Meclofenamic acid

Meclofenamic acid is a Cyclooxygenase-2 (COX-2) inhibitor / non-steroidal anti-inflammatory drug (NSAIDs) belonging to the class Analgesic.

Meclofenamic acid is an NSAID used to treat mild to moderate pain for no more than a week, and primary dysmenorrhea.

Meclofenamic acid is rapidly absorbed after oral administration. The apparent volume of distribution of Meclofenamic acid is 9.1 to 43.2 L. Meclofenamic acid is Greater than 99% bound to plasma proteins over a wide drug concentration range. Meclofenamate acid is Primarily excreted via urine (70%; primarily as metabolites); feces (30%).

Meclofenamic acid Shows side effects like Diarrhea, constipation, gas, sores in the mouth, headache, ringing in the ears, blurred vision, unexplained weight gain, fever, blisters, rash, itching, hives, swelling of the eyes, face, lips, tongue, throat, arms, hands, feet, ankles, or lower legs, hoarseness, difficulty breathing or swallowing, yellowing of the skin or eyes, excessive tiredness, unusual bleeding or bruising, lack of energy, nausea, loss of appetite, pain in the upper right part of the stomach, flu-like symptoms, pale skin, fast heartbeat, cloudy, discoloured, or bloody urine, back pain, difficult or painful urination.

Meclofenamic acid is available in the form of an Oral Capsule.

Meclofenamic acid is available in India, US, UK, Singapore, Canada, Germany, France, Italy, Spain, and Australia.

Meclofenamic acid is Analgesic a belonging to the class Cyclooxygenase-2 (COX-2) inhibitor / non-steroidal anti-inflammatory drug (NSAIDs).

Meclofenamic acid binds the prostaglandin synthetase receptors COX-1 and COX-2, inhibiting the action of prostaglandin synthetase. As these receptors have a role as a major mediator of inflammation and/or a role for proteinoid signaling in activity-dependent plasticity, the symptoms of pain are temporarily reduced.

The effect of Meclofenamic acid and its duration of action is not clinically established.

The Tmax of Meclofenamic acid is approximately 2-4 hours.

Meclofenamic acid is available in the form of an Oral Capsule.

Meclofenamic acid Capsule is taken orally usually in divided dose.

Meclofenamic acid is an NSAID used to treat mild to moderate pain, primary dysmenorrhea, heavy menstrual blood loss, rheumatoid arthritis, and osteoarthritis.

Meclofenamic acid is a Cyclooxygenase-2 (COX-2) inhibitor / non-steroidal anti-inflammatory drug (NSAIDs) belonging to the class Analgesic.

Meclofenamic acid was found to inhibit prostaglandin synthesis and to compete for binding at the prostaglandin receptor site.

Meclofenamic acid is approved for use in the following clinical indications

• Meclofenamate sodium is indicated for the relief of mild to moderate pain.
• Meclofenamate sodium is also indicated for treating primary dysmenorrhea and for treating idiopathic heavy menstrual blood loss.
• Meclofenamate sodium is also indicated for relief of the signs and symptoms of acute and chronic rheumatoid arthritis and osteoarthritis.

• Abnormal uterine bleeding, nonacute

Oral: 500 mg 3 times daily or 500 mg once followed by 250 mg 4 times daily. Begin at the first sign of menses and continue for 2 to 3 days or until cessation of bleeding; maximum dose: 1.5 g/day.

• Dysmenorrhea, primary

Oral: Initial: 500 mg beginning at the onset of bleeding and associated symptoms, followed by 250 mg every 6 hours or 500 mg 3 times daily; usually not to exceed 3 days.

• Pain, mild to moderate

Oral: Initial: 500 mg, then 250 mg every 6 hours as needed; usually not to exceed 1 week.

Meclofenamic acid is available in various strengths as 50 mg; 100 mg.

Meclofenamic acid is available in the form of Oral Capsule.

