Updated
Reviewed
Jun. 03, 2021

Drug-Drug Interactions

HIV-1 gp120-Directed Attachment Inhibitors and Other Drugs

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 judgement to select the most appropriate alternative medication to use in cases where an interacting drug needs to be replaced with an alternative.

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.
Antibacterials
Antimycobacterials
Rifabutin

With Rifabutin 300 mg once daily and without RTV

  • TMR AUC ↓ 30%

With Rifabutin 150 mg once daily and with RTV 100 mg once daily

  • TMR AUC ↑ 66%

If Used Without PI/r:

  • No dosage adjustment needed.

If Used With PI/r:

  • Recommended dose is rifabutin 150 mg once daily.
  • No dosage adjustment of FTR.
Rifampin TMR AUC ↓ 72% Contraindicated
Rifapentine ↓ MVC expected Do not coadminister.
Anticonvulsants
Carbamazepine, Phenobarbital, Phenytoin ↓ TMR expected Contraindicated.
Hepatitis C Direct-Acting Antivirals
Daclatasvir ↔ expected No dose adjustment needed.
Dasabuvir plus Ombitasvir/Paritaprevir/RTV ↔ expected No dose adjustment needed.
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 ↑ voxilaprevir expected Use an alternative HCV regimen if possible.
Herbal Products
St. John’s Wort ↓ TMR expected Contraindicated.
Hormonal Therapies
Contraceptives: Oral

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.
Menopausal Hormone Replacement Therapy No data No data available to make dose recommendation. 
Gender-Affirming Hormone Therapies No data No data available to make dose recommendation. 
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
CCR5 Antagonist
MVC

↔ TMR

MVC AUC ↑ 25%

No dose adjustment needed.
INSTIs
BIC, CAB (IM or PO), DTG, EVG/c ↔ TMR expected No dose adjustment needed.
RAL + TDF ↔ TMR No dose adjustment needed.
NRTIs
TDF

↔ TMR

↔ TDF

No dose adjustment needed.
NNRTIs
DOR, RPV (IM or 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 + DRV/r

TMR Cmax and AUC ↑ 34% to 53%

↔ DRV, RTV

ETR AUC ↑ 28%

No dose adjustment needed.
PIs
ATV, ATV/c

↑ TMR possible

↔ 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.
LPV/r

↑ TMR possible

↔ LPV expected

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
↔ = no change

Key: ALT = alanine aminotransferase; ARV = antiretroviral; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; BIC = bictegravir; Cmax = maximum plasma concentration; CAB = cabotegravir; DOR = doravirine; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; FTR = fostemsavir; INSTI = integrase strand transfer inhibitor; HCV = hepatitis C virus; IM = intramuscular; LPV = lopinavir; LPV/r = lopinavir/ritonavir; MVC = maraviroc; NNRTI = non-nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PI/r = ritonavir-boosted PI; PO = by mouth; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; TDF = tenofovir disoproxil fumarate; TMR = temsavir

Drug-Drug Interactions

HIV-1 gp120-Directed Attachment Inhibitors and Other Drugs

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 judgement to select the most appropriate alternative medication to use in cases where an interacting drug needs to be replaced with an alternative.

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.
Antibacterials
Antimycobacterials
Rifabutin

With Rifabutin 300 mg once daily and without RTV

  • TMR AUC ↓ 30%

With Rifabutin 150 mg once daily and with RTV 100 mg once daily

  • TMR AUC ↑ 66%

If Used Without PI/r:

  • No dosage adjustment needed.

If Used With PI/r:

  • Recommended dose is rifabutin 150 mg once daily.
  • No dosage adjustment of FTR.
Rifampin TMR AUC ↓ 72% Contraindicated
Rifapentine ↓ MVC expected Do not coadminister.
Anticonvulsants
Carbamazepine, Phenobarbital, Phenytoin ↓ TMR expected Contraindicated.
Hepatitis C Direct-Acting Antivirals
Daclatasvir ↔ expected No dose adjustment needed.
Dasabuvir plus Ombitasvir/Paritaprevir/RTV ↔ expected No dose adjustment needed.
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 ↑ voxilaprevir expected Use an alternative HCV regimen if possible.
Herbal Products
St. John’s Wort ↓ TMR expected Contraindicated.
Hormonal Therapies
Contraceptives: Oral

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.
Menopausal Hormone Replacement Therapy No data No data available to make dose recommendation. 
Gender-Affirming Hormone Therapies No data No data available to make dose recommendation. 
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
CCR5 Antagonist
MVC

↔ TMR

MVC AUC ↑ 25%

No dose adjustment needed.
INSTIs
BIC, CAB (IM or PO), DTG, EVG/c ↔ TMR expected No dose adjustment needed.
RAL + TDF ↔ TMR No dose adjustment needed.
NRTIs
TDF

↔ TMR

↔ TDF

No dose adjustment needed.
NNRTIs
DOR, RPV (IM or 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 + DRV/r

TMR Cmax and AUC ↑ 34% to 53%

↔ DRV, RTV

ETR AUC ↑ 28%

No dose adjustment needed.
PIs
ATV, ATV/c

↑ TMR possible

↔ 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.
LPV/r

↑ TMR possible

↔ LPV expected

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
↔ = no change

Key: ALT = alanine aminotransferase; ARV = antiretroviral; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; AUC = area under the curve; BIC = bictegravir; Cmax = maximum plasma concentration; CAB = cabotegravir; DOR = doravirine; DRV = darunavir; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; FTR = fostemsavir; INSTI = integrase strand transfer inhibitor; HCV = hepatitis C virus; IM = intramuscular; LPV = lopinavir; LPV/r = lopinavir/ritonavir; MVC = maraviroc; NNRTI = non-nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; PI/r = ritonavir-boosted PI; PO = by mouth; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; TDF = tenofovir disoproxil fumarate; TMR = temsavir

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