Drug-Drug Interactions by Common Medication Class

Drug-Drug Interactions by Common Medication Class

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

The following tables are not meant to serve as a definitive resource on all possible drug-drug interactions between common antiretroviral (ARV) and non-ARV drugs. Instead, they offer a brief introduction to the management of interactions between medications used to treat HIV and comorbidities commonly seen in primary care settings. The tables are organized by common disease state and prioritized by those most commonly seen in primary care. Within each table, the medications are prioritized according to the preference the NYSDOH AI and the U.S. Department of Health and Human Services gives each class of medications in the initial management of HIV. The appropriate management of HIV should be individualized according to patient-specific factors, and not all ARVs may be suitable for all patients.

In the event that an ARV does not have a clinically significant interaction with the class of medications described, it is still listed in the table. If an interaction is theoretical but its significance is unknown, the recommendation to monitor for safety and efficacy is provided. Drugs within a class that may have a significant interaction are described within the table. Other drugs that do not have clinically significant drug-drug interactions with ARVs but were reviewed are described in the footnotes of the individual tables. If a drug does not appear in the table or the footnotes, exercise extra caution when prescribing this medication to patients with HIV or AIDS. The resources provided here might be valuable for clinicians who seek more guidance on drug-drug interactions related to ARV medications.

The informational material found within these tables is based on previously referenced primary, secondary, and tertiary literature, as well as the various publically available databases described in the Resources section. Further information may be found in the literature, including the U.S. Food and Drug Administration’s reports or manufacturer’s prescribing information (package inserts), which are also available online for each of the listed pharmacologic agents. If healthcare providers are interested in learning more about specific drug-drug interactions or seek further information about the methodology of the research or the mechanisms and management of these interactions, they are encouraged to utilize these resources.

Consultation with an experienced HIV care provider is also recommended when assistance is needed in choosing an antiretroviral therapy regimen for a patient who has multiple comorbidities and may have multiple drug-drug interactions. For help locating an experienced HIV care provider, contact the Clinical Education Initiative at 866-637-2342.

KEY POINT
  • Medications used to treat epilepsy, various types of malignancies, and tuberculosis, and those used to prevent graft-versus-host disease in solid organ transplants are known to interact with several ARV agents. Because of the serious nature of these conditions and the complexity of their treatment, many details of the specific interactions of these drugs have not been reviewed here. Clinicians should consult with the appropriate specialty service when questions arise pertaining to the management of these conditions.

Common Oral Antibiotics

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 15: Common Oral Antibiotics
→ Penicillins, cephalosporins, tetracyclines, macrolides, fluoroquinolones, sulfamethoxazole-trimethoprim*, linezolid, dapsone
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Dolutegravir (DTG)
  • Bictegravir (BIC)
  • Raltegravir (RAL)
  • Elvitegravir (EVG), boosted
  • Boosted PIs
  • Rilpivirine (RPV)
  • Efavirenz (EFV)
  • Etravirine (ETR)
No significant interactions. No dose adjustments necessary.

Abbreviations: NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; TDF, tenofovir disproxil fumarate

Note: Penicillins and cefalexin are eliminated mainly by organic anion transporters, so may compete with TDF for active tubular excretion, thus increasing concentrations of both drugs. Because of the limited duration of most penicillin regimens, the significance of this interaction is expected to be quite small.

*Trimethoprim blocks creatinine secreation and could accentuate the effects of cobicistat, BIC, and DTG.

Drugs Used as Antihypertensive Agents

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 16: Drugs Used as Antihypertensive Agents
→ Angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), beta blockers, direct renin inhibitors, diuretics
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Raltegravir (RAL)
  • Rilpivirine (RPV)

No significant interactions expected.

No dose adjustments necessary.
Dolutegravir (DTG) or bictegravir (BIC)
  • Atenolol: Eliminated via OCT2 and MATE1, which are inhibited by DTG and BIC; limited potential for atenolol levels to increase if given with these INSTIs.
  • ACE inhibitors, ARBs, CCBs, aliskiren, diuretics: No significant interactions expected.
  • Atenolol: Start at lower dose and adjust until desired clinical effect is achieved. Ifa patient is already on atenolol but starting DTG or BIC, monitor for atenolol-related adverse events. Reduce dose of atenolol if necessary or switch to another ARV agent.
  • ACE inhibitors, ARBs, CCBs, aliskiren, diuretics: No dose adjustments necessary.
Elvitegravir (EVG), boosted
  • Aliskiren: Inhibitors of P-gP, including boosted EVG, decrease aliskiren elimination, increasing adverse events of medication.
  • Atenolol: COBI-boosted EVG may increase atenolol via inhibition of MATE1 elimination.
  • CCBs: Boosted EVG may increase CCB concentrations by as much as 50%.
  • ACE inhibitors, ARBs, beta blockers, carvedilol, diuretics: No significant interactions expected.
  • Aliskiren: Do not coadminister.
  • Atenolol: Start patient at lowest possible dose and monitor for adverse events before slowly increasing dose to effect. If a patient is already on atenolol but starting COBI-boosted EVG, monitor for atenolol-related adverse events. Reduce dose of atenolol as needed.
  • CCBs: Decrease original dose by as much as 50% when using with boosted EVG and slowly titrate to effect.
  • Beta blockers other than atenolol, diuretics: No dose adjustments necessary.
Boosted PIs
  • Aliskiren: Inhibitors of P-gP, including boosted PIs, decrease aliskiren elimination, increasing adverse events of medication.
  • Atenolol: COBI-boosted PIs may increase atenolol via inhibition of MATE1 elimination. Similar interaction is not seen with RTV-boosted PIs.
  • CCBs: Boosted PIs may increase CCB concentrations by as much as 50%.
  • ACE inhibitors, ARBs, beta blockers, carvedilol, diuretics: No significant interactions expected.
  • Aliskiren: Do not coadminister.
  • Atenolol: Start patient at lowest possible dose and monitor for adverse events before slowly increasing dose to effect. If patient is already on atenolol, but starting a COBI-boosted PI, monitor for atenolol-related adverse events. Reduce dose of atenolol as needed. RTV is the preferred PK booster when a patient is also taking atenolol.
  • CCBs: Decrease original dose by as much as 50% when using with boosted PIs and slowly titrate to effect.
  • ACE inhibitors, ARBs, beta blockers, diuretics: No dose adjustments necessary
Efavirenz (EFV) or etravirine (ETR)
  • Aliskiren: ETR is a minor inhibitor of P-gP and may minimally increase concentrations of aliskiren, but this has not been studied. EFV is not expected to interact.
  • ACE inhibitors, ARBs, CCBs, diuretics: No significant interactions expected.
  • Aliskiren: When using with ETR, monitor for aliskiren-related adverse events. If present, switch to alternative antihypertensive agent or ARV agent.
  • ACE inhibitors, ARBs, beta blockers, CCBs, diuretics: No dose adjustments necessary.

Abbreviations: INSTIs, integrase strand transfer inhibitors; MATE, multidrug and toxin extrusion; NRTI, nucleoside reverse transcriptase inhibitor; NSAID, non-steroidal anti-inflammatory drug; OCT, organic cation transporter; P-gP, P-glycoprotein; PI, protease inhibitor; PK, pharmacokinetic; RTV, ritonavir; TDF, tenofovir disoproxil fumarate.

Note: Although not typically nephrotoxic, ACE inhibitors can, rarely, contribute to renal dysfunction, particularly when combined with high-dose NSAIDs. Clinicians are advised to ask patients who are taking TDF about their use of ACE inhibitors, such as lisinopril, with NSAIDs, such as ibuprofen or naproxen, and to monitor the patient’s renal function.

