Home page A B C D E F G H I K L M N O P Q R S T U V W X Y Z

Isordil (Isosorbide Dinitrate) Side Effects, Interactions, Warning


Udocheals.orgIsordil
3.14.2017 | Logan Miers
Isordil
Isordil (Isosorbide Dinitrate) Side Effects, Interactions, Warning

home drugs a-z list side effects drug center isordil (isosorbide dinitrate) drug.

Aspirin and/or acetaminophen, on the other hand, often successfully relieve isosorbide dinitrate-induced headaches with no deleterious effect on isosorbide dinitrate's anti-anginal efficacy. Patients should resist the temptation to avoid headaches by altering the schedule of their treatment with isosorbide dinitrate, since loss of headache may be associated with simultaneous loss of anti-anginal efficacy. Patients should be told that the anti-anginal efficacy of isosorbide dinitrate is strongly related to its dosing regimen, so the prescribed schedule of dosing should be followed carefully. In patients who get these headaches, the headaches are a marker of the activity of the drug. In particular, daily headaches sometimes accompany treatment with isosorbide dinitrate.

When methemoglobinemia is diagnosed, the treatment of choice is methylene blue, 1 to 2 mg/kg intravenously.

Manufactured by: MEDA Manufacturing GmbH Cologne, Germany D-51063. Revised: Jan 2015. For: Valeant Pharmaceuticals North America LLC Bridgewater, NJ 08807 USA.

Anti-anginal activity is present about 1 hour after dosing. In clinical trials, immediate-release oral isosorbide dinitrate has been administered in a variety of regimens, with total daily doses ranging from 30 mg to 480 mg. Controlled trials of single oral doses of isosorbide dinitrate have demonstrated effective reductions in exercise-related angina for up to 8 hours.

Pill Identifier Tool Quick, Easy, Pill Identification.

Isordil (isosorbide dinitrate) Oral Titradose Tablets are available as follows:

Safety and effectiveness in pediatric patients have not been established.

As also noted under CLINICAL PHARMACOLOGY, the effects of the second and later doses have been smaller and shorter-lasting than the effects of the first.

round, peach, imprinted with 3613 IL.

Amplification of the vasodilatory effects of Isordil 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 extr emities and with central volume expansion.

With an overall half-life of about 5 hours, the 5-mononitrate is cleared from the serum by denitration to isosorbide, glucuronidation to the 5-mononitrate glucuronide, and denitration/hydration to sorbitol. Both metabolites have biological activity, especially the 5-mononitrate. The 2-mononitrate has been less well studied, but it appears to participate in the same metabolic pathways, with a half-life of about 2 hours.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

The optimal interval will vary with the individual patient, dose and regimen. A daily dose-free interval of at least 14 hours is advisable to minimize tolerance. As with all titratable drugs, it is important to administer the minimum dose which produces the desired clinical effect. For maintenance therapy, 10 mg to 40 mg, two or three times daily is recommended. The usual starting dose of Isordil Titradose is 5 mg to 20 mg, two or three times daily. Some patients may require higher doses.

In one such trial, however, subjects receiving nitroglycerin had less exercise tolerance at the end of the daily dose-free interval than the parallel group receiving placebo. The incidence, magnitude, and clinical significance of similar phenomena in patients receiving ISDN have not been studied. Few well-controlled clinical trials of organic nitrates have been designed to detect rebound or withdrawal effects.

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.

The average bioavailability of ISDN is about 25%; most studies have observed progressive increases in bioavailability during chronic therapy. Absorption of isosorbide dinitrate after oral dosing is nearly complete, but bioavailability is highly variable (10% to 90%), with extensive first-pass metabolism in the liver. Serum levels reach their maxima about an hour after ingestion.

Drug Interaction Tool Check Potential Drug Interactions.

