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Drug Interactions between Probenecid and Colchicine and radium 223 dichloride

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

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Interactions between your drugs

Major

colchicine radium Ra 223 dichloride

Applies to: Probenecid and Colchicine (colchicine / probenecid) and radium 223 dichloride

MONITOR CLOSELY: Coadministration of radium Ra 223 dichloride (Ra-223 dichloride) with other agents that can cause bone marrow suppression or myelosuppression may result in additive toxicity. Ra-223 dichloride alone is associated with thrombocytopenia, neutropenia, pancytopenia, and leukopenia; death from bone marrow failure has also been reported. In a randomized clinical trial in patients with metastatic castration-resistant prostrate cancer with bone metastases, 2% of the patients on Ra-223 dichloride experienced bone marrow failure or ongoing pancytopenia compared to no patients in the placebo group. Grade 3-4 adverse reactions of thrombocytopenia and neutropenia were more commonly reported in patients who had received prior docetaxel. However, data from clinical drug interaction studies are lacking.

MANAGEMENT: Caution and close monitoring for additive hematologic toxicity are recommended if concomitant use of Ra-223 dichloride with other agents that can cause bone marrow suppression or myelosuppression is required. The manufacturer advises that Ra-223 dichloride be discontinued in patients requiring administration of chemotherapy, other systemic radioisotopes, or hemibody external radiotherapy. If concomitant use is required, the manufacturer's product labeling should be consulted for specific hematologic monitoring and dose adjustment recommendations. Some authorities recommend not initiating subsequent systemic cancer treatment for at least 30 days after the last administration of Ra-223 dichloride. Patients should be advised to contact their physician if they develop signs or symptoms of myelosuppression or infection including but not limited to pallor, dizziness, fatigue, lethargy, fainting, easy bruising or bleeding, fever, chills, sore throat, body aches, and/or other influenza-like symptoms.

References

  1. (2019) "Product Information. Xofigo (radium Ra 223 dichloride)." Bayer Pharmaceutical Inc
  2. (2022) "Product Information. Xofigo (radium (Ra-223) dichloride)." Bayer Plc
  3. (2019) "Product Information. Xofigo (radium (223Ra) dichloride)." Bayer Australia Limited
  4. Bayer Inc. (2023) Product monograph xofigo radium Ra 223 dichloride solution for injection 1100 kBq/mL (29.7 microcurie/mL) radium-223 dichloride https://pdf.hres.ca/dpd_pm/00052465.PDF
View all 4 references

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Drug and food interactions

Major

colchicine food

Applies to: Probenecid and Colchicine (colchicine / probenecid)

GENERALLY AVOID: Coadministration with grapefruit juice may increase the serum concentrations of colchicine. Clinical toxicity including myopathy, neuropathy, multiorgan failure, and pancytopenia may occur. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism and P-glycoprotein efflux in the gut wall by certain compounds present in grapefruits. A published case report describes an eight-year-old patient with familial Mediterranean fever who developed acute clinical colchicine intoxication after ingesting approximately one liter of grapefruit juice per day for two months prior to hospital admission while being treated with colchicine 2 mg/day. Her condition progressed to circulatory shock and multiorgan failure, but she recovered with supportive therapy after 24 days in the hospital. In a study of 21 healthy volunteers, administration of 240 mL grapefruit juice twice a day for 4 days was found to have no significant effect on the pharmacokinetics of a single 0.6 mg dose of colchicine. However, significant interactions have been reported with other CYP450 3A4 inhibitors such as clarithromycin, diltiazem, erythromycin, ketoconazole, ritonavir, and verapamil.

MANAGEMENT: Patients treated with colchicine should be advised to avoid the consumption of grapefruit and grapefruit juice, and to contact their physician if they experience symptoms of colchicine toxicity such as abdominal pain, nausea, vomiting, diarrhea, fatigue, myalgia, asthenia, hyporeflexia, paresthesia, and numbness.

References

  1. Pettinger WA (1975) "Clonidine, a new antihypertensive drug." N Engl J Med, 293, p. 1179-80
  2. Caraco Y, Putterman C, Rahamimov R, Ben-Chetrit E (1992) "Acute colchicine intoxication: possible role of erythromycin administration." J Rheumatol, 19, p. 494-6
  3. Schiff D, Drislane FW (1992) "Rapid-onset colchicine myoneuropathy." Arthritis Rheum, 35, p. 1535-6
  4. Putterman C, Ben-Chetrit E, Caraco Y, Levy M (1991) "Colchicine intoxication: clinical pharmacology, risk factors, features, and management." Semin Arthritis Rheum, 21, p. 143-55
  5. Boomershine KH (2002) "Colchicine-induced rhabdomyolysis." Ann Pharmacother, 36, p. 824-6
  6. (2003) "Severe colchicine-macrolide interactions." Prescrire Int, 12, p. 18-9
  7. Tateishi T, Soucek P, Caraco Y, Guengerich FP, Wood AJ (1996) "Colchicine biotransformation by human liver microsomes. Identification of CYP3A4 as the major isoform responsible for colchicine demethylation." Biochem Pharmacol, 53, p. 111-6
  8. Dogukan A, Oymak FS, Taskapan H, Guven M, Tokgoz B, Utas C (2001) "Acute fatal colchicine intoxication in a patient on continuous ambulatory peritoneal dialysis (CAPD). Possible role of clarithromycin administration." Clin Nephrol, 55, p. 181-2
  9. Rollot F, Pajot O, Chauvelot-Moachon L, Nazal EM, Kelaidi C, Blanche P (2004) "Acute colchicine intoxication during clarithromycin administration." Ann Pharmacother, 38, p. 2074-7
  10. Wilbur K, Makowsky M (2004) "Colchicine myotoxicity: case reports and literature review." Pharmacotherapy, 24, p. 1784-92
  11. Hung IF, Wu AK, Cheng VC, et al. (2005) "Fatal interaction between clarithromycin and colchicine in patients with renal insufficiency: a retrospective study." Clin Infect Dis, 41, p. 291-300
  12. Cheng VC, Ho PL, Yuen KY (2005) "Two probable cases of serious drug interaction between clarithromycin and colchicine." South Med J, 98, p. 811-3
  13. Akdag I, Ersoy A, Kahvecioglu S, Gullulu M, Dilek K (2006) "Acute colchicine intoxication during clarithromycin administration in patients with chronic renal failure." J Nephrol, 19, p. 515-7
  14. van der Velden W, Huussen J, Ter Laak H, de Sevaux R (2008) "Colchicine-induced neuromyopathy in a patient with chronic renal failure: the role of clarithromycin." Neth J Med, 66, p. 204-6
  15. Goldbart A, Press J, Sofer S, Kapelushnik J (2000) "Near fatal acute colchicine intoxication in a child. A case report." Eur J Pediatr, 159, p. 895-7
  16. (2008) "Colchicine: serious interactions." Prescrire Int, 17, p. 151-3
  17. (2009) "Product Information. Colcrys (colchicine)." AR Scientific Inc
  18. Dahan A, Amidon GL (2009) "Grapefruit juice and its constitueants augment colchicine intestinal absorption: potential hazardous interaction and the role of p-glycoprotein." Pharm Res, 26, p. 883-92
  19. McKinnell J, Tayek JA (2009) "Short term treatment with clarithromycin resulting in colchicine-induced rhabdomyolysis." J Clin Rheumatol, 15, p. 303-5
View all 19 references

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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.

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