• New York State Department of Health. HIV drug-drug interactions. New York (NY): New York State Department of Health; 2008 Mar. 48 p. [32 references]

This is the current release of the guideline.

This guideline updates a previous version: New York State Department of Health. HIV drug-drug interactions. New York (NY): New York State Department of Health; 2007 Feb. 44 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 therapy for comorbid conditions and for prophylaxis of opportunistic infections

Counseling
Management
Prevention
Risk Assessment

Allergy and Immunology
Family Practice
Infectious Diseases
Internal Medicine
Pharmacology
Preventive Medicine

Advanced Practice Nurses
Health Care Providers
Pharmacists
Physician Assistants
Physicians
Public Health Departments

• To provide an overview of known and potential drug interactions encountered with the use of highly active antiretroviral therapy (HAART)
• To provide recommendations for prevention and management of these drug interactions

Human immunodeficiency virus (HIV)-infected patients

1. Thorough medication history at each visit including prescription medications, over-the-counter medications, recreational drugs, and herbal and alternative therapies
2. Classification of common substrates, inducers, and inhibitors of the cytochrome P-450 (CYP450) system to predict significant drug interaction
3. Identification of dietary restrictions with antiretroviral (ARV) drugs to avoid food-drug interactions
4. Provision of detailed list of drugs contraindicated with the use of highly active antiretroviral therapy (HAART)
5. Avoidance of certain drug combinations (refer to the original guideline document for details)
6. Dose adjustments during HAART regimens

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.

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.

The clinician should classify common substrates, inducers, and inhibitors of the cytochrome P-450 (CYP450) system used in highly active antiretroviral therapy (HAART) to accurately predict drugs that may lead to significant drug interactions (refer to Table below titled "Select CYP450 Inducers, Inhibitors, and Substrates").

Refer to Appendix B in the original guideline document for information on routes of elimination of HAART and the effect on CYP450.

The clinician should identify dietary restrictions with antiretroviral (ARV) drugs so that food-drug interactions can be avoided.

Key Points:

• Clinicians should instruct their patients to notify them of any new medication the patient is taking.
• Providing patients with a detailed list of drugs that are contraindicated with HAART may help the patient to identify significant drug interactions.

Classification of Drug Interactions

Key Point:

Induction can be problematic during HAART due to concerns for virologic failure when protease inhibitors (PI) and/or non-nucleoside reverse transcriptase inhibitor (NNRTI) drug concentrations are reduced.

HAART-Related Drug Interactions

Anticonvulsants

Clinicians should monitor anticonvulsant levels in patients taking concurrent HAART and anticonvulsant therapy.

Clinicians should avoid prescribing carbamazepine, phenobarbital, and phenytoin for patients receiving non-nucleoside reverse transcriptase inhibitors (NNRTIs) or PIs. Valproic acid or levetiracetam may be considered.

Antifungal Drugs

Clinicians should not prescribe voriconazole for patients taking ritonavir (400 mg every 12 hours). Clinicians should avoid or use caution when combining voriconazole with the other NNRTIs or unboosted PIs.

Antimycobacterial Drugs

Clinicians should not use rifampin with any PI. Consider rifabutin with proper dose adjustment.

Erectile Dysfunction Agents

The following is generally recommended when erectile dysfunction agents are combined with PIs:

Sildenafil - use reduced initial dose of 25 mg every 48 hours and monitor for adverse effects

Tadalafil - use initial dose of 5 mg, and do not exceed a single dose of 10 mg in 72 hours

Vardenafil - use initial dose of 2.5 mg, and do not exceed a single 2.5-mg dose in 72 hours

Ergot Alkaloids

Clinicians should not prescribe ergotamine derivatives in patients receiving concurrent PI therapy. Alternative medications should be considered.

Herbal Therapy

In the setting of PI- or NNRTI-based HAART, supplemental garlic and St. John's Wort are contraindicated.

All herbal products should be used with caution until further data are available regarding their effects with concurrent HAART.

Key Point:

Because most providers cannot accurately predict which patients use herbal therapy, it is important to discuss ARV/herbal drug interactions with all patients.

Hydroxymethyl Glutaryl Coenzyme A (HMG-CoA) Reductase Inhibitors

Clinicians should not prescribe simvastatin or lovastatin for patients taking PIs.

Key Points:

• Lovastatin and simvastatin are contraindicated with all PIs and delavirdine (DLV).
• Pravastatin is the safest drug for treating hyperlipidemia during concurrent PI therapy.
• Atorvastatin can be used cautiously at lower doses (5 to 10 mg) with careful titration.
• Rosuvastatin can be used at lower doses (5mg) with careful titration.

