aminophylline
Phyllocontin, Truphylline

Available forms
Available by prescription only
Injection: 250 mg/10 ml
Liquid: 105 mg/5 ml
Rectal suppositories: 250 mg, 500 mg
Tablets: 100 mg, 200 mg
Tablets (controlled-release): 225 mg

Indications and dosages
 Symptomatic relief of acute bronchospasm. Patients not currently receiving theophylline who need rapid relief of symptoms: Loading dose is 6 mg/kg (equivalent to 4.7 mg/kg anhydrous theophylline) I.V. slowly (25 mg/minute or less); then maintenance infusion.
 Maintenance infusions. Adults (nonsmokers): 0.7 mg/kg/hour I.V. for 12 hours; then 0.5 mg/kg/hour I.V. Or, 3 mg/kg P.O. q 6 hours for two doses; then 3 mg/kg P.O. q 8 hours.
Otherwise healthy adult smokers: 1 mg/kg/hour I.V. for 12 hours; then 0.8 mg/kg/hour I.V. Or, 3 mg/kg P.O. q 4 hours for three doses; then 3 mg/kg P.O. q 6 hours.
Older patients; adults with cor pulmonale: 0.6 mg/ kg/hour I.V. for 12 hours; then 0.3 mg/kg/hour I.V. Or, 2 mg/kg P.O. q 6 hours for two doses; then 2 mg/kg P.O. q 8 hours.
Adults with heart failure or liver disease: 0.5 mg/ kg/hour I.V. for 12 hours; then 0.1 to 0.2 mg/kg/ hour I.V. Or, 2 mg/kg P.O. q 8 hours for two doses; then 1 to 2 mg/kg P.O. q 12 hours.
Children ages 9 to 16: 1 mg/kg/hour I.V. for 12 hours; then 0.8 mg/kg/hour I.V. Or, 3 mg/kg P.O. q 4 hours for three doses; then 3 mg/kg P.O. q 6 hours.
Children ages 6 months to 9 years: 1.2 mg/kg/hour I.V. for 12 hours; then 1 mg/kg/hour I.V. Or, 4 mg/kg P.O. q 4 hours for three doses; then 4 mg/kg P.O. q 6 hours.
Patients currently receiving theophylline: Aminophylline loading infusions of 0.63 mg/kg (0.5 mg/kg anhydrous theophylline) will increase plasma levels of theophylline by 1 mcg/ml, after serum levels have been evaluated. Some clinicians recommend a loading dose of 3.1 mg/kg I.V. (2.5 mg/kg anhydrous theophylline) if no obvious signs of theophylline toxicity are present; then maintenance infusion.
 Chronic bronchial asthma. Adults and children: 16 mg/kg or 400 mg (whichever is less) P.O. daily in three or four divided doses q 6 to 8 hours if using rapidly absorbed dosage forms. Dosage may be increased, if tolerated, in increments of 25% q 2 to 3 days. Alternatively, if using extended-release preparations, 12 mg/kg or 400 mg (whichever is less) P.O. daily in two or three divided doses q 8 to 12 hours. Dosage may be increased, if tolerated, by 2 to 3 mg/kg daily q 3 days.
 Regardless of dosage form, the following are recommended maximum doses. For adults and children age 16 and older, 13 mg/kg daily or 900 mg daily (whichever is less); for children ages 12 to 16, 18 mg/kg daily; for children ages 9 to 12, 20 mg/kg daily; and for children ages 1 to 9, 24 mg/kg daily.
 When recommended maximum dose is reached, dosage adjustment is based on peak serum theophylline levels. Monitor serum levels to ensure that theophylline levels range from 10 to 20 mcg/ml.
 Note: Rectal dose is the same as that recommended for oral dose.
 To treat paroxysmal nocturnal dyspnea or periodic apnea with Cheyne-Stokes respirations; to promote diuresis ◇. Adults: 200 to 400 mg I.V. bolus.
 Reduction of severe bronchospasm in infants with cystic fibrosis ◇. Infants: 10 to 12 mg/kg I.V. daily.

Pharmacodynamics
Bronchodilating action: Aminophylline acts at the cellular level after it’s converted to theophylline. (Aminophylline [theophylline ethylenediamine] is 79% theophylline.) Theophylline acts by either inhibiting phosphodiesterase or blocking adenosine receptors in the bronchi, thereby relaxing smooth muscle. Drug also stimulates the respiratory center in the medulla and prevents diaphragmatic fatigue.

Pharmacokinetics
Absorption: Most dosage forms are absorbed well; absorption of the suppository, however, is unreliable and slow. Rate and onset of action also depend on the dosage form selected. Food may alter the rate, but not the extent of absorption, of oral doses.
Distribution: Distributed in all tissues and extracellular fluids except fatty tissue.
Metabolism: Converted to theophylline, then metabolized to inactive compounds.
Excretion: Excreted in urine as theophylline (10%).