Anticoagulants

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 17: Anticoagulants
→ Warfarin, non-VKA oral anticoagulants (NOACs), low molecular weight heparins (LMWHs)
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Dolutegravir (DTG) or bictegravir (BIC)
  • Raltegravir (RAL)
  • Rilpivirine (RPV)
No significant interactions expected. No dose adjustments necessary.
  • Elvitegravir (EVG), boosted
  • Boosted PIs
  • Warfarin: Could potentially decrease (or more rarely) increase metabolism of warfarin.
  • Rivaroxaban, dabigatran, apixaban: May increase concentrations, increasing bleeding risk.
  • LMWHs: No significant interaction expected.
  • Warfarin: Use cautiously with warfarin, and if use is necessary, increase monitoring of INR. Decrease dose if INR increases. Increase dose slowly if INR decreases.
  • Rivaroxaban, dabigatran, apixaban: Avoid use of boosted PIs if possible.
  • Apixaban: Reduce dose to 2.5 mg twice per day, and if patient is already taking 2.5 mg twice per day, avoid concomitant use.
  • Dabigatran: 1) Separate doses of dabigatran and boosted PIs by at least 2 hours. 2) RTV-boosted PIs may be safer than COBI boosting [Kakadiya, et al. 2018]. 3) Avoid in patients taking boosted PIs if patient also has severe renal impairment.
  • LMWHs: No dose adjustments necessary.
  • Efavirenz (EFV) or etravirine (ETR)
  • Warfarin: Could potentially increase (or more rarely decrease) metabolism of warfarin.
  • NOACs, LMWHs: No significant interactions expected.
  • Warfarin: Use cautiously with warfarin, and if use is necessary, increase monitoring of INR. Increase dose slowly if INR decreases. Decrease dose if INR increases.
  • NOACs, LMWHs: No dose adjustments necessary.
Abbreviations: COBI, cobicistat; INR, international normalized ratio; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; RTV, ritonavir.
Reference

Kakadiya PP, Higginson RT, Fulco PP. Ritonavir-boosted protease inhibitors but not cobicistat appear safe in HIV-positive patients ingesting dabigatran. Antimicrob Agents Chemother 2018;62(2). [PMID: 29133562]

Antiplatelet Drugs

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 18: Antiplatelet Drugs
→ Adenosine phosphate receptor inhibitors, cilostazol, dipyridamole
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Dolutegravir (DTG) or
    bictegravir (BIC)
  • Raltegravir (RAL)
  • Rilpivirine (RPV)
No significant interactions expected. No dose adjustments necessary.
Elvitegravir (EVG), boosted
  • Cilostazol: Metabolized by CYP3A and boosted EVG will increase concentrations of this drug.
  • Ticagrelor: Results in increased exposure to ticagrelor.
  • Clopidogrel: Results in decreased concentration of clopidogrel’s active metabolite.
  • Cilostazol: Monitor for antiplatelet effect. May be necessary to use an alternative antiplatelet drug or alternative ARV agent.
  • Ticagrelor: Do not use with boosted EVG.
  • Clopidogrel: Do not use with boosted EVG unless an alternative antiplatelet drug (or ARV agent) cannot be used.
Boosted PIs
  • Cilostazol: Metabolized by CYP3A, and boosted PIs will increase concentrations of this drug.
  • Dipyridamole: RTV-boosted PIs may induce UGT enzymes, which are responsible for metabolism of dipyridamole (not seen with COBI).
  • Ticagrelor: Results in increased exposure to ticagrelor.
  • Clopidogrel: Results in decreased concentration of clopidogrel’s active metabolite.
  • Cilostazol: Monitor for antiplatelet effect. May be necessary to use an alternative antiplatelet drug or alternative ARV agent.
  • Dipyridamole: Monitor for antiplatelet effect. Use another ARV agent or boost with COBI if necessary.
  • Ticagrelor: Do not used with boosted PIs.
  • Clopidogrel: Do not use with boosted PIs unless an alternative antiplatelet drug (or ARV agent) cannot be used
Efavirenz (EFV) or etravirine (ETR)
  • Cilostazol: May reduce concentrations of cilostazol.
  • Dipyridamole: EFV and ETR may induce UGT enzymes, which are responsible for metabolism.
  • Ticagrelor, clopidogrel: EFV and ETR reduce ticagrelor concentrations and the conversion of clopidogrel to its active metabolite
  • Cilostazol: Monitor for antiplatelet effect; may be necessary to use an alternative antiplatelet drug or alternative ARV agent.
  • Dipyridamole: Monitor for antiplatelet effect; use another ARV agent if necessary.
  • Ticagrelor, clopidogrel: Use with EFV or ETR may reduce the antiplatelet effect; monitor closely and use an alternative ARV agent if necessary.
Abbreviations: ARV, antiretroviral; COBI, cobicistat, CYP, cytochrome P450; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; RTV, ritonavir; UGT, uridine diphosphate glucuronosyltransferase.

Statins

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 19: Statins
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Dolutegravir (DTG) or
    bictegravir (BIC)
  • Raltegravir (RAL)
  • Rilpivirine (RPV)
No significant interactions expected. No dose adjustments necessary.
  • Elvitegravir (EVG), boosted
  • Boosted PIs
  • Simvastatin, lovastatin: Greatly increases concentrations.
  • Atorvastatin, rosuvastatin: May moderately increase concentrations.
  • Fluvastatin: Interaction has not been studied, but potential for moderate increase is possible.
  • Pitavastatin, pravastatin: Although moderate increases are possible, low doses are considered safe when used with boosted PIs.
  • Simvastatin, lovastatin: Do not use; choose another statin drug.
  • Atorvastatin, rosuvastatin: Use with lowest effective doses; monitor closely for safety and efficacy before increasing statin dose.
  • Fluvastatin: Do not use, but if clinical use is desired, use the lowest effective dose; monitor closely for safety and efficacy before increasing statin dose.
  • Pitavastatin, pravastatin: Use with lowest effective doses; dose adjustments are not necessary when using these statins with boosted EVG.
Efavirenz (EFV) or etravirine (ETR)
  • Simvastatin, lovastatin: Could potentially decrease concentrations.
  • Atorvastatin, pravastatin, fluvastatin: May modestly reduce concentrations.
  • Pitavastatin, rosuvastatin: No significant interactions expected.
  • Simvastatin, lovastatin: Monitor for efficacy. May warrant increases in statin dose. Do not increase dose above maximum recommended statin dose.
  • Atorvastatin, pravastatin, fluvastatin: Monitor cholesterol-lowering effect of statins. May require increased dose.
  • Pitavastatin, rosuvastatin: No dose adjustments necessary.

Abbreviations: NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Note: Ritonavir-boosted PIs and EFV are known to cause metabolic dysfunction, which may increase blood cholesterol levels.

Antidiabetic Drugs

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 20: Antidiabetic Drugs
 Metformin, sulfonylureas, thiazolidinediones (TZDs), dipeptidyl peptidase IV (DPP-4) inhibitors, a glucosidase inhibitors, glucagon-like peptide 1 (GLP-1) agonists, sodium glucose cotransporter 2 (SGLT-2) inhibitors
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Raltegravir (RAL)
No significant interactions expected. No dose adjustment necessary.
Dolutegravir (DTG) or bictegravir (BIC)
  • Metformin: DTG increases metformin levels, but clinical significance is not yet known.
  • Sulfonylureas, TZDs, DPP-4 inhibitors, GLP-1 agonists, SGLT-2 inhibitors: No significant interactions expected.
  • Metformin: 1) Administer at lowest dose possible to achieve glycemic control; monitor for adverse effects. 2) Titrate metformin and do not exceed 1,000 mg when coadministered with DTG; monitor for adverse effects, including lactic acidosis.
  • Sulfonylureas, TZDs, DPP-4 inhibitors, GLP-1 agonists, SGLT-2 inhibitors: No dose adjustments necessary.
Elvitegravir (EVG), boosted
  • Metformin: COBI is known to inhibit MATE1, which plays a role in the elimination of metformin, thus increasing metformin concentrations.
  • Glyburide: Mainly metabolized by CYP3A; concentrations are increased by inhibitors of this enzyme. 
  • TZDs, GLP-1 agonists, SGLT-2 inhibitors: No significant interactions noted.
  • Metformin: Monitor for metformin-related adverse events and reduce dose as needed.
  • Glyburide or alternative sulfonylureas: Use lowest effective doses with boosted EVG; monitor for signs of hypoglycemia.
  • Saxagliptin: Limit dose to 2.5 mg once per day.
  • Canagliflozin: Monitor glycemic control.
  • TZDs, GLP-1 agonists, SGLT-2 inhibitors: No dose adjustments necessary.
  • Boosted PIs
  • Atazanavir (ATV), boosted
  • Metformin: COBI is known to inhibit MATE1, which plays a role in the elimination of metformin, thus increasing metformin concentrations.
  • Glyburide: Mainly metabolized by CYP3A, and thus concentrations are increased by inhibitors of this enzyme.
  • Saxagliptin: Substrate of CYP3A, so levels may be increased.
  • Canagliflozin: Use with ATV may decrease concentrations of canagliflozin.
  • GLP-1 agonists: Caution needed when coadministering ATV and GLP-1 agonists, such as exenatide, due to their potential to inhibit gastric secretion, thereby reducing the absorption of ATV. Exenatide also has the potential to slow gastric emptying.
  • TZDs, exenatide: No significant interactions expected.
  • Metformin: Monitor for metformin-related adverse events and reduce dose as needed.
  • Glyburide or alternative sulfonylureas: Use lowest effective doses with boosted PIs; monitor for signs of hypoglycemia.
  • Saxagliptin: Limit dose to 2.5 mg once per day.
  • Canagliflozin: With RTV-boosted ATV and inadequate glycemic control, consider increasing dose to 300 mg per day if patient is tolerating 100 mg per day and has GFR >60 mL/min/1.73 m2.
  • GLP-1 agonist: Consider taking ATV 4 hours before.
  • TZDs: No dose adjustments necessary.
Rilpivirine (RPV)
  • GLP-1 agonists: Caution needed when coadministering with RPV and GLP-1 agonists, such as exenatide, due to their potential to inhibit gastric secretion, thereby reducing absorption of RPV. Exenatide also has the potential to slow gastric emptying.
  • Metformin, sulfonylureas, TZDs, DPP-4 inhibitors, SGLT-2 inhibitors: No significant interactions noted.
  • GLP-1 agonist: Consider taking RPV 4 hours before.
  • Metformin, sulfonylureas, TZDs, DPP-4 inhibitors, SGLT-2 inhibitors: No dose adjustments necessary.
Efavirenz (EFV) or etravirine (ETR)
  • Pioglitazone: EFV may increase concentrations by inhibition of CYP2C8. No significant interactions expected.
  • Saxagliptin, sitagliptin: EFV and ETR may decrease concentration.
  • Metformin, sulfonylureas, TZDs, GLP-1 agonists, SGLT-2 inhibitors: No significant interactions noted.
  • Pioglitazone: Monitor for signs of adverse events with EFV; decrease dose if necessary.
  • Saxagliptin, sitagliptin: Monitor for efficacy; if necessary, increase dose of the DPP-4 inhibitor.
  • Metformin, sulfonylureas, TZDs, GLP-1 agonists, SGLT-2 inhibitors: No dose adjustment necessary.

