DrugindexOnline^{2nd edition}

( Theophylline Ethylenediamine ) Pronouncation: (am-in-AHF-ih-lin)
Class: Xanthine derivative

Trade Names:
Aminophylline
- Injection 250 mg (equiv. to 197 mg theophylline) per 10 mL

Trade Names:
Aminophylline
- Liquid, oral 105 mg (equiv. to 90 mg theophylline) per 5 mL

Trade Names:
Phyllocontin
- Tablets, controlled-release (12 h) 225 mg (equiv. to 178 mg theophylline)

Trade Names:
Truphylline
- Suppositories 250 mg (equiv. to 197.5 mg theophylline)
- Suppositories 500 mg (equiv. to 395 mg theophylline)

Phyllocontin (Canada)
Phyllocontin-350 (Canada)

Mechanism of Action

Pharmacology

Relaxes bronchial smooth muscle and pulmonary blood vessels; stimulates central respiratory drive; increases diaphragmatic contractility.

Pharmacokinetics

Absorption

(Note: Information for the pharmacokinetics/dynamics section was taken from theophylline because aminophylline is a mixture of theophylline and base.) Rapidly and completely absorbed in solution or immediate-release. C _max is 10 mcg/mL (5 to 15 mcg/mL). T _max is 1 to 2 h. Food and antacid does not cause any clinically significant changes; therapeutic range (10 to 20 mcg/mL).

Distribution

40% protein bound (primarily albumin). Unbound theophylline distributes throughout the body water, but distributes poorly into body fat. Vd is 0.45 L/kg (0.3 to 0.7 L/kg) based on idea body weight. Freely passes across the placenta into breast milk and into CSF.

Metabolism

Does not undergo any measurable first-pass elimination. About 90% of dose is metabolized in the liver in adults and children older than 1 yr of age. Caffeine and 3-methylxanthine are the only theophylline metabolites with pharmacological activity.

Elimination

In neonates, about 50% of theophylline dose is excreted unchanged in the urine (ie, excretion is by the kidneys). 10% of theophylline dose is excreted unchanged in the urine in children 0 to 3 months of age.

Special Populations

Renal Function Impairment

No dosage adjustment required in adults and children over 3 mo. Neonates with reduced renal function, dose reduction and frequent monitoring of serum concentrations are required.

Special risk patients

Pharmacokinetics vary widely among similar patients and cannot be predicted by age, sex, body weight or other demographic parameters. However, a prolonged t _½ may occur in CHF, liver dysfunction, alcoholism, and respiratory infection patients.

Indications and Usage

Prevention or treatment of reversible bronchospasm associated with asthma or COPD.

Unlabeled Uses

Treatment of apnea and bradycardia of prematurity.

Contraindications

Hypersensitivity to xanthines (eg, caffeine, theobromine) or ethylenediamine; peptic ulcer; seizure disorders not treated with medication. Aminophylline suppositories are contraindicated in presence of irritation or infection of rectum or lower colon.

Dosage and Administration

Dosage is calculated on basis of lean body weight.

Oral/Rectal

Dose is determined by percentage of theophylline content in aminophylline salt. Aminophylline is 79% theophylline.

Loading Dose Adults and children

PO/PR 5 mg/kg.

Maintenance Dose Healthy nonsmokers

PO/PR 3 mg/kg every 8 h.

Elderly and patients with cor pulmonale

2 mg/kg every 8 h.

CHF patients

1 to 2 mg/kg every 12 h.

Children 9 to 16 yr of age and young adult smokers

3 mg/kg every 6 h.

Children 1 to 9 yr of age

4 mg/kg every 6 h.

Parenteral
Loading Dose Adults and children not receiving theophylline

IV 6 mg/kg.

Adults and children receiving theophylline

IV 0.6 to 3.1 mg/kg.

Maintenance Dose Healthy nonsmokers

IV 0.5 to 0.7 mg/kg/h.

Elderly and patients with cor pulmonale

IV 0.3 to 0.6 mg/kg/h.

CHF patients

IV 0.1 to 0.5 mg/kg/h.

Children 9 to 16 yr of age and young adult smokers

IV 0.8 to 1 mg/kg/h.

