Drug-Drug Interactions
Table 24f. Drug Interactions Between HIV-1 gp120-Directed Attachment Inhibitors and Other Drugs (Including Antiretroviral Agents)
Fostemsavir (FTR), an HIV-1 gp120-directed attachment inhibitor, is a prodrug of temsavir (TMR). In this table, the effect on gp120-directed attachment inhibitor refers to TMR concentrations. Recommendations for managing a particular drug interaction may differ depending on whether a new antiretroviral (ARV) drug is being initiated in a patient on a stable concomitant medication or whether a new concomitant medication is being initiated in a patient on a stable ARV regimen. The magnitude and significance of drug interactions are difficult to predict when several drugs with competing metabolic pathways are prescribed concomitantly. Providers should exercise their clinical judgment to select the most appropriate alternative medication to use in cases where an interacting drug needs to be replaced with an alternative.
| Concomitant Drug Class/Name | Effect on gp120-Directed Attachment Inhibitor and/or Concomitant Drug Concentrations | Dosing Recommendations and Clinical Comments |
|---|---|---|
| Acid Reducers | ||
| H2 Receptor Antagonists | ↔ TMR | No dose adjustment needed |
| Anticonvulsants | ||
| Carbamazepine, Phenobarbital, Phenytoin | ↓ TMR expected | Contraindicated |
| Antibacterials—Antimycobacterials | ||
| Rifabutin | With Rifabutin 300 mg Once Daily and Without RTV
With Rifabutin 150 mg Once Daily and With RTV 100 mg Once Daily
| If Used Without PI/r
If Used With PI/r
|
| Rifampin | TMR AUC ↓ 82% | Contraindicated |
| Rifapentine | Daily and Weekly Dosing ↓ TMR expected | Do not coadminister. |
| Antivirals—Hepatitis C Direct-Acting Antivirals | ||
| Elbasvir/Grazoprevir | ↑ grazoprevir expected | Increased grazoprevir exposures may increase the risk of ALT elevations. Use an alternative HCV regimen. |
| Ledipasvir/Sofosbuvir | ↔ expected | No dose adjustment needed |
| Glecaprevir/Pibrentasvir | ↔ expected | No dose adjustment needed |
| Sofosbuvir | ↔ expected | No dose adjustment needed |
| Sofosbuvir/Velpatasvir | ↔ expected | No dose adjustment needed |
| Sofosbuvir/Velpatasvir/Voxilaprevir | ↑ voxilaprevir expected | Use an alternative HCV regimen if possible. |
| Antivirals—Miscellaneous (e.g., for CMV, Mpox) | ||
| Brincidofovir | ↑ brincidofovir possible | Give FTR dose at least 3 hours after administering brincidofovir, and monitor for brincidofovir-related adverse events (i.e., elevations in ALT/AST and bilirubin and GI adverse events). |
| Cidofovir | ↔ TMR expected | No dose adjustment needed |
| Tecovirimat | ↔ TMR expected | No dose adjustment needed |
| Antivirals—SARS-CoV-2 | ||
| Molnupiravir | ↔ expected | No dose adjustment needed |
| Ritonavir-Boosted Nirmatrelvir | TMR AUC ↑ 45% | No dose adjustment needed |
| Remdesivir | ↔ expected | No dose adjustment needed |
| Herbal Products | ||
| St. John’s Wort | ↓ TMR expected | Contraindicated |
| Hormonal Therapies | ||
| Hormonal Contraceptives | Ethinyl estradiol AUC ↑ 40% ↔ norethindrone | Prescribe oral contraceptive that contains no more than 30 mcg of ethinyl estradiola or use alternative ARV or contraceptive methods. |
Gender-Affirming Hormone Therapies (e.g., estradiol, 5-alpha reductase inhibitors, testosterone) | ↑ estradiol possible | Use lowest effective dose for estrogen-containing regimens. |
Menopausal Hormone Replacement Therapy (e.g., conjugated estrogens, drospirenone, estradiol, medroxyprogesterone, progesterone) | ↑ estrogens, estradiol possible | Use lowest effective dose for estrogen-containing regimens. |
| Lipid-Modifying Agents | ||
| Atorvastatin, Fluvastatin, Pitavastatin, Simvastatin | ↑ statin possible ↔ expected | Increased statin concentration may not be clinically relevant. Follow clinical guidelines. Administer the lowest effective statin dose while monitoring for adverse events. |
| Rosuvastatin | Rosuvastatin AUC ↑ 69% | Increased rosuvastatin concentration may not be clinically relevant. Follow clinical guidelines. Administer the lowest effective dose while monitoring for adverse events. |
| Narcotics and Treatment for Opioid Dependence | ||
| Buprenorphine/Naloxone | Buprenorphine AUC ↑ 30% Norbuprenorphine (active metabolite) AUC ↑ 39% | No dose adjustment needed |
