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Drug Interactions between avacopan and cladribine

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

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Interactions between your drugs

Major

cladribine avacopan

Applies to: cladribine and avacopan

GENERALLY AVOID: The use of cladribine with other immunosuppressive or myelosuppressive agents may increase the risk of infections. Cladribine alone may cause severe and prolonged myelosuppression, lymphopenia, and opportunistic infections. The risk may theoretically increase when coadministered with other immunosuppressive therapy. Agents that may be significantly myelo- or immunosuppressive include antineoplastic agents, radiation, zidovudine, linezolid, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents (greater than 10 mg/day to 1 mg/kg/day, whichever is less, of prednisone or equivalent for more than 2 weeks), and long-term topical or inhaled corticosteroids.

MANAGEMENT: Concomitant use of oral cladribine with immunosuppressive or myelosuppressive agents should be avoided if possible. Acute short-term therapy with corticosteroids can be administered. Caution is advised if IV cladribine must be used in patients who have recently received or are receiving treatment with other immunosuppressive or myelosuppressive drugs, and vice versa. Close clinical and laboratory monitoring for the development of severe hematologic adverse effects is recommended both during and after discontinuation of therapy. In patients who have previously been treated with immunomodulatory or immunosuppressive drugs, consider potential additive effect, mode of action, and duration of effect of the other drugs prior to initiation of cladribine. Patients should be advised to contact their physician if they develop signs and symptoms of infection such as fever, chills, diarrhea, sore throat, muscle aches, shortness of breath, blood in phlegm, weight loss, red or inflamed skin, body sores, and pain or burning during urination.

References

  1. (2001) "Product Information. Leustatin (cladribine)." Ortho Biotech Inc
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."

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Drug and food interactions

Moderate

cladribine food

Applies to: cladribine

ADJUST DOSING INTERVAL: Oral cladribine may increase the bioavailability of other drugs, which may increase the risk or severity of adverse reactions. Cladribine tablets may contain hydroxypropyl betadex, which could form a complex with the active ingredients of other drugs, especially agents with low solubility. The clinical relevance of this interaction remains unknown.

MANAGEMENT: Administration of oral cladribine should be separated from any other oral drug by at least 3 hours.

References

  1. (2001) "Product Information. Leustatin (cladribine)." Ortho Biotech Inc
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Cerner Multum, Inc. "Australian Product Information."

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Moderate

avacopan food

Applies to: avacopan

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of avacopan. When a 30 mg capsule of avacopan was administered with a high-fat, high-calorie meal, avacopan peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 8% and 72%, respectively, while the time to reach peak concentration (Tmax) was delayed by approximately 4 hours (from 2.0 hours to 6.0 hours).

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of avacopan. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for itraconazole, a potent CYP450 3A4 inhibitor. When avacopan was administered with itraconazole (200 mg once daily for 4 days), avacopan peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.9-fold and 2.2-fold, respectively. 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. Increased exposure to avacopan may increase the risk and/or severity of serious adverse reactions such as hepatotoxicity and infections.

MANAGEMENT: To ensure maximal oral absorption, avacopan should be administered with food. Patients should preferably avoid or limit consumption of grapefruit, grapefruit juice, or any supplement containing grapefruit extract during avacopan therapy.

References

  1. (2021) "Product Information. Tavneos (avacopan)." ChemoCentryx, Inc.
  2. (2023) "Product Information. Tavneos (avacopan)." Vifor Fresenius Medical Care Renal Pharma UK Ltd

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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.

See also

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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

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