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Drug Interactions between allopurinol and Probenecid and Colchicine

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

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Interactions between your drugs

Minor

allopurinol probenecid

Applies to: allopurinol and Probenecid and Colchicine (colchicine / probenecid)

The renal excretion allopurinol's active metabolite, oxypurinol, may be increased when coadministered with probenecid and/or large doses of salicylates (e.g., aspirin). At the same time, both probenecid and large doses of salicylates may have a hypouricemic effect; allopurinol may also inhibit probenecid metabolism. The clinical significance of this interaction is unknown. Patients should be monitored for altered effects of both allopurinol and probenecid.

References (10)
  1. Elion GB, Yu TF, Gutman AB, Hitchings GH (1968) "Renal clearance of oxipurinol, the chief metabolite of allopurinol." Am J Med, 45, p. 69-77
  2. Tjandramaga TB, Cucinell SA, Israili ZH, et al. (1972) "Observations on the disposition of probenecid in patients receiving allopurinol." Pharmacology, 8, p. 259-72
  3. Kelley WN (1976) "Current therapy of gout and hyperuricemia." Hosp Pract, 11, p. 69-76
  4. Stocker S (2011) "Pharmacokinetic and pharmacodynamic interaction between allopurinol and probenecid in patients with gout" J Rheumatol, 38, p. 904-910
  5. Reinders M (2007) "Biochemical effectiveness of allopurinol and allopurinol-probenecid in previously benzbromarone-treated gout patients" Clin Rheumatol, 26, p. 1459-1465
  6. Price GE (1963) "The Effects of Oral Salicylate on Serum Uric Acid Levels" Can Med Assoc J, 88, p. 1065-1067
  7. (2024) "Product Information. Allopurinol (Sandoz) (allopurinol)." Sandoz Pty Ltd
  8. (2021) "Product Information. Zyloric (allopurinol)." Aspen Pharma Trading Ltd
  9. (2021) "Product Information. Zyloprim (allopurinol)." AA Pharma Inc, 248178
  10. (2024) "Product Information. Allopurinol (allopurinol)." Actavis U.S. (Purepac Pharmaceutical Company)

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 (19)
  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
Moderate

allopurinol food

Applies to: allopurinol

ADJUST DOSING INTERVAL: The tolerability of allopurinol may be improved by giving it after a meal. Additionally, when the dose is greater than 300 mg, dividing the total daily dose into smaller doses administered more often may be appropriate to help minimize gastrointestinal irritation.

MONITOR: Concomitant use of allopurinol with central nervous system (CNS) depressants, including alcohol, may potentiate adverse effects such as somnolence and sedation.

MANAGEMENT: To improve tolerability, some manufacturers suggest administering allopurinol after a meal. Additionally, if the daily dose is greater than 300 mg, administering allopurinol in divided doses may help reduce gastrointestinal intolerance. Patients should also be counseled to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until they know how the medication affects them.

References (4)
  1. (2024) "Product Information. Allopurinol (Sandoz) (allopurinol)." Sandoz Pty Ltd
  2. (2021) "Product Information. Zyloric (allopurinol)." Aspen Pharma Trading Ltd
  3. (2021) "Product Information. Zyloprim (allopurinol)." AA Pharma Inc, 248178
  4. (2024) "Product Information. Allopurinol (allopurinol)." Actavis U.S. (Purepac Pharmaceutical Company)

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Anti-gout agents

Therapeutic duplication

The recommended maximum number of medicines in the 'anti-gout agents' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'anti-gout agents' category:

  • allopurinol
  • Probenecid and Colchicine (colchicine/probenecid)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.


Report options

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.