What happens if I overdose I.S.D.?
Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local, or emergency room immediately.
Proper storage of I.S.D. extended-release capsules:
Store I.S.D. extended-release capsules at room temperature between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep I.S.D. extended-release capsules out of the reach of children and away from pets.
Overdose of I.S.D. in details
Hemodynamic Effects
The ill effects of I.S.D. overdose are generally the results of I.S.D.'s capacity to induce vasodilatation, venous pooling, reduced cardiac output, and hypotension. These hemodynamic changes may have protean manifestations, including increased intracranial pressure, with any or all of persistent throbbing headache, confusion, and moderate fever; vertigo; palpitations; visual disturbances; nausea and vomiting (possibly with colic and even bloody diarrhea); syncope (especially in the upright posture); air hunger and dyspnea, later followed by reduced ventilatory effort; diaphoresis, with the skin either flushed or cold and clammy; heart block and bradycardia, paralysis; coma; seizures; and death.
Laboratory determinations of serum levels of I.S.D. and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of I.S.D. overdose.
There are no data suggesting what dose of I.S.D. is likely to be life-threatening in humans. In rats, the median acute lethal dose (LD50) was found to be 1100 mg/kg.
No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of I.S.D. and its active metabolites. Similarly, it is not known which, if any, of these substances can usefully be removed from the body by hemodialysis.
No specific antagonist to the vasodilator effects of I.S.D. is known, and no intervention has been subject to controlled studies as a therapy for I.S.D. overdose. Because the hypotension associated with I.S.D. overdose is the result of venodilatation and arterial hypovolemia, prudent therapy in this situation should be directed toward increase in central fluid volume. Passive elevation of the patient's legs may be sufficient, but intravenous infusion of normal saline or similar fluid may also be necessary.
The use of epinephrine or other arterial vasoconstrictors in this setting is likely to do more harm than good.
In patients with renal disease or congestive heart failure, therapy resulting in central volume expansion is not without hazard. Treatment of I.S.D. overdosage in these patients may be subtle and difficult, and invasive monitoring may be required.
Methemoglobinemia
Nitrate ions liberated during metabolism of I.S.D. can oxidize hemoglobin into methemoglobin. Even in patients totally without cytochrome b5reductase activity, however, and even assuming that the nitrate moieties of I.S.D. are quantitatively applied to oxidation of hemoglobin, about 1 mg/kg of I.S.D. should be required before any of these patients manifests clinically significant (≥10%) methemoglobinemia. In patients with normal reductase function, significant production of methemoglobin should require even larger doses of I.S.D.. In one study in which 36 patients received 2 to 4 weeks of continuous nitroglycerin therapy at 3.1 to 4.4 mg/hr (equivalent, in total administered dose of nitrate ions, to 4.8 to 6.9 mg of bioavailable I.S.D. per hour), the average methemoglobin level measured was 0.2%; this was comparable to that observed in parallel patients who received placebo.
Notwithstanding these observations, there are case reports of significant methemoglobinemia in association with moderate overdoses of organic nitrates. None of the affected patients had been thought to be unusually susceptible.
Methemoglobin levels are available from most clinical laboratories. The diagnosis should be suspected in patients who exhibit signs of impaired oxygen delivery despite adequate cardiac output and adequate arterial pO2. Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air.
When methemoglobinemia is diagnosed, the treatment of choice is methylene blue, 1 to 2 mg/kg intravenously.
What should I avoid while taking I.S.D.?
I.S.D. can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.
Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.
Avoid drinking alcohol. It can increase some of the side effects of I.S.D..
I.S.D. warnings
Amplification of the vasodilatory effects of I.S.D. by sildenafil can result in severe hypotension. The time course and dose dependence of this interaction have not been studied. Appropriate supportive care has not been studied, but it seems reasonable to treat this as a nitrate overdose, with elevation of the extremities and with central volume expansion.
The benefits of immediate-release oral I.S.D. in patients with acute myocardial infarction or congestive heart failure have not been established. If one elects to use I.S.D. in these conditions, careful clinical or hemodynamic monitoring must be used to avoid the hazards of hypotension and tachycardia. Because the effects of oral I.S.D. are so difficult to terminate rapidly, this formulation is not recommended in these settings.
What should I discuss with my healthcare provider before taking I.S.D.?
Do not use I.S.D. if you are taking sildenafil (Viagra). Serious, life-threatening side effects can occur if you take I.S.D. while you are using sildenafil.
You should not use this medication if you are allergic to I.S.D., I.S.D. mononitrate (Imdur, ISMO, Monoket), or nitroglycerin, or if you have early signs of a heart attack (chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling).