Hypotension induced by isosorbide dinitrate may be accompanied by paradoxical bradycardia and increased angina pectoris. This drug should therefore be used with caution in patients who may be volume depleted or who, for whatever reason, are already hypotensive. Severe hypotension, particularly with upright posture, may occur with even small doses of isosorbide dinitrate.

Dilatation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end- diastolic pressure and pulmonary capillary wedge pressure (preload). Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure (afterload). The principal pharmacological action of isosorbide dinitrate is relaxation of vascular smooth muscle and consequent dilatation of peripheral arteries and veins, especially the latter. The relative importance of preload reduction, afterload reduction, and coronary dilatation remains undefined. Dilatation of the coronary arteries also occurs.

Because many drugs are excreted in human milk, caution should be exercised when isosorbide dinitrate is administered to a nursing woman. It is not known whether isosorbide dinitrate is excreted in human milk.

Treatment with isosorbide dinitrate 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.

Only after nitrates have been absent from the body for several hours has their anti-anginal efficacy been restored.

Headache may be recurrent with each daily dose, especially at higher doses. Adverse reactions to isosorbide dinitrate are generally dose-related, and almost all of these reactions are the result of isosorbide dinitrate's activity as a vasodilator. Transient episodes of lightheadedness, occasionally related to blood pressure changes, may also occur. Headache, which may be severe, is the most commonly reported side effect. Syncope, crescendo angina, and rebound hypertension have been reported but are uncommon. Hypotension occurs infrequently, but in some patients it may be severe enough to warrant discontinuation of therapy.

Isordil (isosorbide dinitrate) Titradose tablets are indicated for the prevention of angina pectoris due to coronary artery disease. The onset of action of immediate-release oral isosorbide dinitrate is not sufficiently rapid for this product to be useful in aborting an acute anginal episode.

Even in patients totally without cytochrome b5 reductase activity, however, and even assuming that the nitrate moieties of isosorbide dinitrate are quantitatively applied to oxidation of hemoglobin, about 1 mg/kg of isosorbide dinitrate 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 isosorbide dinitrate. Nitrate ions liberated during metabolism of isosorbide dinitrate can oxidize hemoglobin into methemoglobin. 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 isosorbide dinitrate per hour), the average methemoglobin level measured was 0.2%; this was comparable to that observed in parallel patients who received placebo.

Dispense in a light-resistant, tight container.

Data are not available to allow estimation of the frequency of adverse reactions during treatment with Isordil Titradose tablets.

round, blue, imprinted with par 009.

Keep bottles tightly closed.

Concomitant use can cause severe hypotension, syncope, or myocardial ischemia. Do not use Isordil Titradose in patients who are taking certain drugs for erectile dysfunction (phosphodiesterase inhibitors), such as sildenafil, tadalafil, or vardenafil.

Isordil Titradose (isosorbide dinitrate) Tablets.

Because the effects of oral isosorbide dinitrate are so difficult to terminate rapidly, this formulation is not recommended in these settings. The benefits of immediate-release oral isosorbide dinitrate in patients with acute myocardial infarction or congestive heart failure have not been established. If one elects to use isosorbide dinitrate in these conditions, careful clinical or hemodynamic monitoring must be used to avoid the hazards of hypotension and tachycardia.

Isosorbide dinitrate is freely soluble in organic solvents such as acetone, alcohol, and ether, but is only sparingly soluble in water. Isosorbide dinitrate is a white, crystalline, odorless compound which is stable in air and in solution, has a melting point of 70°C and has an optical rotation of +134° (c=1.0, alcohol, 20°C).

Isosorbide dinitrate (ISDN) is 1,4:3,6-dianhydro-D-glucitol 2,5-dinitrate, an organic nitrate whose structural formula is.

Dosing regimens for most chronically used drugs are designed to provide plasma concentrations that are continuously greater than a minimally effective concentration. This strategy is inappropriate for organic nitrates. Attempts to overcome nitrate tolerance by dose escalation, even to doses far in excess of those used acuy, have consistently failed. Several well-controlled clinical trials have used exercise testing to assess the anti-anginal efficacy of continuously-delivered nitrates. In the large majority of these trials, active agents were no more effective than placebo after 24 hours (or less) of continuous therapy.

