Usage
Paracetamol + Promethazine is prescribed for the short-term symptomatic relief of pain and discomfort associated with common cold and flu, including headache, fever, body aches, and nasal congestion. Additionally, it may be used to treat allergic conditions like hay fever and urticaria, as well as nausea and vomiting associated with motion sickness. It is also sometimes used as a sedative for insomnia.
Pharmacological Classification:
This combination drug falls under multiple classifications due to the presence of two active ingredients:
- Paracetamol: Analgesic (pain reliever) and Antipyretic (fever reducer)
- Promethazine: Antihistamine (H1 receptor antagonist) and Sedative-Hypnotic and Antiemetic.
Mechanism of Action:
- Paracetamol: Inhibits prostaglandin synthesis in the central nervous system, which reduces pain and fever. Its exact mechanism is not fully understood, but it appears to act primarily on cyclooxygenase (COX) enzymes in the brain and spinal cord.
- Promethazine: Competes with histamine for H1-receptor sites, reducing allergic symptoms. Additionally, it has an anticholinergic effect that contributes to its sedative and antiemetic properties.
Alternate Names
This combination drug is sometimes referred to as Paracetamol/Promethazine or Promethazine/Paracetamol.
Brand Names: Some examples of Brand Names include: (Please be aware that brand names can vary regionally)
- Phenergan with Codeine (some formulations)
- Night Nurse (some formulations)
- Painstop Night-Time Pain Reliever (some formulations)
How It Works
Pharmacodynamics:
- Paracetamol: Reduces fever and pain by inhibiting COX enzymes in the CNS, and minimally peripherally.
- Promethazine: Antagonizes H1 receptors, leading to a decrease in allergic symptoms. It also possesses anticholinergic, sedative, and antiemetic properties through central nervous system depression and muscarinic receptor blockade.
Pharmacokinetics:
- Paracetamol: Rapidly absorbed from the gastrointestinal tract. Metabolized primarily in the liver, mainly by glucuronidation and sulfation, and excreted in the urine. A minor pathway involves hepatic cytochrome P450 (CYP2E1 and CYP3A4) metabolism to a reactive intermediate, NAPQI. This is detoxified by glutathione.
- Promethazine: Well absorbed after oral administration. Metabolized in the liver, primarily via CYP2D6, and excreted in urine and feces.
Mode of Action:
- Paracetamol: Primarily inhibits COX enzymes, decreasing prostaglandin production.
- Promethazine: Competitive antagonist at H1 receptors. It blocks muscarinic acetylcholine receptors contributing to its antiemetic and sedative effects.
Elimination Pathways:
- Paracetamol: Primarily renal excretion.
- Promethazine: Primarily hepatic metabolism (CYP2D6) with renal and fecal excretion.
Dosage
Standard Dosage
Adults:
The typical adult dose is 500-1000 mg of Paracetamol and 12.5-25 mg of Promethazine, usually taken at bedtime. As of today, 2025-02-16 it is recommended not to exceed a maximum daily dose of 4000mg of Paracetamol, from all sources.
Children:
Promethazine is generally not recommended for children under 2 years of age. For children older than 2 years, the dose should be carefully calculated based on the child’s weight and age, and only administered under the guidance of a healthcare professional. This is crucial due to the risk of respiratory depression.
Special Cases:
- Elderly Patients: Start with a lower dose and monitor closely due to increased sensitivity to side effects, particularly drowsiness and confusion.
- Patients with Renal Impairment: Use with caution. Dose adjustment might be necessary.
- Patients with Hepatic Dysfunction: Paracetamol dosage should be reduced, and Promethazine should be used with caution due to the risk of further liver damage.
- Patients with Comorbid Conditions: Use with caution in patients with respiratory diseases (e.g., asthma, COPD), cardiovascular disease, glaucoma, and benign prostatic hyperplasia.
Clinical Use Cases
The Paracetamol + Promethazine combination is not typically used in clinical settings like intubation, surgical procedures, mechanical ventilation, or ICU care. It may be used for short-term pain and symptom relief associated with mild to moderate post-operative discomfort.
