Drug Interactions: Another Complication in HIV Care

In 1988, the most common question about drug interactions went something like this: "Do I take my AZT with or without food?"

What a difference 10 years can make. Today, with the ever-growing list of antiretroviral medications, the possibility of adverse drug interactions is confusing to patients, physicians and pharmacists alike. Witness the recent reports of medication dispensation errors, wherein pharmacists have mixed up Viramune with Viracept or Retrovir with ritonavir, as examples of how simple mistakes can lead to harmful interactions.

Two categories

Drug interactions can be divided into two categories: pharmacokinetic interactions and pharmacodynamic interactions.

Pharmacokinetic interactions are those that describe how a drug is processed by the body, influencing absorption, metabolism, distribution and excretion. An example of an adverse pharmacokinetic reaction would be taking ddI with food, which would decrease absorption of the drug. Other effects of pharmacokinetic interactions include nausea (experienced with many drugs) anemia (experienced with AZT, for example) and kidney stones (experienced with Crixivan).

Pharmacodynamic interactions involve drug activity and toxicity. To make it easier to understand the difference between the two categories, think of pharmacokinetics as what the body does to the drug while pharamcodynamics describe what the drug does to the body.

A combination of AZT and ganciclovir are both potential bone marrow suppressors and could increase the risk of such suppression. Another example is the peripheral neuropathy many people have experienced with either ddI or ddC, which has led to the recommendation that the two drugs not be taken together in order to prevent a significant increase in toxicity. A protease inhibitor like Norvir (ritonavir) can have serious interactions with a large number of drugs, anything from reducing the effects of oral contraceptives to decreasing the levels of AZT and ddI.

Red flags

So what are some red-flag areas?

Besides potential pharmacist dispensation errors, mistakes leading to drug-drug interactions can occur because the patient is getting prescription medications from more than one medical provider. Many people with HIV see a primary care physician and several specialists. This sort of fragmentation can lead to potential interactions. While patients may intend to be open with their providers about all of the medication they are taking, some patients may not be aware of what they are taking or neglect to mention non-prescription drugs.

Adherence and correct dosing also play important roles in preventing certain drug-drug interactions. Non-adherence may lead to certain drug-resistant mutations or taking more than the prescribed amount of certain medications may lead to adverse side effects, toxic reactions or worse.

Other areas of concern involve interactions between drugs and food, which are primarily of the pharmacokinetic variety, as they may affect absorption, metabolism and other body functions. The chart on this page describes which antiretroviral medications must be taken with or without food.

To reduce the risk of any potential drug-drug interactions, the following steps may prove helpful:

• Bring all of your medications, including non-prescription medications and complimentary/alternative therapies, with you to each medical appointment and ask that the provider review all of them with you, including proper dosing and meal requirements. Be sure to include mention of health foods, vitamins, herbal remedies, investigational drugs or street drugs.

• If given any new prescriptions, verify with your care provider, including your pharmacist, that there are no possible interactions with your other medications.

• Two excellent web sites with complete drug interaction charts are the HealthCare Communications Group (www.healthcg.com) and Project Inform (www.projinf.org).

• Contact a treatment advocate or HIV nutrition advocate to review your interaction concerns.

• Maintain consistency with your care-providers and pharmacists. If you switch around a lot, make sure you keep them informed of your drug regimens, past and present.

• Avoid taking meds from other prescriptions, such as those given to you by friends and relatives. What works for them may not necessarily work for you.

As most interaction studies look at only two drugs at a time, a lot of this information is difficult to apply to the majority of people with HIV, who take more than two drugs. That is why discussing potential interactions with your medical provider, pharmacist, treatment advocate and registered dietitian is more important than ever.

In coming months in Positive Living, we will look at specific drug-drug interactions, particularly concerning protease inhibitors, reverse transcriptase inhibitors and opportunistic infection therapies.

With or without food?
Retrovir (Zidovudine - ZDV - AZT)	Take before meals to maximize absorption or with a meal if it causes nausea.
Epivir (lamivudine - 3TC)	Either
Zerit (stavudine - d4T)	Either
Videx (didanosine - ddI)	Take on an empty stomach to maximize absorption.
Hivid (zalcitabine - ddC)	Take on an empty stomach to maximize absorption.
Combivir (AZT - 3TC)	Take before meals to maximize absorption or with a meal if it causes nausea.
Viramune (nevirapine)	Either
Rescriptor (delavidine mesylate)	Avoid taking with fatty foods.
Crixivan (indinavir)	Take on empty stomach or with light snack or low-fat drink (<2g fat, <5.6g protein, <65g carbohydrate, <300 calories). Drink at least 10-12 cups of fluids/day.
Fortovase (saquinavir)	Take within 2 hours after a full meal.
Viracept (nelfinavir mesylate)	Take with a meal or substantial snack.
Norvir (ritonavir)	Take with a meal.
Fortovase (saquinavir)	Take within 2 hours after a full meal.
Preveon (adefovir dipivoxil)	Either
Abacavir (GW 1592)	Either (Pending FDA approval)
Sustiva (efavirenz, DMP266)	Either (Pending FDA approval)

Glenn Gaylord is a community health advocate at AIDS Project Los Angeles.

This article has been reprinted at The Body with the permission of AIDS Project Los Angeles (APLA).