Boipulmonale Sol

Potassium Iodide:

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

Boipulmonale Sol (Potassium Iodide) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

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

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

Boipulmonale Sol (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq is an electrolyte replenisher. The chemical name of the active ingredient is Boipulmonale Sol (Potassium Iodide) chloride, and the structural formula is KCl. Boipulmonale Sol (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.

Boipulmonale Sol (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulation (not enteric coated or wax matrix) containing individually microencapsulated Boipulmonale Sol (Potassium Iodide) chloride crystals which disperse upon tablet disintegration. In simulated gastric fluid at 37°C and in the absence of outside agitation, Boipulmonale Sol (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 Boipulmonale Sol (Potassium Iodide) chloride.

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

CLINICAL PHARMACOLOGY

The Boipulmonale Sol (Potassium Iodide) ion is the principal intracellular cation of most body tissues. Boipulmonale Sol (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 Boipulmonale Sol (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.

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

Boipulmonale Sol (Potassium Iodide) depletion will occur whenever the rate of Boipulmonale Sol (Potassium Iodide) loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of Boipulmonale Sol (Potassium Iodide) intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of Boipulmonale Sol (Potassium Iodide) in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Boipulmonale Sol (Potassium Iodide) depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. Boipulmonale Sol (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 Boipulmonale Sol (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 Boipulmonale Sol (Potassium Iodide) in the form of high Boipulmonale Sol (Potassium Iodide) food or Boipulmonale Sol (Potassium Iodide) chloride may be able to restore normal Boipulmonale Sol (Potassium Iodide) levels.

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

INDICATIONS AND USAGE

BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH CONTROLLED-RELEASE Boipulmonale Sol (Potassium Iodide) CHLORIDE PREPARATIONS, THESE DRUGS SHOULD BE RESERVED FOR THOSE PATIENTS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIQUID OR EFFERVESCENT Boipulmonale Sol (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 Boipulmonale Sol (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 Boipulmonale Sol (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 Boipulmonale Sol (Potassium Iodide) salts may be indicated.

CONTRAINDICATIONS

Boipulmonale Sol (Potassium Iodide) supplements are contraindicated in patients with hyperkalemia since a further increase in serum Boipulmonale Sol (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 Boipulmonale Sol (Potassium Iodide) chloride have produced esophageal ulceration in certain cardiac patients with esophageal compression due to enlarged left atrium. Boipulmonale Sol (Potassium Iodide) supplementation, when indicated in such patients, should be given as a liquid preparation or as an aqueous (water) suspension of Boipulmonale Sol (Potassium Iodide) Chloride (see PRECAUTIONS: Information for Patients , and DOSAGE AND ADMINISTRATION sections).

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

Interaction with Potassium-Sparing Diuretics

Hypokalemia should not be treated by the concomitant administration of Boipulmonale Sol (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 Boipulmonale Sol (Potassium Iodide) retention by inhibiting aldosterone production. Boipulmonale Sol (Potassium Iodide) supplements should be given to patients receiving ACE inhibitors only with close monitoring.

Gastrointestinal Lesions

Solid oral dosage forms of Boipulmonale Sol (Potassium Iodide) chloride can produce ulcerative and/or stenotic lesions of the gastrointestinal tract. Based on spontaneous adverse reaction reports, enteric-coated preparations of Boipulmonale Sol (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. Boipulmonale Sol (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulated to provide a controlled rate of release of microencapsulated Boipulmonale Sol (Potassium Iodide) chloride and thus to minimize the possibility of a high local concentration of Boipulmonale Sol (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 Boipulmonale Sol (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 Boipulmonale Sol (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 Boipulmonale Sol (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. Boipulmonale Sol (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 Boipulmonale Sol (Potassium Iodide) salt such as Boipulmonale Sol (Potassium Iodide) bicarbonate, Boipulmonale Sol (Potassium Iodide) citrate, Boipulmonale Sol (Potassium Iodide) acetate, or Boipulmonale Sol (Potassium Iodide) gluconate.