Dosage Adjustments
Dose adjustments are necessary based on patient-specific factors such as renal or hepatic dysfunction, age, and body weight. Always use the lowest effective dose.
Side Effects
Common Side Effects:
Drowsiness, dizziness, dry mouth, blurred vision, constipation, urinary retention, nausea, and restlessness.
Rare but Serious Side Effects:
Allergic reactions (e.g., skin rash, itching, swelling), difficulty breathing, abnormal heart rhythms, neuroleptic malignant syndrome (NMS), and severe liver damage (with Paracetamol overdose).
Long-Term Effects:
Tardive dyskinesia (with prolonged Promethazine use).
Adverse Drug Reactions (ADR):
Severe allergic reactions (anaphylaxis), agranulocytosis, Stevens-Johnson syndrome.
Contraindications
Hypersensitivity to paracetamol or promethazine, severe respiratory depression, acute asthma attack, comatose state, use of MAOIs within the past two weeks, children under 2 years of age.
Drug Interactions
Alcohol, CNS depressants (e.g., benzodiazepines, opioids), anticholinergics (e.g., atropine), MAOIs, and other medications metabolized by CYP2D6.
Pregnancy and Breastfeeding
This combination is generally avoided during pregnancy, especially in the first trimester, due to potential risks to the fetus. The use of paracetamol alone is generally considered safe during breastfeeding; however, promethazine should be used with caution.
Drug Profile Summary
- Mechanism of Action: Paracetamol: Analgesic and antipyretic; Promethazine: Antihistamine, sedative, antiemetic.
- Side Effects: Drowsiness, dizziness, dry mouth, blurred vision, constipation, nausea.
- Contraindications: Hypersensitivity, severe respiratory depression, MAOI use, children under 2.
- Drug Interactions: Alcohol, CNS depressants, anticholinergics, MAOIs.
- Pregnancy & Breastfeeding: Generally avoided during pregnancy. Use Promethazine with caution when breastfeeding.
- Dosage: Adults: Paracetamol 500-1000mg, Promethazine 12.5-25mg; Pediatric: consult healthcare professional.
- Monitoring Parameters: Liver function tests, respiratory rate, blood pressure.
Popular Combinations
Paracetamol and Promethazine are commonly combined with dextromethorphan in some over-the-counter cold and flu medications.
Precautions
Avoid alcohol, operate machinery with caution, monitor liver function, and be aware of potential drug interactions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Paracetamol + Promethazine?
A: Adults: Paracetamol 500-1000mg, Promethazine 12.5-25mg. Pediatric dosing should be determined by a healthcare professional based on weight and age.
Q2: Can Paracetamol + Promethazine be used in children?
A: Promethazine is contraindicated in children under 2 years. Use with caution and according to a physician’s directions for children over 2 years.
Q3: Is Paracetamol + Promethazine safe during pregnancy?
A: Generally avoided, especially in the first trimester. Consult with an obstetrician.
Q4: What are the common side effects of Paracetamol + Promethazine?
A: Drowsiness, dizziness, dry mouth, blurred vision, constipation, and nausea.
Q5: Can I drink alcohol while taking Paracetamol + Promethazine?
A: No, alcohol should be avoided as it can potentiate the sedative effects and increase the risk of liver damage.
A: Allergic reactions (rash, itching, swelling), difficulty breathing, abnormal heart rhythms, seizures, severe liver injury.
Q7: What should I do if I miss a dose?
A: Take the missed dose as soon as you remember, unless it is close to the next scheduled dose. Do not double the dose to catch up.
Q8: Can I take other medications along with Paracetamol + Promethazine?
A: Consult with a doctor or pharmacist before taking other medications, including over-the-counter drugs and supplements, as there are potential drug interactions.
Q9: Can patients with liver or kidney problems take this medication?
A: Use with extreme caution. Dosage adjustments may be necessary. Consult with a healthcare professional.
Q10: Can this medication be used for long-term treatment?
A: It is intended for short-term use only (typically no more than 3-10 days). Prolonged use of Promethazine can carry the risk of tardive dyskinesia.
