Chlorpheniramine Maleate + Dextromethorphan Hydrobromide + Phenylephrine

Usage

• This combination medication is primarily prescribed for the relief of symptoms associated with the common cold, flu, or other upper respiratory tract infections. These symptoms include sneezing, runny nose, nasal congestion, cough, and itchy or watery eyes.
• Pharmacological Classification: This is a combination product containing a first-generation antihistamine (chlorpheniramine), a cough suppressant (dextromethorphan), and a decongestant (phenylephrine). It can be classified as an antihistamine, antitussive, and decongestant combination.
• Mechanism of Action: Chlorpheniramine blocks the effects of histamine, reducing allergic symptoms. Dextromethorphan suppresses the cough reflex by acting on the cough center in the brain. Phenylephrine constricts blood vessels in the nasal passages, reducing swelling and congestion.

Alternate Names

• This combination doesn’t have a specific international nonproprietary name (INN). It’s often referred to by its component drugs.
• Brand Names: Many brand names exist for this combination, varying regionally. It’s crucial to check the composition of specific brands, as formulations can differ.

How It Works

• Pharmacodynamics: Chlorpheniramine antagonizes H1 histamine receptors. Dextromethorphan acts centrally on sigma opioid receptors and may affect NMDA receptors, suppressing the cough reflex without analgesic effects at usual doses. Phenylephrine is an α1-adrenergic receptor agonist, causing vasoconstriction in the nasal mucosa.

• Pharmacokinetics:

  • Absorption: All three components are absorbed orally.
  • Metabolism: Chlorpheniramine is extensively metabolized in the liver, primarily by CYP450 enzymes. Dextromethorphan undergoes significant first-pass metabolism, also in the liver. Phenylephrine is metabolized by monoamine oxidase (MAO).
  • Elimination: Metabolites of all three drugs are primarily excreted in the urine.

• Mode of Action/Receptor Binding: As described above, chlorpheniramine acts as an H1 receptor antagonist, dextromethorphan acts on sigma opioid and possibly NMDA receptors, and phenylephrine acts as an α1-adrenergic receptor agonist.

• Elimination Pathways: Primarily renal excretion of metabolites after hepatic metabolism. Specific CYP enzymes involved in chlorpheniramine metabolism include CYP2D6, CYP3A4, and CYP1A2.

Dosage

Standard Dosage

Adults: The dosage varies depending on the specific formulation. Always refer to the product’s packaging or prescribing information. A typical dose could be one or two tablets every 4-6 hours, not exceeding a specified maximum daily dose.

Children: Pediatric dosing is based on age and weight, and some formulations are not suitable for young children. Consult pediatric dosing guidelines and avoid use in children under the age of 6 unless directed by a healthcare provider.

Special Cases:

• Elderly Patients: Start with a lower dose due to potential age-related decline in organ function and monitor closely.
• Patients with Renal Impairment: Dose adjustment is required. The exact modification depends on the degree of impairment (creatinine clearance or GFR).
• Patients with Hepatic Dysfunction: Reduce the dose and monitor closely, as these drugs are metabolized in the liver.
• Patients with Comorbid Conditions: Exercise caution in patients with cardiovascular disease, diabetes, hyperthyroidism, glaucoma, or prostatic hypertrophy. Adjust dosage as needed.

Clinical Use Cases The provided sources do not supply information about clinical use cases for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations in relation to the combination medication Chlorpheniramine Maleate + Dextromethorphan Hydrobromide + Phenylephrine. Therefore I will focus on the medication’s primary indicated use, which is treating cold and flu symptoms.

Dosage Adjustments

• Dosage adjustments are necessary for patients with renal or hepatic impairment, considering creatinine clearance or GFR and liver function tests.
• Consider comorbidities like diabetes, cardiovascular conditions and adjust based on clinical judgment.

Side Effects

Common Side Effects:

• Drowsiness, dizziness, dry mouth, blurred vision, constipation, nausea, restlessness, or excitability (especially in children).

Rare but Serious Side Effects:

• Allergic reactions (rash, itching, swelling), difficulty breathing, hallucinations, seizures, fast or irregular heartbeat.

Long-Term Effects:

• Long-term use of dextromethorphan at doses exceeding the recommended can lead to dependence and neurotoxicity. The other ingredients don’t typically pose long-term risks if used according to guidelines.

