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Drug Interactions between Liptruzet and verapamil

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

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Moderate

verapamil atorvastatin

Applies to: verapamil and Liptruzet (atorvastatin / ezetimibe)

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of HMG-CoA reductase inhibitors (i.e., statins) that are metabolized by the isoenzyme. Lovastatin and simvastatin are particularly susceptible because of their low oral bioavailability, but others such as atorvastatin and cerivastatin may also be affected. High levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death. Clinically significant interactions have been reported with potent CYP450 3A4 inhibitors such as macrolide antibiotics, azole antifungals, protease inhibitors and nefazodone, and moderate inhibitors such as amiodarone, cyclosporine, danazol, diltiazem and verapamil.

MANAGEMENT: Caution is recommended if atorvastatin, cerivastatin, lovastatin, simvastatin, or red yeast rice (which contains lovastatin) is prescribed with a CYP450 3A4 inhibitor. It is advisable to monitor lipid levels and use the lowest effective statin dose. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed. Fluvastatin, pravastatin, and rosuvastatin are not expected to interact with CYP450 3A4 inhibitors.

References

  1. Spach DH, Bauwens JE, Clark CD, Burke WG "Rhabdomyolysis associated with lovastatin and erythromycin use." West J Med 154 (1991): 213-5
  2. Ayanian JZ, Fuchs CS, Stone RM "Lovastatin and rhabdomyolysis." Ann Intern Med 109 (1988): 682-3
  3. Corpier CL, Jones PH, Suki WN, et al. "Rhabdomyolysis and renal injury with lovastatin use. Report of two cases in cardiac transplant recipients." JAMA 260 (1988): 239-41
  4. East C, Alivizatos PA, Grundy SM, Jones PH, Farmer JA "Rhabdomyolysis in patients receiving lovastatin after cardiac transplantation." N Engl J Med 318 (1988): 47-8
  5. Norman DJ, Illingworth DR, Munson J, Hosenpud J "Myolysis and acute renal failure in a heart-transplant recipient receiving lovastatin." N Engl J Med 318 (1988): 46-7
  6. "Product Information. Mevacor (lovastatin)." Merck & Co., Inc PROD (2002):
  7. "Product Information. Zocor (simvastatin)." Merck & Co., Inc PROD (2001):
  8. Dallaire M, Chamberland M "Severe rhabdomyolysis in a patient receiving lovastatin, danazol and doxycycline." Can Med Assoc J 150 (1994): 1991-4
  9. Campana C, Iacona I, Regassi MB, et al. "Efficacy and pharmacokinetics of simvastatin in heart transplant recipients." Ann Pharmacother 29 (1995): 235-9
  10. Lees RS, Lees AM "Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole." N Engl J Med 333 (1995): 664-5
  11. Zhou LX, Finley DK, Hassell AE, Holtzman JL "Pharmacokinetic interaction between isradipine and lovastatin in normal, female and male volunteers." J Pharmacol Exp Ther 273 (1995): 121-7
  12. Neuvonen PJ, Jalava KM "Itraconazole drastically increases plasma concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther 60 (1996): 54-61
  13. Horn M "Coadministration of itraconazole with hypolipidemic agents may induce rhabdomyolysis in healthy individuals." Arch Dermatol 132 (1996): 1254
  14. "Product Information. Lipitor (atorvastatin)." Parke-Davis PROD (2001):
  15. Jacobson RH, Wang P, Glueck CJ "Myositis and rhabdomyolysis associated with concurrent use of simvastatin and nefazodone." JAMA 277 (1997): 296
  16. Jody DN "Myositis and rhabdomyolysis associated with concurrent use of simvastatin and nefazodone." JAMA 277 (1997): 296-7
  17. "Product Information. Baycol (cerivastatin)." Bayer PROD (2001):