Children 1 to 9 yr of age

IV 1 to 1.2 mg/kg/h.

Newborns to infants under 6 mo

Not recommended. Weigh benefits against risks.

Infants 26 to 52 wk

Divide into every 6 h dosing.

Infants under  26 wk

Divide into every 8 h dosing.

Infants 6 to 52 wk

24 h dosage (mg).

Premature infants older than 4 days postnatal

IV 1.5 mg/kg every 12 h.

Premature infants less than 24 days postnatal

IV 1 mg/kg every 12 h.

General Advice

IV infusion

• Do not administer if solution is discolored or if crystals are present.
• Dilute in Dextrose or saline solutions or Lactated Ringer's. Administer diluted drug at rate of 25 mg/min (max). Once mixed, solution must be refrigerated and used within 24 h.

Storage/Stability

Store at room temperature.

Drug Interactions

Allopurinol, nonselective beta blockers, calcium channel blockers, cimetidine, oral contraceptives, corticosteroids, disulfiram, ephedrine, influenza virus vaccine, interferon, macrolide antibiotics, mexiletine, quinolone antibiotics, thyroid hormones

May increase aminophylline levels.

Aminoglutethimide, barbiturates, hydantoins, ketoconazole, rifampin, smoking (tobacco and marijuana), sulfinpyrazone, sympathomimetics

May decrease aminophylline levels.

Benzodiazepines, propofol

Aminophylline may antagonize sedative effects.

Beta-agonists

Effects of both drugs may be antagonized.

Carbamazepine, isoniazid, loop diuretics

May increase or decrease aminophylline levels.

Food

Sustained-released medications are taken on empty stomach to avoid rapid drug release. Low-protein, high-carbohydrate diet may increase aminophylline levels. Charcoal-broiled foods or high-protein, low-carbohydrate diet may decrease aminophylline levels.

Halothane

May cause catecholamine-induced arrhythmias.

Ketamine

May result in seizures.

Lithium

Aminophylline may reduce lithium levels.

Nondepolarizing muscle relaxants

May antagonize neuromuscular blockade.

Incompatibility

Do not mix with anileridine hydrochloride, ascorbic acid, chlorpromazine, codeine phosphate, dimenhydrinate, dobutamine hydroxide, 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, verapamil, vitamin B complex with vitamin C.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Palpitations; tachycardia; hypotension; arrhythmias.

CNS

Irritability; headache; insomnia; muscle twitching; seizures.

GI

Nausea; vomiting; anorexia, diarrhea; gastroesophageal reflux; epigastric pain.

Genitourinary

Proteinuria; diuresis.

Respiratory

Tachypnea; respiratory arrest.

Miscellaneous

Fever; flushing; hyperglycemia; inappropriate antidiuretic hormone secretion; sensitivity reactions (exfoliative dermatitis and urticaria).

Precautions

Monitor Serum theophylline levels In patients receiving theophylline products, monitor serum theophylline levels for toxicity. If levels are above therapeutic range (10 to 20 mcg/mL), report to health care provider.

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established in children under 1 yr of age.

Cardiac effects

Aminophylline may cause or worsen preexisting arrhythmias.

GI effects

Aminophylline may cause or worsen preexisting ulcers or gastroesophageal reflux.

Status asthmaticus

In this medical emergency parenteral medication and close monitoring in intensive care unit are recommended.

Toxicity

Patients with liver impairment or cardiac failure and those more than 55 yr of age are at greatest risk.

Patient Information

• Advise patient not to smoke. If patient changes smoking habits or stops smoking, dosage adjustment may be necessary.
• Instruct patient to report the following symptoms to health care provider: unusual worsening of symptoms, nausea, vomiting, excessive nervousness, insomnia, irregular heartbeat.
• For patients taking theophylline, emphasize that serum theophylline levels should be tested every 6 to 12 mo.
• Advise elderly patients to take safety precautions (eg, rise slowly, use handrails, request assistance in ambulation) if dizziness occurs.
• Instruct patient to avoid foods or beverages containing caffeine and to limit intake of charcoal-broiled foods.