icon-menu
icon-menu

Products

Theophylline KI, elixir

Drug formLiquid (for oral use)

ATC categoryPulmonology

ATC subcategoryBronchodilator and expectorant agents

Brand nameTheophylline KI

Generic nameTheophylline / Potassium iodide

Composition

Each 15 ml of Theophylline KI Elixir contains:

active ingredients: theophylline – 80 mg, potassium iodide – 130 mg;
excipients: benzoic acid, sodium benzoate, ethyl alcohol 96%, propylene glycol, sucrose, aroma orange, color yellow E-102, methylparaben, sodium saccharin ,water purified.

Pharmacological group and ATC code
Bronchodilating agent, mucolitic; R03DA04, H03CA.

Pharmacology

Theophylline directly relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels, thus acting as a bronchodilator and smooth muscle relaxant. It has also been demonstrated that aminophylline has a potent effect on diaphragmatic contractility in normal persons and may then be capable of reducing fatigability and thereby improve contractility in patients with chronic obstructive airways disease. The exact mode of action remains unsettled. Although theophylline does cause inhibition of phosphodiesterase with a resultant increase in intracellular cyclic AMP, other agents similarly inhibit the enzyme producing a rise of cyclic AMP, but are unassociated with any demonstrable bronchodilation. Other mechanisms proposed include an effect on translocation of intracellular calcium; prostaglandin antagonism; stimulation of catecholamines endogenously; inhibition of cyclic guanosine monophospate metabolism and adenosine receptor antagonism. None of these mechanisms has been proved, however.

In vitro , theophylline has been shown to act synergistically with beta agonists and there are now available data which do demonstrate an additive effect in vitro with combined use.

Potassium iodide acts as an expectorant by liquifying tenacious bronchial secretions.

Pharmacokinetics
The half-life of theophylline is influenced by a number of known variables. It may be prolonged in chronic alcoholics, particularly those with liver disease (cirrhosis or alcoholic liver disease), in patients with congestive heart failure, and in those patients taking certain other drugs. Newborns and neonates have extremely slow clearance rate compared to older infants and children (i.e., those over 1 year). Older children have rapid clearance rates while most non-smoking adults have clearance rates between these two extremes. In premature neonates the decreased clearance is related to oxidative pathways that have yet to be established.

Theophylline Elimination Characteristics
Half-Life (in hours)
Range
Half-Life (in hours)
Mean
Children 1-9 3.7
Adults >3-15 7.7



In cigarette smokers (1 to 2 packs/day) the mean half-life is 4 to 5 hours, much shorter than in non-smokers. The increase in clearance associated with smoking is presumably due to stimulation of the hepatic metabolic pathway by components of cigarette smoke. The duration of this effect after cessation of smoking is unknown, but may require 6 months to 2 years before the rate approaches that of the non-smoker.

Uses
For excessive tenacious mucus and for relief and/or prevention of symptoms from asthma and reversible bronchospasm associated with chronic bronchitis and emphysema.
Dosage and administration
Effective use of theophylline (i.e., the concentration of drug in the serum associated with optimal benefit and minimal risk of toxicity) is considered to occur when the theophylline concentration is maintained from 10 to 20 mcg/ml. The early studies from which these levels are derived were carried out in patients immediately or shortly after recovery from acute exacerbations of their disease (some hospitalized with status asthmaticus).

Although the 20 mcg/ml level remains appropriate as a critical value (above which toxicity is more likely to occur) for safety purposes, additional data are now available which indicate that the serum theophylline concentrations required to produce maximum physiologic benefit may, in fact, fluctuate with the degree of bronchospasm present and are variable. Therefore, the physician should individualize the range appropriate to the patient’s requirements, based on both symptomatic response and improvement in pulmonary function. It should be stressed that serum theophylline concentrations maintained at the upper level of the 10 to 20 mcg/ml range may be associated with potential toxicity when factors known to reduce theophylline clearance are operative.

If it is not possible to obtain serum level determinations, restrictions of the daily dose (in otherwise healthy adults) to not greater than 13 mg/kg/day, to a maximum of 900 mg of theophylline in divided doses, will result in relatively few patients exceeding serum levels of 20 mcg/ml and the resultant greater risk of toxicity.

Caution should be exercised for younger children who cannot complain of minor side effects. Older adults, those with cor pulmonale, congestive heart failure, and/or liver disease may have unusually low dosage requirements and thus may experience toxicity at the maximal dosage recommended below.

Theophylline does not distribute into fatty tissue. Dosage should be calculated on the basis of lean (ideal) body weight where mg/kg doses are presented.

