Mefenamic Acid + Tizanidine

Usage

Mefenamic acid + tizanidine is prescribed for the management of pain associated with muscle spasms and painful menstrual periods (dysmenorrhea).

Pharmacological Classification:

• Mefenamic acid: Non-Steroidal Anti-inflammatory Drug (NSAID)
• Tizanidine: Skeletal Muscle Relaxant, α₂-adrenergic agonist

Mechanism of Action:

Mefenamic acid inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis, thereby decreasing inflammation and pain. Tizanidine acts centrally as an α₂-adrenergic agonist, reducing the release of excitatory neurotransmitters, leading to muscle relaxation and decreased muscle spasm.

Alternate Names

This combination doesn’t have a widely recognized international non-proprietary name (INN). It is often referred to by the names of its components. Brand names include Meftal-MR, Mefedrot MR, and Mefcan TN.

How It Works

Pharmacodynamics:

Mefenamic acid reduces pain and inflammation by inhibiting COX-1 and COX-2 enzymes, which are responsible for prostaglandin synthesis. Tizanidine acts on α₂-adrenergic receptors in the central nervous system, inhibiting the release of excitatory amino acids, leading to a decrease in muscle tone and spasm.

Pharmacokinetics:

• Absorption: Both drugs are well-absorbed orally.
• Metabolism: Mefenamic acid is metabolized in the liver. Tizanidine is primarily metabolized by the cytochrome P450 enzyme CYP1A2.
• Elimination: Both drugs are primarily excreted by the kidneys.

Mode of Action:

Mefenamic acid’s mode of action involves inhibiting COX enzymes, reducing prostaglandin production. These prostaglandins are involved in pain and inflammation pathways. Tizanidine binds to α₂-adrenergic receptors in the central nervous system, leading to a decrease in the release of excitatory neurotransmitters, thereby decreasing muscle tone and spasms.

Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation:

Mefenamic acid inhibits COX-1 and COX-2 enzymes. Tizanidine is an α₂-adrenergic agonist.

Elimination Pathways:

Both drugs are primarily eliminated through renal excretion with some hepatic metabolism. Tizanidine metabolism involves CYP1A2.

Dosage

Standard Dosage

Adults:

One tablet (typically containing 500mg mefenamic acid and 2mg tizanidine) every 6-8 hours as needed for pain, up to a maximum of 3 doses (tablets) in 24 hours. The maximum daily dose of tizanidine is 36mg.

Children:

Not recommended for use in children below 18 years of age.

Special Cases:

• Elderly Patients: Use with caution due to increased risk of adverse effects; consider lower doses and close monitoring.
• Patients with Renal Impairment: Avoid in patients with severe renal impairment. Caution and dose adjustment are needed in patients with mild to moderate renal impairment.
• Patients with Hepatic Dysfunction: Avoid in patients with severe hepatic impairment. Caution and dose adjustment may be needed in patients with mild to moderate hepatic impairment.
• Patients with Comorbid Conditions: Use with caution in patients with cardiovascular disease, gastrointestinal conditions (e.g., peptic ulcers, gastritis), lung diseases, and bleeding disorders.

Clinical Use Cases

This medication is not typically used in the clinical settings described (intubation, surgical procedures, mechanical ventilation, ICU use, emergency situations). It is primarily indicated for the management of pain from muscle spasm and dysmenorrhea.

Dosage Adjustments

Adjust dosage based on patient’s renal and hepatic function, age, and comorbidities. Close monitoring is recommended, especially in elderly patients and those with renal or hepatic impairment.

Side Effects

Common Side Effects

Nausea, vomiting, diarrhea, indigestion, abdominal pain, weakness, dry mouth, dizziness, drowsiness, and hypotension.

Rare but Serious Side Effects

Liver damage, gastrointestinal bleeding or ulcers, heart attack, stroke, allergic reactions, hallucinations, changes in vision, slow heartbeat.

