Recreational Drugs and HIV Antiretrovirals a Guide to Interactions for Clinicians

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Recreational Drugs and HIV Antiretrovirals A Guide to Interactions for Clinicians

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Recreational Drugs and HIV Antiretrovirals — A Guide to Interactions for Clinicians

Prepared by: Antonio Urbina, MD, John Faragon, PharmD, BCPS, AAHIVP

This clinical support tool is sponsored by the New York/New Jersey AIDS Education Training Center (NY/NJ AETC).The NY/NJ AETC is funded by the Health Resources and Services Administration (HRSA) and is part of the National AIDS Education Training Center Program, a network of federally funded regional and national centers that conduct targeted multidisciplinary HIV/AIDS education and training programs for health care providers. The authors would like to acknowledge authors involved with previous versions of this guide, Christine Kubin, PharmD and Audrey Castillo, MPH. Providers are encouraged to also review our guide entitled Opioid Pain Management and Addiction Management Medications: Drug Interactions with HIV Antiretrovirals: A Guide to Interactions for Clinicians that may be found on our website. Disclaimer: Neither the AIDS Education and Training Centers nor HRSA condone or recommend the use of illicit drugs in any context. The data in this guide are intended for use by clinicians and other health care providers to provide advice that may reduce harm to patients who use these substances in conjunction with antiretroviral agents. The data in this guide are a compilation of information obtained from published and anecdotal studies through January 2014.

* PLEASE REFER TO PAGE 14 OF THIS GUIDE FOR IMPORTANT HARM REDUCTION THAT SHOULD BE SHARED WITH PATIENTS.

NY/NJ AIDS Education and Training Center Columbia University College of Physicians and Surgeons Department of Psychiatry 100 Haven Avenue, Suite 3IG NewYork, NY 10032 212-304-5530 www.nynjaetc.org [email protected] 862060_Rec Drug Guide.qxd 2/5/14 1:06 PM Page 3

ALCOHOL AMPHETAMINES (Crystal) Confusion, disorientation, incoordination, loss of Paranoia, anxiety, depression, hallucinations, tachycardia, hypertension balance and judgement, respiratory depression, stroke, myocardial infarction, hyperthermia, rhabdomyolysis, diarrhea, GENERAL stupor, coma erectile dysfunction, teeth grinding PHARMACOKINETICS Metabolized by alcohol dehydrogenase and Metabolized by hydroxylation and deamination via CYP2D6 pathway; CYP2D6 aldehyde dehydrogenase; alcohol may induce inhibitors may increase amphetamine levels (try to avoid) CYP2E1 and CYP3A

KNOWN DRUG INTERACTIONS KNOWN DRUG INTERACTIONS NNRTI’s I NNRTI’s I delavirdine (Rescriptor) I I No known interactions specific to delavirdine (Rescriptor) I I No known interactions specific to efavirenz (Sustiva) I this combination efavirenz (Sustiva) I this combination nevirapine (Viramune) I nevirapine (Viramune) I etravirine (Intelence) I etravirine (Intelence) I rilpivirine (Edurant) rilpivirine (Edurant)

NRTI’s I I Increases abacavir AUC ~40% (decreased NRTI’s I *abacavir (ABC, Ziagen) abacavir metabolism by alcohol * abacavir (ABC,Ziagen) *Atripla (EFV/TDF/FTC) dehydrogenase) *Atripla (EFV/TDF/FTC) *Combivir (AZT/3TC) *Combivir (AZT/3TC) Complera (RPV/TDF/FTC) I I Increased risk of pancreatitis Complera (RPV/TDF/FTC) I didanosine (ddl, Videx) I didanosine (ddl, Videx) I *SEE INDIVIDUAL COMPONENTS *emtricitabine (FTC, Emtriva) * emtricitabine (FTC, Emtriva) Epzicom (3TC/ABC) I *SEE INDIVIDUAL COMPONENTS Elapmzicvuodmin(e3(T3CTC/A, EBpCiv) ir) I lamivudine (3TC, Epivir) I I stavudine (d4T, Zerit) I stavudine (d4T, Zerit) I *tenofovir (TDF,Viread) * tenofovir (TDF,Viread) *Trizivir (AZT/3TC/ABC) *Trizivir (AZT/3TC/ABC) Truvada (FTC/TDF) I Truvada (FTC/TDF) I zidovudine (AZT, ZDV, Retrovir) zidovudine (AZT, ZDV, Retrovir) I I Use of full dose ritonavir or low dose Protease Inhibitor) s I I No known interactions specific to Protease Inhibitors I ritonavir for boosting other protease fosamprenavir (Lexiva I this combination. amprenavir (Agenerase) I inhibitors has the potential to increase atazanavir (Reyataz) I fosamprenavir (Lexiva) I amphetamine levels in the blood. darunavir (Prezista) I atazanavir (Reyataz) I I No known interactions specific to indinavir (Crixivan) I darunavir (Prezista) I this combination. Refer to comments lopinavir/ritonavir (Kaletra) I indinavir (Crixivan) I for this drug class in general. nelfinavir (Viracept) I lopinavir/ritonavir (Kaletra) I ritonavir (Norvir) I nelfinavir (Viracept) I I Increases amphetamine blood saquinavir (Fortovase, Invirase) I ritonavir (Norvir) I levels 2-3 times tipranavir (Aptivus) saquinavir (Fortovase, Invirase) I tipranavir (Aptivus) Continued next page