• Dosage Adjustment in Kidney Patient

eGFR 30 to <60 mL/minute/1.73 m²: Temporarily discontinue in patients with intercurrent disease that increases risk of acute kidney injury.

eGFR <30 mL/minute/1.73 m²: Avoid use.

• Dosage Adjustment in Hepatic impairment Patient

Use with caution in patients with hepatic impairment. Patients with advanced hepatic disease are at an increased risk of GI bleeding and kidney failure with NSAIDs.

Meclofenamic acid is contraindicated in patients with

• Meclofenamate sodium should not be used in patients who have previously exhibited hypersensitivity to it.
• Because the potential exists for cross-sensitivity to aspirin or other non-steroidal anti-inflammatory drugs, meclofenamate sodium should not be given to patients in whom these drugs induce symptoms of bronchospasm, allergic rhinitis, or urticaria.

• Anaphylactoid reactions

Even in patients without prior exposure anaphylactoid reactions may occur; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Contraindicated in patients who experience bronchospasm, asthma, rhinitis, or urticaria with nonsteroidal anti-inflammatory drug (NSAID) or aspirin therapy.

• Cardiovascular events

Relative risk appears to be similar in those with and without known cardiovascular disease or risk factors for cardiovascular disease; however, absolute incidence of serious cardiovascular thrombotic events (which may occur early during treatment) was higher in patients with known cardiovascular disease or risk factors and in those receiving higher doses. New-onset hypertension or exacerbation of hypertension may occur (NSAIDs may also impair response to ACE inhibitors, thiazide diuretics, or loop diuretics); may contribute to cardiovascular events; monitor BP; use with caution in patients with hypertension. May cause sodium and fluid retention; use with caution in patients with edema. Avoid use in heart failure. Avoid use in patients with recent MI unless benefits outweigh risk of cardiovascular thrombotic events. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk.

• CNS effects

May cause drowsiness, dizziness, blurred vision, and other neurologic effects, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).

• Drug reaction with eosinophilia and systemic symptoms

Potentially serious, sometimes fatal, drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity reactions, has been reported with NSAIDs. Monitor for signs and symptoms (eg, fever, rash, lymphadenopathy, eosinophilia) in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis). Early symptoms of hypersensitivity reaction (eg, lymphadenopathy, fever) may occur without rash; discontinue therapy and further evaluate if DRESS is suspected.

• GI events

Avoid use in patients with active GI bleeding. In patients with a history of acute lower GI bleeding, avoid use of non-aspirin NSAIDs, especially if due to angioectasia or diverticulosis. Use caution with a history of GI ulcers, concurrent therapy known to increase the risk of GI bleeding (eg, aspirin, anticoagulants and/or corticosteroids, selective serotonin reuptake inhibitors), advanced hepatic disease, coagulopathy, smoking, use of alcohol, or in the elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with aspirin, a substantial increase in the risk of GI complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended.

• Hematologic effects

Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Anemia may occur; patients on long-term NSAID therapy should be monitored for anemia. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).

• Hepatic effects

Transaminase elevations have been reported with use; closely monitor patients with any abnormal LFT. Rare (sometimes fatal ) severe hepatic reactions (eg, fulminant hepatitis, hepatic necrosis, hepatic failure) have occurred with NSAID use; discontinue immediately if clinical signs or symptoms of hepatic disease develop or if systemic manifestations occur.

• Hyperkalemia

NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE-inhibitors). Monitor potassium closely.

• Renal effects

NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow, which may cause renal decompensation (usually reversible). Patients with impaired renal function, dehydration, hypovolemia, heart failure, hepatic impairment, those taking diuretics and ACE inhibitors, and the elderly are at greater risk of renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Long-term NSAID use may result in renal papillary necrosis and other renal injury.

• Skin reactions

NSAIDs may cause potentially fatal serious skin adverse events including drug reaction with eosinophilia and systemic symptoms, exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis; may occur without warning; discontinue use at first appearance of skin rash (or any other hypersensitivity).

