Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, oral:

Atripla: Efavirenz 600 mg, emtricitabine 200 mg, and tenofovir disoproxil fumarate 300 mg

Pharmacology

Mechanism of Action

Efavirenz: Non-nucleoside reverse transcriptase inhibitor of HIV-1. It consequently blocks the RNA-dependent and DNA-dependent DNA polymerase activities including HIV-1 replication.

Emtricitabine: Nucleoside reverse transcriptase inhibitor; cytosine analogue that is phosphorylated intracellularly to emtricitabine 5'-triphosphate which interferes with HIV viral RNA dependent DNA polymerase resulting in inhibition of viral replication.

Tenofovir disoproxil fumarate: Nucleotide reverse transcriptase inhibitor; analog of adenosine 5'-monophosphate that interferes with the HIV viral RNA dependent DNA polymerase resulting in inhibition of viral replication. TDF is first converted intracellularly by hydrolysis to tenofovir and subsequently phosphorylated to the active tenofovir diphosphate. Tenofovir inhibits replication of HBV by inhibiting HBV polymerase.

Use: Labeled Indications

HIV-1 infection: Treatment of HIV-1 infection in adult and pediatric patients weighing ≥40 kg (may be used alone or in combination with other antiretroviral agents)

Contraindications

Clinically significant hypersensitivity (eg, Stevens-Johnson syndrome, erythema multiforme, toxic skin reactions) to efavirenz, emtricitabine, tenofovir disoproxil fumarate or any component of the formulation; coadministration with voriconazole or elbasvir/grazoprevir

Canadian labeling: Additional contraindications (not in US labeling): Concomitant use with astemizole (not marketed in Canada), bepridil (not marketed in Canada), cisapride (not marketed in Canada), ergot derivatives (eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine), midazolam, pimozide, St. John's wort, terfenadine (not marketed in Canada), or triazolam

Dosage and Administration

Dosing: Adult

HIV-1 infection: Patients ≥40 kg: Oral: One tablet once daily.

Dosage adjustment for concomitant rifampin (only if patient weighs ≥50 kg): Administer additional efavirenz 200 mg once daily.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

HIV-1 infection, treatment: May be used alone or in combination with other antiretroviral agents:

Children <12 years or <40 kg: Product is a fixed-dose combination; safety and efficacy have not been established; use in patients <40 kg would result in an excessive efavirenz dose

Children ≥12 years and Adolescents; weighing ≥40 kg: Oral: 1 tablet once daily

Dosing adjustment for concomitant rifampin: Patients weighing ≥50 kg: Administer an extra 200 mg/day of efavirenz

Administration

Administer on an empty stomach; dosing at bedtime may improve tolerability of CNS symptoms.

Dietary Considerations

Consider calcium and vitamin D supplementation.

Storage

Store at 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). Dispense only in original container.

Drug Interactions

Abemaciclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Abemaciclib. Avoid combination

Acyclovir-Valacyclovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Acyclovir-Valacyclovir. Monitor therapy

Adefovir: May diminish the therapeutic effect of Tenofovir Products. Adefovir may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Adefovir. Avoid combination

Alcohol (Ethyl): Efavirenz may enhance the adverse/toxic effect of Alcohol (Ethyl). Efavirenz may decrease the serum concentration of Alcohol (Ethyl). Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Aminoglycosides: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Monitor therapy

Amodiaquine: Efavirenz may enhance the hepatotoxic effect of Amodiaquine. Efavirenz may increase the serum concentration of Amodiaquine. Avoid combination

Antihepaciviral Combination Products: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Antihepaciviral Combination Products. Avoid combination

Artemether: Efavirenz may decrease the serum concentration of Artemether. Concentrations of dihydroartemisinin (active metabolite of artemether) may also be decreased by efavirenz Monitor therapy

Asunaprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Asunaprevir. Avoid combination

Atazanavir: Tenofovir Disoproxil Fumarate may decrease the serum concentration of Atazanavir. Atazanavir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Management: Must use boosted atazanavir in adults; give combo (atazanavir/ritonavir or atazanavir/cobicistat with tenofovir) as a single daily dose with food. Pediatric patients, pregnant patients, and users of H2-blockers require other dose changes. Consider therapy modification

