Drug-Drug Interactions: Capsid Inhibitors and Other Drugs

Updated September 12, 2024 Reviewed September 12, 2024

Drug-Drug Interactions

Table 24g. Drug Interactions Between the Capsid Inhibitor Lenacapavir and Other Drugs (Including Antiretroviral Drugs)

This table provides information on the known or predicted interactions between lenacapavir (LEN), an HIV capsid inhibitor, and other drugs, including antiretroviral (ARV) drugs.

LEN is available as an oral tablet (to be used only as initial therapy) and a long-acting injectable formulation that is administered every 6 months. LEN is a moderate cytochrome P450 (CYP) 3A4 inhibitor and may increase the concentration of drugs metabolized by CYP3A4. Due to the long half-life of the injectable formulation, this inhibitory effect may persist, and clinicians should continue to assess for drug interactions for up to 9 months after the last LEN injection. Recommendations for managing a particular drug interaction may differ depending on whether LEN is being initiated in a patient on a stable concomitant medication or whether a new medication is being initiated in a patient on a stable LEN-containing 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. People with HIV should be counseled about the importance of informing all their health care providers about their HIV regimen prior to starting any new concomitant medications (e.g., prescription, over-the-counter, and herbal or dietary supplements) to minimize the risk of drug–drug interactions.

Concomitant Drug Class/ Name	Effect on LEN and/or Concomitant Drug Concentrations	Dosing Recommendations and Clinical Comments
Acid Reducers
Antacids, H2 Receptor Antagonists, Proton Pump Inhibitors	↔ expected	No dose adjustment needed
Alpha-Adrenergic Antagonists for Benign Prostatic Hyperplasia
Alfuzosin	↑ alfuzosin expected	Consider an alternative to alfuzosin or an alternative ARV. If coadministered, monitor blood pressure.
Doxazosin	↑ doxazosin possible	No dose adjustment needed. Monitor blood pressure.
Tamsulosin	↑ tamsulosin possible	Initiate tamsulosin at 0.4 mg/day. Monitor blood pressure.
Terazosin	↔ expected	No dose adjustment needed
Silodosin	↑ silodosin possible	No dose adjustment needed
Antibacterials—Antimycobacterials
Bedaquiline	↑ bedaquiline expected	Consider alternatives unless benefits outweigh risks. Monitor liver function and ECG for QTc prolongation.
Rifabutin	↓ LEN expected	Do not coadminister.
Rifampin	LEN AUC ↓ 84%	Contraindicated
Rifapentine	Daily and Weekly Dosing ↓ LEN expected	Do not coadminister
Antibacterials—Macrolides
Azithromycin	↔ expected	No dose adjustment needed
Clarithromycin	↑ LEN possible	No dose adjustment needed
Erythromycin	↑ LEN possible	No dose adjustment needed
Anticoagulants
Apixaban	↑ apixaban possible	No dose adjustment needed Monitor for apixaban-related adverse events, such as increased bleeding.
Dabigatran	↑ dabigatran possible	No dose adjustment needed Monitor for dabigatran-related adverse events, such as increased bleeding.
Edoxaban	↑ edoxaban possible	No dose adjustment needed Monitor for edoxaban-related adverse events, such as increased bleeding.
Rivaroxaban	↑ rivaroxaban possible	Monitor for rivaroxaban-related adverse events, such as increased bleeding, and adjust rivaroxaban dose accordingly.
Warfarin	↑ warfarin possible	Monitor INR and adjust warfarin dose accordingly.
Antidepressants, Anxiolytics, and Antipsychotics Also see the Sedative/Hypnotics section below.
Bupropion	↔ expected	No dose adjustment needed
Buspirone	↑ buspirone expected	Administer lowest dose of buspirone with caution and titrate buspirone dose based on clinical response. Dose reduction may be necessary. Monitor for buspirone-related adverse events.
Desvenlafaxine	↔ expected	No dose adjustment needed
Duloxetine	↔ expected	No dose adjustment needed
Mirtazapine	↑ mirtazapine possible	No dose adjustment needed. Monitor for mirtazapine-related adverse events.
