Imdur

Generic Name: isosorbide mononitrate

Dosage Form: tablet, extended release
Imdur®

(isosorbide mononitrate)

Extended Release Tablets

Imdur Description

Isosorbide mononitrate (ISMN), an organic nitrate and the major biologically active metabolite of isosorbide dinitrate (ISDN), is a vasodilator with effects on both arteries and veins.

Imdur® Tablets, for oral administration, contain either 30 mg, 60 mg or 120 mg of isosorbide mononitrate in an extended-release formulation. In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, hydrogenated castor oil, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose and talc.

The molecular formula of ISMN is C6H9NO6 and the molecular weight is 191.14. The chemical name for ISMN is 1,4:3,6-dianhydro-,D-glucitol 5-nitrate; the compound has the following structural formula:

ISMN is a white, crystalline, odorless compound which is stable in air and in solution, has a melting point of about 90°C, and an optical rotation of +144° (2% in water, 20°C).

Isosorbide mononitrate is freely soluble in water, ethanol, methanol, chloroform, ethyl acetate, and dichloromethane.

Imdur - Clinical Pharmacology

Mechanism of Action

The Imdur product is an oral extended-release formulation of ISMN, the major active metabolite of isosorbide dinitrate; most of the clinical activity of the dinitrate is attributable to the mononitrate.

The principal pharmacological action of ISMN and all organic nitrates in general is relaxation of vascular smooth muscle, producing dilatation of peripheral arteries and veins, especially the latter. Dilatation of the veins promotes peripheral pooling of blood, 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 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 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. Imdur Tablets, during long-term use over 42 days dosed at 120 mg once daily, continued to improve exercise performance at 4 hours and at 12 hours after dosing but its effects (although better than placebo) are less than or at best equal to the effects of the first dose of 60 mg.

Pharmacokinetics and Metabolism

After oral administration of ISMN as a solution or immediate-release tablets, maximum plasma concentrations of ISMN are achieved in 30 to 60 minutes, with an absolute bioavailability of approximately 100%. After intravenous administration, ISMN is distributed into total body water in about 9 minutes with a volume of distribution of approximately 0.6-0.7 L/kg. Isosorbide mononitrate is approximately 5% bound to human plasma proteins and is distributed into blood cells and saliva. Isosorbide mononitrate is primarily metabolized by the liver, but unlike oral isosorbide dinitrate, it is not subject to first-pass metabolism. Isosorbide mononitrate is cleared by denitration to isosorbide and glucuronidation as the mononitrate, with 96% of the administered dose excreted in the urine within 5 days and only about 1% eliminated in the feces. At least six different compounds have been detected in urine, with about 2% of the dose excreted as the unchanged drug and at least five metabolites. The metabolites are not pharmacologically active. Renal clearance accounts for only about 4% of total body clearance. The mean plasma elimination half-life of ISMN is approximately 5 hours.

The disposition of ISMN in patients with various degrees of renal insufficiency, liver cirrhosis, or cardiac dysfunction was evaluated and found to be similar to that observed in healthy subjects. The elimination half-life of ISMN was not prolonged, and there was no drug accumulation in patients with chronic renal failure after multiple oral dosing.

The pharmacokinetics and/or bioavailability of Imdur Tablets have been studied in both normal volunteers and patients following single- and multiple-dose administration. Data from these studies suggest that the pharmacokinetics of ISMN administered as Imdur Tablets are similar between normal healthy volunteers and patients with angina pectoris. In single- and multiple-dose studies, the pharmacokinetics of ISMN were dose proportional between 30 mg and 240 mg.

In a multiple-dose study, the effect of age on the pharmacokinetic profile of Imdur 60 mg and 120 mg (2 × 60 mg) was evaluated in subjects ≥45 years. The results of that study indicate that there are no significant differences in any of the pharmacokinetic variables of ISMN between elderly (≥65 years) and younger individuals (45–64 years) for the Imdur 60 mg dose. The administration of Imdur Tablets 120 mg (2 × 60 mg tablets every 24 hours for 7 days) produced a dose-proportional increase in Cmax and AUC, without changes in Tmax or the terminal half-life. The older group (65-74 years) showed 30% lower apparent oral clearance (Cl/F) following the higher dose, i.e., 120 mg, compared to the younger group (45-64 years); Cl/F was not different between the two groups following the 60 mg regimen. While Cl/F was independent of dose in the younger group, the older group showed slightly lower Cl/F following the 120 mg regimen compared to the 60 mg regimen. Differences between the two age groups, however, were not statistically significant. In the same study, females showed a slight (15%) reduction in clearance when the dose was increased. Females showed higher AUCs and Cmax compared to males, but these differences were accounted for by differences in body weight between the two groups. When the data were analyzed using age as a variable, the results indicated that there were no significant differences in any of the pharmacokinetic variables of ISMN between older (≥65 years) and younger individuals (45-64 years). The results of this study, however, should be viewed with caution due to the small number of subjects in each age subgroup and consequently the lack of sufficient statistical power.

The following table summarizes key pharmacokinetic parameters of ISMN after single- and multiple-dose administration of ISMN as an oral solution or Imdur Tablets:

	SINGLE-DOSE STUDIES		MULTIPLE-DOSE STUDIES
PARAMETER	ISMN 60 mg	Imdur 60 mg	Imdur 60 mg	Imdur 120 mg
Cmax(ng/mL)	1242-1534	424-541	557-572	1151-1180
Tmax(hr)	0.6-0.7	3.1-4.5	2.9-4.2	3.1-3.2
AUC (ng∙hr/mL)	8189-8313	5990-7452	6625-7555	14241-16800
T½ (hr)	4.8-5.1	6.3-6.6	6.2-6.3	6.2-6.4
Cl/F (mL/min)	120-122	151-187	132-151	119-140

Food Effects

The influence of food on the bioavailability of ISMN after single-dose administration of Imdur Tablets 60 mg was evaluated in three different studies involving either a "light" breakfast or a high-calorie, high-fat breakfast. Results of these studies indicate that concomitant food intake may decrease the rate (increase in Tmax) but not the extent (AUC) of absorption of ISMN.

Clinical Trials

Controlled trials with Imdur Tablets have demonstrated antianginal activity following acute and chronic dosing. Administration of Imdur Tablets once daily, taken early in the morning on arising, provided at least 12 hours of antianginal activity.

