Ambroxol + Doxofylline

Usage

• Medical Conditions: Ambroxol + Doxofylline is prescribed for respiratory conditions like bronchial asthma, chronic obstructive pulmonary disease (COPD), and bronchitis, particularly when cough with mucus is a prominent symptom. It is also used to treat and prevent respiratory disorders like asthma attacks and COPD exacerbations.
• Pharmacological Classification: This is a combination drug containing a mucolytic (Ambroxol) and a bronchodilator (Doxofylline).
• Mechanism of Action: Ambroxol reduces the viscosity of mucus by breaking down mucopolysaccharide fibers, making it easier to cough up. Doxofylline relaxes the bronchial smooth muscles, widening the airways and improving airflow to the lungs.

Alternate Names

• While “Ambroxol + Doxofylline” is the standard generic name, regional variations may exist.
• Brand names for this combination include Doxo A, Doxjafy AM, Ventidox-Bro and Nutra Respiro. Several other brand names are available in India as fixed-dose combinations of ambroxol 30 mg and doxofylline 400 mg have been approved since December 23, 2009.

How It Works

• Pharmacodynamics: Ambroxol acts as a mucolytic, decreasing the viscosity of sputum. Doxofylline, a xanthine derivative similar to theophylline, acts as a bronchodilator by inhibiting phosphodiesterase enzymes, leading to increased intracellular cyclic AMP (cAMP) levels and subsequent smooth muscle relaxation in the airways. It may also have some anti-inflammatory effects.
• Pharmacokinetics: Doxofylline is rapidly absorbed with an absolute bioavailability of approximately 62.6%. It reaches peak plasma concentration in about 1.19 hours. It has a volume of distribution of about 1 L/kg and is approximately 48% bound to plasma proteins. Doxofylline is extensively metabolized in the liver (about 90%) to inactive metabolites, primarily hydroxyethyltheophylline. Less than 4% is excreted unchanged in the urine. Ambroxol is also well absorbed after oral administration.
• Mode of Action: Ambroxol stimulates the serous cells in the bronchial mucosa, resulting in increased secretion of fluid into the airways, hence thinning the mucus. It also activates the cilia to enhance mucus transport. Doxofylline increases cAMP levels in bronchial smooth muscle cells, promoting relaxation and bronchodilation. It also inhibits the release of inflammatory mediators.
• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Doxofylline inhibits phosphodiesterase enzymes, primarily PDE4. It has a lower affinity for adenosine receptors compared to theophylline, potentially reducing some of theophylline’s side effects. Ambroxol may modulate the activity of sodium channels and also interacts with surfactant protein systems.
• Elimination Pathways: Doxofylline is primarily metabolized by the liver with <4% excreted unchanged in the urine. Ambroxol is also extensively metabolized in the liver.

Dosage

Standard Dosage

Adults:

• One tablet (400 mg Doxofylline and 30 mg Ambroxol) two to three times daily.
• Maximum daily Doxofylline dosage is usually 1200 mg.

Children:

• Not generally recommended for children under 6 years of age.
• Children over 6 years: 6-9 mg/kg of Doxofylline twice daily (consult product-specific guidelines; safety and efficacy are not fully established).
• Children >12 years: 200 mg of Doxofylline, twice or thrice daily, or 10ml syrup, twice or thrice daily.
• Children <12 years: 6-9mg/kg/dose Doxofylline, twice daily, as syrup.
• Pediatric use should be under strict medical supervision.

Special Cases:

• Elderly Patients: Start with a reduced dose of 200 mg Doxofylline, twice or thrice daily.
• Patients with Renal Impairment: Dosage reduction is usually needed.
• Patients with Hepatic Dysfunction: Dosage reduction may be required.
• Patients with Comorbid Conditions: Use with caution and monitor closely in patients with diabetes, cardiovascular disease, hyperthyroidism, epilepsy, or peptic ulcer. Doxofylline may increase blood glucose levels and can interact with other medications.

Clinical Use Cases

Dosage in specific clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations should be determined on a case-by-case basis by the attending physician, considering the patient’s condition and response to therapy.

Dosage Adjustments

Dose modifications are based on patient-specific factors, including renal/hepatic function, age, and coexisting medical conditions.

Side Effects

Common Side Effects:

• Nausea, vomiting, epigastric pain, headache, dizziness, insomnia, irritability, tachycardia, palpitations, extrasystoles, hyperglycemia, tachypnea, and rarely seizures.

Rare but Serious Side Effects:

• Seizures, severe arrhythmias, gastrointestinal bleeding, hypotension, difficulty urinating, rash.