Frequency of Dosing:

When immediate release products with rapid absorption are used, dosing to maintain serum levels generally requires administration every 6 hours. This is particularly true in children, but dosing intervals up to 8 hours may be satisfactory in adults since they eliminate the drug at a slower rate. Some children, and adults requiring higher than average doses (those having rapid rates of clearance, e.g., half-lives of under 6 hours) may benefit and be more effectively controlled during chronic therapy when given products with sustained release characteristics since these provide longer dosing intervals and/or less fluctuation in serum concentration between dosing.

Dosage guidelines are approximations only and the wide range of theophylline clearance between individuals (particularly those with concomitant disease) makes indiscriminate usage hazardous.

Dosage Guidelines

Acute Symptoms

NOTE:

Status asthmaticus should be considered a medical emergency and is defined as that degree of bronchospasm which is not rapidly responsive to usual doses of conventional bronchodilators. Optimal therapy for such patients frequently requires both additional medication, parenterally administered, and close monitoring, preferably in an intensive care setting.

Patients Not Currently Receiving Theophylline Products

Theophylline Dosage
Oral Loading
Maintenance
Children age 9 to under 16 years; and smokers 5mg/kg 3mg/kg q 6 hours
Otherwise healthy non-smoking adults 5mg/kg 3 mg/kg q 8 hours
Older patients and patients with cor pulmonale 5mg/kg 2mg/kg q 8 hours
Patients with congestive heart failure 5mg/kg 1-2mg/kg q 12hours



Patients Currently Receiving Theophylline Products

Determine, where possible, the time, amount, dosage form, and route of administration of the last dose the patient received.

The loading dose for theophylline is based on the principle that each 0.5 mg/kg of theophylline administered as a loading dose will result in a 1.0 mcg/ml increase in serum theophylline concentration. Ideally, the loading dose should be deferred if a serum theophylline concentration can be obtained rapidly.

If this is not possible, the clinician must exercise judgment in selecting a dose based on the potential for benefit and risk. When there is sufficient respiratory distress to warrant a small risk, then 2.5 mg/kg of theophylline administered in rapidly absorbed form is likely to increase serum concentration by approximately 5 mcg/ml. If the patient is not experiencing theophylline toxicity, this is unlikely to result in dangerous adverse effects.

Subsequent to the decision regarding use of a loading dose for this group of patients, the maintenance dosage recommendations are the same as those described above.

Chronic Therapy

Theophylline is a treatment for the management of reversible bronchospasm (asthma, chronic bronchitis and emphysema) to prevent symptoms and maintain patient airways. A dosage form which allows small incremental doses is desirable for initiating therapy. A liquid preparation should be considered for children to permit easier and more accurate dosage adjustment. Slow clinical titration is generally preferred to help assure acceptance and safety of the medication and to allow the patient to develop tolerance to transient caffeine-like side effects.

Initial Dose

16 mg/kg/24 hours or 400 mg/24 hours (whichever is less) of theophylline in divided doses at 6 or 8 hour intervals.

Increasing Dose

The above dosage may be increased in approximately 25 percent increments at 3 day intervals so long as the drug is tolerated: until clinical response is satisfactory or the maximum dose as indicated in Maximum Dose of Theophylline Where the Serum Concentration is not Measured is reached. The serum concentration may be checked at these intervals, but at a minimum, should be determined at the end of this adjustment period.

It is important that no patient be maintained on any dosage that is not tolerated. When instructing patients to increase dosage according to the schedule above, they should be told not to take a subsequent dose if apparent side effects occur and to resume therapy at a lower dose once adverse effects have disappeared.

Maximum Dose of Theophylline Where the Serum Concentration is not Measured

WARNING: DO NOT ATTEMPT TO MAINTAIN ANY DOSE THAT IS NOT TOLERATED.

Not to exceed the following dosage (or 900 mg, whichever is less).
Age 1 – under 9 years: 24 mg/kg/day
Age 9 – under 12 years: 20 mg/kg/day
Age 12 – under 16 years: 18 mg/kg/day
Age 16 years and older: 13 mg/kg/day

Contraindications
This product is contraindicated in individuals who have shown hypersensitivity to its components. It is also contraindicated in patients with active peptic ulcer disease, and in individuals with underlying seizure disorders (unless receiving appropriate anticonvulsant medication).

Adverse effects

The following adverse reactions have been observed, but there has not been enough systematic collection of data to support an estimate of their frequency. The most consistent adverse reactions are usually due to overdosage.

Gastrointestinal: Nausea, vomiting, epigastric pain, hematemesis, diarrhea.