  18. Grunden JW, Fisher KA "Lovastatin-induced rhabdomyolysis possibly associated with clarithromycin and azithromycin." Ann Pharmacother 31 (1997): 859-63
  19. Wong PW, Dillard TA, Kroenke K "Multiple organ toxicity from addition of erythromycin to long-term lovastatin therapy." South Med J 91 (1998): 202-5
  20. Neuvonen PJ, Kantola T, Kivisto KT "Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole." Clin Pharmacol Ther 63 (1998): 332-41
  21. Agbin NE, Brater DC, Hall SD "Interaction of diltiazem with lovastatin and pravastatin." Clin Pharmacol Ther 61 (1997): 201
  22. Kivisto KT, Kantola T, Neuvonen PJ "Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatin." Br J Clin Pharmacol 46 (1998): 49-53
  23. Kantola T, Kivisto KT, Neuvonen PJ "Effect of itraconazole on the pharmacokinetics of atorvastatin." Clin Pharmacol Ther 64 (1998): 58-65
  24. Kantola T, Kivisto KT, Neuvonen PJ "Erythromycin and verapamil considerably increase serum simvastatin and simvastatin acid concentrations." Clin Pharmacol Ther 64 (1998): 177-82
  25. Azie NE, Brater DC, Becker PA, Jones DR, Hall SD "The interaction of diltiazem with lovastatin and pravastatin." Clin Pharmacol Ther 64 (1998): 369-77
  26. Lomaestro BM, Piatek MA "Update on drug interactions with azole antifungal agents." Ann Pharmacother 32 (1998): 915-28
  27. Kantola T, Kivisto KT, Neuvonen PJ "Effect of itraconazole on cerivastatin pharmacokinetics." Eur J Clin Pharmacol 54 (1999): 851-5
  28. Malaty LI, Kuper JJ "Drug interactions of HIV protease inhibitors." Drug Safety 20 (1999): 147-69
  29. Siedlik PH, Olson SC, Yang BB, Stern RH "Erythromycin coadministration increases plasma atorvastatin concentrations." J Clin Pharmacol 39 (1999): 501-4
  30. Barry M, Mulcahy F, Merry C, Gibbons S, Back D "Pharmacokinetics and potential interactions amongst antiretroviral agents used to treat patients with HIV infection." Clin Pharmacokinet 36 (1999): 289-304
  31. Rodriguez JA, CrespoLeiro MG, Paniagua MJ, Cuenca JJ, Hermida LF, Juffe A, CastroBeiras A "Rhabdomyolysis in heart transplant patients on HMG-CoA reductase inhibitors and cyclosporine." Transplant Proc 31 (1999): 2522-3
  32. Gruer PJK, Vega JM, Mercuri MF, Dobrinska MR, Tobert JA "Concomitant use of cytochrome P450 3A4 inhibitors and simvastatin." Am J Cardiol 84 (1999): 811-5
  33. Gilad R, Lampl Y "Rhabdomyolysis induced by simvastatin and ketoconazole treatment." Clin Neuropharmacol 22 (1999): 295-7
  34. Gullestad L, Nordal KP, Berg KJ, Cheng H, Schwartz MS, Simonsen S "Interaction between lovastatin and cyclosporine A after heart and kidney transplantation." Transplant Proc 31 (1999): 2163-5
  35. Yeo KR, Yeo WW, Wallis EJ, Ramsay LE "Enhanced cholesterol reduction by simvastatin in diltiazem-treated patients." Br J Clin Pharmacol 48 (1999): 610-5
  36. Maltz HC, Balog DL, Cheigh JS "Rhabdomyolysis associated with concomitant use of atorvastatin and cyclosporine." Ann Pharmacother 33 (1999): 1176-9
  37. Dresser GK, Spence JD, Bailey DG "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet 38 (2000): 41-57
  38. Jardine A, Holdaas H "Fluvastatin in combination with cyclosporin in renal transplant recipients: a review of clinical and safety experience." J Clin Pharm Ther 24 (1999): 397-408
  39. Mousa O, Brater DC, Sundblad KJ, Hall SD "The interaction of diltiazem with simvastatin." Clin Pharmacol Ther 67 (2000): 267-74
  40. Westphal JF "Macrolide - induced clinically relevant drug interactions with cytochrome P-450 (CYP) 3A4: an update focused on clarithromycin, azithromycin, and dirithromycin." Br J Clin Pharmacol 50 (2000): 285-95