Atazanavir: Efavirenz may decrease the serum concentration of Atazanavir. Management: When used with efavirenz, the adult atazanavir dose should be 400 mg daily, boosted with ritonavir 100 mg daily or cobicistat 150 mg daily, for treatment-naive patients only; treatment-experienced patients should not use atazanavir with efavirenz. Consider therapy modification

AtorvaSTATin: Efavirenz may decrease the serum concentration of AtorvaSTATin. Monitor therapy

Atovaquone: Efavirenz may decrease the serum concentration of Atovaquone. Management: Consider alternatives to the use of atovaquone with efavirenz when possible. If this combination must be used, monitor for evidence of reduced atovaquone clinical effectiveness. Consider therapy modification

Avapritinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Avapritinib. Avoid combination

Axitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Axitinib. Avoid combination

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Bedaquiline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bedaquiline. Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Bosutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Bosutinib. Avoid combination

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Monitor therapy

Brigatinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Brigatinib. Management: Avoid concurrent use of brigatinib with moderate CYP3A4 inducers when possible. If combined, increase the daily dose of brigatinib in 30 mg increments after 7 days of treatment with the current brigatinib dose, up to maximum of twice the dose. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

Buprenorphine: Efavirenz may decrease serum concentrations of the active metabolite(s) of Buprenorphine. Efavirenz may decrease the serum concentration of Buprenorphine. Monitor therapy

BuPROPion: Efavirenz may decrease the serum concentration of BuPROPion. Management: Monitor for decreased response to bupropion in patients treated with efavirenz. Increased bupropion doses may be required. Avoid the use of naltrexone/bupropion for weight management in patients receiving efavirenz. Monitor therapy

Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Monitor therapy

Calcium Channel Blockers: Efavirenz may decrease the serum concentration of Calcium Channel Blockers. Monitor therapy

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

CarBAMazepine: May decrease the serum concentration of Efavirenz. Efavirenz may decrease the serum concentration of CarBAMazepine. Avoid combination

Caspofungin: Inducers of Drug Clearance may decrease the serum concentration of Caspofungin. Management: Consider using an increased caspofungin dose of 70 mg daily in adults (or 70 mg/m², up to a maximum of 70 mg, daily in pediatric patients) when coadministered with known inducers of drug clearance. Consider therapy modification

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Cidofovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Cidofovir. Monitor therapy

Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Avoid combination

Clarithromycin: Efavirenz may enhance the QTc-prolonging effect of Clarithromycin. Efavirenz may decrease the serum concentration of Clarithromycin. Additionally, efavirenz may increase the active metabolite of clarithromycin Management: Consider using an alternative antibiotic in patients taking efavirenz. If concomitant therapy cannot be avoided, monitor for decreased therapeutic effect of clarithromycin and for QT interval prolongation. Consider therapy modification

CloZAPine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of CloZAPine. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Cobicistat: May enhance the adverse/toxic effect of Tenofovir Products. More specifically, cobicistat may impair proper tenofovir monitoring and dosing. Monitor therapy

Cobimetinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Cobimetinib. Avoid combination

CycloSPORINE (Systemic): Efavirenz may decrease the serum concentration of CycloSPORINE (Systemic). Management: Increase monitoring of cyclosporine concentrations when starting, stopping, or adjusting doses of concurrent efavirenz, particularly within the first 2 weeks. Cyclosporine dose adjustment may be required. Consider therapy modification

CYP2B6 Substrates (High risk with Inducers): CYP2B6 Inducers (Moderate) may decrease the serum concentration of CYP2B6 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Substrates (High risk with Inducers): CYP3A4 Inducers (Moderate) may decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Exceptions: Apixaban; Rivaroxaban. Monitor therapy

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Daclatasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Daclatasvir. Management: Increase the daclatasvir dose to 90 mg once daily if used with a moderate CYP3A4 inducer. Consider therapy modification

Darunavir: May increase the serum concentration of Efavirenz. Efavirenz may decrease the serum concentration of Darunavir. Management: Monitor for decreased concentrations and effects of darunavir and/or increased concentrations and effects of efavirenz when darunavir/ritonavir is combined with efavirenz. The use of darunavir/cobicistat in combination with efavirenz is not recommended. Consider therapy modification

Dasabuvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Dasabuvir. Avoid combination

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Deflazacort: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Deflazacort. Avoid combination

Diclofenac (Systemic): May enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to this combination whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose. Consider therapy modification

Didanosine: Tenofovir Disoproxil Fumarate may diminish the therapeutic effect of Didanosine. Tenofovir Disoproxil Fumarate may increase the serum concentration of Didanosine. Management: Avoid concomitant treatment with tenofovir disoproxil fumarate and didanosine. Consider altering even existing, stable treatment to avoid this combination. Avoid combination

DilTIAZem: Efavirenz may decrease the serum concentration of DilTIAZem. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Dolutegravir: Efavirenz may decrease the serum concentration of Dolutegravir. Management: Increase dolutegravir dose to 50 mg twice daily in adults or children. Consider alternatives to efavirenz for INSTI experienced patients with clinically suspected INSTI resistance or certain INSTI associated resistance substitutions. Consider therapy modification

Doravirine: Efavirenz may decrease the serum concentration of Doravirine. Avoid combination

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Consider therapy modification

Elbasvir: Efavirenz may decrease the serum concentration of Elbasvir. Avoid combination

Elexacaftor, Tezacaftor, and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Elexacaftor, Tezacaftor, and Ivacaftor. Monitor therapy

Elvitegravir: Efavirenz may decrease the serum concentration of Elvitegravir. Avoid combination

Encorafenib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Encorafenib. Avoid combination

Entrectinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Entrectinib. Avoid combination

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erdafitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Erdafitinib. Management: Dose modifications of erdafitinib may be required. See full monograph for details. Consider therapy modification

Ergonovine: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of Ergonovine. Specifically, this would be most likely with delavrdine, while other Non-Nucleoside Reverse Transcriptase Inhibitors may be more likely to decrease the concentration of Ergonovine. Avoid combination

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Estriol (Systemic): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estriol (Systemic). Monitor therapy

Estriol (Topical): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Estriol (Topical). Monitor therapy

Etonogestrel: Efavirenz may diminish the therapeutic effect of Etonogestrel. Management: Use a reliable barrier contraceptive if efavirenz is used in combination with etonogestrel. Continue using barrier contraception for 12 weeks after discontinuation of efavirenz. Consider therapy modification

Etravirine: Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of Etravirine. This has been observed with the NNRTIs efavirenz and nevirapine. Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of Etravirine. This has been observed with delavirdine. Avoid combination

Everolimus: Efavirenz may decrease the serum concentration of Everolimus. Management: Closely monitor everolimus serum concentrations when starting, stopping, or changing doses of efavirenz, particularly during the first 2 weeks after any change. Dose adjustment of everolimus may be required. Consider therapy modification

Fedratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Fedratinib. Avoid combination

Flibanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Flibanserin. Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

Fosamprenavir: Efavirenz may decrease serum concentrations of the active metabolite(s) of Fosamprenavir. Management: For once-daily fosamprenavir/ritonavir with efavirenz, an increased ritonavir dose to 300 mg/day is recommended in adult patients. No ritonavir dose adjustment is required if using twice-daily fosamprenavir/ritonavir. Consider therapy modification

Fosphenytoin: May decrease the serum concentration of Efavirenz. Efavirenz may increase the serum concentration of Fosphenytoin. Consider therapy modification

Ganciclovir-Valganciclovir: Tenofovir Products may increase the serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase the serum concentration of Tenofovir Products. Monitor therapy

Ginkgo Biloba: May decrease the serum concentration of Efavirenz. Monitor therapy

Glecaprevir and Pibrentasvir: Efavirenz may decrease the serum concentration of Glecaprevir and Pibrentasvir. Avoid combination

Grazoprevir: Efavirenz may decrease the serum concentration of Grazoprevir. Avoid combination

GuanFACINE: CYP3A4 Inducers (Moderate) may decrease the serum concentration of GuanFACINE. Management: Increase the guanfacine dose by up to double when initiating guanfacine in a patient taking a moderate CYP3A4 inducer. Increase guanfacine dose gradually over 1 to 2 weeks if initiating a moderate CYP3A4 inducer in a patient already taking guanfacine. Consider therapy modification