Abbreviations: COBI, cobicistat; CYP, cytochrome P450; GFR, glomerular filtration rate; MATE, multidrug and toxin extrusion; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; TDF, tenofovir disoproxil fumarate.

Note: Ritonavir-boosted PIs are known to cause metabolic abnormalities, which may cause increased blood glucose and decreased insulin sensitivity. An increased risk for bone fractures has been reported with canagliflozin, particularly in patients with a history of or who are at high risk of cardiovascular disease; therefore, caution is recommended when coadministering SGLT-2 inhibitors in the long term with TDF due to potential additive bone toxicities.

Acid-Reducing Agents

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 21: Acid-Reducing Agents
→ Proton pump inhibitors (PPIs) and histamine-2 receptor agonists (H2RAs)
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Dolutegravir (DTG) or bictegravir (BIC)
  • Raltegravir (RAL)
  • Elvitegravir (EVG), boosted
  • Efavirenz (EFV) or etravirine (ETR)
No clinically significant interactions noted. No dose adjustments needed.
Atazanavir (ATV), unboosted PPIs: Markedly reduce ATV concentration and AUC.
  • PPIs: 1) Do not coadminister if alternatives are possible; use alternative acid-reducing agent, alternative PI, or boost ATV with RTV or COBI. 2) For ART-naive patients, if use cannot be avoided, do not exceed omeprazole 20 mg per day or equivalent [a] and administer 12 hours prior to ATV. 3) For ART-experienced patients [b], consult with an experienced HIV care provider or a GI specialist.
  • H2RAs: 1) For ART-naive patients, administer ATV 400 mg (unboosted) with food at least 2 hours before or 10 hours after. 2) Do not exceed dose equivalent to famotidine 20 mg of any H2RA; total daily dose should not exceed 40 mg famotidine or equivalent. 3) Do not use unboosted ATV + famotidine in combination in PI-experienced patients.
Atazanavir (ATV), boosted H2RAs: Reduce ATV absorption.
  • PPIs: 1) Do not exceed dose equivalent to omeprazole 20 mg per day in PI-naive patients. 2) Administer at least 12 hours before RTV- or COBI-boosted ATV.
  • H2RAs: 1) For ART-naive patients, administer ATV 300 mg + RTV 100 mg simultaneously with, or at least 10 hours after H2RA. 3) Do not exceed famotidine 20 mg twice per day or equivalent [c] if patient is not taking TFV. 4) Do not exceed famotidine 40 mg twice per day or equivalent [c] if patient is taking TFV. 5) Do not exceed dose equivalent to famotidine 40 mg twice per day in ART-naive patients or 20 mg twice per day in ART-experienced [b] patients. 6) Administer ATV 300 mg + COBI 150 mg or RTV 100 mg simultaneously with and/or ≥10 hours after dose of H2RA. 7) In ART-experienced [b] patients taking TDF [d], use ATV 400 mg + COBI 150 mg or RTV 100 mg. 8) In second and third trimesters of pregnancy [e], increase dose to 400 mg per day. 9) H2RA use is contraindicated if pregnant patient takes TFV + boosted ATV.
Darunavir (DRV)/ ritonavir (RTV) No clinically significant interaction noted.
  • Omeprazole: Do not exceed omeprazole 40 mg per day.
  • No dose adjustment needed.
Rilpivirine (RPV) Significant reduction in plasma concentration of RPV.
  • PPIs: Do not coadminister.
  • H2RAs: Use lowest effective dose, administered no more than once per day and at least 12 hours before or 4 hours after RPV; administer with food.

Abbreviations: ARV, antiretroviral; AUC, area under the curve; COBI, cobicistat; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; PK, pharmacokinetic; RTV, ritonavir; TFV, tenofovir; TDF, tenofovir disoproxil fumarate.

Notes:

  1. PPI dose equivalents per day: Omeprazole 20 mg; pantoprazole 40 mg; lansoprazole 30 mg; esomeprazole 20 mg.
  2. Treatment-experienced patients have taken ART and, in most cases, have experienced treatment failure. Heavily ART-experienced patients are more likely to experience resistance mutations, which increase the risk of virologic failure, and achlorhydria in the stomach, which reduces gastric acid and thus gastric pH.
  3. H2RA dose equivalents twice per day: Famotidine 20 mg (40 mg); ranitidine 150 mg (300 mg); nizatidine 150 mg (300 mg).
  4. Tenofovir significance: TFV has been shown to decrease ATV concentrations via an unknown mechanism. PK boosting typically overcomes this decrease in concentration, but when given along with an H2RA, adequate loss of concentration is seen to reduce ARV effect.
  5. The volume of distribution increases as duration of pregnancy increases, which changes the PK parameters of medications, such as some PIs. PK boosting protects some of these PIs, but caution is required during the second and third trimesters of pregnancy to ensure adequate therapeutic concentrations.

Polyvalent Cations

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 22: Polyvalent Cations
→ Supplements, antacids, and laxatives that contain aluminum, calcium, magnesium, zinc, and iron
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Darunavir (DRV), boosted or unboosted
  • Efavirenz (EFV) or etravirine (ETR)
No clinically significant interactions noted. No dose adjustments needed.
All INSTIs These form complexes with cations, resulting in reduced concentrations of both INSTIs and cations. For specific recommendations, see individual INSTIs below. Any polyvalent cation: If coadministration is necessary, administer at least 2 hours before or at least 6 hours after, and monitor for virologic efficacy.
Dolutegravir (DTG) Binds to cations, reducing effect of ARV agent and cations.
  • Antacids: Administer at least 2 hours before or at least 6 hours after antacids containing polyvalent cations.
  • Supplements containing calcium or iron: DTG and supplement can be taken simultaneously with food.
Bictegravir (BIC) Binds to cations, reducing effect of ARV agent and cations
  • Antacids containing polyvalent cations: Administer at least 2 hours before or at least 6 hours after.
  • Supplements containing calcium or iron: BIC and supplement can be taken simultaneously with food.
Elvitegravir (EVG), boosted Binds to cations, reducing effect of ARV agent and cations.
  • Polyvalent cations: Administer at least 2 hours before or 6 hours after.
  • Al, Mg (+/- Ca) containing antacids: When taken with EVG, separate doses by at least 2 hours.
Raltegravir (RAL) Binds to cations, reducing effect of ARV agent and cations.
  • Aluminum-magnesium hydroxide antacids: Contraindicated; use alternative acid-reducing agent.
  • CaCO3 antacids: 1) RAL HD once per day is contraindicated. 2) RAL 400 mg twice per day: No dose adjustment or separation necessary.
  • Other polyvalent cations: Administer at least 2 hours before or 6 hours after.
Atazanavir (ATV), boosted or unboosted Antacids containing calcium, magnesium, or aluminum: May reduce absorption. Antacids or buffered medications: Administer at least 2 hours before or 1 to 2 hours after.
Rilpivirine (RPV) Antacids: May reduce absorption. Antacids: Administer at least 2 hours before or at least 4 hours after.
Abbreviations: ARV, antiretroviral; INSTI, integrase strand transfer inhibitor; NRTI, nucleoside reverse transcriptase inhibitor.

