Theophylline

Theophylline is a methylxanthine derivative with bronchodilator, smooth muscle relaxant, mild diuretic, cardiac stimulant, and central nervous system stimulant properties. It exerts its effects primarily by inhibiting phosphodiesterase, blocking adenosine receptors, and activating histone deacetylase, leading to relaxation of airway smooth muscle and improved airflow. Theophylline is used mainly for the treatment of asthma, bronchospasm, and chronic obstructive pulmonary disease (COPD).

Theophylline is a xanthine used to manage the symptoms of asthma, COPD, and other lung conditions caused by reversible airflow obstruction.

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.

• Asthma
• Bronchitis
• Bronchoconstriction
• Bronchospasm
• Chronic Obstructive Pulmonary Disease (COPD)
• Chronic bronchial inflammation
• Airway secretion clearance therapy
• Bronchodilation

Theophylline, an xanthine derivative chemically similar to caffeine and theobromine, is used to treat asthma and bronchospasm. Theophylline 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).

Theophylline relaxes the smooth muscle of the bronchial airways and pulmonary blood vessels and reduces airway responsiveness to histamine, methacholine, adenosine, and allergen. Theophylline 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. Theophylline also binds to the adenosine A2B receptor and blocks adenosine mediated bronchoconstriction. In inflammatory states, theophylline activates histone deacetylase to prevent transcription of inflammatory genes that require the acetylation of histones for transcription to begin.

Theophylline is rapidly and completely absorbed after oral administration in solution or immediate-release solid oral dosage form.

• 0.3 to 0.7 L/kg

40%, primarily to albumin.

Theophylline does not undergo any appreciable pre-systemic elimination, distributes freely into fat-free tissues and is extensively metabolized in the liver. Renal excretion of unchanged theophylline in neonates amounts to about 50% of the dose, compared to about 10% in children older than three months and in adults.

8 hours

• 0.29 mL/kg/min [Premature neonates, postnatal age 3-15 days]
• 0.64 mL/kg/min [Premature neonates, postnatal age 25-57 days]
• 1.7 mL/kg/min [Children 1-4 years]
• 1.6 mL/kg/min [Children 4-12 years]
• 0.9 mL/kg/min [Children 13-15 years]
• 1.4 mL/kg/min [Children 16-17 years]
• 0.65 mL/kg/min [Adults (16-60 years), otherwise healthy non-smoking asthmatics]
• 0.41 mL/kg/min [Elderly (>60 years), non-smokers with normal cardiac, liver, and renal function]
• 0.33 mL/kg/min [Acute pulmonary edema]
• 0.54 mL/kg/min [COPD >60 years, stable, non-smoker >1 year]
• 0.48 mL/kg/min [COPD with cor pulmonale]
• 1.25 mL/kg/min [Cystic fibrosis (14-28 years)]
• 0.31 mL/kg/min [Liver disease cirrhosis]
• 0.35 mL/kg/min [acute hepatitis]
• 0.65 mL/kg/min [cholestasis]
• 0.47 mL/kg/min [Sepsis with multi-organ failure]
• 0.38 mL/kg/min [hypothyroid]
• 0.8 mL/kg/min [hyperthyroid]

Symptoms of overdose include seizures, arrhythmias, and GI effects.

• Avoid excessive or chronic alcohol consumption. Ingesting alcohol may reduce the clearance, and therefore increase the serum concentrations of theophylline.
• Avoid St. John's Wort.
• Take with or without food. Take consistently with regard to food.

• 16 years or older: 10 mg/Kg/day (Do not exceed 900 mg/day)
• 12 years-15 years: 13 mg/Kg/day
• 9-11 years: 16 mg/Kg/day
• 1 year-8 years: 24-24 mg/Kg/day
• 6 months-1 year: 12-18 mg/Kg/day
• 1-6 months: 10 mg/Kg/day.