Central nervous system: Headaches, irritability, restlessness, insomnia, reflex hyperexcitability, muscle twitching, clonic and tonic generalized convulsions.

Cardiovascular: Palpitation, tachycardia, extrasystoles, flushing, hypotension, circulatory failure, ventricular arrhythmias.

Respiratory: Tachypnea

Renal: Potentiation of diuresis

Others: Alopecia, hyperglycemia, inappropriate ADH syndrome, rash.Potassium Iodide-Thyroid adenoma, goiter and myxedema are possible side effects of potassium iodide.Hypersensitivity to iodides may be manifested by angioneurotic edema, cutaneous and mucosal hemorrhages, and symptoms resembling serum sickness, such as fever, arthralgia, lymph node enlargement and eosinophilia.

Iodism or chronic iodine poisoning may occur during prolonged treatment. The symptoms of iodism include: a metallic taste, soreness of the mouth, increased salivation, coryza, sneezing, and swelling of the eyelids. There may be a severe headache, productive cough, pulmonary edema and swelling and tenderness of the salivary glands. Acneform skin lesions are seen in the seborrheic areas. Severe and sometimes fatal skin eruptions may develop. Gastric disturbance and diarrhea are common. If iodism appears, the drug should be withdrawn and the patient given appropriate supportive therapy.

Precautions

General

On the average, theophylline half-life is shorter in cigarette and marijuana smokers than in non-smokers, but smokers can have half-lives as long as non-smokers. Potassium iodide; theophylline anhydrous should not be administered concurrently with other xanthine medications. Use with caution in patients with hypoxemia, hypertension or those with history of peptic ulcer. Theophylline preparations should be used cautiously in patients with history of peptic ulcer, since they may occasionally act as a local irritant to the G.I. tract. Gastrointestinal symptoms, however, are more commonly centrally mediated and associated with serum drug concentrations over 20 mcg/ml.

Occasionally, persons are markedly sensitive to iodides and care should be used in administering potassium iodide; theophylline anhydrous for the first time. Caution is recommended in patients sensitive to iodides and in patients receiving potassium sparing diuretics or potassium supplements.

Information for the Patient

The importance of taking only the prescribed dose and time interval between doses should be reinforced.

Laboratory Tests

Serum levels should be monitored periodically to determine the theophylline level associated with observed clinical response and as the method of predicting toxicity. For such measurements, the serum sample should be obtained at the time of peak concentration, 1 to 2 hours after administration. It is important that the patient will not have missed or taken additional doses during the previous 48 hours and that dosing intervals will have been reasonably equally spaced.DOSAGE ADJUSTMENT BASED ON SERUM THEOPHYLLINE MEASUREMENTS WHEN THESE INSTRUCTIONS HAVE NOT BEEN FOLLOWED MAY RESULT IN RECOMMENDATIONS THAT PRESENT RISK OF TOXICITY TO THE PATIENT.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term carcinogenicity studies have not been performed with theophylline.

Chromosome-breaking activity was detected in human cell cultures at concentrations of theophylline up to 50 times the therapeutic serum concentration in humans. Theophylline was not mutagenic in the dominant lethal assay in male mice given theophylline intraperitoneally in doses up to 30 times the maximum daily human oral dose.

Studies to determine the effect on fertility have not been performed with theophylline.

Pregnancy, Teratogenic Effects, Pregnancy Category C

Animal reproduction studies have not been conducted with theophylline. It is also not known whether theophylline can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Xanthines should be given to a pregnant woman only if clearly needed.

Nursing Mothers

Theophylline is distributed into breast milk and may cause irritability or other signs of toxicity in nursing infants. Iodides are also secreted in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Since safety and effectiveness in children have not been established, it is recommended that potassium iodide; theophylline anhydrous not be used in children under 12 years of age.

Laboratory Test Interactions

Currently available analytical methods, including high pressure liquid chromatography and immunoassay techniques, for measuring serum theophylline levels are specific. Metabolites and other drugs generally do not affect the results. Other new analytic methods are also now in use. The physician should be aware of the laboratory method used and whether other drugs will interfere with the assay for theophylline.

Warnings
Serum levels above 20 mcg/ml are rarely found after appropriate administration of the recommended doses. However, in individuals in whom theophylline plasma clearance is reduced for any reason, even conventional doses may result in increased serum levels and potential toxicity. Reduced theophylline clearance has been documented in the following readily identifiable groups:

1.Patients with impaired renal or liver function.

2.Patients over 55 years of age, particularly males and those with chronic lung disease.

3.Those with cardiac failure from any cause.

4.Patients with sustained high fever.

