Interaction between Erythromycin and Relugolix
Major
Synergy
Absorption
| ID | DDInter670 and DDInter1577 |
| Interaction | Coadministration with inhibitors of the P-glycoprotein (P-gp) efflux transporter may increase the plasma concentrations of relugolix, particularly when the inhibitors are given orally. Relugolix is a substrate for intestinal P-gp. In vitro, it is metabolized primarily by CYP450 3A and, to a lesser extent, by CYP450 2C8. When relugolix was coadministered with erythromycin, a combined P-gp and moderate CYP450 3A inhibitor, relugolix peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 6.2-fold. Increased exposure to relugolix may increase the risk and/or severity of adverse effects such as hot flushes; weight gain; decreased sex drive; erectile function difficulties; QT interval prolongation; musculoskeletal pain; constipation; diarrhea; increases in glucose, triglyceride, and liver transaminase levels; and decreased hemoglobin. Long-term androgen deprivation therapy, including relugolix, can prolong the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. |
| Management | Concomitant use of relugolix with orally administered P-gp inhibitors should be avoided when possible. In addition, the benefits of androgen deprivation therapy such as relugolix should be carefully assessed against the potential risk in patients receiving other drugs known to prolong the QT interval, many of which are also P-gp inhibitors (e.g., amiodarone, azithromycin, bepridil, cabozantinib, clarithromycin, crizotinib, dronedarone, elagolix, erythromycin, ketoconazole, lapatinib, mifepristone, nilotinib, osimertinib, propafenone, quinidine, quinine, ranolazine, tacrolimus, telithromycin, valbenazine, vemurafenib). If coadministration is required, the manufacturer recommends taking relugolix first and separating the dosing by at least 6 hours. Electrolyte abnormalities should be corrected prior to initiating therapy, and periodic monitoring of electrocardiograms and electrolytes should be considered. Alternatively, treatment with relugolix may be interrupted for up to two weeks if a short course of treatment with a P-gp inhibitor is necessary. |
| References | |
| Alternative for Erythromycin |
J01F
D10A Dexamethasone (ophthalmic)
Clindamycin (topical)
Fluorometholone
Resorcinol (topical)
Tretinoin
Clindamycin
More
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| Alternative for Relugolix | - |
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.