Long-Term Effects:

Chronic complications from prolonged use are not well documented, but monitoring for cardiovascular and metabolic effects is advised.

Adverse Drug Reactions (ADR):

Clinically significant ADRs can include severe allergic reactions, seizures, and cardiac arrhythmias.

Contraindications

• Acute myocardial infarction (MI).
• Hypotension.
• Hypersensitivity to Ambroxol or Doxofylline.
• Lactation.
• Pregnancy.

Drug Interactions

• Other xanthine derivatives (avoid concomitant use due to potential for toxic synergism).
• Ephedrine (toxic synergism).
• Erythromycin, troleandomycin, lincomycin, clindamycin, allopurinol, cimetidine, ranitidine, propranolol, and anti-flu vaccine (may decrease doxofylline clearance).
• Beta-2 agonists, corticosteroids, and diuretics (may potentiate hypokalemia caused by hypoxia).
• Caffeine-containing products (may enhance adverse effects of doxofylline).

Pregnancy and Breastfeeding

• Pregnancy: Contraindicated.
• Breastfeeding: Contraindicated as Doxofylline is excreted in breast milk.

Drug Profile Summary

• Mechanism of Action: Ambroxol: Mucolytic; Doxofylline: Bronchodilator (phosphodiesterase inhibitor).
• Side Effects: Nausea, vomiting, headache, dizziness, insomnia, gastrointestinal issues, cardiovascular effects (tachycardia, palpitations), rarely seizures.
• Contraindications: Acute MI, hypotension, hypersensitivity, lactation, pregnancy.
• Drug Interactions: Other xanthines, ephedrine, certain antibiotics, cimetidine, propranolol.
• Pregnancy & Breastfeeding: Contraindicated.
• Dosage: Adults: 400/30 mg tablet BID-TID (max 1200 mg Doxofylline/day). Adjust for elderly and renal/hepatic impairment. Children: consult specific product guidelines for >6 years of age.
• Monitoring Parameters: Heart rate, respiratory rate, CNS effects (irritability, insomnia), blood glucose levels, potassium levels.

Popular Combinations

A common drug combination used in clinical practice is Ambroxol + Doxofylline itself. The combination provides synergistic effects by addressing both mucus clearance and bronchodilation. No other combinations were found in the sources for this drug.

Precautions

• General Precautions: Pre-screening for allergies, metabolic disorders, organ dysfunction.
• Specific Populations: As mentioned in contraindications and dosage sections.
• Lifestyle Considerations: Limit alcohol intake as it may interact with doxofylline. Smoking may reduce the effectiveness of the medication and may require dosage adjustments.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Ambroxol + Doxofylline?

A: The standard adult dosage is one tablet (400 mg doxofylline/30 mg ambroxol) two to three times daily. Dosages should be adjusted for the elderly, patients with renal or hepatic impairment, and other specific patient populations. Children’s dosages must be carefully determined based on weight and age, with caution for those under 6.

Q2: What are the primary uses of this combination medication?

A: It is primarily used to treat respiratory conditions such as COPD, asthma, and bronchitis, particularly when accompanied by mucus build-up and cough.

Q3: What are the common side effects?

A: Common side effects can include nausea, vomiting, headache, stomach pain, dizziness, and insomnia.

Q4: Are there any serious side effects I should be aware of?

A: While rare, serious side effects like seizures, severe arrhythmias, and hypotension can occur. Immediate medical attention is required if these occur.

Q5: Can this medication be used during pregnancy or breastfeeding?

A: No, this medication is contraindicated during pregnancy and breastfeeding.

Q6: Are there any drug interactions I should know about?

A: Yes, this medication can interact with other xanthine derivatives, ephedrine, certain antibiotics (like erythromycin), cimetidine, propranolol, and others. Always inform your doctor about all other medications you are taking.

Q7: What should I do if I miss a dose?

A: Take the missed dose as soon as possible. However, if it is almost time for your next dose, skip the missed dose and return to your regular dosing schedule. Do not double the dose to catch up.

Q8: Does this medicine affect the liver and heart?

A: The medication has rarely been seen to affect the heart; however, it is generally considered safe for the liver.

Q9: What are the storage instructions for Ambroxol + Doxofylline tablets?

A: Store in a cool and dry place away from sunlight, below 30°C.

Q10: Can Ambroxol + Doxofylline be administered to children less than 6 years of age?

A: Ambroxol + Doxofylline is generally not recommended for children less than 6 years of age. Your doctor will decide the dose depending on the condition of the child’s disease and age.