Clinical Guide > ARV Effects > Drug Interactions

Drug-Drug Interactions with HIV-Related Medications

Author: Kirsten Balano, PharmD
January 2011

Chapter Contents


Drug-drug interactions are common concerns of patients with HIV and their health care providers. The issues involved in evaluating drug interactions are complex. Although many questions can be articulated simply (e.g., "What antidepressant is least likely to have drug interactions with antiretroviral medications?"), the responses to these questions involve more complex concerns (e.g., "In choosing an antidepressant for my patient with HIV, I must consider efficacy, adverse effects, and tolerability as well as drug interactions.").

This complexity is increased because antiretroviral (ARV) agents, particularly protease inhibitors (PIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and the CCR5 antagonist maraviroc, can cause or be affected by alterations in the activity of the cytochrome (CYP) P450 enzyme system in the liver, as well as by other mechanisms of drug metabolism. Interactions between an ARV and another drug (whether another ARV or a different type of medication) may result in an increase or a decrease in the serum levels of either the ARV or the interacting drug, potentially changing the effectiveness or the toxicity risk of substrate drugs. Understanding drug-drug interactions is challenging because of several factors, including the following:

Information on various drug-drug interactions is available in guidelines and via the Internet (see "Resources," below). Such resources can provide data regarding two-drug combinations, but rarely consider all the complexities outlined above. What follows, therefore, is a suggested approach to considering drug-drug interactions in managing HIV-infected patients and making patient-specific decisions.

S: Subjective

A new patient arrives for a clinic intake appointment. The patient receives medical care from a local infectious disease physician who treats only a handful of HIV-infected patients. The patient was recently released from hospital with a discharge diagnosis of pneumonia and Mycobacterium avium complex (MAC). The patient is not yet taking ARVs, but is likely to start in the next several weeks after the establishment of care and adherence support programs. Other problems include hyperlipidemia, erectile dysfunction, diabetes, depression, gastroesophageal reflux disease (GERD), and herpes. The clinician wants to review the patient's medication list to check for any potential drug-drug interactions.

O: Objective

Review the patient's pharmacy records for current medications, and ask about use of over-the-counter (OTC), herbal or natural products, and dietary supplements. As requested, the patient has brought in all medications from home for review. The current medication list includes the following:

A: Assessment

Step 1: Identify interactions and classify them as follows:

Definite Drug Interactions

A drug interaction is definite if a high level of evidence is available regarding the drug combination, the clinical significance of the interaction is well understood, and consensus exists regarding the management strategy (e.g., whether dosage adjustments are required, or concurrent use is contraindicated). Common definite interactions for HIV patients include the following:

Probable Drug Interactions

A drug interaction is probable if the limited available evidence suggests that an interaction may occur, even if the clinical outcome or significance may not be clearly established. Effective management of a probable interaction is based on assessment and clinical judgment about the risks and benefits of a particular combination for each patient. Examples of probable interactions with HIV-related medications include the following:

Possible Drug Interactions

Possible drug interactions may be difficult to distinguish from probable drug interactions, but in these cases, only theoretical evidence is available. The proper management of such interactions requires weighing the risks and benefits of the combination and making sound clinical judgments. Examples of possible drug interactions with HIV medications include the following:

Memorizing all the potential drug interactions is impossible. It is possible, however, to remember a few commonly encountered drug combinations that have the potential for clinically significant interactions. It is also important to recognize that PIs (particularly ritonavir) and NNRTIs very commonly interact with other medications. The above examples of definite, probable, and possible interactions are reasonable "red flag" drug combinations that can be recalled easily. In addition, certain Internet resources allow providers to submit all of a patient's current medications and planned additions (e.g., atazanavir/ritonavir as part of a new ARV regimen) and receive information on potential interactions (see "Resources," below). Finally, consultation with clinical pharmacists can aid in identifying and classifying potential interactions.

P: Plan

Step 2: The patient described above will start an ARV regimen of atazanavir/ritonavir + tenofovir + emtricitabine. The PI may cause problematic drug-drug interactions with some of the patient's preexisting medications, and tenofovir interacts with atazanavir. Develop a plan for management when these ARVs are added. For this patient, the following definite interactions should be of concern:

Refer to available references for management suggestions. Such references include the following:

Most of these resources include specific dosage adjustments or alternative agents to consider when managing these drug combinations. The suggestions for this patient are as follows:

Although this patient's current medication list does not contain an erectile dysfunction agent, the patient should be educated about the definite interactions and dosage adjustments recommended for patients using those agents with PIs. Some patients may obtain erectile dysfunction agents outside the care of their physician and, if unaware of the interactions and suggested dosage adjustments, may be at risk of life-threatening consequences.

The following probable or possible interactions should be considered if PIs are begun, including:

The web-based resources and other references listed above include some information about these potential interactions. The following are suggestions:

Consultation with clinical pharmacy services may assist in evaluating the potential significance of drug interactions and developing management strategies.

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