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Drug Interactions between Jynarque and mavorixafor

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

tolvaptan mavorixafor

Applies to: Jynarque (tolvaptan) and mavorixafor

MONITOR CLOSELY: Coadministration with P-glycoprotein (P-gp) and/or moderate CYP450 3A4 inhibitors may increase the plasma concentrations and effects of mavorixafor, which is both a substrate of the P-gp efflux transporter and primarily metabolized by CYP450 3A4. When a single dose of mavorixafor (200 mg) was coadministered with the strong CYP450 3A4 and P-gp inhibitor itraconazole (200 mg at steady state), mavorixafor's systemic exposure (AUC) increased approximately 2-fold. The resulting AUC was similar to that expected from a single dose of 400 mg given alone to healthy subjects. Clinical data with drugs that are less potent inhibitors or only inhibit CYP450 3A4 or P-gp are not available. As mavorixafor causes concentration-dependent QT interval prolongation, an increase in its AUC could increase the possibility of experiencing this adverse effect. Likewise, this risk may be further increased if the P-gp and/or CYP450 3A4 inhibitor being used also carries a risk of QT prolongation (e.g., amiodarone, azithromycin, bepridil, ciprofloxacin, clofazimine, crizotinib, dronedarone, erythromycin, fluconazole, lapatinib, oral lefamulin, nilotinib, osimertinib, pacritinib, quinidine, quinine, ranolazine, ribociclib).

MANAGEMENT: Caution and close clinical monitoring for adverse effects associated with mavorixafor, such as QT prolongation, are advised if concurrent use with a P-gp and/or moderate CYP450 3A4 inhibitor is required. Any modifiable risk factors for QT prolongation, such as electrolyte abnormalities, should be corrected. The QTc (QT interval corrected for heart rate) should be assessed at baseline and as clinically indicated during concomitant therapy. If adverse reactions associated with mavorixafor develop, its daily dose should be reduced by steps of 100 mg, as described in the labeling, but not to a dose less than 200 mg. If the P-gp and/or CYP450 3A4 inhibitor also carries a risk of QTc prolongation, its labeling should be consulted as well for more specific guidance on monitoring and potential adjustments to treatment should this adverse effect occur.

References (1)
  1. (2024) "Product Information. Xolremdi (mavorixafor)." X4 Pharmaceuticals, Inc.

Drug and food interactions

Major

mavorixafor food

Applies to: mavorixafor

GENERALLY AVOID: Grapefruit products may significantly increase the plasma concentrations and effects of mavorixafor, which is primarily metabolized by the isoenzyme CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. A study examining mavorixafor in combination with the strong CYP450 3A4 and P-glycoprotein inhibitor, itraconazole, suggests an increase in mavorixafor's systemic exposure (AUC) of approximately 2-fold. Clinical data with grapefruit products are not available. Pharmacokinetic interactions involving grapefruit are subject to a high degree of interpatient variability and can also be affected by the product and amount consumed; therefore, the extent to which a given patient may be affected is difficult to predict. Additionally, since mavorixafor is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

ADJUST DOSING INTERVAL: Food may significantly reduce the peak plasma concentration (Cmax) and systemic exposure (AUC) of mavorixafor. When a single-dose of mavorixafor (400 mg) was administered with a high-fat meal (1000 calories, 50% fat) to healthy subjects, the Cmax and AUC decreased by 66% and 55%, respectively. Similarly, when the same dose was given with a low-fat meal (500 calories, 25% fat) to healthy subjects, mavorixafor's Cmax and AUC decreased by 55% and 51%, respectively. Additionally, a single dose of mavorixafor (400 mg) administered with a low-fat meal to healthy subjects following an overnight fast resulted in a 14% higher Cmax and an 18% lower AUC than those obtained from subjects who fasted for an additional 4 hours after the dose.

MANAGEMENT: Mavorixafor should be taken on an empty stomach after an overnight fast, 30 minutes before food. Patients should be advised to avoid eating or drinking products containing grapefruit, as this could increase the risk of experiencing adverse effects from mavorixafor such as QT prolongation.

References (1)
  1. (2024) "Product Information. Xolremdi (mavorixafor)." X4 Pharmaceuticals, Inc.
Moderate

tolvaptan food

Applies to: Jynarque (tolvaptan)

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of tolvaptan. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the product labeling, administration of tolvaptan with grapefruit juice resulted in a 1.8-fold increase in tolvaptan systemic exposure. The clinical significance is unknown, although increased pharmacologic effects may be expected. Too rapid correction of hyponatremia increases the risk of osmotic demyelination syndrome, which is associated with dysarthria, mutism, dysphagia, lethargy, affective changes, spastic quadriparesis, seizures, coma, and death.

MANAGEMENT: Patients treated with tolvaptan should avoid consumption of grapefruits and grapefruit juice.

References (1)
  1. (2009) "Product Information. Samsca (tolvaptan)." Otsuka American Pharmaceuticals Inc

Therapeutic duplication warnings

No 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.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor 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.
Unknown No interaction information available.

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