Inderal LA Sustained-Release Capsules

Pronunciation: proe-PRAN-oh-lol
Generic Name: Propranolol
Brand Name: Inderal LA

Do not suddenly stop taking Inderal LA Sustained-Release Capsules. Sharp chest pain, irregular heartbeat, and, sometimes, heart attack may occur if you suddenly stop Inderal LA Sustained-Release Capsules. The risk may be greater if you have certain types of heart disease. Your doctor should slowly lower your dose over several weeks if you need to stop taking Inderal LA Sustained-Release Capsules. This should be done even if you only take Inderal LA Sustained-Release Capsules for high blood pressure. Heart disease is common and you may not know you have it. Limit physical activity while you are lowering your dose. If new or worsened chest pain or other heart problems occur, contact your doctor right away. You may need to start taking Inderal LA Sustained-Release Capsules again.

Inderal LA Sustained-Release Capsules are used for:

Treating high blood pressure. It is used in patients with angina to decrease angina frequency and increase exercise tolerance. It is used to manage a heart condition called hypertrophic subaortic stenosis and to prevent migraine headaches. It may also be used for other conditions as determined by your doctor.

Inderal LA Sustained-Release Capsules are a beta-blocker. It works by slowing down the heart and decreasing the amount of blood it pumps out. This decreases blood pressure, helps the heart pump more efficiently, and reduces the workload on the heart. Exactly how Inderal LA Sustained-Release Capsules works to treat migraines is not known.

Do NOT use Inderal LA Sustained-Release Capsules if:

• you are allergic to any ingredient in Inderal LA Sustained-Release Capsules


• you have moderate to severe heart block, sick sinus syndrome, or a very slow heartbeat and you do not have a permanent pacemaker


• you have uncontrolled heart failure or shock caused by serious heart problems


• you have asthma


• the patient is a child with diabetes or heart failure


• you are taking mibefradil

Contact your doctor or health care provider right away if any of these apply to you.

Before using Inderal LA Sustained-Release Capsules:

Some medical conditions may interact with Inderal LA Sustained-Release Capsules. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have a history of other heart problems (eg, angina, congestive heart failure, slow heartbeat)


• if you have a history of liver or kidney problems, blood vessel disease, lung or breathing problems (eg, chronic bronchitis, chronic obstructive pulmonary disease [COPD], emphysema), diabetes, low blood sugar, overactive thyroid, or glaucoma


• if you have Wolff-Parkinson-White syndrome, Down syndrome, Raynaud syndrome, or an adrenal gland tumor (pheochromocytoma)


• if you smoke or drink alcohol


• if you are scheduled to have surgery or receive anesthesia

Some MEDICINES MAY INTERACT with Inderal LA Sustained-Release Capsules. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Mibefradil because the risk of serious heart side effects may be increased


• Diphenhydramine because it may increase the risk of Inderal LA Sustained-Release Capsules's side effects. Before you start any new medicine, including over-the-counter medicines, check the label to see if it contains diphenhydramine. If it does or you are not sure, check with your doctor or pharmacist


• Many prescription and nonprescription medicines (eg, used for infections, inflammation, aches and pains, high blood pressure, heart problems, irregular heartbeat, diabetes, prostate problems, blood thinning, thyroid problems, depression, mental or mood problems, immune system suppression, allergic reactions, asthma or other lung or breathing problems, high cholesterol, seizures, multiple sclerosis [MS]), multivitamin products, and herbal or dietary supplements (eg, herbal teas, coenzyme Q10, garlic, ginseng, ginkgo, St. John's wort) may interact with Inderal LA Sustained-Release Capsules, increasing the risk of side effects

This may not be a complete list of all interactions that may occur. Ask your health care provider if Inderal LA Sustained-Release Capsules may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Inderal LA Sustained-Release Capsules:

Use Inderal LA Sustained-Release Capsules as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Inderal LA Sustained-Release Capsules by mouth with or without food.


• Swallow Inderal LA Sustained-Release Capsules whole. Do not break, crush, or chew before swallowing.


• If you are taking an antacid with aluminum in it, take it at least 2 hours after you take Inderal LA Sustained-Release Capsules.


• Take Inderal LA Sustained-Release Capsules on a regular schedule to get the most benefit from it. Taking Inderal LA Sustained-Release Capsules at the same time each day will help you remember to take it.


• Continue to use Inderal LA Sustained-Release Capsules even if you feel well. Do not miss any doses.


• Do not suddenly stop taking Inderal LA Sustained-Release Capsules. You may have an increased risk of side effects. If you need to stop Inderal LA Sustained-Release Capsules, your doctor will gradually lower your dose.


• If you miss a dose of Inderal LA Sustained-Release Capsules, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Inderal LA Sustained-Release Capsules.

Important safety information:

• Inderal LA Sustained-Release Capsules may cause drowsiness, dizziness, light-headedness, or vision changes. These effects may be worse if you take it with alcohol or certain medicines. Use Inderal LA Sustained-Release Capsules with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Check with your doctor before you drink alcohol while you are taking Inderal LA Sustained-Release Capsules; it may increase the risk of Inderal LA Sustained-Release Capsules's side effects.


• Do NOT take more than the recommended dose, change your dose, or stop taking Inderal LA Sustained-Release Capsules without checking with your doctor. When taking Inderal LA Sustained-Release Capsules for high blood pressure, it may take a few days to several weeks for Inderal LA Sustained-Release Capsules to reach its full effect.


