Usage
Mefenamic acid + paracetamol is a combination medication primarily prescribed for the short-term management of mild to moderate pain, including pain associated with:
- Headache (including migraine)
- Toothache
- Musculoskeletal pain (such as muscle aches, back pain)
- Postoperative pain
- Menstrual pain (dysmenorrhea)
- Fever
Pharmacological Classification:
- Analgesic (pain reliever)
- Antipyretic (fever reducer)
- Nonsteroidal anti-inflammatory drug (NSAID) - specifically mefenamic acid
Mechanism of Action:
This combination exerts its effects through two distinct mechanisms:
- Mefenamic Acid: Inhibits cyclooxygenase (COX) enzymes, which are responsible for producing prostaglandins, substances that mediate pain and inflammation.
- Paracetamol: The exact mechanism is not fully understood, but it is believed to inhibit COX enzymes predominantly in the central nervous system, reducing pain and fever. The combination provides synergistic analgesic and antipyretic effects.
Alternate Names
No widely recognized alternate names for the combination exist. However, the individual drugs have other names:
- Mefenamic Acid: Ponstan, Ponstyl
- Paracetamol: Acetaminophen (primarily used in the United States)
How It Works
Pharmacodynamics:
- Mefenamic Acid: Reduces pain and inflammation by inhibiting prostaglandin synthesis.
- Paracetamol: Reduces pain and fever through central COX inhibition, and it may also have some effects on serotonergic and endocannabinoid systems.
Pharmacokinetics:
- Mefenamic Acid:
- Absorption: Well-absorbed orally.
- Metabolism: Metabolized in the liver.
- Elimination: Excreted primarily in the urine, with some elimination in the feces.
- Paracetamol:
- Absorption: Rapidly absorbed orally.
- Metabolism: Primarily metabolized in the liver.
- Elimination: Excreted in the urine, primarily as conjugates.
Mode of Action:
Both drugs primarily act by inhibiting COX enzymes, reducing prostaglandin production. Mefenamic acid is a non-selective COX inhibitor, while paracetamol’s COX inhibition is thought to be more selective for the central nervous system.
Dosage
Standard Dosage
Adults:
Initial dose: Mefenamic acid 500 mg + paracetamol 325-500 mg, followed by 250 mg of mefenamic acid + 325-500 mg of paracetamol every 6 hours as needed. The maximum daily dose for mefenamic acid is 1500 mg and for paracetamol it varies depending on the preparation, consult specific product guidelines. Do not exceed seven days of continuous use unless directed by a physician.
Children:
Use in children under 12 years of age is generally not recommended unless under the guidance of a healthcare professional. Dosages in children are weight-based and should be carefully calculated. Always consult pediatric dosage guidelines or a pediatrician for specific recommendations.
Special Cases:
- Elderly Patients: Use with caution and at the lowest effective dose due to increased risk of adverse effects.
- Patients with Renal Impairment: Use with caution; dose adjustment may be necessary. Severe renal impairment may be a contraindication.
- Patients with Hepatic Dysfunction: Use with caution; dose adjustment may be necessary. Severe hepatic impairment may be a contraindication.
- Patients with Comorbid Conditions: Careful consideration is required in patients with conditions such as cardiovascular disease, gastrointestinal ulcers, or bleeding disorders.
Clinical Use Cases Clinical use cases and dosage adjustments are similar to the standard dosage guidelines. Special considerations for specific settings (Intubation, Surgical Procedures, Mechanical Ventilation, ICU Use, Emergency Situations) may warrant expert consultation.
Dosage Adjustments Adjustments are made based on individual patient factors like renal or hepatic dysfunction.
Side Effects
Common Side Effects:
- Nausea
- Vomiting
- Diarrhea
- Abdominal pain
- Indigestion
- Dizziness
- Headache
Rare but Serious Side Effects:
- Gastrointestinal bleeding or ulcers
- Allergic reactions (skin rash, itching, swelling)
- Liver damage (hepatotoxicity) - primarily associated with paracetamol overuse
- Kidney damage
Long-Term Effects:
Prolonged use, especially of paracetamol at high doses, can increase the risk of liver and kidney damage.
