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 judgement 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 herbs 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 |
---|---|---|
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 |
No dose adjustment needed. Monitor blood pressure. |
Terazosin |
↔ terazosin expected |
No dose adjustment needed. |
Silodosin |
↑ silodosin possible |
No dose adjustment needed. |
Antibacterials—Antimycobacterials | ||
Bedaquiline |
↑ bedaquiline possible |
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 |
↓ LEN expected |
Do not coadminister. |
Antibacterials—Macrolides | ||
Azithromycin |
↔ LEN 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. |
Anticonvulsants | ||
Carbamazepine |
↓ LEN expected |
Contraindicated. |
Eslicarbazepine |
↓ LEN expected |
Do not coadminister. Consider alternative anticonvulsant or ARV. |
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. Consider alternative anticonvulsant or ARV. |
Phenobarbital |
↓ LEN expected |
Do not coadminister. Consider alternative anticonvulsant or ARV. |
Phenytoin |
↓ LEN expected |
Contraindicated. |
Valproic Acid |
↔ expected |
No dose adjustment needed. |
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. |
Nefazodone |
↑ LEN possible |
No dose adjustment needed. |
Trazodone |
↑ trazodone expected |
Administer lowest dose of trazodone and monitor for CNS and CV adverse events. |
Tricyclic Antidepressants Amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, maprotiline, nortriptyline, protriptyline, trimipramine |
↔ expected |
No dose adjustment needed. |
Selective Serotonin Reuptake Inhibitor Paroxetine |
↑ paroxetine possible |
Dose reduction may be necessary. Monitor for paroxetine-related adverse events. |
Selective Serotonin Reuptake Inhibitors (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, sertraline) |
↔ expected |
No dose adjustment needed. |
Antipsychotics |
||
Aripiprazole |
↑ aripiprazole possible |
No dose adjustment needed. |
Brexpiprazole |
↑ aripiprazole expected |
If patient is known CYP2D6 poor metabolizer, then administer 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 |
Recommended dose of lumateperone is 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 |
↔ expected |
No dose adjustment needed. |
Pimavanserin |
↑ pimavanserin possible |
No dose adjustment needed. Monitor ECG for QTc prolongation. |
Pimozide |
↑ pimozide expected |
Do not coadminister. |
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. |
Antifungals | ||
Fluconazole |
↔ expected |
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. |
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. |
Prasurgrel |
↔ 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. |
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. |
NVP |
↓ LEN expected |
Do not coadminister. |
RPV (IM or PO) |
↑ RPV possible |
No dose adjustment needed. |
PIs | ||
ATV unboosted, 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. |
LPV/r |
↑ LEN expected |
No dose adjustment needed. |
Antivirals—Orthopoxviruses (Mpox, Smallpox) | ||
Brincidofovir |
↔ expected |
No dose adjustment needed. |
Cidofovir |
↔ expected |
No dose adjustment needed. |
Tecovirimat |
↓ LEN possible |
No dose adjustment needed. |
Beta-Agonists, Long-Acting Inhaled | ||
Arformoterol, Formoterol, Indacaterol, Olodaterol, Salmeterol |
↔ expected |
No dose adjustment needed. |
Cardiac Medications | ||
Amiodarone |
↑ amiodarone expected ↑ LEN possible |
Do not coadminister. |
Disopyramide |
↑ disopyramide expected |
Do not coadminister. |
Lidocaine, Propafenone |
↑ lidocaine possible ↑ propafenone possible |
Consider alternative ARV or antiarrhythmics. If coadministered, monitor for antiarrhythmic-related adverse events and monitor concentrations, if available. |
Dofetilide, Fecainide, Mexiletine |
↔ expected |
No dose adjustment needed. |
Dronedarone |
↑ dronedarone possible ↑ LEN possible |
Consider alternative ARV or cardiac medication. If coadminstered, monitor for dronedarone-related adverse events. |
Quinidine |
↑ quinidine expected |
Do not coadminster. |
Beta Blockers (e.g., carvediol, metoprolol, timolol) |
↔ expected |
No dose adjustment needed. |
Bosentan |
↓ LEN expected |
Do not coadminister. |
Calcium Channel Blockers | ||
Diltiazem, Verapamil |
↑ diltiazem and verapamil possible |
Monitor and dose adjust according to clinical response and adverse events. |
Digoxin |
↑ digoxin expected |
Consider alternative ARV or antiarrhythmic. If coadministered, monitor digoxin therapeutic concentration. |
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. |
