an alternative antiretroviral should be considered.
· Immune reconstitution syndrome has been reported in patients receiving combination antiretroviral therapy, including ZERIT.
· Adverse reactions reported in ZERIT-containing combination therapy are: nausea (53%), headache (46%), diarrhea (45%), rash (30%), vomiting (30%), and neuropathy (21%). When ZERIT is used in combination with other agents with similar toxicities, the incidence of adverse reactions may be higher than when stavudine is used alone.
· The use of ZERIT in combination with zidovudine should be avoided. The use of ZERIT in combination with doxorubicin or ribavirin should be undertaken with caution. SEE DRUG INTERACTIONS section of the Full Prescribing Information for additional information.
· Because of the potential for HIV transmission and serious adverse reaction in nursing infants, mothers should be instructed not to breast-feed if they are receiving ZERIT.
It is recommended that the ZERIT dosage be modified in patients with reduced creatinine clearance and in patients receiving maintenance hemodialysis. SEE DOSAGE AND ADMINISTRATION section of the Full Prescribing Information for additional information.
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