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Acunivive 90 Injection System and Clofarabine

Determining the interaction of Acunivive 90 Injection System and Clofarabine and the possibility of their joint administration.

Check result:
Acunivive 90 Injection System <> Clofarabine
Relevance: 11.12.2022 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Clofarabine may cause kidney and liver problems, and combining it with other medications that can also affect the kidney and liver such as ketorolac may increase that risk. In addition, ketorolac may interfere with the elimination of clofarabine from the body via the urine. This may lead to elevated blood levels of clofarabine and potentially increased risk of other side effects such as nausea, vomiting, blood pressure changes, anemia, bleeding problems, and infections. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. Contact your doctor if you experience signs and symptoms that may suggest kidney damage such as nausea, vomiting, loss of appetite, increased or decreased urination, sudden weight gain or weight loss, fluid retention, swelling, shortness of breath, bone pain, muscle cramps, tiredness, weakness, dizziness, confusion, and irregular heart rhythm. You should also seek immediate medical attention if you develop signs and symptoms of liver damage such as fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, dark colored urine, light colored stools, and yellowing of the skin or eyes. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Professional:

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
  • Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  • "Product Information. Clolar (clofarabine)." sanofi-aventis, Bridgewater, NJ.
Acunivive 90 Injection System

Generic Name: ketorolac

Brand name: Sprix, Toradol

Synonyms: Ketorolac (nasal), Ketorolac (Nasal)

Clofarabine

Generic Name: clofarabine

Brand name: Clolar

Synonyms: n.a.

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

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