Drug Interactions from The Medical Letter

Drug Interactions from The Medical Letter

About the Program
Drug Interactions from The Medical Letter offers a quick guide to potential interactions between pairs of drugs and provides recommendations for precautionary measures. Interacting pairs of drugs are listed alphabetically, followed by the main effect(s) and clinical significance of the interaction, management recommendations, the mechanism of the interaction, discussion of clinical and research data related to the interaction, description of how similar drugs may or may not interact, and a list of supporting references. Interactions can be searched by generic or brand name; brand names for combination products are not always listed. Reports of interactions between more than two drugs have begun to appear in the medical literature; where these have been documented, they are noted in the discussion section of the monograph.

Criteria for Listing Interactions
The interactions included in this program are primarily based on clinical reports from the literature and clinical and/or pharmacokinetic data listed in the manufacturer’s prescribing information. Theoretical interactions that might be predicted based on a drug’s pharmacokinetic properties are also included. If a drug or pair of drugs does not have an interaction listed in the program, a message will appear stating “No Interactions Found”.

The following types of interactions may not be included (depending on the strength of the evidence):
  • Interactions extrapolated from animal studies or from interactions reported with related drugs
  • Effects expected from conflicting mechanisms of action (e.g. a drug that increases blood pressure taken with an antihypertensive)
  • Drug-food interactions
  • Interactions based on dosage form (e.g. two ophthalmic drugs)

The following types of interactions are not included:
  • Information regarding the compatibility of drugs administered intravenously through the same line
  • Interactions between general anesthetics and drugs likely to be administered during surgery, such as autonomic drugs and local anesthetics
  • Interactions useful in therapy

New interactions between drugs are continually being reported; the absence of a listing does not necessarily mean that the drugs will not interact when given concurrently. Any drug that is not included in the index of this program has not been evaluated and any interactions with it have not been included. Searching a single drug will provide a list of interacting drugs that are included in this program, but may not provide a complete list of potential interactions for that drug.

Mechanisms of Interactions
Some drugs interact by changing the metabolism of other drugs, either through inhibition or induction of hepatic enzyme activities or through alterations in hepatic blood flow. Many drugs are metabolized by cytochrome P450 isozymes. These isozymes are named according to a standard system, e.g. CYP3A4. Drugs that are substrates or inhibitors of the same isozyme in vitro may be predicted to interact if taken concomitantly, but often the interaction is not detected, or may not be clinically significant, in vivo.

Additive effects of drugs that may be of clinical significance are usually included, such as CNS depression and serotonin syndrome. When two drugs that prolong the QT interval are taken concurrently, the additive effects noted are based on the individual effect of each drug on the QT interval.

Elimination of a drug can also be affected by the P-glycoprotein membrane-bound transport system. Drugs that inhibit P-glycoprotein activity can increase the serum concentration or toxicity of drugs that are P-glycoprotein substrates. Other transport systems (e.g. OATP) that can affect the elimination and metabolism of drugs are continuously being identified; interactions based on these systems may not be listed.

Some drugs interact by altering the binding of another drug to plasma proteins or tissue receptors, altering the distribution of drugs to active receptor sites, delaying or enhancing absorption or excretion, or causing additive or synergistic effects.

In some cases, serum concentrations of the affected drugs can be measured to monitor the extent of the interaction and make appropriate adjustments in drug dosage, but for the majority of interactions, monitoring of clinical status is recommended. Monitoring is most important when one of the interacting drugs is started, stopped or changed in dosage.