  41. Kusus M, Stapleton DD, Lertora JJL, Simon EE, Dreisbach AW "Rhabdomyolysis and acute renal failure in a cardiac transplant recipient due to multiple drug interactions." Am J Med Sci 320 (2000): 394-7
  42. Lee AJ, Maddix DS "Rhabdomyolysis secondary to a drug interaction between simvastatin and clarithromycin." Ann Pharmacother 35 (2001): 26-31
  43. Yeo KR, Yeo WW "Inhibitory effects of verapamil and diltiazem on simvastatin metabolism in human liver microsomes." Br J Clin Pharmacol 51 (2001): 461-70
  44. Arnadottir M, Eriksson LO, Thysell H, Karkas JD "Plasma concentration profiles of simvastatin 3-hydroxy- 3-methylglutaryl-coenzyme A reductase inhibitory activity in kidney transplant recipients with and without ciclosporin." Nephron 65 (1993): 410-3
  45. Corsini A, Bellosta S, Baetta R, Fumagalli R, Paoletti R, Bernini F "New insights into the pharmacodynamic and pharmacokinetic properties of statins." Pharmacol Ther 84 (1999): 413-28
  46. Garnett WR "Interactions with hydroxymethylglutaryl-coenzyme A reductase inhibitors." Am J Health Syst Pharm 52 (1995): 1639-45
  47. Omar MA, Wilson JP "FDA adverse event reports on statin-associated rhabdomyolysis." Ann Pharmacother 36 (2002): 288-95
  48. Fichtenbaum CJ, Gerber JG, Rosenkranz SL, et al. "Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047." AIDS 16 (2002): 569-577
  49. Amsden GW, Kuye O, Wei GC "A study of the interaction potential of azithromycin and clarithromycin with atorvastatin in healthy volunteers." J Clin Pharmacol 42 (2002): 444-9
  50. Williams D, Feely J "Pharmacokinetic-Pharmacodynamic Drug Interactions with HMG-CoA Reductase Inhibitors." Clin Pharmacokinet 41 (2002): 343-70
  51. Thompson M, Samuels S "Rhabdomyolysis with simvastatin and nefazodone." Am J Psychiatry 159 (2002): 1607
  52. Huynh T, Cordato D, Yang F, et al. "HMG coA reductase-inhibitor-related myopathy and the influence of drug interactions." Intern Med J 32(9-10) (2002): 486-90
  53. Paoletti R, Corsini A, Bellosta S "Pharmacological interactions of statins." Atheroscler Suppl 3 (2002): 35-40
  54. Sipe BE, Jones RJ, Bokhart GH "Rhabdomyolysis Causing AV Blockade Due to Possible Atorvastatin, Esomeprazole, and Clarithromycin Interaction." Ann Pharmacother 37 (2003): 808-11
  55. de Denus S, Spinler SA "Amiodarone's role in simvastatin-associated rhabdomyolysis." Am J Health Syst Pharm 60 (2003): 1791; author reply 1791-2
  56. Skrabal MZ, Stading JA, Monaghan MS "Rhabdomyolysis associated with simvastatin-nefazodone therapy." South Med J 96 (2003): 1034-5
  57. Andreou ER, Ledger S "Potential drug interaction between simvastatin and danazol causing rhabdomyolysis." Can J Clin Pharmacol 10 (2003): 172-4
  58. Roten L, Schoenenberger RA, Krahenbuhl S, Schlienger RG "Rhabdomyolysis in association with simvastatin and amiodarone." Ann Pharmacother 38 (2004): 978-81
  59. Jacobson TA "Comparative pharmacokinetic interaction profiles of pravastatin, simvastatin, and atorvastatin when coadministered with cytochrome P450 inhibitors." Am J Cardiol 94 (2004): 1140-6
  60. Chouhan UM, Chakrabarti S, Millward LJ "Simvastatin interaction with clarithromycin and amiodarone causing myositis." Ann Pharmacother 39 (2005): 1760-1
  61. Karnik NS, Maldonado JR "Antidepressant and statin interactions: a review and case report of simvastatin and nefazodone-induced rhabdomyolysis and transaminitis." Psychosomatics 46 (2005): 565-8
  62. Neuvonen PJ, Backman JT, Niemi M "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin." Clin Pharmacokinet 47 (2008): 463-74
  63. "Product Information. Qelbree (viloxazine)." Supernus Pharmaceuticals Inc (2021):
View all 63 references

