Theophylline

Trade Names:
Elixophyllin
- Elixir 80 mg per 15 mL (26.7 mg per 5 mL)

Trade Names:
Theo-24
- Capsules, timed-release (24 hours) 100 mg
- Capsules, timed-release (24 hours) 200 mg
- Capsules, timed-release (24 hours) 300 mg
- Capsules, timed-release (24 hours) 400 mg

Trade Names:
Theochron
- Tablets, extended-release 100 mg
- Tablets, extended-release 200 mg
- Tablets, extended-release 300 mg
- Tablets, extended-release 450 mg

Trade Names:
Uniphyl
- Tablets, timed-release (24 hours) 400 mg
- Tablets, timed-release (24 hours) 600 mg

Pharmacology

Relaxes bronchial smooth muscle and stimulates central respiratory drive.

Pharmacokinetics

Absorption

Theophylline is rapidly and completely absorbed in solution or immediate-release. Theophylline C _max is 10 mcg/mL (range, 5 to 15 mcg/mL) and T _max is 1 to 2 h. Food and antacids do no cause any clinically significant changes. The therapeutic range is 10 to 20 mcg/mL.

Distribution

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

Metabolism

Theophylline does not undergo any measurable first-pass elimination. In adults and children older than 1 yr of age, about 90% of the dose is metabolized in the liver. Caffeine and 3-methylxanthine are the only theophylline metabolites with pharmacologic activity.

Elimination

Excretion is via the kidneys. In neonates, approximately 50% of a theophylline dose is excreted unchanged in urine. Beyond 0 to 3 mo, 10% of a theophylline dose is excreted unchanged in urine.

Special Populations

No dosage adjustment is required for renal function impairment in adults and children older than 3 mo of age. In neonates with reduced renal function, dose reduction and frequent monitoring of serum concentrations is required.

A prolonged t _½ may occur in liver dysfunction.

Pharmacokinetics vary widely among similar patients and cannot be predicted by age, sex, body weight, or other demographic characteristics. A prolonged t _½ may occur in CHF, alcoholism, and respiratory infections.

Indications and Usage

Prevention or treatment of reversible bronchospasm associated with asthma or chronic obstructive pulmonary disease.

Unlabeled Uses

Treatment of apnea and bradycardia of prematurity; reduction of essential tremor.

Contraindications

Hypersensitivity to xanthines; seizure disorders not adequately controlled with medication.

Dosage and Administration

Dosage based on lean body weight.

PO 5 mg/kg.

PO 3 mg/kg every 6 h.

PO 4 mg/kg every 6 h.

PO 2 mg/kg every 8 h.

PO 1 to 2 mg/kg every 12 h.

PO 3 mg/kg every 8 h.

Each 0.5 mg/kg theophylline administered as a loading dose will increase serum theophylline concentration approximately 1 mcg/mL. If a serum theophylline concentration can be obtained rapidly, defer the loading dose. If this is not possible, clinical judgment must be exercised, using close monitoring. Maintenance doses as per above.

Slow clinical titration preferred.

16 mg/kg/24 h or 400 mg/24 h, whichever is less.

Increase the above dosage 25% increments at 3-day intervals as long as the drug is tolerated or until the following maximum dose is reached (not to exceed 900 mg, whichever is less).

Do not attempt to maintain any dose that is not tolerated.

13 mg/kg/day.

18 mg/kg/day.

24 mg/kg/day.

24 mg/kg/day.

If serum theophylline concentration is within the desired range (10 to 20 mcg/mL), maintain dosage if tolerated. If too high (20 to 25 mcg/mL) decrease doses by approximately 10% and recheck in 3 days; (25 to 30 mcg/mL) skip the next dose, decrease subsequent doses by about 25% and recheck after 3 days; (over 30 mcg/mL) skip the next 2 doses, decrease subsequent doses by approximately 50% and recheck in 3 days. If too low (less than 10 mcg/mL) increase dosage 25% at 3-day intervals until either the desired clinical response or serum concentration is achieved.

Dosing interval is every 6 h.

Dosing interval is every 8 h.

PO 24 h dose in mg [(0.2 × age in wk) + 5] × weight in kg.

PO 1.5 mg/kg every 12 h.

PO 1 mg/kg every 12 h. Final dosage guided by serum concentration after steady state is achieved.

Drug Interactions

Increase theophylline levels.

Decrease theophylline levels.

Theophylline may antagonize sedative effects.

CV adverse reactions may be additive. However, may be used together for additive beneficial effects.

May increase or decrease theophylline levels.

Coadministration has caused catecholamine-induced arrhythmias.

Coadministration may result in seizures.

Theophylline may reduce lithium levels.

Theophylline may antagonize neuromuscular blockade.

Incompatibility

Do not mix following solutions with theophylline in IV fluids: ascorbic acid; chlorpromazine; corticotropin; dimenhydrinate; epinephrine hydrochloride; erythromycin gluceptate; hydralazine; hydroxyzine hydrochloride; insulin; levorphanol tartrate; meperidine; methadone; methicillin sodium; morphine sulfate; norepinephrine bitartrate; oxytetracycline; papaverine; penicillin G potassium; phenobarbital sodium; phenytoin sodium; procaine; prochlorperazine maleate; promazine; promethazine; tetracycline; vancomycin; vitamin B complex with C.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Palpitations; tachycardia; hypotension; arrhythmias.

CNS

Irritability; headache; insomnia; muscle twitching; seizures.

GI

Nausea; vomiting; 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

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Cardiac effects

Theophylline may cause or worsen preexisting arrhythmias.

GI effects

Theophylline may cause or worsen preexisting ulcers or gastroesophageal reflux.

Toxicity

Patients with liver impairment, cardiac failure, or older than 55 yr of age are at greatest risk; monitor theophylline levels to prevent toxicity.

Overdosage

Symptoms

Anorexia, nausea and vomiting, nervousness, insomnia, agitation, irritability, headache, tachycardia, extrasystoles, tachypnea, fasciculations, seizures, ventricular arrhythmias, hyperamylasemia.

Patient Information

• Emphasize importance of follow-up with health care provider to monitor drug levels.
• Explain to patient that the medication is used to prevent asthma attacks and should be used continuously.
• Explain that some sustained-release forms should be taken on empty stomach. Sustained-release products should not be crushed or chewed.
• Explain that low-protein, high-carbohydrate diets may increase theophylline levels while high-protein, low-carbohydrate diets and charcoal-broiled foods may decrease theophylline levels.
• Alert patients to common adverse reactions including stomach upset, nausea, insomnia, tremors, palpitations, exfoliative dermatitis, and urticaria.
• Tell patient to avoid food products containing caffeine.
• Instruct patient not to take extra doses of theophylline for acute asthma attack.

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