Chlorpheniramine Maleate + Dextromethorphan Hydrobromide + Phenylpropanolamine

Usage

This combination medication is primarily prescribed for the temporary relief of symptoms associated with the common cold, flu, hay fever, and other upper respiratory allergies. These symptoms include cough, nasal congestion, runny nose, sneezing, itchy eyes/nose/throat, and watery eyes.

Pharmacological Classification:

This is a combination drug belonging to three classes:

• Antihistamine (Chlorpheniramine Maleate): Reduces allergic symptoms.
• Cough Suppressant (Dextromethorphan Hydrobromide): Suppresses the cough reflex.
• Decongestant (Phenylpropanolamine): Relieves nasal congestion.

Mechanism of Action:

• Chlorpheniramine maleate: A first-generation antihistamine that competes with histamine for H1-receptor sites, thus reducing the effects of histamine, which causes allergic symptoms.

• Dextromethorphan hydrobromide: Acts centrally in the medulla to elevate the cough threshold.

• Phenylpropanolamine: An alpha-adrenergic agonist that causes vasoconstriction in the nasal mucosa, reducing swelling and congestion.

Alternate Names

There is no widely recognized international non-proprietary name (INN) for the combination product. The individual components have the following INNs: chlorphenamine (chlorpheniramine), dextromethorphan, and phenylpropanolamine.

Brand Names: Brand names vary depending on the country and manufacturer. Some examples include (but are not limited to) Menthodex-DM, and various generic formulations.

How It Works

Pharmacodynamics:

• Chlorpheniramine: Reduces histamine-mediated responses such as sneezing, rhinorrhea, pruritus, and lacrimation.

• Dextromethorphan: Suppresses the cough reflex by increasing the threshold for coughing in the central nervous system.

• Phenylpropanolamine: Constricts blood vessels in the nasal mucosa, decreasing blood flow and reducing swelling.

Pharmacokinetics:

• Absorption: All three components are well-absorbed from the gastrointestinal tract.

• Metabolism: Chlorpheniramine is extensively metabolized in the liver, primarily via CYP2D6 enzymes. Dextromethorphan undergoes significant first-pass metabolism in the liver, with CYP2D6 being the primary enzyme involved. Phenylpropanolamine is partially metabolized in the liver.

• Elimination: Primarily renal excretion for all three components.

Mode of Action:

• Chlorpheniramine: Competitive antagonist at H1 histamine receptors.

• Dextromethorphan: Acts centrally on sigma-1 receptors and NMDA receptors.

• Phenylpropanolamine: Agonist at alpha-adrenergic receptors.

Dosage

Dosage guidelines for this combination medication are complex and vary significantly depending on age, formulation, and the specific product being used. Always refer to the manufacturer’s instructions for the particular product prescribed.

Standard Dosage

Adults: A common dose is one to two tablets/capsules or 10-20 ml of syrup every 4-6 hours as needed. However, this can vary.

Children: Dosage varies widely depending on age and formulation. Liquid formulations are often preferred for pediatric administration, with doses calculated by weight or age. Never give this combination medication to children under 6 years of age without a doctor’s express recommendation and supervision.

Special Cases:

• Elderly Patients: Start with the lower end of the adult dose range and titrate based on patient tolerance and response.

• Patients with Renal Impairment: Dose adjustment may be necessary. Consult a nephrologist.

• Patients with Hepatic Dysfunction: Dose adjustment may be necessary. Consult a hepatologist.

• Patients with Comorbid Conditions: Caution is advised in patients with cardiovascular disease, hypertension, hyperthyroidism, diabetes, glaucoma, and prostatic hypertrophy. Dose adjustments or alternative medications may be considered.

Clinical Use Cases

This combination medication is generally not indicated for use in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its use is restricted to symptomatic relief of common cold and allergy symptoms.

Dosage Adjustments

Dose adjustments may be necessary based on factors like age, organ function, and concomitant medications. Always consult with a specialist when considering such adjustments.

Side Effects

Common Side Effects:

• Drowsiness
• Dizziness
• Dry mouth
• Nausea
• Constipation
• Blurred vision
• Headache
• Insomnia
• Restlessness or excitability (especially in children)

Rare but Serious Side Effects:

• Allergic reactions (rash, itching, swelling, severe dizziness, trouble breathing)
• Hallucinations
• Seizures
• Cardiac arrhythmias
• Hypertensive crisis
• Stroke

Long-Term Effects:

Chronic use of phenylpropanolamine can potentially lead to cardiovascular complications. Long-term use of antihistamines can also be associated with tolerance.

