Altered absorption

Some drugs, especially opiates such as morphine and codeine, slow the digestive process and may alter the absorption rate of a drug. Conversely, other drugs, such as metoclopramide, speed up the digestive process and may affect the speed and extent to which a drug is absorbed.

Calcium is one drug that interacts with a range of medications. It can interfere with the absorption of tetracyclines and quinolone antibiotics and diminish their effectiveness. When taken with corticosteroids, it is the effect of calcium that is lessened. Combined with an oestrogen, absorption of calcium increases, thus helping improve bone density. The effects caused by calcium can generally be avoided by spacing intake of the interacting drugs several hours apart. It is a good idea to check with a pharmacist regularly for potential drug interactions and to also check in whenever a drug is added or removed from the daily regimen.  

With the original formulations of ddI (didanosine, Videx ), absorption after oral administration was variable due to its poor solubility in an acidic environment (i.e. with citrus juices such as orange or grapefruit). Drugs that lowered stomach acidity, such as cimetidine (Dyspamet/Tagamet ), ranitidine (Zantac ), and antacids (Rennies) and magnesium trisilicate increased ddI absorption and perhaps its toxicity. In 2000, a reformulated version of ddI containing enteric-coated beadlets of ddI was licensed. This version does have a negative effect on drugs that need stomach acid to be absorbed, including dapsone, ketoconazole, and ciprofloxacin. 

A similar interaction can occur between protease inhibitors and acid-reducing agents, such as ranitidine. The use of acid-reducing agents can reduce blood levels of the protease inhibitors that need stomach acid to facilitate drug absorption into the bloodstream. A number of acid-lowering agents are available without prescription and over-the-counter in chemists, so many patients may be unaware of these risks when they buy drugs to treat heartburn or indigestion.

The protease inhibitor most affected by acid-reducing agents is atazanavir (Reyataz ). The extent of its interactions with different acid-reducing agents is still being explored, so caution and consultation with a pharmacist is advised if planning to take atazanavir (or other protease inhibitors) with an acid-reducing agent.   

In a retrospective Kenyan hospital study of HIV-positive patients, clinically significant drug interactions affected a quarter of 1000 consecutive patients followed for a median of nine months. Major common drug interactions (possibly life-threatening, requiring dose modification of one or both medications, or resulting in >50% ARV AUC) were found between NNRTI drugs efavirenz or nevirapine with the TB drug rifampicin or azoles and between PIs boosted lopinavir and nelfinavir with antacids and rifampicin. Steroids, azoles, and anti-malarials caused moderate ARV drug interactions.¹

This result has implications for the use of fixed-dose ARVs with other drugs and also indicates a need for refinement of treatment protocols in areas with co-existing epidemics of HIV, TB, and malaria.

For more detailed information, check the individual drug listings to be found in A to Z of antiretroviral drugs. Also, to check specific drug interactions and create specialised interaction profiles, consult the University of Liverpool website found at www.hiv-druginteractions.org.