Atazanavir with Garlic Interaction Details

Brand Names Associated with Atazanavir

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Feb 29, 2024

Interaction Effect

Decreased protease inhibitor concentrations and an increased risk of antiretroviral resistance and treatment failure

Interaction Summary

Since all protease inhibitors are metabolized primarily by cytochrome P450 3A4, patients taking any protease inhibitor should be instructed not to start or stop taking garlic supplements without their physician's advice. Garlic significantly decreased mean saquinavir levels in healthy subjects by approximately 50% after 19 days, with the effect lasting at least 10 days after garlic discontinuation[1]. Short-term administration (4 days) of garlic did not significantly alter single-dose ritonavir pharmacokinetics in 10 healthy subjects [2]. A low dose of garlic was used in this study (equivalent to 1 gram fresh garlic daily) compared with [1] in which a dose of garlic equivalent to 8 grams fresh garlic daily was used. An in vitro study demonstrated that garlic extracts inhibited cytochrome P450 enzymes and p-glycoprotein [3], which is contrary to the findings of decreased saquinavir levels in humans.

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Avoid concomitant use of garlic and protease inhibitors. If a patient is found to be taking garlic supplements while taking a protease inhibitor, discontinue garlic and monitor blood levels and symptoms of toxicity of the protease inhibitor and adjust the dose of the protease inhibitor as necessary.

Mechanism Of Interaction

Induction of CYP450 and P-glycoprotein by garlic

Literature Reports

A) Short-term garlic administration did not significantly alter ritonavir pharmacokinetics in an open-label, randomized, crossover study of 10 healthy subjects. Subjects received garlic extract 10 milligrams (mg) (Natural Source Odourless Garlic Life Brand) (equivalent to 1 gram of fresh garlic) daily for 4 days. Ritonavir 400 mg was administered on day 4. The dose and duration of garlic used in this study were much lower than that used by [1] in which garlic reduced saquinavir levels. The authors stated that their results should not be extrapolated to steady-state conditions [2].

B) Garlic significantly decreased the mean area under the curve (AUC), trough levels, and peak levels of saquinavir in 9 healthy volunteers, with variability in individual response. Saquinavir (Fortovase(R)) 1200 milligrams (mg) was administered orally three times daily with meals for 4 days. On study days 5 though 24, garlic (GarliPure(R), Maximum Allicin Formula; Natrol) from a single lot was administered orally twice daily with meals. The garlic caplets contained 4.64 milligrams allicin and 11.2 milligrams alliin per caplet determined by an independent lab, the daily dose was roughly equivalent to two 4 gram garlic cloves. Saquinavir was administered on days 22 through 24, and blood samples were drawn on day 25. Mean area under the curve (AUC) decreased by 51% (p = 0.007), with a range of -84% to +12%. Mean trough levels decreased by 49% (p = 0.002), with a range of -82% to +33%. Mean peak levels decreased by 54% (p = 0.006), with a range of -88% to +30%. Following a 10-day washout period, saquinavir was administered again for 3 days, and levels were measured on day 4. Saquinavir AUC, trough, and peak levels returned to 65%, 70%, and 61% of baseline levels, respectively. In 3 of the 9 volunteers, no difference in saquinavir pharmacokinetics were observed until after the 10-day washout period [1].

C) Hypotheses for the mechanism of the interaction included: (1) garlic may induce cytochrome P450 enzymes in the gut mucosa which metabolize saquinavir, (2) garlic may induce P-glycoprotein which also metabolizes saquinavir, (3) formation of a garlic metabolite with a long half-life which induces enzymes, (4) accumulation of a saquinavir metabolite with induces saquinavir metabolism (which may explain the delay in the reduction of saquinavir levels in some subjects) [1].

D) Various forms of fresh garlic and garlic extracts inhibited cytochrome P450 isoenzymes and P-glycoprotein in vitro. Cytochrome P450 2C9(1), 2C19, 3A4, 3A5, and 3A7 were all inhibited by various forms of garlic. CYP2D6 was unaffected. Garlic had a low to moderate effect on P-glycoprotein as compared with verapamil. Three varieties of fresh garlic (common, Chinese, and elephant) and 10 commercial garlic products (including aged garlic, odorless garlic, garlic oil, and freeze-dried garlic) were tested. All types of garlic inhibited CYP3A4. Freeze-dried garlic only inhibited CYP3A4 (by 95%). Aged garlic inhibited CYP3A4 by 44% and 2C9 by 31%. Odorless garlic products inhibited CYP3A4 by 31% to 56%, 2C9 by 21% to 33%, and 2C19 by 21% to 37%. Garlic oil inhibited CYP3A4 by 31% and 2C9 by 22%. Fresh garlic inhibited CYP3A4 by 44% to 59% depending on the variety tested, with common garlic the most inhibitory. Fresh garlic had little effect on 2C19 and 2D6, and strongly stimulated 2C9(2) [3].

References

1 ) Piscitelli SC, Burstein AH, Welden N, et al: The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis 2002; 34(2):234-238.

2 ) Gallicano K, Foster B, & Choudhri S: Effect of short-term administration of garlic supplements on single-dose ritonavir pharmacokinetics in healthy volunteers. Br J Clin Pharmacol 2003; 55(2):199-202.

3 ) Foster BC, Foster MS, Vandenhoek S, et al: An in vitro evaluation of human cytochrome P450 3A4 and P-glycoprotein inhibition by garlic. J Pharm Pharmaceut Sci 2001; 4(2):176-184.

Atazanavir Overview

• Atazanavir is used along with other medications to treat human immunodeficiency virus (HIV) infection in adults and children who are at least 3 months of age and weigh at least 22 lb (10 kg). Atazanavir is in a class of medications called protease inhibitors. It works by decreasing the amount of HIV in the blood. Although atazanavir does not cure HIV, it may decrease your chance of developing acquired immunodeficiency syndrome (AIDS) and HIV-related illnesses such as serious infections or cancer. Atazanavir must be given with other medications that treat HIV infection to completely treat the infection. Taking these medications along with practicing safer sex and making other lifestyle changes may decrease the risk of transmitting the HIV virus to other people.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.