• Patients who take medicine for high blood pressure often feel tired or run down for a few weeks after starting treatment. Be sure to take your medicine even if you may not feel "normal." Tell your doctor if you develop any new symptoms.


• Tell your doctor or dentist that you take Inderal LA Sustained-Release Capsules before you receive any medical or dental care, emergency care, or surgery.


• If you have a history of any severe allergic reaction, talk with your doctor. You may be at risk of an even more severe allergic reaction if you come into contact with the substance that caused your allergy. Some medicines used to treat severe allergies may also not work as well while you are using Inderal LA Sustained-Release Capsules.


• Inderal LA Sustained-Release Capsules may lower your blood sugar levels. This is most likely to happen in infants and children, or in patients who have diabetes or kidney problems. It may also occur after prolonged physical activity or during fasting. Low blood sugar may make you anxious, sweaty, weak, dizzy, drowsy, or faint. It may also make your heart beat faster; make your vision change; give you a headache, chills, or tremors; or make you more hungry. If this occurs, eat or drink a quick source of sugar like table sugar, honey, candy, orange juice, or non-diet soda. This will raise your blood sugar level quickly. Tell your doctor right away if this happens.


• Diabetes patients - Inderal LA Sustained-Release Capsules may hide signs of low blood sugar, such as a rapid heartbeat. Be sure to watch for other signs of low blood sugar. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.


• Inderal LA Sustained-Release Capsules may interfere with certain lab tests, including glaucoma screening test and dobutamine stress echocardiography. Be sure your doctor and lab personnel know you are taking Inderal LA Sustained-Release Capsules.


• Lab tests, including blood pressure and heart function tests, may be performed while you use Inderal LA Sustained-Release Capsules. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Use Inderal LA Sustained-Release Capsules with caution in the ELDERLY; they may be more sensitive to its effects.


• Caution is advised when using Inderal LA Sustained-Release Capsules in CHILDREN; they may be more sensitive to its effects, especially low blood sugar levels, certain heart problems, or shortness of breath.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Inderal LA Sustained-Release Capsules while you are pregnant. Inderal LA Sustained-Release Capsules are found in breast milk. If you are or will be breast-feeding while you use Inderal LA Sustained-Release Capsules, check with your doctor. Discuss any possible risks to your baby.

If you stop taking Inderal LA Sustained-Release Capsules suddenly, you may have WITHDRAWAL symptoms. These may include worsening chest pain along with possible heart attack.

Possible side effects of Inderal LA Sustained-Release Capsules:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Constipation; diarrhea; dizziness; drowsiness; fatigue; light-headedness; nausea; stomach upset or cramping; trouble sleeping; vomiting; weakness.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain; confusion; fainting; fever with aching and sore throat; hallucinations; irregular heartbeat; memory loss; mental or mood changes (eg, depression); numbness or tingling of the hands; red, swollen, blistered, or peeling skin; severe or persistent dizziness or light-headedness; shortness of breath or wheezing; sudden, unusual weight gain; swelling of the hands, ankles, or feet; unusual bruising or bleeding; unusually slow heartbeat; very cold or blue fingers or toes; vision changes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Inderal LA side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include fainting; severe dizziness or light-headedness; shortness of breath; swelling of the hands, ankles, or feet; trouble breathing; very slow heart rate.

Proper storage of Inderal LA Sustained-Release Capsules:

Store Inderal LA Sustained-Release Capsules between 68 and 77 degrees F (20 and 25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Inderal LA Sustained-Release Capsules out of the reach of children and away from pets.

General information:

• If you have any questions about Inderal LA Sustained-Release Capsules, please talk with your doctor, pharmacist, or other health care provider.


• Inderal LA Sustained-Release Capsules are to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Inderal LA Sustained-Release Capsules. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Inderal LA resources

• Inderal LA Side Effects (in more detail)
• Inderal LA Use in Pregnancy & Breastfeeding
• Drug Images
• Inderal LA Drug Interactions
• Inderal LA Support Group
• 5 Reviews for Inderal LA - Add your own review/rating

Compare Inderal LA with other medications

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• Aortic Stenosis
• High Blood Pressure
• Migraine Prevention
• Mitral Valve Prolapse
• Thyrotoxicosis

Intal Nebulizer Solution

Pronunciation: KROE-moe-lin
Generic Name: Cromolyn
Brand Name: Intal

Intal Nebulizer Solution is used for:

Preventing bronchial asthma and decreasing the severity of asthma attacks. It is not used to treat sudden asthma attacks. It may also be used to treat other conditions as determined by your doctor.

Intal Nebulizer Solution is a mast cell stabilizer. It works by stabilizing mast cells and preventing them from releasing their irritating chemicals. Some forms of recurrent or chronic asthma are due to the release of irritating chemicals from mast cells located in the breathing tubes (bronchial tubes of the lung).

Do NOT use Intal Nebulizer Solution if:

• you are allergic to any ingredient in Intal Nebulizer Solution

Contact your doctor or health care provider right away if any of these apply to you.

Before using Intal Nebulizer Solution:

Some medical conditions may interact with Intal Nebulizer Solution. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have liver or kidney problems

Some MEDICINES MAY INTERACT with Intal Nebulizer Solution. However, no specific interactions with Intal Nebulizer Solution are known at this time.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Intal Nebulizer Solution may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Intal Nebulizer Solution:

Use Intal Nebulizer Solution as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Intal Nebulizer Solution is for inhalation only.