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Ibrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ibrutinib. Monitor therapy

Ifosfamide: CYP3A4 Inducers (Moderate) may decrease serum concentrations of the active metabolite(s) of Ifosfamide. CYP3A4 Inducers (Moderate) may increase serum concentrations of the active metabolite(s) of Ifosfamide. Monitor therapy

Indinavir: Efavirenz may decrease the serum concentration of Indinavir. Management: The appropriate dose adjustments for indinavir when used together with efavirenz are unknown. The use of higher unboosted indinavir doses is not likely an adequate approach. Use of a ritonavir-boosted indinavir regimen could be considered. Consider therapy modification

Istradefylline: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Istradefylline. Monitor therapy

Itraconazole: Efavirenz may decrease the serum concentration of Itraconazole. Avoid combination

Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ivacaftor. Monitor therapy

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Ketoconazole (Systemic): Efavirenz may decrease the serum concentration of Ketoconazole (Systemic). Avoid combination

LamiVUDine: May enhance the adverse/toxic effect of Emtricitabine. Avoid combination

Ledipasvir: May increase the serum concentration of Tenofovir Disoproxil Fumarate. Management: Avoidance of this combination is recommended under some circumstances. Refer to full monograph for details. Consider therapy modification

Lefamulin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin with moderate CYP3A4 inducers unless the benefits outweigh the risks. Consider therapy modification

Lefamulin (Intravenous): CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lefamulin (Intravenous). Management: Avoid concomitant use of lefamulin (intravenous) with moderate CYP3A4 inducers unless the benefits outweigh the risks. Consider therapy modification

Lemborexant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lemborexant. Avoid combination

Letermovir: May increase the serum concentration of UGT1A1 Inducers. Avoid combination

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

Lopinavir: Efavirenz may decrease the serum concentration of Lopinavir. Management: Avoid once daily use of lopinavir/ritonavir with efavirenz. Avoid use of this combination in patients less than 6 months of age. See lopinavir/ritonavir prescribing information for specific recommended dose increases in particular patient populations. Consider therapy modification

Lorlatinib: CYP3A4 Inducers (Moderate) may enhance the hepatotoxic effect of Lorlatinib. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lorlatinib. Management: Avoid use of lorlatinib with moderate CYP3A4 inducers. If such a combination must be used, monitor AST, ALT, and bilirubin within 48 hours of starting the combination and at least three times within the first week of combined use. Consider therapy modification

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification

Lovastatin: Efavirenz may decrease the serum concentration of Lovastatin. Monitor therapy

Lumateperone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lumateperone. Avoid combination

Lurasidone: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Lurasidone. Management: Monitor for decreased lurasidone effects if combined with moderate CYP3A4 inducers and consider increasing the lurasidone dose if coadministered with a moderate CYP3A4 inducer for 7 or more days. Consider therapy modification

Macimorelin: Efavirenz may diminish the diagnostic effect of Macimorelin. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Maraviroc: Efavirenz may decrease the serum concentration of Maraviroc. Of note, this effect only applies in the absence of a strong CYP3A4 inhibitor Management: Increase maraviroc adult dose to 600 mg twice daily if used with efavirenz. This does not apply to patients also receiving strong CYP3A4 inhibitors. This combination is contraindicated in patients with CrCl less than 30 mL/min. Consider therapy modification

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirodenafil: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Mirodenafil. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Naldemedine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Naldemedine. Monitor therapy

Neratinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Neratinib. Avoid combination

Nevirapine: Efavirenz may enhance the adverse/toxic effect of Nevirapine. Nevirapine may enhance the adverse/toxic effect of Efavirenz. Nevirapine may decrease the serum concentration of Efavirenz. Avoid combination

NiMODipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of NiMODipine. Monitor therapy

Nisoldipine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Nisoldipine. Avoid combination

Nonsteroidal Anti-Inflammatory Agents: May enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose. Consider therapy modification

Norgestimate: Efavirenz may decrease serum concentrations of the active metabolite(s) of Norgestimate. Management: Use a reliable barrier contraceptive if efavirenz is used in combination with norgestimate. Continue using barrier contraception for 12 weeks after discontinuation of efavirenz. Consider therapy modification

Olaparib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Olaparib. Avoid combination

