Updated Reviewed

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 ConcentrationsDosing Recommendations and Clinical Comments
Alpha-Adrenergic Antagonists for Benign Prostatic Hyperplasia
Antibacterials—Antimycobacterials
Antibacterials—Macrolides
Anticoagulants
Anticonvulsants
Antifungals
Antimalarials
Antiplatelets
Antiretroviral Drugs
CCR5 Antagonist
CD4 Post Attachment Inhibitor
gp120 Attachment Inhibitor
INSTIs
NRTIs
NNRTIs
PIs
Antivirals—Orthopoxviruses (Mpox, Smallpox)
Beta-Agonists, Long-Acting Inhaled
Cardiac Medications
Calcium Channel Blockers
Corticosteroids
Glucose-Lowering Medications
Hepatitis C Direct-Acting Antiviral Agents
Herbal Products
Hormonal Therapies
Gender-Affirming Therapy
Menopausal Hormone Replacement Therapy
Immunosuppressants
Lipid-Modifying Agents
Narcotics and Treatment for Opioid Dependence
PDE5 Inhibitors
Sedative/Hypnotics
Miscellaneous Drugs
Alfuzosin↑ alfuzosin expectedConsider an alternative to alfuzosin or an alternative ARV. If coadministered, monitor blood pressure.
Doxazosin↑ doxazosin possibleNo dose adjustment needed. Monitor blood pressure.
Tamsulosin↑ tamsulosin possibleNo dose adjustment needed. Monitor blood pressure.
Terazosin↔ terazosin expectedNo dose adjustment needed.
Silodosin↑ silodosin possibleNo dose adjustment needed.
Bedaquiline↑ bedaquiline possibleConsider alternatives unless benefits outweigh risks. Monitor liver function and ECG for QTc prolongation.
Rifabutin↓ LEN expectedDo not coadminister.
RifampinLEN AUC ↓84%Contraindicated.
Rifapentine↓ LEN expectedDo not coadminister.
Azithromycin↔ LEN expectedNo dose adjustment needed.
Clarithromycin↑ LEN possibleNo dose adjustment needed.
Erythromycin↑ LEN possibleNo dose adjustment needed.
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 possibleMonitor for rivaroxaban-related adverse events, such as increased bleeding, and adjust rivaroxaban dose accordingly.
Warfarin↑ warfarin possibleMonitor INR and adjust warfarin dose accordingly.
Carbamazepine↓ LEN expectedContraindicated.
Eslicarbazepine↓ LEN expectedDo not coadminister. Consider alternative anticonvulsant or ARV.
Ethosuximide↑ ethosuximide possibleMonitor for ethosuximide-related adverse events and adjust ethosuximide dose accordingly.
Lamotrigine↔ expectedNo dose adjustment needed.
Oxcarbazepine↓ LEN expectedDo not coadminister. Consider alternative anticonvulsant or ARV.
Phenobarbital↓ LEN expectedDo not coadminister. Consider alternative anticonvulsant or ARV.
Phenytoin↓ LEN expectedContraindicated.
Valproic Acid↔ expectedNo dose adjustment needed.
Antidepressants, Anxiolytics, and Antipsychotics
Also see the Sedative/Hypnotics section below.
Bupropion↔ expectedNo dose adjustment needed.
Buspirone↑ buspirone expectedAdminister 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 possibleNo dose adjustment needed.
Trazodone↑ trazodone expectedAdminister lowest dose of trazodone and monitor for CNS and CV adverse events.

Tricyclic Antidepressants

Amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, maprotiline, nortriptyline, protriptyline, trimipramine

↔ expectedNo dose adjustment needed.

Selective Serotonin Reuptake Inhibitor

Paroxetine

↑ paroxetine possibleDose reduction may be necessary. Monitor for paroxetine-related adverse events.

