Rescriptor Warnings, Precautions, Pregnancy, Nursing, Abuse - Delavirdine mesylate

Rescriptor Warnings, Precautions, Pregnancy, Nursing, Abuse - Delavirdine mesylate

WARNINGS

Coadministration of RESCRIPTOR Tablets with certain nonsedating antihistamines, sedative hypnotics, antiarrhythmics, calcium channel blockers, ergot alkaloid preparations, amphetamines, cisapride, and sildenafil, may result in potentially serious and/or life-threatening adverse events due to possible effects of RESCRIPTOR on the hepatic metabolism of certain drugs (see

PRECAUTIONS

General: Delavirdine is metabolized primarily by the liver. Therefore, caution should be exercised when administering RESCRIPTOR Tablets to patients with impaired hepatic function.

Resistance/Cross-Resistance: Non-nucleoside reverse transcriptase inhibitors, when used alone or in combination, may confer cross-resistance to other non-nucleoside reverse transcriptase inhibitors.

Skin Rash: Skin rash attributable to RESCRIPTOR has occurred in 18% of all patients in combination regimens in phase II and III controlled trials who received RESCRIPTOR 400 mg tid. Forty-two percent to 50% of patients treated with RESCRIPTOR 400 mg tid in Studies 0021 and 0017 experienced rash compared with 24% to 32% of patients receiving monotherapy with zidovudine or didanosine, respectively. In Studies 0021 and 0017, 4.3% of patients treated with RESCRIPTOR 400 mg tid discontinued treatment due to rash.

Dose titration did not significantly reduce the incidence of rash. Rash was typically diffuse, maculopapular, erythematous, and often pruritic. Skin rash was more common in patients with lower CD4 cell counts and usually occurred within 1 to 3 weeks (median = 11 days) of treatment. Rash classified as severe was observed in 3.6% of patients in Studies 0021 and 0017. In most cases, the duration of the rash was less than 2 weeks and did not require dose reduction or discontinuation of RESCRIPTOR. Most patients were able to resume therapy after rechallenge with RESCRIPTOR following a treatment interruption due to rash. The distribution of the rash was mainly on the upper body and proximal arms, with decreasing intensity of the lesions on the neck and face, and progressively less on the rest of the trunk and limbs. Erythema multiforme and Stevens-Johnson syndrome were rarely seen and resolved after withdrawal of RESCRIPTOR. Any patient experiencing severe rash or rash accompanied by symptoms such as fever, blistering, oral lesions, conjunctivitis, swelling, muscle or joint aches should discontinue RESCRIPTOR and consult a physician. Occurrence of a delavirdine-related rash after 1 month of therapy is uncommon unless prolonged interruption of treatment with RESCRIPTOR occurs. Symptomatic relief has been obtained using diphenhydramine hydrochloride, hydroxyzine hydrochloride, and/or topical corticosteroids.

Information for Patients: Patients should be informed that RESCRIPTOR is not a cure for HIV-1 infection and that they may continue to acquire illnesses associated with HIV-1 infection, including opportunistic infections. Treatment with RESCRIPTOR has not been shown to reduce the incidence or frequency of such illnesses, and patients should be advised to remain under the care of a physician when using RESCRIPTOR.

Patients should be advised that the long-term effects of treatment with RESCRIPTOR are unknown at this time. They should be advised that the use of RESCRIPTOR has not been shown to reduce the risk of transmission of HIV-1.

Patients should be instructed that the major toxicity of RESCRIPTOR is rash and should be advised to promptly notify their physician should rash occur. The majority of rashes associated with RESCRIPTOR occur within 1 to 3 weeks after initiating treatment with RESCRIPTOR. The rash normally resolves in 3 to 14 days and may be treated symptomatically while therapy with RESCRIPTOR is continued. Any patient experiencing severe rash or rash accompanied by symptoms such as fever, blistering, oral lesions, conjunctivitis, swelling, muscle or joint aches should discontinue medication and consult a physician.

Patients should be informed to take RESCRIPTOR every day as prescribed. Patients should not alter the dose of RESCRIPTOR without consulting their doctor. If a dose is missed, patients should take the next dose as soon as possible. However, if a dose is skipped, the patient should not double the next dose.

Patients with achlorhydria should take RESCRIPTOR with an acidic beverage (eg, orange or cranberry juice). However, the effect of an acidic beverage on the absorption of delavirdine in patients with achlorhydria has not been investigated.

Patients taking both RESCRIPTOR and antacids should be advised to take them at least one hour apart.

Because RESCRIPTOR may interact with certain drugs, patients should be advised to report to their doctor the use of any prescription or over-the-counter medications.