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ALCOHOL (Cont’d) AMPHETAMINES (Crystal) (Cont’d) Confusion, disorientation, incoordination, loss of Paranoia, anxiety, depression, hallucinations, tachycardia, hypertension balance and judgement, respiratory depression, stroke, myocardial infarction, hyperthermia, rhabdomyolysis, diarrhea, GENERAL stupor, coma erectile dysfunction, teeth grinding PHARMACOKINETICS Metabolized by alcohol dehydrogenase and Metabolized by hydroxylation and deamination via CYP2D6 pathway; CYP2D6 aldehyde dehydrogenase; alcohol may induce inhibitors may increase amphetamine levels (try to avoid) CYP2E1 and CYP3A

KNOWN DRUG INTERACTIONS KNOWN DRUG INTERACTIONS

CCR5 Inhibitor I I No known interactions specific to CCR5 Inhibitor I I No known interactions specific to Maraviroc (Selzentry) this combination Maraviroc (Selzentry) this combination

Integrase Inhibitor I I No known interactions specific to Integrase Inhibitor I I Potential to increase amphetamine Elvitegravir/cobicistat/ this combination Elvitegravir/cobicistat/ levels in the blood TDF/FTC) (Stribild) I TDF/FTC) (Stribild) I I No known interactions specific to Dolutegravir (Tivicay) I Dolutegravir (Tivicay) I this combination Raltegravir (Isentress ) Raltegravir (Isentress)

AMYL NITRITE (amyl nitrate, poppers) BENZODIAZEPINES Reduces glutathioine levels; inhaling the fumes CNS depression, drowsiness, memory loss, impaired coordination acts as a vasodilator (hypotension, tachycardia, GENERAL headaches), skin flushing PHARMACOKINETICS Most agents extensively metabolized in the liver by the CYP3A4 system; lorazepam, oxazepam, and temazepam metabolized by onjugation via glucuronidation.

KNOWN DRUG INTERACTIONS KNOWN DRUG INTERACTIONS NNRTI’s I NNRTI’s I delavirdine (Rescriptor) I I No known interactions specific to delavirdine (Rescriptor) I I Likely inhibits benzodiazepine efavirenz (Sustiva) I this combination efavirenz (Sustiva) I metabolism through CYP3A4 nevirapine (Viramune) I nevirapine (Viramune) I inhibitionand increases risk of etravirine (Intelence) I etravirine (Intelence) I adverse effects; concomitant use rilpivirine (Edurant) rilpivirine (Edurant) should be avoided I Diazepam drug levels may be increased by etravirine; a decrease in diazepam dosage may be needed Continued next page

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AMYL NITRITE (amyl nitrate, poppers) (Cont’d) BENZODIAZEPINES (Cont’d) Reduces glutathioine levels; inhaling the fumes CNS depression, drowsiness, memory loss, impaired coordination acts as a vasodilator (hypotension, tachycardia, GENERAL headaches), skin flushing PHARMACOKINETICS Most agents extensively metabolized in the liver by the CYP3A4 system; lorazepam, oxazepam, and temazepam metabolized by conjugation via glucuronidation.

