Coxbro

Coxbro Uses, Dosage, Side Effects, Food Interaction and all others data.

Ambroxol is a metabolite of Bromhexine. It possesses mucokinetic (improvement in mucus transport) and secretolytic (liquefies secretions) properties. Ambroxol stimulates the serous cells of the glands of the mucous membrane of bronchi, increasing the content of mucus secretion. The mucolytic effect is associated with depolymerization and splitting of mucoproteins and mucopolysaccharide fibres, which leads to reduction in the viscosity of mucus. Expectoration of mucus is facilitated and breathing is eased considerably. Ambroxol stimulates production of phospholipids of surfactant by alveolar cells. Ambroxol has anti-inflammatory properties. In patients with COPD, it improves airway patency. Beside these, Ambroxol also exhibits anti-oxidant activity. Long-term use is possible because of the good tolerability of the preparation.

Doxophylline is a novel bronchodilator. It structurally differs from Theophylline due to the presence of a dioxolane group in position 7.

Doxophylline selectively inhibits phosphodiesterase 4 thereby relaxes bronchial smooth muscle. However, differently from Theophylline, Doxophylline appears to have decreased affinities toward adenosine A1 and A2 receptors, which may account for the better safety profile of the drug. Doxophylline is reported to inhibit platelet activating factor (PAF) and generation of leukotriene production.

Doxofylline is a methylxanthine bronchodilator with potent bronchodilator activity comparable to that of theophylline. In animal studies, doxofylline demonstrated to attenuate bronchoconstriction, inflammatory actions and the release of thromboxane A2 (TXA2) when challenged with platelet-activating factor .

Doxofylline does not demonstrate direct inhibition of any histone deacetylase (HDAC) enzymes or known PDE enzyme isoforms and did not act as an antagonist at A2 or A2 receptors. The affinity for adenosine A1, A2A and A2B receptors are reported to be all higher than 100 µM . It only displays an inhibitory action against PDE2A1 and antagonism at adenosine A(2A) at high concentrations [A31642]. A study demonstrated that doxofylline interacts with β2-adrenoceptors to induce blood vessel relaxation and airway smooth muscle relaxation. In dog studies, doxofylline decreased airway responsiveness at a dose that did not affect heart rate and respiratory rate .

Coxbro
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Coxbro
Generic	Ambroxol + Doxofylline
Weight	30mg
Type	Tablet
Therapeutic Class
Manufacturer	Iscon Life Sciences
Available Country	India
Last Updated:	September 19, 2023 at 7:00 am

Uses

• Acute and chronic diseases of respiratory tracts associated with viscid mucus including acute and chronic bronchitis
• Productive cough
• Inflammatory diseases of Rhinopharyngeal tract (e.g. Laryngitis, Pharyngitis, Sinusitis and Rhinitis) associated with viscid mucus
• Asthmatic bronchitis, Bronchial asthma with difficult departure of mucus
• Bronchiectasis
• Chronic pneumonia.

Doxophylline is used to treat asthma, COPD and bronchospasm.

Coxbro is also used to associated treatment for these conditions: Airway secretion clearance therapyBronchial Asthma, Chronic Obstructive Pulmonary Disease (COPD), Pulmonary Diseases

How Coxbro works

Ambroxol is a mucolytic agent. Excessive Nitric oxide (NO) is associated with inflammatory and some other disturbances of airways function. NO enhances the activation of soluble guanylate cyclase and cGMP accumulation. Ambroxol has been shown to inhibit the NO-dependent activation of soluble guanylate cyclase. It is also possible that the inhibition of NO-dependent activation of soluble guanylate cyclase can suppress the excessive mucus secretion, therefore it lowers the phlegm viscosity and improves the mucociliary transport of bronchial secretions.

The main mechanism of action of doxofylline is unclear. One of the mechanisms of action of is thought to arise from the inhibition of phosphodiesterase activity thus increasing the levels of cAMP and promoting smooth muscle relaxation.

The interaction of doxofylline with beta-2 adrenoceptors was demonstrated by a study using nonlinear chromatography, frontal analysis and molecular docking [A31646]. Serine 169 and serine 173 residues in the receptor are thought to be critical binding sites for doxofylline where hydrogen bonds are formed [A31646]. Via mediating the actions of beta-2 adrenoceptors, doxofylline induces blood vessel relaxation and airway smooth muscle relaxation.

There is also evidence that doxofylline may exert anti-inflammatory actions by reducing the pleurisy induced by the inflammatory mediator platelet activating factor (PAF) according to a rat study [A31646]. It is suggested that doxofylline may play an important role in attenuating leukocyte diapedesis, supported by mouse preclinical studies where doxofylline administration was associated with inhibited leukocyte migration across vascular endothelial cells in vivo and in vitro .Unlike theophylline, doxofylline does not inhibit tumor necrosis factor-induced interleukin (IL)-8 secretion in ASM cells.

Dosage

Coxbro dosage

Average daily dose (preferably after meal):Pediatric Drops:

0-6 months: 0.5 ml 2 times a day
6-12 months: 1 ml 2 times a day
1-2 years: 1.25 ml 2 times a day

Syrup:

2-5 years: 2.5 ml (1/2 teaspoonful) 2-3 times a day
5-10 years: 5 ml (1 teaspoonful) 2-3 times a day
10 years and adults: 10 ml (2 teaspoonful) 3 times a day.

