Usage
- This drug is prescribed for the relief of mild to moderate pain and fever. It is commonly used for headaches (including tension headaches and migraines), toothaches, menstrual cramps, muscular aches, back pain, arthritis pain, and symptoms of cold and flu.
- Pharmacological classification: Analgesic, Antipyretic
- Mechanism of action: This combination medication works through the synergistic action of its components. Paracetamol and phenazone reduce pain and fever by inhibiting prostaglandin synthesis in the central nervous system. Caffeine enhances the analgesic effect of paracetamol by increasing its absorption and reducing its metabolism. It also acts as a mild stimulant, promoting alertness and reducing fatigue, and constricts blood vessels, which can further contribute to pain relief, particularly in headaches.
Alternate Names
- Paracetamol/Acetaminophen + Propyphenazone + Caffeine
- Brand names: Saridon, Dart, Trimol
How It Works
- Pharmacodynamics: Paracetamol and phenazone inhibit prostaglandin synthesis, which are mediators of pain and fever, primarily in the central nervous system. Caffeine acts as a central nervous system stimulant and a vasoconstrictor. It also increases paracetamol absorption and decreases its metabolism.
- Pharmacokinetics: All three components are absorbed well orally. Paracetamol is metabolized in the liver, primarily by glucuronidation and sulfation, with a small fraction undergoing CYP450-mediated metabolism to a reactive metabolite. Phenazone is also metabolized in the liver. Caffeine is metabolized by CYP1A2. All three drugs are primarily eliminated renally.
- Mode of action: Paracetamol and phenazone act primarily by inhibiting cyclooxygenase (COX) enzymes in the central nervous system, reducing prostaglandin synthesis. Caffeine’s mechanism in pain relief is complex and not fully elucidated but involves adenosine receptor antagonism, phosphodiesterase inhibition, and calcium mobilization.
- Elimination pathways: Primarily renal excretion for all three components.
Dosage
Standard Dosage
Adults:
- 1-2 tablets every 4-6 hours as needed.
- Maximum daily dose: Not to exceed 6 tablets in a 24-hour period.
- Typical formulation: 250mg paracetamol, 150mg phenazone (or propyphenazone), and 50mg caffeine per tablet.
Children:
- Not generally recommended for children under 12 years of age.
- Adolescents (12-16 years): 1 tablet every 4-6 hours as needed, not exceeding 3 tablets in 24 hours.
- Pediatric safety considerations: Monitor for caffeine-related side effects (insomnia, anxiety, increased heart rate). Consult a pediatrician for appropriate dosing.
Special Cases:
- Elderly Patients: Start with the lowest effective dose (1 tablet every 4-6 hours) due to potential age-related decline in hepatic and renal function. Monitor closely for adverse events.
- Patients with Renal Impairment: Dose reduction and careful monitoring are advised.
- Patients with Hepatic Dysfunction: Dose reduction and careful monitoring are recommended.
- Patients with Comorbid Conditions: Use with caution in patients with heart disease, hypertension, peptic ulcers, and anxiety disorders.
Clinical Use Cases
The combination is not typically used in specific medical settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. Its use is generally limited to the outpatient management of mild to moderate pain and fever.
Dosage Adjustments
Dose adjustments are necessary based on individual patient factors such as renal/hepatic impairment, age, and other medical conditions.
Side Effects
Common Side Effects
- Nausea, vomiting, stomach discomfort, dizziness, insomnia, dyspepsia, tremor, irritability, swelling, rash, diarrhea.
Rare but Serious Side Effects
- Liver damage, Steven-Johnson syndrome, anaphylactic reaction, anemia, edema, blood dyscrasias (thrombocytopenia, leukopenia, agranulocytosis, pancytopenia).
Long-Term Effects
- Potential for liver damage with chronic overuse.
- Gastric ulcers or bleeding with prolonged use.
Adverse Drug Reactions (ADR)
- Allergic reactions (skin rash, itching, angioedema, breathing difficulties).
- Hepatotoxicity.
- Blood dyscrasias.
Contraindications
- Hypersensitivity to any of the components (paracetamol, phenazone, caffeine).
- Severe liver or kidney disease.
- Heart disease, high blood pressure, peripheral vascular disease.
- Peptic ulcers, gastrointestinal bleeding.
- Pregnancy (especially the first trimester and last six weeks).