NDC, bottles of 100.

The use of epinephrine or other arterial vasoconstrictors in this setting is likely to do more harm than good.

round, pink, imprinted with GG 259.

With immediate-release ISDN, it appears that one daily dose-free interval must be at least 14 hours long. As noted under CLINICAL PHARMACOLOGY, multiple-dose studies with ISDN and other nitrates have shown that maintenance of continuous 24-hour plasma levels results in refractory tolerance. Every dosing regimen for Isordil Titradose tablets must provide a daily dose-free interval to minimize the development of this tolerance.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

Concomitant use can cause hypotension. Do not use Isordil Titradose in patients who are taking the soluble guanylate cyclase stimulator riociguat.

round, yellow, imprinted with W1.

Less serious side effects may.

round, white, imprinted with par 021.

RxList does not provide medical advice, diagnosis or treatment. 2017 by RxList Inc. See additional information.

Find Lowest Prices on.

NDC, bottles of 100.

round, green, imprinted with 772, W W, WW.

Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy.

In rats, the median acute lethal dose (LD50) was found to be 1100 mg/kg. There are no data suggesting what dose of isosorbide dinitrate is likely to be life-threatening in humans.

One study of 8 patients, who were administered a pretitrated dose (average 27.5 mg) of immediate-release ISDN at 0800, 1300, and 1800 hours for 2 weeks, revealed that significant anti-anginal effectiveness was discontinuous and totaled about 6 hours in a 24 hour period. From large, well-controlled studies of other nitrates, it is reasonable to believe that the maximal achievable daily duration of anti-anginal effect from isosorbide dinitrate is about 12 hours. No dosing regimen for isosorbide dinitrate, however, has ever actually been shown to achieve this duration of effect.

round, white, imprinted with W W, 771.

Clearance is affected primarily by denitration to the 2-mononitrate (15 to 25%) and the 5-mononitrate (75 to 85%). Once absorbed, the volume of distribution of isosorbide dinitrate is 2 to 4 L/kg, and this volume is cleared at the rate of 2 to 4 L/min, so ISDN's half-life in serum is about an hour. Since the clearance exceeds hepatic blood flow, considerable extra hepatic metabolism must also occur.

round, green, imprinted with par 022.

Concomitant use of Isordil Titradose with phosphodiesterase inhibitors in any form is contraindicated (see CONTRAINDICATIONS ).

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. The ill effects of isosorbide dinitrate overdose are generally the results of isosorbide dinitrate's capacity to induce vasodilatation, venous pooling, reduced cardiac output, and hypotension.

round, white, imprinted with West-Ward 769.

Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air. The diagnosis should be suspected in patients who exhibit signs of impaired oxygen delivery despite adequate cardiac output and adequate arterial pO2. Methemoglobin levels are available from most clinical laboratories.

40 mg, round, light green tablets imprinted “BPI 192” on one side and deeply scored on reverse side:

Large controlled studies with other nitrates suggest that no dosing regimen with Isordil Titradose tablets should be expected to provide more than about 12 hours of continuous anti-anginal efficacy per day.

The effects of the second and later doses have been smaller and shorter-lasting than the effect of the first. Once-daily regimens, and regimens with one daily dose-free interval of at least 14 hours (e.g., a regimen providing doses at 0800, 1400, and 1800 hours), have shown efficacy after the first dose of each day that was similar to that shown in the single-dose studies cited above. Most controlled trials of multiple-dose oral ISDN taken every 12 hours (or more frequently) for several weeks have shown statistically significant anti-anginal efficacy for only 2 hours after dosing.

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. In industrial workers who have had long-term exposure to unknown (presumably high) doses of organic nitrates, tolerance clearly occurs.

