Ammonium Chloride + Chlorpheniramine Maleate + Guaifenesin + Sodium Citrate

Usage

This combination medication is primarily prescribed for the symptomatic relief of cough and cold symptoms, particularly those associated with allergies or the common cold. It is also used to relieve chest congestion caused by excess mucus in the airways.

• Pharmacological Classification: This combination drug includes components belonging to several classes:

  • Ammonium Chloride: Expectorant
  • Chlorpheniramine Maleate: First-generation antihistamine (H1 receptor antagonist)
  • Guaifenesin: Expectorant
  • Sodium Citrate: Mucolytic

• Mechanism of Action: This combination works through the synergistic actions of its components:

  • Ammonium Chloride and Guaifenesin thin and loosen mucus in the airways, making it easier to cough up.
  • Chlorpheniramine Maleate blocks the action of histamine, reducing allergy symptoms like runny nose, sneezing, and watery eyes.
  • Sodium Citrate also helps to thin the mucus, further aiding in its removal.

Alternate Names

There is no single international non-proprietary name (INN) for this specific four-drug combination. It is often identified by the names of its individual active ingredients. Various brand names exist depending on the manufacturer and region. Some examples include (though not exhaustive):

• Brand Names: Kofril Expectorant, Grilinctus, and various other regional brand names. Note that some brand names may contain additional active ingredients such as dextromethorphan or menthol.

How It Works

• Pharmacodynamics: The combined effect of this drug is to reduce cough, clear airways, and alleviate allergy symptoms. Ammonium chloride and guaifenesin primarily act on the respiratory system by increasing hydration and reducing the viscosity of mucus secretions. Chlorpheniramine maleate acts systemically by blocking H1 histamine receptors, thereby counteracting the effects of histamine release in allergic reactions. Sodium citrate acts locally within the respiratory tract to break down mucus.

• Pharmacokinetics:

  • Absorption: All components are absorbed from the gastrointestinal tract, though at varying rates.
  • Metabolism: Chlorpheniramine maleate is extensively metabolized in the liver, primarily by CYP450 enzymes. Ammonium chloride is metabolized in the liver to urea. Guaifenesin and Sodium Citrate have minimal hepatic metabolism.
  • Elimination: The metabolites of chlorpheniramine and the products of ammonium chloride metabolism are primarily excreted renally. Guaifenesin is also primarily excreted in the urine.

• Mode of Action: Ammonium chloride and guaifenesin act by increasing respiratory tract fluids, thereby reducing mucus viscosity. Chlorpheniramine competitively binds to H1 histamine receptors, preventing histamine from exerting its effects. Sodium citrate directly breaks down mucoproteins in mucus.

• Receptor Binding/Enzyme Inhibition: Chlorpheniramine maleate competitively and reversibly binds to H1 histamine receptors. The other components do not have specific receptor binding or enzyme inhibition properties relevant to their therapeutic effects in this combination.

• Elimination Pathways: Primarily renal excretion for all components after metabolism (where applicable).

Dosage

Standard Dosage

Adults: The typical adult dose varies depending on the specific formulation and brand. Generally, 10ml of syrup every 4-6 hours is recommended. Always follow the prescribed dosage and consult the specific product information for details.

Children: Pediatric dosage is dependent upon age and weight. It is crucial to consult a pediatrician or refer to the specific product’s pediatric dosage guidelines. This combination is generally not recommended for children under 6 years of age. Some formulations containing this combination are not recommended for children under 12 years of age.

Special Cases:

• Elderly Patients: Dose adjustments may be necessary due to age-related decline in renal and hepatic function.
• Patients with Renal Impairment: Dose reduction is typically required.
• Patients with Hepatic Dysfunction: Caution is advised, and dose adjustments may be needed.
• Patients with Comorbid Conditions: Careful consideration is necessary for patients with asthma, glaucoma, prostatic hypertrophy, hypertension, cardiovascular disease, or other chronic illnesses.

Clinical Use Cases

The combination is typically not used in clinical settings like intubation, surgical procedures, mechanical ventilation, or ICU care. Its use is primarily limited to outpatient management of common cold and cough symptoms.

