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Drug Interactions between clofarabine and Nexcede

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

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Interactions between your drugs

Moderate

ketoprofen clofarabine

Applies to: Nexcede (ketoprofen) and clofarabine

GENERALLY AVOID: Coadministration of clofarabine with other potentially nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of renal impairment due to additive effects on the kidney. Moreover, renal impairment secondary to the use of these agents may reduce the clearance of clofarabine, which is primarily eliminated by renal excretion. This may increase the risk of other adverse effects such as nausea, vomiting, stomatitis, hypertension, hypotension, myelosuppression, hemorrhage, and hepatotoxicity. In clinical trials for clofarabine, grade 3 or 4 elevations in creatinine occurred in 8% of patients, and acute renal failure was reported in 3% at grade 3 and 2% at grade 4. Hematuria was observed in 13% of patients overall. NSAIDs can also adversely affect the kidney, particularly when given at high dosages or for prolonged periods. Elevations in serum creatinine and BUN, tubular necrosis, glomerulitis, renal papillary necrosis, acute interstitial nephritis, nephrotic syndrome, and renal failure have been reported during chronic use. In patients with prerenal conditions whose renal perfusion may be dependent on the function of prostaglandins, NSAIDs may precipitate overt renal decompensation via dose-related inhibition of prostaglandin synthesis. Patients at greatest risk include patients with impaired renal function, heart failure, liver dysfunction, or substantial sodium and/or volume depletion (e.g., due to diuretics).

GENERALLY AVOID: The liver is a known target organ for clofarabine toxicity, and concomitant use of other potentially hepatotoxic agents such as NSAIDs may increase the risk of liver injury. Severe and fatal hepatotoxicity has occurred with the use of clofarabine alone. In clinical studies, grade 3 to 4 liver enzyme elevations were frequently observed in pediatric patients during treatment, with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevations reported in 36% and 44% of patients, respectively. Liver enzyme elevations typically occurred within 10 days of clofarabine administration and returned to grade 2 or lower within 15 days. Grade 3 or 4 bilirubin elevations occurred in 13% of patients, with 2 cases reported as grade 4 hyperbilirubinemia (2%), one of which resulted in treatment discontinuation and the other in multi-organ failure and death. Eight patients (7%) had grade 3 or 4 elevations in serum bilirubin at the last time point measured, all of whom died due to sepsis and/or multi-organ failure. NSAIDs can also adversely affect the liver. Borderline elevations of serum transaminases, LDH, and alkaline phosphatase have been reported in up to 15% of patients treated with NSAIDs. These abnormalities may progress, remain unchanged, or regress with continuing therapy. Notable liver enzyme elevations exceeding 3 times the upper limit of normal have occurred in approximately 1% of patients in clinical trials. In addition, rare cases of severe hepatotoxicity including liver necrosis, hepatic failure, jaundice, and fatal fulminant hepatitis have been reported. Some NSAIDs such as bromfenac, nimesulide, and lumiracoxib have been withdrawn from most markets, or have never been marketed, due to severe hepatotoxicity.

MANAGEMENT: If possible, drugs that are potentially nephrotoxic including NSAIDs should be avoided during the 5 days of clofarabine administration. Because NSAIDs can also be hepatotoxic, it may be appropriate to avoid them altogether in some patients during clofarabine therapy. If an NSAID is required, ibuprofen appears to have the highest liver safety profile among NSAIDs, while diclofenac and sulindac have been linked to a higher frequency of liver damage. Patients treated with clofarabine should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Renal and hepatic function should be monitored prior to and daily during clofarabine therapy, and administration discontinued immediately if substantial increases (e.g., grade 3 or higher) in creatinine, liver enzymes, or bilirubin are noted. Clofarabine therapy may be reinstated when the patient is stable and organ function has returned to baseline, generally with a 25% dose reduction.

References

  1. (2005) "Product Information. Clolar (clofarabine)." sanofi-aventis
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."

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Drug and food interactions

Moderate

ketoprofen food

Applies to: Nexcede (ketoprofen)

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

References

  1. (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn

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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.


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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.