Selective Serotonin Reuptake Inhibitors

(e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, sertraline)

↔ expectedNo dose adjustment needed.
Antipsychotics
Aripiprazole↑ aripiprazole possibleNo dose adjustment needed.
Brexpiprazole↑ aripiprazole expectedIf patient is known CYP2D6 poor metabolizer, then administer quarter of usual brexpiprazole dose.
Cariprazine↑ cariprazine possibleNo dose adjustment needed.
Iloperidone↑ iloperidone possibleNo dose adjustment needed or consider dose reduction. Monitor for iloperidone-related adverse events.
Lumateperone↑ lumateperone expectedRecommended 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↔ expectedNo dose adjustment needed.
Pimavanserin↑ pimavanserin possibleNo dose adjustment needed. Monitor ECG for QTc prolongation.
Pimozide↑ pimozide expectedDo not coadminister.
Quetiapine↑ quetiapine expectedConsider alternatives unless benefits outweigh risks. Monitor ECG for QTc prolongation and consider dose reduction accordingly.
Ziprasidone↔ expectedNo dose adjustment needed.
Fluconazole↔ expectedNo dose adjustment needed.
Isavuconazole↔ expectedNo dose adjustment needed.
Itraconazole↑ LEN possibleNo dose adjustment needed.
Posaconazole↑ LEN possibleNo dose adjustment needed.
Voriconazole↑ LEN AUC 41%No dose adjustment needed.
Artemether/Lumefantrine↑ artemether and lumefantrine possibleMonitor for lumefantrine-related adverse events, including QTc prolongation.
Atovaquone/Proguanil↔ expectedNo dose adjustment needed.
Mefloquine↑ mefloquine possibleMonitor for mefloquine-related adverse events, including QTc prolongation.
Clopidogrel↓ clopidogrel active metabolite possibleConsider alternative ARV or antiplatelet drug. If coadministered, monitor for clopidogrel-related adverse events.
Prasurgrel↔ expectedNo dose adjustment needed.
Ticagrelor↑ ticagrelor possibleNo dose adjustment needed. Monitor for ticagrelor-related adverse events.
Vorapaxar↑ vorapaxar possibleNo dose adjustment needed.
MVC↔ expectedNo dose adjustment needed.
IBA↔ expectedNo dose adjustment needed.
FTR↔ expectedNo dose adjustment needed.
BIC, CAB (IM or PO), DTG, EVG/c, RAL↔ expectedNo dose adjustment needed.
ABC, 3TC, FTC↔ expectedNo dose adjustment needed.
TAFTAF AUC ↑ 32%No dose adjustment needed.
TDFTDF AUC ↑ 47%No dose adjustment needed.
EFVLEN AUC↓ 56%Do not coadminister.
ETR↓ LEN expectedDo not coadminister.
DOR↑ DOR possibleNo dose adjustment needed.
NVP↓ LEN expectedDo not coadminister.
RPV (IM or PO)↑ RPV possibleNo dose adjustment needed.
ATV unboosted, ATV/r↑ LEN expectedDo not coadminister.
ATV/cLEN AUC ↑ 4-foldDo not coadminister.
DRV/cDRV/c AUC ↑ 94%No dose adjustment needed.
DRV/r↑ LEN expectedNo dose adjustment needed.
LPV/r↑ LEN expectedNo dose adjustment needed.
Brincidofovir↔ expectedNo dose adjustment needed.
Cidofovir↔ expectedNo dose adjustment needed.
Tecovirimat↓ LEN possibleNo dose adjustment needed.
Arformoterol, Formoterol, Indacaterol, Olodaterol, Salmeterol↔ expectedNo dose adjustment needed.
Amiodarone

↑ amiodarone expected

↑ LEN possible

Do not coadminister.
Disopyramide↑ disopyramide expectedDo 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↔ expectedNo dose adjustment needed.
Dronedarone

↑ dronedarone possible

↑ LEN possible

Consider alternative ARV or cardiac medication. If coadminstered, monitor for dronedarone-related adverse events.
Quinidine↑ quinidine expectedDo not coadminster.

Beta Blockers

(e.g., carvediol, metoprolol, timolol)

↔ expectedNo dose adjustment needed.
Bosentan↓ LEN expectedDo not coadminister.
Diltiazem, Verapamil↑ diltiazem and verapamil possibleMonitor and dose adjust according to clinical response and adverse events.
Digoxin↑ digoxin expectedConsider 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 expectedLimit ranolazine to 500 mg twice daily.
Ivabradine↑ ivabradine expectedDo not coadminister.

Beclomethasone

Inhaled or intranasal

Ciclesonide

Inhaled

↔ expectedNo dose adjustment needed.