In a placebo-controlled parallel study, 30, 60, 120 and 240 mg of Imdur Tablets were administered once daily for up to 6 weeks. Prior to randomization, all patients completed a 1- to 3-week single-blind placebo phase to demonstrate nitrate responsiveness and total exercise treadmill time reproducibility. Exercise tolerance tests using the Bruce Protocol were conducted prior to and at 4 and 12 hours after the morning dose on days 1, 7, 14, 28 and 42 of the double-blind period. Imdur Tablets 30 and 60 mg (only doses evaluated acutely) demonstrated a significant increase from baseline in total treadmill time relative to placebo at 4 and 12 hours after the administration of the first dose. At day 42, the 120 and 240 mg dose of Imdur Tablets demonstrated a significant increase in total treadmill time at 4 and 12 hours post dosing, but by day 42, the 30 and 60 mg doses no longer were differentiable from placebo. Throughout chronic dosing, rebound was not observed in any Imdur treatment group.

Pooled data from two other trials, comparing Imdur Tablets 60 mg once daily, ISDN 30 mg QID, and placebo QID in patients with chronic stable angina using a randomized, double-blind, three-way crossover design found statistically significant increases in exercise tolerance times for Imdur Tablets compared to placebo at hours 4, 8 and 12 and to ISDN at hour 4. The increases in exercise tolerance on day 14, although statistically significant compared to placebo, were about half of that seen on day 1 of the trial.

Indications and Usage for Imdur

Imdur 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

Imdur Tablets are contraindicated in patients who have shown hypersensitivity or idiosyncratic reactions to other nitrates or nitrites.

Warnings

Amplification of the vasodilatory effects of Imdur 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 ISMN 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 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 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 Imdur Tablets can be maintained by carefully following the prescribed schedule of dosing. For most patients, this can be accomplished by taking the dose on arising.

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 or acetaminophen often successfully relieves isosorbide mononitrate-induced headaches with no deleterious effect on isosorbide mononitrate's antianginal efficacy.

Treatment with isosorbide mononitrate may be associated with light-headedness 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.

Drug/Laboratory Test Interactions

Nitrates and nitrites may interfere with the Zlatkis-Zak color reaction, causing falsely low readings in serum cholesterol determinations.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence of carcinogenicity was observed in rats exposed to isosorbide mononitrate in their diets at doses of up to 900 mg/kg/day for the first 6 months and 500 mg/kg/day for the remaining duration of a study in which males were dosed for up to 121 weeks and females were dosed for up to 137 weeks. No evidence of carcinogenicity was observed in mice exposed to isosorbide mononitrate in their diets for up to 104 weeks at doses of up to 900 mg/kg/day.

Isosorbide mononitrate did not produce gene mutations (Ames test, mouse lymphoma test) or chromosome aberrations (human lymphocyte and mouse micronucleus tests) at biologically relevant concentrations.

No effects on fertility were observed in a study in which male and female rats were administered doses of up to 750 mg/kg/day beginning, in males, 9 weeks prior to mating, and in females, 2 weeks prior to mating.

Pregnancy

Teratogenic Effects

Pregnancy Category B

In studies designed to detect effects of isosorbide mononitrate on embryo-fetal development, doses of up to 240 or 248 mg/kg/day, administered to pregnant rats and rabbits, were unassociated with evidence of such effects. These animal doses are about 100 times the maximum recommended human dose (120 mg in a 50 kg woman) when comparison is based on body weight; when comparison is based on body surface area, the rat dose is about 17 times the human dose and the rabbit dose is about 38 times the human dose. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Imdur Tablets should be used during pregnancy only if clearly needed.

Nonteratogenic Effects

Neonatal survival and development and incidence of stillbirths were adversely affected when pregnant rats were administered oral doses of 750 (but not 300) mg isosorbide mononitrate/kg/day during late gestation and lactation. This dose (about 312 times the human dose when comparison is based on body weight and 54 times the human dose when comparison is based on body surface area) was associated with decreases in maternal weight gain and motor activity and evidence of impaired lactation.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ISMN is administered to a nursing mother.

Pediatric Use

The safety and effectiveness of ISMN in pediatric patients have not been established.

Geriatric Use

Clinical studies of Imdur Tablets did not include sufficient information on patients age 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience for Imdur has not identified differences in response between elderly and younger patients. Clinical experience for organic nitrates reported in the literature identified a potential for severe hypotension and increased sensitivity to nitrates in the elderly. 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.

Elderly patients may have reduced baroreceptor function and may develop severe orthostatic hypotension when vasodilators are used. Imdur should therefore be used with caution in elderly patients who may be volume depleted, on multiple medications or who, for whatever reason, are already hypotensive. Hypotension induced by isosorbide mononitrate may be accompanied by paradoxical bradycardia and increased angina pectoris.

Elderly patients may be more susceptible to hypotension and may be at a greater risk of falling at therapeutic doses of nitroglycerin.

Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy, particularly in the elderly.

Adverse Reactions

The table below shows the frequencies of the adverse events that occurred in >5% of the subjects in three placebo-controlled North American studies in which patients in the active treatment arm received 30 mg, 60 mg, 120 mg, or 240 mg of isosorbide mononitrate as Imdur Tablets once daily. In parentheses, the same table shows the frequencies with which these adverse events were associated with the discontinuation of treatment. Overall, 8% of the patients who received 30 mg, 60 mg, 120 mg, or 240 mg of isosorbide mononitrate in the three placebo-controlled North American studies discontinued treatment because of adverse events. Most of these discontinued because of headache. Dizziness was rarely associated with withdrawal from these studies. Since headache appears to be a dose-related adverse effect and tends to disappear with continued treatment, it is recommended that Imdur treatment be initiated at low doses for several days before being increased to desired levels.

FREQUENCY AND ADVERSE EVENTS (DISCONTINUED)*

Three Controlled North American Studies
Dose	Placebo	30 mg	60 mg	120 mg†	240 mg†
* Some individuals discontinued for multiple reasons. † Patients were started on 60 mg and titrated to their final dose.
Patients	96	60	102	65	65
Headache	15% (0%)	38% (5%)	51% (8%)	42% (5%)	57% (8%)
Dizziness	4% (0%)	8% (0%)	11% (1%)	9% (2%)	9% (2%)

In addition, the three North American trials were pooled with 11 controlled trials conducted in Europe. Among the 14 controlled trials, a total of 711 patients were randomized to Imdur Tablets. When the pooled data were reviewed, headache and dizziness were the only adverse events that were reported by >5% of patients. Other adverse events, each reported by ≤5% of exposed patients, and in many cases of uncertain relation to drug treatment, were:

Autonomic Nervous System Disorders: Dry mouth, hot flushes.