| Methadone | ↔ Total methadone ↔ R(−) methadone (active metabolite) ↔ S(+) methadone | No dose adjustment needed |
| Antiretroviral Drugs | ||
| Capsid Inhibitor | ||
| LEN (SQ and PO) | ↔ TMR expected ↔ LEN expected | No dose adjustment needed |
| CCR5 Antagonist | ||
| MVC | ↔ TMR MVC AUC ↑ 25% | No dose adjustment needed |
| CD4 Post-Attachment Inhibitor | ||
| IBA | ↔ expected | No dose adjustment needed |
| INSTIs | ||
| BIC, CAB (IM and PO), DTG, EVG/c | ↔ TMR expected | No dose adjustment needed |
| RAL plus TDF | ↔ TMR | No dose adjustment needed |
| NRTIs | ||
| TDF | ↔ TMR ↔ TDF | No dose adjustment needed |
| NNRTIs | ||
| DOR, RPV (IM and PO) | ↔ TMR expected | No dose adjustment needed |
| EFV | ↓ TMR possible ↔ EFV expected | No dose adjustment needed |
| ETR | TMR AUC ↓ 50% ↔ ETR | No dose adjustment needed |
| ETR plus DRV/r | TMR Cmax and AUC ↑ 34% to 53% ↔ DRV, RTV ETR AUC ↑ 28% | No dose adjustment needed |
| PIs | ||
| ATV/c | ↑ TMR expected ↔ ATV expected | No dose adjustment needed |
| ATV/r | TMR Cmax and AUC ↑ 54% to 58% ↔ ATV, RTV | No dose adjustment needed |
| DRV/c | TMR Cmax and AUC ↑ 79% to 97% ↔ DRV, RTV expected | No dose adjustment needed |
| DRV/r | TMR Cmax and AUC ↑ 52% to 63% ↔ DRV, RTV | No dose adjustment needed |
| a The following products contain no more than 30 mcg of ethinyl estradiol combined with norethindrone or norgestimate: Lo Minastrin Fe; Lo Loestrin Fe; Loestrin 1/20, 1.5/30; Loestrin Fe 1/20, 1.5/30; Loestrin 24 Fe; Minastrin 24 Fe; Ortho Tri-Cyclen Lo. Generic formulations also may be available. Key to Symbols: ↑ = increase ↓ = decrease ↔ = less than 20% change in AUC Key: ALT = alanine aminotransferase; ARV = antiretroviral; AST = aspartate aminotransferase; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; BIC = bictegravir; Cmax = maximum plasma concentration; CAB = cabotegravir; CCR5 = C-C chemokine receptor type 5; CMV = cytomegalovirus; DOR = doravirine; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG/c = elvitegravir/cobicistat; FTR = fostemsavir; GI = gastrointestinal; gp120 = glycoprotein 120; HCV = hepatitis C virus; IBA = ibalizumab; IM = intramuscular; INSTI = integrase strand transfer inhibitor; LEN = lenacapavir; MVC = maraviroc; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PI/r = ritonavir-boosted PI; PO = orally; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SQ = subcutaneous; TDF = tenofovir disoproxil fumarate; TMR = temsavir | ||
Drug-Drug Interactions
Table 24f. Drug Interactions between HIV-1 gp120-Directed Attachment Inhibitors and Other Drugs (Including Antiretroviral Agents)
| Concomitant Drug Class/Name | Effect on gp120-Directed Attachment Inhibitor and/or Concomitant Drug Concentrations | Dosing Recommendations and Clinical Comments |
|---|---|---|
| Acid Reducers | ||
| H2 Receptor Antagonists | ↔ TMR | No dose adjustment needed |
| Anticonvulsants | ||
| Carbamazepine, Phenobarbital, Phenytoin | ↓ TMR expected | Contraindicated |
| Antibacterials—Antimycobacterials | ||
| Rifabutin | With Rifabutin 300 mg Once Daily and Without RTV
With Rifabutin 150 mg Once Daily and With RTV 100 mg Once Daily
| If Used Without PI/r
If Used With PI/r
|
| Rifampin | TMR AUC ↓ 82% | Contraindicated |
| Rifapentine | Daily and Weekly Dosing ↓ TMR expected | Do not coadminister. |
| Antivirals—Hepatitis C Direct-Acting Antivirals | ||
| Elbasvir/Grazoprevir | ↑ grazoprevir expected | Increased grazoprevir exposures may increase the risk of ALT elevations. Use an alternative HCV regimen. |
| Ledipasvir/Sofosbuvir | ↔ expected | No dose adjustment needed |
| Glecaprevir/Pibrentasvir | ↔ expected | No dose adjustment needed |
| Sofosbuvir | ↔ expected | No dose adjustment needed |
| Sofosbuvir/Velpatasvir | ↔ expected | No dose adjustment needed |
| Sofosbuvir/Velpatasvir/Voxilaprevir | ↑ voxilaprevir expected | Use an alternative HCV regimen if possible. |
| Antivirals—Miscellaneous (e.g., for CMV, Mpox) | ||
| Brincidofovir | ↑ brincidofovir possible | Give FTR dose at least 3 hours after administering brincidofovir, and monitor for brincidofovir-related adverse events (i.e., elevations in ALT/AST and bilirubin and GI adverse events). |