PRECAUTIONS

General

The diagnosis of Boipulmonale Sol depletion is ordinarily made by demonstrating hypokalemia in a patient with a clinical history suggesting some cause for Boipulmonale Sol (Potassium Iodide) depletion. In interpreting the serum Boipulmonale Sol (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 Boipulmonale Sol (Potassium Iodide) while acute acidosis per se can increase the serum Boipulmonale Sol (Potassium Iodide) concentration into the normal range even in the presence of a reduced total body Boipulmonale Sol (Potassium Iodide). The treatment of Boipulmonale Sol (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 Boipulmonale Sol (Potassium Iodide) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Boipulmonale Sol (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 Boipulmonale Sol 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. Boipulmonale Sol is a normal dietary constituent.

Pregnancy Category C

Animal reproduction studies have not been conducted with Boipulmonale Sol (Potassium Iodide) Chloride Extended Release Tablets USP, 20 mEq. It is unlikely that Boipulmonale Sol (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 Boipulmonale Sol ion content of human milk is about 13 mEq per liter. Since oral Boipulmonale Sol (Potassium Iodide) becomes part of the body Boipulmonale Sol (Potassium Iodide) pool, so long as body Boipulmonale Sol (Potassium Iodide) is not excessive, the contribution of Boipulmonale Sol (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 Boipulmonale Sol (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 Boipulmonale Sol (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 Boipulmonale Sol (Potassium Iodide) salts to persons with normal excretory mechanisms for Boipulmonale Sol (Potassium Iodide) rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired or if Boipulmonale Sol (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 Boipulmonale Sol (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 Boipulmonale Sol (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 Boipulmonale Sol (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 Boipulmonale Sol (Potassium Iodide) by the average adult is 50 to 100 mEq per day. Boipulmonale Sol (Potassium Iodide) depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of Boipulmonale Sol (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 Boipulmonale Sol (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 Boipulmonale Sol (Potassium Iodide) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of Boipulmonale Sol (Potassium Iodide) chloride.

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

HOW SUPPLIED

Boipulmonale Sol (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

Boipulmonale Sol (Potassium Iodide) chloride 20 Meq

Promethazine Hydrochloride:

• Indications and usage
• Contraindications
• Warnings
• Use in pediatric patients
• Other considerations
• Precautions
• Adverse reactions
• Drug abuse and dependence
• Overdosage
• Dosage and administration
• How supplied
• Boipulmonale Sol (Promethazine Hydrochloride) reviews

INDICATIONS AND USAGE

Boipulmonale Sol (Promethazine Hydrochloride) with codeine syrup is indicated for the temporary relief of coughs and upper respiratory symptoms associated with allergy or the common cold.

CONTRAINDICATIONS

The combination of Boipulmonale Sol (Promethazine Hydrochloride) hydrochloride and codeine phosphate is contraindicated in pediatric patients less than 6 years of age, because the combination may cause fatal respiratory depression in this age population.

Codeine is contraindicated in patients with a known hypersensitivity to the drug.

Boipulmonale Sol (Promethazine Hydrochloride) is contraindicated in comatose states, and in individuals known to be hypersensitive or to have had an idiosyncratic reaction to Boipulmonale Sol (Promethazine Hydrochloride) or to other phenothiazines.

Antihistamines and codeine are both contraindicated for use in the treatment of lower respiratory tract symptoms, including asthma.

WARNINGS

WARNING:

The combination of Boipulmonale Sol hydrochloride and codeine phosphate is contraindicated in pediatric patients less than 6 years of age. Concomitant administration of Boipulmonale Sol (Promethazine Hydrochloride) products with other respiratory depressants has an association with respiratory depression, and sometimes death, in pediatric patients.

Postmarketing cases of respiratory depression, including fatalities, have been reported with use of Boipulmonale Sol (Promethazine Hydrochloride) hydrochloride in pediatric patients less than 2 years of age. A wide range of weight-based doses of Boipulmonale Sol (Promethazine Hydrochloride) hydrochloride have resulted in respiratory depression in these patients.