Nefazodone	↑ LEN possible	No dose adjustment needed.
Selective Serotonin Reuptake Inhibitor (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vortioxetine)	↑ paroxetine possible ↔ citalopram, escitalopram, fluoxetine, fluvoxamine, sertraline, vortioxetine expected	Dose reduction may be necessary with paroxetine. No dose adjustment needed
Trazodone	↑ trazodone expected	Administer lowest dose of trazodone and monitor for CNS and CV adverse events.
Tricyclic Antidepressants (e.g., amitriptyline, doxepin, nortriptyline)	↔ expected	No dose adjustment needed
Venlafaxine	↔ expected	No dose adjustment needed
Antipsychotics
Aripiprazole	↑ aripiprazole possible	No dose adjustment needed
Brexpiprazole	↑ brexpiprazole expected	If patient is a known CYP2D6 poor metabolizer, then administer one-quarter of usual brexpiprazole dose.
Cariprazine	↑ cariprazine possible	No dose adjustment needed
Iloperidone	↑ iloperidone possible	No dose adjustment needed or consider dose reduction. Monitor for iloperidone-related adverse events.
Lumateperone	↑ lumateperone expected	Reduce dose of lumateperone to 21 mg once daily.
Lurasidone	↑ lurasidone expected	If LEN is added to lurasidone therapy, administer half of lurasidone dose. If lurasidone is added to LEN therapy, the recommended starting dose of lurasidone is 20 mg daily, and the maximum recommended dose is 80 mg daily.
Olanzapine Olanzapine/Samidorphan	↔ LEN olanzapine expected ↑ samidorphan possible	No dose adjustment needed
Other Antipsychotics (e.g., clozapine, risperidone, thioridazine)	↑ clozapine possible	No dose adjustment needed. Monitor for clozapine-related adverse events.
	↑ risperidone possible	No dose adjustment needed
	↑ thioridazine possible ↓ LEN possible	Do not coadminister.
Pimavanserin	↑ pimavanserin possible	No dose adjustment needed. Monitor ECG for QTc prolongation.
Pimozide	↑ pimozide expected	Contraindicated
Quetiapine	↑ quetiapine expected	Consider alternatives unless benefits outweigh risks. Monitor ECG for QTc prolongation and consider dose reduction accordingly.
Ziprasidone	↔ expected	No dose adjustment needed
Antimigraine
Ergot Derivatives	↑ dihydroergotamine, ergotamine, and methylergonovine expected	Do not coadminister.
Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonists
Atogepant	↑ atogepant expected	No dose adjustment needed
Rimegepant	↑ rimegepant expected	Avoid a second dose of rimegepant within 48 hours.
Ubrogepant	↑ ubrogepant expected	Avoid a second dose of ubrogepant within 24 hours.
Zavegepant	↔ expected	No dose adjustment needed
Serotonin 5-HT1B, 1D Receptor Agonist
Almotriptan	↔ expected	No dose adjustment needed
Eletriptan	↑ eletriptan expected	No dose adjustment needed. Monitor for eletriptan-related adverse events.
Frovatriptan, Naratriptan, Rizatriptan, Sumatriptan Zolmitriptan	↔ expected	No dose adjustment needed
Antifungals
Fluconazole	↑ LEN possible	No dose adjustment needed
Ibrexafungerp	↑ ibrexafungerp possible	No dose adjustment needed
Isavuconazole	↔ expected	No dose adjustment needed
Itraconazole	↑ LEN possible	No dose adjustment needed
Posaconazole	↑ LEN possible	No dose adjustment needed
Voriconazole	↑ LEN AUC 41%	No dose adjustment needed
Antimalarials
Artemether/Lumefantrine	↑ artemether and lumefantrine possible	Monitor for lumefantrine-related adverse events, including QTc prolongation.
Artesunate	↔ expected	No dose adjustment needed
Atovaquone/Proguanil	↔ expected	No dose adjustment needed
Mefloquine	↑ mefloquine possible	Monitor for mefloquine-related adverse events, including QTc prolongation.
