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Drug Interactions between Mitigare and Quinaglute Dura-Tabs

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

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Interactions between your drugs

Major

quiNIDine colchicine

Applies to: Quinaglute Dura-Tabs (quinidine) and Mitigare (colchicine)

ADJUST DOSE: Coadministration with inhibitors of P-glycoprotein (P-gp) may significantly increase the serum concentrations of colchicine. The mechanism involves enhanced absorption as well as reduced excretion of colchicine due to inhibition of P-gp efflux transporter in the intestine, renal proximal tubule, and liver. In a study of 23 healthy volunteers, administration of a single 0.6 mg dose of colchicine in combination with a single 100 mg dose of the potent P-gp inhibitor cyclosporine resulted in an approximately 3.5-fold increase in colchicine peak plasma concentration (Cmax) and systemic exposure (AUC). Clinical manifestations associated with the interaction have included neuromyopathy, rhabdomyolysis, hepato- and nephrotoxicity, cardiotoxicity, bone marrow suppression, multiorgan failure, and fatality. In a retrospective study of renal transplant recipients at a French hospital, investigators reported that five out of ten patients who received cyclosporine in combination with colchicine experienced muscular symptoms, while none did in the control group that received only cyclosporine. Muscular histology, when performed, was consistent with previous reports of colchicine (i.e., vacuolar) myopathy. Mean duration of colchicine therapy was 12.2 months in the patients with muscular symptoms and 6.8 months in the patients without muscular symptoms. All five patients improved after colchicine withdrawal. No significant differences were found for age, gender ratio, transplant duration, serum creatinine levels, or cumulative steroid dose between case patients and controls. Data are not available for colchicine in combination with other P-gp inhibitors. However, a similar interaction is expected.

MANAGEMENT: Due to the risk of life-threatening and fatal toxicity, patients with renal or hepatic impairment should not be given colchicine in combination with P-glycoprotein inhibitors such as cyclosporine, carvedilol, amiodarone, bepridil, quinidine, quinine, propafenone, ranolazine, spironolactone, tamoxifen, ulipristal, and some tyrosine kinase inhibitors. In patients with normal renal and hepatic function, the dosage of colchicine should be reduced when used with P-gp inhibitors or within 14 days of using them. Some authorities have specified dose adjustments for gout (treatment and prophylaxis) and familial Mediterranean fever. For the treatment of acute gout flares, the adjusted dosage recommended is 0.6 mg for one dose. Administration should not be repeated for at least three days. For the treatment of familial Mediterranean fever, the maximum dosage of colchicine is 0.6 mg/day (may be given as 0.3 mg twice a day) when used in the presence of a P-gp inhibitor. Patients should be advised to contact their physician if they experience symptoms of toxicity such as abdominal pain, nausea, vomiting, diarrhea, fatigue, myalgia, asthenia, hyporeflexia, paresthesia, and numbness.

