Mefenamic acid

OVERVIEW

Mefenamic acid is a nonsteroidal anti-inflammatory drug (NSAID) used primarily for the treatment of mild to moderate pain, including dysmenorrhea (menstrual cramps). It belongs to the anthranilic acid derivative class of NSAIDs, which also includes other drugs such as flufenamic acid and tolfenamic acid. Mefenamic acid is available in capsule form and is usually prescribed for short-term use due to its potential side effects.

DOSAGE

For Pain Relief:

Initial Dose: 500 mg orally once
Following Dose: 250 mg every 6 hours as needed
Duration: Typically not to exceed 1 week

For Dysmenorrhea:

Initial Dose: 500 mg orally once
Following Dose: 250 mg every 6 hours as needed
Duration: Usually 2 to 3 days after bleeding and related symptoms begin

Pediatric Dosage (Ages 14 and Older)

Initial Dose: 500 mg orally once
Following Dose: 250 mg every 6 hours as needed
Duration: Same limits as for adults

Mefenamic Acid – Dosage
Indication	Age Group	Initial Dose	Subsequent Dose	Maximum Duration
Acute Pain	Adults (18 years+)	500 mg orally once	250 mg every 6 hours as needed	Not to exceed 1 week
	Adolescents (14-17)	500 mg orally once	250 mg every 6 hours as needed	Not to exceed 1 week
Dysmenorrhea	Adults (18 years+)	500 mg orally once	250 mg every 6 hours as needed	Usually for 2 to 3 days
	Adolescents (14-17)	500 mg orally once	250 mg every 6 hours as needed	Usually for 2 to 3 days

MECHANISM OF ACTION

Inhibition of Cyclooxygenase Enzymes

COX-1 and COX-2 inhibition: Mefenamic acid inhibits COX-1 and COX-2 enzymes, which are important for the conversion of arachidonic acid to prostaglandins. Prostaglandins are lipid compounds that play an important role in reducing inflammation, pain, and fever, as well as regulating various physiological functions such as hemostasis and gastric mucosal protection.

Competitive and non-competitive inhibition: Research suggests that mefenamic acid acts as a weak competitive inhibitor for COX-2 and a potent non-competitive inhibitor for some other pathways related to prostaglandin synthesis. This dual mechanism may explain its effectiveness in reducing pain and inflammation, as well as highlight the complexity of its interactions with these enzymes.

Reduction of Prostaglandin Synthesis

Relief from pain and inflammation: By inhibiting the COX enzyme, mefenamic acid reduces the production of prostaglandins. This reduction decreases the sensitivity of pain receptors and reduces inflammatory responses, thereby reducing symptoms associated with conditions such as dysmenorrhea, arthritis and post-operative pain.

ADVERSE DRUG REACTIONS

Gastrointestinal Issues:

• Nausea
• Vomiting
• Diarrhea
• Constipation
• Abdominal pain
• Heartburn

Common Reactions:

• Dizziness
• Headaches
• Skin rash or itching
• Tinnitus (ringing in the ears)

Bleeding and Ulcers:

There is an increased risk of gastrointestinal bleeding, peptic ulcers, and gastrointestinal perforation, which can occur without warning. Symptoms include bloody or tarry stools, vomiting blood, and severe abdominal pain.

Cardiovascular Risks:

Possible increase in risk of heart attack, stroke, and heart failure. Symptoms may include chest pain, shortness of breath, swelling in the feet or ankles, and rapid weight gain.

Kidney Damage:

Potential kidney problems, including interstitial nephritis and acute kidney failure. Symptoms include decreased urination, swelling in the feet or ankles, and unusual fatigue.

Liver Damage:

Risk of liver damage, symptoms of which include nausea, fatigue, jaundice (yellowing of the skin/eyes), dark urine, and stomach pain.

Severe Allergic Reactions:

Symptoms include difficulty breathing, swelling of the face or throat, hives, and a specific condition called DRESS (drug reaction with eosinophilia and systemic symptoms), which can affect multiple organs.

Severe Skin Reactions:

Rare but serious skin conditions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be life-threatening. Symptoms can include painful red or purple skin rashes that blister and peel.

DRUG-DRUG INTERACTIONS

Anticoagulants

Impact: Increased risk of bleeding due to synergistic effects on hemostasis.

Recommendation: Monitor for signs of bleeding when used together.

Other NSAIDs and Salicylates

Impact: Increased risk of gastrointestinal toxicity without additional therapeutic benefit.

Recommendation: Avoid concomitant use.

Methotrexate

Impact: May increase methotrexate toxicity by reducing its renal clearance.

Recommendation: Monitor for signs of toxicity during concurrent use.

Lithium

Impact: May increase lithium levels by reducing renal excretion.

Recommendations: Monitor lithium levels closely.

Cyclosporine and Tacrolimus

Impact: Increased risk of nephrotoxicity.

Recommendation: Monitor renal function during concomitant treatment.

Pemetrexed

Impact: May increase risk of myelosuppression and gastrointestinal toxicity.

Recommendations: Monitor for adverse effects, especially in patients with renal impairment.

Antihypertensives

Impact: Mefenamic acid may decrease the effectiveness of these medications and increase the risk of kidney damage.

Recommendations: Monitor blood pressure and kidney function.

Antacids

Impact: May increase mefenamic acid levels, increasing the risk of side effects.

Recommendations: Use with caution; monitor for adverse events.

USE

Pain Relief

• Muscle and Back Pain
• Toothache
• Postoperative Pain

Dysmenorrhea

Menstrual cramps: It is particularly effective in reducing the pain associated with dysmenorrhea (menstrual cramps). Mefenamic acid can be taken at the beginning of menstrual symptoms to help reduce pain.

Menorrhagia

Heavy menstrual bleeding: Mefenamic acid has been shown to be effective in treating menorrhagia or heavy menstrual bleeding. Studies indicate that it may offer similar benefits to other treatments such as the levonorgestrel intrauterine system in managing heavy menstrual flow.

Migraine Prophylaxis

Perimenstrual Migraine: There is evidence supporting the use of mefenamic acid for the prevention of menstrual migraine headaches. Treatment is usually started for the prevention of menstrual migraine headaches and continued during menstruation.

Arthritis

Rheumatoid arthritis and osteoarthritis: Although less common, mefenamic acid can also be used to manage the pain and inflammation associated with rheumatoid arthritis and osteoarthritis.