Stavudine Methadone

Drugs that may affect didanosine include allopurinol, methadone, and ganciclovir. Drugs that may be affected by didanosine include ganciclovir, antacids, antifungal agents, antiretroviral drugs, fluoroquinolones, and stavudine. 

Drugs that may interact with stavudine include didanosine, doxorubicin, hydroxyurea, methadone, ribavirin, and zidovudine. 

Drugs that may affect zidovudine include acetaminophen, atovaquone, bone marrow suppressive/cytotoxic agents (eg, adriamycin, dapsone), clarithromycin, doxorubicin, fluconazole, ganciclovir, methadone, nelfinavir/ritonavir, phenytoin, probenecid, ribavirin, rifamycins, stavudine, trimethoprim, and valproic acid. 

Drugs that may be affected by peginterferon alfa-2a include theophylline, methadone, and NRTIs (eg, didanosine, zidovudine, stavudine). 

A 35-year old Caucasian man with AIDS and multiple opportunistic infections, including Mycobacterium kansasii and Mycobacterium avium complex (MAC) disease developed moderate to severe primary sensorineural hearing loss after 4—5 months of therapy with oral azithromycin 500 mg/day. Other medications included ethambutol, isoniazid, rifabutin, ciprofloxacin, co-trimoxazole, fluconazole, zidovudine (later switched to stavudine), lamivudine, indinavir, methadone, mod-ified-release oral morphine, pseudoephedrine, diphenhydramine, megestrol acetate, trazodone, sorbitol, salbutamol by metered-dose inhaler and nebulizer, ipratropium, and oral morphine solution as needed. Significant improvement of the hearing impairment was documented 3 weeks after drug withdrawal. 

In those who are opioid-dependent, methadone can facilitate adherence to HAART regimens. The pharmacokinetics of the tablet formulations of didanosine and stavudine have been studied in 17 individuals taking stable methadone therapy in comparison with 10 untreated controls (33). Methadone reduced the AUCo 6 by 63% for didanosine and by 25% for stavudine and the C ax by 66% and 44% respectively. These effects appeared to result primarily from reduced systemic availability. Trough concentrations of methadone were comparable to those seen in historical controls, suggesting that the nucleoside analogues did not affect methadone disposition. The authors concluded that larger doses of the tablet formulation (or another type of formulation) may be necessary to provide HAART in subjects taking methadone. 

Zidovudine had no effect on methadone levels in one study, but there is one report of a patient requiring a modest increase in methadone dose after starting zidovudine. Similarly case reports describe patients requiring a modest increase in methadone dose after starting abacavir. Methadone can increase zidovudine serum levels, and reduce levels of abacavir, stavudine, and didano-sine from the tablet formulation, but not the enteric-coated capsule preparation. Tenofovir, and a single dose of zidovu-dine/lamivudine had no effect on methadone pharmacokinetics. 

A study in 17 subjects taking methadone found that the AUC and maximum levels of stavudine were 23% and 44% lower, respectively, when compared with 10 control subjects. Trough levels of methadone did not differ from historical controls suggesting that stavudine had no effect on methadone pharmacokinetics. ... 

Uncertain. It appears that methadone reduces the bioavailability of dida-nosine, and to a lesser extent, stavudine, possibly because it delays gastric emptying. Thus, the enteric-coated didanosine preparation appears not to be affected. Conversely, methadone apparently reduces the glucuroni-dation of the zidovudine by the liver, resulting in an increase in its serum levels. Methadone may also reduce renal clearance of zidovudine."... 

The reduction in stavudine levels and the changes in abacavir peak levels with methadone are probably not clinically relevant, but again, further data are required. The reports with abacavir suggest that it would be prudent to monitor methadone dose requirements when this drug is started. Tenofovir does not appear to affect methadone levels. 

An HIV-positive patient taking methadone 90 mg daily with indinavir, lamivudine and zidovudine, developed withdravral symptoms and was hospitalised within a week of stopping these HIV drugs and starting ritonavir 400 mg, saquinavir 400 mg and stavudine 40 mg twice daily. The patient was eventually re-stabilised taking methadone 130 mg daily. ... 

Simultaneous didanosine, folic acid, ganciclovir, lamivudine, nevirapine, pyrazinamide, ranitidine, rifampin, stavudine, sulfamethoxazole, trimethoprim, zidovudine Noninterfering adefovir, amprenavir, delavirdine, efavirenz, fluconazole, indinavir, itraconazole, methadone, nelfinavir, oxazepam, pyrimethamine, rifampin, ritonavir, saquinavir, zalcitabine... 

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