Asthma and Allergy Medications

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 23: Asthma and Allergy Medications
→ Albuterol, tiotropium, aclidinium, montelukast, loratadine, cetirizine, diphenhydramine
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Dolutegravir (DTG) or bictegravir (BIC)
  • Raltegravir (RAL)
  • Elvitegravir (EVG), boosted
  • Boosted PIs
  • Rilpivirine (RPV)
  • Efavirenz (EFV) or etravirine (ETR)
No significant interactions noted. No dose adjustments necessary.
Abbreviations: NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Long-Acting Beta Agonists (LABAs)

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 24: Long-Acting Beta Agonists (LABAs)
→ Salmeterol, formoterol, etc.
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Dolutegravir (DTG) or bictegravir (BIC)
  • Raltegravir (RAL)
  • Efavirenz (EFV) or etravirine (ETR)
No significant interactions noted. No dose adjustment necessary.
Elvitegravir (EVG), boosted Increased risk of salmeterol-associated cardiovascular events. Do not coadminister; consider use of alternative ARV agent.
Boosted PIs Inhibition of CYP3A4 enzyme increases plasma concentrations of salmeterol.
  • Contraindicated unless benefits outweigh possible risks; consider use of alternative ARV agent.
  • If coadministration is necessary, monitor frequently for QT prolongation, palpitations, and sinus tachycardia.
  • Boosted PIs may also increase QT prolongation.
Rilpivirine (RPV) Both drugs may theoretically increase QT interval, especially at high doses.
  • No dose adjustment necessary.
  • Do not use more LABA than recommended; this can increase risk of QT prolongation.
Abbreviations: ARV, antiretroviral; CYP, cytochrome P450; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Inhaled and Injected Corticosteroids

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 25: Inhaled and Injected Corticosteroids
→ Fluticasone, triamcinolone, budesonide, and methyl prednisone
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Dolutegravir (DTG) or bictegravir (BIC)
  • Raltegravir (RAL)
No significant interactions noted. No dose adjustment necessary.
Elvitegravir (EVG), boosted

Risk of Cushing’s syndrome when coadministered with the following:

  • Intranasal or inhaled: Fluticasone, mometasone, ciclesonide, budesonide, triamcinolone.
  • Systemic: Betamethasone, budesonide, prednisolone, prednisone, dexamethasone.
  • Injectable: Betamethasone, triamcinolone.
  • Intranasal or inhaled fluticasone, mometasone, ciclesonide, budesonide, triamcinolone: Do not coadminister unless potential benefits outweigh risk; consider alternative corticosteroid (e.g., beclomethasone).
  • Systemic betamethasone, budesonide: Do not coadminister unless potential benefits outweigh risk.
  • Systemic prednisolone, prednisone: Do not coadminister unless potential benefits outweigh risk; if use cannot be avoided, use for shortest effective duration.
  • Injectable betamethasone, triamcinolone: Do not coadminister unless potential benefits outweigh risk.
  • Systemic dexamethasone: Do not coadminister unless potential benefits outweigh risk; consider alternative corticosteroid.
Boosted PIs

Risk of Cushing’s syndrome when coadministered with the following corticosteroids:

  • Intranasal or inhaled: Fluticasone, mometasone, ciclesonide, budesonide, triamcinolone.
  • Systemic: Betamethasone, budesonide, dexamethasone.
  • Injectable: Betamethasone, triamcinolone.
  • Intranasal or inhaled fluticasone, mometasone, ciclesonide, budesonide, triamcinolone: Do not coadminister unless potential benefits outweigh risk; consider alternative corticosteroid (e.g., beclomethasone).
  • Systemic betamethasone, budesonide: Do not coadminister unless potential benefits outweigh risk.
  • Systemic prednisolone, prednisone: Contraindicated unless potential benefits outweigh risk; if use cannot be avoided, use for shortest effective duration.
  • Injectable betamethasone, triamcinolone: Contraindicated unless potential benefits outweigh risk.
  • Systemic dexamethasone: Contraindicated unless potential benefits outweigh risk; consider alternative corticosteroid.
Rilpivirine (RPV) Potential decrease in RPV concentration. Systemic dexamethasone: 1) Contraindicated; consider use of alternative agents. 2) If using more than single dose, do not coadminister.
Efavirenz (EFV) or etravirine (ETR) Coadministration may reduce concentrations of corticosteroids. Systemic dexamethasone: Consider alternative corticosteroid for long-term use; if benefits of use outweigh risks, monitor virologic response.

Abbreviations: ARV, antiretroviral; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Note: Short-term therapy with oral prednisone or prednisolone is not expected to cause significant drug-drug interactions with ARV agents in most cases; however, increased monitoring may be required if a patient is taking an ARV agent, including a boosted PI, that has adverse effects that are the same as those of prednisone, such as insulin resistance. Particular caution may be necessary in patients predisposed to insulin hypersensitivity. Long-term therapy with oral steroids (>2 weeks) is not recommended unless undertaken with guidance from an experienced HIV care provider.

Antidepressants

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 26: Antidepressants
→ Including selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), trazodone, bupropion, and monoamine oxidase inhibitors (MAOIs)
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Dolutegravir (DTG) or bictegravir (BIC)
  • Raltegravir (RAL)
  • Rilpivirine (RPV)
No significant interactions noted. No dose adjustments necessary.
  • Elvitegravir (EVG), boosted
  • Boosted PIs
Trazodone: May increase trazodone concentrations. Trazodone: Monitor antidepressant and/or sedative effects.
Efavirenz (EFV) or etravirine (ETR)
  • Trazodone: May decrease trazodone concentrations.
  • Bupropion: EFV induces bupropion metabolism.
  • Trazodone: Monitor antidepressant and/or sedative effects.
  • Bupropion: Monitor clinical effect and increase as needed, but do not exceed recommended maximum dose.
Abbreviations: NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

 

Benzodiazepines

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 27: Benzodiazepines
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Dolutegravir (DTG) or bictegravir (BIC)
  • Raltegravir (RAL)
  • Rilpivirine (RPV)
No significant interactions noted. No dose adjustments necessary.
Elvitegravir (EVG), boosted Boosted ARV agents may increase benzodiazepine concentrations via CYP3A4 inhibition. Alprazolam, clonazepam, diazepam: 1) Consider alternative benzodiazepine. 2) If used, administer lowest effective dose; monitor closely for adverse effects.
Boosted PIs
  • Alprazolam: Boosted ARV agents may increase alprazolam concentrations via CYP3A4 inhibition.
  • Diazepam: Metabolism of diazepam may be reduced via inhibition of CYP3A4.
  • Alprazolam, clonazepam, diazepam: Consider alternative benzodiazepine; if used, administer lowest effective dose; monitor closely for adverse effects.
  • Diazepam: Monitor for excess sedation.
Efavirenz (EFV) Alprazolam, diazepam: Potential for reduced alprazolam and diazepam concentrations.
  • Alprazolam: Monitor for benzodiazepine withdrawal if EFV is added.
  • Alprazolam, clonazepam, diazepam: Monitor for benzodiazepine efficacy; titrate slowly as needed for effect.
Etravirine (ETR) Alprazolam, diazepam: Potential for reduced alprazolam and diazepam concentrations. Alprazolam: Monitor for benzodiazepine withdrawal.

Abbreviations: ARV, antiretroviral; CYP, cytochrome P450; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Note: Lorazepam, oxazepam, and temazepam do not interact clinically with and do not require dose adjustments when coadministered with ARV agents.

Sleep Medications

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 28: Sleep Medications
→ Non-benzodiazepine “Z-drugs,” melatonin, ramelteon, suvorexant
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Dolutegravir (DTG) or bictegravir (BIC)
  • Raltegravir (RAL)
  • Rilpivirine (RPV)
No significant interactions noted. No dose adjustment necessary.
  • Elvitegravir (EVG), boosted
  • Boosted PIs
  • Zolpidem, suvorexant: Potential for increased concentrations of zolpidem and suvorexant.
  • Ramelteon: RTV-boosted PIs may reduce efficacy.
  • Zolpidem: Administer lowest effective dose; monitor for adverse effects, including excess sedation.
  • Eszopiclone: Start with 1 mg per day; titrate slowly to effect; monitor for adverse effects, including excess sedation.
  • Suvorexant: Coadministration is not recommended; use alternative sleep medication or ARV agent.
  • Ramelteon: Monitor efficacy in cigarette smokers.
Efavirenz (EFV) or etravirine (ETR) Zolpidem: Potential for reduced concentrations of zolpidem.
  • Zolpidem, eszopiclone: Monitor for efficacy; no dose adjustments recommended.
  • Suvorexant: Monitor for efficacy; do not exceed 20 mg per day.
Abbreviations: ARV, antiretroviral; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; RTV, ritonavir.