Antiplatelets
Clopidogrel	↓ clopidogrel active metabolite possible	Consider alternative ARV or antiplatelet drug. If coadministered, monitor for clopidogrel-related adverse events.
Prasugrel	↔ expected	No dose adjustment needed
Ticagrelor	↑ ticagrelor possible	No dose adjustment needed. Monitor for ticagrelor-related adverse events.
Vorapaxar	↑ vorapaxar possible	No dose adjustment needed
Antipneumocystis and Antitoxoplasmosis
Atovaquone Oral suspension	↔ expected	No dose adjustment needed
Antiseizure
Carbamazepine	↓ LEN expected	Contraindicated
Eslicarbazepine	↓ LEN expected	Do not coadminister.
Ethosuximide	↑ ethosuximide possible	Monitor for ethosuximide-related adverse events and adjust ethosuximide dose accordingly.
Lamotrigine	↔ expected	No dose adjustment needed
Oxcarbazepine	↓ LEN expected	Do not coadminister.
Phenobarbital	↓ LEN expected	Do not coadminister.
Phenytoin	↓ LEN expected	Contraindicated
Primidone	↓ LEN expected	Do not coadminister.
Valproic Acid	↔ expected	No dose adjustment needed
Antivirals—Hepatitis C
Elbasvir/Grazoprevir	↔ expected	No dose adjustment needed
Glecaprevir/Pibrentasvir	↔ expected	No dose adjustment needed
Ledipasvir/Sofosbuvir	↔ expected	No dose adjustment needed
Sofosbuvir/Velpatasvir	↔ expected	No dose adjustment needed
Sofosbuvir/Velpatasvir/Voxilaprevir	↔ expected	No dose adjustment needed
Antivirals—Miscellaneous (e.g., for CMV, Mpox)
Brincidofovir	↔ expected	No dose adjustment needed
Cidofovir	↔ expected	No dose adjustment needed
Maribavir	↔ expected	No dose adjustment needed
Tecovirimat	↓ LEN possible	No dose adjustment needed
Valganciclovir	↔ expected	No dose adjustment needed
Antivirals—SARS-CoV-2
Molnupiravir	↔ expected	No dose adjustment needed
Ritonavir-Boosted Nirmatrelvir	↑ LEN possible	No dose adjustment needed
Remdesivir	↔ expected	No dose adjustment needed
Antiretroviral Drugs
CCR5 Antagonist
MVC	↔ expected	No dose adjustment needed
CD4 Post-attachment Inhibitor
IBA	↔ expected	No dose adjustment needed
gp120 Attachment Inhibitor
FTR	↔ expected	No dose adjustment needed
INSTIs
BIC, CAB (IM or PO), DTG, EVG/c, RAL	↔ expected	No dose adjustment needed
NRTIs
ABC, 3TC, FTC	↔ expected	No dose adjustment needed
TAF	TAF AUC ↑ 32%	No dose adjustment needed
TDF	TDF AUC ↑ 47%	No dose adjustment needed
NNRTIs
EFV	LEN AUC↓ 56%	Do not coadminister.
ETR	↓ LEN expected	Do not coadminister.
DOR	↑ DOR possible	No dose adjustment needed
RPV (IM or PO)	↑ RPV possible	No dose adjustment needed
PIs
ATV/r	↑ LEN expected	Do not coadminister.
ATV/c	LEN AUC ↑ 4-fold	Do not coadminister.
DRV/c	DRV/c AUC ↑ 94%	No dose adjustment needed
DRV/r	↑ LEN expected	No dose adjustment needed
Beta-Agonists, Long-Acting Inhaled
Arformoterol, Formoterol, Indacaterol, Olodaterol, Salmeterol	↔ expected	No dose adjustment needed
Cardiac Medications
Antiarrhythmics
Amiodarone	↑ amiodarone expected ↑ LEN possible	Do not coadminister.
Digoxin	↑ digoxin expected	Consider alternative ARV or antiarrhythmic. If coadministered, monitor digoxin therapeutic concentration.
Disopyramide	↑ disopyramide expected	Do not coadminister.