Oral Contraceptives

Clinicians should use caution when prescribing oral contraceptives for patients receiving HAART because of the variations in effect on ethinyl estradiol levels.

Clinicians should advise women who are taking efavirenz, nevirapine, lopinavir/ritonavir, nelfinavir, ritonavir, tipranavir/ritonavir, darunavir/ritonavir, or saquinavir to use alternate or additional forms of birth control.

Psychotropic Therapies

Drug interactions with most psychotropic therapies are summarized in Table 3 in the original guideline document.

Sedative/Hypnotics

Clinicians should not prescribe alprazolam, midazolam, or triazolam for patients receiving PIs. Lorazepam or oxazepam may be considered.

None provided

The type of evidence supporting the recommendations is not specifically stated.

Identification of risk, prevention, and appropriate management of human immunodeficiency virus (HIV) drug-drug interactions

Refer to the "Major Recommendations" field above and to Appendix A in the original guideline document for specific cautions concerning various drug combinations.

Refer to the "Major Recommendations" field above and to Appendix A in the original guideline document for specific contraindicated drug 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. HIV drug-drug interactions. New York (NY): New York State Department of Health; 2008 Mar. 48 p. [32 references]

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

2004 (revised 2008 Mar)

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

New York State Department of Health

Medical Care Criteria Committee

Chair: Jessica E Justman, MD, Columbia University, New York, New York

Vice-Chair: Barry S Zingman, MD, Montefiore Medical Center, Bronx, New York

Members: Judith A Aberg, MD, New York University School of Medicine, New York, New York; Bruce D Agins, MD, MPH, New York State Department of Health AIDS Institute, New York, New York; Barbara H Chaffee, MD, MPH, Binghamton Family Care Center, Binghamton, New York; Steven M Fine, MD, PhD, University of Rochester Medical Center, Rochester, New York; Barbara E Johnston, MD, Saint Vincent's-Manhattan Comprehensive HIV Center, New York, New York; Jason M Leider, MD, PhD, North Bronx Healthcare Network of Jacobi and North Central Bronx Hospitals, Bronx, New York; Joseph P McGowan, MD, FACP, Center for AIDS Research & Treatment, North Shore University Hospital, Manhasset, New York; Samuel T Merrick, MD, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, New York; Rona M Vail, MD, Callen-Lorde Community Health Center, New York, New York

Liaisons: Sheldon T Brown, MD, Liaison to the Department of Veterans Affairs Medical Center, Bronx Veteran Affairs Medical Center, Bronx, New York; Douglas G Fish, MD, Liaison to the New York State Department of Corrections, Albany Medical College; Albany, New York; Peter G Gordon, MD, Liaison to the HIV Quality of Care Advisory Committee, Columbia University College of Physicians and Surgeons, New York, New York; Fabienne Laraque, MD, MPH, Liaison to the New York City Department of Health and Mental Hygiene, Treatment and Housing Bureau of HIV/AIDS Prevention and Control, New York, New York; Joseph R Masci, MD, Liaison to New York City Health and Hospitals Corporation, Elmhurst Hospital Center; Elmhurst, New York

AIDS Institute Staff Physician: Charles J Gonzalez, MD, New York State Department of Health AIDS Institute, New York, New York

Principal Investigator: John G Bartlett, MD, The Johns Hopkins University, Baltimore, Maryland

Principal Contributor: Paul Pham, PharmD, The Johns Hopkins University, Baltimore, Maryland

Not stated

This is the current release of the guideline.

This guideline updates a previous version: New York State Department of Health. HIV drug-drug interactions. New York (NY): New York State Department of Health; 2007 Feb. 44 p.

None available

This NGC summary was completed by ECRI on January 17, 2005. This summary was updated on April 15, 2005 following the withdrawal of Bextra (valdecoxib) from the market and the release of heightened warnings for Celebrex (celecoxib) and other nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). This summary was updated by ECRI on June 16, 2005, following the U.S. Food and Drug Administration (FDA) advisories on Sustiva (efavirenz) and COX-2 selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs). This summary was updated by ECRI on July 15, 2005 following the FDA advisory on Cialis, Levitra, and Viagra. This NGC summary was updated by ECRI Institute on September 18, 2007. This summary was updated by ECRI Institute on November 6, 2007, following the updated U.S. Food and Drug Administration advisory on Viagra, Cialis, Levitra, and Revatio. This summary was updated by ECRI Institute on March 28, 2008, following the FDA advisory on Prezista (darunavir). This NGC summary was updated most recently by ECRI Institute on June 5, 2008.