Contraindications and precautions
Contraindicated in patients hypersensitive to xanthine compounds (caffeine, theobromine) and ethylenediamine and in patients with active peptic ulcer disease and seizure disorders (unless adequate anticonvulsant therapy is given). Rectal suppositories are also contraindicated in patients who have an irritation or infection of the rectum or lower colon.
  Use cautiously in neonates, infants, young children, elderly patients, and patients with heart failure, CV disorders, COPD, cor pulmonale, renal or hepatic disease, hyperthyroidism, diabetes mellitus, peptic ulcer, severe hypoxemia, or hypertension.

Interactions
Drug-drug. Alkali-sensitive drugs: Reduce aminophylline activity. Don’t add these drugs to I.V. fluids containing aminophylline.
Allopurinol (high dose), cimetidine, corticosteroids, erythromycin, interferon, mexiletine, oral contraceptives, propranolol, quinolones, troleandomycin: May increase serum aminophylline level by decreasing hepatic clearance. Use together cautiously.
Aminoglutethimide, carbamazepine, phenobarbital, phenytoin, rifampin: Decrease aminophylline effects. Use together cautiously.
Lithium: Increases lithium excretion. Monitor lithium levels.
Drug-lifestyle. Tobacco and marijuana use: Decrease aminophylline effects. Discourage use.

Adverse reactions
CNS: nervousness, restlessness, headache, insomnia,seizures, muscle twitching, irritability, fever.
CV: palpitations, sinus tachycardia, extrasystoles, flushing, marked hypotension, arrhythmias.
GI: nausea, vomiting, diarrhea, epigastric pain, hematemesis.
Metabolic: hyperglycemia, increased urinary catecholamines.
Respiratory: tachypnea, respiratory arrest.
Skin: urticaria.
Other: local irritation (with rectal suppositories).

Effects on lab test results
• May increase glucose and free fatty acid levels.

Overdose and treatment
Signs and symptoms of overdose include nausea, vomiting, insomnia, irritability, tachycardia, extrasystoles, tachypnea, and tonic-clonic seizures. Onset of toxicity may be sudden and severe; arrhythmias and seizures are the first signs.
 Induce emesis, except in patients with seizures, then use activated charcoal and cathartics. Charcoal hemoperfusion may be beneficial. Treat arrhythmias with lidocaine and seizures with I.V. benzodiazepine; support respiratory and CV systems.

Special considerations
• Aminophylline may alter the assay for uric acid, depending on method used. Theophylline levels are falsely elevated in the presence of furosemide, phenylbutazone, probenecid, theobromine, caffeine, tea, chocolate, cola beverages, and acetaminophen, depending on type of assay used. These substances don’t interfere with levels if measured using high-pressure liquid chromatography.
• Check that patient hasn’t had recent theophylline therapy before giving loading dose.
• Don’t combine in fluids for I.V. infusion with ascorbic acid, chlorpromazine, codeine phosphate, dimenhydrinate, dobutamine, epinephrine, erythromycin gluceptate, hydralazine, insulin, levorphanol tartrate, meperidine, methadone, methicillin, morphine sulfate, norepinephrine bitartrate, oxytetracycline, penicillin G potassium, phenobarbital, phenytoin, prochlorperazine, promazine, promethazine, tetracycline, vancomycin, or vitamin B complex with vitamin C.
• Don’t crush controlled-release tablets.
• I.V. drug administration includes I.V. push at a very slow rate or an infusion with 100 to 200 ml of D₅W or normal saline solution.
• Patients metabolize xanthines at different rates. Adjust dose by monitoring response, tolerance, pulmonary function, and theophylline blood levels. Therapeutic level is 10 to 20 mcg/ml but some patients may respond at lower levels; toxicity occurs at levels over 20 mcg/ml.
• Monitor serum theophylline levels. Plasma clearance may be decreased in patients with heart failure, hepatic dysfunction, or pulmonary edema. Smokers show accelerated clearance. Dosage adjustments are needed.
• GI symptoms may be relieved by taking oral drug with full glass of water at meals, although food in stomach delays absorption. Enteric-coated tablets may also delay absorption. There’s no evidence that antacids reduce GI adverse reactions.
• Suppositories are slowly and erratically absorbed; retention enemas may be absorbed more rapidly. Rectally administered preparations can be given when patient can’t take drug orally. Schedule after evacuation, if possible; may be retained better if given before meal. Advise patient to remain recumbent 15 to 20 minutes after insertion.
Breast-feeding patients
• Drug appears in breast milk and may cause irritability, insomnia, or fretfulness in the breast-fed infant.
Pediatric patients
• Drug isn’t recommended for infants younger than age 6 months.
Geriatric patients
• Use reduced doses and monitor patient closely. Warn geriatric patients of dizziness, a common adverse reaction at start of therapy.

Patient education
• Teach patient rationale for therapy and importance of compliance with prescribed regimen; if a dose is missed, patient should take it as soon as possible but shouldn’t double the dose.
• Advise patient of adverse effects and possible signs of toxicity.
• Tell patient not to eat or drink large quantities of xanthine-containing foods and beverages.
• Warn patient that OTC remedies may contain ephedrine with theophylline salts; excessive CNS stimulation may result. Tell patient to seek medical approval before taking any other medications.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use