Adverse Drug Reactions (ADR):

• Severe allergic reactions (anaphylaxis), cardiac arrhythmias, serotonin syndrome if combined with MAOI or other serotonergic drugs.

Contraindications

• Hypersensitivity to any component of the drug, severe respiratory disease, narrow-angle glaucoma, MAOI use within 14 days, use in infants and young children.

Drug Interactions

• MAOIs, antidepressants, sedatives, tranquilizers, alcohol, other medications with anticholinergic or sympathomimetic effects.
• CYP2D6 inhibitors can increase dextromethorphan levels, while CYP3A4 inducers may lower chlorpheniramine effectiveness.

Pregnancy and Breastfeeding

• Consult a healthcare professional before taking this medication. Its safety during pregnancy and breastfeeding has not been well-established. Consider safer alternatives if possible.

Drug Profile Summary

• Mechanism of Action: Antihistamine (H1 antagonist), cough suppressant (sigma receptor agonist), decongestant (α1-adrenergic agonist).
• Side Effects: Drowsiness, dizziness, dry mouth, blurred vision, constipation, rare serious reactions.
• Contraindications: Hypersensitivity, severe respiratory disease, glaucoma, MAOI use.
• Drug Interactions: MAOIs, antidepressants, sedatives, alcohol.
• Pregnancy & Breastfeeding: Consult a doctor. Safety not well-established.
• Dosage: Varies by product; see product labeling.
• Monitoring Parameters: Blood pressure, respiratory function, heart rate, mental status in susceptible individuals.

Popular Combinations

• This combination itself is widely used. Sometimes, it’s found in combination with analgesics like acetaminophen or ibuprofen. The rationale is to provide broader symptomatic relief for cold and flu.

Precautions

• General Precautions: Assess renal and hepatic function before prescribing, screen for drug interactions.
• Specific Populations:
  • Pregnant Women: Consult a doctor. Risk vs. benefit assessment is essential.
  • Breastfeeding Mothers: Exercise caution. Consider safer alternatives.
  • Children & Elderly: Start with lower doses and monitor for side effects.
• Lifestyle Considerations: Avoid alcohol. May impair alertness; caution with driving.

FAQs (Frequently Asked Questions)

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

A: The dose depends on the formulation and patient factors (age, weight, comorbidities, organ function). Always check the specific product labeling. Typical adult dose might be one or two tablets every 4-6 hours. Pediatric doses are lower and vary by age/weight. Adjustments are needed in renal/hepatic impairment.

Q2: Can this combination be used in children?

A: Some formulations are suitable for children, but always consult pediatric dosing guidelines. Avoid use in children under 6 unless specifically directed by a physician.

Q3: What are the most common side effects?

A: Drowsiness, dry mouth, blurred vision, dizziness, and constipation.

Q4: Are there any serious drug interactions I should be aware of?

A: Yes, avoid co-administration with MAOIs. Be cautious with other medications with anticholinergic or sympathomimetic properties, including certain antidepressants and sedatives.

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

A: Safety during pregnancy and breastfeeding hasn’t been conclusively established. Consult a physician to weigh the benefits and risks. Consider safer alternatives if possible.

Q6: How should dosage be adjusted for patients with renal insufficiency?

A: Base dose modifications on creatinine clearance (CrCl) or glomerular filtration rate (GFR). Refer to drug dosing guidelines for chronic kidney disease for specific recommendations.

Q7: What precautions should be taken for patients with hepatic impairment?

A: Reduce the dose and monitor liver function tests. The combination is metabolised in the liver, therefore dosage adjustments are necessary for patients with hepatic impairment.

Q8: Can this medication be used in patients with cardiovascular disease?

A: Use with caution. The decongestant component (phenylephrine) can increase blood pressure and heart rate. Close monitoring is necessary. Dosage adjustment might be necessary.

Q9: Can this medication be combined with other cold and flu medications?

A: Avoid combining with other medications containing the same ingredients. Overdosing can occur if multiple products with acetaminophen, dextromethorphan, or decongestants are used together.

Q10: What if a patient experiences excessive drowsiness?

A: Reduce the dose or consider an alternative. Advise patients not to operate machinery or drive while experiencing drowsiness.