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Drug Interactions between bepridil and Mitigare

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

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Major

colchicine bepridil

Applies to: Mitigare (colchicine) and bepridil

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

bepridil food

Applies to: bepridil

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.

References

  1. Edgar B, Bailey D, Bergstrand R, et al. "Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics on felodipine and its potential clinical relevance." Eur J Clin Pharmacol 42 (1992): 313-7
  2. Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55
  3. Bailey DG, Arnold JM, Munoz C, Spence JD "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther 53 (1993): 637-42
  4. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8
  5. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie 49 (1994): 522-4
  6. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther 54 (1993): 589-94
  7. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG "Drug-food interactions in clinical practice." J Fam Pract 40 (1995): 376-84
  8. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
  9. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther 58 (1995): 127-31
  10. 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
  11. Majeed A, Kareem A "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol 10 (1996): 395
  12. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol 42 (1996): p662
  13. Josefsson M, Zackrisson AL, Ahlner J "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol 51 (1996): 189-93
  14. Kantola T, Kivisto KT, Neuvonen PJ "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther 63 (1998): 397-402
  15. Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A "Interaction between grapefruit juice and diazepam in humans." Eur J Drug Metab Pharmacokinet 23 (1998): 55-9
  16. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  17. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther 64 (1998): 248-56
  18. Garg SK, Kumar N, Bhargava VK, Prabhakar SK "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther 64 (1998): 286-8
  19. Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther 64 (1998): 477-83
  20. Fuhr U, Maier-Bruggemann A, Blume H, et al. "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther 36 (1998): 126-32
  21. Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther 66 (1999): 118-27
  22. Eagling VA, Profit L, Back DJ "Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components." Br J Clin Pharmacol 48 (1999): 543-52
  23. Damkier P, Hansen LL, Brosen K "Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine." Br J Clin Pharmacol 48 (1999): 829-38
  24. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther 21 (1999): 1890-9
  25. Dresser GK, Spence JD, Bailey DG "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet 38 (2000): 41-57
  26. Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41
  27. Takanaga H, Ohnishi A, Maatsuo H, et al. "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol 49 (2000): 49-58
  28. Libersa CC, Brique SA, Motte KB, et al. "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol 49 (2000): 373-8
  29. 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
  30. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit 23 (2001): 369-73
  31. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8
  32. Flanagan D "Understanding the grapefruit-drug interaction." Gen Dent 53 (2005): 282-5; quiz 286
View all 32 references

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Moderate

bepridil food

Applies to: bepridil

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References

  1. Sternbach H "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med 101 (1984): 498-9
  3. Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139
  4. Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75
  8. Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595
View all 8 references

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Moderate

bepridil food

Applies to: bepridil

MONITOR: Calcium-containing products may decrease the effectiveness of calcium channel blockers by saturating calcium channels with calcium. Calcium chloride has been used to manage acute severe verapamil toxicity.

MANAGEMENT: Management consists of monitoring the effectiveness of calcium channel blocker therapy during coadministration with calcium products.

References

  1. Henry M, Kay MM, Viccellio P "Cardiogenic shock associated with calcium-channel and beta blockers: reversal with intravenous calcium chloride." Am J Emerg Med 3 (1985): 334-6
  2. Moller IW "Cardiac arrest following intravenous verapamil combined with halothane anaesthesia." Br J Anaesth 59 (1987): 522-6
  3. Oszko MA, Klutman NE "Use of calcium salts during cardiopulmonary resuscitation for reversing verapamil-associated hypotension." Clin Pharm 6 (1987): 448-9
  4. Schoen MD, Parker RB, Hoon TJ, et al. "Evaluation of the pharmacokinetics and electrocardiographic effects of intravenous verapamil with intravenous calcium chloride pretreatment in normal subjects." Am J Cardiol 67 (1991): 300-4
  5. O'Quinn SV, Wohns DH, Clarke S, Koch G, Patterson JH, Adams KF "Influence of calcium on the hemodynamic and anti-ischemic effects of nifedipine observed during treadmill exercise testing." Pharmacotherapy 10 (1990): 247
  6. Woie L, Storstein L "Successful treatment of suicidal verapamil poisoning with calcium gluconate." Eur Heart J 2 (1981): 239-42
  7. Morris DL, Goldschlager N "Calcium infusion for reversal of adverse effects of intravenous verapamil." JAMA 249 (1983): 3212-3
  8. Guadagnino V, Greengart A, Hollander G, Solar M, Shani J, Lichstein E "Treatment of severe left ventricular dysfunction with calcium chloride in patients receiving verapamil." J Clin Pharmacol 27 (1987): 407-9
  9. Luscher TF, Noll G, Sturmer T, Huser B, Wenk M "Calcium gluconate in severe verapamil intoxication." N Engl J Med 330 (1994): 718-20
  10. Bar-Or D, Gasiel Y "Calcium and calciferol antagonise effect of verapamil in atrial fibrillation." Br Med J (Clin Res Ed) 282 (1981): 1585-6
  11. Lipman J, Jardine I, Roos C, Dreosti L "Intravenous calcium chloride as an antidote to verapamil-induced hypotension." Intensive Care Med 8 (1982): 55-7
  12. McMillan R "Management of acute severe verapamil intoxication." J Emerg Med 6 (1988): 193-6
  13. Perkins CM "Serious verapamil poisoning: treatment with intravenous calcium gluconate." Br Med J 2 (1978): 1127
  14. Moroni F, Mannaioni PF, Dolara A, Ciaccheri M "Calcium gluconate and hypertonic sodium chloride in a case of massive verapamil poisoning." Clin Toxicol 17 (1980): 395-400
View all 14 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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