• New York State Department of Health. Drug-drug interactions between HAART, medications used in substance use treatment, and recreational drugs. New York (NY): New York State Department of Health; 2008 Jan. 18 p. [69 references]

This is the current release of the guideline.

This guideline updates a previous version: New York State Department of Health. Drug-drug interactions between HAART, medications used in substance use treatment, and recreational drugs. New York (NY): New York State Department of Health; 2005 Jul. 22 p.

• Human immunodeficiency virus (HIV) infection
• Conditions associated with drug interactions encountered in HIV-infected patients using highly active antiretroviral therapy (HAART) as well as medications used in substance use treatment and recreational drugs

Management
Prevention
Risk Assessment

Allergy and Immunology
Family Practice
Infectious Diseases
Internal Medicine
Pharmacology

Advanced Practice Nurses
Health Care Providers
Physician Assistants
Physicians
Public Health Departments
Substance Use Disorders Treatment Providers

• To present an overview of known and potential interactions between medications used in the treatment of substance use, recreational drugs, and highly active antiretroviral therapy (HAART)
• To provide guidelines for prevention and management of drug-drug interactions between HAART and medications used in substance use treatment and recreational drugs

Human immunodeficiency virus (HIV)-infected patients

1. Conducting a thorough medication history at each visit, including
   • Prescription medications
   • Over-the-counter medications
   • Recreational drugs
   • Herbal and alternative therapies
2. Classifying common inhibitors, inducers, and substrates of the cytochrome P-450 (CYP450) system to predict significant drug interaction
3. Discussing potential drug interactions with patients receiving methadone or using recreational drugs before initiating antiretroviral therapy (ARV)
4. Monitoring patients receiving concurrent methadone or using recreational drugs and highly active antiretroviral therapy (HAART) for drug-interaction symptoms, such as withdrawal symptom or excess sedation and zidovudine toxicity (in patients taking methadone), as well as for signs of hepatotoxicity (in patients taking recreational drugs)
5. Reporting all prescribed HAART-related drug changes for patients receiving methadone to the patient's methadone maintenance program, particularly if changes include initiating efavirenz or nevirapine
6. Avoiding certain drug combinations likely to produce adverse reactions (refer to the original guideline document for details)

Morbidity/adverse effects associated with drug-drug interactions

Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases

Not stated

Not stated

Expert Consensus (Committee)

Not applicable

Review

Not stated

Expert Consensus

AIDS Institute clinical guidelines are developed by distinguished committees of clinicians and others with extensive experience providing care to people with HIV infection. Committees* meet regularly to assess current recommendations and to write and update guidelines in accordance with newly emerging clinical and research developments.

The Committees* rely on evidence to the extent possible in formulating recommendations. When data from randomized clinical trials are not available, Committees rely on developing guidelines based on consensus, balancing the use of new information with sound clinical judgment that results in recommendations that are in the best interest of patients.

* Current committees include:

• Medical Care Criteria Committee
• Committee for the Care of Children and Adolescents with HIV Infection
• Dental Standards of Care Committee
• Mental Health Committee
• Women's Health Committee
• Substance Use Committee
• Physician's Prevention Advisory Committee
• Pharmacy Committee

Not applicable

A formal cost analysis was not performed and published cost analyses were not reviewed.

External Peer Review

All guidelines developed by the Committee are externally peer reviewed by at least two experts in that particular area of patient care, which ensures depth and quality of the guidelines.

General Recommendation

The clinician should conduct a thorough medication history at each visit that includes prescription medications, including those prescribed by other providers, over-the-counter medications, recreational drugs, and herbal/alternative therapies.

Drug Interactions Related to the Metabolism of Highly Active Antiretroviral Therapy (HAART)

Table 2 in the original guideline document shows the potential interactions among antiretroviral (ARV) agents and the most common medications used to treat substance use disorders according to how they are metabolized.

Drug Interactions with Methadone

Clinicians should discuss potential drug interactions with patients receiving methadone before initiating ARV therapy.

Clinicians should report all prescribed HAART-related drug changes for patients receiving methadone to the patient's methadone maintenance program.

Clinicians should monitor human immunodeficiency virus (HIV)-infected substance users receiving concurrent methadone and ARV therapy for symptoms of withdrawal and/or excess sedation when ARV therapy is initiated or changed.

Key Point:

Interactions between HAART and methadone may precipitate symptoms of oversedation or withdrawal.

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)

When using didanosine in patients receiving methadone, clinicians should consider using the enteric-coated capsule formulation because it does not lead to a clinically significant interaction when given concurrently with methadone.

Clinicians should monitor patients for symptoms of zidovudine toxicity, such as anemia, nausea, and headaches, when zidovudine and methadone are used concurrently.

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Clinicians initiating a HAART regimen consisting of efavirenz or nevirapine in patients receiving methadone should contact the methadone maintenance program clinicians to ensure that the onset of withdrawal symptoms, if they occur, is promptly addressed by increasing the patient's methadone dose.

Clinicians prescribing methadone maintenance therapy should closely monitor patients when adding efavirenz or nevirapine to their ARV regimens.

Recreational Drugs and HAART

Clinicians should assess adherence and be alert for signs of hepatotoxicity in HIV-infected patients receiving HAART who are concurrently using recreational drugs.

See Appendix XI in the original guideline document for a list of known drug interactions with HAART and recreational drugs.

Amphetamines

Clinicians should not prescribe ritonavir, even in low doses for boosting, if patients report using amphetamines.

Barbiturates

Clinicians treating HIV-infected patients misusing barbiturates should:

• Avoid co-administration of NNRTIs and phenobarbital
• Use caution if maraviroc and phenobarbital are used concomitantly
• Consider doubling the raltegravir dose when co-administered with phenobarbital

Benzodiazepines

Clinicians should avoid concurrent use of alprazolam, midazolam, and triazolam with all protease inhibitors (PIs), delavirdine, and efavirenz.