Budesonide, Fluticasone, Mometasone

Inhaled or intranasal

↑ budesonide, fluticasone, mometasone possibleInitiate with the lowest starting dose and titrate carefully and monitor for adrenal insufficiency, Cushing’s syndrome, and other corticosteroid-related adverse events.

Betamethasone

Systemic

↔ expectedNo dose adjustment needed.

Budesonide, Prednisone, Prednisolone

Systemic

↑ glucocorticoids expectedInitiate 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 possibleMonitor for adrenal insufficiency, Cushing’s syndrome, and other corticosteroid-related adverse events.
Canagliflozin↔ expectedNo dose adjustment needed.
Saxagliptin↑ saxagliptin possibleNo dose adjustment needed.
Dapagliflozin/Saxagliptin↑ saxagliptin possibleNo dose adjustment needed.
Elbasvir/Grazoprevir↔ expectedNo dose adjustment needed.
Glecaprevir/Pibrentasvir↔ expectedNo dose adjustment needed.
Ledipasvir/Sofosbuvir↔ expectedNo dose adjustment needed.
Sofosbuvir/Velpatasvir↔ expectedNo dose adjustment needed.
Sofosbuvir/Velpatasvir/Voxilaprevir↔ expectedNo dose adjustment needed.
St. John’s Wort↓ LEN expectedContraindicated.

Contraceptives—Injectable

Depot MPA

↑ MPA possibleNo 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 possibleNo dose adjustment needed.

Emergency Contraceptives

Levonorgestrel (oral)

↑ levonorgestrel possibleNo dose adjustment needed.
Estradiol, Goserelin, Leuprolide Acetate, Finasteride↔ expectedNo dose adjustment needed.
Dutasteride, Testosterone↑ dutasteride and testosterone possibleNo dose adjustment needed.
Conjugated Estrogen (equine and synthetic), Micronized Progesterone, Medroxyprogesterone↑ estrogen and progesterone possibleNo dose adjustment needed.
Drospirenone↑ drospirenone possibleNo dose adjustment needed.
Cyclosporine, Everolimus, Sirolimus, Tacrolimus↑ immunosuppressant expectedInitiate 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.
Atorvastatin↑ atorvastatin possibleNo dose adjustment needed.
Lomitapide↑ lomitapide expectedContraindicated.
Lovastatin↑ lovastatin expectedAdminister the lowest effective lovastatin dose while monitoring for adverse events
Pitavastatin↔ expectedNo dose adjustment needed.
Pravastatin↔ expectedNo dose adjustment needed.
Rosuvastatin↑ rosuvastatin possibleNo dose adjustment needed.
Simvastatin↑ simvastatin expectedAdminister the lowest effective simvastatin dose while monitoring for adverse events.

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 possibleMonitor for fentanyl-related adverse events, including potentially fatal respiratory depression. Fentanyl dose reduction may be necessary.
Lofexidine↔ expectedNo dose adjustment needed.
Methadone↑ methadone possibleNo dose adjustment needed.
Oxycodone↑ oxycodone possibleMonitor for opioid-related adverse events, including potentially fatal respiratory depression. Oxycodone dose reduction may be necessary.
Tramadol↑ tramadol possibleTramadol dose adjustments may be necessary. Monitor for clinical response and tramadol-related adverse events.
Avanafil↑ avanafil expectedAvanafil 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 expectedNo dose adjustment needed.
Vardenafil↑ vardenafil expectedVardenafil dose should not exceed 5 mg once every 24 hours.
Alprazolam↑ alprazolam expectedConsider lowest dose and monitor for alprazolam-related adverse events.
Clonazepam↑ clonazepam possibleConsider alternative benzodiazepines.
Diazepam↑ diazepam possibleConsider lowest dose and monitor for benzodiazepine-related events.
Lorazepam, Oxazepam, Temazepam↔ expectedNo dose adjustment needed.
Midazolam (Oral)↑ midazolam expectedUse with caution and consider alternative benzodiazepine.
Suvorexant↑ midazolam expectedInitiate 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 expectedUse with caution and consider alternative benzodiazepine.
Zolpidem↑ zolpidem possibleConsider initiating zolpidem at a low dose.
Cisapride↑ cisapride expectedDo 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 expectedDo not coadminister.
Flibanserin↑ flibanserin expectedDo not coadminister.
Naloxegol↑ naloxegol expectedAvoid 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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