Dosage Adjustments

Dosage adjustments may be required based on patient-specific factors like renal/hepatic impairment, age, and other medical conditions. Consult product-specific guidelines or an expert for adjustments in these populations.

Side Effects

Common Side Effects:

• Drowsiness
• Dizziness
• Dry mouth, nose, and throat
• Nausea
• Headache
• Constipation

Rare but Serious Side Effects:

• Allergic reactions (rash, itching, swelling)
• Difficulty breathing
• Paradoxical excitation (especially in children)

Long-Term Effects:

Generally not intended for long-term use. Prolonged use of chlorpheniramine can lead to tolerance and decreased effectiveness.

Adverse Drug Reactions (ADR): See rare but serious side effects.

Contraindications

• Hypersensitivity to any of the components.
• Severe liver or kidney disease.
• Narrow-angle glaucoma.
• Urinary retention.
• Concurrent use of monoamine oxidase inhibitors (MAOIs).

Drug Interactions

• Alcohol (increases sedation).
• Other CNS depressants (e.g., sedatives, hypnotics, opioids).
• Anticholinergic drugs (e.g., atropine).
• MAOIs.
• Medications metabolized by CYP450 enzymes.

Pregnancy and Breastfeeding

• Pregnancy: Use with caution and only if clearly needed. The safety profile during pregnancy has not been firmly established.

• Breastfeeding: Small, occasional doses may be acceptable, but prolonged use or higher doses are not recommended. Chlorpheniramine is excreted in breast milk. The non-sedating antihistamines are preferred if an antihistamine is necessary.

Drug Profile Summary

• Mechanism of Action: See above.
• Side Effects: See above.
• Contraindications: See above.
• Drug Interactions: See above.
• Pregnancy & Breastfeeding: See above.
• Dosage: See above.
• Monitoring Parameters: Observe for adverse reactions, especially drowsiness, dizziness, and allergic reactions. Monitor respiratory function in patients with underlying respiratory conditions.

Popular Combinations

This combination itself is a popular combination for cough and cold relief. Sometimes, dextromethorphan, a cough suppressant, is added for more comprehensive symptom control. Other potential additions may include decongestants like phenylephrine.

Precautions

• General Precautions: Assess renal and hepatic function before initiating therapy. Screen for allergies.
• Specific Populations: See above.
• Lifestyle Considerations: Avoid alcohol, as it can exacerbate drowsiness. Caution is advised while driving or operating machinery due to potential sedative effects.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Ammonium Chloride + Chlorpheniramine Maleate + Guaifenesin + Sodium Citrate?

A: The dosage varies depending on the specific product, age, and medical condition. Consult the prescribing information or a healthcare professional. For adults, a common dose is 10ml of syrup every 4-6 hours.

Q2: Can this combination be used in children?

A: Dosage in children depends on their age and weight, and is generally not recommended for children younger than 6 years old. Consult a pediatrician for appropriate dosage guidelines.

Q3: What are the common side effects?

A: Common side effects include drowsiness, dizziness, dry mouth, nausea, and constipation.

Q4: Are there any serious side effects to watch out for?

A: Rare but potentially serious side effects include allergic reactions and paradoxical excitation.

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

A: Use cautiously during pregnancy only if the potential benefit justifies the potential risk to the fetus. Small, occasional doses may be acceptable during breastfeeding, but discuss with a physician. Non-sedating antihistamines are generally preferred.

Q6: What are the major drug interactions?

A: Significant interactions can occur with alcohol, other CNS depressants, anticholinergic drugs, and MAOIs.

Q7: What should patients be advised regarding lifestyle?

A: Patients should avoid alcohol and exercise caution while driving or operating machinery.

Q8: What if a dose is missed?

A: Take the missed dose as soon as remembered, unless it is almost time for the next dose. Do not double the dose.

Q9: Can this be used for a chronic cough?

A: This combination is intended for short-term symptomatic relief of cough associated with the common cold or allergies, not for chronic cough. Consult a physician for chronic cough management.

Q10: How long should this medication be taken?

A: This medication is typically used for short-term symptom relief. Do not exceed the recommended duration of use without consulting a physician. Most coughs related to the common cold resolve within a week or two.