5.Neonates and infants under 1 year of age.

6.Those patients taking certain drugs (see DRUG INTERACTIONS). Frequently such patients have markedly prolonged theophylline serum levels following discontinuation of the drug.

Reduction of dosage and laboratory monitoring is especially appropriate in the above individuals.

Serious side effects such as ventricular arrhythmias, convulsions or even death may appear as the first sign of toxicity without any previous warning. Less serious signs of theophylline toxicity (i.e., nausea and restlessness) may occur frequently when initiating therapy, but are usually transient; when such signs are persistent during maintenance therapy, they are often associated with serum concentrations above 20 mcg/ml. Stated differently; serious toxicity is not reliably preceded by less severe side effects. A serum concentration measurement is the only reliable method of predicting potentially life-threatening toxicity.

Many patients who require theophylline exhibit tachycardia due to their underlying disease process so that the cause/effect relationship to elevated serum theophylline concentrations may not be appreciated.

Theophylline products may cause or worsen arrhythmias and any significant change in rate and/or rhythm warrants monitoring and further investigation.

Studies in laboratory animals (minipigs, rodents, and dogs) recorded the occurrence of cardiac arrhythmias and sudden death (with histologic evidence of myocardia necrosis) when beta-agonists and methylxanthines were administered concurrently. The significance of these findings when applied to humans is currently unknown.

Potassium iodide can cause fetal harm when administered to a pregnant woman. Because of the possible development of fetal goiter if this drug is used during pregnancy, or if the patient becomes pregnant while taking it, the patient should be apprised of the potential hazard to the fetus.

Contains sodium bisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.

Overdosage
Management

It is suggested that the management principles (consistent with the clinical status of the patient when first seen) outlined below be instituted and that simultaneous contact with a Regional Poison Control Center be established. In this way both updated information and individualization regarding required therapy may be provided.

1. When potential oral overdose is established and seizure has not occurred:

a. If patient is alert and seen within the early hours after ingestion, induction of emesis may be of value. Gastric lavage has been demonstrated to be of no value in influencing outcome in patients who present more than 1 hour after ingestion.
b. Administer a cathartic. Sorbitol solution is reported to be of value.
c. Administer repeated dose of activated charcoal and monitor theophylline serum levels.
d. Prophylactic administration of phenobarbital has been shown to increase the seizure threshold in laboratory animals, and administration of this drug can be considered.

2. If patient presents with a seizure:

a. Establish an airway.
b. Administer oxygen.
c. Treat the seizure with intravenous diazepam, 0.1 to 0.3 mg/kg up to 10 mg. If seizures cannot be controlled, the use of general anesthesia should be considered.
d. Monitor vital signs, maintain blood pressure and provide adequate hydratio

3. If post-seizure coma is present:

a. Maintain airway and oxygenation.
b. If a result of oral medication, follow above recommendations to prevent absorption of the drug, but intubation and lavage will have to be performed instead of inducing emesis, and the cathartic and charcoal will need to be introduced via a large bore gastric lavage tube.
c. Continue to provide full supportive care and adequate hydration until the drug is metabolized. In general, drug metabolism is sufficiently rapid so as not to warrant dialysis. If repeated, oral activated charcoal is ineffective (as noted by stable or rising serum levels) charcoal hemoperfusion may be indicated.

Drug interactions

Toxic synergism with ephedrine has been documented and may occur with other sympathomimetic bronchodilators. In addition, the drug interactions below have been demonstrated with theophylline.

Allopurinal (high dose): Increased serum theophylline levels.
Cimetidine: Increased serum theophylline levels.
Ciprofloxacin: Increased serum theophylline levels.
Erythromycin Troleandomycin: Increased serum theophylline levels.
Lithium Carbonate: Increased renal excretion of lithium.
Oral Contraceptives: Increased serum theophylline levels.
Phenytoin: Decreased theophylline and phenytoin serum levels.
Propranolol: Increased serum theophylline levels.
Rifampin: Decreased serum theophylline levels.
Potassium Iodide With Lithium Carbonate: Increased hypothyroid and goitrogenic effect.
Potassium Iodide: Thyroid function tests may be altered by iodides. As with any potassium-containing medication, the potential for developing hyperkalemia is increased.
Drug-Laboratory: Test Interactions.

Identification

Orange colored liquid with orange flavor.

Presentation

Elixir, 120 ml in the bottle inserted with leaflet in cardboard box.

Expiry date

3 years. Do not use after the expiration date.

Prescription status

To be dispensed with prescription.

Storage conditions

Store at a room temperature, in a dry place, out of the reach of children. Protect from light.