Body as a Whole: Asthenia, back pain, chest pain, edema, fatigue, fever, flu-like symptoms, malaise, rigors.

Cardiovascular Disorders, General: Cardiac failure, hypertension, hypotension.

Central and Peripheral Nervous System Disorders: Dizziness, headache, hypoesthesia, migraine, neuritis, paresis, paresthesia, ptosis, tremor, vertigo.

Gastrointestinal System Disorders: Abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gastric ulcer, gastritis, glossitis, hemorrhagic gastric ulcer, hemorrhoids, loose stools, melena, nausea, vomiting.

Hearing and Vestibular Disorders: Earache, tinnitus, tympanic membrane perforation.

Heart Rate and Rhythm Disorders: Arrhythmia, arrhythmia atrial, atrial fibrillation, bradycardia, bundle branch block, extrasystole, palpitation, tachycardia, ventricular tachycardia.

Liver and Biliary System Disorders: SGOT increase, SGPT increase.

Metabolic and Nutritional Disorders: Hyperuricemia, hypokalemia.

Musculoskeletal System Disorders: Arthralgia, frozen shoulder, muscle weakness, musculoskeletal pain, myalgia, myositis, tendon disorder, torticollis.

Myo-, Endo-, Pericardial and Valve Disorders: Angina pectoris aggravated, heart murmur, heart sound abnormal, myocardial infarction, Q wave abnormality.

Platelet, Bleeding and Clotting Disorders: Purpura, thrombocytopenia.

Psychiatric Disorders: Anxiety, concentration impaired, confusion, decreased libido, depression, impotence, insomnia, nervousness, paroniria, somnolence.

Red Blood Cell Disorder: Hypochromic anemia.

Reproductive Disorders, Female: Atrophic vaginitis, breast pain.

Resistance Mechanism Disorders: Bacterial infection, moniliasis, viral infection.

Respiratory System Disorders: Bronchitis, bronchospasm, coughing, dyspnea, increased sputum, nasal congestion, pharyngitis, pneumonia, pulmonary infiltration, rales, rhinitis, sinusitis.

Skin and Appendages Disorders: Acne, hair texture abnormal, increased sweating, pruritus, rash, skin nodule.

Urinary System Disorders: Polyuria, renal calculus, urinary tract infection.

Vascular (Extracardiac) Disorders: Flushing, intermittent claudication, leg ulcer, varicose vein.

Vision Disorders: Conjunctivitis, photophobia, vision abnormal.

In addition, the following spontaneous adverse event has been reported during the marketing of isosorbide mononitrate: syncope.

Overdosage

Hemodynamic Effects

The ill effects of isosorbide mononitrate overdose are generally the result 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 (eg, 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 manifest 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 2-4 weeks of continuous nitroglycerin therapy at 3.1 to 4.4 mg/hr (equivalent, in total administered dose of nitrate ions, to 7.8-11.1 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, 1-2 mg/kg intravenously.

Imdur Dosage and Administration

The recommended starting dose of Imdur Tablets is 30 mg (given as a single 30 mg tablet or as 1/2 of a 60 mg tablet) or 60 mg (given as a single tablet) once daily. After several days, the dosage may be increased to 120 mg (given as a single 120 mg tablet or as two 60 mg tablets) once daily. Rarely, 240 mg may be required. The daily dose of Imdur Tablets should be taken in the morning on arising. Imdur Extended Release Tablets should not be chewed or crushed and should be swallowed together with a half-glassful of fluid. Do not break the 30 mg tablet.

How is Imdur Supplied

Imdur Extended Release Tablets 30 mg are white, capsule-shaped tablets scored on one side and engraved "Imdur" on the unscored side. They are supplied as follows:

Bottles of 100

NDC 0085-1374-01

Imdur Extended Release Tablets 60 mg are white, capsule-shaped tablets scored on one side with "60-60" and engraved "Imdur" on the unscored side. They are supplied as follows:

Bottles of 100

NDC 0085-2028-01

Imdur Extended Release Tablets 120 mg are white, capsule-shaped tablets engraved "Imdur" on one side and "120" on the other side. They are supplied as follows:

Bottles of 100

NDC 0085-0091-01

Store at controlled room temperature 20°-25°C (68°-77°F) [See USP].

Imdur®

(isoserbide mononitrate)

Extended Release Tablets

Copyright © 1993, 2006 Schering Corporation, a subsidiary of Merck & Co., Inc. All rights reserved.

Rev. 12/10

PRINCIPAL DISPLAY PANEL - 30 mg Tablet Bottle Label

NDC 0085-1374-01

100 Tablets

Imdur®

(isosorbide mononitrate)

Extended Release Tablets

30 mg

Rx only

PRINCIPAL DISPLAY PANEL- 60 mg Tablet Bottle Label

NDC 0085-2028-01

100 Tablets

Imdur®

(isosorbide mononitrate)

Extended Release Tablets

60 mg

Rx only

PRINCIPAL DISPLAY PANEL - 120 mg Tablet Bottle Label

NDC 0085-0091-01

100 Tablets

Imdur®

(isosorbide mononitrate)

Extended Release Tablets

120 mg

Rx only

Imdur  isosorbide mononitrate  tablet, extended release

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0085-1374 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength isosorbide mononitrate (isosorbide) isosorbide mononitrate 30 mg

Inactive Ingredients Ingredient Name Strength silicon dioxide   hydrogenated castor oil   hypromelloses   lactose monohydrate   magnesium stearate   cellulose, microcrystalline   talc

Product Characteristics Color WHITE Score 2 pieces Shape OVAL (capsule-shaped) Size 9mm Flavor Imprint Code Imdur Contains

Packaging # NDC Package Description Multilevel Packaging 1 0085-1374-01 100 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA075155	01/05/2006

Imdur  isosorbide mononitrate  tablet, extended release

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0085-2028 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength isosorbide mononitrate (isosorbide) isosorbide mononitrate 60 mg

Inactive Ingredients Ingredient Name Strength silicon dioxide   hydrogenated castor oil   hypromelloses   lactose monohydrate   magnesium stearate   cellulose, microcrystalline   talc

Product Characteristics Color WHITE Score 2 pieces Shape OVAL (capsule-shaped) Size 15mm Flavor Imprint Code Imdur;60;60 Contains

