IDM Expectorant

Guaifenesin:

• IDM Expectorant (Guaifenesin) reviews

Indication: Used to assist the expectoration of phlegm from the airways in acute respiratory tract infections.

IDM Expectorant (Guaifenesin) is an expectorant which increases the output of phlegm (sputum) and bronchial secretions by reducing adhesiveness and surface tension. The increased flow of less viscous secretions promotes ciliary action and changes a dry, unproductive cough to one that is more productive and less frequent. By reducing the viscosity and adhesiveness of secretions, IDM Expectorant (Guaifenesin) increases the efficacy of the mucociliary mechanism in removing accumulated secretions from the upper and lower airway.

Potassium Iodide:

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• IDM Expectorant (Potassium Iodide) reviews

IDM Expectorant (Potassium Iodide) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

The IDM Expectorant (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq product is an immediately dispersing extended release oral dosage form of IDM Expectorant (Potassium Iodide) chloride containing 1500 mg of microencapsulated IDM Expectorant (Potassium Iodide) chloride, USP equivalent to 20 mEq of IDM Expectorant (Potassium Iodide) in a tablet.

These formulations are intended to slow the release of IDM Expectorant (Potassium Iodide) so that the likelihood of a high localized concentration of IDM Expectorant (Potassium Iodide) chloride within the gastrointestinal tract is reduced.

IDM Expectorant (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq is an electrolyte replenisher. The chemical name of the active ingredient is IDM Expectorant (Potassium Iodide) chloride, and the structural formula is KCl. IDM Expectorant (Potassium Iodide) chloride, USP occurs as a white, granular powder or as colorless crystals. It is odorless and has a saline taste. Its solutions are neutral to litmus. It is freely soluble in water and insoluble in alcohol.

IDM Expectorant (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulation (not enteric coated or wax matrix) containing individually microencapsulated IDM Expectorant (Potassium Iodide) chloride crystals which disperse upon tablet disintegration. In simulated gastric fluid at 37°C and in the absence of outside agitation, IDM Expectorant (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq begin disintegrating into microencapsulated crystals within seconds and completely disintegrates within 1 minute. The microencapsulated crystals are formulated to provide an extended release of IDM Expectorant (Potassium Iodide) chloride.

Inactive Ingredients: Colloidal silicon dioxide, crospovidone, diethyl phthalate, ethyl-cellulose, microcrystalline cellulose.

CLINICAL PHARMACOLOGY

The IDM Expectorant (Potassium Iodide) ion is the principal intracellular cation of most body tissues. IDM Expectorant (Potassium Iodide) ions participate in a number of essential physiological processes including the maintenance of intracellular tonicity; the transmission of nerve impulses; the contraction of cardiac, skeletal, and smooth muscle; and the maintenance of normal renal function.

The intracellular concentration of IDM Expectorant (Potassium Iodide) is approximately 150 to 160 mEq per liter. The normal adult plasma concentration is 3.5 to 5 mEq per liter. An active ion transport system maintains this gradient across the plasma membrane.

IDM Expectorant (Potassium Iodide) is a normal dietary constituent and under steady-state conditions the amount of IDM Expectorant (Potassium Iodide) absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. The usual dietary intake of IDM Expectorant (Potassium Iodide) is 50 to 100 mEq per day.

IDM Expectorant (Potassium Iodide) depletion will occur whenever the rate of IDM Expectorant (Potassium Iodide) loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of IDM Expectorant (Potassium Iodide) intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of IDM Expectorant (Potassium Iodide) in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. IDM Expectorant (Potassium Iodide) depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. IDM Expectorant (Potassium Iodide) depletion may produce weakness, fatigue, disturbances or cardiac rhythm (primarily ectopic beats), prominent U-waves in the electrocardiogram, and in advanced cases, flaccid paralysis and/or impaired ability to concentrate urine.

If IDM Expectorant (Potassium Iodide) depletion associated with metabolic alkalosis cannot be managed by correcting the fundamental cause of the deficiency, eg, where the patient requires long-term diuretic therapy, supplemental IDM Expectorant (Potassium Iodide) in the form of high IDM Expectorant (Potassium Iodide) food or IDM Expectorant (Potassium Iodide) chloride may be able to restore normal IDM Expectorant (Potassium Iodide) levels.

In rare circumstances (eg, patients with renal tubular acidosis) IDM Expectorant (Potassium Iodide) depletion may be associated with metabolic acidosis and hyperchloremia. In such patients IDM Expectorant (Potassium Iodide) replacement should be accomplished with IDM Expectorant (Potassium Iodide) salts other than the chloride, such as IDM Expectorant (Potassium Iodide) bicarbonate, IDM Expectorant (Potassium Iodide) citrate, IDM Expectorant (Potassium Iodide) acetate, or IDM Expectorant (Potassium Iodide) gluconate.

INDICATIONS AND USAGE

BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH CONTROLLED-RELEASE IDM Expectorant (Potassium Iodide) CHLORIDE PREPARATIONS, THESE DRUGS SHOULD BE RESERVED FOR THOSE PATIENTS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIQUID OR EFFERVESCENT IDM Expectorant (Potassium Iodide) PREPARATIONS OR FOR PATIENTS IN WHOM THERE IS A PROBLEM OF COMPLIANCE WITH THESE PREPARATIONS.

1. For the treatment of patients with hypokalemia with or without metabolic alkalosis, in digitalis intoxication, and in patients with hypokalemic familial periodic paralysis. If hypokalemia is the result of diuretic therapy, consideration should be given to the use of a lower dose of diuretic, which may be sufficient without leading to hypokalemia.

2. For the prevention of hypokalemia in patients who would be at particular risk if hypokalemia were to develop, eg, digitalized patients or patients with significant cardiac arrhythmias.

The use of IDM Expectorant (Potassium Iodide) salts in patients receiving diuretics for uncomplicated essential hypertension is often unnecessary when such patients have a normal dietary pattern and when low doses of the diuretic are used. Serum IDM Expectorant (Potassium Iodide) should be checked periodically, however, and if hypokalemia occurs, dietary supplementation with potassium-containing foods may be adequate to control milder cases. In more severe cases, and if dose adjustment of the diuretic is ineffective or unwarranted, supplementation with IDM Expectorant (Potassium Iodide) salts may be indicated.

CONTRAINDICATIONS

IDM Expectorant (Potassium Iodide) supplements are contraindicated in patients with hyperkalemia since a further increase in serum IDM Expectorant (Potassium Iodide) concentration in such patients can produce cardiac arrest. Hyperkalemia may complicate any of the following conditions: chronic renal failure, systemic acidosis, such as diabetic acidosis, acute dehydration, extensive tissue breakdown as in severe burns, adrenal insufficiency, or the administration of a potassium-sparing diuretic (eg, spironolactone, triamterene, amiloride) (see OVERDOSAGE ).

Controlled-release formulations of IDM Expectorant (Potassium Iodide) chloride have produced esophageal ulceration in certain cardiac patients with esophageal compression due to enlarged left atrium. IDM Expectorant (Potassium Iodide) supplementation, when indicated in such patients, should be given as a liquid preparation or as an aqueous (water) suspension of IDM Expectorant (Potassium Iodide) Chloride (see PRECAUTIONS: Information for Patients , and DOSAGE AND ADMINISTRATION sections).

All solid oral dosage forms of IDM Expectorant (Potassium Iodide) chloride are contraindicated in any patient in whom there is structural, pathological (eg, diabetic gastroparesis), or pharmacologic (use of anticholinergic agents or other agents with anticholinergic properties at sufficient doses to exert anticholinergic effects) cause for arrest or delay in tablet passage through the gastrointestinal tract.

WARNINGS

Hyperkalemia (see OVERDOSAGE )

In patients with impaired mechanisms for excreting IDM Expectorant (Potassium Iodide), the administration of IDM Expectorant (Potassium Iodide) salts can produce hyperkalemia and cardiac arrest. This occurs most commonly in patients given IDM Expectorant (Potassium Iodide) by the intravenous route but may also occur in patients given IDM Expectorant (Potassium Iodide) orally. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of IDM Expectorant (Potassium Iodide) salts in patients with chronic renal disease, or any other condition which impairs IDM Expectorant (Potassium Iodide) excretion, requires particularly careful monitoring of the serum IDM Expectorant (Potassium Iodide) concentration and appropriate dosage adjustment.

Interaction with Potassium-Sparing Diuretics

Hypokalemia should not be treated by the concomitant administration of IDM Expectorant (Potassium Iodide) salts and a potassium-sparing diuretic (eg, spironolactone, triamterene, or amiloride) since the simultaneous administration of these agents can produce severe hyperkalemia.

Interaction with Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE) inhibitors (eg, captopril, enalapril) will produce some IDM Expectorant (Potassium Iodide) retention by inhibiting aldosterone production. IDM Expectorant (Potassium Iodide) supplements should be given to patients receiving ACE inhibitors only with close monitoring.

Gastrointestinal Lesions

Solid oral dosage forms of IDM Expectorant (Potassium Iodide) chloride can produce ulcerative and/or stenotic lesions of the gastrointestinal tract. Based on spontaneous adverse reaction reports, enteric-coated preparations of IDM Expectorant (Potassium Iodide) chloride are associated with an increased frequency of small bowel lesions (40-50 per 100,000 patient years) compared to sustained release wax matrix formulations (less than one per 100,000 patient years). Because of the lack of extensive marketing experience with microencapsulated products, a comparison between such products and wax matrix or enteric-coated products is not available. IDM Expectorant (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulated to provide a controlled rate of release of microencapsulated IDM Expectorant (Potassium Iodide) chloride and thus to minimize the possibility of a high local concentration of IDM Expectorant (Potassium Iodide) near the gastrointestinal wall.

Prospective trials have been conducted in normal human volunteers in which the upper gastrointestinal tract was evaluated by endoscopic inspection before and after 1 week of solid oral IDM Expectorant (Potassium Iodide) chloride therapy. The ability of this model to predict events occurring in usual clinical practice is unknown. Trials which approximated usual clinical practice did not reveal any clear differences between the wax matrix and microencapsulated dosage forms. In contrast, there was a higher incidence of gastric and duodenal lesions in subjects receiving a high dose of a wax matrix controlled-release formulation under conditions which did not resemble usual or recommended clinical practice (ie, 96 mEq per day in divided doses of IDM Expectorant (Potassium Iodide) chloride administered to fasted patients, in the presence of an anticholinergic drug to delay gastric emptying). The upper gastrointestinal lesions observed by endoscopy were asymptomatic and were not accompanied by evidence of bleeding (Hemoccult testing). The relevance of these findings to the usual conditions (ie, non-fasting, no anticholinergic agent, smaller doses) under which controlled-release IDM Expectorant (Potassium Iodide) chloride products are used is uncertain; epidemiologic studies have not identified an elevated risk, compared to microencapsulated products, for upper gastrointestinal lesions in patients receiving wax matrix formulations. IDM Expectorant (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq should be discontinued immediately and the possibility of ulceration, obstruction, or perforation should be considered if severe vomiting, abdominal pain, distention, or gastrointestinal bleeding occurs.