Codeine:

Dosage of codeine SHOULD NOT BE INCREASED if cough fails to respond; an unresponsive cough should be reevaluated in 5 days or sooner for possible underlying pathology, such as foreign body or lower respiratory tract disease.

Codeine may cause or aggravate constipation.

Respiratory depression leading to arrest, coma, and death has occurred with the use of codeine antitussives in young children, particularly in the under-one-year infants whose ability to deactivate the drug is not fully developed.

Administration of codeine may be accompanied by histamine release and should be used with caution in atopic children.

Head Injury And Increased Intracranial Pressure:

The respiratory-depressant effects of narcotic analgesics and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, intracranial lesions or a pre-existing increase in intracranial pressure. Narcotics may produce adverse reactions which may obscure the clinical course of patients with head injuries.

Asthma And Other Respiratory Conditions:

Narcotic analgesics or cough suppressants, including codeine, should not be used in asthmatic patients. Nor should they be used in acute febrile illness associated with productive cough or in chronic respiratory disease where interference with ability to clear the tracheobronchial tree of secretions would have a deleterious effect on the patient's respiratory function.

Hypotensive Effect:

Codeine may produce orthostatic hypotension in ambulatory patients.

Boipulmonale Sol :

CNS Depression –

Boipulmonale Sol may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. The impairment may be amplified by concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore, such agents should either be eliminated or given in reduced dosage in the presence of Boipulmonale Sol (Promethazine Hydrochloride) HCl (see PRECAUTIONS - Information For Patients and Drug Interactions ).

Respiratory Depression –

Boipulmonale Sol (Promethazine Hydrochloride) may lead to potentially fatal respiratory depression.

Use of Boipulmonale Sol (Promethazine Hydrochloride) in patients with compromised respiratory function (e.g., COPD, sleep apnea) should be avoided.

Lower Seizure Threshold –

Boipulmonale Sol may lower seizure threshold. It should be used with caution in persons with seizure disorders or in persons who are using concomitant medications, such as narcotics or local anesthetics, which may also affect seizure threshold.

Bone-Marrow Depression –

Boipulmonale Sol (Promethazine Hydrochloride) should be used with caution in patients with bone marrow depression. Leukopenia and agranulocytosis have been reported, usually when Boipulmonale Sol (Promethazine Hydrochloride) HCl has been used in association with other known marrow-toxic agents.

Neuroleptic Malignant Syndrome –

A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with Boipulmonale Sol (Promethazine Hydrochloride) HCl alone or in combination with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmias).

The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology.

The management of NMS should include 1) immediate discontinuation of Boipulmonale Sol (Promethazine Hydrochloride) HCl, antipsychotic drugs, if any, and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.

Since recurrences of NMS have been reported with phenothiazines, the reintroduction of Boipulmonale Sol (Promethazine Hydrochloride) HCl should be carefully considered.

Use In Pediatric Patients

The combination of Boipulmonale Sol (Promethazine Hydrochloride) hydrochloride and codeine phosphate is contraindicated in pediatric patients less than 6 years of age. Concomitant administration of Boipulmonale Sol (Promethazine Hydrochloride) products with other respiratory depressants has an association with respiratory depression, and sometimes death, in pediatric patients. The association does not directly relate to individualized weight-based dosing, which might otherwise permit safe administration.

Excessively large dosages of antihistamines, including Boipulmonale Sol (Promethazine Hydrochloride) hydrochloride, in pediatric patients may cause sudden death (see OVERDOSAGE ). Hallucinations and convulsions have occurred with therapeutic doses and overdoses of Boipulmonale Sol (Promethazine Hydrochloride) hydrochloride in pediatric patients. In pediatric patients who are acutely ill associated with dehydration, there is an increased susceptibility to dystonias with the use of Boipulmonale Sol (Promethazine Hydrochloride) HCl.