Long-Term Effects

Chronic use of NSAIDs can increase the risk of cardiovascular and gastrointestinal complications. Long-term use of tizanidine can lead to liver damage.

Adverse Drug Reactions (ADR)

Severe allergic reactions, liver injury, gastrointestinal bleeding, Stevens-Johnson syndrome.

Contraindications

Hypersensitivity to mefenamic acid or tizanidine, severe renal or hepatic impairment, active peptic ulcer, gastrointestinal bleeding, third trimester of pregnancy. Concurrent use with potent CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin).

Drug Interactions

CYP1A2 inhibitors (fluvoxamine, ciprofloxacin, zileuton), other CNS depressants (alcohol, opioids, sedatives), anticoagulants (warfarin), other NSAIDs, antihypertensives, oral contraceptives. Alcohol may potentiate drowsiness and increase the risk of gastrointestinal bleeding.

Pregnancy and Breastfeeding

Pregnancy:

Contraindicated in the third trimester. Use with caution in the first and second trimesters only if the potential benefit outweighs the risk to the fetus.

Breastfeeding:

Mefenamic acid is present in breast milk. Tizanidine may also be excreted in breast milk. Caution should be exercised when administering to breastfeeding women. If use is necessary, consider using the lowest effective dose for the shortest duration.

Drug Profile Summary

• Mechanism of Action: Mefenamic acid: COX inhibitor. Tizanidine: α₂-adrenergic agonist.
• Side Effects: Nausea, vomiting, dizziness, drowsiness, hypotension, GI upset, liver damage (rare).
• Contraindications: Hypersensitivity, severe renal/hepatic impairment, active peptic ulcer, 3rd-trimester pregnancy, CYP1A2 inhibitors.
• Drug Interactions: CYP1A2 inhibitors, CNS depressants, anticoagulants, other NSAIDs.
• Pregnancy & Breastfeeding: Use with caution. Contraindicated in the third trimester.
• Dosage: One tablet every 6-8 hours as needed, maximum 3 tablets/day (maximum 36mg tizanidine/day).
• Monitoring Parameters: Liver function tests, renal function, blood pressure, signs of GI bleeding.

Popular Combinations

No popular drug combinations are documented for this specific fixed-dose combination. However, in practice, other medications may be prescribed concomitantly to manage other symptoms or conditions, but cautious assessment of potential interactions is crucial.

Precautions

Screen for allergies, renal/hepatic dysfunction, cardiovascular disease, GI conditions. Avoid alcohol. Caution in pregnant/breastfeeding women, children, and the elderly. May cause drowsiness; avoid driving or operating machinery.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Mefenamic Acid + Tizanidine?

A: One tablet (500mg mefenamic acid/2mg tizanidine) every 6-8 hours as needed, maximum 3 tablets/day. Maximum tizanidine dose is 36mg/day.

Q2: Can this combination be used in children?

A: No, it is not recommended for patients under 18 years of age.

Q3: Is it safe to take this medication during pregnancy?

A: It is contraindicated in the third trimester. Use with caution in the first two trimesters only if the benefit outweighs the risk.

Q4: Can this combination be used while breastfeeding?

A: Use with caution as both drugs can be excreted in breast milk. Consider the lowest effective dose for the shortest duration if use is necessary.

Q5: What are the common side effects?

A: Nausea, vomiting, diarrhea, indigestion, dizziness, drowsiness, dry mouth, hypotension.

Q6: What are the serious side effects to watch out for?

A: Allergic reactions, liver damage, GI bleeding, cardiovascular events.

Q7: What are the drug interactions I should be aware of?

A: CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine), other CNS depressants (alcohol, opioids), anticoagulants.

Q8: Can I drink alcohol while taking this medication?

A: No, alcohol can increase drowsiness and the risk of GI bleeding.

Q9: What should I do if I miss a dose?

A: Take the missed dose as soon as you remember, unless it is almost time for your next dose. Do not double the dose to catch up.

Q10: What should I do in case of an overdose?

A: Immediately seek medical attention.