Packaging # NDC Package Description Multilevel Packaging 1 0085-2028-01 100 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA075155	01/05/2006

Imdur  isosorbide mononitrate  tablet, extended release

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0085-0091 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength isosorbide mononitrate (isosorbide) isosorbide mononitrate 120 mg

Inactive Ingredients Ingredient Name Strength silicon dioxide   hydrogenated castor oil   hypromelloses   lactose monohydrate   magnesium stearate   cellulose, microcrystalline   talc

Product Characteristics Color WHITE Score no score Shape OVAL (capsule-shaped) Size 16mm Flavor Imprint Code Imdur;120 Contains

Packaging # NDC Package Description Multilevel Packaging 1 0085-0091-01 100 TABLET In 1 BOTTLE None

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA075155	01/05/2006

Labeler - Schering Corporation (001317601)

Registrant - Kremers Urban Pharmaceuticals Inc. (006422406)

Establishment
Name	Address	ID/FEI	Operations
Kremers Urban Pharmaceuticals Inc.		006422406	MANUFACTURE

Revised: 02/2011Schering Corporation

More Imdur resources

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

• Imdur Advanced Consumer (Micromedex) - Includes Dosage Information


• Imdur Consumer Overview


• Imdur Sustained-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)


• Isosorbide Mononitrate Professional Patient Advice (Wolters Kluwer)


• ISMO MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Imdur with other medications

• Angina Pectoris Prophylaxis
• Heart Failure

Estazolam

Class: Benzodiazepines
VA Class: CN302
Chemical Name: 8-Chloro-6-phenyl-4H -[1,2,4]triazolo[4,3-a][1,4]benzodiazepine
Molecular Formula: C₁₆H₁₁ClN₄
CAS Number: 29975-16-4

Introduction

Benzodiazepine, sedative and hypnotic.^e

Uses for Estazolam

Insomnia

Short-term management of insomnia characterized by difficulty in falling asleep, nocturnal awakenings, and/or early morning awakening.^e Has been used effectively for periods of up to 12 weeks in duration.

Decreases sleep latency, increases the duration of sleep, and decreases the number of nocturnal awakenings.^e

Estazolam Dosage and Administration

General

• 
  

  Use only when able to get a full night's sleep of sleep before being active again.^e

  
  


• 
  

  Avoid prolonged administration. Generally limit hypnotic therapy to 7–10 days.^e

  
  


• 
  

  Avoid abrupt discontinuance in patients who have received prolonged therapy (e.g., 6 weeks) because of potential for precipitating withdrawal manifestations and rebound insomnia. Gradually taper dosage, particularly in patients with a seizure history.^e (See Withdrawal Effects under Cautions.)

  
  

Administration

Oral Administration

Administer at bedtime.^e

Dosage

Individualize dosage; use smallest effective dosage.

Adults

Insomnia

Oral

Initially, 1 mg at bedtime.^e

If drug is well-tolerated, gradually increase dosage to 2 mg if needed.^e

Special Populations

Hepatic Impairment

No specific dosage recommendations.^e

Renal Impairment

No specific dosage recommendations.^e

Geriatric or Debilitated Patients

Use smallest effective dosage. In small or debilitated geriatric patients, initially, 0.5 mg at bedtime.^e

Cautions for Estazolam

Contraindications

• 
  

  Known hypersensitivity to estazolam or any ingredient in the formulation. ^c

  
  


• 
  

  Pregnancy.^{e f}

  
  


• 
  

  Concomitant use of ketoconazole or itraconazole.^e (See Specific Drugs under Interactions.)

  
  

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; use contraindicated during pregnancy.^{b e f} If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.^{b e f}

Adequate Patient Evaluation

Insomnia may be a manifestation of an underlying physical and/or psychiatric disorder; carefully evaluate patient before providing symptomatic treatment.^{b e}

Worsening of insomnia or emergence of new abnormal thinking or behavior may indicate the presence of an underlying psychiatric and/or medical condition.^b

Complex Sleep-related Behaviors

Potential risk of complex sleep-related behaviors such as sleep-driving (i.e., driving while not fully awake after ingesting a sedative-hypnotic drug with no memory of the event), making phone calls, or preparing and eating food while asleep.^{c e}

CNS Depression

Performance of activities requiring mental alertness and physical coordination may be impaired.^e Risk of residual daytime sedation and impaired performance.^e

Concurrent use of other CNS depressants may cause additive or potentiated CNS depression.^e (See Specific Drugs under Interactions.)

Adverse Psychiatric Events

Abnormal thinking and behavioral changes (e.g., aggressiveness, uncharacteristic extroversion, excitement, bizarre behavior, agitation, hallucinations, depersonalization, amnesia) may occur unpredictably in patients receiving benzodiazepines.^{b e}

Some adverse effects appear to be dose related; use the lowest effective dose.^a

Withdrawal Effects

Abrupt discontinuance may result in symptoms of withdrawal (similar to barbiturates or alcohol).^{b e}

Interactions

Concomitant use with drugs that are potent inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole) is contraindicated.^e Concomitant use with lesser inhibitors of CYP3A4 (e.g., nefazodone, fluvoxamine, cimetidine, diltiazem, isoniazid, macrolide antibiotics) requires particular caution.^e (See Specific Drugs under Interactions.)

Sensitivity Reactions

Potential risk of anaphylaxis and angioedema; may occur even with the first dose of drug.^c

General Precautions

Respiratory Effects

Possible dose-related respiratory depression, especially in patients with compromised respiratory function.^{b e} Monitor patients with compromised respiratory function.^e

Suicide

Use with caution in depressed patients; potential for suicidal tendencies.^e Prescribe and dispense drug in the smallest feasible quantity.^e

Specific Populations

Pregnancy

Category X. ^{e f} (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Benzodiazepines generally are distributed into milk.^b Estazolam is distributed into milk in rats; not known whether the drug is distributed into human milk.^{e f} Use not recommended in nursing women.^e

Pediatric Use

Safety and efficacy not established in children <18 years of age.^e

Geriatric Use

Potential increased sensitivity to dose related adverse effects (e.g., oversedation, dizziness, confusion, ataxia); use low initial dosage and monitor closely, especially in small or debilitated elderly patients. ^e

Hepatic Impairment

Potential increased sensitivity to adverse CNS effects (e.g., oversedation, dizziness, confusion, ataxia); use with caution and monitor closely.^{b e}