Other Considerations

Administration of Boipulmonale Sol (Promethazine Hydrochloride) has been associated with reported cholestatic jaundice.

PRECAUTIONS

Animal reproduction studies have not been conducted with the drug combination-promethazine and codeine. It is not known whether this drug combination can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Boipulmonale Sol hydrochloride and codeine phosphate should be given to a pregnant woman only if clearly needed.

General:

Narcotic analgesics, including codeine, should be administered with caution and the initial dose reduced in patients with acute abdominal conditions, convulsive disorders, significant hepatic or renal impairment, fever, hypothyroidism, Addison's disease, ulcerative colitis, prostatic hypertrophy, in patients with recent gastrointestinal or urinary tract surgery, and in the very young or elderly or debilitated patients.

Drugs having anticholinergic properties should be used with caution in patients with narrow-angle glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloroduodenal obstruction, and bladder-neck obstruction.

Boipulmonale Sol (Promethazine Hydrochloride) should be used cautiously in persons with cardiovascular disease or with impairment of liver function.

Ultra-Rapid Metabolizers of Codeine

Some individuals may be ultra-rapid metabolizers due to a specific CYP2D6*2x2 genotype. These individuals convert codeine into its active metabolite, morphine, more rapidly and completely than other people. This rapid conversion results in higher than expected serum morphine levels. Even at labeled dosage regimens, individuals who are ultra-rapid metabolizers may experience overdose symptoms such as extreme sleepiness, confusion, or shallow breathing.

The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0.5 to 1% in Chinese and Japanese, 0.5 to 1% in Hispanics, 1–10% in Caucasians, 3% in African Americans, and 16–28% in North Africans, Ethiopians and Arabs. Data is not available for other ethnic groups.

When physicians prescribe codeine-containing drugs, they should choose the lowest effective dose for the shortest period of time and should inform their patients about these risks and the signs of morphine overdose.

Information For Patients:

Patients should be advised to measure Boipulmonale Sol (Promethazine Hydrochloride) with codeine syrup with an accurate measuring device. A household teaspoon is not an accurate measuring device and could lead to overdosage, especially when a half a teaspoon is measured. A pharmacist can recommend an appropriate measuring device and can provide instructions for measuring the correct dose.

Boipulmonale Sol (Promethazine Hydrochloride) and codeine may cause marked drowsiness or may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a vehicle or operating machinery. Ambulatory patients should be told to avoid engaging in such activities until it is known that they do not become drowsy or dizzy from Boipulmonale Sol (Promethazine Hydrochloride) and codeine therapy. Pediatric patients should be supervised to avoid potential harm in bike riding or in other hazardous activities.

The concomitant use of alcohol or other central-nervous-system depressants, such as sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers may enhance impairment and should be avoided or their dosage reduced (see WARNINGS -CNS Depression and PRECAUTIONS-Drug Interactions ).

Patients should be advised to report any involuntary muscle movements.

Avoid prolonged exposure to the sun.

Codeine, like other narcotic analgesics, may produce orthostatic hypotension in some ambulatory patients. Patients should be cautioned accordingly.

Caution patients that some people have a variation in a liver enzyme and change codeine into morphine more rapidly and completely than other people. These people are ultra-rapid metabolizers and are more likely to have higher-than-normal levels of morphine in their blood after taking codeine which can result in overdose symptoms such as extreme sleepiness, confusion, or shallow breathing. In most cases, it is unknown if someone is an ultra-rapid codeine metabolizer.

Nursing mothers taking codeine can also have higher morphine levels in their breast milk if they are ultra-rapid metabolizers. These higher levels of morphine in breast milk may lead to life-threatening or fatal side effects in nursing babies. Instruct nursing mothers to watch for signs of morphine toxicity in their infants including increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness. Instruct nursing mothers to talk to the baby's doctor immediately if they notice these signs and, if they cannot reach the doctor right away, to take the baby to an emergency room or call 911 (or local emergency services).