• This medication should be used in a power-driven nebulizer with an adequate airflow rate equipped with a suitable face mask or mouthpiece. Do not mix with other medicines in the nebulizer.


• Squeeze the contents of the ampule into the solution container in your nebulizer. Once the nebulizer has been assembled and contains cromolyn inhalation solution, hold the mask close to the face and switch on the device. Breathe through the mouth and out through the nose in a normal, relaxed manner. Nebulization should take 5 to 10 minutes.


• Any solution remaining in the nebulizer after treatment needs to be discarded.


• Continue to use Intal Nebulizer Solution even if you feel well. Do not miss any doses.


• If you miss a dose of Intal Nebulizer Solution, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Intal Nebulizer Solution.

Important safety information:

• Intal Nebulizer Solution may cause drowsiness. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Intal Nebulizer Solution.


• It may take up to 4 weeks for the benefits of this medication to be noticeable.


• Before you have any medical or dental treatments, emergency care, or surgery, tell the doctor or dentist that you are using Intal Nebulizer Solution.


• Carry an identification card at all times that says you are taking Intal Nebulizer Solution.


• Intal Nebulizer Solution is not recommended for use in CHILDREN younger than 2 years of age. Safety and effectiveness in this age group have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you are pregnant or plan on becoming pregnant, discuss with your doctor the benefits and risks of using Intal Nebulizer Solution during pregnancy. It is unknown if Intal Nebulizer Solution is excreted in breast milk. If you are or will be breast-feeding, check with your doctor to discuss the benefits and risks to your baby.

Possible side effects of Intal Nebulizer Solution:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Bad taste; cough; drowsiness; hoarseness; nausea; sneezing; throat irritation; tightness in the lungs; wheezing.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); breathing problems; severe nasal congestion.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Intal side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Intal Nebulizer Solution may be harmful if swallowed.

Proper storage of Intal Nebulizer Solution:

Store at controlled room temperature between 68 and 77 degrees F (20 and 25 degrees C), away from heat, moisture, and light. Do not store in the bathroom. Do not use the solution if it is discolored or contains particles. Store ampules in foil pouch until ready for use. Keep Intal Nebulizer Solution out of the reach of children and away from pets.

General information:

• If you have any questions about Intal Nebulizer Solution, please talk with your doctor, pharmacist, or other health care provider.


• Intal Nebulizer Solution is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Intal Nebulizer Solution. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Intal resources

• Intal Side Effects (in more detail)
• Intal Use in Pregnancy & Breastfeeding
• Intal Drug Interactions
• Intal Support Group
• 2 Reviews for Intal - Add your own review/rating

Compare Intal with other medications

• Asthma, Maintenance

Ismo

isosorbide mononitrate

Dosage Form: tablets

Ismo Description

Isosorbide mononitrate is 1,4:3,6-dianhydro-D-glucitol, 5-nitrate, an organic nitrate whose structural formula is:

and whose molecular weight is 191.14. The organic nitrates are vasodilators, active on both arteries and veins. Each Ismo® tablet contains 20 mg of isosorbide mononitrate. The inactive ingredients in each tablet are colloidal silicon dioxide, D&C Yellow 10 Aluminum Lake, FD&C Yellow 6 Aluminum Lake, hydroxypropyl methylcellulose, lactose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 20, povidone, sodium starch glycolate, titanium dioxide and hydroxypropyl cellulose.

Ismo - Clinical Pharmacology

Isosorbide mononitrate is the major active metabolite of isosorbide dinitrate (ISDN), and most of the clinical activity of the dinitrate is attributable to the mononitrate.

The principal pharmacological action of isosorbide mononitrate, due to its nitric oxide metabolite, is direct relaxation of vascular smooth muscle. The result is dilatation of peripheral arteries and veins, especially the latter. Dilation 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). Dilatation of the coronary arteries also occurs. The relative importance of preload reduction, afterload reduction, and coronary dilatation remains undefined.

Pharmacodynamics

Dosing regimens for most chronically used drugs are designed to provide plasma concentrations that are continu-ously greater than a minimally effective concentration. This strategy is inappropriate for organic nitrates. Several well-controlled clinical trials have used exercise testing to assess the antianginal efficacy of continuously delivered nitrates. In the large majority of these trials, active agents were indistinguishable from placebo after 24 hours (or less) of continuous therapy. Attempts to overcome tolerance by dose escalation, even to doses far in excess of those used acutely, have consistently failed. Only after nitrates have been absent from the body for several hours has their antianginal efficacy been restored. The drug-free interval sufficient to avoid tolerance to isosorbide mononitrate has not been completely defined. In the only regimen of twice-daily isosorbide mononitrate that has been shown to avoid development of tolerance, the two doses of Ismo tablets are given 7 hours apart, so there is a gap of 17 hours between the second dose of each day and the first dose of the next day. Taking account of the relatively long half-life of isosorbide mononitrate this result is consistent with those obtained for other organic nitrates. The same twice-daily regimen of Ismo tablets successfully avoided significant rebound/withdrawal effects. The incidence and magnitude of such phenomena have appeared, in studies of other nitrates, to be highly dependent upon the schedule of nitrate administration.