- Breastfeeding.
- Children under 12 years of age.
- Alcoholism.
- Blood disorders (e.g., haemophilia, von Willebrand disease, thrombocytopenia).
- Glucose-6-phosphate dehydrogenase deficiency.
- Acute hepatic porphyria.
Drug Interactions
- Alcohol: Avoid concomitant use due to increased risk of liver damage.
- Anticoagulants (e.g., warfarin): May increase bleeding risk.
- Anticonvulsants (e.g., carbamazepine, phenytoin): May alter metabolism of paracetamol.
- Metoclopramide, domperidone: May affect paracetamol absorption.
- Barbiturates: May reduce the effectiveness of paracetamol.
- Antibiotics (e.g., isoniazid, rifampicin): May interact with paracetamol metabolism.
- Anti-gout medications (e.g., probenecid): May affect renal excretion of paracetamol.
- Other medications containing paracetamol: Avoid concomitant use to prevent exceeding the maximum daily dose.
- Caffeine-containing products: Limit intake to avoid excessive caffeine consumption.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Contraindicated, especially during the first trimester and the last six weeks, due to potential fetal risks.
- Breastfeeding: Contraindicated as caffeine can be excreted in breast milk and affect the infant.
Drug Profile Summary
- Mechanism of Action: Analgesic and antipyretic via prostaglandin inhibition (paracetamol, phenazone) and CNS stimulation/vasoconstriction (caffeine).
- Side Effects: Nausea, vomiting, stomach discomfort, dizziness, insomnia. Rarely, liver damage, allergic reactions, blood disorders.
- Contraindications: Hypersensitivity, severe liver/kidney disease, pregnancy, breastfeeding, children under 12.
- Drug Interactions: Alcohol, anticoagulants, anticonvulsants, metoclopramide, barbiturates, antibiotics.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: 1-2 tablets every 4-6 hours, max 6 tablets/24 hours. Children (12-16): 1 tablet every 4-6 hours, max 3 tablets/24 hours.
- Monitoring Parameters: Liver function tests with prolonged use.
Popular Combinations
This combination itself is a popular combination for pain and fever relief. It is not generally combined with other drugs.
Precautions
- Pre-existing medical conditions: Assess liver and kidney function before prescribing.
- Pregnant Women: Avoid use.
- Breastfeeding Mothers: Avoid use.
- Children & Elderly: Use with caution, dose adjustment may be needed.
- Lifestyle Considerations: Limit caffeine intake from other sources, avoid alcohol, driving restrictions if dizziness or drowsiness occurs.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Caffeine + Paracetamol + Phenazone?
A: Adults: 1-2 tablets every 4-6 hours, not exceeding 6 tablets in 24 hours. Adolescents (12-16 years): 1 tablet every 4-6 hours, not exceeding 3 tablets/24 hours. Not recommended for children under 12.
Q2: What are the primary uses of this medication?
A: Relief of mild to moderate pain and fever associated with conditions like headache, toothache, menstrual cramps, muscle aches, and cold/flu symptoms.
Q3: Are there any serious side effects I should be aware of?
A: Although rare, serious side effects can include liver damage, allergic reactions (skin rash, breathing difficulty), and blood disorders. Seek immediate medical attention if these occur.
Q4: Can this medication be used during pregnancy or breastfeeding?
A: No, this combination is contraindicated during pregnancy and breastfeeding.
Q5: What are the major drug interactions?
A: Significant interactions can occur with alcohol, anticoagulants, anticonvulsants, metoclopramide, and other medications containing paracetamol or caffeine.
Q6: What precautions should I take when prescribing this medication to elderly patients?
A: Start with the lowest effective dose and monitor closely for adverse effects due to potential age-related decline in liver and kidney function.
A: Yes, contraindications include severe liver or kidney disease, heart disease, hypertension, peptic ulcers, and alcoholism.
Q8: What should I advise my patients regarding lifestyle considerations while taking this medication?
A: Advise patients to limit caffeine intake from other sources, avoid alcohol, and refrain from driving or operating machinery if dizziness or drowsiness occurs.
Q9: How does caffeine contribute to the effectiveness of this combination?
A: Caffeine enhances paracetamol absorption, reduces its metabolism, acts as a stimulant to counteract drowsiness, and constricts blood vessels, potentially contributing to headache relief.
