1. Known hypersensitivity to cardiac glycosides.
2. Caution in preterm infants, especially extreme immaturity.
3. Caution in infants with renal impairment.
4. Caution in infants with acute myocarditis, bradyarrhythmias (especially heart block).
5. Ventricular dysrhythmias.
6. Pre-existing hypokalaemia may precipitate adverse reactions.

Clinical Pharmacology

Digoxin is a digitalis glycoside with positive inotropic and negative chronotopic actions. Increases myocardial catecholamine levels (low doses) and inhibits sarcolemmal sodium potassium - ATPase (higher doses) to enhance contractility. Indirectly increases vagal activity, thereby slowing SA and AV node conduction. Other effects include peripheral, splanchnic, and perhaps pulmonary vasoconstriction, and reduced CSF production.

Rapid but variable absorption (52-79%) from the gastrointestinal tract. IM absorption similar variability but IM injection causes pain and local soft tissue injury. Large distribution volume: Vd in term infant (12-16 L/kg) > preterm infant (4-6 L/kg). Rapid distribution to peripheral tissue compartments (elimination half life is reported as 61-170 hours in preterm infants and 35-45 hours in term infants) but the time to reach steady state is much slower. Serum concentration peaks 30-90 minutes after an oral dose with myocardial peak occurring after 4-6 hours. Accumulates in the myocardium: myocardial to serum ratio 149:1. Low binding (20%) to human plasma protein. Probably not significantly metabolised. Eliminated mainly via the kidneys (75% unchanged) by glomerular filtration and tubular secretion.

Main pharmacodynamic property of digoxin is its ability to increase the force of contraction of the myocardium - positive inotropic action. Also slows the heart rate and produces changes in activity of SA node, the atria, and AV node - negative chronotropic effect. Inotropic effect occurs within 30 minutes. Non toxic cardiac effects include shortening of QTC interval, depression of STsegment, diminished amplitude of T wave, and slowing of heart rate.

Possible Adverse Effects

1. Gastrointestinal disturbances (nausea, vomiting, diarrhoea).
2. Lethargy
3. Bradycardia
4. Cardiac arrhythmias (PVCs, PAT with block, bigeminy, sinus arrhythmia, sinoatrial block, atrioventricular junctional or multifocal ventricular tachycardia).
5. Toxicity is enhanced by hypokalaemia.

Special Considerations

1. Dosing regime determined by maturity and renal function.
2. Serum electrolytes should be stabilised prior to digitalisation. Monitor urea, electrolytes, creatinine during therapy.
3. Obtain baseline ECG prior to first digitalising dose of digoxin, prior to the final digitalising dose and at intervals throughout treatment.
4. Serum digoxin levels should be measured during treatment. Obtain specimen 10 - 12 hours after last loading dose and repeat at intervals. Repeat after dose changed. Usual therapeutic range 1.0-2.6 nmol/L. Serum levels >4.6 nmol/L are considered to be in the toxic range.
5. Management of digoxin toxicity: stop digoxin, stabilise fluids and electrolytes, treat arrhythmias.

Interactions

1. Cisapride and metoclopramide may decrease absorption of digoxin.
2. Indomethacin, amiodarone, erythromycin and spironolactone may increase digoxin levels
3. Amiloride inhibits digoxin effect.
4. Amphotericin B, corticosteroids, diuretics and ticarcillin: hypokalaemia or hypomagnesaemia predisposing patient to digitalis toxicity.