Doxofylline

Usage

• Doxofylline is prescribed for the treatment of bronchial asthma, chronic obstructive pulmonary disease (COPD), and other pulmonary diseases with a spastic bronchial component. It helps manage symptoms like wheezing, chest tightness, and shortness of breath.
• Pharmacological Classification: Bronchodilator, Xanthine derivative.
• Mechanism of Action: Doxofylline is a phosphodiesterase-4 inhibitor, which increases intracellular cyclic AMP (cAMP). This leads to bronchial smooth muscle relaxation, improving airflow in the lungs. It also exhibits some anti-inflammatory properties and inhibits platelet-activating factor (PAF).

Alternate Names

• Doxophylline
• Brand Names: Doxofree, Doxolator, Dilatair, Doxofix, Ansimar and others.

How It Works

• Pharmacodynamics: Doxofylline relaxes the bronchial smooth muscles by inhibiting phosphodiesterase 4, leading to increased intracellular cAMP levels. This results in bronchodilation, reducing airway resistance and improving lung function. It also possesses some anti-inflammatory actions and may inhibit PAF.
• Pharmacokinetics:
  • Absorption: Well-absorbed orally. Peak plasma concentrations reached within 1 hour. Absolute bioavailability is around 63%.
  • Metabolism: Extensively metabolized in the liver (90%), primarily to the inactive metabolite beta-hydroxymethyltheophylline.
  • Elimination: Primarily via hepatic metabolism. Less than 4% excreted unchanged in the urine. Elimination half-life is 7-10 hours, permitting twice-daily dosing. Steady state reached in about 4 days.
• Mode of Action: Doxofylline selectively inhibits phosphodiesterase 4, leading to bronchodilation. It has a lower affinity for adenosine receptors compared to theophylline, potentially contributing to its better safety profile.
• Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Primarily acts by inhibiting phosphodiesterase 4, leading to increased cAMP levels. It has lower affinity for adenosine receptors compared to theophylline.
• Elimination Pathways: Mainly hepatic metabolism with less than 4% renal excretion.

Dosage

Standard Dosage

Adults:

• 400 mg twice or thrice daily. Maximum dose: 1200 mg daily.
• Administer orally with food to minimize gastrointestinal discomfort.

Children:

• Children over 6 years: 6-9 mg/kg twice daily, up to 18mg/kg/day based on clinical response. Doxofylline sachet formulation is available for pediatric use.
• Children over 12 years: 200 mg twice or thrice daily.
• Children younger than 6 years: Dosage not well established, use with caution.

Special Cases:

• Elderly Patients: Start with 200 mg twice or thrice daily, due to age-related decline in renal and hepatic function.
• Patients with Renal Impairment: Dose reduction may be necessary. Monitor closely for adverse events.
• Patients with Hepatic Dysfunction: Dose reduction may be required. Monitor closely for adverse events.
• Patients with Comorbid Conditions: Exercise caution in patients with cardiovascular disease (hypertension, congestive heart failure, arrhythmias), hyperthyroidism, peptic ulcers, and hypoxemia. Adjust dosage as needed.

Clinical Use Cases

Dosage recommendations for specific clinical scenarios are not explicitly defined in the provided sources, and standard dosing guidelines generally apply. For intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations, consult specialist literature or an expert pulmonologist for guidance.

Dosage Adjustments

• Adjust dosage based on individual patient response and tolerance.
• Reduce dosage in patients with renal or hepatic impairment, congestive heart failure, or concomitant infections.
• Increase dosage may be needed for smokers or those taking anticonvulsants.

Side Effects

Common Side Effects:

• Nausea
• Vomiting
• Headache
• Epigastric pain
• Irritability
• Insomnia
• Tachycardia

Rare but Serious Side Effects:

• Seizures
• Severe arrhythmias
• Hypotension

Long-Term Effects:

Limited data is available on the long-term effects of doxofylline.

Adverse Drug Reactions (ADR):

• Severe allergic reactions (rare).
• Seizures (rare).
• Severe cardiovascular events (rare).

Contraindications

• Hypersensitivity to doxofylline or other xanthine derivatives.
• Acute myocardial infarction.
• Hypotension.
• Lactation.

