Therapeutic Indications
Heart failure. Supraventricular tachyarrythmias (particularly atrial fibrillation).
Posology and Methods of Administration
When given orally, loading dose of digoxin for rapid digitalisation is 0.5 –
mg,then the drug is used 0.25 mg at 6-hourly intervals until the necessarytherapeutic effect is reached. Maximum daily dose is 1.5 mg. If rapiddigitalisation is not required the dose may be 0.25 mg once or twice aday. Steady-state plasma-digoxin concentrations are reached withinapproximately 7 days. The usual maintenance dose is 0.125 to 0.25 mgdaily. In elderly patients therapy should generally be initiatedgradually and with lower digitalisation.
In case of renalimpairment the dose should be reduced according to glomerularfiltration rate (GFR) (GFR 20–50 ml/min — 0.25 mg daily; GFR
10-20 ml/min — 0.125-0.25 mg daily; GFR < 10 ml/min — up to 0.125 mg daily).
Children. DIGOXIN–GRINDEKS is not used in pediatric practice.
Elderlypatients. Because of poor renal status and small body-mass the dose forelderly patients should be smaller than for middle-aged patients. Incase of elderly patients serum-digoxin concentration should bemonitored and hypokalemia avoided.
Contraindications
Ventriculartachycardia, atrial fibrillation, hypertrophic obstructivecardiomyopathy (except severe cardiac failure), Wolff-Parkinson-Whitesyndrome (especially if it is accompanied by atrial fibrillation),periodically complete or II level heart block, hypersensitivity todigoxin or other cardiac glycosides. Digoxin is contraindicated ifheart rate disturbance is caused by intoxication with cardiac digitalisglycosides.
Special Warnings and Special Precautions for Use
Digoxinshould be used with caution in patients with acute myocardial failure(myocarditis, recent myocardial infarction), in case of advanced heartfailure or severe pulmonary disease. Large maintenance doses should beavoided.
Digoxin should be used with caution in patients with heartblock of various levels and sinus node disorders if they have atrialfibrillation.
Reduced initial doses should be given to patients who have received other cardiac glycosides within the previous two weeks.
Digoxin should be withdrawn 24-48 before planned cardioversion because it may provoke life-threatening heat rate failure.
Digoxindoses should be generally reduced and plasma-digoxin concentrationsmonitored in patients with renal impairment, in the elderly, and inpremature infants.
The effects of digoxin are enhanced byhypokalaemia, hypomagnesaemia, hypercalcaemia, hypoxia andhypothyroidism and doses may need to be reduced. Resistance to theeffects of digoxin may occur in hyperthyroidism.
When digoxin isused at maintenance doses ECG may show prolonged PR (pulse rate)interval and lowered (reduced) ST segment. When using digoxin exerciseECG showed misleading ST-T segment changes, which are not the evidenceof intoxication but are temporary changes associated with the mechanismof this drug effect.
DIGOXIN–GRINDEKS tablets contain sucrose andglucose. Patients with rare hereditary problems of fructoseintolerance, glucose-galactose malabsorption or sucrase-isomaltaseinsufficiency should not take this medicine.
Interaction with Other Medicinal Products and Other Forms of Interaction
Thiazidesand loop diuretics when used together with digoxin may causehypokalaemia and also hypomagnesaemia which may lead to cardiacarrhytmias. Other causes of hypokalaemia include treatment withcorticosteroids, amphotericin or carbenoxolone. Hypercalcaemia may alsoincrease toxicity and intravenous administration of calcium salts isbest avoided in patients taking cardiac glycosides.
Plasma - digoxinconcentrations may be significantly increased by quinidine, amiodaroneand propafenone. Other antiarrhythmic drugs may have additive effectson the myocardium increasing the likelihood of adverse effects. Betablockers may potentiate bradycardia due to digoxin. Verapamil mayincrease digoxin concentrations in plasma. Nifedipine may also increaseconcentrations of digoxin in plasma but it does not occur always.Concomitant use of digoxin and verapamil or beta blockers increases thelikelihood of atrioventricular heart block.
Erythromycin,tetracycline, trimethoprim, angiotensin-converting enzyme inhibitors(for example, captopril), angiotensin II receptor blockers (forexample, telmisartane), proton pump inhibitors, and non-steroidanti-inflammatory drugs may increase digoxin concentrations in plasma.
Rifampicin may reduce serum-digoxin concentrations by inducing its metabolism, reducing digoxin concentration in plasma.
Cholestyramine,cholestipol, sulfasalazine, sucralfate, neomycin, magnesium containingantidiarrhoea drugs and antacids reduce the absorption of digoxin.
Pregnancy and Lactation
Digoxincrosses the placenta; studies have shown that digoxin is distributedinto breast milk, although the amount was considered too small to havean effect on the child. No significant adverse effects associated withuse of digoxin have been observed in foetus or neonate. If digoxin hasbeen used during pregnancy it may result in low birth-weights ininfants. Overdose of digoxin may cause foetal death. During pregnancythe clearance of digoxin increases.
Effects on ability to drive and use machines
Digoxin does not affect ability to drive and operate machines.
Undesirable Effects
Digoxincommonly produces adverse effects. These are rarely observed if usualtherapeutic doses are administered taking into account patient’s healthstatus and other concomitantly used drugs. Adverse effects aredifferent in adults and children.
Adverse effects on the heart.Toxic doses may cause heart rate and conduction disorders; most oftenare ventricular extrasystoles of bigeminy and trigeminy type. Reportedare atrial tachycardia with atrioventricular block, in case of whichthe pulse frequency is not high. ECG may show prolonged PR (pulse rate)interval and lowered (reduced) ST segment, which are not the evidenceof digoxin intoxication if there are no other symptoms.
Extracardial adverse effects.More often these are gastrointestinal disorders: loss of appetite,nausea, vomiting and diarrhoea. Common are weakness, apathy, fatigue,headache, visual disturbances, depression and even psychosis. Prolongeduse of digoxin cause gynaecomastia. Skin itch, urticaria andthrombocytopenia are rare. In connection with oral administration ofdigoxin reported are bowel ischemia and bowel necrosis.
Children. Extracardial adverse effects in children are reported rarely.
Mainintoxication symptoms are various heart rate disorders, for example,conduction disorders, supraventricular tachyarrythmias, etc. Inchildren, particularly, in infants, digoxin intoxication manifestsitself in sinus bradycardia. If at the result of digoxin administrationin children heart rate disorders occur, first of all, overdose shouldbe suspected, and when this case is excluded, other reasons should befound.
Overdose
The margin between thetherapeutic and toxic doses is small. Administration of digoxin 10-15mg may be fatal to 50% of adult persons. Symptoms of digoxin toxicityappear gradually and are described in Undesirable Effects. The mostserious are heat rate disorders, which may be fatal due to asystolecaused by atrial fibrillation or block. If a large dose have been takenoccasionally or in attempt of suicide immediately after gastric lavageshould be done. Activated charcoal may be given to reduce theabsorption from gastrointestinal tract. Dialysis is not effective incase of life-threatening poisoning.
Atropine is given intravenouslyto correct bradycardia. Pacing may be necessary if atropine is noteffective. Lidocaine or phenytoin are effective in case of ventriculararrhythmia. In case of bradyarrhythmia or ventricular arrhythmiaspecific digoxin antisubstances, –F (ab) fragments, may be introduced(Digibind).