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Orlistat: May decrease the serum concentration of Antiretroviral Agents. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Palbociclib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Palbociclib. Management: The US label does not provide specific recommendations concerning use with moderate CYP3A4 inducers, but the Canadian label recommends avoiding use of moderate CYP3A4 inducers. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Perampanel: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Perampanel. Management: Increase the perampanel starting dose to 4 mg/day when perampanel is used concurrently with moderate and strong CYP3A4 inducers. Consider therapy modification

Pexidartinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pexidartinib. Monitor therapy

Phenytoin: May decrease the serum concentration of Efavirenz. Efavirenz may increase the serum concentration of Phenytoin. Consider therapy modification

Pimavanserin: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pimavanserin. Avoid combination

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pitolisant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pitolisant. Monitor therapy

Posaconazole: Efavirenz may decrease the serum concentration of Posaconazole. Avoid combination

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Pravastatin: Efavirenz may decrease the serum concentration of Pravastatin. Monitor therapy

Pretomanid: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Pretomanid. Avoid combination

Progestins (Contraceptive): Efavirenz may decrease the serum concentration of Progestins (Contraceptive). Management: Use an alternative or additional method of contraception due to possibly decreased contraceptive effectiveness. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. Consider therapy modification

Proguanil: Efavirenz may decrease serum concentrations of the active metabolite(s) of Proguanil. Efavirenz may decrease the serum concentration of Proguanil. Efavirenz may increase the serum concentration of Proguanil. Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Ranolazine: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ranolazine. Avoid combination

Reverse Transcriptase Inhibitors (Non-Nucleoside): May increase the serum concentration of Efavirenz. Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of Efavirenz. Avoid combination

Rifabutin: Efavirenz may decrease the serum concentration of Rifabutin. Rifabutin may decrease the serum concentration of Efavirenz. Management: If efavirenz is to be used with daily rifabutin, increase the planned rifabutin adult dose by 50%. If used with regimens where rifabutin is administered 2-3 times per week, consider doubling the rifabutin dose. Consider therapy modification

RifAMPin: May decrease the serum concentration of Efavirenz. Monitor therapy

Rilpivirine: Reverse Transcriptase Inhibitors (Non-Nucleoside) may increase the serum concentration of Rilpivirine. This mechanism applies to coadministration of delavirdine. Reverse Transcriptase Inhibitors (Non-Nucleoside) may decrease the serum concentration of Rilpivirine. This mechanism applies to coadministration of efavirenz, etravirine, and nevirapine. Avoid combination

Ritonavir: Efavirenz may enhance the adverse/toxic effect of Ritonavir. Efavirenz may increase the serum concentration of Ritonavir. Ritonavir may increase the serum concentration of Efavirenz. Monitor therapy

Rolapitant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Rolapitant. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Saquinavir: May enhance the adverse/toxic effect of Efavirenz. Efavirenz may decrease the serum concentration of Saquinavir. Management: When used together with efavirenz, saquinavir should not be used as the sole protease inhibitor. Appropriate doses of the combination of efavirenz with saquinavir/ritonavir have not been established. Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Sertraline: Efavirenz may decrease the serum concentration of Sertraline. Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Simeprevir. Avoid combination

Simvastatin: Efavirenz may decrease the serum concentration of Simvastatin. Monitor therapy

Sirolimus: Efavirenz may decrease the serum concentration of Sirolimus. Management: Closely monitor sirolimus serum concentrations when starting, stopping, or changing doses of efavirenz, particularly during the first 2 weeks after any change. Dose adjustment of sirolimus may be required. Consider therapy modification

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Sonidegib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Sonidegib. Avoid combination

St John's Wort: May decrease the serum concentration of Efavirenz. Avoid combination

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tacrolimus (Systemic): Efavirenz may decrease the serum concentration of Tacrolimus (Systemic). Management: Closely monitor tacrolimus serum concentrations when starting, stopping, or changing doses of efavirenz, particularly during the first 2 weeks after any change. Dose adjustment of tacrolimus may be required. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Tazemetostat: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tazemetostat. Avoid combination

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tezacaftor and Ivacaftor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Tezacaftor and Ivacaftor. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Thiotepa: May increase the serum concentration of CYP2B6 Substrates (High risk with Inhibitors). Monitor therapy