Pharmacokinetics

In humans, isosorbide mononitrate is not subject to first pass metabolism in the liver. The absolute bioavailability of isosorbide mononitrate from Ismo tablets is nearly 100%. Maximum serum concentrations of isosorbide mononitrate are achieved 30 to 60 minutes after ingestion of Ismo. The volume of distribution of isosorbide mononitrate is approximately 0.6 L/kg, and less than 4% is bound to plasma proteins. It is cleared from the serum by denitration to isosorbide; glucuronidation to the mononitrate glucuronide; and denitration/hydration to sorbitol. None of these metabolites is vasoactive. Less than 1% of administered isosorbide mononitrate is eliminated in the urine. The overall elimination half-life of isosorbide mononitrate is about 5 hours; the rate of clearance is the same in healthy young adults , in patients with various degrees of renal, hepatic, or cardiac dysfunction, and in the elderly. In a single-dose study, the pharmacokinetics of isosorbide mononitrate were dose-proportional up to at least 60 mg.

Clinical Trials

Controlled trials of single doses of Ismo tablets have demonstrated that antianginal activity is present about 1 hour after dosing, with peak effect seen from 1 to 4 hours after dosing. In placebo-controlled trials lasting 2 to 3 weeks, Ismo tablets were administered twice daily, in asymmetric regimens (with interdosing intervals of 7 and 17 hours) designed to avoid tolerance. One trial tested doses of 10 mg and 20 mg; one trial tested doses of 20 mg, 40 mg, and 60 mg; and three trials tested only doses of 20 mg. In each trial, the subjects were persons with known chronic stable angina, and the primary measure of efficacy was exercise tolerance on a standardized treadmill test. After initial dosing and for at least 3 weeks, exercise tolerance in patients treated with Ismo 20 mg tablets was significantly greater than that seen in patients treated with placebo, although there was some attenuation of effect with time. Treatment with Ismo tablets was superior to placebo for at least 12 hours after the first dose (i.e., 5 hours after the second dose) of each day. Significant tolerance and rebound phenomena were not observed. The 10-mg dose was not unequivocally superior to placebo, while the effect of the 40-mg dose was similar to that of the 20-mg dose. The 60-mg dose appeared to be less effective, and it was associated with a rebound phenomenon (early-morning worsening).

Indications and Usage for Ismo

Ismo tablets are indicated for the prevention of angina pectoris due to coronary artery disease. The onset of action of oral isosorbide mononitrate is not sufficiently rapid for this product to be useful in aborting an acute anginal episode.

Contraindications

Allergic reactions to organic nitrates are extremely rare, but they do occur. Isosorbide mononitrate is contraindicated in patients who are allergic to it.

Warnings

Amplification of the vasodilatory effects of Ismo 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 isosorbide mononitrate in patients with acute myocardial infarction or congestive heart failure have not been established. Because the effects of isosorbide mononitrate are difficult to terminate rapidly, this drug is not recommended in these settings. If isosorbide mononitrate is used in these conditions, careful clinical or hemo-dynamic monitoring must be used to avoid the hazards of hypotension and tachycardia.

Precautions

General

Severe hypotension, particularly with upright posture, may occur with even small doses of isosorbide mononitrate. 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 isosorbide mononitrate may be accompanied by paradoxical bradycardia and increased angina pectoris. Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy. 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. The importance of these observations to the routine, clinical use of oral isosorbide mononitrate is not known.

Information for Patients

Patients should be told that the antianginal efficacy of Ismo tablets can be maintained by carefully following the prescribed schedule of dosing (two doses taken 7 hours apart). For most patients, this can be accomplished by taking the first dose on awakening and the second dose 7 hours later. As with other nitrates, daily headaches sometimes accompany treatment with isosorbide mononitrate. 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 isosorbide mononitrate, since loss of headache may be associated with simultaneous loss of antianginal efficacy. Aspirin and/or acetaminophen, on the other hand, often successfully relieve isosorbide mononitrate-induced headaches with no deleterious effect on isosorbide mononitrate’s antianginal efficacy. Treatment with isosorbide mononitrate 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 isosorbide mononitrate may be additive with those of other vasodilators. Alcohol, in particular, has been found to exhibit additive effects of this variety. Marked symptomatic orthostatic hypotension has been reported when calcium channel blockers and organic nitrates were used in combination. Dose adjustments of either class of agents may be necessary.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

No carcinogenic effects were observed in mice exposed to oral isosorbide mononitrate for 104 weeks at doses of up to 900 mg/kg/day (102 X the human exposure comparing body surface area). Rats treated with 900 mg/kg/day for 26 weeks (225 X the human exposure comparing body surface area) and 500 mg/kg/day for the remaining 95 to 111 weeks (males and females, respectively) showed no evidence of tumors. No mutagenic activity was seen in a variety of in vitro and in vivo assays. No adverse effects on fertility were observed when isosorbide mononitrate was administered to male and female rats at doses of up to 500 mg/kg/day (125 X the human exposure comparing body surface area).

Pregnancy Category C

Isosorbide mononitrate has been shown to be associated with stillbirths and neonatal death in rats receiving 500 mg/kg/day of isosorbide mononitrate (125 X the human exposure comparing body surface area). At 250 mg/kg/day, no adverse effects on reproduction and development were reported. In rats and rabbits receiving isosorbide mononitrate at up to 250 mg/kg/day, no developmental abnormalities, fetal abnormalities, or other effects upon reproductive performance were detected; these doses are larger than the maximum recommended human dose by factors between 70 (body-surface-area basis in rabbits) and 310 (body-weight basis, either species). In rats receiving 500 mg/kg/day, there were small but statistically significant increases in the rates of prolonged gestation, prolonged parturition, stillbirth, and neonatal death; and there were small but statistically significant decreases in birth weight, live litter size, and pup survival.

