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Nimodipine

Potential for Drug-Drug Interactions in the Elderly

  • Clinical Pharmacology
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Summary

Nimodipine is indicated for a variety of conditions in elderly patients. Elderly patients often have multiple morbidity and receive treatment with a variety of drugs. Therefore, it is important to investigate the possible pharmacokinetic and pharmacodynamic interactions of nimodipine with various drugs commonly prescribed for elderly patients.

There were no clinically relevant interactions of nimodipine with any of the following specific agents studied: the antiarrhythmics mexiletine, propafenone, disopyramide or quinidine, digoxin, the β-adrenoceptor antagonists propranolol or atenolol, nifedipine, warfarin, diazepam, indomethacin, ranitidine or gliben-clamide (glyburide).

However, there were some notable interactions. In epileptic patients taking the anticonvulsants carbamazepine, phénobarbital (phenobarbitone) and/or phenytoin, there was a 7-fold decrease in the area under the plasma concentration versus time curve (AUC) and an 8- to 10-fold decrease in the maximum plasma concentration of nimodipine. These effects were to be expected, considering the hepatic enzyme-inducing properties of these anticonvulsant drugs. Therefore concomitant use of these agents with oral nimodipine is not recommended. In contrast, epileptic patients treated with nimodipine and valproic acid (sodium valproate) showed an increase in both the AUC (approximately 50%) and maximum plasma concentrations (approximately 30%) of nimodipine, which may be explained by valproic acid inhibiting the presystemic oxidative metabolism of nimodipine.

Concomitant administration of cimetidine produced an approximate doubling of the bioavailability of nimodipine. This again was to be expected, considering the known inhibitory effect of cimetidine on cytochrome P450. However, no changes in haemodynamics, clinical or laboratory status or tolerability were observed, and dose adjustment did not appear to be clinically necessary.

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References

  1. Kazda S, Garthoff B, Krause HP, et al. Cerebrovascular effects of the calcium antagonistic dihydropyridine derivative nimodipine in animal experiments. Arzneimittelforschung 1982; 32: 331–8

    PubMed  CAS  Google Scholar 

  2. Murphy JJ. The role of calcium antagonists in the treatment of cerebrovascular disease. Drugs Aging 1992; 2: 1–6

    Article  PubMed  CAS  Google Scholar 

  3. Scriabine A, Schuurman T, Traber J. Pharmacological basis for the use of nimodipine in central nervous system disorders. FASEB J 1989; 3: 1799–1806

    PubMed  CAS  Google Scholar 

  4. Traber J, Gispen WH, editors. Nimodipine and central nervous system function: new vistas. Stuttgart: Schattauer-Verlag, 1989

    Google Scholar 

  5. Langley MS, Sorkin EM. Nimodipine: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in cerebrovascular disease. Drugs 1989; 37: 669–99

    Article  PubMed  CAS  Google Scholar 

  6. Wadworth AN, McTavish D. Nimodipine: a review of its pharmacological properties, and therapeutic efficacy in cerebral disorders. Drugs Aging 1992; 2: 262–86

    Article  PubMed  CAS  Google Scholar 

  7. Tettenborn D, Dycka J. Prevention and treatment of delayed ischaemic dysfunction in patients with aneurysmal subarachnoid hemorrhage. Stroke 1990; 21 Suppl. 4: IV85–9

    PubMed  CAS  Google Scholar 

  8. Bergener M, Reisberg B, editors. Diagnosis and treatment of senile-dementia: workshop papers held in Seefeld, Austria. Berlin: Springer-Verlag, 1989

    Google Scholar 

  9. Kelly JG, O’Malley K. Clinical pharmacokinetics of calcium antagonists: an update. Clin Pharmacokinet 1992; 22: 416–33

    Article  PubMed  CAS  Google Scholar 

  10. Ramsch K-D, Lücker PW, Wetzelsberger N, et al. Pharmacokinetics of intravenously and orally administered nimodipine. Clin Pharmacol Ther 1987; 41: 216

    Google Scholar 

  11. Eicher H, Hilgert D, Zeeh J, et al. Pharmacokinetics of nimodipine in multimorbid elderly patients with chronic brain failure. Arch Gerontol Geriatr 1992; 14: 309–19

    Article  PubMed  CAS  Google Scholar 

  12. Maruhn D, Siefert HM, Weber H, et al. Pharmacokinetics of nimodipine, I. communication: absorption, concentration in plasma and excretion after single administration of [14C] nimodipine in rat, dog and monkey. Arzneimittelforschung 1985; 35: 1781–6

    PubMed  CAS  Google Scholar 

  13. Suwelack D, Weber H, Maruhn D. Pharmacokinetics of nimodipine, II: communication — distribution, elimination and placental transfer in rats following single and multiple doses of [14C]nimodipine. Arzneimittel Forschung 1985; 35: 1787–94

    PubMed  CAS  Google Scholar 

  14. Rämsch K-D, Ahr G, Tettenborn D, et al. Overview on pharmacokinetics of nimodipine in healthy volunteers and in patients with subarachnoid hemorrhage. Neurochirurgia 1985; 28: 74–8

