Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV

Table 5. Significant Pharmacokinetic Interactions between Drugs Used to Treat or Prevent Opportunistic Infections

This table lists the known, predicted, or suspected PK interactions between drugs used for the treatment or prevention of HIV-associated OIs. Many of the drugs listed in this table may also interact with ARV drugs. Clinicians should see the Drug-Drug Interactions tables in the most current Adult and Adolescent Antiretroviral Guidelines to assess interaction potentials between OI drugs and ARV drugs.

Throughout the table, three recommendations are commonly used when concomitant administration of two drugs may lead to untoward consequences. The rationale for these recommendations are summarized below:

Do not coadminister.
There is either strong evidence or strong likelihood that the drug-drug interaction cannot be managed with a dose modification of one or both drugs, and will or may result in either:

• Increase in concentrations of one or both drugs, which may lead to excessive risk of toxicity; or
• Decrease in concentrations of one or both drugs, which may render one or both drugs ineffective.

Coadministration should be avoided, if possible.
There is a potential for significant PK interactions. If other more favorable options exist, clinicians are advised to consider changing components of the regimen to accommodate a safer or more effective regimen. However, coadministration of the drugs may be necessary when there are no other acceptable therapeutic options that provide a more favorable benefit-to-risk ratio.

Use with caution.
Drug combinations are recommended to be used with caution when:

• PK studies have shown a moderate degree of interaction of unknown clinical significance; or
• Based on the known metabolic pathway of the two drugs, there is a potential for PK interaction of unknown clinical significance.

Rifamycin Antibiotics-Related Interactions
Rifamycin antibiotics are potent inducers of Phase 1 and Phase 2 drug metabolizing reactions. Studies have demonstrated that with daily doses of rifampin, enzyme induction increases over a week or more. Based on limited data, larger doses of rifampin (e.g., 1,200 mg) appear to produce the same maximum induction as lower doses, but more rapidly. Single doses of rifampin may not produce significant induction. In general, rifabutin as a CYP3A4 inducer is about 40% of the potency of rifampin, but this can vary by substrate and enzymatic reaction. In general, daily rifapentine (for active TB disease) is at least as potent an inducer as rifampin. However, the potential of drug interactions with once weekly rifapentine (prescribed with isoniazid for latent TB infection) is not well studied, and may result in reduced exposure of drugs that are CYP3A4 substrates. When using a rifamycin antibiotic with a potential interacting drug is necessary, close monitoring for clinical efficacy of the coadministered agent is advised.

Note: To avoid redundancy, drug-drug interactions are listed only once by primary drug (listed alphabetically). Subsequently, when an interacting agent becomes the primary drug, guideline users are referred to the entry for the initial primary drug. See the Clarithromycin row for the first example of this format.