Ranolazine |
↑ ranolazine expected |
Limit ranolazine to 500 mg twice daily. |
Ivabradine |
↑ ivabradine expected |
Do not coadminister. |
Corticosteroids | ||
Beclomethasone Inhaled or intranasal Ciclesonide Inhaled |
↔ expected |
No dose adjustment needed. |
Budesonide, Fluticasone, Mometasone Inhaled or intranasal |
↑ budesonide, fluticasone, mometasone 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 |
↔ expected |
No dose adjustment needed. |
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, Methylprednisoline, Triamicinolone 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 Medications | ||
Canagliflozin |
↔ expected |
No dose adjustment needed. |
Saxagliptin |
↑ saxagliptin possible |
No dose adjustment needed. |
Dapagliflozin/Saxagliptin |
↑ saxagliptin possible |
No dose adjustment needed. |
Hepatitis C Direct-Acting Antiviral Agents | ||
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. |
Herbal Products | ||
St. John’s Wort |
↓ LEN expected |
Contraindicated. |
Hormonal Therapies | ||
Contraceptives—Injectable Depot MPA |
↑ MPA possible |
No dose adjustment needed. |
Contraceptives—Oral Drosperinone, Ethinyl Estradiol, Levonorgestrel, Norethindrone, Norgestimate Subdermal Implant Etonogstrel Subdermal Implant Levonorgestrel Transdermal Ethinyl Estradiol/Norelgestromin Vaginal Ring Etonogestrel/Ethinyl Estradiol Vaginal Ring Segesterone/Ethinyl Estradiol |
↑ contraceptive exposures possible |
No dose adjustment needed. |
Emergency Contraceptives Levonorgestrel (oral) |
↑ levonorgestrel possible |
No dose adjustment needed. |
Gender-Affirming Therapy | ||
Estradiol, Goserelin, Leuprolide Acetate, Finasteride |
↔ expected |
No dose adjustment needed. |
Dutasteride, Testosterone |
↑ dutasteride and testosterone possible |
No dose adjustment needed. |
Menopausal Hormone Replacement Therapy | ||
Conjugated Estrogen (equine and synthetic), Micronized Progesterone, Medroxyprogesterone |
↑ estrogen and progesterone possible |
No dose adjustment needed. |
Drospirenone |
↑ 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 Agents | ||
Atorvastatin |
↑ atorvastatin possible |
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 |
No dose adjustment needed. |
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 |
No dose adjustment needed. |
Vardenafil |
↑ vardenafil expected |
Vardenafil dose should not exceed 5 mg once every 24 hours. |
Sedative/Hypnotics | ||
Alprazolam |
↑ alprazolam expected |
Consider lowest dose and monitor for alprazolam-related adverse events. |
Clonazepam |
↑ clonazepam possible |
Consider alternative benzodiazepines. |
Diazepam |
↑ diazepam possible |
Consider lowest dose and monitor for benzodiazepine-related events. |
Lorazepam, Oxazepam, Temazepam |
↔ expected |
No dose adjustment needed. |
Midazolam (Oral) |
↑ midazolam expected |
Use with caution and consider alternative benzodiazepine. |
Suvorexant |
↑ midazolam expected |
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. |
Triazolam |
↑ triazolam expected |
Use with caution and consider alternative benzodiazepine. |
Zolpidem |
↑ zolpidem possible |
Consider initiating zolpidem at a low dose. |
Miscellaneous Drugs | ||
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). |
Ergot Derivatives Dihydroergotamine, ergotamine, methylergonovine |
↑ dihydroergotamine, ergotamine, methylergonovine expected |
Do not coadminister. |
Flibanserin |
↑ flibanserin expected |
Do not coadminister. |
Naloxegol |
↑ naloxegol expected |
Avoid use; if coadministration is necessary, decrease dosage of naloxegol and monitor for naloxegol-related adverse events. |
Key to Symbols ↑ = increase ↓ = decrease ↔ = no change Key: 3TC = lamivudine; ABC = abacavir; AUC = area under the curve; ARV = antiretroviral; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; BIC = bictegravir; CAB = cabotegravir; CHF = congestive heart failure; CNS = central nervous system; CV = cardiovascular; CYP = cytochrome P 450; DOR = doravirine; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; ECG = electrocardiogram; EFV = efavirenz; ETV = 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; LPV/r = lopinavir/ritonavir; MI = myocardial infarction; MPA = medroxyprogesterone acetate; MVC = maraviroc; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PAH = pulmonary arterial hypertension; PDE5 = phosphodiesterase type 5; PI = protease inhibitor; PO = orally; RAL = raltegravir; RPV = rilpivirine; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate |
Drug-Drug Interactions
Table 24g. Drug Interactions Between the Capsid Inhibitor Lenacapavir and Other Drugs (Including Antiretroviral Drugs)