Antipsychotics

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 29: Antipsychotics*
→ First-generation, second-generation, and atypical
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Dolutegravir (DTG) or bictegravir (BIC)
  • Raltegravir (RAL)
No significant interactions expected. No dose adjustments necessary.
Elvitegravir (EVG), boosted
  • Risperidone: Potential for moderate increase in risperidone levels.
  • Clozapine: Interaction has not been studied but may theoretically increase concentrations of clozapine, increasing risk of adverse events
  • Quetiapine: Reduce dose to 1/6 if initiating ARV in patient stabilized on quetiapine; monitor for adverse effects.
  • Lurasidone: No data; avoid coadministration; consider alternative antipsychotic or ARV agent. If initiating in patient stabilized on boosted EVG, use lowest dose and titrate slowly to desired effect.
  • Risperidone: Initiate at low dose; titrate slowly; monitor for adverse events.
  • Clozapine: Interaction has not been studied but may theoretically increase concentrations of clozapine, increasing risk of adverse events.
Ritonavir (RTV) Olanzapine: May induce CYP1A2, especially in cigarette smokers, which may decrease olanzapine concentrations. Olanzapine: Monitor for efficacy; titrate slowly as needed.
Boosted PIs
  • Haloperidol: Potential for moderately increased haloperidol concentrations with boosted PIs.
  • Aripiprazole, brexpiprazole: RTV-boosted PIs may increase levels of aripiprazole and brexpiprazole.
  • Risperidone: Potential for moderate increase in risperidone levels.
  • Clozapine: Interaction has not been studied but may theoretically increase concentrations of clozapine, increasing risk of adverse events.
  • Quetiapine: Reduce dose to 1/6 original dose if initiating boosted PI in patient stabilized on quetiapine; monitor for QT prolongation. If initiating in patient stabilized on boosted PI, use lowest dose and titrate slowly to desired effect; monitor for QT prolongation.
  • Lurasidone: No data; avoid coadministration; consider alternative antipsychotic or ARV agent.
  • Haloperidol: Monitor for QT prolongation.
  • Aripiprazole: Initiate at 50% of standard starting dose and titrate slowly; monitor carefully and adjust dose as necessary.
  • Brexpiprazole: Monitor carefully and adjust dose as necessary.
  • Risperidone: Initiate at low dose; titrate slowly; monitor for adverse events.
  • Clozaril: Monitor carefully for adverse Clozaril-related events.
Atazanavir (ATV), unboosted

Lurasidone: Decreases lurasidone metabolism via CYP3A.

Lurasidone: Reduce dose by 50%; monitor for adverse effects, including QT prolongation.

Rilpivirine (RPV)

No significant interactions noted.

No dose adjustments necessary, but avoid excess doses of either antipsychotic or RPV because excess doses of both drugs may increase risk of QT prolongation.

Efavirenz (EFV)
  • Quetiapine: Concentrations of quetiapine may be reduced.
  • Aripiprazole, brexpiprazole: Concentrations of aripiprazole and brexpiprazole may be decreased.
  • Risperidone, olanzapine: May decrease efficacy of risperidone and olanzapine.
  • Quetiapine: Monitor for efficacy; titrate slowly as needed; monitor for adverse effects.
  • Aripiprazole, brexpiprazole: Monitor for efficacy; titrate dose slowly as needed; monitor for adverse effects.
  • Risperidone, olanzapine: Monitor for efficacy; titrate slowly as needed; monitor for adverse effects.
Etravirine (ETR)
  • Aripiprazole, brexpiprazole: Concentrations of aripiprazole and brexpiprazole may be decreased.
  • Risperidone: May decrease efficacy of risperidone.
  • Aripiprazole, brexpiprazole: Monitor for efficacy; titrate dose slowly as needed; monitor for adverse effects.
  • Risperidone: Monitor for efficacy; titrate slowly; monitor for adverse effects.

Abbreviations: ARV, antiretroviral; CYP, cytochrome P450; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

*Coadministration of antipsychotic and ARV agents may result in QT prolongation; monitor closely.

Anticonvulsants

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 30: Anticonvulsants
→ Including phenytoin, phenobarbital, carbamazepine, oxcarbazepine, lamotrigine, valproic acid, gabapentin, topiramate, zonisamide
Class or Drug Mechanism of Action Clinical Comments
Tenofovir disoproxil fumarate (TDF) Zonisamide: May increase concentration of zonisamide.
  • Topiramate: Monitor renal function when coadministered (topiramate may cause kidney stones; TDF is associated with renal toxicity).
  • Zonisamide: Monitor for adverse events of zonisamide.
Tenofovir alafenamide (TAF) Coadministration with strong inducers of CYP3A (phenytoin, phenobarbital, etc.) may decrease TAF concentrations. Coadministration with strong inducers of CYP3A are not recommended because they may reduce concentrations of TAF.
Other NRTIs No interactions noted. No dose adjustments necessary.
Dolutegravir (DTG) or bictegravir (BIC)
  • Valproic acid: Coadministration may significantly decrease DTG or BIC concentrations.
  • Coadministration with strong inducers of CYP3A (phenytoin, phenobarbital, etc.) may decrease DTG or BIC concentrations
Valproic acid: 1) Coadministration is not recommended; if alternative anticonvulsant cannot be used, monitor for safety and efficacy, including therapeutic drug monitoring. 2) Coadministration with strong inducers of CYP3A are not recommended because they may reduce concentrations of INSTIs.
Raltegravir (RAL) Coadministration with strong inducers of UGT1A1 (phenytoin, phenobarbital, etc.) may decrease RAL concentrations. Coadministration with strong inducers of UGT1A1 are not recommended.
Elvitegravir (EVG), boosted Carbamazepine, oxcarbazepine, phenobarbital, phenytoin: Coadministration may significantly reduce concentrations of ARV agents through induction of CYP450 system. Carbamazepine, oxcarbazepine, phenobarbital, phenytoin: 1) Coadministration is not recommended; use alternative anticonvulsant. 2) If benefit of use outweighs risk, monitor carefully for efficacy and toxicity. 3) Perform therapeutic drug monitoring.
Ritonavir (RTV)
  • Phenytoin: Concurrent use may reduce concentrations of RTV and phenytoin, resulting in loss of viral suppression and seizure control.
  • Lamotrigine: RTV-boosted ARV agents may reduce efficacy of lamotrigine.
  • Valproic acid: RTV may reduce concentrations of valproic acid.
  • Phenytoin: 1) Coadministration is not recommended; use alternative anticonvulsant. 2) If benefit of use outweighs risk, monitor carefully for efficacy and toxicity. 3) Perform therapeutic drug monitoring.
  • Lamotrigine: Monitor efficacy; titrate dose slowly as needed.
  • Valproic acid: Consider use of COBI when boosting of ARV agent is required.
Boosted PIs
  • Carbamazepine, oxcarbazepine, phenobarbital, phenytoin: Coadministration may significantly reduce concentrations of ARV agents through induction of CYP450 system.
  • Zonisamide: Zonisamide concentrations may be increased through CYP3A4 inhibition.
  • Carbamazepine, oxcarbazepine, phenobarbital, phenytoin: 1) Coadministration is not recommended; use alternative anticonvulsant. 2) If benefit of use outweighs risk, monitor carefully for efficacy and toxicity. 3) Perform therapeutic drug monitoring.
  • Zonisamide: Monitor efficacy and adverse effects; adjust dose as needed.
NNRTIs Carbamazepine, oxcarbazepine, phenobarbital, phenytoin: Coadministration may significantly reduce concentrations of ARV agents through induction of CYP450 system. Carbamazepine, oxcarbazepine, phenobarbital, phenytoin: 1) Coadministration is not recommended; use alternative anticonvulsant. 2) If benefit of use outweighs risk, monitor carefully for efficacy and toxicity. 3) Perform therapeutic drug monitoring if use cannot be avoided.
Rilpivirine (RPV) Gabapentin, topiramate, zonisamide:
No significant interactions expected.
Gabapentin, topiramate, zonisamide: No dose adjustments necessary.
Efavirenz (EFV) or etravirine (ETR)
  • Lamotrigine, zonisamide: May reduce efficacy of lamotrigine or zonisamide.
  • Gabapentin, topiramate: No significant interactions noted.
  • Lamotrigine, zonisamide: Monitor efficacy; titrate dose slowly as needed.
  • Gabapentin, topiramate: No dose adjustments necessary.
Abbreviations: ARV, antiretroviral; COBI, cobicistat; CYP, cytochrome P450; INSTI, integrase strand transfer inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor;  UGT1A1, uridine diphosphate glucuronosyltransferase 1A1.

Non-Opioid Pain Medications

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 31: Non-Opioid Pain Medications
→ Triptans, tricyclic antidepressants (TCAs), pregabalin, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Dolutegravir (DTG) or bictegravir (BIC)
  • Raltegravir (RAL)
  • Rilpivirine (RPV)
  • Efavirenz (EFV) or etravirine (ETR)
No significant interactions expected. No dose adjustment necessary.
Elvitegravir (EVG), boosted
  • Eletriptan: Metabolism inhibited by boosted EVG.
  • Other non-opioid pain medications: No significant interactions expected.
Eletriptan: Do not coadminister; use alternative triptan medication.
Boosted PIs
  • Eletriptan: Metabolism inhibited by boosted PIs.
  • TCAs: PIs and TCAs can both cause QT prolongation.
  • Pregabalin: No significant interactions expected.
  • Eletriptan: Do not coadminister; use alternative triptan medication.
  • TCAs: When using high-dose TCAs and PIs, consider monitoring for QT prolongation or other cardiac adverse events or using alternative medications.