There are no adequate and well-controlled studies in pregnant women. Isosorbide mononitrate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers:

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

Pediatric Use:

Safety and effectiveness of isosorbide mononitrate in pediatric patients have not been established.

Geriatric Use

Clinical studies of Ismo® 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, although age, renal, hepatic or cardiac dysfunction do not appear to have a clinically significant effect on the clearance of Ismo®.

Adverse Reactions

The table below shows the frequencies of the adverse reactions observed in more than 1% of the subjects (a) in 6 placebo-controlled domestic studies in which patients in the active-treatment arm received 20 mg of isosorbide mononitrate twice daily, and (b) in all studies in which patients received isosorbide mononitrate in a variety of regimens. In parentheses, the same table shows the frequencies with which these adverse reactions led to discontinuation of treatment. Overall, 11% of the patients who received isosorbide mononitrate in the six controlled U.S. studies discontinued treatment because of adverse reactions. Most of these discontinued because of headache. “Dizziness” and nausea were also frequently associated with withdrawal from these studies.

Frequency of Adverse Reactions (Discontinuations)*
* Some individuals discontinued for multiple reasons.
	6 Controlled Studies		92 Clinical Studies
Dose	Placebo	20 mg	(varied)
Patients	204	219	3344
Headache	9% (0%)	38% (9%)	19% (4.3%)
Dizziness	1% (0%)	5% (1%)	3% (0.2%)
Nausea, Vomiting	<1% (0%)	4% (3%)	2% (0.2%)

Other adverse reactions, each reported by fewer than 1% of exposed patients, and in many cases of uncertain relation to drug treatment, were::

Cardiovascular: angina pectoris, arrhythmias, atrial fibrillation, hypotension, palpitations, postural hypotension, premature ventricular contractions, supraventricular tachycardia, syncope.

Dermatologic: pruritus, rash.

Gastrointestinal: abdominal pain, diarrhea, dyspepsia, tenesmus, tooth disorder, vomiting.

Genitourinary: dysuria, impotence, urinary frequency.

Miscellaneous: asthenia, blurred vision, cold sweat, diplopia, edema, malaise, neck stiffness, rigors.

Musculoskeletal: arthralgia.

Neurological: agitation, anxiey, confusion, dyscoordination, hypoesthesia, hypokinesia, increased appetite, insomnia, nervousness, nightmares.

Respiratory: bronchitis, pneumonia, upper-respiratory tract infection.

Extremely rarely, ordinary doses of organic nitrates have caused methemoglobinemia in normal-seeming patients; for futher discussion of its diagnosis and treatment see under OVERDOSAGE.

Overdosage

Hemodynamic Effects

The ill effects of isosorbide mononitrate overdose are generally the results of isosorbide mononitrate’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 isosorbide mononitrate and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of isosorbide mononitrate overdose. There are no data suggesting what dose of isosorbide mononitrate is likely to be life-threatening in humans. In rats and mice, there is significant lethality at doses of 2000 mg/kg and 3000 mg/kg, respectively. No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of isosorbide mononitrate. In particular, dialysis is known to be ineffective in removing isosorbide mononitrate from the body. No specific antagonist to the vasodilator effects of isosorbide mononitrate is known, and no intervention has been subject to controlled study as a therapy of isosorbide mononitrate overdose. Because the hypotension associated with isosorbide mononitrate overdose is the result of venodilatation and arterial hypovolemia, prudent therapy in this situation should be directed toward an 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 isosorbide mononitrate overdose in these patients may be subtle and difficult, and invasive monitoring may be required.

Methemoglobinemia

Methemoglobinemia has been reported in patients receiving other organic nitrates, and it probably could also occur as a side effect of isosorbide mononitrate. Certainly nitrate ions liberated during metabolism of isosorbide mononitrate can oxidize hemoglobin into methemoglobin. Even in patients totally without cytochrome b5 reductase activity, however, and even assuming that the nitrate moiety of isosorbide mononitrate is quantitatively applied to oxidation of hemoglobin, about 2 mg/kg of isosorbide mononitrate 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 mononitrate. 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 7.8 to 11.1 mg of isosorbide mononitrate 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.

DOSAGE AND ADMINISTRATION (SEE INDICATIONS AND USAGE)

The recommended regimen of Ismo tablets is 20 mg (one tablet) twice daily, with the two doses given 7 hours apart. For most patients, this can be accomplished by taking the first dose on awakening and the second dose 7 hours later. Dosage adjustments are not necessary for elderly patients or patients with altered renal or hepatic function. As noted above (CLINICAL PHARMACOLOGY), multiple studies of organic nitrates have shown that maintenance of continuous 24-hour plasma levels results in refractory tolerance. The dosing regimen for Ismo tablets provides a daily nitrate-free interval to avoid the development of this tolerance.

As also noted under CLINICAL PHARMACOLOGY, well-controlled studies have shown that tolerance to Ismo tablets is avoided when using the twice-daily regimen in which the two doses are given 7 hours apart. This regimen has been shown to have antianginal efficacy beginning 1 hour after the first dose and lasting at least 5 hours after the second dose. The duration (if any) of antianginal activity beyond 12 hours has not been studied; large controlled studies with other nitrates suggest that no dosing regimen should be expected to provide more than about 12 hours of continuous antianginal efficacy per day.

In clinical trials, Ismo tablets have been administered in a variety of regimens. Single doses less than 20 mg have not been adequately studied, while single doses greater than 20 mg have demonstrated no greater efficacy than doses of 20 mg.

