Why Pharmacists Need to Discuss Potential OTC Drug-Drug Interactions with Antiretroviral Therapy

When asking patients what medications they take, many often only acknowledge daily prescription medications and fail to consider OTC medications as having a potential to interact with their antiretroviral (ART) medications for HIV/AIDS.

One study reported that 55% of patients living with HIV/AIDS were taking OTC medications.¹ Based on this information, it is important that pharmacists ask and document which prescription and OTC (including herbal and supplement) medications the patient is currently taking.

This articles will focus on the most common OTC drug-drug interactions with ARTs and provide recommendations on medication administration and counseling patients.

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

Tenofovir disoproxil fumarate (TDF) has the potential to cause renal impairment since it is eliminated primarily by the kidney. For this reason, TDF use with concurrent or recent use of high-dose or multiple nonsteroidal anti-inflammatory drugs (NSAIDs) should be avoided. For patients receiving NSAID agents, low doses should be recommended and kidney function should be assessed routinely.²

Although the risk for renal impairment appears to be less with tenofovir alafenamide (TAF), there is still a risk. Low-dose NSAIDs should still be recommended since those with impaired renal function who take nephrotoxic agents, such as NSAIDs, are at an increased risk of developing renal-related adverse reactions.³

Agents that contain TDF: Atripla, Complera, Stribild, Truvada, and Viread.

Currently available agents that contain TAF: Genvoya, Odefsey.

Non-NRTIs (NNRTIs)

The major interaction of concern with the NNRTI rilpivirine is acid suppressants since an acidic environment is required for maximal absorption and activity of rilpivirine. Antacids and H2-receptor antagonists should be used with caution as co-administration may cause significant decreases in rilpivirine plasma concentrations due to an increase in gastric pH.

The use of proton pump inhibitors (PPIs) are contraindicated with rilpivirine because significant decreases in rilpivirine plasma concentrations may occur due to gastric pH increase. This may result in loss of virologic response and possible resistance to rilpivirine or to the class of NNRTIs.⁴

Agents that contain rilpivirine: Complera, Edurant, and Odefsey

Acid suppressants

Dosing recommendation with rilpivirine

Antacids (containing aluminum, magnesium hydroxide, or calcium carbonate)

Take antacids at least 2 hours before or 4 hours after rilpivirine.

H2-receptor antagonists (cimetidine, famotidine, nizatidine, ranitidine)

Take H2-receptor antagonists at least 12 hours before or 4 hours after rilpivirine.

PPIs (esomeprazole, lansoprazole, omeprazole, pantoprazole sodium*, rabeprazole*)

Contraindicated. Do not co-administer.

*Not available OTC

Protease Inhibitors (PIs)

Although PIs are known to interact with many drugs due to CYP3A interactions, the most notable interaction with OTC medications occurs between atazanavir and acid suppressants. The solubility of atazanavir decreases when gastric pH increases.

Therefore, reduced plasma concentrations are expected when antacids, H2-receptor antagonists, and PPIs are administered with atazanavir.⁵ The use of PPIs is not recommended in treatment-experienced patients.

Agents that contain atazanavir: Evotaz, Reyataz

Acid suppressant

Treatment-naïve dosing recommendation with atazanavir

Treatment-experienced recommendation with atazanavir

Antacids

Administer atazanavir-containing products at least 2 hours apart.

H2-receptor antagonists (H2RA)

Boosted atazanavir with food should be administered simultaneously with, and/or at least 10 hours after H2RA (comparable with famotidine 20 mg once daily up to a dose comparable with famotidine 40 mg twice daily).

Unboosted atazanavir 400 mg once daily with food should be administered at least 2 hours before and at least 10 hours after H2RA. (No single dose of the H2RA should exceed a dose comparable with famotidine 20 mg. The total daily dose should not exceed a dose comparable with famotidine 40 mg.)

H2RA dose should not exceed a dose comparable with famotidine 20 mg twice daily, and atazanavir doses should be administered simultaneously with, and/or at least 10 hours after the dose of the H2RA.

Proton pump inhibitors (PPIs)

Administer atazanavir at least 12 hours after PPI. (Dose of PPI should not exceed a dose comparable with omeprazole 20 mg daily.)

Use is not recommended.

Integrase Strand Transfer Inhibitors (INSTIs)

The use of integrase inhibitors has risen consistently since being recommended as first-line antiretroviral therapy for HIV. Available integrase inhibitors include once-daily dolutegravir and elvitegravir, as well as twice-daily raltegravir. Polyvalent cations, such as aluminum, calcium, iron, magnesium, and zinc, may chelate with integrase inhibitors and reduce their efficacy as an ART. For aluminum, magnesium, and calcium-containing antacids, as well as other polyvalent cation supplements, including multivitamins with minerals, administration should be separated from integrase inhibitors. The use of aluminum-magnesium hydroxide antacids should not be co-administered with raltegravir.⁶

Dolutegravir

Elvitegravir

Raltegravir

Antacids (containing aluminum, calcium, or magnesium)

Give at least 2 hours before or at least 6 hours after antacid.

Separate elvitegravir and antacid administration by at least 2 hours.

Do not co-administer with aluminum- magnesium hydroxide antacids.

No dosing separation is needed with the use of calcium carbonate antacids.

Polyvalent cations supplements (aluminum, calcium, iron, magnesium, zinc, and multivitamins with minerals)

Take integrase strand transfer inhibitors at least 2 hours before or at least 6 hours after supplements containing polyvalent cations.

May take dolutegravir and supplements containing calcium or iron simultaneously with food.

Many oral multivitamins contain varying amounts of polyvalent cations; the extent and significance of chelation is unknown.

Agents that contain dolutegravir: Tivicay, Triumeq

Agents that contain elvitegravir: Genvoya, Stribild, Viteka

Agents that contain raltegravir: Isentress

References:

1. Zhou S, Martin K, Corbett A, et al. Total Daily Pill Burden in HIV-Infected Patients in the Southern United States. AIDS Patient Care STDS. 2014; 28(6): 311—7.

2. Viread [package insert]. Foster City, CA: Gilead Sciences Inc; 2016.

3. Genvoya [package insert]. Foster City, CA: Gilead Sciences Inc; 2016.

4. Edurant [package insert]. Titusville, NJ: Janssen Therapeutics, Division of Janssen Products; 2015.

5. Reyataz [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2015.

6. Panel on antiretroviral guidelines for adults and adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/AdultandAdolescentGL.pdf. Accessed March 31, 2016.