Adverse Drug Reactions (ADR):

Any severe or unusual reactions should be considered a potential ADR and should be reported immediately.

Contraindications

• Hypersensitivity to any component of the medication
• Concurrent use of MAO inhibitors
• Severe hypertension or coronary artery disease
• Severe hyperthyroidism
• Narrow-angle glaucoma
• Urinary retention due to prostatic hypertrophy

Drug Interactions

This combination can interact with a multitude of medications, including:

• MAO inhibitors: Concomitant use is contraindicated.
• Antihypertensives: May reduce their effectiveness.
• Tricyclic antidepressants: Increased anticholinergic effects.
• Other antihistamines: Additive sedative effects.
• Alcohol and CNS depressants: Increased drowsiness.
• CYP2D6 inhibitors/inducers: May affect the metabolism of chlorpheniramine and dextromethorphan.

Always consult a drug interaction database or a pharmacist to check for potential interactions with other medications the patient might be taking, including OTC drugs and herbal supplements.

Pregnancy and Breastfeeding

Pregnancy Safety Category: C (FDA Classification – Phenylephrine alone is Category C, the combination is not specifically categorized). Use only if the potential benefit justifies the potential risk to the fetus.

Breastfeeding: Chlorpheniramine and dextromethorphan are excreted in breast milk. Phenylpropanolamine may reduce milk production. Not recommended for breastfeeding women.

Drug Profile Summary

• Mechanism of Action: Antihistamine, cough suppressant, and decongestant.
• Side Effects: Drowsiness, dizziness, dry mouth, nausea, constipation.
• Contraindications: Hypersensitivity, MAOI use, severe cardiovascular disease, hyperthyroidism.
• Drug Interactions: MAOIs, antihypertensives, antidepressants, alcohol, CNS depressants.
• Pregnancy & Breastfeeding: Not recommended unless the benefits outweigh the risks.
• Dosage: Varies widely depending on age, formulation, and specific product. See product labeling for details.
• Monitoring Parameters: Blood pressure, heart rate, respiratory rate, alertness, any signs of adverse reactions.

Popular Combinations

This specific combination is itself a common combination. Sometimes it is combined with analgesics like acetaminophen or ibuprofen to also address fever and body aches.

Precautions

• General Precautions: Assess for allergies, pre-existing medical conditions, concomitant medications.
• Specific Populations: Caution is advised in pregnant/breastfeeding women, children, and the elderly.
• Lifestyle Considerations: Avoid alcohol, operating machinery, or driving while taking this medication.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Chlorpheniramine Maleate + Dextromethorphan Hydrobromide + Phenylpropanolamine?

A: The dosage varies considerably depending on the specific product, age, and indication. Consult the product’s prescribing information for detailed dosing instructions.

Q2: Can this combination be used in children?

A: It is not recommended for children under 6 years of age without explicit medical direction. For older children, use age-appropriate formulations and follow the recommended dosing guidelines.

Q3: What are the common side effects?

A: Drowsiness, dizziness, dry mouth, nausea, and constipation are common.

Q4: Can this combination be used during pregnancy or while breastfeeding?

A: Generally not recommended. If deemed necessary, consult an obstetrician/gynecologist to weigh the benefits against potential risks.

Q5: What are the major drug interactions?

A: Avoid concurrent use with MAO inhibitors. Caution is required with antihypertensives, antidepressants, and other CNS depressants.

Q6: What should patients do if they miss a dose?

A: Take the missed dose as soon as remembered, unless it is close to the next scheduled dose. Do not double the dose.

Q7: Are there any dietary restrictions while taking this medication?

A: Avoid alcohol. No specific dietary restrictions, but maintaining adequate hydration is important.

Q8: Can patients drive or operate machinery while taking this medication?

A: No, it can cause drowsiness and impair alertness. Avoid driving or operating heavy machinery while taking this combination.

Q9: What should patients do if they experience an allergic reaction?

A: Stop taking the medication and seek immediate medical attention. Allergic reactions can be serious and may require treatment with epinephrine.