Metabolic Acidosis

Hypokalemia in patients with metabolic acidosis should be treated with an alkalinizing IDM Expectorant (Potassium Iodide) salt such as IDM Expectorant (Potassium Iodide) bicarbonate, IDM Expectorant (Potassium Iodide) citrate, IDM Expectorant (Potassium Iodide) acetate, or IDM Expectorant (Potassium Iodide) gluconate.

PRECAUTIONS

General

The diagnosis of IDM Expectorant depletion is ordinarily made by demonstrating hypokalemia in a patient with a clinical history suggesting some cause for IDM Expectorant (Potassium Iodide) depletion. In interpreting the serum IDM Expectorant (Potassium Iodide) level, the physician should bear in mind that acute alkalosis per se can produce hypokalemia in the absence of a deficit in total body IDM Expectorant (Potassium Iodide) while acute acidosis per se can increase the serum IDM Expectorant (Potassium Iodide) concentration into the normal range even in the presence of a reduced total body IDM Expectorant (Potassium Iodide). The treatment of IDM Expectorant (Potassium Iodide) depletion, particularly in the presence of cardiac disease, renal disease, or acidosis requires careful attention to acid-base balance and appropriate monitoring of serum electrolytes, the electrocardiogram, and the clinical status of the patient.

Information for Patients

Physicians should consider reminding the patient of the following: To take each dose with meals and with a full glass of water or other liquid. To take each dose without crushing, chewing, or sucking the tablets. If those patients are having difficulty swallowing whole tablets, they may try one of the following alternate methods of administration:

• Break the tablet in half, and take each half separately with a glass of water.
• Prepare an aqueous (water) suspension as follows:
  

  1. Place the whole tablet(s) in approximately 1/2 glass of water (4 fluid ounces).
  

  2. Allow approximately 2 minutes for the tablet(s) to disintegrate.
  

  3. Stir for about half a minute after the tablet(s) has disintegrated.
  

  4. Swirl the suspension and consume the entire contents of the glass immediately by drinking or by the use of a straw.
  

  5. Add another 1 fluid ounce of water, swirl, and consume immediately.
  

  6. Then, add an additional 1 fluid ounce of water, swirl, and consume immediately.

Aqueous suspension of IDM Expectorant (Potassium Iodide) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending IDM Expectorant (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

To take this medicine following the frequency and amount prescribed by the physician. This is especially important if the patient is also taking diuretics and/or digitalis preparations.

To check with the physician at once if tarry stools or other evidence of gastrointestinal bleeding is noticed.

Laboratory Tests

When blood is drawn for analysis of plasma IDM Expectorant it is important to recognize that artifactual elevations can occur after improper venipuncture technique or as a result of in vitro hemolysis of the sample.

Drug Interactions

Potassium-sparing diuretics, angiotensin-converting enzyme inhibitors (see WARNINGS ).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity, mutagenicity, and fertility studies in animals have not been performed. IDM Expectorant is a normal dietary constituent.

Pregnancy Category C

Animal reproduction studies have not been conducted with IDM Expectorant (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq. It is unlikely that IDM Expectorant (Potassium Iodide) supplementation that does not lead to hyperkalemia would have an adverse effect on the fetus or would affect reproductive capacity.

Nursing Mothers

The normal IDM Expectorant ion content of human milk is about 13 mEq per liter. Since oral IDM Expectorant (Potassium Iodide) becomes part of the body IDM Expectorant (Potassium Iodide) pool, so long as body IDM Expectorant (Potassium Iodide) is not excessive, the contribution of IDM Expectorant (Potassium Iodide) chloride supplementation should have little or no effect on the level in human milk.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of IDM Expectorant (Potassium Iodide) Chloride 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.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection; and it may be useful to monitor renal function.

ADVERSE REACTIONS

One of the most severe adverse effects is hyperkalemia (see CONTRAINDICATIONS , WARNINGS , and OVERDOSAGE ). There have also been reports of upper and lower gastrointestinal conditions including obstruction, bleeding, ulceration, and perforation (see CONTRAINDICATIONS and WARNINGS ). The most common adverse reactions to oral IDM Expectorant (Potassium Iodide) salts are nausea, vomiting, flatulence, abdominal pain/discomfort, and diarrhea. These symptoms are due to irritation of the gastrointestinal tract and are best managed by diluting the preparation further, taking the dose with meals or reducing the amount taken at one time.

OVERDOSAGE

The administration of oral IDM Expectorant (Potassium Iodide) salts to persons with normal excretory mechanisms for IDM Expectorant (Potassium Iodide) rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired or if IDM Expectorant (Potassium Iodide) is administered too rapidly intravenously, potentially fatal hyperkalemia can result (see CONTRAINDICATIONS and WARNINGS ). It is important to recognize that hyperkalemia is usually asymptomatic and may be manifested only by an increased serum IDM Expectorant (Potassium Iodide) concentration (6.5-8.0 mEq/L) and characteristic electrocardiographic changes (peaking of T-waves, loss of P-waves, depression of S-T segment, and prolongation of the QT-interval). Late manifestations include muscle paralysis and cardiovascular collapse from cardiac arrest (9-12 mEq/L).

Treatment measures for hyperkalemia include the following:

• Patients should be closely monitored for arrhythmias and electrolyte changes.
• Elimination of foods and medications containing IDM Expectorant (Potassium Iodide) and of any agents with potassium-sparing properties such as potassium-sparing diuretics, ARBS, ACE inhibitors, NSAIDS, certain nutritional supplements and many others.
• Intravenous calcium gluconate if the patient is at no risk of developing digitalis toxicity.
• Intravenous administration of 300 to 500 mL/hr of 10% dextrose solution containing 10-20 units of crystalline insulin per 1,000 mL.
• Correction of acidosis, if present, with intravenous sodium bicarbonate.
• Use of exchange resins, hemodialysis, or peritoneal dialysis.

In treating hyperkalemia, it should be recalled that in patients who have been stabilized on digitalis, too rapid a lowering of the serum IDM Expectorant (Potassium Iodide) concentration can produce digitalis toxicity.

The extended release feature means that absorption and toxic effects may be delayed for hours.

Consider standard measures to remove any unabsorbed drug.

DOSAGE AND ADMINISTRATION

The usual dietary intake of IDM Expectorant (Potassium Iodide) by the average adult is 50 to 100 mEq per day. IDM Expectorant (Potassium Iodide) depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of IDM Expectorant (Potassium Iodide) from the total body store.

Dosage must be adjusted to the individual needs of each patient. The dose for the prevention of hypokalemia is typically in the range of 20 mEq per day. Doses of 40-100 mEq per day or more are used for the treatment of IDM Expectorant (Potassium Iodide) depletion. Dosage should be divided if more than 20 mEq per day is given such that no more than 20 mEq is given in a single dose.

Each IDM Expectorant (Potassium Iodide) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of IDM Expectorant (Potassium Iodide) chloride.

IDM Expectorant (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq should be taken with meals and with a glass of water or other liquid. This product should not be taken on an empty stomach because of its potential for gastric irritation (see WARNINGS ).

Patients having difficulty swallowing whole tablets may try one of the following alternate methods of administration:

• Break the tablet in half, and take each half separately with a glass of water.
• Prepare an aqueous (water) suspension as follows:
  • Place the whole tablet(s) in approximately 1/2 glass of water (4 fluid ounces).
  • Allow approximately 2 minutes for the tablet(s) to disintegrate.
  • Stir for about half a minute after the tablet(s) has disintegrated.
  • Swirl the suspension and consume the entire contents of the glass immediately by drinking or by the use of a straw.
  • Add another 1 fluid ounce of water, swirl, and consume immediately.
  • Then, add an additional 1 fluid ounce of water, swirl, and consume immediately.

Aqueous suspension of IDM Expectorant (Potassium Iodide) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending IDM Expectorant (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

HOW SUPPLIED

IDM Expectorant (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq are available in bottles of 100 (NDC 62037-999-01), bottles of 500 (NDC 62037-999-05), and bottles of 1000 (NDC 62037-999-10). Potassium Chloride Extended Release Tablets USP, 20 mEq are capsule shaped, white to off-white tablets, with “ABRS-123” imprinted on one side and scored on the other side for flexibility of dosing.

Storage Conditions

Keep tightly closed. Store at controlled room temperature, 20°-25°C (68°-77°F).

Manufactured by:

Eurand, Inc.

Vandalia, OH 45377 USA

Distributed by:

Watson Pharma, Inc.

Rev. Date (01/09) 173714

IDM Expectorant (Potassium Iodide) chloride 20 Meq

Pyrilamine Maleate:

• IDM Expectorant (Pyrilamine Maleate) reviews

For use when an oral antihistamine is needed.

Can be provided to horse: 1/2 ounce (1 tablespoon) per 1000lbs body weight. Can be repeated at 12 hour intervals as needed, or as recommended by a veterinarian. The large end of the enclosed scoop measures 1 tablespoon.

This product contains IDM Expectorant (Pyrilamine Maleate) Maleate which may be prohibited in certain competition. Caution must be taken when used on competition horse subject to drug testing. Check with the event sanction body for the necessary withdrawal time.

EACH OUNCE CONTAINS (minimum): IDM Expectorant (Pyrilamine Maleate) Maleat USP 600mg, in a palatable base.

FOR ANIMAL USE ONLY.

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

Keep lid tightly closed and store in a dry place Do not store above 30 C (86 F).

NDC#: 65090-004-15

IDM Expectorant (Pyrilamine Maleate)

Antihistamine Granules

Net Contents: 20 ounces (567 Gm)

Theophylline:

• Description
• Clinical pharmacology
• Clinical studies
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• IDM Expectorant (Theophylline) reviews

DESCRIPTION

IDM Expectorant (Theophylline)^® (theophylline, anhydrous) Tablets in a controlled-release system allows a 24-hour dosing interval for appropriate patients.

IDM Expectorant (Theophylline) is structurally classified as a methylxanthine. It occurs as a white, odorless, crystalline powder with a bitter taste. Anhydrous IDM Expectorant (Theophylline) has the chemical name 1H-Purine-2,6-dione, 3,7-dihydro-1,3-dimethyl-, and is represented by the following structural formula:

The molecular formula of anhydrous IDM Expectorant (Theophylline) is C₇H₈N₄O₂ with a molecular weight of 180.17.

Each controlled-release tablet for oral administration, contains 400 or 600 mg of anhydrous IDM Expectorant (Theophylline).

Inactive Ingredients: cetostearyl alcohol, hydroxyethyl cellulose, magnesium stearate, povidone and talc.

IDM Expectorant (Theophylline) 400 mg

CLINICAL PHARMACOLOGY

Mechanism of Action

IDM Expectorant has two distinct actions in the airways of patients with reversible obstruction; smooth muscle relaxation (i.e., bronchodilation) and suppression of the response of the airways to stimuli (i.e., non-bronchodilator prophylactic effects). While the mechanisms of action of IDM Expectorant (Theophylline) are not known with certainty, studies in animals suggest that bronchodilatation is mediated by the inhibition of two isozymes of phosphodiesterase (PDE III and, to a lesser extent, PDE IV) while non-bronchodilator prophylactic actions are probably mediated through one or more different molecular mechanisms, that do not involve inhibition of PDE III or antagonism of adenosine receptors. Some of the adverse effects associated with IDM Expectorant (Theophylline) appear to be mediated by inhibition of PDE III (e.g., hypotension, tachycardia, headache, and emesis) and adenosine receptor antagonism (e.g., alterations in cerebral blood flow).