Abbreviations: NRTI, nucleoside reverse transcriptase inhibitor; NSAID, non-steroidal anti-inflammatory drug; PI, protease inhibitor; TDF, tenofovir disoproxil fumarate.

Note: Although TDF and NSAIDs (such as ibuprofen, meloxicam, or naproxen) are not absolutely contraindicated, NSAIDs may increase the risk of impaired renal function in patients taking high doses of these drugs, and particularly in patients who are predisposed to renal dysfunction. Clinicians are advised to ask patients about their use of over-the-counter or prescribed NSAIDs and to counsel patients to limit NSAID use to the lowest effective dose. Clinicians should also ask patients who are taking TDF as part of a pre-exposure prophylaxis regimen (PrEP) about their use of NSAIDs.

Opioid Analgesics and Tramadol

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 32: Opioid Analgesics and Tramadol
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Dolutegravir (DTG) or bictegravir (BIC)
  • Raltegravir (RAL)
  • Rilpivirine (RPV)
  • Etravirine (ETR)
No significant interactions noted. No dose adjustments required.
Elvitegravir (EVG), boosted
  • Opioid analgesics: Complex mechanisms of metabolism and formation of both active and inactive metabolites create interactions of unclear significance between these drugs and boosted EVG.
  • Tramadol: Tramadol exposure is increased with inhibition of CYP3A, but this reduces conversion to the more potent active metabolite seen when tramadol is metabolized by CYP2D6.
  • Opioid analgesics: Monitor for signs of opiate toxicity and analgesic effect and dose these analgesics accordingly.
  • Tramadol: When tramadol is given with COBI, monitoring for tramadol-related side effects and for the analgesic effect may be required as clinically indicated; adjust tramadol dosage if needed.
Boosted PIs
  • Opioid analgesics: Complex mechanisms of metabolism and the formation of both active and inactive metabolites create interactions of unclear significance between these drugs and boosted PIs.
  • Tramadol: Tramadol exposure is increased with inhibition of CYP3A, but this reduces conversion to the more potent active metabolite seen when tramadol is metabolized by CYP2D6.
  • Opioid analgesics: Monitor for signs of opiate toxicity and analgesic effect and dose these analgesics accordingly.
  • Tramadol: When tramadol is given with COBI or RTV, monitoring for tramadol-related side effects and for the analgesic effect may be required as clinically indicated; adjust tramadol dosage if needed.
Efavirenz (EFV)
  • Morphine, hydromorphone: Metabolism could potentially be reduced by EFV.
  • Oxycodone: May be metabolized faster to an inactive metabolite by EFV.
  • Meperidine: Coadministration can potentially increase amount of neurotoxic metabolite and thereby increase risk of seizures.
  • Tramadol: May reduce concentration of tramadol without affecting pathway that increases development of more potent active metabolites.
  • Morphine, hydromorphone: Monitor for signs of opiate toxicity when using with EFV.
  • Oxycodone: Dose adjustment of oxycodone may be required when dosing with EFV.
  • Meperidine: If possible, avoid concomitant use; use alternative opiate pain medication or ARV agent.
  • Tramadol: When given with tramadol, a priori dose adjustments are necessary.
Abbreviations: ARV, antiretroviral; COBI, cobicistat; CYP, cytochrome P450; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor; RTV, ritonavir.

Hormonal Contraceptives

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 33: Hormonal Contraceptives
→ Combined oral contraceptives, including ethinyl estradiol, norethindrone, and levonorgestrel
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Dolutegravir (DTG) or bictegravir (BIC)
  • Raltegravir (RAL)
No significant drug interactions noted. No dose adjustments necessary.
Elvitegravir (EVG), boosted Drospirenone: Potential for hyperkalemia.
  • Ethinyl estradiol, norgestimate, metabolites; norethindrone: Weigh risks/benefits; consider alternative contraceptive method.
  • Drospirenone: Monitor for hyperkalemia; consider alternative contraceptive or alternative ARV agent.
  • Etonogestrel: No data; consider alternative or additional contraceptive method or alternative ARV agent.
All PIs Combination has not been studied. Etonogestrel: No data; consider alternative or additional contraceptive method or alternative ARV agent.
Atazanavir (ATV), unboosted Complex drug interaction potential has been described.
  • Ethinyl estradiol: Do not exceed 30 mcg (no data on doses lower than 25 mcg).
  • Norethindrone: Do not exceed 30 mcg (no data on oral contraceptives with <25 mcg of ethinyl estradiol or progestins other that norethindrone or norgestimate).
Atazanavir (ATV), boosted
  • Complex drug interaction potential has been described.
  • Drospirenone: Potential for hyperkalemia.
  • Ethinyl estradiol; norgestimate and metabolites: Dose with at least 35 mcg (no data on other progestins).
  • Drospirenone: Do not coadminister.
Darunavir (DRV)/ ritonavir (RTV) Combination appears to decrease oral norethindrone concentrations. Norethindrone: Consider alternative or additional contraceptive method or alternative ARV agent.
DRV/cobicistat (COBI) Combination has not been studied, but since COBI does not induce glucuronidation, it is expected to increase concentrations of norethindrone. Norethindrone: Consider alternative contraceptive method or alternative ARV agent.
Other Boosted PIs Drospirenone: Potential for hyperkalemia.
  • Ethinyl estradiol: Consider alternative or additional contraceptive method or alternative ARV agent.
  • Drospirenone: Monitor for hyperkalemia; consider alternative contraceptive or alternative ARV agent.
Efavirenz (EFV) Decreased concentrations of combined progestins.
  • Ethinyl estradiol; norgestimate, metabolites: Use alternative or additional contraceptive methods; unintended pregnancies have been reported in individuals using levonorgestrel implant.
  • Norethindrone, drospirenone, etonogestrel: Consider alternative or additional contraceptive method or alternative ARV agent.
  • Ulipristal: Efficacy may be reduced; monitor closely.
Etravirine (ETR) Information is based on what is known with EFV drug interactions.
  • Etonogestrel: No data; consider alternative or additional contraceptive method or alternative ARV agent.
  • Ulipristal: Efficacy may be reduced; monitor closely.
Abbreviations: ARV, antiretroviral; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Erectile and Sexual Dysfunction Agents

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 34: Erectile and Sexual Dysfunction Agents
→ Sildenafil [a], vardenafil, tadalafil [b,c], and alprostadil for men; flibanserin [d] for women
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Dolutegravir (DTG) or
    bictegravir (BIC)
  • Raltegravir (RAL)
  • Rilpivirine (RPV)
No significant interactions noted. No dose adjustment necessary.
Elvitegravir (EVG), boosted
  • PDE5 inhibitor: Increased PDE5 inhibitor concentrations expected.
  • Flibanserin: Increased flibanserin concentrations expected.
  • Sildenafil: Start with 25 mg every 48 hours; monitor for adverse effects.
  • Tadalafil: Start with 5 mg; do not exceed 10 mg every 72 hours; monitor for adverse effects.
  • Vardenafil: Administer 2.5 mg every 72 hours; monitor for adverse effects.
  • Flibanserin: Coadministration is contraindicated.
Atazanavir (ATV), unboosted Avanafil: Increased concentration of avanafil expected (for other oral erectile dysfunction drugs, see above). Avanafil: Do not exceed 50 mg every 24 hours.
Boosted PIs
  • PDE5 inhibitor: Increased PDE5 inhibitor concentrations expected.
  • Flibanserin: Increased flibanserin concentrations expected.
  • Sildenafil: Start with 25 mg every 48 hours; monitor for adverse effects.
  • Tadalafil: Start with 5 mg; do not exceed 10 mg every 72 hours; monitor for adverse effects.
  • Vardenafil: Administer 2.5 mg every 72 hours; monitor for adverse effects.
  • Avanafil: Do not coadminister.
  • Flibanserin: Do not coadminister.
Efavirenz (EFV) or etravirine (ETR)
  • PDE5 inhibitor: Potential for reduced effectiveness of PDE5 inhibitors (sildenafil, vardenafil, and tadalafil).
  • Flibanserin: Potential for reduced concentrations of flibanserin.
  • PDE5 inhibitors: Monitor clinical effect; if dose increase is needed to achieve desired clinical effect, titrate under medical supervision to lowest effective dose.
  • Flibanserin: Do not coadminister.

Abbreviations: COBI, cobicistat; NRTI, nucleoside reverse transcriptase inhibitor; PDE5, phosphodiesterase type 5; PI, protease inhibitor.