Concomitant Drug Class/ Name |
Effect on LEN and/or Concomitant Drug Concentrations | Dosing Recommendations and Clinical Comments |
---|---|---|
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 |
No dose adjustment needed. Monitor blood pressure. |
Terazosin |
↔ terazosin expected |
No dose adjustment needed. |
Silodosin |
↑ silodosin possible |
No dose adjustment needed. |
Antibacterials—Antimycobacterials | ||
Bedaquiline |
↑ bedaquiline possible |
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 |
↓ LEN expected |
Do not coadminister. |
Antibacterials—Macrolides | ||
Azithromycin |
↔ LEN 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. |
Anticonvulsants | ||
Carbamazepine |
↓ LEN expected |
Contraindicated. |
Eslicarbazepine |
↓ LEN expected |
Do not coadminister. Consider alternative anticonvulsant or ARV. |
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. Consider alternative anticonvulsant or ARV. |
Phenobarbital |
↓ LEN expected |
Do not coadminister. Consider alternative anticonvulsant or ARV. |
Phenytoin |
↓ LEN expected |
Contraindicated. |
Valproic Acid |
↔ expected |
No dose adjustment needed. |
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. |
Nefazodone |
↑ LEN possible |
No dose adjustment needed. |
Trazodone |
↑ trazodone expected |
Administer lowest dose of trazodone and monitor for CNS and CV adverse events. |
Tricyclic Antidepressants Amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, maprotiline, nortriptyline, protriptyline, trimipramine |
↔ expected |
No dose adjustment needed. |
Selective Serotonin Reuptake Inhibitor Paroxetine |
↑ paroxetine possible |
Dose reduction may be necessary. Monitor for paroxetine-related adverse events. |
Selective Serotonin Reuptake Inhibitors (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, sertraline) |
↔ expected |
No dose adjustment needed. |
Antipsychotics |
||
Aripiprazole |
↑ aripiprazole possible |
No dose adjustment needed. |
Brexpiprazole |
↑ aripiprazole expected |
If patient is known CYP2D6 poor metabolizer, then administer 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 |
Recommended dose of lumateperone is 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 |
↔ expected |
No dose adjustment needed. |
Pimavanserin |
↑ pimavanserin possible |
No dose adjustment needed. Monitor ECG for QTc prolongation. |
Pimozide |
↑ pimozide expected |
Do not coadminister. |
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. |
Antifungals | ||
Fluconazole |
↔ expected |
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. |
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. |
Prasurgrel |
↔ 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. |
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. |
NVP |
↓ LEN expected |
Do not coadminister. |
RPV (IM or PO) |
↑ RPV possible |
No dose adjustment needed. |
PIs | ||
ATV unboosted, 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. |
LPV/r |
↑ LEN expected |
No dose adjustment needed. |
Antivirals—Orthopoxviruses (Mpox, Smallpox) | ||
Brincidofovir |
↔ expected |
No dose adjustment needed. |
Cidofovir |
↔ expected |
No dose adjustment needed. |
Tecovirimat |
↓ LEN possible |
No dose adjustment needed. |
Beta-Agonists, Long-Acting Inhaled | ||
Arformoterol, Formoterol, Indacaterol, Olodaterol, Salmeterol |
↔ expected |
No dose adjustment needed. |
Cardiac Medications | ||
Amiodarone |
↑ amiodarone expected ↑ LEN possible |
Do not coadminister. |
Disopyramide |
↑ disopyramide expected |
Do not coadminister. |
Lidocaine, Propafenone |
↑ lidocaine possible ↑ propafenone possible |
Consider alternative ARV or antiarrhythmics. If coadministered, monitor for antiarrhythmic-related adverse events and monitor concentrations, if available. |
Dofetilide, Fecainide, Mexiletine |
↔ expected |
No dose adjustment needed. |
Dronedarone |
↑ dronedarone possible ↑ LEN possible |
Consider alternative ARV or cardiac medication. If coadminstered, monitor for dronedarone-related adverse events. |
Quinidine |
↑ quinidine expected |
Do not coadminster. |
Beta Blockers (e.g., carvediol, metoprolol, timolol) |
↔ expected |
No dose adjustment needed. |
Bosentan |
↓ LEN expected |
Do not coadminister. |
Calcium Channel Blockers | ||
Diltiazem, Verapamil |
↑ diltiazem and verapamil possible |
Monitor and dose adjust according to clinical response and adverse events. |
Digoxin |
↑ digoxin expected |
Consider alternative ARV or antiarrhythmic. If coadministered, monitor digoxin therapeutic concentration. |