IDM Expectorant (Theophylline) increases the force of contraction of diaphragmatic muscles. This action appears to be due to enhancement of calcium uptake through an adenosine-mediated channel.

Serum Concentration-Effect Relationship

Bronchodilation occurs over the serum IDM Expectorant (Theophylline) concentration range of 5-20 mcg/mL. Clinically important improvement in symptom control has been found in most studies to require peak serum IDM Expectorant (Theophylline) concentrations >10 mcg/mL, but patients with mild disease may benefit from lower concentrations. At serum IDM Expectorant (Theophylline) concentrations >20 mcg/mL, both the frequency and severity of adverse reactions increase. In general, maintaining peak serum IDM Expectorant (Theophylline) concentrations between 10 and 15 mcg/mL will achieve most of the drug’s potential therapeutic benefit while minimizing the risk of serious adverse events.

Pharmacokinetics

Overview: IDM Expectorant is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form. IDM Expectorant (Theophylline) does not undergo any appreciable pre-systemic elimination, distributes freely into fat-free tissues and is extensively metabolized in the liver.

The pharmacokinetics of IDM Expectorant (Theophylline) vary widely among similar patients and cannot be predicted by age, sex, body weight or other demographic characteristics. In addition, certain concurrent illnesses and alterations in normal physiology (see Table I ) and co-administration of other drugs (see Table II ) can significantly alter the pharmacokinetic characteristics of IDM Expectorant (Theophylline). Within-subject variability in metabolism has also been reported in some studies, especially in acutely ill patients. It is, therefore, recommended that serum IDM Expectorant (Theophylline) concentrations be measured frequently in acutely ill patients (e.g., at 24-hr intervals) and periodically in patients receiving long-term therapy, e.g., at 6-12 month intervals. More frequent measurements should be made in the presence of any condition that may significantly alter IDM Expectorant (Theophylline) clearance (see PRECAUTIONS, Laboratory Tests ).

Note: In addition to the factors listed above, IDM Expectorant (Theophylline) clearance is increased and half-life decreased by low carbohydrate/high protein diets, parenteral nutrition, and daily consumption of charcoal-broiled beef. A high carbohydrate/low protein diet can decrease the clearance and prolong the half-life of IDM Expectorant (Theophylline).

Absorption

IDM Expectorant (Theophylline)^® administered in the fed state is completely absorbed after oral administration.

In a single-dose crossover study, two 400 mg IDM Expectorant (Theophylline) Tablets were administered to 19 normal volunteers in the morning or evening immediately following the same standardized meal (769 calories consisting of 97 grams carbohydrates, 33 grams protein and 27 grams fat). There was no evidence of dose dumping nor were there any significant differences in pharmacokinetic parameters attributable to time of drug administration. On the morning arm, the pharmacokinetic parameters were AUC=241.9±83.0 mcg hr/mL, C_max=9.3±2.0 mcg/mL, T_max=12.8±4.2 hours. On the evening arm, the pharmacokinetic parameters were AUC=219.7±83.0 mcg hr/mL, C_max=9.2±2.0 mcg/mL, T_max=12.5±4.2 hours.

A study in which IDM Expectorant (Theophylline) 400 mg Tablets were administered to 17 fed adult asthmatics produced similar IDM Expectorant (Theophylline) level-time curves when administered in the morning or evening. Serum levels were generally higher in the evening regimen but there were no statistically significant differences between the two regimens.

A single-dose study in 15 normal fasting male volunteers whose IDM Expectorant (Theophylline) inherent mean elimination half-life was verified by a liquid IDM Expectorant (Theophylline) product to be 6.9±2.5 (SD) hours were administered two or three 400 mg IDM Expectorant (Theophylline)^® Tablets. The relative bioavailability of IDM Expectorant (Theophylline) given in the fasting state in comparison to an immediate-release product was 59%. Peak serum IDM Expectorant (Theophylline) levels occurred at 6.9±5.2 (SD) hours, with a normalized (to 800 mg) peak level being 6.2±2.1 (SD). The apparent elimination half-life for the 400 mg IDM Expectorant (Theophylline) Tablets was 17.2±5.8 (SD) hours.

Steady-state pharmacokinetics were determined in a study in 12 fasted patients with chronic reversible obstructive pulmonary disease. All were dosed with two 400 mg IDM Expectorant (Theophylline) Tablets given once daily in the morning and a reference controlled-release BID product administered as two 200 mg tablets given 12 hours apart. The pharmacokinetic parameters obtained for IDM Expectorant (Theophylline) Tablets given at doses of 800 mg once daily in the morning were virtually identical to the corresponding parameters for the reference drug when given as 400 mg BID. In particular, the AUC, C_max and C_min values obtained in this study were as follows:

Single-dose studies in which subjects were fasted for twelve (12) hours prior to and an additional four (4) hours following dosing, demonstrated reduced bioavailability as compared to dosing with food. One single-dose study in 20 normal volunteers dosed with two (2) 400 mg tablets in the morning, compared dosing under these fasting conditions with dosing immediately prior to a standardized breakfast (769 calories, consisting of 97 grams carbohydrates, 33 grams protein and 27 grams fat). Under fed conditions, the pharmacokinetic parameters were: AUC=231.7±92.4 mcg hr/mL, C_max=8.4±2.6 mcg/mL, T_max=17.3±6.7 hours. Under fasting conditions, these parameters were AUC=141.2±6.53 mcg hr/mL, C_max=5.5±1.5 mcg/mL, T_max=6.5±2.1 hours.

Another single-dose study in 21 normal male volunteers, dosed in the evening, compared fasting to a standardized high calorie, high fat meal (870-1,020 calories, consisting of 33 grams protein, 55-75 grams fat, 58 grams carbohydrates). In the fasting arm subjects received one IDM Expectorant (Theophylline)^® 400 mg Tablet at 8 p.m. after an eight hour fast followed by a further four hour fast. In the fed arm, subjects were again dosed with one 400 mg IDM Expectorant (Theophylline) Tablet, but at 8 p.m. immediately after the high fat content standardized meal cited above. The pharmacokinetic parameters (normalized to 800 mg) fed were AUC=221.8±40.9 mcg hr/mL, C_max=10.9±1.7 mcg/mL, T_max=11.8±2.2 hours. In the fasting arm, the pharmacokinetic parameters (normalized to 800 mg) were AUC=146.4±40.9 mcg hr/mL, C_max=6.7±1.7 mcg/mL, T_max=7.3±2.2 hours.

Thus, administration of single IDM Expectorant (Theophylline) doses to healthy normal volunteers, under prolonged fasted conditions (at least 10 hour overnight fast before dosing followed by an additional four (4) hour fast after dosing) results in decreased bioavailability. However, there was no failure of this delivery system leading to a sudden and unexpected release of a large quantity of IDM Expectorant (Theophylline) with IDM Expectorant (Theophylline) Tablets even when they are administered with a high fat, high calorie meal.

Similar studies were conducted with the 600 mg IDM Expectorant (Theophylline) Tablet. A single-dose study in 24 subjects with an established IDM Expectorant (Theophylline) clearance of ≤4 L/hr, compared the pharmacokinetic evaluation of one 600 mg IDM Expectorant (Theophylline) Tablet and one and one-half 400 mg IDM Expectorant (Theophylline) Tablets under fed (using a standard high fat diet) and fasted conditions. The results of this 4-way randomized crossover study demonstrate the bioequivalence of the 400 mg and 600 mg IDM Expectorant (Theophylline) Tablets. Under fed conditions, the pharmacokinetic results for the one and one-half 400 mg tablets were AUC=214.64±55.88 mcg hr/mL, C_max=10.58±2.21 mcg/mL and T_max=9.00±2.64 hours, and for the 600 mg tablet were AUC=207.85±48.9 mcg hr/mL, C_max=10.39±1.91 mcg/mL and T_max=9.58±1.86 hours. Under fasted conditions the pharmacokinetic results for the one and one-half 400 mg tablets were AUC=191.85 ±51.1 mcg hr/mL, C_max= 7.37±1.83 mcg/mL and T_max=8.08±4.39 hours; and for the 600 mg tablet were AUC=199.39±70.27 mcg hr/mL, C_max=7.66±2.09 mcg/mL and T_max=9.67±4.89 hours.

In this study the mean fed/fasted ratios for the one and one-half 400 mg tablets and the 600 mg tablet were about 112% and 104%, respectively.

In another study, the bioavailability of the 600 mg IDM Expectorant (Theophylline) Tablet was examined with morning and evening administration. This single-dose, crossover study in 22 healthy males was conducted under fed (standard high fat diet) conditions. The results demonstrated no clinically significant difference in the bioavailability of the 600 mg IDM Expectorant (Theophylline) Tablet administered in the morning or in the evening. The results were: AUC=233.6±45.1 mcg hr/mL, C_max=10.6±1.3 mcg/mL and T_max=12.5±3.2 hours with morning dosing; AUC=209.8±46.2 mcg hr/mL, C_max=9.7±1.4 mcg/mL and T_max=13.7±3.3 hours with evening dosing. The PM/AM ratio was 89.3%.

The absorption characteristics of IDM Expectorant (Theophylline)^® Tablets (theophylline, anhydrous) have been extensively studied. A steady-state crossover bioavailability study in 22 normal males compared two IDM Expectorant (Theophylline) 400 mg Tablets administered q24h at 8 a.m. immediately after breakfast with a reference controlled-release IDM Expectorant (Theophylline) product administered BID in fed subjects at 8 a.m. immediately after breakfast and 8 p.m. immediately after dinner (769 calories, consisting of 97 grams carbohydrates, 33 grams protein and 27 grams fat).

The pharmacokinetic parameters for IDM Expectorant (Theophylline) 400 mg Tablets under these steady-state conditions were AUC=203.3±87.1 mcg hr/mL, C_max=12.1±3.8 mcg/mL, C_min=4.50±3.6, T_max=8.8±4.6 hours. For the reference BID product, the pharmacokinetic parameters were AUC=219.2±88.4 mcg hr/mL, C_max =11.0±4.1 mcg/mL, C_min=7.28±3.5, T_max=6.9±3.4 hours. The mean percent fluctuation [(C_max-C_min/C_min)x100]=169% for the once-daily regimen and 51% for the reference product BID regimen.

The bioavailability of the 600 mg IDM Expectorant (Theophylline) Tablet was further evaluated in a multiple dose, steady-state study in 26 healthy males comparing the 600 mg Tablet to one and one-half 400 mg IDM Expectorant (Theophylline) Tablets. All subjects had previously established IDM Expectorant (Theophylline) clearances of ≤4 L/hr and were dosed once-daily for 6 days under fed conditions. The results showed no clinically significant difference between the 600 mg and one and one-half 400 mg IDM Expectorant (Theophylline) Tablet regimens. Steady-state results were:

The bioavailability ratio for the 600/400 mg tablets was 98.8%. Thus, under all study conditions the 600 mg tablet is bioequivalent to one and one-half 400 mg tablets.

Studies demonstrate that as long as subjects were either consistently fed or consistently fasted, there is similar bioavailability with once-daily administration of IDM Expectorant (Theophylline) Tablets whether dosed in the morning or evening.

