What is the maximum dose of Imdur (isosorbide mononitrate) for a patient with impaired renal function on dialysis?

Maximum Dose of Imdur (Isosorbide Mononitrate) in Dialysis Patients

For patients on dialysis, the maximum dose of Imdur (isosorbide mononitrate) is 240 mg once daily, as there is no need for dose adjustment in renal impairment including dialysis.

Pharmacokinetics in Renal Impairment

Isosorbide mononitrate's pharmacokinetics are favorable in patients with renal dysfunction:

• The FDA label clearly states that "the disposition of ISMN in patients with various degrees of renal insufficiency, liver cirrhosis, or cardiac dysfunction was evaluated and found to be similar to that observed in healthy subjects" 1
• The elimination half-life of ISMN is not prolonged in renal failure, and there is no drug accumulation in patients with chronic renal failure after multiple oral dosing 1
• Isosorbide mononitrate is primarily metabolized by the liver and is not subject to first-pass metabolism 1
• Only about 4% of total body clearance is attributed to renal clearance 1

Dosing Recommendations

Initial Dosing

• Start with 30 mg (given as a single 30 mg tablet or as 1/2 of a 60 mg tablet) or 60 mg (given as a single tablet) once daily in the morning 1
• After several days, the dosage may be increased to 120 mg once daily 1
• In rare cases, 240 mg may be required 1

Administration Considerations

• The daily dose should be taken in the morning upon arising 1
• Tablets should not be chewed or crushed and should be swallowed with half a glass of fluid 1
• No special timing relative to dialysis is required since the drug is not significantly removed by dialysis

Clinical Considerations for Dialysis Patients

Potential Benefits

• Studies have shown that sustained-release isosorbide mononitrate can be beneficial in maintenance hemodialysis patients:
  • May help control blood pressure
  • Can decrease left ventricular hypertrophy
  • May reduce the incidence of acute left heart failure 2

Monitoring

• Monitor for hypotension, especially in patients with fluid shifts during dialysis
• Watch for headache, which is the most common adverse effect but usually mild to moderate and improves with continued therapy 3
• Be alert for signs of tolerance development with long-term use

Important Precautions

Tolerance Management

• Attempts to overcome tolerance by dose escalation have consistently failed 1
• Nitrates need to be absent from the body for several hours to restore antianginal efficacy 1
• Morning dosing helps create a nitrate-free interval overnight

Discontinuation

• Abrupt discontinuation during long-term treatment may exacerbate symptoms 3
• If discontinuation is necessary, consider gradual dose reduction

Conclusion

The pharmacokinetic profile of isosorbide mononitrate is not significantly altered in patients with renal impairment, including those on dialysis. Therefore, the maximum dose remains 240 mg once daily, the same as for patients with normal renal function. The dose should be titrated based on clinical response and tolerance, starting with 30-60 mg once daily and increasing as needed.