References

  1. Arellano F, Krupp P "Muscular disorders associated with cyclosporin." Lancet 337 (1991): 915
  2. Kuncl RW, Duncan G, Watson D, et al. "Colchicine myopathy and neuropathy." N Engl J Med 316 (1987): 1562-8
  3. Rieger EH, Halasz NA, Wahlstrom HE "Colchicine neuromyopathy after renal transplantation." Transplantation 49 (1990): 1196-8
  4. Speeg KV, Maldonado AL, Liaci J, Muirhead D "Effect of cyclosporine on colchicine secretion by the kidney multidrug transporter studied in vivo." J Pharmacol Exp Ther 261 (1992): 50-5
  5. Yussim A, Barnathan N, Lustig S, Shaharabani E, Geier E, Shmuely D, Nakache R, Shapira Z "Gastrointestinal, hepatorenal, and neuromuscular toxicity caused by cyclosporine-colchicine interaction in renal transplantation." Transplant Proc 26 (1994): 2825-6
  6. Rumpf KW, Henning HV "Is myopathy in renal transplant patients induced by cyclosporin or colchicine?." Lancet 335 (1990): 800-1
  7. Menta R, Rossi E, Guariglia A, David S, Cambi V "Reversible acute cyclosporin nephrotoxicity induced by colchicine administration." Nephrol Dial Transplant 2 (1987): 380-1
  8. Jonsson J, Gelpi JR, Light JA, Aquino A, Maszaros S "Colchicine-induced myoneuropathy in a renal transplant patient." Transplantation 53 (1992): 1369-71
  9. Gruberg L, Har-Zahav Y, Agranat O, Freimark D "Acute myopathy induced by colchicine in a cyclosporine treated heart transplant recipient: possible role of the multidrug resistance transporter." Transplant Proc 31 (1999): 2157-8
  10. Caglar K, Safali M, Yavuz I, Odabasi Z, Yenicesu M, Vural A "Colchicine-induced myopathy with normal creatine phosphokinase level in a renal transplant patient." Nephron 92 (2002): 922-924
  11. Fujii Y, Arimura Y, Takahashi N, et al. "[A case of Behcet's disease associated with neuromyopathy induced by combination therapy with colchicine and cyclosporin]" Ryumachi 43 (2003): 44-50
  12. Minetti EE, Minetti L "Multiple organ failure in a kidney transplant patient receiving both colchicine and cyclosporine." J Nephrol 16 (2003): 421-5
  13. Vasudevan AR, Uthamalingam S, Kumar S, Tamarin F, Brensilver JM "Colchicine-induced rhabdomyolysis: the whole is greater than the sum of its parts!" Am J Med 115 (2003): 249
  14. Wilbur K, Makowsky M "Colchicine myotoxicity: case reports and literature review." Pharmacotherapy 24 (2004): 1784-92
  15. Englund G, Hallberg P, Artursson P, Michaelsson K, Melhus H "Association between the number of coadministered P-glycoprotein inhibitors and serum digoxin levels in patients on therapeutic drug monitoring." BMC Med 2 (2004): 8
  16. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  17. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  18. Francis L, Bonilla E, Soforo E, et al. "Fatal toxic myopathy attributed to propofol, methylprednisolone, and cyclosporine after prior exposure to colchicine and simvastatin." Clin Rheumatol 27 (2008): 129-31
  19. Eleftheriou G, Bacis G, Fiocchi R, Sebastiano R "Colchicine-induced toxicity in a heart transplant patient with chronic renal failure." Clin Toxicol (Phila) 46 (2008): 827-30
  20. "Colchicine: serious interactions." Prescrire Int 17 (2008): 151-3
  21. "Product Information. Colcrys (colchicine)." AR Scientific Inc (2009):
  22. Lee BI, Shin SJ, Yoon SN, Choi YJ, Yang CW, Bang BK "Acute myopathy induced by colchicine in a cyclosporine-treated renal transplant recipient--a case report and review of the literature." J Korean Med Sci 12 (1997): 160-1
  23. Ducloux D, Schuller V, Bresson-Vautrin C, Chalopin JM "Colchicine myopathy in renal transplant recipients on cyclosporin." Nephrol Dial Transplant 12 (1997): 2389-92
  24. Garrouste C, Philipponnet C, Kaysi S, Enache I, Tiple A, Heng AE "Severe colchicine intoxication in a renal transplant recipient on cyclosporine." Transplant Proc 44 (2012): 2851-2
  25. Volpe DA, Hamed SS, Zhang LK "Use of different parameters and equations for calculation of IC50 values in efflux assays: potential sources of variability in IC 50 determination." AAPS J 16 (2014): 172-80
  26. Nakamura T, Kakumoto M, Yamashita K, et al. "Factors influencing the prediction of steady state concentrations of digoxin." Biol Pharm Bull 24 (2001): 403-8
  27. Mounier G, Guy C, Beyens MN, Ratrema M, Massol A, Ollagnier M "Colchicine-induced pancytopenia during therapeutic dose administratioin. French parmacovigilance database survey and literature review." Drug Saf 29 (2006): 911-1010
  28. FDA. U.S. Food and Drug Administration "Postmarket drug safty information for patients and providers. Drugs. Colchicine (marketed as Colcrys) information. http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm174382.htm" (2015):
  29. FDA. U.S. Food and Drug Administration "Information for Healthcare Professionals: New safety information for Colchicine (marketed as Colcrys). http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm174315.htm" (2015):
View all 29 references

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Drug and food interactions

Major

colchicine food

Applies to: Mitigare (colchicine)

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

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Moderate

quiNIDine food

Applies to: Quinaglute Dura-Tabs (quinidine)

GENERALLY AVOID: In a small, randomized, crossover study, the administration of quinidine with grapefruit juice (compared to water) to healthy volunteers significantly prolonged the time to reach peak plasma quinidine concentrations and decreased the plasma concentrations of its major metabolite, 3-hydroxyquinidine. These changes were associated pharmacodynamically with both a delay and a reduction in the maximal effect on QTc interval. The proposed mechanism is delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Given the drug's narrow therapeutic index, patients receiving quinidine therapy should avoid the consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels.

References

  1. Ace LN, Jaffe JM, Kunka RL "Effect of food and an antacid on quinidine bioavailability." Biopharm Drug Dispos 4 (1983): 183-90
  2. Min DI, Ku YM, Geraets DR, Lee HC "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol 36 (1996): 469-76
  3. Ha HR, Chen J, Leuenberger PM, Freiburghaus AU, Follah F "In vitro inhibition of midazolam and quinidine metabolism by flavonoids." Eur J Clin Pharmacol 48 (1995): 367-71
  4. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77
View all 4 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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