Coughdip P

Uses

Bromhexineis used for the treatment of respiratory disorders associated with productive cough. These include; tracheobronchitis, bronchitis with emphysema, bronchiectasis, bronchitis with bronchospasm, chronic inflammatory pulmonary conditions and pneumoconiosis.

Dextromethorphan is used for Chronic dry cough or unproductive cough; Acute dry cough which is interfering with normal function or sleep.

Phenylephrine is an alpha-1 adrenergic agonist used in the management of hypotension, generally in the surgical setting associated with the use of anesthetics.

Phenylephrine injections are indicated to treat hypotension caused by shock or anesthesia, an ophthalmic formulation is indicated to dilate pupils and induce vasoconstriction, an intranasal formulation is used to treat congestion, and a topical formulation is used to treat hemorrhoids. Off-label uses include situations that require local blood flow restriction such as the treatment of priapism.

Coughdip P is also used to associated treatment for these conditions: Bronchiectasis, Common Cold, Cough, Cough caused by Common Cold, Nasal Congestion, Whooping Cough, Airway secretion clearance therapyAllergic cough, Common Cold, Common Cold/Flu, Cough, Cough caused by Common Cold, Coughing caused by Allergies, Coughing caused by Bronchitis, Coughing caused by Flu caused by Influenza, Fever, Flu caused by Influenza, Headache, Irritative cough, Itching of the nose, Itching of the throat, Nasal Congestion, Pseudobulbar affect, Rhinorrhoea, Sneezing, Upper respiratory symptoms, Watery itchy eyes, Airway secretion clearance therapy, Bronchodilation, Oropharyngeal antisepsisAllergic Rhinitis (AR), Anorectal discomfort, Cold, Common Cold, Common Cold/Flu, Congestion of the Conjunctivas, Conjunctivitis allergic, Cough, Cough caused by Common Cold, Eye allergy, Eye redness, Fever, Flu caused by Influenza, Headache, Headache caused by Allergies, Headache caused by Common Cold, Headache caused by Pollen Allergy, Hemorrhoids, Hypotension, Irritative cough, Itching of the nose, Itching of the throat, Laryngotracheitis, Nasal Congestion, Nose discomfort, Ocular Inflammation, Ocular Irritation, Paroxysmal Supraventricular Tachycardia, Pollen Allergy, Respiratory tract congestion, Respiratory tract irritation, Rhinopharyngitis, Rhinorrhoea, Seasonal Allergies, Shock, Cardiogenic, Sinus Congestion, Sinus pressure, Sinusitis, Sneezing, Sore Throat, Tracheobronchitis, Upper respiratory tract hypersensitivity reaction, site unspecified, Vasomotor Rhinitis, Aching caused by Flu caused by Influenza, Bronchial congestion, Itchy throat, Minor aches and pains, Watery itchy eyes, Airway secretion clearance therapy, Antihistamine, Dilatation of the pupil, Vasoconstrictor in regional analgesia therapy

How Coughdip P works

Inflammation of the airways, increased mucus secretion, and altered mucociliary clearance are the hallmarks of various diseases of the respiratory tract. Mucus clearance is necessary for lung health; bromhexine aids in mucus clearance by reducing the viscosity of mucus and activating the ciliary epithelium, allowing secretions to be expelled from the respiratory tract.

Recent have studies have demonstrated that bromhexine inhibits the transmembrane serine protease 2 receptor (TMPRSS2) in humans. Activation of TMPRSS2 plays an important role in viral respiratory diseases such as influenza A and Middle East Respiratory Syndrome (MERS). Inhibition of receptor activation and viral entry by bromhexine may be effective in preventing or treating various respiratory illnesses, including COVID-19. In vitro studies have suggested the action of ambroxol (a metabolite of bromhexine) on the angiogensin-converting enzyme receptor 2 (ACE2), prevents entry of the viral envelope-anchored spike glycoprotein of SARS-Cov-2 into alveolar cells or increases the secretion of surfactant, preventing viral entry.

Dextromethorphan is an agonist of NMDA and sigma-1 receptors. It is also an antagonist of α3/β4 nicotinic receptors.[A10589] However, the mechanism by which dextromethorphan's receptor agonism and antagonism translates to a clinical effect is not well understood.

Phenylephrine is an alpha-1 adrenergic agonist that mediates vasoconstriction and mydriasis depending on the route and location of administration. Systemic exposure to phenylephrine also leads to agonism of alpha-1 adrenergic receptors, raising systolic and diastolic pressure as well as peripheral vascular resistance. Increased blood pressure stimulates the vagus nerve, causing reflex bradycardia.

Dosage

Coughdip P dosage

BromhexineTablet:

Adults and children over 10 years: 8-16 mg 3 times daily. Children 5-10 years: 4 mg 3 times daily.

BromhexineSyrup:

Adults: The recommended daily dose is 2 to 4 teaspoonful 3 times. Initially 4 teaspoonful 3 times daily and then as required.

Children: Suggested dosage for children under 2 years is 1/4 teaspoonful 3 times daily, for 2-5 years 1/2 teaspoonful 3 times daily and for children aged 5-10 years 1 teaspoonful 3 times daily.

Adults and Children over 12 years: 15 to 30 mg three to four times per day. However, 60 mg doses up to four times per day have been used without increased side effects.

Children between 6 and 12 years: 5-15 mg up to four times per day.