Tipranavir: Tenofovir Disoproxil Fumarate may decrease the serum concentration of Tipranavir. Tipranavir may decrease the serum concentration of Tenofovir Disoproxil Fumarate. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Ubrogepant: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a moderate CYP3A4 inducer. Consider therapy modification

Ulipristal: Efavirenz may decrease the serum concentration of Ulipristal. Avoid combination

Upadacitinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Upadacitinib. Monitor therapy

Velpatasvir: CYP2B6 Inducers (Moderate) may decrease the serum concentration of Velpatasvir. Avoid combination

Velpatasvir: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Velpatasvir. Avoid combination

Venetoclax: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Venetoclax. Avoid combination

Vitamin K Antagonists (eg, warfarin): Efavirenz may decrease the serum concentration of Vitamin K Antagonists. Efavirenz may increase the serum concentration of Vitamin K Antagonists. Monitor therapy

Voriconazole: Efavirenz may decrease the serum concentration of Voriconazole. Voriconazole may increase the serum concentration of Efavirenz. Management: Use of standard doses of these drugs is contraindicated. The voriconazole oral maintenance dose should be increased to 400 mg every 12 hours, and the efavirenz dose should be reduced to 300 mg/day. Consider therapy modification

Voxelotor: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Voxelotor. Management: Avoid concomitant use of voxelotor and moderate CYP3A4 inducers. If concomitant use is unavoidable, increase the voxelotor dose to 2,500 mg once daily. Consider therapy modification

Voxilaprevir: Tenofovir Disoproxil Fumarate may increase the serum concentration of Voxilaprevir. Voxilaprevir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Monitor therapy

Zanubrutinib: CYP3A4 Inducers (Moderate) may decrease the serum concentration of Zanubrutinib. Avoid combination

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Test Interactions

False-positive test for cannabinoids have been reported with some screening assays used in HIV-infected and uninfected subjects receiving efavirenz. Confirmation of screening tests for cannabinoids by a more specific method is recommended.

Adverse Reactions

The complete adverse reaction profile of combination therapy has not been established. Also see individual agents. The following adverse effects were noted in clinical trials with combination therapy.

>10%:

Central nervous system: Abnormal dreams

Endocrine & metabolic: Hypercholesterolemia (22%)

1% to 10%:

Cardiovascular: Increased serum creatine kinase (9%)

Central nervous system: Depression (9%), fatigue (9%), dizziness (8%), headache (6%), anxiety (5%), insomnia (5%)

Dermatologic: Skin rash (7%)

Endocrine & metabolic: Increased serum triglycerides (4%), hyperglycemia (2%)

Gastrointestinal: Diarrhea (9%), nausea (9%), increased serum amylase (8%), vomiting (2%)

Genitourinary: Hematuria (3%)

Hematologic & oncologic: Decreased neutrophils (3%)

Hepatic: Increased serum aspartate aminotransferase (3%), increased serum alanine aminotransferase (2%), increased serum alkaline phosphatase (1%)

Respiratory: Sinusitis (8%), upper respiratory tract infection (8%), nasopharyngitis (5%)

<1%: Glycosuria

Warnings/Precautions

Concerns related to adverse effects:

