Delavirdine (Rescriptor®)
Delavirdine is a bis (heteroaryl) piperazine compound.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are highly selective for HIV-1 but do not exhibit activity against other viruses.
NNRTIs bind noncompetitively to an active site of the reverse transcriptase molecule. Reverse transcriptase directs the polymerization of DNA from viral RNA. NNRTIs inhibit this polymerization by altering the position of critical amino acids within the catalytic site.
Resistance of NNRTIs occurs through mutations of the reverse transcriptase gene in the viral genome. When nonnucleoside reverse transcriptase inhibitors are used as monotherapy for HIV-1 infection, drug resistance develops rapidly.
NNRTI naďve patients with prior nucleoside analogue reverse transcriptase inhibitor (NRTI) exposure, who have isolates with resistance mutations and phenotypic resistance to NRTIs, appear more likely to have hypersusceptibility to the NNRTI class of drugs.
The in vitro 50% inhibitory concentration of delavirdine for HIV-1 averages 0.26 µM.
Delavirdine is rapidly absorbed after oral administration and maximum concentrations are reached within 1.5 hours after a dose.
Delavirdine is highly (98%) plasma protein bound, which restricts systemic distribution. Delavirdine is extensively metabolized by the cytochrome P450 system. Delavirdine is an inhibitor of CYP450 3A4 and thus leads to inhibition of its own metabolism.
Hepatitis and rash are common adverse effects. Rash usually occurs between 7 and 15 days after initiating treatment. Rash occurs more commonly in patients with CD4+ counts less than 100 cells/mm3. Continuing treatment is possible in >85% of patients who develop rash. Other adverse effects are headache, fatigue, and gastrointestinal complaints, including occasional increases in transaminase levels.
Tablet, as mesylate - 100mg (360 tablet bottle), 200mg (180 tablet bottle)
Adult dosing:
400 mg tid
Administer with or without food
Safety and effectiveness of delavirdine have not been established in HIV-1 infected individuals younger than 16 years of age.
Disease state based dosing:
Dose adjustments in renal dysfunction are necessary.
Use with caution in patients with impaired hepatic function.
Contraindications/Warnings/Precautions:
Do not give in combination with agents that are highly dependent on metabolism by CYP450 3A4.
Delavirdine is a potent inhibitor of CYP450 3A4. Concomitant use of other medications that are metabolized by CYP450 3A4 can lead to drug interactions.
Category C: Risk unknown. Human studies inadequate.
Delavirdine has demonstrated rodent teratogenicity and has been associated with some ventricular septal defects.
Liver function tests should be monitored.
Brand names/Manufacturer:
Rescriptor®
100mg tablet – Pfizer and Agouron Pharmaceuticals Inc
200mg tablet – Agouron Pharmaceuticals Inc.