How is Ismo Supplied

Ismo® (isosorbide mononitrate) tablets, 20 mg, are available in bottles of 100 (NDC 67857-702-01). Each orange, round, film-coated tablet is engraved “Ismo 20” on one side and scored on the reverse side.

Store at 20 - 25° C (68 -77° F) [See USP Controlled Room Temperature].

Dispense in tight container.

Manufactured by:

West-ward Pharmaceutical Corp.

Eatontown, NJ 07724

Manufactured for:

Reddy Pharmaceuticals, LLC

Bridgewater, NJ 08807

Ismo  isosorbide mononitrate  tablet, film coated

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 67857-702 Route of Administration ORAL DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength isosorbide mononitrate (isosorbide mononitrate) Active 20 MILLIGRAM  In 1 TABLET colloidal silicon dioxide Inactive   D&C Yellow 10 Aluminum Lake Inactive   FD&C Yellow 6 Aluminum Lake Inactive   hydroxypropyl methylcellulose Inactive   lactose Inactive   magnesium stearate Inactive   microcrystalline cellulose Inactive   polyethylene glycol Inactive   polysorbate 20 Inactive   povidone Inactive   sodium starch glycolate Inactive   titanium dioxide Inactive   hydroxypropyl cellulose Inactive

Product Characteristics Color ORANGE (orange) Score 2 pieces Shape ROUND (round) Size 8mm Flavor Imprint Code Ismo;20 Contains          Coating true Symbol false

Packaging # NDC Package Description Multilevel Packaging 1 67857-702-01 100 TABLET In 1 BOTTLE, PLASTIC None

Revised: 03/2007Reddy Pharmaceuticals, LLC

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• Ismo Side Effects (in more detail)
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• Ismo Advanced Consumer (Micromedex) - Includes Dosage Information


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Ionil Plus Shampoo

Pronunciation: sal-ih-SILL-ik AS-id
Generic Name: Salicylic Acid
Brand Name: Examples include Ionil Plus and Neutrogena Healthy Scalp

Ionil Plus Shampoo is used for:

Relieving scalp itching, flaking, irritation, redness, and scaling due to psoriasis or seborrhea. It may also be used for other conditions as determined by your doctor.

Ionil Plus Shampoo is a topical salicylate. It works by causing the skin to swell, soften, and then slough or peel in areas where it is applied.

Do NOT use Ionil Plus Shampoo if:

• you are allergic to any ingredient in Ionil Plus Shampoo

Contact your doctor or health care provider right away if any of these apply to you.

Before using Ionil Plus Shampoo:

Some medical conditions may interact with Ionil Plus Shampoo. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to aspirin or a nonsteroidal anti-inflammatory drug (NSAID) (eg, ibuprofen, naproxen, celecoxib)


• if you have liver or kidney problems, a skin infection, skin irritation, diabetes, or poor blood circulation

Some MEDICINES MAY INTERACT with Ionil Plus Shampoo. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Anticoagulants, (eg, heparin, warfarin), aspirin, methotrexate, or sulfonylureas (eg, glipizide) because the risk of side effects may be increased by Ionil Plus Shampoo

This may not be a complete list of all interactions that may occur. Ask your health care provider if Ionil Plus Shampoo may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Ionil Plus Shampoo:

Use Ionil Plus Shampoo as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Wet hair, apply Ionil Plus Shampoo to scalp, and massage vigorously. Rinse and repeat. Be sure to wash your hands after each use.


• If you miss a dose of Ionil Plus Shampoo, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Ionil Plus Shampoo.

Important safety information:

• Ionil Plus Shampoo is for external use only. Avoid getting Ionil Plus Shampoo in your eyes, nose, or mouth, or on the genitals. If contact with your eyes occurs, flush with water for 15 minutes. Do not inhale the vapors of Ionil Plus Shampoo.


• Overuse of topical products may worsen your condition.


• Do not use Ionil Plus Shampoo longer or more often than recommended by your doctor or on the package label.


• Check with your doctor before use if you have a condition that covers a large area of the body.


• Be sure to apply Ionil Plus Shampoo only to the affected area and not to normal healthy skin.


• Do not use Ionil Plus Shampoo on skin that is irritated, infected, or reddened.


• Do not use Ionil Plus Shampoo on open skin wounds, moles, birthmarks, genital warts, warts on the face, or warts growing hair.


• Do not use any other medicines or drying products on your skin unless your doctor instructs you otherwise.


• Ionil Plus Shampoo may interfere with certain lab test results. Make sure your doctor and lab personnel know you are using Ionil Plus Shampoo.


• Ionil Plus Shampoo is extremely flammable. Do not store or use Ionil Plus Shampoo near a fire or other open flame.


• Ionil Plus Shampoo may be harmful if swallowed. If you may have taken Ionil Plus Shampoo by mouth, contact your local poison control center or emergency room immediately.


• Ionil Plus Shampoo contains a salicylate, which has been linked to Reye syndrome. Do not use Ionil Plus Shampoo on children or teenagers during or after chickenpox, flu, or other viral infections without checking with your doctor or pharmacist.


• Use of Ionil Plus Shampoo is not recommended in CHILDREN younger than 2 years of age without a doctor's instructions.


• Caution is advised when using Ionil Plus Shampoo in CHILDREN because they may be more sensitive to its effects.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, discuss with your doctor the benefits and risks of using Ionil Plus Shampoo during pregnancy. It is unknown if Ionil Plus Shampoo is excreted in breast milk. Do not breast-feed while you are using Ionil Plus Shampoo.