Adverse Drug Reactions (ADR):
- Stevens-Johnson Syndrome (rare)
- Toxic epidermal necrolysis (rare)
Contraindications:
- Hypersensitivity to mefenamic acid or paracetamol
- Active or history of recurrent peptic ulcer disease
- Severe heart failure
- Severe liver or kidney impairment
- Asthma exacerbated by aspirin or other NSAIDs
- Last trimester of pregnancy
- Perioperative pain in the setting of coronary artery bypass graft (CABG) surgery
Drug Interactions:
- Anticoagulants (warfarin)
- Other NSAIDs (aspirin, ibuprofen)
- Antihypertensives
- Lithium
- Methotrexate
- Cyclosporine
Pregnancy and Breastfeeding:
- Pregnancy: Contraindicated in the third trimester. Use during the first and second trimesters should be only if clearly needed and under careful medical supervision.
- Breastfeeding: Mefenamic acid is excreted in breast milk. Use with caution and only if clearly needed. Paracetamol is generally considered compatible with breastfeeding.
Drug Profile Summary
- Mechanism of Action: Inhibits COX enzymes, reducing prostaglandin synthesis (mefenamic acid); central COX inhibition with potential effects on other pathways (paracetamol).
- Side Effects: Nausea, vomiting, diarrhea, GI upset, dizziness, headache; rarely, GI bleeding, allergic reactions, liver or kidney damage.
- Contraindications: Hypersensitivity, peptic ulcer disease, severe heart failure, severe liver/kidney impairment, aspirin-exacerbated asthma, third-trimester pregnancy, CABG surgery.
- Drug Interactions: Anticoagulants, other NSAIDs, antihypertensives, lithium, methotrexate, cyclosporine.
- Pregnancy & Breastfeeding: Contraindicated in third-trimester pregnancy; use with caution in breastfeeding.
- Dosage: See dosage section.
- Monitoring Parameters: Monitor for signs of GI bleeding, liver or kidney dysfunction, and allergic reactions.
Popular Combinations
Mefenamic acid and paracetamol are sometimes combined with other analgesics such as codeine or caffeine to enhance pain relief. However, this is not universally recommended due to added side effects and interactions.
Precautions
- Pre-existing medical conditions (renal/hepatic dysfunction, cardiovascular disease, GI disorders) require careful evaluation.
- Pregnancy: Use with caution in the first and second trimesters, contraindicated in the third.
- Breastfeeding: Mefenamic acid is excreted in breast milk; use with caution. Paracetamol is generally compatible.
- Children and Elderly: Use with caution and at lower doses.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Mefenamic Acid + Paracetamol?
A: See the dosage section.
Q2: Can mefenamic acid + paracetamol be used in children?
A: Not generally recommended for children under 12 years unless specifically directed by a physician. Pediatric dosages are weight-based.
Q3: What are the serious side effects to watch out for?
A: Gastrointestinal bleeding, allergic reactions, liver damage (especially with paracetamol overdose), kidney damage.
Q4: Can this combination be used during pregnancy?
A: Contraindicated in the third trimester. Use with caution during the first and second trimesters only if the benefits outweigh the risks.
Q5: What are the common drug interactions?
A: Anticoagulants, other NSAIDs, antihypertensives, lithium, methotrexate, cyclosporine.
Q6: How does this combination work?
A: Mefenamic acid and paracetamol both inhibit COX enzymes, reducing prostaglandin production, but through slightly different mechanisms.
Q7: What should patients avoid while taking this medication?
A: Alcohol, other NSAIDs, and medications listed under drug interactions. Patients should also consult their doctor before starting any new medications or supplements.
Q8: What are the symptoms of an overdose?
A: Paracetamol overdose can lead to liver damage, while mefenamic acid overdose may cause symptoms like nausea, vomiting, abdominal pain, and drowsiness. Seek immediate medical attention if overdose is suspected.
Q9: Can mefenamic acid + paracetamol be used for long-term pain management?
A: No. This combination is generally recommended for short-term use (up to 7 days unless otherwise directed by a physician).
Q10: What are the alternatives if this combination is not suitable?
A: Other pain relievers such as other NSAIDs or opioids, depending on the type and severity of pain, may be considered.