Renal Impairment

Potential increased sensitivity to adverse CNS effects (e.g., oversedation, dizziness, confusion, ataxia); use with caution and monitor closely.^{b e}

Common Adverse Effects

Somnolence, hypokinesia, dizziness, abnormal coordination.^e

Interactions for Estazolam

Metabolized principally by CYP3A4.^e

Does not inhibit CYP isoenzymes 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, or 3A in vitro.^e Pharmacokinetic interactions with drugs metabolized by these isoenzymes unlikely.^e Not known whether estazolam induces drug metabolizing enzymes.^e

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: potential pharmacokinetic interaction (increased plasma estazolam concentrations).^e Concomitant use with potent CYP3A inhibitors is contraindicated.^e Use less potent CYP3A inhibitors with caution; estazolam dosage reduction may be indicated (see table).^e

Inducers of CYP3A4: potential pharmacokinetic interaction (decreased plasma estazolam concentrations).^e

Specific Drugs

Drug	Interaction	Comments
Antifungals, azoles (fluconazole, itraconazole, ketoconazole)	Increased estazolam plasma concentrationsb e	Concomitant use of itraconazole and ketoconazole contraindicatede
Barbiturates	Possible decreased plasma estazolam concentrationsc Additive CNS depressant effectse	Use concomitantly with cautionb
Calcium-channel blocking agents (diltiazem, nicardipine, nifedipine, verapamil)	Possible decreased clearance of estazolam and increased plasma estazolam concentrations e	Use with caution; consider estazolam dosage reductione
Carbamazepine	Possible decreased plasma estazolam concentrationsb e
Cigarette smoking	Possible decreased sedative effect due to increased clearance of estazolame
Cimetidine	Possible decreased clearance of estazolam and increased plasma estazolam concentrations e	Use with caution; consider estazolam dosage reductione
CNS depressants (e.g., alcohol, anticonvulsants, antihistamines, narcotics, psychotropic agents, sedatives)	Additive CNS depressant effectse	Avoid concomitant use of alcohol;e use other CNS depressants with cautionb
Fluoxetine	Pharmacokinetic interactions unlikelye
Fluvoxamine	Possible decreased clearance of estazolam and increased plasma estazolam concentrations e	Use with caution; consider estazolam dosage reductione
Isoniazid	Possible decreased clearance of estazolam and increased plasma estazolam concentrations e	Use with caution; consider estazolam dosage reductione
Macrolide antibiotics	Possible decreased clearance of estazolam and increased plasma estazolam concentrations e	Use with caution; consider estazolam dosage reductione
MAO inhibitors	Additive CNS depressant effectse
Nefazodone	Possible decreased clearance of estazolam and increased plasma estazolam concentrations e	Use with caution; consider estazolam dosage reductione
Phenytoin	Possible decreased plasma estazolam concentrationsb e
Rifampin	Possible decreased plasma estazolam concentrationsb e

Estazolam Pharmacokinetics

Absorption

Bioavailability

Rapidly and well absorbed following oral administration, with peak plasma concentration achieved within 2 hours.^e

Food

Effect of food on GI absorption not determined.

Distribution

Extent

Benzodiazepines are widely distributed into body tissues and cross the blood-brain barrier.^b

Benzodiazepines generally cross the placenta and are distributed into milk;^{b f} not known whether estazolam crosses the placenta or distributes into milk.^f

Plasma Protein Binding

93%.^e

Elimination

Metabolism

Rapidly and extensively metabolized in the liver, principally to 4-hydroxy-estazolam and 1-oxo-estazolam.^e

Elimination Route

Excreted in urine (91%) mainly as inactive metabolites and in feces (4%).

Half-life

14–19 hours (range: 10–24 hours) following single or multiple doses.^{e f}

Special Population

In smokers, clearance of estazolam is increased compared with nonsmokers.^e

Stability

Storage

Oral

Tablets

Tight, light-resistant containers at 20–25°C. ^e

ActionsActions

• 
  

  Effects appear to be mediated through the inhibitory neurotransmitter GABA; the sites and mechanisms of action within the CNS appear to involve a macromolecular complex (GABA_A-receptor-chloride ionophore complex) that includes GABA_A receptors, high-affinity benzodiazepine receptors, and chloride channels.

  
  

Advice to Patients

• 
  

  Provide patient a copy of the manufacturer's patient information.^{c e}

  
  


• 
  

  Potential for drug to impair mental alertness or physical coordination; avoid driving or operating machinery until effects on individual are known.^e

  
  


• 
  

  Importance of informing clinicians of any behavioral or mental changes, memory impairment, sleep driving, tolerance, or dependence/withdrawal symptoms.^{c e}

  
  


• 
  

  Importance of informing clinicians about any concomitant illnesses (e.g., respiratory disorders, depression).^e

  
  


• 
  

  Risk of anaphylactoid or hypersensitivity reactions.^c

  
  


• 
  

  Importance of taking only as prescribed; do not increase dosage or duration of therapy unless otherwise instructed by a clinician.^e

  
  


• 
  

  Importance of not consuming alcoholic beverages.^e

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed;^{e f} necessity for clinicians to advise women to avoid pregnancy during therapy.^e

  
  


• 
  

  Importance of informing patients of other precautionary information.^a (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Subject to control under the Federal Controlled Substances Act of 1970 as a schedule IV (C-IV) drug.^e

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Estazolam

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	1 mg*	Estazolam Tablets (C-IV)	Par, Teva, Watson
		2 mg*	Estazolam Tablets (C-IV)	Par, Teva, Watson

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Estazolam 1MG Tablets (WATSON LABS): 30/$24.99 or 60/$46.99

Estazolam 2MG Tablets (WATSON LABS): 30/$27.97 or 60/$51.93

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

a. AHFS drug information 2007. McEvoy GK, ed.Estazolam. Bethesda, MD: American Society of Health-System Pharmacists; 2007:pages [2525-2526].

b. AHFS drug information 2007. McEvoy GK, ed. Benzodiazepines General Statement. Bethesda, MD: American Society of Health-System Pharmacists, 2007 pages [2508-2518]

c. Food and Drug Administration. Prosom (estazolam) tablets. [March 14, 2007: Abbott Laboratories] MedWatch drug labeling changes. Rockville, MD; April 2007. From FDA websites () and ().

e. Watson Pharma. Estazolam tablet prescribing and patient information. Corona, CA; 2008 Jan.

f. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2005: 593-4.