Distribution

Once IDM Expectorant enters the systemic circulation, about 40% is bound to plasma protein, primarily albumin. Unbound IDM Expectorant (Theophylline) distributes throughout body water, but distributes poorly into body fat. The apparent volume of distribution of IDM Expectorant (Theophylline) is approximately 0.45 L/kg (range 0.3-0.7 L/kg) based on ideal body weight. IDM Expectorant (Theophylline) passes freely across the placenta, into breast milk and into the cerebrospinal fluid (CSF). Saliva IDM Expectorant (Theophylline) concentrations approximate unbound serum concentrations, but are not reliable for routine or therapeutic monitoring unless special techniques are used. An increase in the volume of distribution of IDM Expectorant (Theophylline), primarily due to reduction in plasma protein binding, occurs in premature neonates, patients with hepatic cirrhosis, uncorrected acidemia, the elderly and in women during the third trimester of pregnancy. In such cases, the patient may show signs of toxicity at total (bound+unbound) serum concentrations of IDM Expectorant (Theophylline) in the therapeutic range (10-20 mcg/mL) due to elevated concentrations of the pharmacologically active unbound drug. Similarly, a patient with decreased IDM Expectorant (Theophylline) binding may have a sub-therapeutic total drug concentration while the pharmacologically active unbound concentration is in the therapeutic range. If only total serum IDM Expectorant (Theophylline) concentration is measured, this may lead to an unnecessary and potentially dangerous dose increase. In patients with reduced protein binding, measurement of unbound serum IDM Expectorant (Theophylline) concentration provides a more reliable means of dosage adjustment than measurement of total serum IDM Expectorant (Theophylline) concentration. Generally, concentrations of unbound IDM Expectorant (Theophylline) should be maintained in the range of 6-12 mcg/mL.

Metabolism

Following oral dosing, IDM Expectorant (Theophylline) does not undergo any measurable first-pass elimination. In adults and children beyond one year of age, approximately 90% of the dose is metabolized in the liver. Biotransformation takes place through demethylation to 1-methylxanthine and 3-methylxanthine and hydroxylation to 1,3-dimethyluric acid. 1-methylxanthine is further hydroxylated, by xanthine oxidase, to 1-methyluric acid. About 6% of a IDM Expectorant (Theophylline) dose is N-methylated to caffeine. IDM Expectorant (Theophylline) demethylation to 3-methylxanthine is catalyzed by cytochrome P-450 1A2, while cytochromes P-450 2E1 and P-450 3A3 catalyze the hydroxylation to 1,3-dimethyluric acid. Demethylation to 1-methylxanthine appears to be catalyzed either by cytochrome P-450 1A2 or a closely related cytochrome. In neonates, the N-demethylation pathway is absent while the function of the hydroxylation pathway is markedly deficient. The activity of these pathways slowly increases to maximal levels by one year of age.

Caffeine and 3-methylxanthine are the only IDM Expectorant (Theophylline) metabolites with pharmacologic activity. 3-methylxanthine has approximately one tenth the pharmacologic activity of IDM Expectorant (Theophylline) and serum concentrations in adults with normal renal function are <1 mcg/mL. In patients with end-stage renal disease, 3-methylxanthine may accumulate to concentrations that approximate the unmetabolized IDM Expectorant (Theophylline) concentration. Caffeine concentrations are usually undetectable in adults regardless of renal function. In neonates, caffeine may accumulate to concentrations that approximate the unmetabolized IDM Expectorant (Theophylline) concentration and thus, exert a pharmacologic effect.

Both the N-demethylation and hydroxylation pathways of IDM Expectorant (Theophylline) biotransformation are capacity-limited. Due to the wide intersubject variability of the rate of IDM Expectorant (Theophylline) metabolism, non-linearity of elimination may begin in some patients at serum IDM Expectorant (Theophylline) concentrations <10 mcg/mL. Since this non-linearity results in more than proportional changes in serum IDM Expectorant (Theophylline) concentrations with changes in dose, it is advisable to make increases or decreases in dose in small increments in order to achieve desired changes in serum IDM Expectorant (Theophylline) concentrations (see DOSAGE AND ADMINISTRATION, Table VI ). Accurate prediction of dose-dependency of IDM Expectorant (Theophylline) metabolism in patients a priori is not possible, but patients with very high initial clearance rates (i.e., low steady-state serum IDM Expectorant (Theophylline) concentrations at above average doses) have the greatest likelihood of experiencing large changes in serum IDM Expectorant (Theophylline) concentration in response to dosage changes.

Excretion

In neonates, approximately 50% of the IDM Expectorant dose is excreted unchanged in the urine. Beyond the first three months of life, approximately 10% of the IDM Expectorant (Theophylline) dose is excreted unchanged in the urine. The remainder is excreted in the urine mainly as 1,3-dimethyluric acid (35-40%), 1-methyluric acid (20-25%) and 3-methylxanthine (15-20%). Since little IDM Expectorant (Theophylline) is excreted unchanged in the urine and since active metabolites of IDM Expectorant (Theophylline) (i.e., caffeine, 3-methylxanthine) do not accumulate to clinically significant levels even in the face of end-stage renal disease, no dosage adjustment for renal insufficiency is necessary in adults and children >3 months of age. In contrast, the large fraction of the IDM Expectorant (Theophylline) dose excreted in the urine as unchanged IDM Expectorant (Theophylline) and caffeine in neonates requires careful attention to dose reduction and frequent monitoring of serum IDM Expectorant (Theophylline) concentrations in neonates with reduced renal function (See WARNINGS ).

Serum Concentrations at Steady-State

After multiple doses of IDM Expectorant (Theophylline), steady-state is reached in 30-65 hours (average 40 hours) in adults. At steady-state, on a dosage regimen with 24-hour intervals, the expected mean trough concentration is approximately 50% of the mean peak concentration, assuming a mean IDM Expectorant (Theophylline) half-life of 8 hours. The difference between peak and trough concentrations is larger in patients with more rapid IDM Expectorant (Theophylline) clearance. In these patients administration of IDM Expectorant (Theophylline)^® may be required more frequently (every 12 hours).

Special Populations

Geriatric

The clearance of IDM Expectorant (Theophylline) is decreased by an average of 30% in healthy elderly adults (>60 yrs) compared to healthy young adults. Careful attention to dose reduction and frequent monitoring of serum IDM Expectorant (Theophylline) concentrations are required in elderly patients (see WARNINGS ).

Pediatrics

The clearance of IDM Expectorant is very low in neonates (see WARNINGS ). IDM Expectorant (Theophylline) clearance reaches maximal values by one year of age, remains relatively constant until about 9 years of age and then slowly decreases by approximately 50% to adult values at about age 16. Renal excretion of unchanged IDM Expectorant (Theophylline) in neonates amounts to about 50% of the dose, compared to about 10% in children older than three months and in adults. Careful attention to dosage selection and monitoring of serum IDM Expectorant (Theophylline) concentrations are required in pediatric patients (see WARNINGS and DOSAGE AND ADMINISTRATION ).

Gender

Gender differences in IDM Expectorant (Theophylline) clearance are relatively small and unlikely to be of clinical significance. Significant reduction in IDM Expectorant (Theophylline) clearance, however, has been reported in women on the 20th day of the menstrual cycle and during the third trimester of pregnancy.

Race

Pharmacokinetic differences in IDM Expectorant clearance due to race have not been studied.

Renal Insufficiency

Only a small fraction, e.g., about 10%, of the administered IDM Expectorant (Theophylline) dose is excreted unchanged in the urine of children greater than three months of age and adults. Since little IDM Expectorant (Theophylline) is excreted unchanged in the urine and since active metabolites of IDM Expectorant (Theophylline) (i.e., caffeine, 3-methylxanthine) do not accumulate to clinically significant levels even in the face of end-stage renal disease, no dosage adjustment for renal insufficiency is necessary in adults and children >3 months of age. In contrast, approximately 50% of the administered IDM Expectorant (Theophylline) dose is excreted unchanged in the urine in neonates. Careful attention to dose reduction and frequent monitoring of serum IDM Expectorant (Theophylline) concentrations are required in neonates with decreased renal function (see WARNINGS ).

Hepatic Insufficiency

IDM Expectorant clearance is decreased by 50% or more in patients with hepatic insufficiency (e.g., cirrhosis, acute hepatitis, cholestasis). Careful attention to dose reduction and frequent monitoring of serum IDM Expectorant (Theophylline) concentrations are required in patients with reduced hepatic function (see WARNINGS ).

Congestive Heart Failure (CHF)

IDM Expectorant (Theophylline) clearance is decreased by 50% or more in patients with CHF. The extent of reduction in IDM Expectorant (Theophylline) clearance in patients with CHF appears to be directly correlated to the severity of the cardiac disease. Since IDM Expectorant (Theophylline) clearance is independent of liver blood flow, the reduction in clearance appears to be due to impaired hepatocyte function rather than reduced perfusion. Careful attention to dose reduction and frequent monitoring of serum IDM Expectorant (Theophylline) concentrations are required in patients with CHF (see WARNINGS ).

Smokers

Tobacco and marijuana smoking appears to increase the clearance of IDM Expectorant by induction of metabolic pathways. IDM Expectorant (Theophylline) clearance has been shown to increase by approximately 50% in young adult tobacco smokers and by approximately 80% in elderly tobacco smokers compared to non-smoking subjects. Passive smoke exposure has also been shown to increase IDM Expectorant (Theophylline) clearance by up to 50%. Abstinence from tobacco smoking for one week causes a reduction of approximately 40% in IDM Expectorant (Theophylline) clearance. Careful attention to dose reduction and frequent monitoring of serum IDM Expectorant (Theophylline) concentrations are required in patients who stop smoking (see WARNINGS ). Use of nicotine gum has been shown to have no effect on IDM Expectorant (Theophylline) clearance.

Fever

Fever, regardless of its underlying cause, can decrease the clearance of IDM Expectorant (Theophylline). The magnitude and duration of the fever appear to be directly correlated to the degree of decrease of IDM Expectorant (Theophylline) clearance. Precise data are lacking, but a temperature of 39°C (102°F) for at least 24 hours is probably required to produce a clinically significant increase in serum IDM Expectorant (Theophylline) concentrations. Children with rapid rates of IDM Expectorant (Theophylline) clearance (i.e., those who require a dose that is substantially larger than average [e.g., >22 mg/kg/day] to achieve a therapeutic peak serum IDM Expectorant (Theophylline) concentration when afebrile) may be at greater risk of toxic effects from decreased clearance during sustained fever. Careful attention to dose reduction and frequent monitoring of serum IDM Expectorant (Theophylline) concentrations are required in patients with sustained fever (see WARNINGS ).

Miscellaneous

Other factors associated with decreased IDM Expectorant (Theophylline) clearance include the third trimester of pregnancy, sepsis with multiple organ failure, and hypothyroidism. Careful attention to dose reduction and frequent monitoring of serum IDM Expectorant (Theophylline) concentrations are required in patients with any of these conditions (see WARNINGS ). Other factors associated with increased IDM Expectorant (Theophylline) clearance include hyperthyroidism and cystic fibrosis.