Drug Interactions:

Codeine:

In patients receiving MAO inhibitors, an initial small test dose is advisable to allow observation of any excessive narcotic effects or MAOI interaction.

Boipulmonale Sol :

CNS Depressants –

Boipulmonale Sol may increase, prolong, or intensify the sedative action of other central-nervous-system depressants, such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered in reduced dosage to patients receiving Boipulmonale Sol (Promethazine Hydrochloride) HCl. When given concomitantly with Boipulmonale Sol (Promethazine Hydrochloride), the dose of barbiturates should be reduced by at least one-half, and the dose of narcotics should be reduced by one-quarter to one-half. Dosage must be individualized. Excessive amounts of Boipulmonale Sol (Promethazine Hydrochloride) HCl relative to a narcotic may lead to restlessness and motor hyperactivity in the patient with pain; these symptoms usually disappear with adequate control of the pain.

Epinephrine –

Because of the potential for Boipulmonale Sol (Promethazine Hydrochloride) to reverse epinephrine's vasopressor effect, epinephrine should NOT be used to treat hypotension associated with Boipulmonale Sol (Promethazine Hydrochloride) overdose.

Anticholinergics –

Concomitant use of other agents with anticholinergic properties should be undertaken with caution.

Monoamine Oxidase Inhibitors –

Drug interactions, including an increased incidence of extrapyramidal effects, have been reported when some MAOI and phenothiazines are used concomitantly.

Drug/Laboratory Test Interactions:

Because narcotic analgesics may increase biliary tract pressure with resultant increases in plasma amylase or lipase levels, determination of these enzyme levels may be unreliable for 24 hours after a narcotic analgesic has been given.

The following laboratory tests may be affected in patients who are receiving therapy with Boipulmonale Sol hydrochloride.

Pregnancy Tests:

Diagnostic pregnancy tests based on immunological reactions between HCG and anti-HCG may result in false-negative or false-positive interpretations.

Glucose Tolerance Test:

An increase in blood glucose has been reported in patients receiving Boipulmonale Sol.

Carcinogenesis, Mutagenesis, Impairment Of Fertility:

Long-term animal studies have not been performed to assess the carcinogenic potential of codeine or of Boipulmonale Sol (Promethazine Hydrochloride), nor are there other animal or human data concerning carcinogenicity, mutagenicity, or impairment of fertility with these agents. Codeine has been reported to show no evidence of carcinogenicity or mutagenicity in a variety of test systems, including the micronucleus and sperm abnormality assays and the Salmonella assay. Boipulmonale Sol (Promethazine Hydrochloride) was nonmutagenic in the Salmonella test system of Ames.

Pregnancy:

Teratogenic Effects - Pregnancy Category C.

Codeine:

A study in rats and rabbits reported no teratogenic effect of codeine administered during the period of organogenesis in doses ranging from 5 to 120 mg/kg. In the rat, doses at the 120-mg/kg level, in the toxic range for the adult animal, were associated with an increase in embryo resorption at the time of implantation. In another study a single 100-mg/kg dose of codeine administered to pregnant mice reportedly resulted in delayed ossification in the offspring.

There are no studies in humans, and the significance of these findings to humans, if any, is not known.

Boipulmonale Sol :

Teratogenic effects have not been demonstrated in rat-feeding studies at doses of 6.25 and 12.5 mg/kg of Boipulmonale Sol (Promethazine Hydrochloride) HCl. These doses are from approximately 2.1 to 4.2 times the maximum recommended total daily dose of Boipulmonale Sol (Promethazine Hydrochloride) for a 50-kg subject, depending upon the indication for which the drug is prescribed. Daily doses of 25 mg/kg intraperitoneally have been found to produce fetal mortality in rats.