Dofetilide	↔ expected	No dose adjustment needed
Dronedarone	↑ dronedarone possible ↑ LEN possible	Consider alternative ARV or cardiac medication. If coadminstered, monitor for dronedarone-related adverse events.
Flecainide	↔ expected	No dose adjustment needed
Lidocaine	↑ propafenone possible	Consider alternative ARV or antiarrhythmics. If coadministered, monitor for antiarrhythmic-related adverse events and monitor concentrations, if available.
Mexiletine	↔ expected	No dose adjustment needed
Propafenone	↑ propafenone possible	Consider alternative ARV or antiarrhythmics. If coadministered, monitor for antiarrhythmic-related adverse events and monitor concentrations, if available.
Quinidine	↑ quinidine expected	Do not coadminster.
Sotalol	↔ expected	No dose adjustment needed
Beta Blockers
Atenolol, Bisoprolol, Carvedilol, Labetalol, Metoprolol, Nebivolol, Timolol	↔ expected	No dose adjustment needed
Calcium Channel Blockers
Amlodipine, Felodipine, Nifedipine	↑ amlodipine, felodipine expected ↑ nifedipine possible	Monitor and dose adjust according to clinical response and adverse events.
Diltiazem, Verapamil	↑ diltiazem possible ↔ verapamil expected	No dose adjustment needed
Cardiac – Other
Bosentan	↓ LEN expected	Do not coadminister.
Eplerenone	↑ eplerenone expected	For Post-MI CHF Dosing of eplerenone should not exceed 25 mg daily. For Hypertension Initiate at 25 mg once daily. Dosing may be increased to a maximum of 25 mg twice daily.
Ivabradine	↑ ivabradine expected	Do not coadminister.
Mavacamten	↓ LEN possible ↑ mavacamten expected	Initiate mavacamten at the recommended starting dose of 5 mg daily in patients who are on stable therapy with LEN. Reduce dose of mavacamten by one level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients who are on mavacamten treatment and intend to initiate LEN.
Ranolazine	↑ ranolazine expected	Limit ranolazine to 500 mg twice daily.
Corticosteroids
Beclomethasone Inhaled or intranasal Ciclesonide Inhaled	↔ expected	No dose adjustment needed
Budesonide, Fluticasone, Mometasone Inhaled or intranasal	↑ glucocorticoids possible	Initiate with the lowest starting dose and titrate carefully and monitor for adrenal insufficiency, Cushing’s syndrome, and other corticosteroid-related adverse events.
Betamethasone Systemic	↑ betamethasone possible ↓ LEN possible	Do not coadminister.
Budesonide, Prednisone, Prednisolone Systemic	↑ glucocorticoids expected	Initiate with the lowest starting dose, titrate carefully, and monitor for adrenal insufficiency, Cushing’s syndrome, and other corticosteroid-related adverse events.
Dexamethasone Systemic	↑ dexamethasone expected ↓ LEN expected if used with dexamethasone >16 mg/day	Initiate with the lowest starting dose, titrate carefully, and monitor for adrenal insufficiency, Cushing’s syndrome, and other corticosteroid-related adverse events. Do not coadminister with dexamethasone >16 mg/day.
Betamethasone, Methylprednisolone, Triamcinolone Local injections, including intra-articular, epidural, or intra-orbital	↑ glucocorticoids possible	Monitor for adrenal insufficiency, Cushing’s syndrome, and other corticosteroid-related adverse events.