Drug Interactions

• Other xanthine derivatives: Avoid concomitant use due to potential for additive effects.
• Ephedrine and other sympathomimetics: Risk of synergistic toxicity.
• Erythromycin, lincomycin, clindamycin, allopurinol, cimetidine, ranitidine, propranolol, ciprofloxacin, troleandomycin, flu vaccine: May decrease doxofylline clearance, increasing serum levels.
• Phenytoin and other anticonvulsants: May increase doxofylline clearance, decreasing serum levels.
• Caffeine-containing products: May enhance adverse effects.
• Beta-2 agonists, corticosteroids, and diuretics: May potentiate hypokalemia.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Not definitively established. Use only if clearly needed and the potential benefits outweigh the risks. Animal studies did not show fetal harm.
• Breastfeeding: Contraindicated. Doxofylline is excreted in breast milk.

Drug Profile Summary

• Mechanism of Action: Phosphodiesterase 4 inhibitor leading to bronchodilation.
• Side Effects: Nausea, vomiting, headache, epigastric pain, irritability, insomnia, tachycardia. Rarely, seizures and severe arrhythmias.
• Contraindications: Hypersensitivity, acute MI, hypotension, lactation.
• Drug Interactions: Other xanthines, ephedrine, certain antibiotics, cimetidine, propranolol, phenytoin, caffeine.
• Pregnancy & Breastfeeding: Use with caution in pregnancy; contraindicated during breastfeeding.
• Dosage: Adults: 400 mg bid-tid, max 1200 mg/day; Elderly: Initiate at 200 mg bid-tid; Children (6+ yrs): 6-9mg/kg bid; Children (12+ years): 200mg bid-tid.
• Monitoring Parameters: Heart rate, respiratory rate, CNS effects (irritability, insomnia).

Popular Combinations

The supplied information does not provide data on specific drug combinations commonly used with doxofylline in clinical practice.

Precautions

• General Precautions: Screen for allergies, cardiovascular disease, renal/hepatic dysfunction, peptic ulcer disease, hyperthyroidism, and hypoxemia before starting therapy.
• Pregnant Women: Use with caution, only if potential benefits outweigh the risks.
• Breastfeeding Mothers: Contraindicated.
• Children & Elderly: Age-specific dosing adjustments are needed.
• Menstruating Individuals: No known specific precautions.
• Lifestyle Considerations: Limit caffeine intake. Effects on driving and operating machinery are not typically significant, but individual responses may vary.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Doxofylline?

A: Adults: 400 mg twice or thrice daily (max 1200 mg/day). Elderly: 200 mg two or three times daily. Children (over 6 years): 6-9 mg/kg twice daily. Children (over 12 years): 200 mg two or three times daily. Dosage adjustments may be necessary for patients with renal or hepatic impairment or certain concomitant medications.

Q2: How does Doxofylline work?

A: Doxofylline is a bronchodilator that inhibits phosphodiesterase 4, leading to increased intracellular cAMP levels and smooth muscle relaxation in the airways.

Q3: What are the common side effects of Doxofylline?

A: Common side effects include nausea, vomiting, headache, epigastric pain, irritability, insomnia, and tachycardia.

Q4: Is Doxofylline safe during pregnancy?

A: Safety in pregnancy hasn’t been definitively established. Use only if clearly needed and the potential benefits outweigh potential risks.

Q5: Can Doxofylline be used during breastfeeding?

A: No, Doxofylline is contraindicated during breastfeeding as it is excreted in breast milk.

Q6: What are the contraindications for Doxofylline?

A: Doxofylline is contraindicated in patients with hypersensitivity to it or other xanthines, acute myocardial infarction, hypotension, and during breastfeeding.

Q7: Does Doxofylline interact with other medications?

A: Yes, Doxofylline can interact with several medications including certain antibiotics (erythromycin, etc.), cimetidine, propranolol, phenytoin, caffeine, and other xanthine derivatives. Consult the Drug Interactions section for detailed information.

Q8: How should Doxofylline be administered?

A: Doxofylline should be administered orally with meals to reduce gastrointestinal discomfort. Intravenous administration is also possible for acute exacerbations under medical supervision.

Q9: What should patients avoid while taking Doxofylline?

A: Patients should limit their intake of caffeine-containing foods and beverages while taking Doxofylline, as it may enhance adverse effects.

Q10: What should I monitor in a patient taking Doxofylline?

A: Monitor heart rate, respiratory rate, and CNS effects like irritability and insomnia. In patients with renal or hepatic dysfunction, monitor drug levels and adjust dosage accordingly.