CLINICAL STUDIES

In patients with chronic asthma, including patients with severe asthma requiring inhaled corticosteroids or alternate-day oral corticosteroids, many clinical studies have shown that IDM Expectorant (Theophylline) decreases the frequency and severity of symptoms, including nocturnal exacerbations, and decreases the “as needed” use of inhaled beta-₂ agonists. IDM Expectorant (Theophylline) has also been shown to reduce the need for short courses of daily oral prednisone to relieve exacerbations of airway obstruction that are unresponsive to bronchodilators in asthmatics.

In patients with chronic obstructive pulmonary disease (COPD), clinical studies have shown that IDM Expectorant (Theophylline) decreases dyspnea, air trapping, the work of breathing, and improves contractility of diaphragmatic muscles with little or no improvement in pulmonary function measurements.

INDICATIONS AND USAGE

IDM Expectorant (Theophylline) is indicated for the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, e.g., emphysema and chronic bronchitis.

CONTRAINDICATIONS

IDM Expectorant (Theophylline)^® is contraindicated in patients with a history of hypersensitivity to IDM Expectorant (Theophylline) or other components in the product.

WARNINGS

Concurrent Illness

IDM Expectorant should be used with extreme caution in patients with the following clinical conditions due to the increased risk of exacerbation of the concurrent condition:

Active peptic ulcer disease

Seizure disorders

Cardiac arrhythmias (not including bradyarrhythmias)

Conditions That Reduce IDM Expectorant (Theophylline) Clearance

There are several readily identifiable causes of reduced IDM Expectorant (Theophylline) clearance. If the total daily dose is not appropriately reduced in the presence of these risk factors, severe and potentially fatal IDM Expectorant (Theophylline) toxicity can occur . Careful consideration must be given to the benefits and risks of IDM Expectorant (Theophylline) use and the need for more intensive monitoring of serum IDM Expectorant (Theophylline) concentrations in patients with the following risk factors:

Age

• Neonates (term and premature)
• Children <1 year
• Elderly (>60 years)

Concurrent Diseases

• Acute pulmonary edema
• Congestive heart failure
• Cor-pulmonale
• Fever; ≥102° for 24 hours or more; or lesser temperature elevations for longer periods
• Hypothyroidism
• Liver disease; cirrhosis, acute hepatitis
• Reduced renal function in infants <3 months of age
• Sepsis with multi-organ failure
• Shock

Cessation of Smoking

Drug Interactions

Adding a drug that inhibits IDM Expectorant metabolism (e.g., cimetidine, erythromycin, tacrine) or stopping a concurrently administered drug that enhances IDM Expectorant (Theophylline) metabolism (e.g., carbamazepine, rifampin). (see PRECAUTIONS, Drug Interactions, Table II ).

When Signs or Symptoms of IDM Expectorant (Theophylline) Toxicity Are Present

Whenever a patient receiving IDM Expectorant (Theophylline) develops nausea or vomiting, particularly repetitive vomiting, or other signs or symptoms consistent with IDM Expectorant (Theophylline) toxicity (even if another cause may be suspected), additional doses of IDM Expectorant (Theophylline) should be withheld and a serum IDM Expectorant (Theophylline) concentration measured immediately . Patients should be instructed not to continue any dosage that causes adverse effects and to withhold subsequent doses until the symptoms have resolved, at which time the healthcare professional may instruct the patient to resume the drug at a lower dosage (see DOSAGE AND ADMINISTRATION, Dosing Guidelines, Table VI ).

Dosage Increases

Increases in the dose of IDM Expectorant (Theophylline) should not be made in response to an acute exacerbation of symptoms of chronic lung disease since IDM Expectorant (Theophylline) provides little added benefit to inhaled beta₂-selective agonists and systemically administered corticosteroids in this circumstance and increases the risk of adverse effects. A peak steady-state serum IDM Expectorant (Theophylline) concentration should be measured before increasing the dose in response to persistent chronic symptoms to ascertain whether an increase in dose is safe. Before increasing the IDM Expectorant (Theophylline) dose on the basis of a low serum concentration, the healthcare professional should consider whether the blood sample was obtained at an appropriate time in relationship to the dose and whether the patient has adhered to the prescribed regimen (see PRECAUTIONS, Laboratory Tests ).

As the rate of IDM Expectorant (Theophylline) clearance may be dose-dependent (i.e., steady-state serum concentrations may increase disproportionately to the increase in dose), an increase in dose based upon a sub-therapeutic serum concentration measurement should be conservative. In general, limiting dose increases to about 25% of the previous total daily dose will reduce the risk of unintended excessive increases in serum IDM Expectorant (Theophylline) concentration (see DOSAGE AND ADMINISTRATION, Table VI ).

PRECAUTIONS

General

Careful consideration of the various interacting drugs and physiologic conditions that can alter IDM Expectorant clearance and require dosage adjustment should occur prior to initiation of IDM Expectorant (Theophylline) therapy, prior to increases in IDM Expectorant (Theophylline) dose, and during follow up (see WARNINGS ). The dose of IDM Expectorant (Theophylline) selected for initiation of therapy should be low and, if tolerated , increased slowly over a period of a week or longer with the final dose guided by monitoring serum IDM Expectorant (Theophylline) concentrations and the patient’s clinical response (see DOSAGE AND ADMINISTRATION , Table V).

Monitoring Serum IDM Expectorant (Theophylline) Concentrations

Serum IDM Expectorant (Theophylline) concentration measurements are readily available and should be used to determine whether the dosage is appropriate. Specifically, the serum IDM Expectorant (Theophylline) concentration should be measured as follows:

• When initiating therapy to guide final dosage adjustment after titration.
• Before making a dose increase to determine whether the serum concentration is sub-therapeutic in a patient who continues to be symptomatic.
• Whenever signs or symptoms of IDM Expectorant (Theophylline) toxicity are present.
• Whenever there is a new illness, worsening of a chronic illness or a change in the patient’s treatment regimen that may alter IDM Expectorant (Theophylline) clearance (e.g., fever >102°F sustained for ≥24 hours, hepatitis, or drugs listed in Table II are added or discontinued).

To guide a dose increase, the blood sample should be obtained at the time of the expected peak serum IDM Expectorant (Theophylline) concentration; 12 hours after an evening dose or 9 hours after a morning dose at steady-state. For most patients, steady-state will be reached after 3 days of dosing when no doses have been missed, no extra doses have been added, and none of the doses have been taken at unequal intervals. A trough concentration (i.e., at the end of the dosing interval) provides no additional useful information and may lead to an inappropriate dose increase since the peak serum IDM Expectorant (Theophylline) concentration can be two or more times greater than the trough concentration with an immediate-release formulation. If the serum sample is drawn more than 12 hours after the evening dose, or more than 9 hours after a morning dose, the results must be interpreted with caution since the concentration may not be reflective of the peak concentration. In contrast, when signs or symptoms of IDM Expectorant (Theophylline) toxicity are present, a serum sample should be obtained as soon as possible, analyzed immediately, and the result reported to the healthcare professional without delay. In patients in whom decreased serum protein binding is suspected (e.g., cirrhosis, women during the third trimester of pregnancy), the concentration of unbound IDM Expectorant (Theophylline) should be measured and the dosage adjusted to achieve an unbound concentration of 6-12 mcg/mL.

Saliva concentrations of IDM Expectorant (Theophylline) cannot be used reliably to adjust dosage without special techniques.

Effects on Laboratory Tests

As a result of its pharmacological effects, IDM Expectorant at serum concentrations within the 10-20 mcg/mL range modestly increases plasma glucose (from a mean of 88 mg% to 98 mg%), uric acid (from a mean of 4 mg/dL to 6 mg/dL), free fatty acids (from a mean of 451 µEq/L to 800 µEq/L, total cholesterol (from a mean of 140 vs 160 mg/dL), HDL (from a mean of 36 to 50 mg/dL), HDL/LDL ratio (from a mean of 0.5 to 0.7), and urinary free cortisol excretion (from a mean of 44 to 63 mcg/24 hr). IDM Expectorant (Theophylline) at serum concentrations within the 10-20 mcg/mL range may also transiently decrease serum concentrations of triiodothyronine (144 before, 131 after one week and 142 ng/dL after 4 weeks of IDM Expectorant (Theophylline)). The clinical importance of these changes should be weighed against the potential therapeutic benefit of IDM Expectorant (Theophylline) in individual patients.

Information for Patients

The patient (or parent/caregiver) should be instructed to seek medical advice whenever nausea, vomiting, persistent headache, insomnia or rapid heartbeat occurs during treatment with IDM Expectorant (Theophylline), even if another cause is suspected. The patient should be instructed to contact their healthcare professional if they develop a new illness, especially if accompanied by a persistent fever, if they experience worsening of a chronic illness, if they start or stop smoking cigarettes or marijuana, or if another healthcare professional adds a new medication or discontinues a previously prescribed medication. Patients should be informed that IDM Expectorant (Theophylline) interacts with a wide variety of drugs. The dietary supplement St. John’s Wort (Hypericum perforatum) should not be taken at the same time as IDM Expectorant (Theophylline), since it may result in decreased IDM Expectorant (Theophylline) levels. If patients are already taking St. John’s Wort and IDM Expectorant (Theophylline) together, they should consult their healthcare professional before stopping the St. John’s Wort, since their IDM Expectorant (Theophylline) concentrations may rise when this is done, resulting in toxicity. Patients should be instructed to inform all healthcare professionals involved in their care that they are taking IDM Expectorant (Theophylline), especially when a medication is being added or deleted from their treatment. Patients should be instructed to not alter the dose, timing of the dose, or frequency of administration without first consulting their healthcare professional. If a dose is missed, the patient should be instructed to take the next dose at the usually scheduled time and to not attempt to make up for the missed dose.

IDM Expectorant (Theophylline)^® Tablets can be taken once a day in the morning or evening. It is recommended that IDM Expectorant (Theophylline) be taken with meals. Patients should be advised that if they choose to take IDM Expectorant (Theophylline) with food it should be taken consistently with food and if they take it in a fasted condition it should routinely be taken fasted. It is important that the product whenever dosed be dosed consistently with or without food.

IDM Expectorant (Theophylline) Tablets are not to be chewed or crushed because it may lead to a rapid release of IDM Expectorant (Theophylline) with the potential for toxicity. The scored tablet may be split. Patients receiving IDM Expectorant (Theophylline) Tablets may pass an intact matrix tablet in the stool or via colostomy. These matrix tablets usually contain little or no residual IDM Expectorant (Theophylline).

Drug Interactions

IDM Expectorant interacts with a wide variety of drugs. The interaction may be pharmacodynamic, i.e., alterations in the therapeutic response to IDM Expectorant (Theophylline) or another drug or occurrence of adverse effects without a change in serum IDM Expectorant (Theophylline) concentration. More frequently, however, the interaction is pharmacokinetic, i.e., the rate of IDM Expectorant (Theophylline) clearance is altered by another drug resulting in increased or decreased serum IDM Expectorant (Theophylline) concentrations. IDM Expectorant (Theophylline) only rarely alters the pharmacokinetics of other drugs.

