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Drug Interactions between azelastine ophthalmic and mavorixafor

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

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Interactions between your drugs

Moderate

azelastine ophthalmic mavorixafor

Applies to: azelastine ophthalmic and mavorixafor

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with mavorixafor may increase the plasma concentrations of drugs that are substrates of the isoenzyme CYP450 2D6, isoenzyme CYP450 3A4, and/or the efflux transporter P-glycoprotein (P-gp). It is important to determine if the isoenzyme in question is responsible for drug clearance or drug activation as these situations may result in either a potential increase in adverse effects or reduction in efficacy, respectively. When mavorixafor (400 mg) was used concurrently with the sensitive CYP450 2D6 substrate dextromethorphan in healthy subjects, dextromethorphan's peak plasma concentration (Cmax) and systemic exposure (AUC) increased by an average of 6- and 9-fold, respectively. On the other hand, when mavorixafor (400 mg) was used concurrently with the sensitive CYP450 3A4 substrate midazolam in healthy subjects, the Cmax and AUC increased by only 1.1- and 1.7-fold, respectively. Likewise, when a single dose of a transporter cocktail containing P-gp substrate digoxin (0.25 mg) was administered to healthy subjects on mavorixafor (400 mg/day at steady state), digoxin's Cmax and AUC increased by 1.5- and 1.6-fold, respectively. Data for less sensitive substrates or drugs metabolized and/or transported by multiple routes are unavailable.

MANAGEMENT: Caution is advised if mavorixafor is used concurrently with medications that are substrates of the P-gp efflux transporter and/or undergo metabolism via CYP450 2D6 and/or 3A4. This may be particularly important in cases where minimal concentration changes may result in serious adverse reactions from the substrate(s) in question. Dose adjustments and/or increased monitoring may be required. For example, digoxin's serum concentrations should be measured before initiating concomitant use with mavorixafor and as clinically indicated during coadministration. The labeling for the substrate(s) in question should be consulted for more specific recommendations.

Drug and food interactions

Major

mavorixafor food

Applies to: mavorixafor

Consumer information for this interaction is not currently available.

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.

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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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