• CNS effects: CNS symptoms (eg, insomnia, abnormal dreams, hallucinations) have been reported with efavirenz; symptoms usually start during first 1 to 2 days of treatment and generally resolve after 2 to 4 weeks; administration at bedtime may improve tolerability of CNS symptoms. May also cause CNS depression (eg, impaired concentration, dizziness, drowsiness); avoid potentially hazardous tasks such as driving or operating machinery. Late-onset neurotoxicity, including ataxia and encephalopathy, may occur months to years after initiation of efavirenz therapy. Some of these events have been reported in patients with CYP2B6 genetic polymorphisms (associated with increase efavirenz levels at standard doses). Promptly assess patients with signs and symptoms of serious neurologic adverse effects and consider discontinuation of therapy.
• Decreased bone mineral density: In clinical trials, tenofovir disoproxil fumarate has been associated with decreases in bone mineral density in HIV-1 infected adults and increases in bone metabolism markers. Serum parathyroid hormone and 1,25 vitamin D levels were also higher. Decreases in bone mineral density have also been observed in clinical trials of HIV-1 infected pediatric patients. Observations in chronic hepatitis B infected pediatric patients (12 to <18 years of age) were similar. In all pediatric clinical trials, skeletal growth (height) appears unaffected. Consider monitoring of bone density in adult and pediatric patients with a history of pathologic fractures or with other risk factors for bone loss or osteoporosis. Consider calcium and vitamin D supplementation for all patients; effect of supplementation has not been studied but may be beneficial. Long-term bone health and fracture risk unknown. If abnormalities are suspected, expert assessment is recommended.
• Fat redistribution: May cause redistribution/accumulation of body fat (eg, central obesity, dorsocervical fat enlargement [buffalo hump], peripheral wasting, facial wasting, breast enlargement, cushingoid appearance).
• Hepatotoxicity: Hepatitis, including fulminant hepatitis sometimes fatal or progressing to hepatic failure requiring transplantation, has been reported, including patients with no preexisting hepatic disease or other identifiable risk factors. Monitor liver function tests at baseline and during treatment in all patients. Consider discontinuation in patients who have persistent elevations of serum transaminases >5 times ULN; discontinue if signs or symptoms of hepatitis or hepatic decompensation occur with serum transaminase elevation.
• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barré syndrome, autoimmune hepatitis) later in therapy; further evaluation and treatment may be required.
• Lactic acidosis/hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis, sometimes fatal, have been reported with use of nucleoside analogs, alone or in combination with other antiretrovirals. Suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (marked transaminase elevation may/may not accompany hepatomegaly and steatosis).
• Osteomalacia and renal dysfunction: Tenofovir disoproxil fumarate may cause osteomalacia with proximal renal tubulopathy. Bone pain, extremity pain, fractures, arthralgias, weakness, and muscle pain have been reported. In patients at risk for renal dysfunction, persistent or worsening bone or muscle symptoms should be evaluated for hypophosphatemia and osteomalacia.
• Psychiatric effects: Serious psychiatric symptoms have been associated with efavirenz, including severe depression, suicide attempts and ideation, paranoia, aggression, and mania. Use with caution in patients with a history of mental illness/drug abuse.
• QT prolongation: QT prolongation has been reported with efavirenz; consider alternative therapy in patients at risk of torsades de pointes or when coadministered with medications with known risk of torsades de pointes.
• Rash: Rash, ranging from mild to moderate maculopapular skin eruptions to life-threatening cutaneous reactions (eg, Stevens-Johnson syndrome), may occur with efavirenz. Mild to moderate rashes occur within 2 weeks (median onset: 11 days) and resolve within 1 month in patients continuing treatment. Treatment may be reinitiated in patients interrupting therapy for mild to moderate rashes; discontinue use and consider alternative therapy if severe rash associated with blistering, desquamation, mucosal involvement, or fever develops. Pediatric patients are more susceptible to development of rash (median time to onset: 28 days); prophylactic antihistamines should be considered.
• Renal toxicity: Tenofovir disoproxil fumarate may cause renal toxicity (acute renal failure and/or Fanconi syndrome); avoid use with concurrent or recent nephrotoxic therapy (including high-dose or multiple nonsteroidal anti-inflammatory drug [NSAID] use). Acute renal failure has occurred in HIV-infected patients with risk factors for renal impairment who were on a stable tenofovir disoproxil fumarate regimen to which a high dose or multiple NSAID therapy was added. Consider alternatives to NSAIDs in patients taking tenofovir and at risk for renal impairment. Prior to initiation of therapy and as clinically appropriate during therapy, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. IDSA guidelines recommend discontinuing tenofovir disoproxil fumarate (and substituting with alternative antiretroviral therapy) in HIV-infected patients who develop a decline in GFR (a >25% decrease in GFR from baseline and to a level of <60 mL/minute/1.73 m²) during use, particularly in presence of proximal tubular dysfunction (eg, euglycemic glycosuria, increased urinary phosphorus excretion and hypophosphatemia, proteinuria [new onset or worsening]) (IDSA [Lucas 2014]). Discontinue if evidence of Fanconi syndrome occurs.