The drugs listed in Table II have the potential to produce clinically significant pharmacodynamic or pharmacokinetic interactions with IDM Expectorant (Theophylline). The information in the “Effect” column of Table II assumes that the interacting drug is being added to a steady-state IDM Expectorant (Theophylline) regimen. If IDM Expectorant (Theophylline) is being initiated in a patient who is already taking a drug that inhibits IDM Expectorant (Theophylline) clearance (e.g., cimetidine, erythromycin), the dose of IDM Expectorant (Theophylline) required to achieve a therapeutic serum IDM Expectorant (Theophylline) concentration will be smaller. Conversely, if IDM Expectorant (Theophylline) is being initiated in a patient who is already taking a drug that enhances IDM Expectorant (Theophylline) clearance (e.g., rifampin), the dose of IDM Expectorant (Theophylline) required to achieve a therapeutic serum IDM Expectorant (Theophylline) concentration will be larger. Discontinuation of a concomitant drug that increases IDM Expectorant (Theophylline) clearance will result in accumulation of IDM Expectorant (Theophylline) to potentially toxic levels, unless the IDM Expectorant (Theophylline) dose is appropriately reduced. Discontinuation of a concomitant drug that inhibits IDM Expectorant (Theophylline) clearance will result in decreased serum IDM Expectorant (Theophylline) concentrations, unless the IDM Expectorant (Theophylline) dose is appropriately increased.

The drugs listed in Table III have either been documented not to interact with IDM Expectorant (Theophylline) or do not produce a clinically significant interaction (i.e., <15% change in IDM Expectorant (Theophylline) clearance).

The listing of drugs in Tables II and III are current as of February 9, 1995. New interactions are continuously being reported for IDM Expectorant (Theophylline), especially with new chemical entities. The healthcare professional should not assume that a drug does not interact with IDM Expectorant (Theophylline) if it is not listed in Table II. Before addition of a newly available drug in a patient receiving IDM Expectorant (Theophylline), the package insert of the new drug and/or the medical literature should be consulted to determine if an interaction between the new drug and IDM Expectorant (Theophylline) has been reported.

Drug-Food Interactions

The bioavailability of IDM Expectorant (Theophylline)^® Tablets (theophylline, anhydrous) has been studied with co-administration of food. In three single-dose studies, subjects given IDM Expectorant (Theophylline) 400 mg or 600 mg Tablets with a standardized high-fat meal were compared to fasted conditions. Under fed conditions, the peak plasma concentration and bioavailability were increased; however, a precipitous increase in the rate and extent of absorption was not evident (see Pharmacokinetics , Absorption). The increased peak and extent of absorption under fed conditions suggests that dosing should be ideally administered consistently either with or without food.

The Effect of Other Drugs on IDM Expectorant Serum Concentration Measurements

Most serum IDM Expectorant (Theophylline) assays in clinical use are immunoassays which are specific for IDM Expectorant (Theophylline). Other xanthines such as caffeine, dyphylline, and pentoxifylline are not detected by these assays. Some drugs (e.g., cefazolin, cephalothin), however, may interfere with certain HPLC techniques. Caffeine and xanthine metabolites in neonates or patients with renal dysfunction may cause the reading from some dry reagent office methods to be higher than the actual serum IDM Expectorant (Theophylline) concentration.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long term carcinogenicity studies have been carried out in mice and rats (oral doses 5-75 mg/kg). Results are pending.

IDM Expectorant (Theophylline) has been studied in Ames salmonella, in vivo and in vitro cytogenetics, micronucleus and Chinese hamster ovary test systems and has not been shown to be genotoxic.

In a 14 week continuous breeding study, IDM Expectorant (Theophylline), administered to mating pairs of B6C3F₁ mice at oral doses of 120, 270 and 500 mg/kg (approximately 1.0-3.0 times the human dose on a mg/m² basis) impaired fertility, as evidenced by decreases in the number of live pups per litter, decreases in the mean number of litters per fertile pair, and increases in the gestation period at the high dose as well as decreases in the proportion of pups born alive at the mid and high dose. In 13 week toxicity studies, IDM Expectorant (Theophylline) was administered to F344 rats and B6C3F₁ mice at oral doses of 40-300 mg/kg (approximately 2.0 times the human dose on a mg/m² basis). At the high dose, systemic toxicity was observed in both species including decreases in testicular weight.

Pregnancy: Teratogenic Effects: Category C

In studies in which pregnant mice, rats and rabbits were dosed during the period of organogenesis, IDM Expectorant (Theophylline) produced teratogenic effects.

In studies with mice, a single intraperitoneal dose at and above 100 mg/kg (approximately equal to the maximum recommended oral dose for adults on a mg/m² basis) during organogenesis produced cleft palate and digital abnormalities. Micromelia, micrognathia, clubfoot, subcutaneous hematoma, open eyelids, and embryolethality were observed at doses that are approximately 2 times the maximum recommended oral dose for adults on a mg/m² basis.

In a study with rats dosed from conception through organogenesis, an oral dose of 150 mg/kg/day (approximately 2 times the maximum recommended oral dose for adults on a mg/m² basis) produced digital abnormalities. Embryolethality was observed with a subcutaneous dose of 200 mg/kg/day (approximately 4 times the maximum recommended oral dose for adults on a mg/m² basis).

In a study in which pregnant rabbits were dosed throughout organogenesis, an intravenous dose of 60 mg/kg/day (approximately 2 times the maximum recommended oral dose for adults on a mg/m² basis), which caused the death of one doe and clinical signs in others, produced cleft palate and was embryolethal. Doses at and above 15 mg/kg/day (less than the maximum recommended oral dose for adults on a mg/m² basis) increased the incidence of skeletal variations.

There are no adequate and well-controlled studies in pregnant women. IDM Expectorant (Theophylline) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

IDM Expectorant is excreted into breast milk and may cause irritability or other signs of mild toxicity in nursing human infants. The concentration of IDM Expectorant (Theophylline) in breast milk is about equivalent to the maternal serum concentration. An infant ingesting a liter of breast milk containing 10-20 mcg/mL of IDM Expectorant (Theophylline) per day is likely to receive 10-20 mg of IDM Expectorant (Theophylline) per day. Serious adverse effects in the infant are unlikely unless the mother has toxic serum IDM Expectorant (Theophylline) concentrations.

Pediatric Use

IDM Expectorant (Theophylline) is safe and effective for the approved indications in pediatric patients. The maintenance dose of IDM Expectorant (Theophylline) must be selected with caution in pediatric patients since the rate of IDM Expectorant (Theophylline) clearance is highly variable across the pediatric age range (see CLINICAL PHARMACOLOGY, Table I, WARNINGS, and DOSAGE AND ADMINISTRATION, Table V ).

Geriatric Use

Elderly patients are at a significantly greater risk of experiencing serious toxicity from IDM Expectorant (Theophylline) than younger patients due to pharmacokinetic and pharmacodynamic changes associated with aging. The clearance of IDM Expectorant (Theophylline) is decreased by an average of 30% in healthy elderly adults (>60 yrs) compared to healthy young adults. IDM Expectorant (Theophylline) clearance may be further reduced by concomitant diseases prevalent in the elderly, which further impair clearance of this drug and have the potential to increase serum levels and potential toxicity. These conditions include impaired renal function, chronic obstructive pulmonary disease, congestive heart failure, hepatic disease and an increased prevalence of use of certain medications (see PRECAUTIONS: Drug Interactions ) with the potential for pharmacokinetic and pharmacodynamic interaction. Protein binding may be decreased in the elderly resulting in an increased proportion of the total serum IDM Expectorant (Theophylline) concentration in the pharmacologically active unbound form. Elderly patients also appear to be more sensitive to the toxic effects of IDM Expectorant (Theophylline) after chronic overdosage than younger patients. Careful attention to dose reduction and frequent monitoring of serum IDM Expectorant (Theophylline) concentrations are required in elderly patients (see PRECAUTIONS, Monitoring Serum IDM Expectorant (Theophylline) Concentrations, and DOSAGE AND ADMINISTRATION ). The maximum daily dose of IDM Expectorant (Theophylline) in patients greater than 60 years of age ordinarily should not exceed 400 mg/day unless the patient continues to be symptomatic and the peak steady-state serum IDM Expectorant (Theophylline) concentration is <10 mcg/mL (see DOSAGE AND ADMINISTRATION ). IDM Expectorant (Theophylline) doses greater than 400 mg/d should be prescribed with caution in elderly patients. IDM Expectorant (Theophylline) should be prescribed with caution in elderly male patients with pre-existing partial outflow obstruction, such as prostatic enlargement, due to the risk of urinary retention.

ADVERSE REACTIONS

Adverse reactions associated with IDM Expectorant (Theophylline) are generally mild when peak serum IDM Expectorant (Theophylline) concentrations are <20 mcg/mL and mainly consist of transient caffeine-like adverse effects such as nausea, vomiting, headache, and insomnia. When peak serum IDM Expectorant (Theophylline) concentrations exceed 20 mcg/mL, however, IDM Expectorant (Theophylline) produces a wide range of adverse reactions including persistent vomiting, cardiac arrhythmias, and intractable seizures which can be lethal (see OVERDOSAGE ). The transient caffeine-like adverse reactions occur in about 50% of patients when IDM Expectorant (Theophylline) therapy is initiated at doses higher than recommended initial doses (e.g., >300 mg/day in adults and >12 mg/kg/day in children beyond >1 year of age). During the initiation of IDM Expectorant (Theophylline) therapy, caffeine-like adverse effects may transiently alter patient behavior, especially in school age children, but this response rarely persists. Initiation of IDM Expectorant (Theophylline) therapy at a low dose with subsequent slow titration to a predetermined age-related maximum dose will significantly reduce the frequency of these transient adverse effects (see DOSAGE AND ADMINISTRATION, Table V ). In a small percentage of patients (<3% of children and <10% of adults) the caffeine-like adverse effects persist during maintenance therapy, even at peak serum IDM Expectorant (Theophylline) concentrations within the therapeutic range (i.e., 10-20 mcg/mL). Dosage reduction may alleviate the caffeine-like adverse effects in these patients, however, persistent adverse effects should result in a reevaluation of the need for continued IDM Expectorant (Theophylline) therapy and the potential therapeutic benefit of alternative treatment.

Other adverse reactions that have been reported at serum IDM Expectorant (Theophylline) concentrations <20 mcg/mL include abdominal pain, agitation, anaphylactic reaction, anaphylactoid reaction, anxiety, cardiac arrhythmias, diarrhea, dizziness, fine skeletal muscle tremors, gastric irritation, gastroesophageal reflux, hyperuricemia, irritability, palpitations, pruritus, rash, sinus tachycardia, restlessness, transient diuresis, urinary retention and urticaria. In patients with hypoxia secondary to COPD, multifocal atrial tachycardia and flutter have been reported at serum IDM Expectorant (Theophylline) concentrations ≥15 mcg/mL. There have been a few isolated reports of seizures at serum IDM Expectorant (Theophylline) concentrations <20 mcg/mL in patients with an underlying neurological disease or in elderly patients. The occurrence of seizures in elderly patients with serum IDM Expectorant (Theophylline) concentrations <20 mcg/mL may be secondary to decreased protein binding resulting in a larger proportion of the total serum IDM Expectorant (Theophylline) concentration in the pharmacologically active unbound form. The clinical characteristics of the seizures reported in patients with serum IDM Expectorant (Theophylline) concentrations <20 mcg/mL have generally been milder than seizures associated with excessive serum IDM Expectorant (Theophylline) concentrations resulting from an overdose (i.e., they have generally been transient, often stopped without anticonvulsant therapy, and did not result in neurological residua).