Children between 2 and 6 years: 2.5-5 mg up to four times per day.

Side Effects

Gastrointestinal side-effects may occur occasionally with Bromhexine and a transient rise in serum aminotransferase values has been reported. Other reported adverse effects include headache, dizziness, sweating and skin rash.

Adverse effects with Dextromethorphan are rare, but nausea and dizziness sometimes occur. The drug produces no analgesia or addiction and little or no CNS depression. Excitation, confusion and respiratory depression may occur after overdosage.

Toxicity

The oral LD50 of bromhexine in rats is 6 g/kg. The observed symptoms of accidental overdose with bromhexine are consistent with the known adverse effects of bromhexine, including headache, nausea, and vomiting, among other symptoms. Provide symptomatic treatment and contact poison control services if an overdose is confirmed or suspected.

A dextromethorphan overdose may present as nausea, vomiting, stupor, coma, respiratory depression, seizures, tachycardia, hyperexcitability, toxic psychosis, ataxia, nystagmus, dystonia, blurred vision, changes in muscle reflexes, and serotonin syndrome. Overdose should be managed through symptomatic and supportive measures.

Patients experiencing and overdose may present with headache, hypertension, reflex bradycardia, tingling limbs, cardiac arrhythmias, and a feeling of fullness in the head. Overdose may be treated by supportive care and discontinuing phenylephrine, chronotropic medications, and vasodilators. Subcutaneous phentolamine may be used to treat tissue extravasation.

Precaution

Since mucolytics may disrupt the gastric mucosa so Bromhexine should be used with care in patients with a history of peptic ulceration.

Do not use Dextromethorphan to control a cough that is associated with smoking, asthma, or emphysema, or a cough that is productive (produces sputum or phlegm).

Interaction

The following medicines should be taken carefully while concomitantly use with Dextromethorphan: Amiodarone, Fluoexetine, Quinidine, CNS depressants and Monoamine oxidase (MAO) inhibitors.

Volume of Distribution

After intravenous administration in a pharmacokinetic study, bromhexine was found to be widely distributed. Bromhexine is known to cross the blood-brain barrier; small concentrations may cross the placenta. The average volume of distribution of bromhexine was 1209 ± 206 L (19 L/kg). Lung tissue concentrations of bromhexine two hours after a dose were 1.5 to 3.2 times higher in bronchial tissues than plasma concentrations. Pulmonary parynchema concentrations were 3.4 to 5.9 times higher when compared to plasma concentrations.

The volume of distribution of dextromethorphan is 5-6.7L/kg.

The volume of distribution of phenylephrine is 340L.

Elimination Route

After oral administration, bromhexine demonstrates linear pharmacokinetics when given in doses of 8-32 mg. Bromhexine is readily absorbed in the gastrointestinal tract at a rapid rate. This drug undergoes extensive first-pass effect in the range of 75-80%. The bioavailability is therefore reduced to approximately 22-27%.

A 30mg oral dose of dextromethorphan reaches a C_max of 2.9 ng/mL, with a T_max of 2.86 h, and an AUC of 17.8 ng*h/mL.

Phenylephrine is 38% orally bioavailable. Clinically significant systemic absorption of ophthalmic formulations is possible, especially at higher strengths and when the cornea is damaged.

Half Life

Following single oral doses ranging from 8 and 32 mg, the terminal half-life of bromhexine has been measured between 6.6 and 31.4 hours.

Dextromethorphan has a half life of 3-30 hours.

Intravenous phenylephrine has an effective half life of 5 minutes and an elimination half life of 2.5 hours.

Clearance

The clearance of bromhexine ranges from 843-1073 mL/min, within the range of the hepatic circulation.

Phenylephrine has an average clearance of 2100mL/min.

Elimination Route

After a dose of bromhexine was administered during a pharmacokinetic study, approximately 97% of the radiolabeled dose was detected in the urine; under 1% was detected as the parent drug.

86% of a dose of phenylephrine is recovered in the urine with 16% as the unmetabolized drug, 57% as the inactive meta-hydroxymendelic acid, and 8% as inactive sulfate conjugates.

Pregnancy & Breastfeeding use

Pregnancy Category B. Bromhexine has been taken by a large number of pregnant women and women of child bearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.

It is not known whether bromhexine is excreted in breast milk or whether it has a harmful effect on the breastfeeding infant. Therefore it is not recommended for breast feeding mothers unless the potential benefits to the patient are weighed against the possible risk to the infant.

Pregnancy: Adequate and well-controlled studies in human have not been done. However, Dextromethorphan has not been reported to cause birth defects.

Lactation: It is not known whether dextromethorphan passes into breast milk. However, Dextromethorphan has not been reported to cause problems in nursing babies.

Contraindication

Contraindicated to those who are hypersensitive to Bromhexine Hydrochloride.

Hypersensitivity to Dextromethorphan or any other component.

Acute Overdose

Symptoms: In mild overdose, tachycardia, hypertension, vomiting, mydriasis, diaphoresis, nystagmus, euphoria, loss of motor coordination, and giggling; in moderate intoxication, in addition to those listed above, hallucinations and a plodding ataxic gait; in severely intoxication, agitation or somnolence.

Management: treatment is symptomatic and supportive. Naloxone may be useful in reversing toxicity.

Storage Condition

Store below 25° C. Protect from light. Keep the container tightly closed.

Store at 15-30° C

Innovators Monograph

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