Theophylline

Authors: Prof. Dr. med. Peter Altmeyer, Prof. Dr. med. Martina Bacharach-Buhles

Last updated on: 29.10.2020

Synonym(s)

1,3-dimethylxanthine. CAS No: 58-55-9; Theocin; Theophyllins; Theophyllinum anhydricum; Theophyllinum Ph.Eur.8

Definition
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Methylxanthine derivative which is used medicinally mainly as a bronchodilator. Theophylline occurs naturally in tea leaves, cocoa beans and coffee beans.

Half-life
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3,6–12,8 h

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Pharmacodynamics (Effect)
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Relaxation of bronchial muscle culture, increase of mucociliary clearance, inhibition of mediator release, increase of respiratory muscle contractility, decrease of pulmonary artery pressure, anti-allergic effect.

Indication
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Bronchial asthma, chronic bronchitis, chronic obstructive bronchitis, emphysema.

Cosmetics: Under the INCI designation "Theophylline" the alkaloid is offered in cellulite products.

Limited indication
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Pregnancy, alcohol addiction, severe heart disease or hypertension, liver disease, kidney disease, porphyria, newborns, epilepsy.

Dosage and method of use
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Intraindividual dosage, initial 5 mg/kg bw/day p.o. or i.v. as short infusion, dose adjustment depending on the theophylline level, maintenance dose approx. 10 mg/kg bw, if necessary dosage depending on the theophylline level in serum.

Notice!

Smokers have an increased theophylline clearance and require a correspondingly higher dosage (approx. 16 mg/kg bw). Acute viral infections, cardiac insufficiency, cor pulmonale and liver cirrhosis reduce the theophylline clearance so that the dosage must be reduced (approx. 5 mg/kg bw)!

Undesirable effects
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Bronchospasm, leukocytosis, lymphadenopathy, gastrointestinal disturbances, increase in transaminases, albuminuria, proteinuria, allergic reactions, hyperhidrosis, cardiac arrhythmia, tachycardia, depression, headaches, seizures, tremors, dizziness, hyperglycemia, hypercalcemia, muscle twitching.

Interactions
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See Table 2.

Contraindication
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Lactation, fresh myocardial infarction, tachyarrhythmia, hypersensitivity to the active substance or xanthine derivatives.

Preparations
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Solosine, Euphylong

Note(s)
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Standard value: The standard value is between 10 and 20 mg/l in serum

Tables
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Dosage of theophylline depending on the theophylline level

Theophylline serum concentration	Recommended dose
Therapeutic range: 8-20 mg/l	Maintain dose; check serum concentration every 3 months
20-25 mg/l	Reduce daily dose by 10%.
25-30 mg/l	Skip next single dose and reduce the total dose by 25%.
> 30 mg/l	Skip next 2 single doses, reduce total dose by 50%.
7,5-10 mg/l	Increase dose by 25%.
5-7.5 mg/l	Increase dose by 25%.

Essential interactions of theophylline

Barbiturates	Theophylline levels ↓
Carbamazepine	reciprocal mirrors ↓
Cimetidine	Theophylline levels ↑
Disulfiram	Theophylline levels ↑
Ephedrine	Mutual toxicity ↑
INFα 2α	Theophylline levels ↑
Ketoconazole	theophylline levels by up to 50% ↓
Lithium salt	Lithium effect ↓
Macrolide antibiotics	Theophylline levels ↑
Phenytoin	reciprocal mirrors ↓
β -receptor blockers	Theophylline excretion ↓
Rifampicin	Theophylline levels ↓
Sulfinpyrazone	Theophylline levels ↓
β -Sympathomimetics	cardiac arrhythmia, tachycardia
Tiabendazole	Theophylline levels ↑
Smoking cigarettes	Theophylline HWZ ↓, possibly 50-100% dose increase required