Cetraphylline - General Information
A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Cetraphylline inhibits the 3&
Pharmacology of Cetraphylline
Cetraphylline, an xanthine derivative chemically similar to caffeine and theobromine, is used to treat asthma and bronchospasm. Cetraphylline has two distinct actions in the airways of patients with reversible (asthmatic) obstruction; smooth muscle relaxation (i.e., bronchodilation) and suppression of the response of the airways to stimuli (i.e., non-bronchodilator prophylactic effects).
Cetraphylline for patients
Immediate Release Products
The patient (or parent/care giver) should be instructed to seek medical advice whenever nausea, vomiting, persistent headache, insomnia or rapid heart beat occurs during treatment with theophylline, even if another cause is suspected. The patient should be instructed to contact their clinician 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 clinician and a new medication or discontinues a previously prescribed medication. Patients should be instructed to inform all clinicians involved in their care that they are taking 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 clinician. 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.
This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.
The physician should reinforce the importance of taking only the prescribed dose and the time interval between doses. As with any controlled-release theophylline product, the patient should alert the physician of symptoms occur repeatedly, especially near the end of the dosing interval.
When prescribing administration by the sprinkle method, details of the proper technique should be explained to patient
Patients should be informed of the need to take this drug in the fasting state, and that drug administration should be 1 hour before or 2 hours after meals.
Theophylline interacts with a wide variety of drugs. The interaction may be pharmacodynamic, i.e., alterations in the therapeutic response to theophylline or another drug or occurrence of adverse effects without a change in serum theophylline concentration. More frequently, however, the interaction is pharmacokinetic, i.e., the rate of theophylline clearance is altered by another drug resulting in increased or decreased serum theophylline concentrations. Theophylline only rarely alters the pharmacokinetics of other drugs.
The drugs listed in TABLES 2A and 2B have the potential to produce clinically significant pharmacodynamic or pharmacokinetic interactions with theophylline. The information in the "Effect" column of TABLES 2A and 2B assumes that the interacting drug is being added to a steady-state theophylline regimen. If theophylline is being initiated in a patient who is already taking a drug that inhibits theophylline clearance (e.g., cimetidine, erythromycin), the dose of theophylline required to achieve a therapeutic serum theophylline concentration will be smaller. Conversely, if theophylline is being initiated in a patient who is already taking a drug that enhances theophylline clearance (e.g., rifampin), the dose of theophylline required to achieve a therapeutic serum theophylline concentration will be larger. Discontinuation of a concomitant drug that increases theophylline clearance will result in accumulation of theophylline to potentially toxic levels, unless the theophylline dose is appropriately reduced. Discontinuation of a concomitant drug that inhibits theophylline clearance will result in decreased serum theophylline concentrations, unless the theophylline dose is appropriately increased.
The listing of drugs in TABLES 2A and 2B is current as of April 3, 1995. New interactions are continuously being reported for theophylline, especially with new chemical entities. The clinician should not assume that a drug does not interact with theophylline if it is not listed in TABLES 2A and 2B.Before addition of a newly available drug in a patient receiving 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 theophylline has been reported.
TABLE 2A - Clinically significant drug interactions with theophylline*
|Drug||Type of Interaction||Effect**|
|Adenosine||Theophylline blocks adenosine receptors.||Higher doses of adenosine may be required to achieve desired effect.|
|Alcohol||A single large dose of alcohol (3 ml/kg of whiskey) decreases theophylline clearance for up to 24 hours.||30% increase|
|Allopurinol||Decreases theophylline clearance at allopurinol doses ³600 mg/day.||25% increase|
|Aminoglutethimide||Increases theophylline clearance by induction of microsomal enzyme activity.||25% decrease|
|Carbamazepine||Similar to aminoglutethimide.||30% decrease|
|Cimetidine||Decreases theophylline clearance by inhibiting cytochrome P450 1A2.||70% increase|
|Ciprofloxacin||Similar to cimetidine.||40% increase|
|Clarithromycin||Similar to erythromycin.||25% increase|
|Diazepam||Benzodiazepines increase CNS concentrations of adenosine, a potent CNS depressant, while theophylline blocks adenosine receptors.||Larger diazepam doses may be required to produce desired level of sedation.|
|Discontinuation of theophylline without reduction of diazepam dose may result in respiratory depression.|
|Disulfiram||Decreases theophylline clearance by inhibiting hydroxylation and demethylation.||50% increase|
|Enoxacin||Similar to cimetidine.||300% increase|
|Ephedrine||Synergistic CNS effects||Increased frequency of nausea, nervousness, and insomnia.|
