Metoclopramide Digoxin

The effects of metoclopramide are antagonized by concurrent administration of anticholinergics or narcotic analgesics. Metoclopramide may decrease the absorption of digoxin and cimetidine and increase absorption of acetaminophen, tetracyclines, and levodopa Metoclopramide may alter die body s insulin requirements. 

Drugs that may affect metoclopramide include levodopa, anticholinergics, and narcotic analgesics. Drugs that may be affected by metoclopramide include alcohol, cimetidine, cyclosporine, digoxin, levodopa, MAO inhibitors, and succinylcholine. 

Manninen V, Melin J, Apajalahti A, Karesoja M. Altered absorption of digoxin in patients given propantheline and metoclopramide. Lancet 1973 1 398-9. 

Kirch W, Janisch HD, Santos SR, Duhrsen U, Dylewicz P, Ohnhaus EE. Effect of cisapride and metoclopramide on digoxin bioavailability. Eur J Drug Metab Pharmacokinet 1986 ll(4) 249-50. 

When digoxin is given in a slowly dissolving form, the plasma concentrations achieved are reduced by about one-third if metoclopramide is given at the same time (22) liquid or readily dissolvable solid forms of digoxin are unlikely to be affected. 

Manninen V, Apajalahti A, Simonen H, Reissell P. Effect of propantheline and metoclopramide on absorption of digoxin. Lancet 1973 1(7812) 1118-19. 

Metoclopramide increases gastric transit time, enhancing the absorption of substances absorbed in the small intestine (e.g., ethanol, cyclosporin) and decreasing the absorption of substances absorbed in the stomach (e.g., cimetidine, digoxin). Anticholinergic drugs and dopamine-function-enhancing substances such as levodopa reduce the effectiveness of metoclopramide. Because metoclopramide releases catecholamine, it should be used cautiously with monoamine oxidase inhibitors such as tranylcypromine. Because metoclopramide inhibits plasma cholinesterase, it increases the effectiveness of succinylcholine, a skeletal muscle relaxant. 

Noninterfering atenolol, deoxyprenaline, digoxin, gentamicin, hyoscine, metoclopramide, metronidazole, rnidodrine, nadolol, netilmicin, prednisolone, ranitidine, verapamil, vitamin B1... 

CAUTION. Bioavailability of digoxin gets altered due to the presence of such drugs as antacids, antineoplastic agents, cholestyramine resins, dietary fibre, erythromycin, neomycin, tetracyclines, metoclopramide, sulphasalazine and propantheline. 

Digoxin is nearly completely absorbed from the gut. In some patients, absorption may be deaeased due to digoxin inactivation by gut bacteria (i.e., Eubacterium lentum) Digoxin absorption is reduced by concomitant administration of antacids, cholestyramine, kaolin/pectin, tetracycline, and neomycin. Radiation malabsorption and gastrointestinal motility drugs such as metoclopramide can also reduce absorption. ... 

Digoxin Metoclopramide Propantheline Reduced digoxin absorption Increased digoxin absorption (due to changes in gut motility)... 

The serum levels of digoxin may be reduced by about one-third if metoclopramide is given with slowly dissolving forms of digoxin. No interaction is likely with digoxin in liquid form or in fast-dissolving preparations. 

A study in 11 patients taking slowly dissolving digoxin tablets Oriori) found that metoclopramide 10 mg three times a day for 10 days reduced the serum digoxin levels by 36%, from 0.72 to 0.46 nanograms/mL. The digoxin concentrations rose to their former levels when the metoclopramide was withdrawn. 

Another study in healthy subjects found metoclopramide 10 mg three times daily caused a 19% reduction in the AUC of digoxin and a 27% reduction in peak serum digoxin levels (digoxin formulation not stated). Yet another study in healthy subjects clearly showed that metoclopramide decreased the absorption of digoxin from tablets Lanoxin) but not capsules (Lanoxicaps) ... 

It would seem that the metoclopramide increases the motility of the gut to such an extent that full dissolution and absorption of some digoxin formulations does not occur. 

Metoclopramide Metoclopramide causes release of acetylcholine from cholinergic nerve terminals and can cause cholinergic adverse reactions, including bradydysrhyth-mias. In one case a patient had 22 episodes of bradycardia/asystole after taking metoclopramide and digoxin for several weeks. 

A 56-year-old man with hypertension suffered a 62% total body surface area burn (day 0) and on day 4 developed atrial fibrillation with a rapid ventricular rate, which was treated with amiodarone and digoxin. After pyloroplasty for a bleeding ulcer on day 20, he developed a postoperative ileus and was given metoclopramide 20 mg intravenously every 6 hours. Beginning on day 54, he started to have episodes of bradycardia and asystole. Some episodes required atropine and others resolved spontaneously. Some converted initially to a junctional rhythm, but all ultimately reverted to sinus tachycardia. Digoxin and metoclopramide were withdrawn and several hours later the bradydysrhythmias stopped. 

Schwartz BG. Metoclopramide and digoxin cause 22 episodes of bradyarrhyth-mias. Am J Med 2010 123 e5-6. 

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