Glucose-Lowering
Canagliflozin	↔ expected	No dose adjustment needed
Saxagliptin	↑ saxagliptin possible	No dose adjustment needed
Dapagliflozin/Saxagliptin	↑ saxagliptin possible	No dose adjustment needed
Herbal Products
St. John’s Wort	↓ LEN expected	Contraindicated
Hormonal Therapies—Contraceptives
Injectable Contraceptives Depot MPA	↑ MPA possible	No dose adjustment needed
Oral Contraceptives (e.g., desogestrel, drospirenone, ethinyl estradiol, levonorgestrel, norgestimate)	↑ contraceptive exposures possible	No dose adjustment needed
Subdermal Implant Contraceptives (e.g., etonogestrel, levonorgestrel)	↑ contraceptive exposures possible	No dose adjustment needed
Transdermal Contraceptives (e.g., ethinyl estradiol/norelgestromin, ethinyl estradiol/levonorgestrel)	↑ contraceptive exposures possible	No dose adjustment needed
Vaginal Ring Contraceptives (e.g., etonogestrel/ethinyl estradiol, segesterone/ethinyl estradiol)	↑ contraceptive exposures possible	No dose adjustment needed
Emergency Contraceptives Levonorgestrel (oral)	↑ levonorgestrel possible	No dose adjustment needed
Hormonal Therapies—Gender Affirming and Menopause
Estradiol	↔ expected	No dose adjustment needed
5-Alpha Reductase Inhibitors (e.g., dutasteride, finasteride)	↑ dutasteride and finasteride possible	No dose adjustment needed
Testosterone	↑ testosterone possible	No dose adjustment needed
Other Gender-Affirming Medications	↔ goserelin, leuprolide acetate expected	No dose adjustment needed
Menopausal Hormone Replacement Therapy (e.g., conjugated estrogens, drospirenone, estradiol, medroxyprogesterone, progesterone)	↑ estrogen and progesterone possible ↑ drospirenone possible	No dose adjustment needed
Immunosuppressants
Cyclosporine, Everolimus, Sirolimus, Tacrolimus	↑ immunosuppressant expected	Initiate with an adjusted dose of immunosuppressant to account for potential increased concentrations of the immunosuppressant and monitor for immunosuppressant-related adverse events. Therapeutic drug monitoring of immunosuppressant is recommended. Consult with a specialist as necessary.
Lipid-Modifying
Atorvastatin	↑ atorvastatin possible	No dose adjustment needed
Fluvastatin	↔ expected	No dose adjustment needed
Lomitapide	↑ lomitapide expected	Contraindicated
Lovastatin	↑ lovastatin expected	Administer the lowest effective lovastatin dose while monitoring for adverse events
Pitavastatin	↔ expected	No dose adjustment needed
Pravastatin	↔ expected	No dose adjustment needed
Rosuvastatin	↑ rosuvastatin possible	No dose adjustment needed
Simvastatin	↑ simvastatin expected	Administer the lowest effective simvastatin dose while monitoring for adverse events.
Narcotics and Treatment for Opioid Dependence
Buprenorphine Sublingual, buccal, or implant	↑ buprenorphine possible	Initiation of Buprenorphine in Patients Taking LEN Titrate buprenorphine dose to desired effect and use the lowest feasible initial dose. Initiation of LEN in Patients Taking Buprenorphine Dose adjustment for buprenorphine may be needed. Monitor for buprenorphine-related adverse events.
Fentanyl	↑ fentanyl possible	Monitor for fentanyl-related adverse events, including potentially fatal respiratory depression. Fentanyl dose reduction may be necessary.
Lofexidine	↔ expected	No dose adjustment needed
Methadone	↑ methadone possible	Initiation of Methadone in Patients Taking LEN Titrate methadone dose to desired effect and use the lowest feasible initial dose. Initiation of LEN in Patients Taking Methadone Dose adjustment for methadone may be needed. Monitor for buprenorphine-related adverse events.
Oxycodone	↑ oxycodone possible	Monitor for opioid-related adverse events, including potentially fatal respiratory depression. Oxycodone dose reduction may be necessary.
Tramadol	↑ tramadol possible	Tramadol dose adjustments may be necessary. Monitor for clinical response and tramadol-related adverse events.
PDE5 Inhibitors
Avanafil	↑ avanafil expected	Avanafil dose should not exceed 50 mg once every 24 hours.
Sildenafil	↑ sildenafil expected	For Treatment of Erectile Dysfunction Start with sildenafil 25 mg and monitor for sildenafil-related adverse events. For Treatment of PAH Reduce the dose of sildenafil to 20 mg three times a day when discontinuing treatment with LEN.