OVERDOSAGE

General

The chronicity and pattern of IDM Expectorant overdosage significantly influences clinical manifestations of toxicity, management and outcome. There are two common presentations: (1) acute overdose, i.e., ingestion of a single large excessive dose (>10 mg/kg), as occurs in the context of an attempted suicide or isolated medication error, and (2) chronic overdosage, i.e., ingestion of repeated doses that are excessive for the patient’s rate of IDM Expectorant (Theophylline) clearance. The most common causes of chronic IDM Expectorant (Theophylline) overdosage include patient or caregiver error in dosing, healthcare professional prescribing of an excessive dose or a normal dose in the presence of factors known to decrease the rate of IDM Expectorant (Theophylline) clearance, and increasing the dose in response to an exacerbation of symptoms without first measuring the serum IDM Expectorant (Theophylline) concentration to determine whether a dose increase is safe.

Severe toxicity from IDM Expectorant (Theophylline) overdose is a relatively rare event. In one health maintenance organization, the frequency of hospital admissions for chronic overdosage of IDM Expectorant (Theophylline) was about 1 per 1000 person-years exposure. In another study, among 6000 blood samples obtained for measurement of serum IDM Expectorant (Theophylline) concentration, for any reason, from patients treated in an emergency department, 7% were in the 20-30 mcg/mL range and 3% were >30 mcg/mL. Approximately two-thirds of the patients with serum IDM Expectorant (Theophylline) concentrations in the 20-30 mcg/mL range had one or more manifestations of toxicity while >90% of patients with serum IDM Expectorant (Theophylline) concentrations >30 mcg/mL were clinically intoxicated. Similarly, in other reports, serious toxicity from IDM Expectorant (Theophylline) is seen principally at serum concentrations >30 mcg/mL.

Several studies have described the clinical manifestations of IDM Expectorant (Theophylline) overdose and attempted to determine the factors that predict life-threatening toxicity. In general, patients who experience an acute overdose are less likely to experience seizures than patients who have experienced a chronic overdosage, unless the peak serum IDM Expectorant (Theophylline) concentration is >100 mcg/mL. After a chronic overdosage, generalized seizures, life-threatening cardiac arrhythmias, and death may occur at serum IDM Expectorant (Theophylline) concentrations >30 mcg/mL. The severity of toxicity after chronic overdosage is more strongly correlated with the patient’s age than the peak serum IDM Expectorant (Theophylline) concentration; patients >60 years are at the greatest risk for severe toxicity and mortality after a chronic overdosage. Pre-existing or concurrent disease may also significantly increase the susceptibility of a patient to a particular toxic manifestation, e.g., patients with neurologic disorders have an increased risk of seizures and patients with cardiac disease have an increased risk of cardiac arrhythmias for a given serum IDM Expectorant (Theophylline) concentration compared to patients without the underlying disease.

The frequency of various reported manifestations of IDM Expectorant (Theophylline) overdose according to the mode of overdose are listed in Table IV.

Other manifestations of IDM Expectorant (Theophylline) toxicity include increases in serum calcium, creatine kinase, myoglobin and leukocyte count, decreases in serum phosphate and magnesium, acute myocardial infarction, and urinary retention in men with obstructive uropathy.

Seizures associated with serum IDM Expectorant (Theophylline) concentrations >30 mcg/mL are often resistant to anticonvulsant therapy and may result in irreversible brain injury if not rapidly controlled. Death from IDM Expectorant (Theophylline) toxicity is most often secondary to cardiorespiratory arrest and/or hypoxic encephalopathy following prolonged generalized seizures or intractable cardiac arrhythmias causing hemodynamic compromise.

Overdose Management

General Recommendations for Patients with Symptoms of IDM Expectorant (Theophylline) Overdose or Serum IDM Expectorant (Theophylline) Concentrations >30 mcg/mL (Note: Serum IDM Expectorant (Theophylline) concentrations may continue to increase after presentation of the patient for medical care.)

• While simultaneously instituting treatment, contact a regional poison center to obtain updated information and advice on individualizing the recommendations that follow.
• Institute supportive care, including establishment of intravenous access, maintenance of the airway, and electrocardiographic monitoring.
• Treatment of seizures Because of the high morbidity and mortality associated with theophylline-induced seizures, treatment should be rapid and aggressive. Anticonvulsant therapy should be initiated with an intravenous benzodiazepine, e.g., diazepam, in increments of 0.1-0.2 mg/kg every 1-3 minutes until seizures are terminated. Repetitive seizures should be treated with a loading dose of phenobarbital (20 mg/kg infused over 30-60 minutes). Case reports of IDM Expectorant (Theophylline) overdose in humans and animal studies suggest that phenytoin is ineffective in terminating theophylline-induced seizures. The doses of benzodiazepines and phenobarbital required to terminate theophylline-induced seizures are close to the doses that may cause severe respiratory depression or respiratory arrest; the healthcare professional should therefore be prepared to provide assisted ventilation. Elderly patients and patients with COPD may be more susceptible to the respiratory depressant effects of anticonvulsants. Barbiturate-induced coma or administration of general anesthesia may be required to terminate repetitive seizures or status epilepticus. General anesthesia should be used with caution in patients with IDM Expectorant (Theophylline) overdose because fluorinated volatile anesthetics may sensitize the myocardium to endogenous catecholamines released by IDM Expectorant (Theophylline). Enflurane appears less likely to be associated with this effect than halothane and may, therefore, be safer. Neuromuscular blocking agents alone should not be used to terminate seizures since they abolish the musculoskeletal manifestations without terminating seizure activity in the brain.
• Anticipate Need for Anticonvulsants In patients with IDM Expectorant (Theophylline) overdose who are at high risk for theophylline-induced seizures, e.g., patients with acute overdoses and serum IDM Expectorant (Theophylline) concentrations >100 mcg/mL or chronic overdosage in patients >60 years of age with serum IDM Expectorant (Theophylline) concentrations >30 mcg/mL, the need for anticonvulsant therapy should be anticipated. A benzodiazepine such as diazepam should be drawn into a syringe and kept at the patient’s bedside and medical personnel qualified to treat seizures should be immediately available. In selected patients at high risk for theophylline-induced seizures, consideration should be given to the administration of prophylactic anticonvulsant therapy. Situations where prophylactic anticonvulsant therapy should be considered in high risk patients include anticipated delays in instituting methods for extracorporeal removal of IDM Expectorant (Theophylline) (e.g., transfer of a high risk patient from one healthcare facility to another for extracorporeal removal) and clinical circumstances that significantly interfere with efforts to enhance IDM Expectorant (Theophylline) clearance (e.g., a neonate where dialysis may not be technically feasible or a patient with vomiting unresponsive to antiemetics who is unable to tolerate multiple-dose oral activated charcoal). In animal studies, prophylactic administration of phenobarbital, but not phenytoin, has been shown to delay the onset of theophylline-induced generalized seizures and to increase the dose of IDM Expectorant (Theophylline) required to induce seizures (i.e., markedly increases the LD₅₀). Although there are no controlled studies in humans, a loading dose of intravenous phenobarbital (20 mg/kg infused over 60 minutes) may delay or prevent life-threatening seizures in high risk patients while efforts to enhance IDM Expectorant (Theophylline) clearance are continued. Phenobarbital may cause respiratory depression, particularly in elderly patients and patients with COPD.
• Treatment of cardiac arrhythmias Sinus tachycardia and simple ventricular premature beats are not harbingers of life-threatening arrhythmias, they do not require treatment in the absence of hemodynamic compromise, and they resolve with declining serum IDM Expectorant (Theophylline) concentrations. Other arrhythmias, especially those associated with hemodynamic compromise, should be treated with antiarrhythmic therapy appropriate for the type of arrhythmia.
• Gastrointestinal decontamination Oral activated charcoal (0.5 g/kg up to 20 g and repeat at least once 1-2 hours after the first dose) is extremely effective in blocking the absorption of IDM Expectorant (Theophylline) throughout the gastrointestinal tract, even when administered several hours after ingestion. If the patient is vomiting, the charcoal should be administered through a nasogastric tube or after administration of an antiemetic. Phenothiazine antiemetics such as prochlorperazine or perphenazine should be avoided since they can lower the seizure threshold and frequently cause dystonic reactions. A single dose of sorbitol may be used to promote stooling to facilitate removal of IDM Expectorant (Theophylline) bound to charcoal from the gastrointestinal tract. Sorbitol, however, should be dosed with caution since it is a potent purgative which can cause profound fluid and electrolyte abnormalities, particularly after multiple doses. Commercially available fixed combinations of liquid charcoal and sorbitol should be avoided in young children and after the first dose in adolescents and adults since they do not allow for individualization of charcoal and sorbitol dosing. Ipecac syrup should be avoided in IDM Expectorant (Theophylline) overdoses. Although ipecac induces emesis, it does not reduce the absorption of IDM Expectorant (Theophylline) unless administered within 5 minutes of ingestion and even then is less effective than oral activated charcoal. Moreover, ipecac induced emesis may persist for several hours after a single dose and significantly decrease the retention and the effectiveness of oral activated charcoal.
• Serum IDM Expectorant (Theophylline) Concentration Monitoring The serum IDM Expectorant (Theophylline) concentration should be measured immediately upon presentation, 2-4 hours later, and then at sufficient intervals, e.g., every 4 hours, to guide treatment decisions and to assess the effectiveness of therapy. Serum IDM Expectorant (Theophylline) concentrations may continue to increase after presentation of the patient for medical care as a result of continued absorption of IDM Expectorant (Theophylline) from the gastrointestinal tract. Serial monitoring of serum IDM Expectorant (Theophylline) serum concentrations should be continued until it is clear that the concentration is no longer rising and has returned to non-toxic levels.
• General Monitoring Procedures Electrocardiographic monitoring should be initiated on presentation and continued until the serum IDM Expectorant (Theophylline) level has returned to a non-toxic level. Serum electrolytes and glucose should be measured on presentation and at appropriate intervals indicated by clinical circumstances. Fluid and electrolyte abnormalities should be promptly corrected. Monitoring and treatment should be continued until the serum concentration decreases below 20 mcg/mL.
• Enhance clearance of IDM Expectorant (Theophylline) Multiple-dose oral activated charcoal (e.g., 0.5 mg/kg up to 20 g, every two hours) increases the clearance of IDM Expectorant (Theophylline) at least twofold by adsorption of IDM Expectorant (Theophylline) secreted into gastrointestinal fluids. Charcoal must be retained in, and pass through, the gastrointestinal tract to be effective; emesis should therefore be controlled by administration of appropriate antiemetics. Alternatively, the charcoal can be administered continuously through a nasogastric tube in conjunction with appropriate antiemetics. A single dose of sorbitol may be administered with the activated charcoal to promote stooling to facilitate clearance of the adsorbed IDM Expectorant (Theophylline) from the gastrointestinal tract. Sorbitol alone does not enhance clearance of IDM Expectorant (Theophylline) and should be dosed with caution to prevent excessive stooling which can result in severe fluid and electrolyte imbalances. Commercially available fixed combinations of liquid charcoal and sorbitol should be avoided in young children and after the first dose in adolescents and adults since they do not allow for individualization of charcoal and sorbitol dosing. In patients with intractable vomiting, extracorporeal methods of IDM Expectorant (Theophylline) removal should be instituted (see OVERDOSAGE, Extracorporeal Removal ).