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Moderate

atorvastatin ezetimibe

Applies to: Liptruzet (atorvastatin / ezetimibe) and Liptruzet (atorvastatin / ezetimibe)

MONITOR: Coadministration with ezetimibe may rarely increase the risk of myopathy and serum transaminase elevations associated with HMG-CoA reductase inhibitors (i.e., statins). The mechanism of interaction is unknown. A case report describes two patients whose serum creatine kinase increased after ezetimibe was added to their statin therapy (atorvastatin and fluvastatin, respectively). One of the patients also developed myalgia and tendinopathy, which resolved promptly after withdrawal of both drugs. Statin therapy was subsequently reintroduced at the previous dosage without incident. In the other patient, serum creatine kinase returned to normal within 4 weeks after discontinuation of ezetimibe while the statin was continued. On the contrary, no cases of myopathy or tendinopathy occurred in a study of 33 hypercholesterolemic patients treated with ezetimibe and atorvastatin or simvastatin. There were also no reports of myopathy or significant increases in serum creatine kinase in a study of 32 subjects treated with ezetimibe and fluvastatin. In controlled clinical studies, the incidence of consecutive elevations (greater than 3 times the upper limit of normal) in serum transaminases was 1.3% for patients treated with ezetimibe in combination with a statin versus 0.4% for patients treated with a statin alone. These elevations were generally asymptomatic, not associated with cholestasis, and returned to baseline after discontinuation of therapy or with continued treatment.

MANAGEMENT: Until further information is available, use of a statin in combination with ezetimibe should be approached with caution. Patients should be advised to promptly report to their physician any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. The drugs should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed. In addition, liver function tests should be performed at initiation of therapy and according to the recommendations of the HMG-CoA reductase inhibitor.

References

  1. Gagne C, Gaudet D, Bruckert E "Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia." Circulation 105 (2002): 2469-75
  2. Fux R, Morike K, Gundel UF, Hartmann R, Gleiter CH "Ezetimibe and statin-associated myopathy." Ann Intern Med 140 (2004): 671-2

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Drug and food interactions

Moderate

verapamil food

Applies to: verapamil

GENERALLY AVOID: Consumption of large quantities of grapefruit juice may be associated with significantly increased plasma concentrations of oral verapamil. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. One study reported no significant effect of a single administration of grapefruit juice on the pharmacokinetics of verapamil in ten hypertensive patients receiving chronic therapy. In another study conducted in nine healthy male volunteers, administration of 120 mg oral verapamil twice daily for 3 days following pretreatment with 200 mL grapefruit juice twice daily for 5 days resulted in a 57% increase in S-verapamil peak plasma concentration (Cmax), a 36% increase in S-verapamil systemic exposure (AUC), a 40% increase in R-verapamil Cmax, and a 28% increase in R-verapamil AUC compared to administration following orange juice. Elimination half-life and renal clearance of both S- and R-verapamil were not affected by grapefruit juice, and there were no significant effects on blood pressure, heart rate, or PR interval. A third study reported a 1.63-fold increase in Cmax and a 1.45-fold increase in AUC of (R,S)-verapamil in 24 young, healthy volunteers given verapamil sustained-release 120 mg twice daily for 7 days with 250 mL grapefruit juice four times daily on days 5 through 7. Two subjects developed PR interval prolongation of more than 350 ms during grapefruit juice coadministration. A high degree of interindividual variability has been observed in these studies. The interaction was also suspected in a case report of a 42-year-old woman who developed complete heart block, hypotension, hypoxic respiratory failure, severe anion gap metabolic acidosis, and hyperglycemia following accidental ingestion of three verapamil sustained-release 120 mg tablets over a span of six hours. The patient's past medical history was remarkable only for migraine headaches, for which she was receiving several medications including verapamil. Prior to admission, the patient had a 2-week history of poorly controlled migraine, and the six hours preceding hospitalization she suffered from worsening headache and palpitations progressing to altered sensorium. An extensive workup revealed elevated verapamil and norverapamil levels more than 4.5 times above the upper therapeutic limits. These levels also far exceeded those reported in the medical literature for patients taking verapamil 120 mg every 6 hours, or 480 mg in a 24-hour period. The patient recovered after receiving ventilator and vasopressor support. Upon questioning, it was discovered that the patient had been drinking large amounts of grapefruit juice (3 to 4 liters total) the week preceding her admission due to nausea. No other sources or contributing factors could be found for the verapamil toxicity.

MANAGEMENT: Patients treated with oral verapamil should avoid the consumption of large amounts of grapefruit or grapefruit juice to prevent any undue fluctuations in serum drug levels. Patients should be advised to seek medical attention if they experience edema or swelling of the lower extremities; sudden, unexplained weight gain; difficulty breathing; chest pain or tightness; or hypotension as indicated by dizziness, fainting, or orthostasis.