More Estazolam resources

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

• Estazolam MedFacts Consumer Leaflet (Wolters Kluwer)


• Estazolam Prescribing Information (FDA)


• Estazolam Professional Patient Advice (Wolters Kluwer)


• estazolam Concise Consumer Information (Cerner Multum)


• estazolam Advanced Consumer (Micromedex) - Includes Dosage Information


• Prosom Prescribing Information (FDA)

Compare Estazolam with other medications

• Insomnia

Effervescent Potassium/Chloride

Generic Name: potassium bicarbonate and potassium chloride (poe TASS ee um bye KAR boe nate and poe TASS ee um KLOR ide)

Brand Names: Effervescent Potassium/Chloride, K-Lyte/Cl

What is Effervescent Potassium/Chloride (potassium bicarbonate and potassium chloride)?

Potassium is a mineral that is found in many foods and is needed for several functions of your body, especially the beating of your heart.

Potassium bicarbonate and potassium chloride is used to prevent or to treat low blood levels of potassium (hypokalemia). Potassium levels can be low as a result of a disease or from taking certain medicines, or after a prolonged illness with diarrhea or vomiting.

Potassium bicarbonate and potassium chloride may also be used for other purposes other than those listed in this medication guide.

What is the most important information I should know about Effervescent Potassium/Chloride (potassium bicarbonate and potassium chloride)?

You should not use this medication if you have kidney failure, Addison's disease, severe burns or other tissue injury, if you are dehydrated, if you take certain diuretics (water pills), or if you have high levels of potassium in your blood (hyperkalemia). Do not chew the effervescent tablet or swallow it whole. It must be dissolved in water or fruit juice before you take it. Avoid lying down for at least 30 minutes after you take this medication. Take this medication with food or just after a meal.

To be sure this medication is helping your condition, your blood may need to be tested often. Your heart rate may also be checked using an electrocardiograph or ECG (sometimes called an EKG), which measures electrical activity of the heart. This will help your doctor determine how long to treat you with potassium. Do not miss any scheduled appointments.

Serious side effects of potassium include uneven heartbeat, muscle weakness or limp feeling, severe stomach pain, and numbness or tingling in your hands, feet, or mouth.

Do not stop taking this medication without first talking to your doctor. If you stop taking potassium suddenly, your condition may become worse.

What should I discuss with my healthcare provider before taking Effervescent Potassium/Chloride (potassium bicarbonate and potassium chloride)?

You should not use this medication if you are allergic to it, or if you have certain conditions. Be sure your doctor knows if you have:

• 
  

  high levels of potassium in your blood (hyperkalemia);

  
  


• 
  

  kidney failure;

  
  


• 
  

  Addison's disease (an adrenal gland disorder);

  
  


• 
  

  a large tissue injury such as a severe burn;

  
  


• 
  

  if you are severely dehydrated; or

  
  


• 
  

  if you are taking a "potassium-sparing" diuretic (water pill) such as amiloride (Midamor, Moduretic), spironolactone (Aldactone, Aldactazide), triamterene (Dyrenium, Dyazide, Maxzide).

  
  

Before using potassium bicarbonate and potassium chloride, tell your doctor if you are allergic to any drugs, or if you have:

• kidney disease;


• 
  

  heart disease or high blood pressure;

  
  


• 
  

  a blockage in your stomach or intestines; or

  
  


• 
  

  chronic diarrhea (such as ulcerative colitis, Crohn's disease).

  
  

If you have any of these conditions, you may need a dose adjustment or special tests to safely take potassium bicarbonate and potassium chloride.

FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether potassium 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.

How should I take Effervescent Potassium/Chloride (potassium bicarbonate and potassium chloride)?

Take this medication exactly as prescribed by your doctor. Do not take it in larger amounts or for longer than recommended. Follow the directions on your prescription label.

Do not chew the effervescent tablet or swallow it whole. Drop the tablet into a glass and add at least 4 ounces (one-half cup) of cold water or fruit juice. When the tablet has completely dissolved, begin drinking the mixture slowly, over 5 to 10 minutes in all.

To make sure you get the entire dose, add a little more water to the same glass, swirl gently and drink right away.

The powder form of this medication should be mixed with at least 4 ounces (one-half cup) of cold water or fruit juice before taking. Drink the mixture slowly, over 5 to 10 minutes in all. To make sure you get the entire dose, add a little more water to the same glass, swirl gently and drink right away. Take this medication with food or just after a meal. Your treatment may include a special diet. It is very important to follow the diet plan created for you by your doctor or nutrition counselor. You should become very familiar with the list of foods you should eat or avoid to help control your condition.

Potassium-rich foods include: squash, baked potatoes (skin on), spinach, lentils, broccoli, brussels sprouts, zucchini, kidney or navy beans, raisins, watermelon, orange juice, bananas, cantaloupe, and low-fat milk or yogurt. Consume only the daily amounts recommended by your doctor or nutrition counselor.

To be sure this medication is helping your condition, your blood may need to be tested often. Your heart rate may also be checked using an electrocardiograph or ECG (sometimes called an EKG) to measure electrical activity of the heart. This test will help your doctor determine how long to treat you with potassium. Do not miss any scheduled appointments.

Do not stop taking this medication without first talking to your doctor. If you stop taking potassium suddenly, your condition may become worse. Store potassium bicarbonate and potassium chloride at room temperature away from moisture and heat. Keep the medication in a closed container.

What happens if I miss a dose?

Take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include heavy feeling in your arms or legs, confusion, weak or shallow breathing, slow or uneven heartbeat, seizure (convulsions), or feeling like you might pass out.

What should I avoid while taking Effervescent Potassium/Chloride (potassium bicarbonate and potassium chloride)?

Avoid lying down for at least 30 minutes after you take this medication.

Avoid taking potassium supplements or using other products that contain potassium without first asking your doctor. Salt substitutes or low-salt dietary products often contain potassium. If you take certain products together you may accidentally get too much potassium. Read the label of any other medicine you are using to see if it contains potassium.

Effervescent Potassium/Chloride (potassium bicarbonate and potassium chloride) side effects

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. Stop using this medication and call your doctor at once if you have any of these serious side effects:

• 
  

  confusion, anxiety, feeling like you might pass out;

  
  


• 
  

  uneven heartbeat;

  
  


• 
  

  extreme thirst, increased urination;

  
  


• 
  

  leg discomfort;

  
  


• 
  

  muscle weakness or limp feeling;

  
  


• 
  

  numbness or tingly feeling in your hands or feet, or around your mouth;

  
  


• 
  

  severe stomach pain, ongoing diarrhea or vomiting;

  
  


• 
  

  black, bloody, or tarry stools; or

  
  


• 
  

  coughing up blood or vomit that looks like coffee grounds.