Notes:

  1. Sildenafil for treatment of pulmonary arterial hypertension (PAH): Concurrent administration of all PIs and EVG/cobicistat is contraindicated.
  2. Tadalafil for treatment of PAH: When coadministered with any PIs or with EVG/COBI, start with 20 mg per day and increase to 40 mg per day based on tolerability.
  3. Tadalafil for treatment of benign prostatic hyperplasia: When coadministered with any PIs, the maximum recommended dose is 2.5 mg per day.
  4. Flibanserin should not be administered with alcohol in any circumstances.

Tobacco and Smoking Cessation Products

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 35: Tobacco and Smoking Cessation Products
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Dolutegravir (DTG) or bictegravir (BIC)
  • Raltegravir (RAL)
  • Elvitegravir (EVG), boosted
  • Boosted PIs
  • Rilpivirine (RPV)
No significant interactions noted. No dose adjustments necessary.
Efavirenz (EFV) or etravirine (ETR)
  • No significant interactions noted.
  • EFV (but not ETR) may increase bupropion metabolism.
  • No dose adjustments necessary.
  • Bupropion: Monitor clinical effect and increase as needed, but do not exceed recommended maximum dose.

Abbreviations: NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Alcohol, Disulfiram, and Acamprosate

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 36: Alcohol, Disulfiram, and Acamprosate
Class or Drug Mechanism of Action Clinical Comments
  • Other NRTIs
  • Dolutegravir (DTG) or bictegravir (BIC)
  • Raltegravir (RAL)
  • Elvitegravir (EVG), boosted
  • Other boosted PIs
  • Rilpivirine (RPV)
  • Efavirenz (EFV) or etravirine (ETR)
No significant interactions noted. No dose adjustments necessary.
Abacavir (ABC) Alcohol: Metabolized via same pathway as alcohol. May increase ABC concentrations; monitor for adverse ABC effects. Does not appear to increase concentrations of alcohol in blood.
  • Ritonavir (RTV) oral solutions
  • Lopinavir/ritonavir (LPV/r; oral suspension or capsules)
All contain alcohol and may potentiate symptoms of consumption of ethanol. Disulfiram: ARV agents formulated with alcohol will induce same aversive effects as consumption of ethanol.

Abbreviations: ARV, antiretroviral; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Note: Clinicians are advised to inform patients that alcohol should be consumed with caution while taking a prescription medication and should educate patients about how medications may affect their response to alcohol. Clinicians are advised to caution patients against driving or operating heavy machinery after consuming alcohol.

Methadone, Buprenorphine, Naloxone, and Naltrexone

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 37: Methadone, Buprenorphine (BUP), Naloxone (NLX), and Naltrexone*
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Dolutegravir (DTG) or bictegravir (BIC)
  • Raltegravir (RAL)
  • Elvitegravir (EVG), boosted
BUP, methadone: No significant interactions expected. No dose adjustments necessary.
Atazanavir (ATV), unboosted
  • BUP, norbuprenorphine: Greatly increases concentrations of BUP and norbuprenorphine; may decrease ATV concentrations.
  • Methadone: No significant interactions expected.
  • BUP: Coadministration is not recommended; RTV boosting may decrease effect.
  • Methadone: No dose adjustments required; exercise caution because both drugs have potential to increase QT prolongation.
Ritonavir (RTV)-boosted PIs BUP: May greatly increase BUP concentrations, but clinical significance of this is unknown because dosing of BUP is based on clinical opiate withdrawal scale. BUP: Monitor for signs of increased opioid toxicity, including sedation, impaired cognition, and respiratory distress.
Cobicistat (COBI)-boosted PIs
  • BUP: May increase BUP concentrations while decreasing NLX concentrations when given with sublingual BUP/NLX.
  • Methadone: COBI does not appear to have any significant effect on the concentration of methadone.
  • BUP, NLX: Use careful dose titration when giving with COBI-boosted ARVs.
  • Methadone: Based on efficacy and safety: Initiate at lowest possible dose and monitor for signs and symptoms of opiate withdrawal and titrate dose to effect.
RTV-boosted darunavir (DRV), taken twice per day
  • BUP, NLX: Combination had no effect on BUP/NLX concentrations.
  • Methadone: May reduce methadone concentrations.
Methadone: Monitor for signs of opiate withdrawal and increase dose of methadone if necessary.
Rilpivirine (RPV)
  • BUP: No significant interactions expected.
  • Methadone: Mildly reduces methadone concentrations.
  • Methadone: Monitor for signs of methadone withdrawal and increase dose as necessary.
  • Methadone, BUP: Use cautiously with RPV because supratherapeutic doses of RPV have been known to cause increase in QT prolongation.
Efavirenz (EFV)
  • BUP: When given with BUP alone (monotherapy), significantly reduces BUP concentrations, but no patients developed opioid withdrawal.
  • Methadone: Reduces methadone concentrations.
  • BUP: When given with BUP, dose adjustments are unlikely to be required, but monitor for withdrawal symptoms. If withdrawal symptoms occur, increase BUP dose accordingly.
  • Methadone: Monitor for signs and symptoms of opioid withdrawal and titrate methadone dose to effect.
Etravirine (ETR)
  • BUP: No significant interactions expected.
  • Methadone: May slightly increase concentrations of methadone.
  • Monitor for signs of withdrawal or opioid toxicity and titrate dose of opioid or antagonist as required.
  • Methadone: Monitor for signs of methadone toxicity and reduce dose if necessary.

*No significant interactions expected between ARVs, naloxone, and naltrexone.

Abbreviations: ARV, antiretroviral; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.

Immunosuppressants

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, April 2019

Table 38: Immunosuppressants*
Class or Drug Mechanism of Action Clinical Comments
  • NRTIs
  • Dolutegravir (DTG)
  • Raltegravir (RAL)
  • Rilpivirine (RPV)
No significant interactions noted. No dose adjustments necessary.
Bictegravir (BIC) Cyclosporine: May increase BIC concentrations to a modest degree via
P-gP inhibition.
Monitor for BIC-related adverse events.
Elvitegravir (EVG), boosted
  • Everolimus, sirolimus: Metabolism decreased by boosted EVG.
  • Cyclosporine, tacrolimus: Metabolism decreased by boosted EVG.
  • Everolimus, sirolimus: Do not use with boosted EVG.
  • Cyclosporine, tacrolimus: Dose based upon therapeutic drug monitoring; monitor closely for adverse events.
Boosted PIs
  • Everolimus, sirolimus: Metabolism decreased by boosted PIs.
  • Cyclosporine, tacrolimus: Metabolism decreased by boosted PIs.
  • Everolimus, sirolimus: Do not use with boosted PIs.
  • Cyclosporine, tacrolimus: Dose based upon therapeutic drug monitoring; monitor closely for adverse events.
Efavirenz (EFV) or etravirine (ETR) Cyclosporine, tacrolimus: Concentrations may be lower when used with EFV or ETR. Cyclosporine, tacrolimus: 1) Dose adjust cyclosporine and tacrolimus based on efficacy and therapeutic drug monitoring (TDM). 2) Conduct TDM more frequently for 2 weeks when starting or stopping NNRTI therapy.

Abbreviations: NNRTI, non-nucleoside reverse transcriptase inhibitors; NRTI, nucleoside reverse transcriptase inhibitor; P-gP, P-glycoprotein; PI, protease inhibitor; TDF, tenofovir disoproxil fumarate.

*Note: Cyclosporine can cause renal toxicity, which may be increased with coadministration of TDF. Clinicians are advised to monitor for signs of renal dysfunction in patients who are taking these two medications at the same time.