    PubMed  Google Scholar 

  15. Scherling D, Bühner K, Krause HP, et al. Biotransformation of nimodipine in rat, dog, and monkey. Arzneimittelforschung 1991; 41: 392–8

    PubMed  CAS  Google Scholar 

  16. Guengerich FP, Brian WR, Iwasaki M, et al. Oxidation of dihydropyridine calcium channel blockers and analogues by human liver cytochrome P-450IIIA 4. J Med Chem 1991; 34: 1838–44

    Article  PubMed  CAS  Google Scholar 

  17. Bailey DG, Spence JD, Munoz C, et al. Interaction of citrus juices with felodipine and nifedipine. Lancet 1991; 337: 268–9

    Article  PubMed  CAS  Google Scholar 

  18. Bailey DG, Arnold JMO, Spence JD. Grapefruit juice and drugs. How significant is the interaction? Clin Pharmacokinet 1994; 26: 91–8

    CAS  Google Scholar 

  19. Fuhr U, Maier A, Blume H, et al. Grapefruit juice increases oral nimodipine bioavailability. Eur J Clin Pharmacol 1994; 47: A100

    Google Scholar 

  20. Woodhouse K. Drugs and the liver, pt III: ageing of the liver and the metabolism of drugs. Biopharm Drug Dispos 1992; 13: 311–20

    Article  PubMed  CAS  Google Scholar 

  21. Gengo FM, Fagan SC, Krol G, et al. Nimodipine disposition and haemodynamic effects in patients with cirrhosis and age-matched controls. Br J Clin Pharmacol 1987; 23: 47–53

    Article  PubMed  CAS  Google Scholar 

  22. Mück W, Schmage N, Hörl W, et al. Pharmacokinetics and haemodynamic effects of nimodipine in patients with renal impairment. Pharm Res 1992; 9: 329

    Google Scholar 

  23. Lettieri JT, Krol GJ, Yeh S, et al. Effect of food on the absorption of nimodipine dosed as capsules. Pharm Res 1990; 7: 250

    Google Scholar 

  24. Kirch W, Kleinbloesem CH, Belz GG. Drug interactions with calcium antagonists. Pharmacol Ther 1990; 45: 109–36

    Article  PubMed  CAS  Google Scholar 

  25. Tartara A, Galimberti CA, Manni R, et al. Differential effects of valproic acid and enzyme-inducing anticonvulsants on nimodipine pharmacokinetics in epileptic patients. Br J Clin Pharmacol 1991; 32: 335–40

    Article  PubMed  CAS  Google Scholar 

  26. Reicher-Reiss H, Barasch E. Calcium antagonists in patients with heart failure: a review. Drugs 1991; 42: 343–64

    Article  PubMed  CAS  Google Scholar 

  27. Schlanz KD, Myre SA, Bottorff MB. Pharmacokinetic interactions with calcium channel antagonists, pt I. Clin Pharmacokinet 1991; 21: 344–56

    Article  PubMed  CAS  Google Scholar 

  28. Bailey DG, Freeman DJ, Melendez LJ, et al. Quinidine interaction with nifedipine and felodipine: pharmacokinetic and pharmacodynamic evaluation. Clin Pharmacol Ther 1993; 53: 354–9

    Article  PubMed  CAS  Google Scholar 

  29. Ziegler R, Wingender W, Horstmann R, et al. Do dihydropyridines influence pharmacokinetic parameters of beta-acetyldigoxin? Acta Pharmacol Toxicol 1986; 59 Suppl. 5: 179

    Google Scholar 

  30. Ziegler R, Horstmann R, Wingender W, et al. Do dihydropyridines influence pharmacokinetic and hemodynamic parameters of digoxin? J Clin Pharmacol 1987; 27: 712

    Google Scholar 

  31. Kuhlmann J. Effects of nifedipine and diltiazem on plasma levels and renal excretion of beta-acetyldigoxin. Clin Pharmacol Ther 1985; 37: 150–6

    Article  PubMed  CAS  Google Scholar 

  32. Kuhlmann J. Effects of verapamil, diltiazem, and nifedipine on plasma levels and renal excretion of digitoxin. Clin Pharmacol Ther 1985; 38: 667–73

    Article  PubMed  CAS  Google Scholar 

  33. Kuhlmann J, Ziegler R, Wingender W, et al. Beeinflussen Nisoldipin, Nitrendipin und Nimodipin die Pharmakokinetik und Wirksamkeit von Herzglykosiden? [Do nisoldipine, nitrendipine and nimodipine influence the pharmacokinetics and efficacy of cardiac glycosides? (abstract 256)] Z Kardiol 1986; 75 Suppl. 4: 78

    Google Scholar 

  34. Breuel HP, Heine PR, Mück W, et al. Chronic administration of nimodipine and propranolol in elderly normotensive subjects — an interaction study. Int J Clin Pharmacol Ther 1995; 33: 103–8

    PubMed  CAS  Google Scholar 

  35. Weber H, Horstmann R, Wingender W, et al. Absence of pharmacokinetic and pharmacodynamic interactions between propranolol and nimodipine in healthy volunteers. Naunyn-Schmiedebergs Arch Pharmacol 1988; 338 (Suppl.): 284