KNOWN DRUG INTERACTIONS KNOWN DRUG INTERACTIONS NRTI’s I NRTI’s I I No known interactions specific to *abacavir (ABC, Ziagen) I No known interactions specific to * abacavir (ABC, Ziagen) this combination *Atripla (EFV/TDF/FTC) this combination. *Atripla (EFV/TDF/FTC) *Combivir (AZT/3TC) *Combivir (AZT/3TC) Complera (RPV/TDF/FTC) I Complera (RPV/TDF/FTC) I *SEE INDIVIDUAL COMPONENTS didanosine (ddl, Videx) I didanosine (ddl, Videx) I *emtricitabine (FTC, Emtriva) SEE INDIVIDUAL COMPONENTS * emtricitabine (FTC, Emtriva) I Use of PIs with benzodiazepines should Epzicom (3TC/ABC) I Elapmzicvuodmin(e3(T3CTC/A, EBpCiv) ir) I be avoided due to increased risk of lamivudine (3TC, Epivir) I I sedation and respiratory depression; stavudine (d4T, Zerit) I stavudine (d4T, Zerit) I midazolam and triazolam specifically *tenofovir (TDF,Viread) * tenofovir (TDF,Viread) contraindicated with all PIs. IV *Trizivir (AZT/3TC/ABC) *Trizivir (AZT/3TC/ABC) midazolam can be used with caution Truvada (FTC/TDF) I Truvada (FTC/TDF) I as a single dose if monitored. zidovudine (AZT, ZDV, Retrovir) zidovudine (AZT, ZDV, Retrovir) I I No known interactions specific to I I No known interactions specific to Protease Inhibitors I this combination Protease Inhibitors I this combination. Refer to comments amprenavir (Ageneras)e) I amprenavir (Agenerase) I for this drug class in general. fosamprenavir (Lexiva I fosamprenavir (Lexiva) I I Decreases therapeutic effect of atazanavir (Reyataz) I atazanavir (Reyata I lorazepam, oxazepam, and darunavir (Prezista) I darunavir (Prezista) I temazepam (monitor for withdrawal) indinavir (Crixivan) I indinavir (Crixivan) I lopinavir/ritonavir (Kaletra) I lopinavir/ritonavir (Kaletra) I I No known interactions specific to nelfinavir (Viracept) I nelfinavir (Viracept) I this combination ritonavir (Norvir) I ritonavir (Norvir) I saquinavir (Fortovase, Invirase) I saquinavir (Fortovase, Invirase) I I May increase AUC of intravenous tipranavir (Aptivus) tipranavir (Aptivus) benzodiazepines; especially midazolam and diazepam. CCR5 Inhibitor I I No known interactions specific to CCR5 Inhibitor I Avoid with oral midazolam and Maraviroc (Selzentry) this combination Maraviroc (Selzentry) triazolam. IV midazolam can be used with caution as a single dose Integrase Inhibitor I I No known interactions specific to Integrase Inhibitor I if monitored. Elvitegravir/cobicistat/ this combination Elvitegravir/cobicistat/ I No known interactions specific to TDF/FTC) (Stribild) I TDF/FTC) (Stribild) I this combination Dolutegravir (Tivicay) I Dolutegravir (Ticivay) I Raltegravir (Isentress ) Raltegravir (Isentress)

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COCAINE (coke, blow) ECSTASY (X, MDMA) Increases rate of HIV viral replication in vitro, hypertension, cardiac Tachycardia, hypertension, hyperthermia, dehydration, dry mouth, dysrhythmias, myocardial infarction, seizures, depression, anxiety tense jaw, teeth grinding, depression GENERAL PHARMACOKINETICS Mainly metabolized by nonspecific tissue a nd CYP2D6 demethylation important in metabolism; 2D6 inhibitors are plasma esterases; some cocaine likely to increase ecstasy levels metabolism (-10%) via CYP3A4

KNOWN DRUG INTERACTIONS KNOWN DRUG INTERACTIONS NNRTI’s I NNRTI’s I delavirdine (Rescriptor) I delavirdine (Rescriptor) I efavirenz (Sustiva) I I No known interactions specific to efavirenz (Sustiva) I I No known interactions specific to nevirapine (Viramune) I this combination nevirapine (Viramune) I this combination etravirine (Intelence) I etravirine (Intelence) I rilpivirine (Edurant) rilpivirine (Edurant)

