Table 1.
Anti-retroviral interactions with methadone and buprenorphine
| Medication | Effect on Methadone (METH) | Effect On Buprenorphine (BUP) | Effect on Anti-Viral (unless BUP or METH specified, both are assumed) | Comments | Ref. |
|---|---|---|---|---|---|
| NRTI | |||||
| Abacavir (ABC)a | ↑ clearance of methadone concentration | No PK study | ↓ Cmax by METH | No dose change required for METH | 137 |
| Didanosine (ddI) | No PK effect | No PK effect | METH ↓ ddI AUC by 57% for buffered tablet, partially corrected by EC capsule No BUP effect on ddI |
No dose adjustments necessary when EC capsule used with METH patients. | 133, 134, 174 |
| Emtricitabine (FTC) | No PK study | No PK study | No PK study | N/A | |
| Lamivudine (3TC) | No PK effect | No PK effect | No PK data on effect by METH No effect of BUP on 3TC |
AZT/3TC co-formulation studied only with METH. No dose adjustments necessary |
132, 174 |
| Stavudine (d4T) | No PK effect | No PK study | ↓ d4T AUC12h by 23% and Cmax by 44% | No dose adjustments necessary | 133 |
| Tenofovir (TDF) | No PK effect | No PK effect | No PK data on effect by METH No significant effect on TDF by BUP |
No dose adjustments necessary | 138, 174 |
| Zalcitabine (ddC) | No PK study | No PK study | No PK study | N/A | |
| Zidovudine (AZT) | No PK effect | No PK data, but patients did not experience opioid withdrawal. | ↑ AZT AUC by 40% by METH. No PK effect by BUP |
Watch for AZT related toxicity (symptoms and laboratory). Dose reductions of AZT may be required. | 129–132 |
| NNRTI | |||||
| Delavirdine (DLV) | ↑ AUC by 19%; ↑Cmax by 10% | ↑ AUC by 400%, without clinical effect | No PK effect | No dose adjustments necessary; however, should be used with caution as long-term effects (>7 days) unknown. | 109, 149, 150, |
| Efavirenz (EFV) | ↓ AUC by 57% | ↓ AUC by 50%, without clinical effect | No PK data on effect by METH No PK effect by BUP |
Opioid withdrawal form METH common. METH dose increase likely necessary. | 107, 109, 146, 147 |
| Etravirine (ETV) | No PK effect (only 100 BID of etravirine studied) | No PK study | No PK effect | No dose adjustments necessary | 151 |
| Lersivirine | No PK effect | No PK study | No PK study | No dose adjustments necessary | 153 |
| Nevirapine (NVP) | ↓ AUC by 41 to 52% (depending on the study) | No PK effect | No PK data on effect by METH No PK effect by BUP |
Opioid withdrawal form METH common. METH dose increase likely necessary. |
108, 110 140–145 |
| Rilpivirine (TMC278) | ↓ AUC of R-METH by 16%% ↓ AUC of S-METH by 16%% |
No PK study | No PK study | Monitoring for symptoms of METH withdrawal is recommended. | 152 |
| PI | |||||
| Amprenavir (AMP) | ↓ AUC of R-METH by 13% and S-METH by 25% | No PK study | ↓ AUC by 30% ↓ Cmax by 27% ↓ Cmin by 25% |
METH dose adjustments unnecessary. Clinical significance of AUC reduction in AMP unknown. | 157 |
| Atazanavir (ATV) | No PK effect | ↑ AUC by 167% | No PK effect with METH. Package insert states BUP may lower ATV plasma concentrations |
Some individuals may experience oversedation. Slower titration upwards of BUP may be advisable in some patients. ATV should be boosted with ritonavir when co-administered with BUP |
158, 177 |
| Darunavir (DRV) | ↓ R-METH AUC by 16% ↓ S-METH AUC by 36% |
↑ nor BUP AUC by 46% | No PK effect | No ARV dose change when combined with METH or BUP. Four subjects out of 16 in METH study reported mild opioid withdrawal, but no dose adjustments were needed. | 169, 181 |
| Fosamprenavir (fAMP) | ↓ AUC R-METH by 18% ↓ AUC S-METH by 43% |
No PK effect | No PK effect | No dose adjustments necessary | 159, 181 |
| Indinavir (IND) | No PK effect | No PK study | ↓ Cmax between 16% and 28% and ↑ Cmin between 50% and 100% | Differences do not appear to be clinically significant | 45, 155 |
| Lopinavir/ritonavir (LPV/r) | ↓ AUC by 26–36% | No PK effect | No PK study for METH No PK effect with BUP |
↓ AUC of METH caused by LPV. One study reported opioid withdrawal symptoms in 27% of patients. METH dose increase may be necessary in some patients. |
154, 163–166, 182, 183 |
| Nelfinavir | ↓ AUC by 40% | No PK effect | ↓ AUC of active M8 metabolite by 48% by METH | Despite ↓ METH AUC, clinical withdrawal is usually absent and a priori dosage adjustments are not needed. Decrease in AUC of M8 unlikely to be clinically significant. | 156, 162, 183 |
| Ritonavir (RTV) | ↓ AUC by 37% in one study and no effect in another (see text) | ↑ AUC by 157% | No PK effect | No dosage adjustments necessary | 154, 183 |
| Saquinavir (SQV) | ↓ AUC by 20–32% | No PK study | No PK study | Saquinavir boosted with ritonavir studied. Despite ↓ METH AUC, clinical withdrawal was not reported. | 160, 161 |
| Tipranavir (TPV) | ↓ METH plasma concentration by 50%a | ↓ Nor-BUP AUC by 80% | No ARV dose change when combined with METH. TPV/r AUC and Cmax decreased 19% and 25% respectively compared to historical controls in the presence of BUP |
METH dose may need to be increased. Clinical significance in the changes in TPV PK parameters in the presence of BUP are unknown. No BUP adjustment necessary. |
167, 184, 185 |
| Integrase | |||||
| Elvitegravir (with cobicistat) | No PK effect | ↑ AUC by 35% | No PK effect | No clinical effect requiring dosage adjustments. Cobicistat dosed at 150 mg daily. | 128 |
| Raltegravir | No PK effect | No PK effect | No PK effect | No clinical effect requiring dosage adjustments | 170, 186 |
| CCR5 Antagonists | |||||
| Maraviroc | No PK study | No PK study | No PK study | N/A | |
a
Decrease in methadone not specified as AUC or Cmax.
NRTI, nucleoside reverse transcriptase inhibitors; NNRTI, non-nucleoside reverse transcriptase inhibitors; PI, protease inhibitor; AUC, area under curve; METH, methadone; BUP, buprenorphine; norBUP, norbuprenorphine. (Updated with permission from Bruce et al. [18]).