Specific studies to test the action of the drug on parturition, lactation, and development of the animal neonate were not done, but a general preliminary study in rats indicated no effect on these parameters. Although antihistamines have been found to produce fetal mortality in rodents, the pharmacological effects of histamine in the rodent do not parallel those in man. There are no adequate and well-controlled studies of Boipulmonale Sol (Promethazine Hydrochloride) in pregnant women.

Boipulmonale Sol (Promethazine Hydrochloride) and codeine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects -

Dependence has been reported in newborns whose mothers took opiates regularly during pregnancy. Withdrawal signs include irritability, excessive crying, tremors, hyperreflexia, fever, vomiting, and diarrhea. Signs usually appear during the first few days of life.

Boipulmonale Sol administered to a pregnant woman within two weeks of delivery may inhibit platelet aggregation in the newborn.

Labor And Delivery:

Narcotic analgesics cross the placental barrier. The closer to delivery and the larger the dose used, the greater the possibility of respiratory depression in the newborn. Narcotic analgesics should be avoided during labor if delivery of a premature infant is anticipated. If the mother has received narcotic analgesics during labor, newborn infants should be observed closely for signs of respiratory depression. Resuscitation may be required (see OVERDOSAGE ).

Limited data suggest that use of Boipulmonale Sol (Promethazine Hydrochloride) hydrochloride during labor and delivery does not have an appreciable effect on the duration of labor or delivery and does not increase the risk of need for intervention in the newborn.

The effect of Boipulmonale Sol (Promethazine Hydrochloride) and/or codeine on the later growth and development of the newborn is unknown.

Nursing Mothers:

It is not known whether Boipulmonale Sol is excreted in human milk.

Codeine is secreted into human milk. In women with normal codeine metabolism (normal CYP2D6 activity), the amount of codeine secreted into human milk is low and dose-dependent. Despite the common use of codeine products to manage postpartum pain, reports of adverse events in infants are rare. However, some women are ultra-rapid metabolizers of codeine. These women achieve higher-than-expected serum levels of codeine's active metabolite, morphine, leading to higher-than-expected levels of morphine in breast milk and potentially dangerously high serum morphine levels in their breastfed infants. Therefore, maternal use of codeine can potentially lead to serious adverse reactions, including death, in nursing infants.

The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0.5 to 1% in Chinese and Japanese, 0.5 to 1% in Hispanics, 1–10% in Caucasians, 3% in African Americans, and 16–28% in North Africans, Ethiopians and Arabs. Data is not available for other ethnic groups.

The risk of infant exposure to codeine and morphine through breast milk should be weighed against the benefits of breastfeeding for both the mother and baby. Caution should be exercised when codeine is administered to a nursing woman. If a codeine-containing product is selected, the lowest dose should be prescribed for the shortest period of time to achieve the desired clinical effect. Mothers using codeine should be informed about when to seek immediate medical care and how to identify the signs and symptoms of neonatal toxicity, such as drowsiness or sedation, difficulty breastfeeding, breathing difficulties, and decreased tone, in their baby. Nursing mothers who are ultra-rapid metabolizers may also experience overdose symptoms such as extreme sleepiness, confusion, or shallow breathing. Prescribers should closely monitor mother-infant pairs and notify treating pediatricians about the use of codeine during breastfeeding (see PRECAUTIONS – General - Ultra-Rapid Metabolizers of Codeine ).

Caution should be exercised when Boipulmonale Sol (Promethazine Hydrochloride) with codeine syrup is administered to a nursing woman.

Pediatric Use:

The combination of Boipulmonale Sol (Promethazine Hydrochloride) hydrochloride and codeine phosphate is contraindicated in pediatric patients less than 6 years of age, because the combination may cause fatal respiratory depression in this age population (see WARNINGS – Box Warning and Use In Pediatric Patients).

The combination of Boipulmonale Sol (Promethazine Hydrochloride) hydrochloride and codeine phosphate should be used with caution in pediatric patients 6 years and older (see Warnings-Use in Pediatric Patients ).

Geriatric Use:

Clinical studies of Boipulmonale Sol (Promethazine Hydrochloride) hydrochloride and codeine phosphate syrup 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.

