Rashes NNRTI

NVP—see SJS advise patient to report first sign of rash recommend avoiding other NNRTIs in patients with severe rash to one NNRTI... 

Deravirdine (Rescnptor) [Antiretroviral/NNRTI] Uses HIV Infxn Action Nonnucleoside RT inhibitor Dose 400 mg PO tid Caution [C, ] CDC recommends HIV-infected mothers not to breast-feed (transmission risk) w/ renal/hepatic impair Contra Use w/ drugs dependent on CYP3A for clearance (Table VI-8) Disp Tabs SE Fat redistribution, immune reconstitution synd, HA, fatigue, rash, T transaminases, N/V/D Interactions T Effects W/ fluoxetine T effects OF benzodiazepines, cisapride, clarithromycin, dapsone, ergotamine, indinavir, lovastatin, midazolam, nifedipine, quinidine, ritonavir, simvastatin, terfena-dine, triazolam, warfarin effects W/ antacids, barbiturates, carbamazepine, cimetidine, famotidine, lansoprazole, nizatidine, phenobarbital, phenytoin, ranitidine, rifabutin, rifampin effects OF didanosine EMS Use of benzodiazepines and CCBs should be avoided may cause a widespread rash located on upper body and arms OD May cause an extension of nl SEs symptomatic and supportive Deferasirox (Exjade) [Iron Chelator] Uses Chronic iron overload d/t transfusion in pts >2 y Action Oral iron chelator Dose Initial 20 mg/kg... 

Efavirenz (Sustiva) [Antiretroviral/NNRTI] Uses Hiv infxns Action Antiretroviral nonnucleoside RTI Dose Adults. 600 mg/d PO qhs Feds. See package insert avoid high-fat meals Caution [D, ] CDC recommends HIV-infected mothers not breast-feed Contra Component sensitivity Disp Caps SE Somnolence, vivid dreams, dizziness, rash, N/V/D Interactions T Effects W/ ritonavir T effects OF CNS depressants, ergot derivatives, midazolam, ritonavir, simvastatin, triazolam, warfarin X effects W/ carbamazepine, phenobarbital, rifabutin, rifampin, saquinavir, St. John s wort i effects OF amprenavir, carbamazepine, clarithromycin, indinavir, phenobarbital, saquinavir, warfarin may alter effectiveness OF OCPs EMS Concurrent EtOH usage can t CNS d ression OD May cause muscle contractions and adverse CNS effects activated charcoal may be effective... 

Efavirenz (Sustiva) is approved for the therapy of HIV infection of adults and children and is also used for postexposure prophylaxis. It is the only NNRTI approved for once-daUy dosing. Rash, although rarely severe, is a common adverse effect of efavirenz. Elevated liver enzymes and serum cholesterol also may occur. Central nervous system (CNS) effects in approximately half of patients may include dizziness, headache, insomnia, drowsiness, euphoria, agitation, impaired cognition, nightmares, vivid dreams, and hallucinations. These effects often subside after several weeks to months of therapy. 

Delavirdine NNRTI 400 mg tid Separate dosing from ddl or antacids by 1 h Rash, t liver enzymes, headache, nausea, diarrhea See footnote 4 for contraindicated medications. Also avoid concurrent fosamprenavir and rifabutin. Teratogenic in rats... 

Etravirine NNRTI 200 mg bid Take after a meal do not take on an empty stomach. Rash, nausea, diarrhea See footnote 4 for contraindicated medications. Do not administer with other NNRTIs, indinavir, atazanavir-ritonavir, fosamprenavir-ritonavir, tipranavir-ritonavir, or any unboosted PI... 

Nevirapine NNRTI 200 mg bid. Adjust dose in hepatic insufficiency Dose-escalate from 200 mg daily over 14 days to decrease frequency of rash Rash, hepatitis (occasionally fulminant), nausea, headache See footnote 4 for contraindicated medications... 

Skin rashes are the most common side effect of the NNRTIs, and efavirenz may cause nervous system symptoms such as headache, dizziness, and insomnia.41... 

Efavirenz NNRTI 600 mg qd Not to be taken with a fatty meal Dizziness, insomnia, rash, transaminitis Embryotoxic see footnote 2 for concurrent drug contraindication s... 

A syndrome of drug hypersensitivity has been described in patients receiving NNRTIs as well as in those receiving amprenavir or abacavir. Serious rashes, including Stevens-Johnson syndrome, have occurred. 

CLARITHROMYCIN NNRTIs 1. i efficacy of clarithromycin but t efficacy and adverse effects of the active metabolite 2. A rash occurs in 46% of patients when efavirenz is given with clarithromycin 1. Uncertain possibly due to altered CYP3A4-mediated metabolism 2. Uncertain 1. Clinical significance unknown no dose adjustment is recommended when clarithromycin is co-adminis-tered with nevirapine, but monitor LFTs and activity against Mycobacterium avium intracellulare complex closely 2. Consider alternatives to clarithromycin for patients on efavirenz... 

In a review of the medical records of HIV-positive patients who had taken nevirapine, delavirdine, or both, the frequency of skin reactions was determined, as were the consequences of rechallenge with the same or the alternative agent (17). The overall incidence of rash attributed to the use of one of the non-nucleoside reverse transcriptase inhibitors (NNRTIs) was 37%. While rash due to delavirdine was more common (8/20 versus 25/69), the rash due to nevirapine was more severe and necessitated more frequent hospitalization. Rash recurred in six of eight patients who were rechallenged with the same agent and in seven of 10 who were switched to the alternative agent. The conclusion was drawn that there is little value in attempting to re-treat patients who have had skin reactions to NNRTIs, except possibly those with limited treatment options. 

The efficacy and safety of abacavir (NRTI) and efavirenz (NNRTI) plus background therapy have been retrospectively evaluated in 50 patients, who had previously been treated with HAART (3). There was some immunological benefit, albeit limited, in most of the patients. Adverse effects were not mentioned in detail, but the dropout rate during the first 4 weeks of treatment was high, owing to skin rashes and hypersensitivity reactions. 

Of 80 injecting drug users who took two NRTIs + nevirapine (NNRTI), 20 discontinued treatment and 20 had treatment failures (4). Adverse events led to withdrawal of therapy in 10 patients eight had a rash (in one case Stevens-Johnson sjmdrome), one... 

In infants and children assigned to different combinations of one or two NRTIs plus an NNRTI and/or a protease inhibitor, the numbers of patients with moderate or severe adverse events were as shown in Table 2 (6). In cases of rash, the rash was worse in those who were taking nevirapine-containing regimens. 

As with any medication, adverse effects occur with antiretroviral agents that may limit the patient s ability to tolerate medication. Several important adverse effects have been recognized with the currently available antiretrovirals. These include mitochondrial toxicity with NRTIs, rash with NNRTIs, and metabolic perturbations with Pis. A discussion on the specific presentation and management of these adverse effects is beyond the scope of this chapter but can be found elsewhere. " ... 

D. Efavirenz This NNRTI has been shown to be effective in HIV treatment when used in combination with two NRTIs. Efavirenz is metabolized by hepatic cytochromes P450 and is frequently involved in drug interactions. Toxicity of efavirenz includes CNS dysfunction, skin rash, and elevations of plasma cholesterol. The drug should be avoided in pregnancy since fetal abnormalities have been reported in animals. 

Normucleoside reverse transcriptase inhibitor (NNRTI) used in combination regimens for HIV. Tox skin rash, CNS effects. Other NNRTIs delavirdine, nevirapine. 

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