Apalutamide with Tacrolimus Interaction Details

Brand Names Associated with Apalutamide

Brand Names Associated with Tacrolimus

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 04, 2024

Interaction Effect

Reduced tacrolimus exposure and an increased risk of organ rejection

Interaction Summary

Concomitant use of tacrolimus with a strong CYP3A inducer may increase the metabolism of tacrolimus, leading to decreased tacrolimus whole blood trough concentrations and a greater risk of rejection. If coadministration is necessary, increase the tacrolimus dose and monitor tacrolimus whole blood trough concentrations[1][2].

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Concomitant use of tacrolimus with a strong CYP3A inducer may increase the metabolism of tacrolimus, leading to decreased tacrolimus whole blood trough concentrations and a greater risk of rejection. If coadministration is necessary, increase the tacrolimus dose and monitor tacrolimus whole blood trough concentrations[1][2].

Mechanism Of Interaction

Induction of CYP3A-mediated tacrolimus metabolism

Literature Reports

A) In a study of 6 normal volunteers, a significant decrease in tacrolimus oral bioavailability (14+/-6% vs. 7+/-3%) was observed with concomitant rifAMPin administration (600 mg). In addition, there was a significant increase in tacrolimus clearance (0.036+/-0.008 L/hr/kg vs. 0.053+/-0.010 L/hr/kg) with concomitant rifAMPin administration [1].

B) In a systematic review of studies of pharmacokinetic interactions involving St. John's Wort, concomitant use with tacrolimus in 1 study (N=10) resulted in a decrease in tacrolimus AUC of 58% with a St. John's Wort dosage of 300 mg 2 times daily (containing hyperforin dosage of 5 mg/day) [3].

C) Six healthy male volunteers participated in a study to quantify the effects of rifAMPin on the pharmacokinetic parameters of tacrolimus. Subjects were randomized in the first phase to receive either tacrolimus 0.1 mg/kg orally as a single dose or tacrolimus 0.25 mg/kg IV over 4 hours. RifAMPin 600 mg orally once daily for 18 days was started on day 15 of the study, and on day 22 subjects received either oral or IV tacrolimus, with the alternate route on study day 29. RifAMPin significantly increased the clearance of tacrolimus (36 mL/hr/kg vs. 52.8 mL/hr/kg), decreased oral bioavailability (14.4% vs. 7%), and decreased intestinal bioavailability (14.8% vs. 7.3%). Despite the large change in tacrolimus clearance, hepatic bioavailability was unchanged. This effect was expected since the clearance of tacrolimus is less than hepatic blood flow. The findings were consistent with rifAMPin inducing both intestinal and hepatic metabolism of tacrolimus, most likely through the induction of CYP3A and P-glycoprotein in the liver and small bowel [4].

D) Coadministration of St. John's Wort and tacrolimus significantly reduced the tacrolimus AUC. In a crossover study, healthy adults (N=10) received a single, oral dose of tacrolimus (approximately 0.1 mg/kg) on study day 1. Serial blood samples were obtained and analyzed over the next 96 hours following tacrolimus dosing. Subjects then received an 18-day oral regimen of St. John's Wort 300 mg 3 times daily, beginning on study day 8. A second, single dose of tacrolimus 0.1 mg/kg was given on study day 22, after which the pharmacokinetic analysis was repeated. St. John's Wort significantly increased the rate of apparent oral clearance for tacrolimus by approximately 40%, significantly reduced the maximum serum concentration by approximately 23%, and reduced the AUC by approximately 35% [5].

References

1 ) Product Information: PROGRAF(R) oral capsules, oral granules for suspension, intravenous injection, tacrolimus oral capsules, oral granules for suspension, intravenous injection. Astellas Pharma US Inc (per FDA), Northbrook, IL, 2023.

2 ) Product Information: ENVARSUS XR(R) oral extended-release tablets, tacrolimus oral extended-release tablets. Veloxis Pharmaceuticals Inc (per FDA), Cary, NC, 2023.

3 ) Chrubasik-Hausmann S, Vlachojannis J, & McLachlan AJ: Understanding drug interactions with St John's wort (Hypericum perforatum L.): impact of hyperforin content. J Pharm Pharmacol 2019; 71(1):129-138.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

4 ) Hebert MF, Fisher RM, Marsh CL, et al: Effects of rifampin on tacrolimus pharmacokinetics in healthy volunteers. J Clin Pharmacol 1999; 39:91-96.

5 ) Hebert MF, Park JM, Chen Y-L, et al: Effects of St. John's Wort (Hypericum perforatum) on tacrolimus pharmacokinetics in healthy volunteers. J Clin Pharmacol 2004; 44:89-94.

Apalutamide Overview

• Apalutamide is used to treat certain types of prostate cancer (cancer in men that begins in the prostate [a male reproductive gland]) and has spread to other parts of the body or that has not spread to other parts of the body but has not been helped by other medical treatments. Apalutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of cancer cells.

Tacrolimus Overview

• Tacrolimus (Astagraf XL, Envarsus XR, Prograf) is used along with other medications to prevent rejection (attack of a transplanted organ by the immune system of a person receiving the organ) in people who have received a kidney transplant. Tacrolimus (Prograf) is also used along with other medications to prevent rejection in people who have received a liver, lung, or heart transplant. Tacrolimus is in a class of medications called immunosupressants. It works by decreasing the activity of the immune system to prevent it from attacking the transplanted organ.

Return To Our Drug Interaction Homepage

Feedback, Question Or Comment About This Information?

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.