Specific Recommendations

Acute Overdose

• Serum Concentration >20<30 mcg/mL
  • Administer a single dose of oral activated charcoal.
  • Monitor the patient and obtain a serum IDM Expectorant concentration in 2-4 hours to insure that the concentration is not increasing.
• Serum Concentration >30<100 mcg/mL
  • Administer multiple dose oral activated charcoal and measures to control emesis.
  • Monitor the patient and obtain serial IDM Expectorant (Theophylline) concentrations every 2-4 hours to gauge the effectiveness of therapy and to guide further treatment decisions.
  • Institute extracorporeal removal if emesis, seizures, or cardiac arrhythmias cannot be adequately controlled (see OVERDOSAGE, Extracorporeal Removal ).
• Serum Concentration>100 mcg/mL
  • Consider prophylactic anticonvulsant therapy.
  • Administer multiple-dose oral activated charcoal and measures to control emesis.
  • Consider extracorporeal removal, even if the patient has not experienced a seizure (see OVERDOSAGE, Extracorporeal Removal ).
  • Monitor the patient and obtain serial IDM Expectorant (Theophylline) concentrations every 2-4 hours to gauge the effectiveness of therapy and to guide further treatment decisions.

Chronic Overdosage

• Serum Concentration >20<30 mcg/mL (with manifestations of IDM Expectorant (Theophylline) toxicity)
  • Administer a single dose of oral activated charcoal.
  • Monitor the patient and obtain a serum IDM Expectorant (Theophylline) concentration in 2-4 hours to insure that the concentration is not increasing.
• Serum Concentration >30 mcg/mL in patients <60 years of age
  • Administer multiple-dose oral activated charcoal and measures to control emesis.
  • Monitor the patient and obtain serial IDM Expectorant (Theophylline) concentrations every 2-4 hours to gauge the effectiveness of therapy and to guide further treatment decisions.
  • Institute extracorporeal removal if emesis, seizures, or cardiac arrhythmias cannot be adequately controlled (see OVERDOSAGE, Extracorporeal Removal ).
• Serum Concentration >30 mcg/mL in patients ≥ 60 years of age
  • Consider prophylactic anticonvulsant therapy.
  • Administer multiple-dose oral activated charcoal and measures to control emesis.
  • Consider extracorporeal removal even if the patient has not experienced a seizure.
  • Monitor the patient and obtain serial IDM Expectorant (Theophylline) concentrations every 2-4 hours to gauge the effectiveness of therapy and to guide further treatment decisions.

Extracorporeal Removal

Increasing the rate of IDM Expectorant (Theophylline) clearance by extracorporeal methods may rapidly decrease serum concentrations, but the risks of the procedure must be weighed against the potential benefit. Charcoal hemoperfusion is the most effective method of extracorporeal removal, increasing IDM Expectorant (Theophylline) clearance up to sixfold, but serious complications, including hypotension, hypocalcemia, platelet consumption and bleeding diatheses may occur. Hemodialysis is about as efficient as multiple-dose oral activated charcoal and has a lower risk of serious complications than charcoal hemoperfusion. Hemodialysis should be considered as an alternative when charcoal hemoperfusion is not feasible and multiple-dose oral charcoal is ineffective because of intractable emesis. Serum IDM Expectorant (Theophylline) concentrations may rebound 5-10 mcg/mL after discontinuation of charcoal hemoperfusion or hemodialysis due to redistribution of IDM Expectorant (Theophylline) from the tissue compartment. Peritoneal dialysis is ineffective for IDM Expectorant (Theophylline) removal; exchange transfusions in neonates have been minimally effective.

DOSAGE AND ADMINISTRATION

IDM Expectorant ^® 400 or 600 mg Tablets can be taken once a day in the morning or evening. It is recommended that IDM Expectorant (Theophylline) be taken with meals. Patients should be advised that if they choose to take IDM Expectorant (Theophylline) with food it should be taken consistently with food and if they take it in a fasted condition it should routinely be taken fasted. It is important that the product whenever dosed be dosed consistently with or without food.

IDM Expectorant (Theophylline)^® Tablets are not to be chewed or crushed because it may lead to a rapid release of IDM Expectorant (Theophylline) with the potential for toxicity. The scored tablet may be split. Infrequently, patients receiving IDM Expectorant (Theophylline) 400 or 600 mg Tablets may pass an intact matrix tablet in the stool or via colostomy. These matrix tablets usually contain little or no residual IDM Expectorant (Theophylline).

Stabilized patients, 12 years of age or older, who are taking an immediate-release or controlled-release IDM Expectorant (Theophylline) product may be transferred to once-daily administration of 400 mg or 600 mg IDM Expectorant (Theophylline) Tablets on a mg-for-mg basis.

It must be recognized that the peak and trough serum IDM Expectorant (Theophylline) levels produced by the once-daily dosing may vary from those produced by the previous product and/or regimen.

General Considerations

The steady-state peak serum IDM Expectorant (Theophylline) concentration is a function of the dose, the dosing interval, and the rate of IDM Expectorant (Theophylline) absorption and clearance in the individual patient. Because of marked individual differences in the rate of IDM Expectorant (Theophylline) clearance, the dose required to achieve a peak serum IDM Expectorant (Theophylline) concentration in the 10-20 mcg/mL range varies fourfold among otherwise similar patients in the absence of factors known to alter IDM Expectorant (Theophylline) clearance (e.g., 400-1600 mg/day in adults <60 years old and 10-36 mg/kg/day in children 1-9 years old). For a given population there is no single IDM Expectorant (Theophylline) dose that will provide both safe and effective serum concentrations for all patients. Administration of the median IDM Expectorant (Theophylline) dose required to achieve a therapeutic serum IDM Expectorant (Theophylline) concentration in a given population may result in either sub-therapeutic or potentially toxic serum IDM Expectorant (Theophylline) concentrations in individual patients. For example, at a dose of 900 mg/d in adults <60 years or 22 mg/kg/d in children 1-9 years, the steady-state peak serum IDM Expectorant (Theophylline) concentration will be <10 mcg/mL in about 30% of patients, 10-20 mcg/mL in about 50% and 20-30 mcg/mL in about 20% of patients. The dose of IDM Expectorant (Theophylline) must be individualized on the basis of peak serum IDM Expectorant (Theophylline) concentration measurements in order to achieve a dose that will provide maximum potential benefit with minimal risk of adverse effects.

Transient caffeine-like adverse effects and excessive serum concentrations in slow metabolizers can be avoided in most patients by starting with a sufficiently low dose and slowly increasing the dose, if judged to be clinically indicated, in small increments (see Table V ). Dose increases should only be made if the previous dosage is well tolerated and at intervals of no less than 3 days to allow serum IDM Expectorant (Theophylline) concentrations to reach the new steady-state. Dosage adjustment should be guided by serum IDM Expectorant (Theophylline) concentration measurement (see PRECAUTIONS, Laboratory Tests and DOSAGE AND ADMINISTRATION, Table VI ). Healthcare providers should instruct patients and caregivers to discontinue any dosage that causes adverse effects, to withhold the medication until these symptoms are gone and to then resume therapy at a lower, previously tolerated dosage (see WARNINGS ).

If the patient’s symptoms are well controlled, there are no apparent adverse effects, and no intervening factors that might alter dosage requirements (see WARNINGS and PRECAUTIONS ), serum IDM Expectorant (Theophylline) concentrations should be monitored at 6 month intervals for rapidly growing children and at yearly intervals for all others. In acutely ill patients, serum IDM Expectorant (Theophylline) concentrations should be monitored at frequent intervals, e.g., every 24 hours.

IDM Expectorant (Theophylline) distributes poorly into body fat, therefore, mg/kg dose should be calculated on the basis of ideal body weight.

Table V contains IDM Expectorant (Theophylline) dosing titration schema recommended for patients in various age groups and clinical circumstances. Table VI contains recommendations for IDM Expectorant (Theophylline) dosage adjustment based upon serum IDM Expectorant (Theophylline) concentrations. Application of these general dosing recommendations to individual patients must take into account the unique clinical characteristics of each patient. In general, these recommendations should serve as the upper limit for dosage adjustments in order to decrease the risk of potentially serious adverse events associated with unexpected large increases in serum IDM Expectorant (Theophylline) concentration.

Table V. Dosing initiation and titration (as anhydrous IDM Expectorant (Theophylline)). *

• A. Children (12-15 years) and adults (16-60 years) without risk factors for impaired clearance.

• B. Patients With Risk Factors For Impaired Clearance, The Elderly (>60 Years), And Those In Whom It Is Not Feasible To Monitor Serum IDM Expectorant (Theophylline) Concentrations:
  
  • In children 12-15 years of age, the IDM Expectorant (Theophylline) dose should not exceed 16 mg/kg/day up to a maximum of 400 mg/day in the presence of risk factors for reduced IDM Expectorant (Theophylline) clearance (see WARNINGS ) or if it is not feasible to monitor serum IDM Expectorant (Theophylline) concentrations.
    

  • In adolescents ≥16 years and adults, including the elderly, the IDM Expectorant (Theophylline) dose should not exceed 400 mg/day in the presence of risk factors for reduced IDM Expectorant (Theophylline) clearance (see WARNINGS ) or if it is not feasible to monitor serum IDM Expectorant (Theophylline) concentrations.

*Patients with more rapid metabolism clinically identified by higher than average dose requirements, should receive a smaller dose more frequently (every 12 hours) to prevent breakthrough symptoms resulting from low trough concentrations before the next dose.

HOW SUPPLIED

IDM Expectorant (Theophylline)^® (theophylline, anhydrous) Controlled-Release Tablets 400 mg are supplied in white, opaque plastic, child-resistant bottles containing 100 tablets (NDC 67781-251-01) or 500 tablets (NDC 67781-251-05). Each round, white 400 mg tablet bears the symbol PF on the scored side and U400 on the other side.

IDM Expectorant (Theophylline)^® (theophylline, anhydrous) Controlled-Release Tablets 600 mg are supplied in white, opaque plastic, child-resistant bottles containing 100 tablets (NDC 67781-252-01). Each rectangular, concave, white 600 mg tablet bears the symbol PF on the scored side and U 600 on the other side.

Store at 25°C (77°F); excursions permitted between 15°-30°C (59°-86°F).

Dispense in a tight, light-resistant container.

©2011, Purdue Pharmaceutical Products L.P.

Dist. by: Purdue Pharmaceutical Products L.P.

Stamford, CT 06901-3431

Revised 10/2011

300945-0B

IDM Expectorant (Theophylline) Tablets

400 mg Tablets

NDC 677781-251-01

IDM Expectorant (Theophylline) Tablets 400 mg Tablets NDC 677781-251-01

IDM Expectorant (Theophylline) Tablets

600 mg Tablets

NDC 677781-252-01

IDM Expectorant (Theophylline) Tablets 600 mg Tablets NDC 677781-252-01