Verapamil dosage

Duchenne muscular dystrophy yerapam may decrease neuromuscular transmission in patients with Duchenne muscular dystrophy and prolong recovery from the neuromuscular blocking agent vecuronium. Decrease in verapamil dosage may be necessary. 

In adult patients without heart failure or sinoatrial or atrioventricular nodal disease, parenteral verapamil can be used to terminate supraventricular tachycardia, although adenosine is the agent of first choice. Verapamil dosage is an initial bolus of 5 mg administered over 2-5 minutes, followed a few minutes later by a second 5 mg bolus if needed. Thereafter, doses of 5-10 mg can be administered every 4-6 hours, or a constant infusion of 0.4 mcg/kg/min may be used. 

A woman taking phenytoin who was then also given verapamil had persistently subnormal plasma verapamil levels (less than 50 nanograms/mL) despite inereases in the verapamil dosage from 80 mg twice daily to 160 mg three times daily. When the phenytoin was stopped, her plasma verapamil levels rose to the expected concentrations. 

Information seems to be limited but the interaction would appear to be established and clinically important, although its incidence is probably low. Anticipate the need to reduce the felodipine or verapamil dosage if erythromycin or clarithromycin, or possibly also telithromycin, is added. Nifedipine may also interact. Other reports suggests that the cardiac toxicity of erythromycin may be increased by verapamil, and diltiazem, and the authors of one of these reports consider that erythromycin should not be used with CYP3A4 inhibitors (that is diltiazem and verapamil). There seem to be no reports of interactions between any of the other calcium-channel blockers and macrolides. However, because of the theoretical possibility of an interaction, many of the manufacturers of calcium-channel blockers warn of the possibility of increased plasma levels and the need to either avoid use with macrolides such as erythromycin, or troleandomycin, or to monitor and reduce doses where necessary. 

All antiarrhythmic dra are used cautiously in patients with renal or hepatic disease. When renal or hepatic dysfunction is present, a dosage reduction may be necessary. All patients should be observed for renal and hepatic dysfunction. Quinidine and procainamide are used cautiously in patients with CHF. Disopyramide is used cautiously in patients with CHF, myasthenia gravis, or glaucoma, and in men with prostate enlargement. Bretylium is used cautiously in patients with digitalis toxicity because the initial release of norepinephrine with digitalis toxicity may exacerbate arrhythmias and symptoms of toxicity. Verapamil is used cautiously in patients with a history of serious ventricular arrhythmias or CHF. Electrolyte disturbances such as hypokalemia, hyperkalemia, or hypomagnesemia may alter the effects of the antiarrhythmic dru . Electrolytes are monitored frequently and imbalances corrected as soon as possible... 

A direct in vivo assessment was carried out with the single-pass perfusion approach in the human jejunum by using the Loc-I-Gut technique with R/S-verapamil (log D6 5 2.7, octanol/water pH 7.4 MW 455 Da) as the model compound for CYP 3A4 and P-gp-mediated local intestinal kinetics [2, 34, 35, 122] (see Figs. 7.7 and 7.9). The Peff for both enantiomers at each of the concentrations (4.0, 40, 120, and 400 mg L-1) was 2.5 x 10 4, 4.7 x 105.5 x 104 and 6.7 x 104 cm s-1, respectively (Fig. 7.15) [34, 35], A luminal concentration of 400 mg L 1 is expected to be achieved in the upper part of the small intestine after oral administration of a 100-mg dose of verapamil in an immediate-release dosage form [1, 34, 35], The three other perfusate concentrations represent fractions of the dose when 30%, 10%, and 1%, respectively are left to be absorbed [34, 35], The increased in vivo jejunal Peff of R/S-vcrapamil, along with its increased luminal perfusate concentration, is in accordance with a saturable efflux mechanism mediated by... 

Angina Usual initial dose is 80 to 120 mg 3 times/day 40 mg 3 times/day may be warranted if patients may have increased response to verapamil (eg, decreased hepatic function, elderly). Base upward titration of safety and efficacy evaluated about 8 hours after dosing. Increase dosage daily (eg, unstable angina) or weekly until optimum clinical response is obtained. 

Hypertension PO 50 mg once a day. If 50 mg once a day produces an inadequate BP response, may increase dosage to 50 mg twice a day. If patient is concurrently receiving erythromycin, saquinavir, verapamil, or fluconazole, reduce initial dose to 25 mg once a day. 

Calcium channel blockers minimally interfere with stimulus-secretion coupling in glands and nerve endings because of differences between calcium channel type and sensitivity in different tissues. Verapamil has been shown to inhibit insulin release in humans, but the dosages required are greater than those used in management of angina. 

Ozkan Y, Yilmaz N, Ozkan SA, Birvol I. 2000. High-performance liquid chromatographic analysis of verapamil and its application to determination in tablet dosage forms and to drug dissolution studies. Farmaco 55(5) 376-382. 

Our first stereospedfic bioequivalence evaluation using verapamil formulations was a pilot study conducted in 24 healthy male volunteers. The study compared the bioavailability of two sustained-release dosage forms and an immediate release formulation of racemic verapamil in a three-way cross-over study. Table 2 summarizes the results observed for verapamil. Table 3 the results for norverapamil. First, pharmacokinetic... 

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... 

A 28-year-old man with migraine and vascular pain of the face was given verapamil 480 mg/day when sumatriptan did not control the pain. Verapamil was withdrawn after 1 month and reintroduced in a dosage of 960 mg/day after a new episode of pain. He then developed arthralgia in the right hand and arm, which disappeared after withdrawal and recurred after rechallenge. 

Verapamil is both a snbstrate and an inhibitor of CYP3A4, which is inhibited by clarithromycin and erythromycin. Giving these macrolide antibiotics dnring verapamil therapy is likely to rednce the first-pass metabolism of verapamil, increase its systemic availability, and impair its elimination. In patients taking this combination, verapamil should be started in a low dosage and its hemodynamic effects should be monitored closely. 

The luminal concentration in the upper part of the small intestine after oral administration of a 100 mg dose of verapamil in an immediate-release dosage form [1, 34, 35] is expected to reach 400 mg/l. The three other... 

Vogelpoel H, Welink J, Amidon GL, et al. Biowaiver monographs for immediate release solid oral dosage forms based on biopharmaceutics classification system (BCS) literature data verapamil hydrochloride, propranolol hydrochloride, and atenolol. J Pharm Sci 2004 93(8) 1945-1956. 

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