Sedating drugs may cause confusion and over-sedation in the elderly; elderly patients generally should be started on low doses of Boipulmonale Sol (Promethazine Hydrochloride) with codeine syrup and observed closely.

ADVERSE REACTIONS

Codeine:

Nervous System – CNS depression, particularly respiratory depression, and to a lesser extent circulatory depression; light-headedness, dizziness, sedation, euphoria, dysphoria, headache, transient hallucination, disorientation, visual disturbances, and convulsions.

Cardiovascular – Tachycardia, bradycardia, palpitation, faintness, syncope, orthostatic hypotension (common to narcotic analgesics).

Gastrointestinal – Nausea, vomiting, constipation, and biliary tract spasm. Patients with chronic ulcerative colitis may experience increased colonic motility; in patients with acute ulcerative colitis, toxic dilation has been reported.

Genitourinary – Oliguria, urinary retention; antidiuretic effect has been reported (common to narcotic analgesics).

Allergic – Infrequent pruritus, giant urticaria, angioneurotic edema, and laryngeal edema.

Other – Flushing of the face, sweating and pruritus (due to opiate-induced histamine release); weakness.

Boipulmonale Sol (Promethazine Hydrochloride):

Central Nervous System – Drowsiness is the most prominent CNS effect of this drug. Sedation, somnolence, blurred vision, dizziness; confusion, disorientation, and extrapyramidal symptoms such as oculogyric crisis, torticollis, and tongue protrusion; lassitude, tinnitus, incoordination, fatigue, euphoria, nervousness, diplopia, insomnia, tremors, convulsive seizures, excitation, catatonic-like states, hysteria. Hallucinations have also been reported.

Cardiovascular – Increased or decreased blood pressure, tachycardia, bradycardia, faintness.

Dermatologic – Dermatitis, photosensitivity, urticaria.

Hematologic – Leukopenia, thrombocytopenia, thrombocytopenic purpura, agranulocytosis.

Gastrointestinal – Dry mouth, nausea, vomiting, jaundice.

Respiratory – Asthma, nasal stuffiness, respiratory depression (potentially fatal) and apnea (potentially fatal). (See WARNINGS - Boipulmonale Sol (Promethazine Hydrochloride); Respiratory Depression.)

Other – Angioneurotic edema. Neuroleptic malignant syndrome (potentially fatal) has also been reported. (See WARNINGS - Boipulmonale Sol (Promethazine Hydrochloride); Neuroleptic Malignant Syndrome.)

Paradoxical Reactions – Hyperexcitability and abnormal movements have been reported in patients following a single administration of Boipulmonale Sol (Promethazine Hydrochloride) HCI. Consideration should be given to the discontinuation of Boipulmonale Sol (Promethazine Hydrochloride) HCl and to the use of other drugs if these reactions occur. Respiratory depression, nightmares, delirium, and agitated behavior have also been reported in some of these patients.

DRUG ABUSE AND DEPENDENCE

Controlled Substance:

Boipulmonale Sol with codeine syrup is a Schedule V Controlled Substance.

Abuse:

Codeine is known to be subject to abuse; however, the abuse potential of oral codeine appears to be quite low. Even parenteral codeine does not appear to offer the psychic effects sought by addicts to the same degree as heroin or morphine. However, codeine must be administered only under close supervision to patients with a history of drug abuse or dependence.

Dependence:

Psychological dependence, physical dependence, and tolerance are known to occur with codeine.

OVERDOSAGE

Codeine:

Serious overdose with codeine is characterized by respiratory depression, extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. The triad of coma, pinpoint pupils, and respiratory depression is strongly suggestive of opiate poisoning. In severe overdosage, particularly by the intravenous route, apnea, circulatory collapse, cardiac arrest, and death may occur. Boipulmonale Sol (Promethazine Hydrochloride) is additive to the depressant effects of codeine.