| Cidofovir | ↔ TMR expected | No dose adjustment needed |
| Tecovirimat | ↔ TMR expected | No dose adjustment needed |
| Antivirals—SARS-CoV-2 | ||
| Molnupiravir | ↔ expected | No dose adjustment needed |
| Ritonavir-Boosted Nirmatrelvir | TMR AUC ↑ 45% | No dose adjustment needed |
| Remdesivir | ↔ expected | No dose adjustment needed |
| Herbal Products | ||
| St. John’s Wort | ↓ TMR expected | Contraindicated |
| Hormonal Therapies | ||
| Hormonal Contraceptives | Ethinyl estradiol AUC ↑ 40% ↔ norethindrone | Prescribe oral contraceptive that contains no more than 30 mcg of ethinyl estradiola or use alternative ARV or contraceptive methods. |
Gender-Affirming Hormone Therapies (e.g., estradiol, 5-alpha reductase inhibitors, testosterone) | ↑ estradiol possible | Use lowest effective dose for estrogen-containing regimens. |
Menopausal Hormone Replacement Therapy (e.g., conjugated estrogens, drospirenone, estradiol, medroxyprogesterone, progesterone) | ↑ estrogens, estradiol possible | Use lowest effective dose for estrogen-containing regimens. |
| Lipid-Modifying Agents | ||
| Atorvastatin, Fluvastatin, Pitavastatin, Simvastatin | ↑ statin possible ↔ expected | Increased statin concentration may not be clinically relevant. Follow clinical guidelines. Administer the lowest effective statin dose while monitoring for adverse events. |
| Rosuvastatin | Rosuvastatin AUC ↑ 69% | Increased rosuvastatin concentration may not be clinically relevant. Follow clinical guidelines. Administer the lowest effective dose while monitoring for adverse events. |
| Narcotics and Treatment for Opioid Dependence | ||
| Buprenorphine/Naloxone | Buprenorphine AUC ↑ 30% Norbuprenorphine (active metabolite) AUC ↑ 39% | No dose adjustment needed |
| Methadone | ↔ Total methadone ↔ R(−) methadone (active metabolite) ↔ S(+) methadone | No dose adjustment needed |
| Antiretroviral Drugs | ||
| Capsid Inhibitor | ||
| LEN (SQ and PO) | ↔ TMR expected ↔ LEN expected | No dose adjustment needed |
| CCR5 Antagonist | ||
| MVC | ↔ TMR MVC AUC ↑ 25% | No dose adjustment needed |
| CD4 Post-Attachment Inhibitor | ||
| IBA | ↔ expected | No dose adjustment needed |
| INSTIs | ||
| BIC, CAB (IM and PO), DTG, EVG/c | ↔ TMR expected | No dose adjustment needed |
| RAL plus TDF | ↔ TMR | No dose adjustment needed |
| NRTIs | ||
| TDF | ↔ TMR ↔ TDF | No dose adjustment needed |
| NNRTIs | ||
| DOR, RPV (IM and PO) | ↔ TMR expected | No dose adjustment needed |
| EFV | ↓ TMR possible ↔ EFV expected | No dose adjustment needed |
| ETR | TMR AUC ↓ 50% ↔ ETR | No dose adjustment needed |
| ETR plus DRV/r | TMR Cmax and AUC ↑ 34% to 53% ↔ DRV, RTV ETR AUC ↑ 28% | No dose adjustment needed |
| PIs | ||
| ATV/c | ↑ TMR expected ↔ ATV expected | No dose adjustment needed |
| ATV/r | TMR Cmax and AUC ↑ 54% to 58% ↔ ATV, RTV | No dose adjustment needed |
| DRV/c | TMR Cmax and AUC ↑ 79% to 97% ↔ DRV, RTV expected | No dose adjustment needed |
| DRV/r | TMR Cmax and AUC ↑ 52% to 63% ↔ DRV, RTV | No dose adjustment needed |
| a The following products contain no more than 30 mcg of ethinyl estradiol combined with norethindrone or norgestimate: Lo Minastrin Fe; Lo Loestrin Fe; Loestrin 1/20, 1.5/30; Loestrin Fe 1/20, 1.5/30; Loestrin 24 Fe; Minastrin 24 Fe; Ortho Tri-Cyclen Lo. Generic formulations also may be available. Key to Symbols: ↑ = increase ↓ = decrease ↔ = less than 20% change in AUC Key: ALT = alanine aminotransferase; ARV = antiretroviral; AST = aspartate aminotransferase; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; BIC = bictegravir; Cmax = maximum plasma concentration; CAB = cabotegravir; CCR5 = C-C chemokine receptor type 5; CMV = cytomegalovirus; DOR = doravirine; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG/c = elvitegravir/cobicistat; FTR = fostemsavir; GI = gastrointestinal; gp120 = glycoprotein 120; HCV = hepatitis C virus; IBA = ibalizumab; IM = intramuscular; INSTI = integrase strand transfer inhibitor; LEN = lenacapavir; MVC = maraviroc; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PI/r = ritonavir-boosted PI; PO = orally; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; SQ = subcutaneous; TDF = tenofovir disoproxil fumarate; TMR = temsavir | ||
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