Thyrotoxic patients are relatively resistant to effects of digitalis glycosides and may need reduced doses as treatment with antithyroid drugs (carbimazole, thiamazole) progresses, whereaspatients with hypothyroidism may need increased doses of digitalis glycosides as treatment with thyroid hormones progresses. Carbimazole has been shown to reduce serum digoxin in healthysubjects.
The observation of relatively low plasma digoxin levels in a patient taking carbimazole prompted a further study in 10 healthy subjects. In 9 out of 10, steady-state peak serum digoxin levels were reduced by 23 % (from
1.72 to 1.33 nanograms/mL) by a single 60mg dose of carbimazole, but in other subject serum digoxin levels were increased. Other pharmacokinetic parameters were unaffected.
Carbimazole abolished systolic blood pressure decrease seen in first 3 hrs with digoxin, and also reduced duration of digoxininduced diastolic blood pressure fall from 12 to 6 hours. The changes in heart rates,cardiac output and stroke volumes were not statistically significant, but inter-individual differences were large (See reference number 1-3).
A study in 12 patients with hyperthyroidism found that normalisation of serum T3 and T4 by thiamazole treatment did not produce significant changes in pharmacokinetics of digoxin (See reference number 4)
One explanation for changed response to digitalis with carbimazole is that there is a direct and altered response of heart due to raised or lowered thyroid hormone levels. Another is that changes in glomerular filtration rate associated with hypo- or hyperthyroidism result in increased or decreased serum digoxin,respectively (See reference number 5). Why carbimazole reduced serum digoxin in healthy subjects (normal thyroid status) is not known.
As thyroid status is returned to normal by use of drugs (antithyroid drugs or thyroid hormones), dosage of digitalis glycosides may need to be adjusted appropriately. Hyperthyroid patients may need to have their digitalis dosage gradually reduced as treatment proceeds (because initially they are relatively resistant to effects of digitalis and start off needing higher doses). They are also relatively insensitive to chronotropic effects of digitalis (See reference number 6,7). Hypothyroid patients on other hand may need a gradually increasing dosage (because initially they are relatively sensitive to digitalis) (See reference number 5,6). In either of these situations it would be prudent to monitor serum digoxin levels and glomerular filtration rate as treatment continues. The reduction of serum digoxin by carbimazole in healthy subjects does not fit with need to decrease digoxin doses when antithyroid drugs are used in patients. Further study is needed.
Petereit G,Ramesh Rao B, Siepmann M, Kirch W. Influence of carbimazole on the steady stateserum levels and haemodynamic effects of digoxin in healthy subjects. Eur J Clin Pharmacol (1995) 49, A159.
Rao BR,Petereit G, Ebert U, Siepmann M, Kirch W. Influence of carbimazole on the steadystate serum levels and haemodynamic effects of digoxin in healthy subjects. Therapie (1995) 50 (Suppl), 406.
Rao R,Petereit G, Ebert U, Kirch W. Influence of carbimazole on serum levels and haemodynamic effects of digoxin. Clin Drug Invest (1997) 13, 350–4.
Gasińska T,Izbicka M, Dec R. Digoxin pharmacokinetics in hyperthyroid patients treated withmethimazole. J Endocrinol (1997) 152 (Suppl), P285.
Croxson MS,Ibbertson HK. Serum digoxin in patients with thyroid disease. BMJ (1975) 3, 566–8.
Lawrence JR,Sumner DJ, Kalk WJ, Ratcliffe WA, Whiting B, Gray K, Lindsay M. Digoxinkinetics in patients with thyroid dysfunction. Clin Pharmacol Ther (1977) 22, 7–13.
Huffman DH,Klaassen CD, Hartman CR. Digoxin in hyperthyroidism. Clin Pharmacol Ther (1977) 22, 533–8.