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Drug Interactions between colchicine / probenecid and Demadex

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

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Interactions between your drugs

Minor

probenecid torsemide

Applies to: colchicine / probenecid and Demadex (torsemide)

Some investigators suggest that probenecid may acutely decrease the pharmacologic effects of loop diuretics by competitively inhibiting their renal secretion in the proximal tubule. A marked increase in diuresis and natriuresis may then follow due to increased amount of diuretic available at renal acceptor sites once probenecid has been cleared from the urine. In a study of eight normal volunteers, pretreatment with probenecid led to an overall increased response to a 40 mg dose of furosemide, as indicated by a 37% increase in sodium excretion and a 28% increase in urine volume over an eight-hour period. However, others have not corroborated these findings. One study reported no effect of probenecid on either cumulative response or time course of response of bumetanide, while another reported an increase in initial diuretic efficiency of furosemide but no change in cumulative urinary sodium excretion over five hours. No particular intervention is necessary during concomitant therapy with these agents, but clinicians should be aware of the potential for interaction.

References

  1. Brater DC, Fox WR, Chennavasin P (1981) "Interaction studies with bumetanide and furosemide: effects of probenecid and of indomethacin on response to bumetanide in man." J Clin Pharmacol, 21, p. 647-53
  2. Brater DC, Chennavasin P (1981) "Effect of probenecid on response to bumetanide in man." J Clin Pharmacol, 21, p. 311-5
  3. Honari J, Blair AD, Cutler RE (1977) "Effects of probenecid on furosemide kinetics and natriuresis in man." Clin Pharmacol Ther, 22, p. 395-401
  4. Chennavasin P, Seiwell R, Brater DC, Liang WM (1979) "Pharmacodynamic analysis of the furosemide-probenecid interaction in man." Kidney Int, 16, p. 187-95
  5. Odlind B, Beermann B (1980) "Renal tubular secretion and effects of furosemide." Clin Pharmacol Ther, 27, p. 784-90
  6. Velasquez MT, Wan SH, Barr JW, Maronde RF (1981) "Effect of probenecid on the natriuresis and renin release induced by bumetanide in man." J Clin Pharmacol, 21, p. 657-62
  7. Brater DC (1978) "Effects of probenecid on furosemide response." Clin Pharmacol Ther, 24, p. 548-54
  8. Homeida M, Roberts C, Branch RA (1977) "Influence of probenecid and spironolactone on furosemide kinetics and dynamics in man." Clin Pharmacol Ther, 22, p. 402-9
  9. Sommers DK, Meyer EC, Moncrieff J (1991) "The influence of co-administered organic acids on the kinetics and dynamics of frusemide." Br J Clin Pharmacol, 32, p. 489-93
  10. Brater DC, Leinfelder J, Anderson SA (1987) "Clinical pharmacology of torasemide, a new loop diuretic." Clin Pharmacol Ther, 42, p. 187-92
  11. Vree TB, van den Biggelaar-Martea M, Verwey-van Wissen CP (1995) "Probenecid inhibits the renal clearance of frusemide and its acyl glucuronide." Br J Clin Pharmacol, 39, p. 692-5
  12. Leary WP, Reyes AJ (1984) "Drug interactions with diuretics." S Afr Med J, 65, p. 455-61
View all 12 references

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Drug and food interactions

Major

colchicine food

Applies to: 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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