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. |
Ranolazine |
↑ ranolazine expected |
Limit ranolazine to 500 mg twice daily. |
Ivabradine |
↑ ivabradine expected |
Do not coadminister. |
Corticosteroids | ||
Beclomethasone Inhaled or intranasal Ciclesonide Inhaled |
↔ expected |
No dose adjustment needed. |
Budesonide, Fluticasone, Mometasone Inhaled or intranasal |
↑ budesonide, fluticasone, mometasone 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 |
↔ expected |
No dose adjustment needed. |
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, Methylprednisoline, Triamicinolone 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 Medications | ||
Canagliflozin |
↔ expected |
No dose adjustment needed. |
Saxagliptin |
↑ saxagliptin possible |
No dose adjustment needed. |
Dapagliflozin/Saxagliptin |
↑ saxagliptin possible |
No dose adjustment needed. |
Hepatitis C Direct-Acting Antiviral Agents | ||
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. |
Herbal Products | ||
St. John’s Wort |
↓ LEN expected |
Contraindicated. |
Hormonal Therapies | ||
Contraceptives—Injectable Depot MPA |
↑ MPA possible |
No dose adjustment needed. |
Contraceptives—Oral Drosperinone, Ethinyl Estradiol, Levonorgestrel, Norethindrone, Norgestimate Subdermal Implant Etonogstrel Subdermal Implant Levonorgestrel Transdermal Ethinyl Estradiol/Norelgestromin Vaginal Ring Etonogestrel/Ethinyl Estradiol Vaginal Ring Segesterone/Ethinyl Estradiol |
↑ contraceptive exposures possible |
No dose adjustment needed. |
Emergency Contraceptives Levonorgestrel (oral) |
↑ levonorgestrel possible |
No dose adjustment needed. |
Gender-Affirming Therapy | ||
Estradiol, Goserelin, Leuprolide Acetate, Finasteride |
↔ expected |
No dose adjustment needed. |
Dutasteride, Testosterone |
↑ dutasteride and testosterone possible |
No dose adjustment needed. |
Menopausal Hormone Replacement Therapy | ||
Conjugated Estrogen (equine and synthetic), Micronized Progesterone, Medroxyprogesterone |
↑ estrogen and progesterone possible |
No dose adjustment needed. |
Drospirenone |
↑ 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 Agents | ||
Atorvastatin |
↑ atorvastatin possible |
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 |
No dose adjustment needed. |
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 |
No dose adjustment needed. |
Vardenafil |
↑ vardenafil expected |
Vardenafil dose should not exceed 5 mg once every 24 hours. |
Sedative/Hypnotics | ||
Alprazolam |
↑ alprazolam expected |
Consider lowest dose and monitor for alprazolam-related adverse events. |
Clonazepam |
↑ clonazepam possible |
Consider alternative benzodiazepines. |
Diazepam |
↑ diazepam possible |
Consider lowest dose and monitor for benzodiazepine-related events. |
Lorazepam, Oxazepam, Temazepam |
↔ expected |
No dose adjustment needed. |
Midazolam (Oral) |
↑ midazolam expected |
Use with caution and consider alternative benzodiazepine. |
Suvorexant |
↑ midazolam expected |
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. |
Triazolam |
↑ triazolam expected |
Use with caution and consider alternative benzodiazepine. |
Zolpidem |
↑ zolpidem possible |
Consider initiating zolpidem at a low dose. |
Miscellaneous Drugs | ||
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). |
Ergot Derivatives Dihydroergotamine, ergotamine, methylergonovine |
↑ dihydroergotamine, ergotamine, methylergonovine expected |
Do not coadminister. |
Flibanserin |
↑ flibanserin expected |
Do not coadminister. |
Naloxegol |
↑ naloxegol expected |
Avoid use; if coadministration is necessary, decrease dosage of naloxegol and monitor for naloxegol-related adverse events. |
Key to Symbols ↑ = increase ↓ = decrease ↔ = no change Key: 3TC = lamivudine; ABC = abacavir; AUC = area under the curve; ARV = antiretroviral; ATV = atazanavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; BIC = bictegravir; CAB = cabotegravir; CHF = congestive heart failure; CNS = central nervous system; CV = cardiovascular; CYP = cytochrome P 450; DOR = doravirine; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; ECG = electrocardiogram; EFV = efavirenz; ETV = 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; LPV/r = lopinavir/ritonavir; MI = myocardial infarction; MPA = medroxyprogesterone acetate; MVC = maraviroc; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine; PAH = pulmonary arterial hypertension; PDE5 = phosphodiesterase type 5; PI = protease inhibitor; PO = orally; RAL = raltegravir; RPV = rilpivirine; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate |
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