Possible side effects of Ionil Plus Shampoo:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Dry, peeling, red, or scaling skin.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); severe irritation.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Ionil Plus side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include agitation; diarrhea; dizziness; loss of appetite; loss of hearing; mental disturbances; nausea; rapid or difficult breathing; ringing in the ears; seizures; sluggishness; vomiting; yellowing of the skin or eyes.

Proper storage of Ionil Plus Shampoo:

Store Ionil Plus Shampoo at room temperature, between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, moisture, and light. Do not freeze. Do not store in the bathroom. Keep Ionil Plus Shampoo out of the reach of children and away from pets.

General information:

• If you have any questions about Ionil Plus Shampoo, please talk with your doctor, pharmacist, or other health care provider.


• Ionil Plus Shampoo is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Ionil Plus Shampoo. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

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Isordil

isosorbide dinitrate

Dosage Form: Sublingual Tablets

Rx only

Isordil Description

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

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

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 is freely soluble in organic solvents such as acetone, alcohol, and ether, but is only sparingly soluble in water.

Each Isordil® Sublingual tablet contains 2.5, 5, or 10 mg of isosorbide dinitrate. The inactive ingredients in each tablet are cellulose, lactose, magnesium stearate, and starch. The 2.5 mg dosage strength also contains D&C Yellow 10 and FD&C Yellow 6, and the 5 mg dosage strength also contains FD&C Red 40.

Isordil - Clinical Pharmacology

The principal pharmacological action of isosorbide dinitrate is relaxation of vascular smooth muscle and consequent dilatation of peripheral arteries and veins, especially the latter. 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). Dilatation of the coronary arteries also occurs. The relative importance of preload reduction, afterload reduction, and coronary dilatation remains undefined.

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. 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. Attempts to overcome nitrate tolerance by dose escalation, even to doses far in excess of those used acutely, have consistently failed. Only after nitrates have been absent from the body for several hours has their anti-anginal efficacy been restored.

Pharmacokinetics

Bioavailability of ISDN after single sublingual doses is 40 to 50%.Multiple-dose studies of sublingual ISDN pharmacokinetics have not been reported; multiple-dose studies of ingested ISDN have observed progressive increases in bioavailability during chronic therapy. Serum levels of ISDN reach their maxima 10 to 15 minutes after sublingual dosing.

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 extrahepatic metabolism must also occur. Clearance is affected primarily by denitration to the 2-mononitrate (15 to 25%) and the 5-mononitrate (75 to 85%).

Both metabolites have biological activity, especially the 5-mononitrate. 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. 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.

The daily dose-free interval sufficient to avoid tolerance to organic nitrates has not been well defined. 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. 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.

Few well-controlled clinical trials of organic nitrates have been designed to detect rebound or withdrawal effects. 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.

Clinical trials

In a controlled trial in which 0.4 mg of sublingual nitroglycerin took 1.9 minutes to begin to produce an anti-anginal effect, 5 mg of sublingual ISDN took 3.4 minutes to begin to produce a similar effect. In the same trial, the anti-anginal effect of the sublingual nitroglycerin was evident for about an hour, while that of the sublingual ISDN lasted about 2 hours.

In other controlled trials, the anti-anginal efficacy of sublingual ISDN has persisted for periods ranging from 30 minutes up to 4 hours.

Multiple-dose trials of sublingual ISDN have not been reported.

Multiple-dose trials of ingested formulations of ISDN have shown that ISDN's anti-anginal efficacy is substantially attenuated by tolerance unless the daily regimen includes a dose-free interval of at least 14 hours. The daily dose-free interval necessary in any chronic regimen using sublingual ISDN is not known.

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 has, however, ever actually been shown to achieve this duration of effect. In the absence of data from multiple-dose trials, and considering the capacity of organic nitrates to induce tolerance, it is not reasonable to assume that multiple sublingual ISDN tablets taken during the course of a day will all have similar effects.

Indications and Usage for Isordil

Isordil (isosorbide dinitrate) Sublingual tablets are indicated for the prevention and treatment of angina pectoris due to coronary artery disease. However, because the onset of action of sublingual ISDN is significantly slower than that of sublingual nitroglycerin, sublingual ISDN is not the drug of first choice for abortion of an acute anginal episode.

Contraindications

Allergic reactions to organic nitrates are extremely rare, but they do occur. Isordil is contraindicated in patients who are allergic to isosorbide dinitrate or any of its other ingredients.

Warnings

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 extremities and with central volume expansion.

The benefits of sublingual 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.

Precautions

General

Severe hypotension, particularly with upright posture, may occur with even small doses of isosorbide dinitrate. 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 isosorbide dinitrate may be accompanied by paradoxical bradycardia and increased angina pectoris.

Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy.

As tolerance to isosorbide dinitrate 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 and decreased exercise tolerance. The importance of these observations to the routine, clinical use of sublingual isosorbide dinitrate 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 isosorbide dinitrate 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 isosorbide dinitrate. 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 isosorbide dinitrate, 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 isosorbide dinitrate-induced headaches with no deleterious effect on isosorbide dinitrate's anti-anginal efficacy.

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.

Drug Interactions

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

Carcinogenesis, Mutagenesis, Impairment of Fertility

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.

Pregnancy Category C

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.

Nursing Mothers

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

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of Isordil (isosorbide dinitrate) Sublingual 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.

