Page 891 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 49 Antiviral Agents 877

TABLE 49–4 Clinically significant drug-drug interactions pertaining to two-drug antiretroviral combinations. 1

Agent Drugs That Increase Its Serum Levels Drugs That Decrease Its Serum Levels
Atazanavir Ritonavir Didanosine, efavirenz, elvitegravir/cobicistat, etravirine,
fosamprenavir, nevirapine, stavudine, tenofovir, tipranavir
Darunavir Indinavir Efavirenz, lopinavir/ritonavir, saquinavir
Delavirdine 2 Didanosine, fosamprenavir
Didanosine Tenofovir Atazanavir, ritonavir
Dolutegravir Efavirenz, etravirine, nevirapine
Efavirenz 2 Darunavir
Elvitegravir 3 Ritonavir Efavirenz, nevirapine
Etravirine Atazanavir, delavirdine, indinavir, lopinavir/ritonavir Efavirenz, nevirapine, ritonavir, saquinavir, tipranavir
Fosamprenavir Atazanavir, delavirdine, etravirine, ritonavir Didanosine, efavirenz, lopinavir/ritonavir, maraviroc, nevirapine,
tipranavir
Indinavir Darunavir, delavirdine, nelfinavir, ritonavir Didanosine, efavirenz, etravirine, nevirapine
Lopinavir/ritonavir Darunavir Didanosine, efavirenz, fosamprenavir, nelfinavir, nevirapine,
tipranavir
Maraviroc Atazanavir, darunavir, lopinavir/ritonavir, nevirapine, Efavirenz, etravirine, tipranavir
saquinavir, ritonavir
Nelfinavir Delavirdine, indinavir, ritonavir, saquinavir
Nevirapine 2 Fosamprenavir
Raltegravir Atazanavir Etravirine, tipranavir
Rilpivirine 2 Darunavir, lopinavir/ritonavir
Saquinavir Atazanavir, delavirdine, indinavir, lopinavir/ritonavir, Efavirenz, etravirine, nevirapine, tipranavir
nelfinavir, ritonavir
Tenofovir alafenamide Ritonavir Darunavir
Tenofovir disoproxil Atazanavir
fumarate
Tipranavir Efavirenz
1 Dose adjustment may be necessary if co-administered.
2
NNRTI-NNRTI drug-drug interactions are not listed.
3 Drug-drug interactions are rare with elvitegravir as a single agent but multiple if co-administered with either cobicistat or ritonavir.

Given the large number of non-HIV medications that are also not unlike those achieved in humans. Thus, pregnancy should be
metabolized by this pathway (see Chapter 4), drug-drug interac- avoided when taking delavirdine.
tions must be expected and looked for; dosage adjustments are Delavirdine is extensively metabolized by CYP3A and CYP2D6
frequently required and some combinations are contraindicated. enzymes. Therefore, there are numerous potential drug-drug
interactions to consider (Tables 49–3 and 49–4). The concur-
rent use of delavirdine with fosamprenavir is not recommended
DELAVIRDINE because of bidirectional interactions. Co-administration of dela-
virdine with indinavir or saquinavir prolongs the elimination
Delavirdine has an oral bioavailability of about 85%, but this half-life of the latter agents, thus allowing them to be dosed twice
is reduced by antacids or H -blockers. It is extensively bound rather than thrice daily.
2
(~98%) to plasma proteins and has correspondingly low cerebro-
spinal fluid levels. Serum half-life is approximately 6 hours.
Skin rash occurs in up to 38% of patients receiving delavir- EFAVIRENZ
dine; it typically occurs during the first 1–3 weeks of therapy
and does not preclude rechallenge. However, severe rash such Efavirenz can be given once daily because of its long half-life
as erythema multiforme and Stevens-Johnson syndrome have (40–55 hours). It is moderately well absorbed following oral
rarely been reported. Other possible adverse effects are headache, administration (45%). Since toxicity may increase owing to
fatigue, nausea, diarrhea, and increased serum aminotransferase increased bioavailability after a high-fat meal, efavirenz should be
levels. Delavirdine has been shown to be teratogenic in rats, caus- taken on an empty stomach. Efavirenz is principally metabolized
ing ventricular septal defects and other malformations at dosages by CYP3A4 and CYP2B6 to inactive hydroxylated metabolites;