ffects of nitrates.
For the treatment of diffuse esophageal spasm† without gastroesophageal reflux.
Oral dosage
Adults
10 to 30 mg PO twice daily; long-acting nitrates can decrease the high-amplitude contractions seen in diffuse esophageal spasm, but may not consistently relieve associated chest pain. In general, the initial dose for a geriatric patient should start at the low end of the dosing range, since some patients may be more sensitive to hypotensive effects. Adjust dosage based on clinical response.
For the treatment of achalasia†.
Oral dosage (sublingual tablets)
Adults
5 mg SL, administered 10—15 minutes before meals. Reserve for patients who refuse or are not candidates for more definitive therapies (pneumatic dilation or surgical myotomy) or who fail to respond to botulinum toxin injections. According to treatment guidelines, ISDN effectively decreases lower esophageal sphincter (LES) pressure by 30—65%, resulting in symptomatic improvement ranging from 53—87%. A comparative study of SL ISDN versus SL nifedipine, demonstrated a nonsignificant advantage in the LES pressure reduction associated with ISDN treatment (65% vs. 49%, respectively). In addition, SL ISDN has a shorter time to maximum reduction in LES pressure (3—27 min) compared to SL nifedipine, but a shorter duration of effect (30—90 min).
†Indicates off-label use
MAXIMUM DOSAGE
Adults
480 mg/day PO for immediate-release preparations; 160mg/day PO for sustained-release preparations; maximum dosage for SL route is not available.
Elderly
480 mg/day PO for immediate-release preparations; 160mg/day PO for sustained-release preparations; maximum dosage for SL route is not available.
Adolescents
Safety and efficacy have not been established.
Children
Safety and efficacy have not been established.
DOSING CONSIDERATIONS
Hepatic Impairment
Specific guidelines for dosage adjustments in hepatic impairment are not available; however, because isosorbide dinitrate plasma concentrations are elevated in patients with cirrhosis, cautious use of isosorbide dinitrate in this population may be prudent.
Renal Impairment
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Intermittent hemodialysis
It appears that a supplemental dose after intermittent hemodialysis is not needed.
ADMINISTRATION
NOTE: When using isosorbide dinitrate chronically, an interdosing ('nitrate-free') interval sufficient to avoid nitrate tolerance is required. For immediate-release products, an interdosing interval of 14 hours has been used successfully to prevent nitrate tolerance. Suggested dosage times include 0700 and 1200 or 0700, 1200, and 1700. An interdosing interval sufficient to avoid tolerance with sustained-release products has not been demonstrated. In an eccentric dosing schedule (i.e., 0800 & 1400), extended-release isosorbide dinitrate was no more effective than placebo after four weeks of therapy. Thus, the necessary interdosing interval sufficient to avoid tolerance when using extended-release products is unknown, but it may be greater than 18 hours. Large controlled trials suggest that no dosing regimen of isosorbide dinitrate (immediate- or extended-release) should be expected to provide more than about 12 hours of continuous anti-anginal efficacy per day.
Oral Administ |
