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Drug Interactions between amlodipine and cyclosporine

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

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Interactions between your drugs

Moderate

cycloSPORINE amLODIPine

Applies to: cyclosporine and amlodipine

MONITOR: Coadministration of amlodipine with cyclosporine may increase the plasma concentrations and the risk of adverse effects of both drugs. The proposed mechanism by which amlodipine increases cyclosporine exposure has not been clearly delineated, but may involve inhibition of CYP450 3A4 and/or P-glycoprotein; cyclosporine may increase amlodipine exposure by inhibiting its metabolism via the CYP450 3A4 enzymatic pathway. Studies have revealed that coadministration of amlodipine with cyclosporine in renal transplant patients resulted in variable increases in trough concentrations of cyclosporine (average 0% to 40%).

MANAGEMENT: Although the interaction has not been studied, caution is advised if amlodipine and cyclosporine are used in combination, particularly in renal transplant patients. Cyclosporine blood levels and renal function should be monitored more closely whenever amlodipine is added to or withdrawn from therapy, and the cyclosporine dosage adjusted as necessary. Similarly, dosage adjustments as well as clinical and laboratory monitoring of amlodipine should be considered whenever cyclosporine is added to or withdrawn from therapy. During concomitant treatment, patients should be advised to notify their physician if they experience signs and symptoms of cyclosporine toxicity such as nausea, vomiting, diarrhea, abdominal pain, dizziness, fatigue, headache, tremors, and convulsions or adverse effects associated with amlodipine such as hypotension or edema. In addition, concurrent use may also increase the risk of gingival overgrowth.

References

  1. "Product Information. Norvasc (amlodipine)." Pfizer U.S. Pharmaceuticals PROD (2002):
  2. "Product Information. SandIMMUNE (cycloSPORINE)." Apothecon Inc (2022):
  3. "Product Information. Neoral (cycloSPORINE)." Sandoz Pharmaceuticals Corporation PROD
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  5. Cerner Multum, Inc. "Australian Product Information." O 0
  6. Cai J, Huang Z, Yang G, et al. "Comparing antihypertensive effect and plasma ciclosporin concentration between amlodipine and valsartan regimens in hypertensive renal transplant patients receiving ciclosporin therapy." Am J Cardiovasc Drugs 11 (2011): 401-9
View all 6 references

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Drug and food interactions

Moderate

cycloSPORINE food

Applies to: cyclosporine

GENERALLY AVOID: Administration with grapefruit juice (compared to water or orange juice) has been shown to increase blood concentrations of cyclosporine with a relatively high degree of interpatient variability. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

GENERALLY AVOID: Administration with red wine or purple grape juice may decrease blood concentrations of cyclosporine. In 12 healthy volunteers, 12 ounces total of a merlot consumed 15 minutes prior to and during cyclosporine administration (single 8 mg/kg dose of Sandimmune) decreased cyclosporine peak blood concentration (Cmax) and systemic exposure (AUC) by 38% and 30%, respectively, compared to water. The time to reach peak concentration (Tmax) doubled, and oral clearance increased 50%. Similarly, one study were 12 healthy patients were administered purple grape juice and a single dose of cyclosporine showed a 30% and a 36% decrease in cyclosporine systemic exposure (AUC) and peak blood concentration (Cmax), respectively. The exact mechanism of interaction is unknown but may involve decreased cyclosporine absorption.

MONITOR: Food has been found to have variable effects on the absorption of cyclosporine. There have been reports of impaired, unchanged, and enhanced absorption during administration with meals relative to the fasting state. The mechanisms are unclear. Some investigators found an association with the fat content of food. In one study, increased fat intake resulted in significantly increased cyclosporine bioavailability and clearance. However, the AUC and pharmacodynamics of cyclosporine were not significantly affected, thus clinical relevance of these findings may be minimal.

MANAGEMENT: Patients receiving cyclosporine therapy should be advised to either refrain from or avoid fluctuations in the consumption of grapefruits and grapefruit juice. Until more data are available, the consumption of red wine or purple grape juice should preferably be avoided or limited. All oral formulations of cyclosporine should be administered on a consistent schedule with regard to time of day and relation to meals so as to avoid large fluctuations in plasma drug levels.

References

  1. Honcharik N, Yatscoff RW, Jeffery JR, Rush DN "The effect of meal composition on cyclosporine absorption." Transplantation 52 (1991): 1087-9
  2. Ducharme MP, Provenzano R, Dehoornesmith M, Edwards DJ "Trough concentrations of cyclosporine in blood following administration with grapefruit juice." Br J Clin Pharmacol 36 (1993): 457-9
  3. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8
  4. Hollander AAMJ, Vanrooij J, Lentjes EGWM, Arbouw F, Vanbree JB, Schoemaker RC, Vanes LA, Vanderwoude FJ, Cohen AF "The effect of grapefruit juice on cyclosporine and prednisone metabolism in transplant patients." Clin Pharmacol Ther 57 (1995): 318-24
  5. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
  6. Tan KKC, Trull AK, Uttridge JA, Metcalfe S, Heyes CS, Facey S, Evans DB "Effect of dietary fat on the pharmacokinetics and pharmacodynamics of cyclosporine in kidney transplant recipients." Clin Pharmacol Ther 57 (1995): 425-33
  7. Yee GC, Stanley DL, Pessa LJ, et al. "Effect of grrapefruit juice on blood cyclosporin concentration." Lancet 345 (1995): 955-6
  8. Ducharme MP, Warbasse LH, Edwards DJ "Disposition of intravenous and oral cyclosporine after administration with grapefruit juice." Clin Pharmacol Ther 57 (1995): 485-91
  9. Ioannidesdemos LL, Christophidis N, Ryan P, Angelis P, Liolios L, Mclean AJ "Dosing implications of a clinical interaction between grapefruit juice and cyclosporine and metabolite concentrations in patients with autoimmune diseases." J Rheumatol 24 (1997): 49-54
  10. Min DI, Ku YM, Perry PJ, Ukah FO, Ashton K, Martin MF, Hunsicker LG "Effect of grapefruit juice on cyclosporine pharmacokinetics in renal transplant patients." Transplantation 62 (1996): 123-5
  11. 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
  12. Tsunoda SM, Harris RZ, Christians U, et al. "Red wine decreases cyclosporine bioavailability." Clin Pharmacol Ther 70 (2001): 462-7
  13. Oliveira-Freitas VL, Dalla Costa T, Manfro RC, Cruz LB, Schwartsmann G "Influence of purple grape juice in cyclosporine availability." J Ren Nutr 20 (2010): 309-13
View all 13 references

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Moderate

amLODIPine food

Applies to: amlodipine

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

amLODIPine food

Applies to: amlodipine

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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Minor

amLODIPine food

Applies to: amlodipine

The consumption of grapefruit juice may slightly increase plasma concentrations of amlodipine. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Data have been conflicting and the clinical significance is unknown. Monitoring for calcium channel blocker adverse effects (e.g., headache, hypotension, syncope, tachycardia, edema) is recommended.

References

  1. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8
  2. 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
  3. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  4. Vincent J, Harris SI, Foulds G, Dogolo LC, Willavize S, Friedman HL "Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine." Br J Clin Pharmacol 50 (2000): 455-63
  5. Josefsson M, Ahlner J "Amlodipine and grapefruit juice." Br J Clin Pharmacol 53 (2002): 405; discussion 406
  6. Kane GC, Lipsky JJ "Drug-grapefruit juice interactions." Mayo Clin Proc 75 (2000): 933-42
View all 6 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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