NRTI’s I NRTI’s I *abacavir (ABC, Ziagen) * abacavir (ABC,Ziagen) *Atripla (EFV/TDF/FTC) *Atripla (EFV/TDF/FTC) *Combivir (AZT/3TC) *Combivir (AZT/3TC) Complera (RPV/TDF/FTC) I *SEE INDIVIDUAL COMPONENTS Complera (RPV/TDF/FTC) I *SEE INDIVIDUAL COMPONENTS didanosine (ddl, Videx) I didanosine (ddl, Videx) I *emtricitabine (FTC, Emtriva) * emtricitabine (FTC, Emtriva) Epzicom (3TC/ABC) I Epzicom (3TC/ABC) ) I lamivudine (3TC, Epivir) I lamivudine (3TC, Epivir) I stavudine (d4T, Zerit) I stavudine (d4T, Zerit) I *tenofovir (TDF,Viread) * tenofovir (TDF,Viread) *Trizivir (AZT/3TC/ABC) *Trizivir (AZT/3TC/ABC) Truvada (FTC/TDF) I Truvada (FTC/TDF) I zidovudine (AZT, ZDV, Retrovir) zidovudine (AZT, ZDV, Retrovir) I I No known interactions specific to I I Increase levels of ecstasy Protease Inhibitors I this combination Protease Inhibitors I I No known interactions specific to this amprenavir (Ageneras)e) I amprenavir (Agenerase) I combination. Refer to comments for fosamprenavir (Lexiva I fosamprenavir (Lexiva) I this drug class in general atazanavir (Reyataz) I atazanavir (Reyataz)) I I Increases risk of kidney stones darunavir (Prezista) I darunavir (Prezista)) I due to dehydration indinavir (Crixivan) I indinavir (Crixivan) I I Potential to increase ecstasy levels lopinavir/ritonavir (Kaletra) I lopinavir/ritonavir (Kaletra) I I Increases ecstasy levels 5-10 times nelfinavir (Viracept) I nelfinavir (Viracept) I (AVOID) ritonavir (Norvir) I ritonavir (Norvir) I saquinavir (Fortovase, Invirase) I saquinavir (Fortovase, Invirase) I tipranavir (Aptivus) tipranavir (Aptivus) Continued next page

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COCAINE (coke, blow) (Cont’d) ECSTASY (X, MDMA) (Cont’d) Increases rate of HIV viral replication in vitro, hypertension, cardiac Tachycardia, hypertension, hyperthermia, dehydration, dry mouth, dysrhythmias, myocardial infarction, seizures, depression, anxiety tense jaw, teeth grinding, depression GENERAL PHARMACOKINETICS Mainly metabolized by nonspecific tissue a nd CYP2D6 demethylation important in metabolism; 2D6 inhibitors are plasma esterases; some cocaine likely to increase ecstasy levels metabolism (-10%) via CYP3A4

KNOWN DRUG INTERACTIONS KNOWN DRUG INTERACTIONS

CCR5 Inhibitor I I No known interactions specific to CCR5 Inhibitor I I No known interactions specific to Maraviroc (Selzentry) this combination Maraviroc (Selzentry) this combination

Integrase Inhibitor I Integrase Inhibitor I I Potential to increase ecstasy levels Elvitegravir/cobicistat/ Elvitegravir/cobicistat/ TDF/FTC) (Stribild) I I No known interactions specific to TDF/FTC) (Stribild) I I No known interactions specific to Dolutegravir (Tivicay) I this combination Dolutegravir (Tivicay) I this combination Raltegravir (Isentress ) Raltegravir (Isentress)

Erectile Dysfunction Agents (avanafil (Stendra), sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra)) Hypotension, tachycardia, arrhythmias (cardiac arrest and death), headache, flushing, rhinitis, dyspepsia, nausea, and visual effects (e.g. GENERAL light sensitivity, changes in color vision), priapism PHARMACOKINETICS Metabolized in the liver via CYP3A4

KNOWN DRUG INTERACTIONS NNRTI’s I delavirdine (Rescriptor) I I Potential to significantly increase avanafil, sildenafil, tadalafil, vardenafil concentrations. Use sildenafil at efavirenz (Sustiva) I reduced doses of 25 mg every 48 hours, tadalafil at reduced doses of 10 mg every 72 hours, vardenafil nevirapine (Viramune) I at reduced doses of no more than 2.5 mg every 72 hours and monitor closely for adverse effects. Do not use with avanafil. etravirine (Intelence) I I No known interactions specific to this combination. rilpivirine (Edurant) I Etravirine has been shown to decrease sildenafil concentrations, though may be used together without sildenafil dosage adjustment. Sildenafil dosage may need to be adjusted based upon clinical effect. Similar interactions are also predicted with tadalafil and vardenafil. Continued next page

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Erectile Dysfunction Agents (Cont’d) (avanafil (Stendra), sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra)) Hypotension, tachycardia, arrhythmias (cardiac arrest and death), headache, flushing, rhinitis, dyspepsia, nausea, and visual effects (e.g. GENERAL light sensitivity, changes in color vision), priapism PHARMACOKINETICS Metabolized in the liver via CYP3A4