If you have any of these other conditions, you may need a dose adjustment or special tests to safely take I.S.D.:
- congestive heart failure;
- low blood pressure; or
- kidney disease.
FDA pregnancy category C. It is not known whether I.S.D. is harmful to an unborn baby. Before you take this medication, tell your doctor if you are pregnant or plan to become pregnant during treatment.
It is not known whether I.S.D. passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.
I.S.D. can cause severe headaches, especially when you first start using it. These headaches may gradually become less severe as you continue to use I.S.D.. Do not stop taking the medication. Ask your doctor before using any headache pain medication.
I.S.D. precautions
Severe hypotension, particularly with upright posture, may occur with even small doses of I.S.D.. This drug should therefore be used with caution in patients who may be volume depleted or who, for whatever reason, are already hypotensive. Hypotension induced by I.S.D. may be accompanied by paradoxical bradycardia and increased angina pectoris.
Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy.
As tolerance to I.S.D. develops, the effect of sublingual nitroglycerin on exercise tolerance, although still observable, is somewhat blunted.
Some clinical trials in angina patients have provided nitroglycerin for about 12 continuous hours of every 24-hour day. During the daily dose-free interval in some of these trials, anginal attacks have been more easily provoked than before treatment, and patients have demonstrated hemodynamic rebound anddecreasedexercise tolerance. The importance of these observations to the routine, clinical use of immediate-release oral I.S.D. is not known.
In industrial workers who have had long-term exposure to unknown (presumably high) doses of organic nitrates, tolerance clearly occurs. Chest pain, acute myocardial infarction, and even sudden death have occurred during temporary withdrawal of nitrates from these workers, demonstrating the existence of true physical dependence.
Information for Patients
Patients should be told that the anti-anginal efficacy of I.S.D. is strongly related to its dosing regimen, so the prescribed schedule of dosing should be followed carefully. In particular, daily headaches sometimes accompany treatment with I.S.D.. In patients who get these headaches, the headaches are a marker of the activity of the drug. Patients should resist the temptation to avoid headaches by altering the schedule of their treatment with I.S.D., since loss of headache may be associated with simultaneous loss of anti-anginal efficacy. Aspirin and/or acetaminophen, on the other hand, often successfully relieve I.S.D.-induced headaches with no deleterious effect on I.S.D.'s anti-anginal efficacy.
Treatment with I.S.D. may be associated with lightheadedness on standing, especially just after rising from a recumbent or seated position. This effect may be more frequent in patients who have also consumed alcohol.
Drug Interactions
The vasodilating effects of I.S.D. may be additive with those of other vasodilators. Alcohol, in particular, has been found to exhibit additive effects of this variety.
Concomitant use of I.S.D. with phosphodiesterase inhibitors in any form is contraindicated.
Concomitant use of I.S.D. with riociguat, a soluble guanylate cyclase stimulator, is contraindicated.
Carcinogenesis and Mutagenesis and Impairment of Fertility
No long-term studies in animals have been performed to evaluate the carcinogenic potential of I.S.D.. In a modified two-litter reproduction study, there was no remarkable gross pathology and no altered fertility or gestation among rats fed I.S.D. at 25 or 100 mg/kg/day.
Pregnancy Category C
At oral doses 35 and 150 times the maximum recommended human daily dose, I.S.D. has been shown to cause a dose-related increase in embryotoxicity (increase in mummified pups) in rabbits. There are no adequate, well-controlled studies in pregnant women. I.S.D. should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers
It is not known whether I.S.D. is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when I.S.D. is administered to a nursing woman.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
Clinical studies of I.S.D. did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
What happens if I miss a dose of I.S.D.?
Since I.S.D. is sometimes used only when needed, you may not be on a dosing schedule.
If you are using the medicine regularly, take the missed dose as soon as you remember. If your next dose is less than 2 hours away, skip the missed dose and use the medicine at your next regularly scheduled time.
If you are using the extended-release capsule or tablet and your next dose is less than 6 hours away, skip the missed dose and use the medicine at your next regularly scheduled time.
Do not use extra medicine to make up a missed dose.
References
- DailyMed. "ISOSORBIDE DINITRATE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- DrugBank. "ISOSORBIDE DINITRATE". http://www.drugbank.ca/drugs/DB00883 (accessed September 17, 2018).
- MeSH. "Nitric Oxide Donors". https://www.ncbi.nlm.nih.gov/mesh/68... (accessed September 17, 2018).
Reviews
Consumer reviews
There are no reviews yet. Be the first to write one! |
Information checked by Dr. Sachin Kumar, MD Pharmacology