Disease-related concerns:

• Chronic hepatitis B: [US Boxed Warning]: Severe, acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and HIV-1 and have discontinued emtricitabine and/or tenofovir disoproxil fumarate. Closely monitor hepatic function with clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue efavirenz/emtricitabine/tenofovir disoproxil fumarate. If appropriate, anti-hepatitis B therapy may be warranted, especially in patients with cirrhosis or advanced liver disease; hepatic decompensation and liver failure may occur with posttreatment exacerbation of hepatitis. All patients with HIV should be tested for HBV prior to initiation of treatment.
• Hepatic impairment: Not recommended in patients with moderate or severe hepatic impairment (Child-Pugh class B, C). Use caution in patients with mild hepatic impairment (Child-Pugh class A). Monitor liver function tests before and during treatment.
• HIV-associated dementia: Avoid efavirenz based regimens if possible in patients with HIV-associated dementia; neuropsychiatric side effects of efavirenz may hinder assessment of the effects of antiretrovirals on the improvement of symptoms associated with HIV-associated dementia (HHS [adult] 2016).
• Renal impairment: Use is not recommended in patients with CrCl <50 mL/minute.
• Seizure disorder: Use efavirenz with caution in patients with a history of seizure disorder; seizures have been associated with use.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Monitoring Parameters

Test for hepatitis B virus infection prior to the initiation of antiretroviral therapy.

CBC with differential, reticulocyte count, creatine kinase, CD4 count, HIV RNA plasma levels; serum creatinine, estimated creatine clearance, urine glucose, and urine protein (prior to initiation and as clinically indicated during therapy); serum phosphorus at baseline and periodically during therapy in patients with chronic kidney disease; hepatic function tests prior to initiation and during treatment (discontinuation of treatment should be considered for persistent serum transaminase elevations >5 times ULN; discontinue if signs or symptoms of hepatitis or hepatic decompensation occur with serum transaminase elevation); bone density (patients with a history of bone fracture or have risk factors for bone loss).

Patients with HIV and HBV coinfection should have hepatic function monitored for several months following discontinuation.

Pregnancy

Pregnancy Considerations

The Health and Human Services (HHS) perinatal HIV guidelines consider this fixed-dose combination an alternative regimen for pregnant females living with HIV who are antiretroviral-naive, who have had antiretroviral therapy (ART) in the past but are restarting, who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen), and who are not yet pregnant but are trying to conceive. In addition, females who become pregnant while taking this fixed-dose combination may continue if viral suppression is effective and the regimen is well tolerated. This fixed dose combination may be considered for women when significant drug interactions would occur with preferred agents or in women who need the convenience of a co-formulated single dose tablet in a once daily regimen but are not eligible for preferred agents (HHS [perinatal] 2019).

Females living with HIV not planning a pregnancy may use any available type of contraception, considering possible drug interactions and contraindications of the specific method. Consult drug interactions database for more detailed information specific to use of this combination and specific contraceptives (HHS [perinatal] 2019). The manufacturer's labeling recommends pregnancy testing prior to therapy, and effective contraception in females of reproductive potential during treatment and for 12 weeks after therapy is discontinued.

Refer to individual monographs for additional information.

Patient Education

What is this drug used for?

• It is used to treat HIV infection.

Frequently reported side effects of this drug

• Headache
• Fatigue
• Nightmares
• Dizziness
• Trouble focusing
• Nausea
• Vomiting
• Diarrhea
• Trouble sleeping
• Common cold symptoms
• Loss of strength and energy
• Skin discoloration

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain
• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes
• Lactic acidosis like fast breathing, fast heartbeat, abnormal heartbeat, vomiting, fatigue, shortness of breath, severe loss of strength and energy, severe dizziness, feeling cold, or muscle pain or cramps
• Depression like thoughts of suicide, anxiety, emotional instability, agitation, irritability, panic attacks, mood changes, behavioral changes, or confusion
• Sensing things that seem real but are not
• Behavioral problems
• Mood changes
• Change in balance
• Abnormal movements
• Trouble with memory
• Confusion
• Fast heartbeat
• Abnormal heartbeat
• Passing out
• Bone pain
• Muscle pain
• Muscle weakness
• Painful extremities
• Seizures
• Change in body fat
• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes
• Infection
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.