Sustained release capsule:

Adult and children over 12 years old: 1 capsule once daily

Specific application features: Ambroxol may be prescribed to patients suffering from diabetes mellitus.

Adult:400 mg daily in the evening. However, in certain cases, 400 mg twice daily is recommended on the basis of the clinical response. Doses as high as 1200 mg/day (400 mg 3 times daily) may also be prescribed. In elderly patients with concomitant cardiovascular, hepatic and renal diseases recommended dosage should be 200 mg twice daily.

Children (above 6 years of age):The recommended dosage of Doxophylline is 6 mg/kg twice daily. The dose may be increased up to 18 mg/kg daily on the basis of clinical response.

Dosage Type: 6 mg/kg b.i.d

Weight of the Child: 10 kg > Dosage: 3 ml
Weight of the Child: 15 kg > Dosage: 4.5 ml
Weight of the Child: 20 kg > Dosage: 6 ml
Weight of the Child: 25 kg > Dosage: 7.5 ml
Weight of the Child: 30 kg > Dosage: 9 ml
Weight of the Child: 35 kg > Dosage: 10.5 ml
Weight of the Child: 40 kg > Dosage: 12 ml

Side Effects

Gastrointestinal side-effects like epigastric pain, gastric fullness may occur occasionally. Rarely allergic responses such as eruption, urticaria or angioneurotic edema may occur.

Patients treated with Xanthine derivatives may suffer nausea, vomiting, epigastric pain, headache, irritability, insomnia, tachycardia, extrasystoles, tachypnea, and in rare cases, hyperglycemia or albuminuria.

Toxicity

Oral LD50 in rat and mouse are 965 mg/kg and 841 mg/kg, respectively. Intraperitoneal LD50 in rat and mouse are 426 mg/kg and 396 mg/kg, respectively .

Precaution

Ambroxol should be given cautiously to patients with gastric and duodenal ulceration or convulsive disorders. Patients with hepatic and renal insufficiency should take it with caution.

Use with caution in patients with hypoxemia, hyperthyroidism, liver disease, renal disease, in those with history of peptic ulcer and in elderly. Frequently, patients with Congestive Heart Failure (CHF) have markedly prolonged drug serum levels following discontinuation of Doxofylline.

Interaction

Ambroxol has no interaction with cardioactive glycosides, corticosteroids, bronchodilators, diuretics and antibiotics (normally used in the treatment of bronchopulmonary affections). But Ambroxol should not be taken simultaneously with antitussives (e.g. Codeine) because mucus, which has been liquefied by Ambroxol, might not be expectorated.

Doxophylline should not be administered together with other xanthine derivatives. Toxic synergism with ephedrine has been documented for xanthines. Like other xanthines, concomitant therapy with erythromycin, troleandomycin, lincomycin, allopurinol, cimetidine, ranitidine, propranolol and anti-flu vaccine may decrease the hepatic clearance of xanthines causing an increase in blood levels.

Volume of Distribution

Doxofylline demonstrates a short distribution phase following intravenous administration of 100 mg given in adults with chronic bronchitis . As methylxanthines are distributed to all body compartments, doxofylline may be detected in breast milk and placenta .

Elimination Route

Rapid and almost complete.

After repeated administrations doxofylline reaches the steady-state in about 4 days. Following oral administration of 400 mg doxofylline twice daily for 5 days in adults with chronic bronchitis, the peak plasma concentrations (Cmax) at steady state ranged from 5.78 to 20.76 mcg/mL. The time to reach maximum concentration (Tmax) was 1.19 ± 0.19 hours . The absolute bioavailability of doxofylline in healthy subjects was 63 ± 25% .

Half Life

7-12 hours

Following administration of a single intravenous dose of 100 mg over 10 minutes in adults with chronic bronchitis, the elimination half life of doxofylline was 1.83 ± 0.37 hours. Following oral administration of 400 mg twice daily for 5 days in adults with chronic bronchitis, the mean elimination half life was 7.01 ± 0.80 hours .

Clearance

Following oral administration of 400 mg doxofylline twice daily for 5 days, the total clearance was 555.2 ± 180.6 mL/min .

Elimination Route

Less than 4% of an orally administered dose is excreted unchanged in the urine due to extensive hepatic metabolism .

Pregnancy & Breastfeeding use

Pregnancy: Teratogenic and fetal toxicity studies have shown no harmful effect of Ambroxol. However, it is advised not to use during pregnancy, especially in the 1st trimester.

Lactation: Safety during lactation has not been established.

Use in pregnancy: Animal reproduction studies indicate that Doxophylline does not cause fetal harm when administered to pregnant animals nor can affect reproduction capacity. However, since there is limited experience in human during pregnancy, Doxophylline should be given to pregnant women only if clearly needed.

Use in nursing mothers: Doxophylline is contraindicated in nursing mothers.

Contraindication

Contraindicated in known hypersensitivity to Ambroxol or Bromhexine.

This is contraindicated for individuals who have shown hypersensitivity to Doxofylline and its components. It is also contraindicated in patients with acute myocardial infarction, hypotension, and in lactating women.

Acute Overdose

In case of overdose severe cardiac arrhythmias and tonic-clonic seizure may occur. These effects may represent the first signs of intoxication. The appearance of side effects may require discontinuation of the treatment which, if necessary, at the physician’s discretion, may be resumed at lower doses after all signs and symptoms of toxicity have subsided.

As there is no specific antidote, in case of overdose a symptomatic treatment of cardiovascular collapse should be instituted.