It is difficult to determine what constitutes a standard toxic or lethal dose. However, the lethal oral dose of codeine in an adult is reported to be in the range of 0.5 to 1.0 gram. Infants and children are believed to be relatively more sensitive to opiates on a body-weight basis. Elderly patients are also comparatively intolerant to opiates.

Boipulmonale Sol (Promethazine Hydrochloride):

Signs and symptoms of overdosage with Boipulmonale Sol (Promethazine Hydrochloride) HCl range from mild depression of the central nervous system and cardiovascular system to profound hypotension, respiratory depression, unconsciousness, and sudden death. Other reported reactions include hyperreflexia, hypertonia, ataxia, athetosis, and extensor-plantar reflexes (Babinski reflex).

Stimulation may be evident, especially in children and geriatric patients. Convulsions may rarely occur. A paradoxical-type reaction has been reported in children receiving single doses of 75 mg to 125 mg orally, characterized by hyperexcitability and nightmares.

Atropine-like signs and symptoms – dry mouth, fixed dilated pupils, flushing, as well as gastrointestinal symptoms may occur.

Treatment:

The treatment of overdosage with Boipulmonale Sol (Promethazine Hydrochloride) and codeine is essentially symptomatic and supportive. Only in cases of extreme overdosage or individual sensitivity do vital signs including respiration, pulse, blood pressure, temperature, and EKG need to be monitored. Activated charcoal orally or by lavage may be given, or sodium or magnesium sulfate orally as a cathartic. Attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation. The narcotic antagonist, naloxone hydrochloride, may be administered when significant respiratory depression occurs with Boipulmonale Sol (Promethazine Hydrochloride) and codeine; any depressant effects of Boipulmonale Sol (Promethazine Hydrochloride) are not reversed with naloxone. Diazepam may be used to control convulsions. Avoid analeptics, which may cause convulsions. Acidosis and electrolyte losses should be corrected. A rise in temperature or pulmonary complications may signal the need for institution of antibiotic therapy.

Severe hypotension usually responds to the administration of norepinephrine or phenylephrine. EPINEPHRINE SHOULD NOT BE USED, since its use in a patient with partial adrenergic blockade may further lower the blood pressure.

Limited experience with dialysis indicates that it is not helpful.

DOSAGE AND ADMINISTRATION

The combination of Boipulmonale Sol (Promethazine Hydrochloride) hydrochloride and codeine phosphate is contraindicated in pediatric patients less than 6 years of age, because the combination may cause fatal respiratory depression in this age population.

It is important that Boipulmonale Sol (Promethazine Hydrochloride) with codeine syrup is measured with an accurate measuring device (see PRECAUTIONS-Information For Patients ). A household teaspoon is not an accurate measuring device and could lead to overdosage, especially when half a teaspoon is to be measured. It is strongly recommended that an accurate measuring device be used. A pharmacist can provide an appropriate device and can provide instructions for measuring the correct dose.

The average effective dose for adults and children 12 years of age and over is: 1 teaspoonful (5 mL) every 4 to 6 hours, not to exceed 30 mL in 24 hours.

The average effective dose for children 6 years to under 12 years of age is 1/2 to 1 teaspoonful (2.5 mL to 5 mL) every 4 to 6 hours, not to exceed 30 mL in 24 hours.

HOW SUPPLIED

Boipulmonale Sol (Promethazine Hydrochloride) with Codeine Syrup, a clear purple syrup with odor of grape menthol, contains Boipulmonale Sol (Promethazine Hydrochloride) hydrochloride 6.25 mg/5 mL, codeine phosphate 10 mg/5 mL and alcohol 7 percent, and is available in 4 fluid ounce (118 mL), 8 fluid ounce (237 mL) and pint (473 mL).

Store at 20°-25°C (68°-77°F).

Dispense in a tight, light-resistant container with a child-resistant closure as defined in the USP.

Manufactured for:

QUALITEST PHARMACEUTICALS

Huntsville, AL 35811

8181652

R1/09-R4