KNOWN DRUG INTERACTIONS NRTI’s I *abacavir (ABC, Ziagen) *Atripla (EFV/TDF/FTC) *Combivir (AZT/3TC) Complera (RPV/TDF/FTC) I didanosine (ddl, Videx) I *emtricitabine (FTC, Emtriva) Epzicom (3TC/ABC) I I No known interactions specific to this combination lamivudine (3TC, Epivir) I *SEE INDIVIDUAL COMPONENTS stavudine (d4T, Zerit) I *tenofovir (TDF,Viread) *Trizivir (AZT/3TC/ABC) Truvada (FTC/TDF) I zidovudine (AZT, ZDV, Retrovir) I I Potential to significantly increase avanafil, sildenafil, tadalafil, vardenafil concentrations. Use sildenafil at Protease Inhibitors I reduced doses of 25 mg every 48 hours, tadalafil at reduced doses of 10 mg every 72 hours, vardenafil amprenavir (Ageneras)e) I at reduced doses of no more than 2.5 mg every 72 hours and monitor closely for adverse effects. Do not use with avanafil. fosamprenavir (Lexiva I I No known interactions specific to this combination. Refer to comments for this drug class in general atazanavir (Reyataz) I I Increases sildenafil AUC ~340% and vardenafil AUC 16-fold. May increase tadalafil concentrations. Refer darunavir (Prezista) I to comments for this drug class in general. Monitor closely for adverse effects. indinavir (Crixivan) I I Increases sildenafil AUC 1000%, tadalafil AUC 124%, and vardenafil AUC 49-fold and half-life 5-6 fold. lopinavir/ritonavir (Kaletra) I Refer to comments for this drug class in general. Monitor closely for adverse effects. nelfinavir (Viracept) I I Increases sildenafil AUC ~210%. May increase tadalafil and vardenafil concentrations. Refer to ritonavir (Norvir) I comments for this drug class in general. Monitor closely for adverse effects. saquinavir (Fortovase, Invirase) I tipranavir (Aptivus) No known interactions specific to this combination CCR5 Inhibitor I I Maraviroc (Selzentry) Potential to significantly increase avanafil, sildenafil, tadalafil, vardenafil concentrations. Use sildenafil at reduced doses of 25 mg every Integrase Inhibitor I I Elvitegravir/cobicistat/ 48 hours, tadalafil at reduced doses of 10 mg every 72 hours, vardenafil at reduced doses of no more than 2.5 mg every 72 hours TDF/FTC) (Stribild) and monitor closely for adverse effects. Do not use with avanafil. I No known interactions specific to this combination Dolutegravir (Tivicay) I I Raltegravir (Isentress )

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GHB HEROIN (smack, brown junk, China White) (gamma-hydroxy-butyrate, grievous bodily harm, liquid X) Dreamlike state of warmth and well-being with small doses; CNS Seizures, bradycardia, severe respiratory depression, drowsiness, respiratory depression, constricted pupils, GENERAL depression, hypotension, vomiting coma, death nausea/vomiting with excessive doses PHARMACOKINETICS Utilizes CYP2D6 pathway for metabolism Utilizes CYP3A4 pathway for metabolism

NRTI’s I NRTI’s I *abacavir (ABC, Ziagen) * abacavir (ABC, Ziagen) *Atripla (EFV/TDF/FTC) *Atripla (EFV/TDF/FTC) *Combivir (AZT/3TC) *SEE INDIVIDUAL COMPONENTS *Combivir (AZT/3TC) *SEE INDIVIDUAL COMPONENTS Complera (RPV/TDF/FTC) I Complera (RPV/TDF/FTC) I didanosine (ddl, Videx) I didanosine (ddl, Videx) I *emtricitabine (FTC, Emtriva) * emtricitabine (FTC, Emtriva) Epzicom (3TC/ABC) I Elapmzicvuodmin(e3(T3CTC/A, EBpCiv) ir) I lamivudine (3TC, Epivir) I I stavudine (d4T, Zerit) I stavudine (d4T, Zerit) I *tenofovir (TDF,Viread) * tenofovir (TDF,Viread) *Trizivir (AZT/3TC/ABC) *Trizivir (AZT/3TC/ABC) Truvada (FTC/TDF) I Truvada (FTC/TDF) I zidovudine (AZT, ZDV, Retrovir) zidovudine (AZT, ZDV, Retrovir) I I Protease Inhibitors I I PIs potentially increase drug levels of GHB Protease Inhibitors I I Possible decrease in heroin levels amprenavir (Ageneras)e) I amprenavir (Agenerase) I fosamprenavir (Lexiva I fosamprenavir (Lexiva) I I No known interactions specific to atazanavir (Reyataz) I I No known interactions specific to atazanavir (Reyataz) I this combination. darunavir (Prezista) I this combination. Refer to comments for darunavir (Prezista) I Refer to comments for this drug class indinavir (Crixivan) I this drug class in general indinavir (Crixivan) I in general. lopinavir/ritonavir (Kaletra) I lopinavir/ritonavir (Kaletra) I nelfinavir (Viracept) I nelfinavir (Viracept) I I Reduces heroin levels by 50% ritonavir (Norvir) I ritonavir (Norvir) I saquinavir (Fortovase, Invirase) I saquinavir (Fortovase, Invirase) I tipranavir (Aptivus) tipranavir (Aptivus)