Adverse Reactions

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. Headache, which may be severe, is the most commonly reported side effect. Headache may be recurrent with each daily dose, especially at higher doses. Transient episodes of lightheadedness, occasionally related to blood pressure changes, may also occur.

Hypotension occurs infrequently, but in some patients it may be severe enough to warrant discontinuation of therapy. Syncope, crescendo angina, and rebound hypertension have been reported but are uncommon.

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

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

Overdosage

Hemodynamic Effects

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. 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 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.

There are no data suggesting what dose of isosorbide dinitrate 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 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.

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. 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. 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 isosorbide dinitrate overdose in these patients may be subtle and difficult, and invasive monitoring may be required.

Methemoglobinemia

Nitrate ions liberated during metabolism of isosorbide dinitrate can oxidize hemoglobin into methemoglobin. 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. 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.

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.

Isordil Dosage and Administration

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 ISDN must provide a daily dose-free interval to minimize the development of this tolerance. In the case of sublingual tablets, it is probably true that one of the daily dose-free intervals must be somewhat longer than 14 hours.

As also noted under CLINICAL PHARMACOLOGY, the efficacy of daily doses after the first has never been demonstrated.

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

A patient anticipating activity likely to cause angina should take one Isordil Sublingual tablet (2.5 to 5 mg) about 15 minutes before the activity is expected to begin. Isordil Sublingual tablets may be used to abort an acute anginal episode, but its use is recommended only in patients who fail to respond to sublingual nitroglycerin.

How is Isordil Supplied

Isordil® (isosorbide dinitrate) Sublingual Tablets are available as follows:

2.5 mg, round, yellow tablets imprinted "2.5" on one side and "W" on reverse side:

NDC 0008-4139-01, bottles of 100.

5 mg, round, pink tablets imprinted "5" on one side and "W" on reverse side:

NDC 0008-4126-01, bottles of 100.

Store at room temperature, approximately 25° C (77° F)

Protect from light

Keep bottles tightly closed

Dispense in a light-resistant, tight container

Use carton to protect blisters from light

10 mg, round, white tablets imprinted "10" on one side and "Wyeth" on reverse side:

NDC 0008-4161-01, bottles of 100.

Store at room temperature, approximately 25° C (77° F)

Keep tightly closed

Dispense in a tight container

ALSO AVAILABLE

Oral Titradose® Tablets in the following dosage strengths:

5 mg, NDC 0008-4152, in bottles of 100 or 1,000.

10 mg, NDC 0008-4153, in bottles of 100 or 1,000.

20 mg, NDC 0008-4154, in bottles of 100 or 500.

30 mg, NDC 0008-4159, in bottles of 100.

40 mg, NDC 0008-4192, in bottles of 100.

Wyeth Laboratories

A Wyeth-Ayerst Company

Philadelphia, PA 19101

CI 4370-3

Isordil  isosorbide dinitrate  tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0008-4139 Route of Administration ORAL DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength isosorbide dinitrate (isosorbide) Active 2.5 MILLIGRAM  In 1 TABLET cellulose Inactive   lactose Inactive   magnesium stearate Inactive   starch Inactive   D&C Yellow 10 Inactive   FD&C Yellow 6 Inactive

Product Characteristics Color YELLOW (YELLOW) Score no score Shape ROUND (ROUND) Size 4mm Flavor Imprint Code 2.5;W Contains          Coating false Symbol false

Packaging # NDC Package Description Multilevel Packaging 1 0008-4139-01 100 TABLET In 1 BOTTLE None

Isordil  isosorbide dinitrate  tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0008-4126 Route of Administration ORAL DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength isosorbide dinitrate (isosorbide) Active 5 MILLIGRAM  In 1 TABLET cellulose Inactive   lactose Inactive   magnesium stearate Inactive   starch Inactive   FD&C Red 40 Inactive

Product Characteristics Color PINK (PINK) Score no score Shape ROUND (ROUND) Size 4mm Flavor Imprint Code 5;W Contains          Coating false Symbol false

Packaging # NDC Package Description Multilevel Packaging 1 0008-4126-01 100 TABLET In 1 BOTTLE None

Isordil  isosorbide dinitrate  tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0008-4161 Route of Administration ORAL DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength isosorbide dinitrate (isosorbide) Active 10 MILLIGRAM  In 1 TABLET cellulose Inactive   lactose Inactive   magnesium stearate Inactive   starch Inactive

Product Characteristics Color WHITE (WHITE) Score no score Shape ROUND (ROUND) Size 4mm Flavor Imprint Code 10;Wyeth Contains          Coating false Symbol false

Packaging # NDC Package Description Multilevel Packaging 1 0008-4161-01 100 TABLET In 1 BOTTLE None

Revised: 03/2006Wyeth Laboratories

More Isordil resources

• Isordil Side Effects (in more detail)
• Isordil Dosage
• Isordil Use in Pregnancy & Breastfeeding
• Drug Images
• Isordil Drug Interactions
• Isordil Support Group
• 0 Reviews for Isordil - Add your own review/rating

• Isordil Advanced Consumer (Micromedex) - Includes Dosage Information


• Isosorbide Dinitrate Professional Patient Advice (Wolters Kluwer)


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• Dilatrate-SR MedFacts Consumer Leaflet (Wolters Kluwer)


• Isordil Titradose MedFacts Consumer Leaflet (Wolters Kluwer)


• Isosorbide Dinitrate/Mononitrate Monograph (AHFS DI)

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