|Erythromycin||Erythromycin metabolite decreases theophylline clearance by inhibiting cytochrome P450 3A3.||35% increase.|
|Erythromycin steady-state serum concentrations decreased by a similar amount.|
|Estrogen||Estrogen containing oral contraceptives decrease theophylline clearance in a dose-dependent fashion. The effect of progesterone on theophylline clearance is unknown.||30% increase|
|Flurazepam||Similar to diazepam.||Similar to diazepam.|
|Fluvoxamine||Similar to cimetidine myocardium to catecholamines, theophylline increases release of endogenous catecholamines.||Similar to cimetidine ventricular arrhythmias.|
|Interferon, human recombinant alpha-A||Decreases theophylline clearance.||100% increase|
|Isoproterenol (IV)||Increases theophylline clearance.||20% decrease|
|Ketamine||Pharmacologic||May lower theophylline seizure threshold.|
|Lithium||Theophylline increases renal lithium clearance.||Lithium dose required to achieve a therapeutic serum concentration increased an average of 60%.|
|Lorazepam||Similar to diazepam.||Similar to diazepam.|
TABLE 2B - Clinically significant drug interactions with theophylline*
|Drug||Type of Interaction||Effect**|
|Methotrexate (MTX)||Decreases theophylline clearance.||20% increase after low dose MTX, higher dose MTX may have a greater effect.|
|Mexiletine||Similar to disulfiram.||80% increase|
|Midazolam||Similar to diazepam.||Similar to diazepam.|
|Moricizine||Increases theophylline clearance.||25% decrease|
|Pancuronium||Theophylline may antagonize non-depolarizing neuromuscular blocking effects; possibly due to phosphodiesterase inhibition.||Larger dose of pancuronium may be required to achieve neuromuscular blockade.|
|Pentoxifylline||Decreases theophylline clearance.||30% increase|
|Phenobarbital (PB)||Similar to aminoglutethimide.||25% decrease after two weeks of concurrent PB.|
|Phenytoin||Phenytoin increases theophylline clearance by increasing microsomal enzyme activity. Theophylline decreases phenytoin absorption.||Serum theophylline and phenytoin concentrations decrease about 40%.|
|Propafenone||Decreases theophylline clearance and pharmacologic interaction.||40% increase. Beta-2 blocking effect may decrease efficacy of theophylline.|
|Propranolol||Similar to cimetidine and pharmacologic interaction.||100% increase. Beta-2 blocking effect may decrease efficacy of theophylline.|
|Rifampin||Increases theophylline clearance by increasing cytochrome P450 1A2 and 3A3 activity.||20-40% decrease|
|Sulfinpyrazone||Increases theophylline clearance by increasing demethylation and hydroxylation.||20% decrease|
|Decreases renal clearance of theophylline.|
|Tacrine||Similar to cimetidine, also increases renal clearance of theophylline.||90% increase|
|Thiabendazole||Decreases theophylline clearance.||190% increase|
|Ticlopidine||Decreases theophylline clearance.||60% increase|
|Troleandomycin||Similar to erythromycin.||33-100% increase depending on troleandomycin dose.|
|Verapamil||Similar to disulfiram.||20% increase|
* Refer to
DRUG INTERACTIONSfor further information regarding table.
** Average effect on steady state theophylline concentration or other clinical effect for pharmacologic interactions. Individual patients may experience larger changes in serum theophylline concentration than the value listed.
The Effect of Other Drugs on Theophylline Serum Concentration Measurements: Most serum theophylline assays in clinical use are immunoassays which are specific for 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 theophylline concentration.
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 anti-convulsant medication).
Additional information about Cetraphylline
Cetraphylline Indication: For the treatment of the symptoms and reversible airflow obstruction associated with chronic asthma and other chronic lung diseases, such as emphysema and chronic bronchitis.
Mechanism Of Action: Cetraphylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Cetraphylline competitively inhibits type III and type IV phosphodiesterase (PDE), the enzyme responsible for breaking down cyclic AMP in smooth muscle cells, possibly resulting in bronchodilation. Cetraphylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction.
Drug Interactions: Not Available
Food Interactions: Avoid alcohol.
Take with food.
Avoid excessive quantities of coffee or tea (Caffeine).
Generic Name: Theophylline
Synonyms: Dimethylxanthine; Theophyline; Theophyllin; Theophylline aminoacetate; Pseudotheophylline; Theophylline Anhydrous
Drug Category: Vasodilator Agents; Bronchodilator Agents; Respiratory Smooth Muscle Relaxants
Drug Type: Small Molecule; Approved
Absorption: Theophylline is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form.
Toxicity (Overdose): Symptoms of overdose include seizures, arrhythmias, and GI effects.
Protein Binding: 40%, primarily to albumin.
Biotransformation: Hepatic. 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 theophylline dose is N-methylated to caffeine. Caffeine and 3-methylxanthine are the only theophylline metabolites with pharmacologic activity.
Half Life: 8 hours
Dosage Forms of Cetraphylline: Solution Intravenous
Tablet, extended release Oral
Chemical IUPAC Name: 1,3-dimethyl-7H-purine-2,6-dione
Chemical Formula: C7H8N4O2
Theophylline on Wikipedia: https://en.wikipedia.org/wiki/Theophylline
Organisms Affected: Humans and other mammals