  
  

Less serious side effects may include:

• 
  

  mild nausea or upset stomach;

  
  


• 
  

  mild or occasional diarrhea; or

  
  


• 
  

  slight tingling in your hands or feet.

  
  

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Effervescent Potassium/Chloride (potassium bicarbonate and potassium chloride)?

The following drugs can interact with potassium bicarbonate and potassium chloride. Tell your doctor if you are using any of these:

• 
  

  eplerenone (Inspra);

  
  


• 
  

  digoxin (digitalis, Lanoxin);

  
  


• 
  

  quinidine (Quinaglute, Quinidex, Quin-Release);

  
  


• 
  

  a bronchodilator such as ipratroprium (Atrovent) or tiotropium (Spiriva);

  
  


• 
  

  an ACE inhibitor such as benazepril (Lotensin), captopril (Capoten), fosinopril (Monopril), enalapril (Vasotec), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), or trandolapril (Mavik); or

  
  


• 
  

  any type of diuretic (water pill) such as bumetanide (Bumex), chlorothiazide (Diuril), chlorthalidone (Hygroton, Thalitone), ethacrynic acid (Edecrin), furosemide (Lasix), hydrochlorothiazide (HCTZ, HydroDiuril, Hyzaar, Lopressor, Vasoretic, Zestoretic), indapamide (Lozol), metolazone (Mykrox, Zarxolyn), or torsemide (Demadex).

  
  

This list is not complete and there may be other drugs that can interact with potassium bicarbonate and potassium chloride. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More Effervescent Potassium/Chloride resources

• Effervescent Potassium/Chloride Use in Pregnancy & Breastfeeding
• Effervescent Potassium/Chloride Drug Interactions
• 0 Reviews for Effervescent Potassium/Chloride - Add your own review/rating

Compare Effervescent Potassium/Chloride with other medications

• Hypokalemia
• Prevention of Hypokalemia

Where can I get more information?

• Your pharmacist can provide more information about potassium bicarbonate and potassium chloride.

Zagam

Generic Name: sparfloxacin (spar FLOX a sin)

Brand Names: Zagam, Zagam Respipac

What is Zagam (sparfloxacin)?

Sparfloxacin has been withdrawn from the U.S. market.

Sparfloxacin is an antibiotic in a class of drugs called fluoroquinolones. It fights bacteria in the body.

Sparfloxacin is used to treat various types of bacterial infections.

Sparfloxacin may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about Zagam (sparfloxacin)?

Sparfloxacin has been withdrawn from the U.S. market.

Take all of the sparfloxacin that has been prescribed for you even if you begin to feel better. Your symptoms may start to improve before the infection is completely treated. Take sparfloxacin with a full glass of water (8 ounces). Drink several extra glasses of fluid each day to prevent sparfloxacin crystals from forming in the urine. Do not take antacids that contain magnesium or aluminum (e.g., Tums or Rolaids), the ulcer medicine sucralfate (Carafate), or vitamin or mineral supplements that contain iron or zinc for a minimum of 4 hours after a dose of sparfloxacin. Taking antacids, sucralfate, or vitamin or mineral supplements too close to a dose of sparfloxacin can greatly decrease the effects of the antibiotic.

What should I discuss with my healthcare provider before taking Zagam (sparfloxacin)?

Before taking this medication, tell your doctor if you have

• kidney disease;


• 
  

  any kind of heart disease or heart problem; or

  
  


• 
  

  seizures or epilepsy.

  
  

You may not be able to take sparfloxacin, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above.

Sparfloxacin is in the FDA pregnancy category C. This means that it is not known whether sparfloxacin will be harmful to an unborn baby. Do not take this medication without first talking to your doctor if you are pregnant or could become pregnant during treatment. Sparfloxacin passes into breast milk and may harm a nursing infant. It may affect bone development. Do not take this medication without first talking to your doctor if you are breast-feeding a baby. Sparfloxacin is not approved for use by children younger than 12 years of age. Sparfloxacin may interfere with bone development.

How should I take Zagam (sparfloxacin)?

Take sparfloxacin exactly as directed by your doctor. If you do not understand these instructions, ask your pharmacist, nurse, or doctor to explain them to you.

Take each dose with a full glass of water (8 ounces). Drink several extra glasses of fluid each day to prevent the formation of sparfloxacin crystals in your urine.

Sparfloxacin may be taken with or without food.

Take sparfloxacin at evenly spaced intervals. Follow your doctor's instructions.

Do not take antacids that contain magnesium or aluminum (e.g., Tums or Rolaids), the ulcer medicine sucralfate (Carafate), or vitamin or mineral supplements that contain iron or zinc for a minimum of 4 hours after a dose of sparfloxacin. Taking antacids, sucralfate, or vitamin or mineral supplements too close to a dose of sparfloxacin can greatly decrease the effects of the antibiotic. Take all of the sparfloxacin that has been prescribed for you even if you begin to feel better. Your symptoms may start to improve before the infection is completely treated. Store this medication at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. However, if it is almost time for the next dose, skip the missed dose and take only the next regularly scheduled dose. Do not take a double dose of this medication unless otherwise directed by your doctor.

What happens if I overdose?

Seek emergency medical attention.

The most common symptom of a sparfloxacin overdose is irregular or slow heartbeats.

What should I avoid while taking Zagam (sparfloxacin)?

Avoid prolonged exposure to sunlight. Sparfloxacin increases the sensitivity of the skin to sunlight, and a severe sunburn may result. If sun exposure is unavoidable, wear protective clothing and sunscreen. Call your doctor if you experience severe burning, redness, itching, rash, or swelling after exposure to the sun. Use caution when driving, operating machinery, or performing other hazardous activities. Sparfloxacin may cause dizziness. If you experience dizziness, avoid these activities.

Zagam (sparfloxacin) side effects

If you experience any of the following serious side effects, stop taking sparfloxacin and seek emergency medical attention:

• 
  

  an allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives);

  
  


• 
  

  irregular heartbeats;

  
  


• 
  

  chest pain, chest discomfort, shortness of breath, or swelling of your legs or feet;

  
  


• 
  

  severe dizziness;

  
  


• 
  

  seizures;

  
  


• 
  

  confusion or hallucinations;

  
  


• 
  

  liver damage (yellowing of the skin or eyes, nausea, abdominal pain or discomfort, unusual bleeding or bruising, severe fatigue); or

  
  


• 
  

  muscle or joint pain.