Rifamycins and Other Anti-Tuberculosis Medications

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, November 2019

Table 39: Rifamycins and Other Anti-Tuberculosis Medications
→ Rifampin, rifabutin, rifapentine [a], isoniazid [b], pyrazinamide [b], ethambutol [b], rifaximin [b]
ARV Class and Drugs Rifabutin Interactions and Recommendations Rifampin Interactions and Recommendations
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
Abacavir (ABC)
  • Rifabutin: No clinically significant interactions.
  • Rifampin: May reduce concentration of ABC.
  • Rifampin: No dose adjustments recommended for concomitant use with ABC.
Emtricitabine (FTC)
  • Rifabutin, rifampin: No clinically significant interactions.
N/A
Lamivudine (3TC)
  • Rifabutin, rifampin: No clinically significant interactions.
N/A
Tenofovir alafenamide (TAF)
  • Rifabutin induction of CYP3A and P-gP is expected to decrease TAF levels.
  • Rifampin induction of CYP3A may reduce concentration of TAF.
  • Rifabutin: Concomitant use with TAF is contraindicated.
  • Rifampin: Concomitant use with TAF is contraindicated.
Tenofovir disoproxil fumarate (TDF)
  • Rifabutin, rifampin: No clinically significant interactions.
N/A
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Doravirine (DOR)
  • Rifabutin induction of CYP3A is expected to decrease DOR levels.
  • Rifampin induction of CYP3A reduces bioavailability of DOR.
  • Rifabutin: When used concomitantly, increase DOR dosage to 100 mg twice per day.
  • Rifampin: Concomitant use with DOR is contraindicated.
Efavirenz (EFV)
  • Rifabutin: EFV induction of CYP3A reduces bioavailability of rifabutin, but coadministration has no effect on EFV levels.
  • Rifampin: No clinically significant interactions.
  • Rifabutin: If EFV and rifabutin are used concomitantly, increase dose of rifabutin by 50%, especially if rifabutin is dosed 3 times weekly.
Etravirine (ETR)
  • Rifabutin: When used concomitantly with ETR, increased rifabutin levels are expected and decreased ETR levels may be seen.
  • Rifampin induction of CYP3A reduces bioavailability of ETR.
  • Rifabutin: If ETR and rifabutin are used concomitantly, rifabutin should be dosed at 300 mg daily, with no changes to the dose of ETR. Continue this dosing until at least 2 weeks after rifabutin is stopped.
    • Concomitant use of a boosted PI with ETR and rifabutin is contraindicated.
  • Rifampin: Concomitant use is contraindicated.
Nevirapine (NVP)
  • Rifampin induction of CYP3A reduces bioavailability of NVP.
  • Rifampin: Concomitant use is contraindicated.
Rilpivirine (RPV)
  • Rifabutin induction of CYP3A and P-gP decreases RPV levels.
  • Rifampin induction of CYP3A reduces bioavailability of RPV.
  • Rifabutin: Concomitant use is contraindicated.
  • Rifampin: Concomitant use is contraindicated.
Protease Inhibitor (PIs) and Boosted PIs
All PIs
  • Rifabutin: Does not affect levels of boosted PIs, but when used concomitantly, bioavailability of rifabutin and its active metabolite is increased.
  • Rifampin induction of CYP3A reduces bioavailability of ALL protease inhibitors.
  • Rifabutin: When used concomitantly, reduce rifabutin dose to 150 mg 3 times per week.
  • Rifampin: Concomitant use of PIs and rifampin is contraindicated.
Integrase Strand Transfer Inhibitors (INSTIs)
Bictegravir (BIC)
  • Rifabutin induction of CYP3A and P-gP decreases BIC levels.
  • Rifampin induction of CYP3A reduces bioavailability.
  • Rifabutin: Concomitant use is contraindicated.
  • Rifampin: Concomitant use is contraindicated.
Dolutegravir (DTG)
  • Rifabutin: No clinically significant interactions.
  • Rifampin induction of CYP3A reduces bioavailability of DTG.
  • Rifampin: When used concomitantly, dose DTG at 50 mg twice per day instead of 50 mg once per day.
Elvitegravir (EVG), boosted
  • Rifabutin induction of CYP3A expected to decrease levels of EVG.
  • Rifampin induction of CYP3A reduces bioavailability of EVG.
  • Rifabutin: Concomitant use is not recommended.
    • When concomitant use cannot be avoided, dose rifabutin at 150 mg 3 times per week and monitor for response to EVG-containing regimen.
  • Rifampin: Concomitant use is contraindicated.
Raltegravir (RAL)
  • Rifabutin: No clinically significant interactions.
  • Rifampin induction of CYP3A reduces bioavailability of RAL.
  • Rifampin: When used concomitantly, dose RAL at 800 mg twice per day instead of 400 mg twice per day.
    • Do not use RAL HD.

Abbreviations: ARV, antiretroviral; CYP, cytochrome P450; P-gP, P-glycoprotein.

Notes:

  1. Rifapentine has not been studied with many antiretrovirals, but its CYP3A inducing effects are expected to be lower than those seen with rifampin but higher than those seen with rifabutin. Global research has suggested that rifapentine combined with isoniazid may be safe and effective for patients using efavirenz or (dose adjusted) raltegravir or dolutegravir, but further studies are required before recommendations can be made about the use of this medicine with other antiretroviral agents.
  2. Isoniazid, pyrazinamide, ethambutol, rifaximin: No clinically significant interactions with ARVs expected; no dose adjustments necessary. Rifaximin is a rifamycin drug that is not used to treat tuberculosis, but may be seen in patients with hepatic encephalopathy or some forms of infectious diarrhea.

Gender Affirming Hormones

Lead author, Joshua R. Sawyer, PharmD, AAHIVP, with the Medical Care Criteria Committee, November 2019

Table 40: Gender Affirming Hormones
→ Cyproterone acetate, estradiol, finasteride, goserelin, leuprolide acetate, spironolactone, testosterone
ARV Drug Class or Medication Mechanism of Action Clinical Comments
ARV medications, all
  • Cyproterone acetate: The interaction with ARVs has not been studied.
  • Estradiol: The interaction between ARVs and estradiol in transgender women has not been studied.
  • Finasteride: The interaction with ARVs has not been studied. Finasteride is metabolized by CYP3A4; levels may increase when taken concomitantly with COBI-boosted ARVs, but clinical significance is expected to be minimal.
  • Goserelin: The interaction with ARVs has not been studied. Based upon what is known about metabolism of goserelin, no clinically significant interactions are expected.
  • Leuprolide acetate: The interaction with ARVs has not been studied. Based upon what is known about metabolism of leuprolide acetate, no clinically significant interactions are expected.
  • Testosterone: The interaction between ARVs and testosterone in transgender men has not been studied. Testosterone has been used in androgen-deficient cisgender men with HIV without clinical drug interactions.
  • Spironolactone: No interactions expected.
  • Estradiol: When prescribing ARVs, consider the use of medications not expected to interact with estradiol.
  • Finasteride: No dose adjustments recommended.
Cobicistat (COBI)
  • Estradiol: Based upon known mechanisms of metabolism, COBI-boosted PIs or other ARVs may have mixed effects on estradiol levels. COBI does not induce CYP1A2, and as such may increase estradiol levels by inhibition of CYP3A.
  • Finasteride: When taken concomitantly, finasteride levels may be increased, but with minimal clinical significance.
  • Testosterone: Based upon known mechanisms of metabolism, there is limited potential that COBI-boosted PIs or other ARVs may increase testosterone levels. The relevance of this interaction is expected to be low in transgender men.
  • Estradiol: When taken concomitantly with COBI-boosted ARVS, monitor for signs of estrogen deficiency or excess.
  • Finasteride: No dose adjustments are recommended.
  • Testosterone: No dose adjustments are recommended.
Doravirine (DOR)
  • Estradiol: No interactions expected.
  • Testosterone: No interactions expected.
N/A
Efavirenz (EFV)
  • Estradiol: EFV could induce CYP3A and could decrease estradiol levels.
  • Finasteride: Levels may decrease when taken concomitantly with EFV.
  • Testosterone: Levels may decrease when taken concomitantly with EFV.
  • Estradiol: No dose adjustments are recommended, but when taken concomitantly with EFV, monitor for signs of estrogen deficiency or excess.
  • Finasteride: No dose adjustments recommended.
  • Testosterone: No dose adjustments recommended.
Etravirine (ETR)
  • Estradiol: ETR could induce CYP3A and could decrease estradiol levels.
  • Finasteride: Levels may decrease when taken concomitantly with ETR.
  • Testosterone: Levels may decrease when taken concomitantly with ETR.
  • Estradiol: No dose adjustments are recommended, but when taken concomitantly with ETR, monitor for signs of estrogen deficiency or excess.
  • Finasteride: No dose adjustments recommended.
  • Testosterone: No dose adjustments recommended.
INSTIs, non-boosted
(dolutegravir, DTG; raltegravir, RAL)
  • Estradiol: No interactions expected.
  • Finasteride: No interactions expected.
  • Testosterone: No interactions expected.
N/A

NRTIs, non-boosted
(abacavir, ABC; emtricitabine, FTC; lamivudine, 3TC; tenofovir alafenamide, TAF; tenofovir disoproxil fumarate, TDF)

  • Estradiol: No interactions expected.
  • Finasteride: No interactions expected.
  • Testosterone: No interactions expected.
N/A
Rilpivirine (RPV)
  • Estradiol: No interactions expected.
  • Finasteride: No interactions expected.
  • Testosterone: No interactions expected.
N/A
Ritonavir (RTV)
  • Estradiol: RTV may induce CYP1A2, which could decrease estradiol levels. This outweighs the RTV inhibition of CYP3A.
  • Testosterone: No interactions expected.
N/A
Abbreviations: ARV, antiretroviral; CYP, cytochrome P450; INSTI, integrase strand transfer inhibitor; N/A, not applicable; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.
References

Hembree WC, Cohen-Kettenis PT, Gooren L, et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons: An Endocrine Society Clinical Practice Guideline. Endocr Pract 2017;23(12):1437. [PMID: 29320642]

Irving A, Lehault WB. Clinical pearls of gender-affirming hormone therapy in transgender patients. Ment Health Clin 2018;7(4):164-167. [PMID: 29955517]