The daily dose-free interval sufficient to avoid tolerance to organic nitrates has not been well defined. Daily dose-free intervals that have succeeded in avoiding tolerance during trials of moderate doses (e.g., 30 mg) of immediate-release ISDN have generally been somewhat longer (at least 14 hours), but this is consistent with the longer half-lives of ISDN and its active metabolites. Studies of nitroglycerin (an organic nitrate with a very short half-life) have shown that daily dose-free intervals of 10 to 12 hours are usually sufficient to minimize tolerance.

The importance of these observations to the routine, clinical use of immediate-release oral isosorbide dinitrate is not known. 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 and decreased exercise tolerance. Some clinical trials in angina patients have provided nitroglycerin for about 12 continuous hours of every 24-hour day.

Isordil Titradose is contraindicated in patients who are allergic to isosorbide dinitrate or any of its ingredients.

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. Clinical studies of Isordil (isosorbide dinitrate) Titradose did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of isosorbide dinitrate and its active metabolites. Similarly, it is not known which, if any, of these substances can usefully be removed from the body by hemodialysis.

Pharmacy Locater Tool Including 24 Hour, Pharmacies.

Call your doctor at once if you have a serious side effect such as:

At oral doses 35 and 150 times the maximum recommended human daily dose, isosorbide dinitrate 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. Isosorbide dinitrate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

The organic nitrates are vasodilators, active on both arteries and veins. and whose molecular weight is 236.14.

No long-term studies in animals have been performed to evaluate the carcinogenic potential of isosorbide dinitrate. In a modified two-litter reproduction study, there was no remarkable gross pathology and no altered fertility or gestation among rats fed isosorbide dinitrate at 25 or 100 mg/kg/day.

round, green, imprinted with WYETH 4192.

Alcohol, in particular, has been found to exhibit additive effects of this variety. The vasodilating effects of isosorbide dinitrate may be additive with those of other vasodilators.

Store at controlled room temperature, 25°C (77°F); excursions permitted to 15 -30° (59-86°F) Protect from light.

5 mg, round, pink tablets imprinted “BPI 152” on one side and deeply scored on reverse side:

round, white, imprinted with W3.

In patients with renal disease or congestive heart failure, therapy resulting in central volume expansion is not without hazard. Treatment of isosorbide dinitrate overdose in these patients may be subtle and difficult, and invasive monitoring may be required.

round, green, imprinted with GG 227.

round, white, imprinted with GG 26.

Laboratory determinations of serum levels of isosorbide dinitrate and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of isosorbide dinitrate overdose.

Concomitant use of Isordil Titradose with riociguat, a soluble guanylate cyclase stimulator, iscontraindicated (see CONTRAINDICATIONS ).

Methemoglobinemia is so infrequent at these doses that further discussion of its diagnosis and treatment is deferred (see OVERDOSAGE ). Extremely rarely, ordinary doses of organic nitrates have caused methemoglobinemia in normal-seeming patients.

As tolerance to isosorbide dinitrate develops, the effect of sublingual nitroglycerin on exercise tolerance, although still observable, is somewhat blunted.

Because the hypotension associated with isosorbide dinitrate overdose is the result of venodilatation and arterial hypovolemia, prudent therapy in this situation should be directed toward increase in central fluid volume. No specific antagonist to the vasodilator effects of isosorbide dinitrate is known, and no intervention has been subject to controlled studies as a therapy for isosorbide dinitrate overdose. Passive elevation of the patient's legs may be sufficient, but intravenous infusion of normal saline or similar fluid may also be necessary.

Each Isordil Titradose tablet contains 5 or 40 mg of isosorbide dinitrate. The 5 mg and 40 mg dosage strengths also contain the following: 5 mg – FD&C Red 40; 40 mg – D&C Yellow 10, FD&C Blue 1, and FD&C Yellow 6. The inactive ingredients in each tablet are lactose, cellulose, and magnesium stearate.

Isordil