    Google Scholar 

  36. Horstmann R, Weber H, Wingender W, et al. Does nimodipine interact with beta-adrenergic blocking agents? Eur J Clin Pharmacol 1989; 36 (Suppl.): A258

    Google Scholar 

  37. McTavish D, Sorkin EM. Verapamil: an updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension. Drugs 1989; 38: 19–76

    Article  PubMed  CAS  Google Scholar 

  38. Buckley MM-T, Grant SM, Goa KL, et al. Diltiazem: a reappraisal of its pharmacological properties and therapeutic use. Drugs 1990; 39: 757–806

    Article  PubMed  CAS  Google Scholar 

  39. Schlanz KD, Myre SA, Bottorff MB. Pharmacokinetic interactions with calcium channel antagonists, pt II. Clin Pharmacokinet 1991; 21: 448–60

    Article  PubMed  CAS  Google Scholar 

  40. Elliott HL, Meredith PA, McNally C, et al. The interactions between nisoldipine and two β-adrenoceptor antagonists — atenolol and propranolol. Br J Clin Pharmacol 1991; 32: 379–85

    Article  PubMed  CAS  Google Scholar 

  41. Shaw-Stiffel TA, Walker SE, Ogilvie RI, et al. Pharmacokinetic and pharmacodynamic interaction during multiple-dose administration of nisoldipine and propranolol. Clin Pharmacol Ther 1994; 55: 661–9

    Article  PubMed  CAS  Google Scholar 

  42. Breuel HP, Mück W, Heine, PR, et al. The influence of nimodipine on haemodynamic parameters and peak and trough plasma concentrations of nifedipine chronically administered to elderly hypertensive patients. Int J Clin Pharmacol Ther 1995; 33: 109–13

    PubMed  CAS  Google Scholar 

  43. Meyer FB, Anderson RE, Sundt Jr TM. Anticonvulsant effects of dihydropyridine Ca2+ antagonists in electrocortical shock seizures. Epilepsia 1990; 31: 68–74

    Article  PubMed  CAS  Google Scholar 

  44. Brandt L, Saeveland H, Ljungren B, et al. Control of epilepsy partialis continuans with intravenous nimodipine. Report of two cases. J Neurosurg 1988; 69: 949–50

    Article  PubMed  CAS  Google Scholar 

  45. Bahls FH, Ozuna J, Ritchie DE. Interactions between calcium channel blockers and the anticonvulsants carbamazepine and phenytoin. Neurology 1991; 41: 740–2

    Article  PubMed  CAS  Google Scholar 

  46. Ketter TA, Post RM, Worthington K. Principles of clinically important drug interactions with carbamazepine, pt II. J Clin Psychopharmacol 1991; 11: 306–13

    PubMed  CAS  Google Scholar 

  47. Heine PR, Weyer G, Breuel HP, et al. Lack of interaction between diazepam and nimodipine during chronic oral administration to healthy elderly subjects. Br J Clin Pharmacol 1994; 38: 39–43

    Article  PubMed  CAS  Google Scholar 

  48. Mück W, Heine PR, Schmage N, et al. Steady-state pharmacokinetics of nimodipine during chronic administration of indomethacin in elderly healthy volunteers. Drug Res. In press

  49. Mück W, Wingender W, Sciberling M, et al. Influence of the H2-receptor antagonists cimetidine and ranitidine on the pharmacokinetics of nimodipine in healthy volunteers. Eur J Clin Pharmacol 1992; 42: 325–8

    Article  PubMed  Google Scholar 

  50. Todd PA, Faulds D. Felodipine: a review of the pharmacology and therapeutic use of the extended release formulation in cardiovascular disorders. Drugs 1992; 44: 251–77

    Article  PubMed  CAS  Google Scholar 

  51. Mück W, Heine PR, Breuel HP, et al. The effect of multiple oral dosing of nimodipine on glibenclamide pharmacodynamics and pharmacokinetics in elderly patients with Type-2 diabetes mellitus. Int J Clin Pharmacol Ther 1995; 33: 89–94

    PubMed  Google Scholar 

  52. Monges AM, Pisano P, Aujoulat P, et al. 1H nuclear magnetic resonance and clinical studies of interaction of calcium antagonists and hypoglycemic sulfonylureas. Fundam Clin Pharmacol 1991; 5: 527–38

    Article  PubMed  CAS  Google Scholar 

  53. Prescott LF. Clinically important drug interactions. In: Speight TM, editor. Avery’s drug treatment. 3rd ed. Auckland: Adis, 1987: 255–82

    Google Scholar 

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  1. Institute of Clinical Pharmacology International, Bayer AG, Wuppertal, D-42096, Germany

    Wolfgang Mück, Gertrud Ahr & Jochen Kuhlmann

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Mück, W., Ahr, G. & Kuhlmann, J. Nimodipine. Drugs & Aging 6, 229–242 (1995). https://doi.org/10.2165/00002512-199506030-00006

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