Ecstasy (Methylenedioxy-methamphetamine [MDMA])

Clinicians should not prescribe protease inhibitors (PIs), even in low doses for boosting, if patients report using ecstasy or gamma hydroxybutyrate (GHB).

Psychotropics

Clinicians should consider medication interactions as a potential cause of mental status changes in persons receiving psychotropic medications and HAART.

None provided

The type of supporting evidence is not specifically stated for each recommendation.

Improved understanding and appropriate management of known and potential interactions between medications used in the treatment of substance use, recreational drugs, and highly active antiretroviral therapy (HAART)

Refer to appendix XII in the original guideline document for agents to be used with caution.

Refer to appendix XII in the original guideline document for contraindicated combinations.

The AIDS Institute's Office of the Medical Director directly oversees the development, publication, dissemination and implementation of clinical practice guidelines, in collaboration with The Johns Hopkins University, Division of Infectious Diseases. These guidelines address the medical management of adults, adolescents and children with HIV infection; primary and secondary prevention in medical settings; and include informational brochures for care providers and the public.

Guidelines Dissemination

Guidelines are disseminated to clinicians, support service providers and consumers through mass mailings and numerous AIDS Institute-sponsored educational programs. Distribution methods include the HIV Clinical Resource website, the Clinical Education Initiative, the AIDS Educational Training Centers (AETC) and the HIV/AIDS Materials Initiative. Printed copies of clinical guidelines are available for order from the NYSDOH Distribution Center for providers who lack internet access.

Guidelines Implementation

The HIV Clinical Guidelines Program works with other programs in the AIDS Institute to promote adoption of guidelines. Clinicians, for example, are targeted through the Clinical Education Initiative (CEI) and the AIDS Education and Training Centers (AETC). The CEI provides tailored educational programming on site for health care providers on important topics in HIV care, including those addressed by the HIV Clinical Guidelines Program. The AETC provides conferences, grand rounds and other programs that cover topics contained in AIDS Institute guidelines.

Support service providers are targeted through the HIV Education and Training initiative which provides training on important HIV topics to non-physician health and human services providers. Education is carried out across the State as well as through video conferencing and audio conferencing.

The HIV Clinical Guidelines Program also works in a coordinated manner with the HIV Quality of Care Program to promote implementation of HIV guidelines in New York State. By developing quality indicators based on the guidelines, the AIDS Institute has created a mechanism for measurement of performance that allows providers and consumers to know to what extent specific guidelines have been implemented.

Finally, best practices booklets are developed through the HIV Clinical Guidelines Program. These contain practical solutions to common problems related to access, delivery or coordination of care, in an effort to ensure that HIV guidelines are implemented and that patients receive the highest level of HIV care possible.

Living with Illness
Staying Healthy

Effectiveness
Patient-centeredness
Safety

• New York State Department of Health. Drug-drug interactions between HAART, medications used in substance use treatment, and recreational drugs. New York (NY): New York State Department of Health; 2008 Jan. 18 p. [69 references]

Not applicable: The guideline was not adapted from another source.

2005 Jul (revised 2008 Jan)

New York State Department of Health - State/Local Government Agency [U.S.]

New York State Department of Health

Substance Use Committee

Chair: Marc N Gourevitch, MD, MPH, New York University School of Medicine , New York, New York

Members: Bruce D Agins, MD, MPH, New York State Department of Health AIDS Institute, New York, New York; Julia H Arnsten, MD, MPH, Montefiore Medical Center, Bronx, New York; Lawrence S Brown, Jr, MD, MPH, FASAM, Addiction Research and Treatment Corporation, Brooklyn, New York; Brenda Chabon, PhD, Montefiore Medical Center, Bronx, New York; Barbara H Chaffee, MD, MPH, Binghamton Family Care Center, Binghamton, New York; Michael L Christie, MD, AIDS Community Health Center, Rochester, New York; Chinazo O Cunningham, MD; Montefiore Medical Center, Bronx, New York; Nereida L Ferran-Hansard, MD, Jacobi Medical Center, Bronx, New York; Steven S Kipnis, MD, FACP, FASAM, New York State Office of Alcoholism and Substance Abuse Services, Orangeburg, New York; Joseph P Merlino, MD, MPA, Mount Sinai School of Medicine, New York, New York; Nancy Murphy, NP, St. Luke's Roosevelt Hospital Center, New York, New York; Edward Nunes, MD, New York State Psychiatric Institute, New York, New York; David C Perlman, MD, Beth Israel Medical Center, New York, New York; Sharon L Stancliff, MD, Harm Reduction Coalition, New York, New York; Robert Whitney, MD, Erie County Medical Center, Buffalo, New York

Liaisons: Daliah I Heller, MPH, Liaison to the New York City Department of Health and Mental Hygiene, New York, New York

AIDS Institute Staff Liaisons: Diane M Rudnick, MEd, Liaison to the New York State Department of Health AIDS Institute, New York, New York

AIDS Institute Staff Physician: Eunmee H Chun, MD, New York State Department of Health AIDS Institute, New York, New York

Principal Contributors: John J Faragon, PharmD, Albany Medical Center, Albany; Paul Pham, PharmD, The Johns Hopkins University, Baltimore

Not stated

This is the current release of the guideline.

This guideline updates a previous version: New York State Department of Health. Drug-drug interactions between HAART, medications used in substance use treatment, and recreational drugs. New York (NY): New York State Department of Health; 2005 Jul. 22 p.

None available

This NGC summary was completed by ECRI on August 18, 2005. This NGC summary was updated by ECRI Institute on June 11, 2008.