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GHB (Cont’d) HEROIN (smack, brown junk, China White) (Cont’d) (gamma-hydroxy-butyrate, grievous bodily harm, liquid X) Dreamlike state of warmth and well-being with small doses; CNS Seizures, bradycardia, severe respiratory depression, drowsiness, respiratory depression, constricted pupils, GENERAL depression, hypotension, vomiting coma, death nausea/vomiting with excessive doses PHARMACOKINETICS Utilizes CYP2D6 pathway for metabolism Utilizes CYP3A4 pathway for metabolism

KNOWN DRUG INTERACTIONS KNOWN DRUG INTERACTIONS

CCR5 Inhibitor I I No known interactions specific to CCR5 Inhibitor I I No known interactions specific to Maraviroc (Selzentry) this combination Maraviroc (Selzentry) this combination

Integrase Inhibitor I I Potential increase in GHB levels Integrase Inhibitor I I No known interactions specific to Elvitegravir/cobicistat/ with cobicistat Elvitegravir/cobicistat/ this combination TDF/FTC) (Stribild) I I No known interactions specific to TDF/FTC) (Stribild) I Dolutegravir (Tivicay) I this combination Dolutegravir (Tivicay) I Raltegravir (Isentress ) Raltegravir (Isentress)

KETAMINE (K, Special K) LSD (acid) Paranoia, anxiety, mania, hallucinations, "K-hole" (semi-catatonic stupor). Paranoia, visual and auditory hallucinations Elevated levels may cause tachycardia, GENERAL hypertension, respiratory depression PHARMACOKINETICS Undergoes N-demethylation and hydroxylation (possibly mediated by CYP3A4); possible weak inhibitor of CPY2D1 and CYP3A4

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KETAMINE (K, Special K) (Cont’d) LSD (acid) (Cont’d) Paranoia, anxiety, mania, hallucinations, "K-hole" (semi-catatonic stupor). Paranoia, visual and auditory hallucinations Elevated levels may cause tachycardia, hypertension, respiratory depression GENERAL PHARMACOKINETICS Undergoes N-demethylation and hydroxylation (possibly mediated by CYP3A4); possible weak inhibitor of CPY2D1 and CYP3A4

KNOWN DRUG INTERACTIONS KNOWN DRUG INTERACTIONS NRTI’s I I No known interactions specific to NRTI’s I I No known interactions specific to *abacavir (ABC, Ziagen) this combination * abacavir (ABC,Ziagen) this combination *Atripla (EFV/TDF/FTC) *Atripla (EFV/TDF/FTC) *Combivir (AZT/3TC) *SEE INDIVIDUAL COMPONENTS *Combivir (AZT/3TC) *SEE INDIVIDUAL COMPONENTS Complera (RPV/TDF/FTC) I Complera (RPV/TDF/FTC) I didanosine (ddl, Videx) I didanosine (ddl, Videx) I *emtricitabine (FTC, Emtriva) * emtricitabine (FTC, Emtriva) Epzicom (3TC/ABC) I Elapmzicvuodmin(e3(T3CTC/A, EBpCiv) ir) I lamivudine (3TC, Epivir) I I stavudine (d4T, Zerit) I stavudine (d4T, Zerit) I *tenofovir (TDF,Viread) * tenofovir (TDF,Viread) *Trizivir (AZT/3TC/ABC) *Trizivir (AZT/3TC/ABC) Truvada (FTC/TDF) I Truvada (FTC/TDF) I zidovudine (AZT, ZDV, Retrovir) zidovudine (AZT, ZDV, Retrovir) I I Likely increase the effect of ketamine I I No known interactions specific to Protease Inhibitors I (more sedation, increased heart rate and blood Protease Inhibitors I this combination amprenavir (Ageneras)e I pressure). Effects last longer amprenavir (Agenerase) I fosamprenavir (Lexiva I I No known interactions specific to fosamprenavir (Lexiva) I atazanavir (Reyataz) I this combination. Refer to comments for atazanavir (Reyataz) I darunavir (Prezista) I this drug class in general darunavir (Prezista) I indinavir (Crixivan) I indinavir (Crixivan) I lopinavir/ritonavir (Kaletra) I lopinavir/ritonavir (Kaletra) I nelfinavir (Viracept) I I Combination may increase risk of nelfinavir (Viracept) I ritonavir (Norvir) I drug induced hepatitis ritonavir (Norvir) I saquinavir (Fortovase, Invirase) I saquinavir (Fortovase, Invirase) I tipranavir (Aptivus) tipranavir (Aptivus)

CCR5 Inhibitor I I No known interactions specific to CCR5 Inhibitor I I No known interactions specific to Maraviroc (Selzentry) this combination Maraviroc (Selzentry) this combination

Integrase Inhibitor I I Potential increase in ketamine levels; Integrase Inhibitor Elvitegravir/cobicistat/ effects may last longer with cobicistat Elvitegravir/cobicistat/ I I No known interactions specific to TDF/FTC) (Stribild) I I No known interactions specific to TDF/FTC) (Stribild) I this combination Dolutegravir (Tivicay) I this combination Dolutegravir (Tivicay) I Raltegravir (Isentress ) Raltegravir (Isentress)

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MARIJUANA (Tetrahydrocannabinol; THC) METHADONE Tachycardia, loss of inhibitions, dry mouth, Generalized CNS depression GENERAL visual hallucinations PHARMACOKINETICS Metabolized in the liver to active metabolite Primarily utilizes CYP3A4 pathway for metabolism; inhibitor of CYP2D6 6 (11-hydroxy THC) via CYP3A4, 2C9, and 2C6; and CYP3A4 inhibitors/inducers of CYP3A4 may interfere with THC metabolism

KNOWN DRUG INTERACTIONS KNOWN DRUG INTERACTIONS NNRTI’s I NNRTI’s I I No known interactions specific to delavirdine (Rescriptor) I delavirdine (Rescriptor) I this combination efavirenz (Sustiva) I efavirenz (Sustiva) I I Decreases methadone AUC significantly nevirapine (Viramune) I nevirapine (Viramune) I (~60%); titrate methadone dose to effect etravirine (Intelence) I etravirine (Intelence) I I Decreases methadone AUC significantly rilpivirine (Edurant) I No known interactions specific to rilpivirine (Edurant) (~40-50%); titrate methadone dose to effect this combination I Increases methadone clearance ~22% NRTI’s I NRTI’s I (an increase in methadone dose may be *abacavir (ABC,Ziagen) *SEE INDIVIDUAL COMPONENTS * abacavir (ABC,Ziagen) required in some patients *Atripla (EFV/TDF/FTC) *Atripla (EFV/TDF/FTC) I Decreases didanosine AUC ~41-60% Combivir (AZT/3TC) Combivir (AZT/3TC) (consider didanosine tablet form dose Complera (RPV/TDF/FTC I Complera (RPV/TDF/FTC I increase or switch to enteric-coated didanosine (ddl, Videx) I didanosine (ddl, Videx) I formulation which may not be affected to *emtricitabine (FTC, Emtriva) * emtricitabine (FTC, Emtriva) the same degree ) Epzicom (3TC/ABC) I Epzicom (3TC/ABC) I I Decreases stavudine AUC~23% lamivudine (3TC, Epivir) I lamivudine (3TC, Epivir) I I Increases zidovudine AUC ~40% (increases stavudine (d4T, Zerit) I stavudine (d4T, Zerit) I AUC ~29% during chronic treatment) *tenofovir (TDF,Viread) * tenofovir (TDF,Viread) *Trizivir (AZT/3TC/ABC) *Trizivir (AZT/3TC/ABC) I Interaction highly variable and patients Truvada (FTC/TDF) I Truvada (FTC/TDF) I should be evaluated on an individual basis zidovudine (AZT, ZDV, Retrovir) zidovudine (AZT, ZDV, Retrovir) I Decreases methadone levels ~13-30%; I I Potential to increase THC levels I monitor for withdrawal and consider Protease Inhibitors I I No known interactions specific to Protease Inhibitors I methadone dose increase if needed amprenavir (Ageneras)e) I this combination. Refer to comments for this amprenavir (Agenerase) I I Decreases methadone AUC ~16-36% fosamprenavir (Lexiva I drug class in general fosamprenavir (Lexiva) I (may require methadone dose increase) atazanavir (Reyataz) I I In one study, concentrations of atazanavir atazanavir (Reyataz) I I Decreases methadone AUC ~26-53% darunavir (Prezista) I were reduced up to 60% in patients using darunavir (Prezista) I (may require methadone dose increase) indinavir (Crixivan) I marijuana. Study did not differentiate indinavir (Crixivan) I I Decreases methadone AUC ~47% lopinavir/ritonavir (Kaletra) I whether atazanavir was boosted with lopinavir/ritonavir (Kaletra) I (may require methadone dose increase) nelfinavir (Viracept) I ritonavir or not. nelfinavir (Viracept) I I Decreases methadone AUC ~37% ritonavir (Norvir) I ritonavir (Norvir) I (may require methadone dose increase) saquinavir (Fortovase, Invirase) I saquinavir (Fortovase, Invirase) I I Decrease methadone AUC by ~50% tipranavir (Aptivus) tipranavir (Aptivus) (may require methadone dosage increase)

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MARIJUANA (Tetrahydrocannabinol; THC) (Cont’d) METHADONE (Cont’d) Tachycardia, loss of inhibitions, dry mouth, Generalized CNS depression GENERAL visual hallucinations PHARMACOKINETICS Metabolized in the liver to active metabolite Primarily utilizes CYP3A4 pathway for metabolism; inhibitor of CYP2D6 6 (11-hydroxy THC) via CYP3A4, 2C9, and 2C6; and CYP3A4 inhibitors/inducers of CYP3A4 may interfere with THC metabolism

KNOWN DRUG INTERACTIONS KNOWN DRUG INTERACTIONS

CCR5 Inhibitor I I No known interactions specific to CCR5 Inhibitor I I No known interactions specific to Maraviroc (Selzentry) this combination Maraviroc (Selzentry) this combination

Integrase Inhibitor I I Potential to increase THC level Integrase Inhibitor I I No known interactions specific to Elvitegravir/cobicistat/ Elvitegravir/cobicistat/ this combination TDF/FTC) (Stribild) I I No known interactions specific to TDF/FTC) (Stribild) I Dolutegravir (Tivicay) I this combination Dolutegravir (Tivicay) I Raltegravir (Isentress ) Raltegravir (Isentress)

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PATIENT INFORMATION TO REDUCE HARM

ALCOHOL AMPHETAMINES (Crystal) If you take ddI, do not drink alcohol. Try to avoid alcohol or Avoid use if you have heart or liver problems, use modestly. or high blood pressure. Recent reports of transmitted HIV resistance in patients using methamphetamine and practicing unsafe sex. AMYL NITRITE (amyl nitrate, poppers) BENZODIAZEPINES Do not use with avana2l (Stendra), sildena2l (Viagra), Avoid with midazolam and triazolam. Caution with other medications vardena2l (Levitra) or adala2l (Cialis). Heart problems, in this class. Discuss with provider to ensure potential interactions are glaucoma, or anemia makepoppers more dangerous. identi2ed.

COCAINE (coke, blow) ECSTASY (X, MDMA) Don’t get so high you forget to stick to your antiretroviral regimen. Start with 1/4 or 1/2 tablet. Drink plenty of water. Avoid cocaine if you have heart or liver problems, or high blood pressure

Erectile Dysfunction Agents HEROIN (smack, brown junk, China, White) Do not mix with amyl or butyl nitrates (poppers). Start with normal dose and increase only if you experience less Combination can cause sudden drop in blood of a hit and less buzz. Safe injecting. Do not mix with other pressure leading to fainting or heart attack. recreational drugs.

GHB METHADONE Start with half-teaspoon, wait half-hour before taking more. Do Any changes to your methadone regimen or HIV medications should be not mix with alcohol, tranquilizers, pain-killers, or allergy reported to both providers to ensure potential interactions are identi2ed. medications. Do not use if you are alone. The dose you used last week can kill you this week. KETAMINE (K, Special K) Start with 1/3 or 1/2 of usual dose. Wait a half-hour before doing more. Always use with a friend, never alone.

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RESOURCES

The National AETC Program also includes the following services:

National HIV/AIDS Clinicians Consultation Center: 1-800-933-3413 Offering treating clinicians current HIV clinical and drug information and individualized, expert case consultation.

Post-Exposure Prophylaxis 24 hour hotline: 1-888-HIV-4911 Providing consulation for occupational exposures.

Perinatal Hotline: 1-888-448-8765 Providing consulation for perinatal exposure and treatment.

AETC HIV/AIDS National Resource Center: http://www.aidsetc.org/ Providing resources (including curricula and lecture slide sets) on HIV disease treatment, education and data.

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FOR FURTHER INFORMATION, PLEASE VISIT ONE OF THE FOLLOWING WEBSITES:

NY/NJ AIDS Education and Training Center www.nynjaetc.org

U.S. DHHS AIDS Info aidsinfo.nih.gov

NYSDOH AIDS Institute Clinical Resources www.hivguidelines.org

Substance Abuse and Mental Health Services Administration www.samhsa.gov

Addiction Technology Transfer Center www.nattc.org

Harm Reduction Coalition www.harmreduction.org