Verapamil interactions

Hedman A, Angelin B, Arvidsson A, et al. Digoxin-verapamil interaction reduction of biliary but not renal digoxin clearance in humans. Clin Pharmacol Ther 1991 49 256-262. 

Talinolol, a good P-gp substrate, is eliminated from the body mainly by intestinal and renal excretion with minimal metabolism in humans. In a clinical study, a P-gp-mediated interaction between talinolol and verapamil has been reported (45). The inhibitory effect of verapamil on the intestinal secretion of talinolol was determined in six healthy volunteers by using the intestinal perfusion technique. While perfusing the small intestine with a verapamil-free solution, the mean intestinal secretion rate of talinolol was 4.0 pg/min after an intravenous dose of talinolol. The intestinal secretion rate decreased to 2.0 pg/min when a verapamil-containing solution was perfused (45). Similar to the clinical data, talinolol-verapamil interaction was also observed in rats. Coadministration of verapamil (4 mg/kg, PO) resulted in a 2.5- and 2.2-fold increase in the plasma oral AUC for S- and //-talinolol, respectively, after an oral dose of racemic talinolol in rats. On the other hand, after an intravenous dose of racemic talinolol, the inhibitory effect of verapamil on talinolol was less significant and there was only a 40% and 30% increase in AUC, respectively, for S- and //-talinolol (46). These results suggest that the larger increase in AUC of talinolol ( 2- to 2.5-fold) after oral administration was likely due to the combination of an... 

SEDA-22,216). Two confirmations of these observations have been published. In a retrospective study of 103 transplant patients verapamil and diltiazem, but not nifedipine or isradipine, caused a significant increase in plasma ciclosporin concentrations (186). The effect of verapamil and diltiazem on ciclosporin concentrations was independent of dosage. In a crossover comparison between verapamil, felodipine, and isradipine in 22 renal transplant recipients, verapamil interacted... 

Pedersen KE, Dorph-Pedersen A, Hvidt S, Klitgaard NA, Nielsen-Kudsk F. Digoxin-verapamil interaction. Clin Pharmacol Ther 1981 30(3) 311-16. 

The effects of a combination of erythromycin and verapamil on the pharmacokinetics of a single dose of simvastatin have been studied in a randomized, double-blind, cross-over study in 12 healthy volunteers simultaneously taking the three drugs. Both erythromycin and verapamil interacted with simvastatin, producing significant increases in the serum concentrations of simvastatin and its active metabolite simvastatin acid. The mean C ax of active simvastatin acid was increased about five-fold and the AUCo 24 four-fold by erythromycin verapamil increased the C ax of simvastatin acid 3.4-fold and the AUCo 24 2.8-fold. There was a substantial interindividual variation in the extent of these interactions. Concomitant use of erythromycin, verapamil, and simvastatin should be avoided (35). 

Keech AC, Harper RW, Harrison PM, Pitt A, McLean AJ. Extent and pharmacokinetic mechanisms of oral atenolol-verapamil interaction in man. EurJClin Pharmacol ( 9SS) 35, 363-6. 

The documentation of the digitoxin and verapamil interaction is limited, but the interaction appears to be established. Downward dosage adjustment may be necessary, particularly in some patients. ... 

RobsonRA,FraenkelM,BarrattLJ,BirkettDJ. Cyclosporin-verapamil interaction. BrJC/m Pharmacol 9 ) 25, 402-3. 

Sabate I, Grino JM, Castelao AM, Ortola J. Evaluation of cyclosporin-verapamil interaction, with observations on parent cyclosporin and metabolites. Clin Chem (1988) 34, 2151. 

The clinical relevance of the verapamil interaction was demonstrated in a 63-year-old man, who developed rhabdomyolysis about 1 month after extended-release verapamil 240 mg daily was added to established treatment with simvastatin 40 mg daily and ciclosporin. Verapamil and simvastatin were discontinued and he recovered over the following 14 days. An in vitro study using human liver microsomes also found that verapamil moderately inhibits simvastatin metabolism. " ... 

Fig. 20.13. Potential H-bonding energy, released upon interaction with the transmembrane domains of P-gp (in arbitrary energy units, EU) for progesterone (1), propranolol (2), amitriptyline (3), diltiazem (4), amiodarone (5), colchicine (7), gramicidin S (8), daunorubicin (9), vinblastine (10), cyclosporin A, in comparison with verapamil...

The type of interaction of verapamil (solid bar) in the presence of one of the other compounds is indicated Cooperative stimulation (hatched bars) allosteric noncompetitive inhibition (cross-hatched bars) and competitive inhibition (gray bars). (Adapted from Ref. [57].)... 

Voigt W, Romanelli MN, Femoine H, Mannhold R, Dei S, Teodori E, Gualtieri F. (1995) Structural dependence of the allosteric interaction of semi-rigid verapamil analogues with dihydropyridine-binding in kitten heart. Eur J Pharmacol 291 255-264. 

Vincristine resistance has been studied in Chinese hamster ovary cell lines cells resistant to vincristine also are resistant to vinblastine and vindesine. Suggestions were made that, in cells with relatively low levels of drug resistance, at least two prominent mechanisms of resistance can occur (22). In the first instance, cellular resistance may be attributable to membrane alterations that are reversible, functionally, by treatment with verapamil. In the second, resistance has been postulated to be due to an altered sensitivity of tubulin to the effects of the drugs the primary basis for postulating an altered interaction with tubulin was that a subgroup of cells resistant to vincristine showed enhanced sensitivity to taxol, a drug that can stabilize microtubules. It should be emphasized that differential sensitivities of tubulins from different tumor cells to the effects of vincristine or vinblastine has been proposed as a basis for the susceptibilities of cells to the cytotoxic effects of such drugs (23). Differences have been described in the electrophoretic patterns for tubulins obtained from vin-... 

Drug/Food interactions Nifedipine, amlodipine, and verapamil may be administered without regard to meals. 

Drugs that interact may include beta blockers, indomethacin, verapamil, and clonidine. 

Drugs that may interact with dantrolene include clofibrate, estrogens, warfarin, and verapamil. 

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