Tadalafil	↑ tadalafil expected	For Treatment of Erectile Dysfunction For once-daily use: Consider maximum dose of 2.5 mg daily. If higher dose is needed, consider alternative PDE5 inhibitor. For use as needed: Consider maximum dose of 10 mg every 72 hours. If higher dosing is needed, consider alternative PDE5 inhibitor. For Treatment of PAH Do not coadminister. For Treatment of Benign Prostatic Hyperplasia Consider maximum dose of 2.5 mg daily. Use caution and monitor for AEs if dose increases to 5 mg.
Vardenafil	↑ vardenafil expected	Vardenafil dose should not exceed 5 mg once every 24 hours.
Sedative/Hypnotics
Benzodiazepines
Alprazolam, Diazepam, Triazolam	↑ alprazolam expected	Consider lowest dose and monitor for benzodiazepine-related adverse events.
Clonazepam	↑ clonazepam possible	Use with caution and consider alternative benzodiazepines.
Lorazepam, Oxazepam, Temazepam	↔ expected	No dose adjustment needed
Midazolam (Oral), Triazolam	↑ midazolam AUC 259-308%	Use with caution and consider alternative benzodiazepine.
Orexin Receptor Antagonist
Daridorexant, Lemborexant, Suvorexant	↑ daridorexant expected ↑ lemborexant expected ↑ suvorexant expected	Maximum recommended daridorexant dose is 25 mg. Do not coadminister with lemborexant. Initiate suvorexant dose at 5 mg daily. Suvorexant dose can be increased to 10 mg once per night if the 5 mg dose is not effective. Do not exceed 10 mg per night.
Other Sedatives
Eszopiclone	↑ eszopiclone expected	Consider lowest dose and monitor for eszopiclone-related adverse events.
Zolpidem	↑ zolpidem possible	Consider initiating zolpidem at a low dose.
Miscellaneous Drugs
Calcifediol	↑ calcifediol possible	No dose adjustment needed
Cisapride	↑ cisapride expected	Do not coadminister.
Colchicine	↑ colchicine expected	For Treatment of Gout Flares Administer single colchicine dose of 1.2 mg. Do not repeat dose for at least 3 days. For Treatment of Familial Mediterranean Fever Colchicine dose should not exceed 1.2 mg daily (may be given as 0.6 mg twice a day).
Dronabinol	↔ expected	No dose adjustment needed
Eluxadoline	↔ expected	No dose adjustment needed
Finerenone	↑ finerenone expected	Monitor serum potassium at initiation and during therapy according to finerenone product labeling.
Flibanserin	↑ flibanserin expected	Contraindicated
Naloxegol	↑ naloxegol expected	Avoid use; if coadministration is necessary, decrease dosage of naloxegol and monitor for naloxegol-related adverse events.
Praziquantel	↑ praziquantel possible	Consider alternative antiretroviral. If coadministration is necessary, monitor for praziquantel-related adverse events.
Key to Symbols ↑ = increase ↓ = decrease ↔ = less than 20% change in AUC Key: 3TC = lamivudine; ABC = abacavir; AE = adverse event; AUC = area under the curve; ARV = antiretroviral; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; BIC = bictegravir; CAB = cabotegravir; CD4 = CD4 T lymphocyte; CHF = congestive heart failure; CMV = cytomegalovirus; CNS = central nervous system; CV = cardiovascular; CYP = cytochrome P450; DOR = doravirine; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; ECG = electrocardiogram; EFV = efavirenz; ETR = etravirine; EVG/c = elvitegravir/cobicistat; FTC = emtricitabine; FTR = fostemsavir; IBA = ibalizumab; IM = intramuscular; INR = international normalized ratio; INSTI = integrase strand transfer inhibitor; QTc = QT corrected for heart rate; LEN = lenacapavir; MI = myocardial infarction; MPA = medroxyprogesterone acetate; MVC = maraviroc; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PAH = pulmonary arterial hypertension; PDE5 = phosphodiesterase type 5; PI = protease inhibitor; PO = orally; RAL = raltegravir; RPV = rilpivirine; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate