Atazanavir drug interactions

As an inhibitor of CYP3A4 and CYP2C9, the potential for drug-drug interactions with atazanavir is great (Tables 49-3 and 49-4). Atazanavir AUC is reduced by 76% when combined with omeprazole thus, the combination is to be avoided. In addition, co-administration of atazanavir with other drugs that inhibit UGT1A1, such as indinavir and irinotecan, is contraindicated because of enhanced toxicity. Tenofovir and efavirenz should not be -administered with atazanavir unless ritonavir is added to boost levels. 

Subsequently, studies have shown that M3 can be administered successfully in a tablet form rather than by an oral solution. Also, two drug interaction clinical trials of M3, in combination with the approved HIV drugs ritonavir and atazanavir. 

NA /D, abd pain, bleeding, fevCT, T QT Interactions t Effects W7 atazanavir, clarithromycin, CT5rthromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfi-navir, ritonavir, saquinavir, telithromycin X effects W7 antacids, carbamazqjine, dexamethasone, phenobarbital, phenytoin, rifampicin, St. John s wort EMS Drug contains lactose, may cause D/abd discomfort in pts w/ lactose intolerance OD Sxs unknown symptomatic and supportive... 

Sunirinib (Sutent) [Kinase Inhibitor] Uses Advanced GI stromal tumor refractory/intolerant of imatinib advanced RCC Action Kinase inhibitor Dose Adults. 50 mg PO daily x 4 wk, followed by 2 wk holiday = 1 cycle 4- to 37.5 mg w/ CYP3A4 inhibitors (Table VI-8), to T 87.5 mg w/ CYP3A4 inducers Contra w/ atazanavir Caution [D, -] Multiple interactions require dose modification (eg, St. John s wort) Disp Caps SE -l WBC pit, bleeding, T BP, -l ejection fraction, T QT interval, pancreatitis, DVT, Sz, adrenal insuff, N/V/D, skin discoloration, oral ulcers, taste perversion, hypothyroidism Interactions Multiple interactions require dose modification (eg, St. John s wort) EMS Monitor ECG for T QT interval grapefruit juice may T adverse effects may affect potassium level (hypo-/hyperkalemia) monitor for S/Sxs of heart failure drug can 4- ejection fraction OD May cause abd pain, muscle weakness, and chills symptomatic and supportive... 

Buffered didanosine decreases the AUC of indinavir, and the drugs shouid be given one hour apart. Buffered didanosine interacts simiiarly with atazanavir. Tipranavir with low-dose ritonavir modestly reduced the AUC of abacavir and zidovudine, and such combinations are not recommended in the UK. The changes in pharmacokinetics seen when giving other combinations of protease inhibitors with NRTIs do not appear to be clinically significant. Protease inhibitors do not affect the intracellular activation of NRTIs. 

Lamivudine metabolism does not involve the cytochrome P450 isoenzyme CYP3A4. Therefore it is unlikely that it will interact with drugs, such as the protease inhibitors, whieh are metabolised by this system. No pharmacokinetic interaction appears to oeeur between lamivudine and amprenavir, - atazanavir, -" indinavir, and nelfinavir. The manufacturer of lopinavir/ritonavir notes that lamivudine did not alter the pharmacokinetics of lopinavir, - and tipranavir plus low-dose ritonavir did not cause a signifieant ehange in the AUC of lamivudine. - ... 

The UK manufacturer of indinavir states that a normal (acidic) gastric pH may be necessary for optimum absorption of indinavir. Any drug that increases the gastric pH could therefore potentially reduce absorption. Altered gastric pH may also account for the interaction with atazanavir. Cimetidine probably boosts saquinavir levels by inhibiting the first-pass metabolism of saquinavir. It is not understood why ranitidine and omeprazole increase saquinavir levels. 

Although information is limited, the pharmacokinetic interaction between the ethinylestradiol component of combined hormonal contraceptives and nelfinavir or ritonavir appears to be established and is likely to be clinically important. Similar decreases in plasma levels of ethinylestradiol caused by other drugs have resulted in reduced efficacy and reliability of combined oral contraceptives, and one retrospective report suggests that this has occurred with nelfinavir. It seem likely that the reduced contraceptive levels seen with fosamprenavir, lopinavir and tipranavir were due to the concurrent use of ritonavir (as would be common in practice). Similarly, although no interaction was reported with saquinavir, and raised contraceptive steroid levels were reported with amprenavir and atazanavir, in practice these drugs would be given with ritonavir (as a pharmacokinetic enhancer), and so the levels of combined hormonal contraceptives can reasonably be expected to be reduced. The Faculty ofFamily Planning... 

The interaction of methadone (20-175 mg/ day) and atazanavir/ritonavir (300/100 mg/ day) has been investigated in 24 HIV-1-positive patients, who were randomized to methadone or just the antiretroviral drugs [125. The dose of methadone correlated significantly with the maximum plasma concentration of atazanavir, resulting in a reduced plasma concentration. 

Drag-drag interactions Etravirine is metabolized by cytochrome P450 enzymes and interacts in vitro with high-dose ritonavir, atazanavir, fosamprenavir, rifampicin, and some antiepileptic drugs [159 ]. 

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