References

  1. McAllister RG, Jr "Clinical pharmacology of slow channel blocking agents." Prog Cardiovasc Dis 25 (1982): 83-102
  2. "Product Information. Covera-HS (verapamil)." Searle PROD (2001):
  3. Zaidenstein R, Dishi V, Gips M, Soback S, Cohen N, Weissgarten J, Blatt A, Golik A "The effect of grapefruit juice on the pharmacokinetics of orally administered verapamil." Eur J Clin Pharmacol 54 (1998): 337-40
  4. Ho PC, Ghose K, Saville D, Wanwimolruk S "Effect of grapefruit juice on pharmacokinetics and pharmacodynamics of verapamil enantiomers in healthy volunteers." Eur J Clin Pharmacol 56 (2000): 693-8
  5. Fuhr U, Muller-Peltzer H, Kern R, et al. "Effects of grapefruit juice and smoking on verapamil concentrations in steady state." Eur J Clin Pharmacol 58 (2002): 45-53
  6. Bailey DG, Dresser GK "Natural products and adverse drug interactions." Can Med Assoc J 170 (2004): 1531-2
  7. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions. 1998." Br J Clin Pharmacol 58 (2004): S831-40; discussion S841-3
  8. Arayne MS, Sultana N, Bibi Z "Review: grape fruit juice - drug interactions." Pak J Pharm Sci 18 (2005): 45-57
  9. Pillai U, Muzaffar J, Sandeep S, Yancey A "Grapefruit juice and verapamil: a toxic cocktail." South Med J 102 (2009): 308-9
View all 9 references

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Moderate

atorvastatin food

Applies to: Liptruzet (atorvastatin / ezetimibe)

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of atorvastatin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. When a single 40 mg dose of atorvastatin was coadministered with 240 mL of grapefruit juice, atorvastatin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 16% and 37%, respectively. Greater increases in Cmax (up to 71%) and/or AUC (up to 2.5 fold) have been reported with excessive consumption of grapefruit juice (>=750 mL to 1.2 liters per day). Clinically, high levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.

ADJUST DOSING INTERVAL: Fibres such as oat bran and pectin may diminish the pharmacologic effects of HMG-CoA reductase inhibitors by interfering with their absorption from the gastrointestinal tract.

MANAGEMENT: Patients receiving therapy with atorvastatin should limit their consumption of grapefruit juice to no more than 1 liter per day. Patients should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed. In addition, patients should either refrain from the use of oat bran and pectin or, if concurrent use cannot be avoided, to separate the administration times by at least 2 to 4 hours.

References

  1. Richter WO, Jacob BG, Schwandt P "Interaction between fibre and lovastatin." Lancet 338 (1991): 706
  2. McMillan K "Considerations in the formulary selection of hydroxymethylglutaryl coenzyme a reductase inhibitors." Am J Health Syst Pharm 53 (1996): 2206-14
  3. "Product Information. Lipitor (atorvastatin)." Parke-Davis PROD (2001):
  4. Boberg M, Angerbauer R, Fey P, Kanhai WK, Karl W, Kern A, Ploschke J, Radtke M "Metabolism of cerivastatin by human liver microsomes in vitro. Characterization of primary metabolic pathways and of cytochrome P45 isozymes involved." Drug Metab Dispos 25 (1997): 321-31
  5. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  6. 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
  7. Neuvonen PJ, Backman JT, Niemi M "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin." Clin Pharmacokinet 47 (2008): 463-74
View all 7 references

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Moderate

verapamil food

Applies to: verapamil

GENERALLY AVOID: Verapamil may increase the blood concentrations and intoxicating effects of ethanol. The exact mechanism of interaction is unknown but may involve verapamil inhibition of ethanol metabolism. In 10 healthy, young volunteers, verapamil (80 mg orally every 8 hours for 6 days) increased the mean peak blood concentration (Cmax) and the 12-hour area under the concentration-time curve (AUC) of ethanol (0.8 g/kg single oral dose) by 17% and 30%, respectively, compared to placebo. Verapamil AUCs were positively correlated to increased ethanol blood AUC values. Subjectively (i.e. each subject's perception of intoxication as measured on a visual analog scale), verapamil also significantly increased the area under the ethanol effect versus time curve but did not change the peak effect or time to peak effect.

MANAGEMENT: Patients treated with verapamil should be counseled to avoid alcohol consumption.

References

  1. Bauer LA, Schumock G, Horn J, Opheim K "Verapamil inhibits ethanol elimination and prolongs the perception of intoxication." Clin Pharmacol Ther 52 (1992): 6-10
  2. "Product Information. Isoptin (verapamil)." Knoll Pharmaceutical Company PROD (2001):

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Moderate

verapamil food

Applies to: verapamil

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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