  
  

If you experience any of the following less serious side effects, continue taking sparfloxacin and talk to your doctor:

• 
  

  nausea, vomiting, diarrhea, or constipation;

  
  


• 
  

  headache, lightheadedness, or drowsiness;

  
  


• 
  

  ringing in the ears; or

  
  


• 
  

  increased sensitivity of the skin to sunlight.

  
  

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

What other drugs will affect Zagam (sparfloxacin)?

Do not take antacids that contain magnesium or aluminum (e.g., Tums or Rolaids), the ulcer medicine sucralfate (Carafate), or vitamin or mineral supplements that contain iron or zinc for a minimum of 4 hours after a dose of sparfloxacin. Taking antacids, sucralfate, or vitamin or mineral supplements too close to a dose of sparfloxacin can greatly decrease the effects of the antibiotic. Do not take sparfloxacin without first talking to your doctor if you are taking any of the following drugs:

• 
  

  the heart medicines amiodarone (Cordarone), disopyramide (Norpace), quinidine (Cardioquin, Quinidex, Quinaglute, others), procainamide (Procan SR, Pronestyl), sotalol (Betapace), and bepridil (Vascor);

  
  


• 
  

  terfenadine (Seldane, Seldane-D) or astemizole (Hismanal);

  
  


• 
  

  a tricyclic antidepressant including amitriptyline (Elavil, Endep), amoxapine (Asendin), imipramine (Tofranil), nortriptyline (Pamelor), doxepin (Sinequan), and others;

  
  


• 
  

  a phenothiazine including chlorpromazine (Thorazine), fluphenazine (Prolixin), perphenazine (Trilafon), mesoridazine (Serentil), thioridazine (Mellaril), and others;

  
  


• 
  

  erythromycin (E-Mycin, Ery-Tab, E.E.S., others); or

  
  


• 
  

  cisapride (Propulsid).

  
  

Sparfloxacin and the drugs listed above may affect the rhythm of your heartbeats. You may not be able to take sparfloxacin, or you may require a dosage adjustment or special monitoring during treatment if you are taking any of the medicines listed above.

Drugs other than those listed here may also interact with sparfloxacin. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including herbal products.

More Zagam resources

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

• Zagam Advanced Consumer (Micromedex) - Includes Dosage Information


• Sparfloxacin Professional Patient Advice (Wolters Kluwer)

Compare Zagam with other medications

• Bronchitis
• Leprosy, Borderline
• Leprosy, Lepromatous
• Pneumonia

Where can I get more information?

• Your pharmacist has additional information about sparfloxacin written for health professionals that you may read.

What does my medication look like?

Sparfloxacin has been withdrawn from the U.S. market.

See also: Zagam side effects (in more detail)

Kalbitor

Generic Name: ecallantide (e KAL an tide)

Brand Names: Kalbitor

What is ecallantide?

Ecallantide is used to treat attacks of hereditary angioedema (an immune system disorder). This medication is used in people who are at least 16 years old.

Ecallantide is not a cure for hereditary angioedema.

Ecallantide may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about ecallantide?

You should not receive ecallantide if you are allergic to it.

Before you receive ecallantide, tell your doctor if you have a history of any type of allergy.

In an emergency situation it may not be possible before you are treated to tell your caregivers about your health conditions or if you are pregnant or breast-feeding. Make sure any doctor caring for you afterward knows that you have received this medication.

What should I discuss with my health care provider before receiving ecallantide?

You should not receive ecallantide if you are allergic to it.

Before you receive ecallantide, tell your doctor if you have a history of any type of allergy.

FDA pregnancy category C. It is not known whether ecallantide will harm an unborn baby. Tell your doctor if you are pregnant. It is not known whether ecallantide passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby. In an emergency situation, it may not be possible before you are treated with ecallantide to tell your caregivers if you are pregnant or breast-feeding. Make sure any doctor caring for your pregnancy or your baby knows you have received this medication.

How is ecallantide given?

Ecallantide is injected under the skin. You will receive this injection in a clinic or hospital setting where you can be monitored in case the medication causes serious side effects.

Ecallantide is usually given in 3 separate injections. If you still have symptoms of the angioedema attack, more injections may be given within 24 hours.

What happens if I miss a dose?

Since ecallantide is given by a healthcare professional, you are not likely to miss a dose.

What happens if I overdose?

Since this medication is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

What should I avoid after receiving ecallantide?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Ecallantide side effects

Tell your caregivers right away if you have any of these signs of an allergic reaction within 1 hour after receiving ecallantide:

• 
  

  chest pain or discomfort, fast or weak heartbeat;

  
  


• 
  

  flushing (warmth, redness, or tingly feeling);

  
  


• 
  

  feeling like you might pass out;

  
  


• 
  

  itching, rash, or hives;

  
  


• 
  

  runny nose, sneezing, stuffy nose;

  
  


• 
  

  wheezing, cough, throat irritation, trouble breathing; or

  
  


• 
  

  swelling of your face, lips, tongue, or throat.

  
  

An allergic reaction to ecallantide can cause symptoms that are very similar to the signs of hereditary angioedema. Your caregivers will watch you closely while you are receiving ecallantide to make sure you are not having an allergic reaction.

Less serious side effects may include:

• 
  

  headache;

  
  


• 
  

  stomach pain, nausea, vomiting, diarrhea;

  
  


• 
  

  fever;

  
  


• 
  

  tired feeling;

  
  


• 
  

  sore throat; or

  
  


• 
  

  pain, bruising, itching, redness, rash, or irritation where the injection was given.

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect ecallantide?

There may be other drugs that can interact with ecallantide. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Kalbitor resources

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

• Kalbitor Prescribing Information (FDA)


• Kalbitor Monograph (AHFS DI)


• Kalbitor Advanced Consumer (Micromedex) - Includes Dosage Information


• Kalbitor Consumer Overview


• Kalbitor MedFacts Consumer Leaflet (Wolters Kluwer)


• Ecallantide Professional Patient Advice (Wolters Kluwer)

Compare Kalbitor with other medications

• Hereditary Angioedema

Where can I get more information?

• Your doctor or pharmacist can provide more information about ecallantide.

See also: Kalbitor side effects (in more detail)