Isosorbide dinitrate Digoxin

A case of heart failure with delirium was reported in a man with a significant history of cardiovascular disease who had taken valerian (500-2000 mg daily) for 5 years and was also taking numerous other medications and supplements (isosorbide dinitrate, digoxin, furosemide, benazepril, aspirin, lovastatin, ibuprofen, potassium, zinc, and vitamins). The reporting physicians stated that valerian is considered to exert a benzodiazepine-like action through the enhancement of y-aminobutyric acid neurotransmission they suggested that symptoms reported in this case were similar to benzodiazepine withdrawal symptoms and hypothesized that the cardiac failure was due to valerian withdrawal (Garges et al. 1998). 

More recently, the value of adding the combination of isosorbide dinitrate 40 mg and hydralazine 75 mg three times daily to therapy including ACE inhibitors, P-blockers, digoxin, and diuretics was evaluated in a prospective, randomized trial26 The study enrolled only African-American patients and demonstrated a significant reduction in mortality, as well as first hospitalization for HF. Quality-of-life scores were also improved over placebo. Combination therapy with hydralazine and isosorbide dinitrate is an appropriate substitute for angiotensin II antagonism... 

Develop a medication regimen to slow the progression of HF with the use of neurohormonal blockers such as vasodilators (ACE inhibitors, ARBs, or hydralazine/ isosorbide dinitrate), P-blockers, and aldosterone antagonists. Utilize digoxin if the patient remains symptomatic despite optimization of the above therapies. 

In eight patients with chronic heart failure taking digoxin 0.25 mg/day, isosorbide dinitrate 10 mg tds caused only a small increase in (15%) and had no effect on the mean steady-state serum concentration or AUC (241). 

Mahgoub AA, El-Medany AH, Abdnlatif AS. A comparison between the effects of diltiazem and isosorbide dinitrate on digoxin pharmacodynamics and kinetics in the treatment of patients with chronic ischemic heart failure. Saudi Med J 2002 23(6) 725-31. 

Compared with placebo, the combination of hydralazine and isosorbide dinitrate (ISDN) reduced mortality in patients receiving diuretics and digoxin (but not ACE inhibitors or /3-blockers). However, another trial comparing the combination with an ACE inhibitor found that mortality was lower in the ACE inhibitor group. Adverse effects (primarily headache and gastrointestinal complaints) with combined hydralazine-ISDN were common, limiting their use in many patients. Patient compliance also was an important issue because hydralazine-ISDN therapy was given four times daily in these trials. Whether less frequent administration provides equivalent benefit is unknown. 

A woman, hospitalised for endocarditis, taking digoxin 250 to 375 micrograms daily, furosemide, aspirin, isosorbide dinitrate and potassium chloride, had a marked fall of about 80% in her serum digoxin level when she was given rifampicin 600 mg daily. The serum digoxin returned to its former level over the 2 weeks following rifampicin withdrawal. She had only moderate renal impairment (serum creatinine 221 micromol/L). 

In a crossover study in 8 patients with chronic heart failure given digoxin 250 micrograms daily for 20 days with isosorbide dinitrate 10 mg three times daily for the last 10 days, there was no change in the mean steady-state concentration, AUC or half-life of digoxin. ... 

Sodium nitroprusside or hydraiazine infusions can reduce serum digoxin levels, but the importance of this is uncertain. Isosorbide dinitrate did not alter digoxin pharmacokinetics in one study. 

No significant adverse events or interactions were reported in a study of Cs-4 in patients with chronic heart failure. Patients were administered 3 to 4 g daily of Cs-4 in addition to their standard prescription medication which included digoxin, hydrochlorothiazide, isosorbide dinitrate, furosemide, lanatoside, dopamine, and dobutamine (Zhang et al. 1995). 

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