Drug Interaction Report
3 potential interactions and/or warnings found for the following 2 drugs:
- emtricitabine / rilpivirine / tenofovir alafenamide
- Lupron Depot (leuprolide)
Interactions between your drugs
leuprolide rilpivirine
Applies to: Lupron Depot (leuprolide), emtricitabine / rilpivirine / tenofovir alafenamide
GENERALLY AVOID: Long-term androgen deprivation therapy (ADT) can prolong the QT interval. Coadministration of ADT with other agents that may prolong the QT interval could also result in additive effects and an increased risk of ventricular arrhythmias including torsade de pointes and sudden death. The risk may be increased in patients with certain underlying risk factors like congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). Studies in young men have shown that endogenous serum testosterone levels are inversely associated with QTc (QT interval corrected for heart rate) duration. Clinical trials in men with low serum testosterone levels have reported testosterone administration being associated with a shortening of QTc. Likewise, studies using ADT have shown that it may prolong the QT interval; however, this effect may vary by drug, dose, or even each drug class that can be used to reduce testosterone levels. A clinical study comparing abarelix to a luteinizing hormone-releasing hormone agonist plus nonsteroidal antiandrogen therapy found that both therapies prolonged the mean Fridericia-corrected QT interval (QTcF) by more than 10 msec from baseline. Approximately 20% of patients in both groups had either changes from baseline QTc of >30 msec or end-of-treatment QTc values >450 msec. Similarly, a study comparing degarelix to leuprolide found that approximately 20% of patients on each drug had QT/QTc intervals >450 msec after 1 year of treatment. From baseline to end of study, the median change in QTcF was 12.3 msec for degarelix and 16.7 msec for leuprolide. Some drugs used to lower testosterone levels may also have other side effects that can predispose a patient to QT prolongation and torsade de pointes. For example, inhibitors of 17 alpha-hydroxylase/C17,20-lyase (CYP17) like abiraterone may cause hypokalemia as a result of increased mineralocorticoid levels. Clinical data on ADT prolonging the QT interval in women and children are lacking.
MANAGEMENT: The benefits of androgen deprivation therapy (ADT) should be carefully assessed against the potential risk in patients receiving other drugs known to prolong the QT interval. Electrolyte abnormalities should be corrected prior to initiating therapy, and monitoring of electrocardiograms and electrolytes may be advisable. The manufacturer's labeling as well as current clinical guidelines should be consulted for monitoring recommendations.
References
- (2002) "Product Information. Lupron (leuprolide)." TAP Pharmaceuticals Inc
- (2001) "Product Information. Zoladex (goserelin)." Astra-Zeneca Pharmaceuticals
- (2001) "Product Information. Trelstar (triptorelin)." Pharmacia and Upjohn
- (2002) "Product Information. Eligard (leuprolide)." Sanofi Winthrop Pharmaceuticals
- (2003) "Product Information. Plenaxis (abarelix)." Praecis Pharmaceuticals Inc
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2010) "Product Information. Vantas (histrelin)." Endo Pharmaceuticals (formally Indevus Pharmaceuticals Inc)
- (2013) "Product Information. Firmagon (degarelix)." Ferring Pharmaceuticals Inc
- Krishna KB, Fuqua JS, rogol ad, et al. (2019) "Use of gonadotropin-releasing hormone analogs in children: update by an international consortium." Horm Res Paediatr, 91, p. 357-72
- Lazzerini PE, Bertolozzi I, Acampa M, et al. (2023) Androgen deprivation therapy for prostatic cancer in patients with torsades de pointes. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239032/
- Gagliano-Juca T, Travison TG, kantoff pw, et al. (2018) "Androgen deprivation therapy is associated with prolongation of QTc interval in men with prostate cancer." J Endocr Soc, 2, p. 485-96
- Gheorghe GS, Hodorogea AS, Ciobanu A, Nanea IT, Gheorghe ACD (2021) "Androgen deprivation therapy, hypogonadism and cardiovascular toxicity in men with advanced prostate cancer." Curr Oncol, 28, p. 3331-46
- (2023) "Product Information. Firmagon (degarelix)." Ferring Pharmaceuticals Pty Ltd
- (2020) "Product Information. Firmagon (degarelix)." Ferring Pharmaceuticals Inc
Drug and food interactions
rilpivirine food
Applies to: emtricitabine / rilpivirine / tenofovir alafenamide
GENERALLY AVOID: Coadministration with grapefruit or grapefruit juice may increase the plasma concentrations of rilpivirine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. In 15 study subjects given rilpivirine (150 mg once daily) with the potent CYP450 3A4 inhibitor ketoconazole (400 mg once daily), mean rilpivirine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) were increased by 30%, 49% and 76%, respectively. In 16 study subjects given a single 500 mg dose of a less potent CYP450 3A4 inhibitor chlorzoxazone two hours after rilpivirine (150 mg once daily), mean rilpivirine Cmax, AUC, and Cmin were increased by 17%, 25%, and 18%, respectively. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.
ADJUST DOSING INTERVAL: The administration of rilpivirine in a fasting state may decrease its oral absorption. Under fasted conditions, the systemic exposure to rilpivirine was 40% lower compared to normal or high-fat caloric meals (533 to 928 Kcal). The systemic exposure was 50% lower when rilpivirine was taken with a protein-rich nutritional beverage.
MANAGEMENT: Coadministration of grapefruit or grapefruit juice with rilpivirine should preferably be avoided. For optimal absorption, it is recommended to take rilpivirine on a regular schedule with a meal.
References
- (2011) "Product Information. Edurant (rilpivirine)." Tibotec Pharmaceuticals
- Cerner Multum, Inc. (2015) "Canadian Product Information."
tenofovir food
Applies to: emtricitabine / rilpivirine / tenofovir alafenamide
Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.
References
- (2001) "Product Information. Viread (tenofovir)." Gilead Sciences
Therapeutic duplication warnings
No duplication warnings were found for your selected drugs.
Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
No interaction information available. |
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