• Asthma

Contraindicated in patients with aspirin-sensitive asthma; severe and potentially fatal bronchospasm may occur. Use caution in patients with other forms of asthma.

• Gastric ulceration: Avoid chronic use of oral nonselective NSAIDs after bariatric surgery; development of anastomotic ulcerations/perforations may occur. Short-term use of celecoxib or IV ketorolac are recommended as part of a multimodal pain management strategy for postoperative pain.
• Coronary artery bypass graft surgery

The risk of MI and stroke may be increased with use following CABG surgery.

Trace amounts of meclofenamic acid are excreted in human milk. Because of the possible adverse effects of prostaglandin-inhibiting drugs on neonates, meclofenamate sodium is not recommended for nursing women.

Pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Common

• Diarrhea, nausea, vomiting, Edema, Pruritus, skin rash, urticaria, Abdominal pain, anorexia, constipation, flatulence, heartburn, peptic ulcer, stomatitis, Dizziness, headache, Tinnitus, Erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, Colitis, gastrointestinal hemorrhage, gastrointestinal perforation, gastrointestinal ulcer, Agranulocytosis, decreased hematocrit, decreased hemoglobin, eosinophilia, hemolytic anemia, immune thrombocytopenia, leukopenia, neutropenia, Abnormal hepatic function tests, cholestatic jaundice, Serum sickness, Lupus erythematosus, Renal failure syndrome.

Rare

• Acute myocardial infarction, cerebrovascular accident, coronary thrombosis, hypertension, Toxic epidermal necrolysis, Gastrointestinal inflammation, Hepatotoxicity ,Drug rash with eosinophilia and systemic symptoms.

• 5-Aminosalicylic Acid Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of 5-Aminosalicylic Acid Derivatives.
• Abrocitinib: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the antiplatelet effect of Abrocitinib.
• Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties.
• Acemetacin: May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents.
• Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties.
• Alcohol (Ethyl): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of GI bleeding may be increased with this combination.
• Aliskiren: Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Aliskiren. Nonsteroidal Anti-Inflammatory Agents may enhance the nephrotoxic effect of Aliskiren.
• Bisphosphonate Derivatives: Nonsteroidal Anti-Inflammatory Agents may enhance the adverse/toxic effect of Bisphosphonate Derivatives. Both an increased risk of gastrointestinal ulceration and an increased risk of nephrotoxicity are of concern.
• Caplacizumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Caplacizumab. Specifically, the risk of bleeding may be increased. Management: Avoid coadministration of caplacizumab with antiplatelets if possible. If coadministration is required, monitor closely for signs and symptoms of bleeding. Interrupt use of caplacizumab if clinically significant bleeding occurs.
• Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased.
• Naftazone: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents.
• Nonsteroidal Anti-Inflammatory Agents: May enhance the adverse/toxic effect of other Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk for gastrointestinal toxicity is increased.
• Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of gastrointestinal (GI) toxicity is increased. Management: Coadministration of systemic nonsteroidal anti-inflammatory drugs (NSAIDs) and topical NSAIDs is not recommended. If systemic NSAIDs and topical NSAIDs, ensure the benefits outweigh the risks and monitor for increased NSAID toxicities.
• Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.
• Rivaroxaban: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: A comprehensive risk to benefit assessment should be done for all patients before any concurrent use of rivaroxaban and nonsteroidal anti-inflammatory drugs (NSAIDs). If combined, monitor patients extra closely for signs and symptoms of bleeding.
• Salicylates: Nonsteroidal Anti-Inflammatory Agents (Nonselective) may enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Management: Nonselective NSAIDs may reduce aspirin's cardioprotective effects. Administer ibuprofen 30-120 minutes after immediate-release aspirin, 2 to 4 hours after extended-release aspirin, or 8 hours before aspirin.
• Selective Serotonin Reuptake Inhibitors: May enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider alternatives to NSAIDs. Monitor for evidence of bleeding and diminished antidepressant effects. It is unclear whether COX-2-selective NSAIDs reduce risk.
• Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties.

The common side effects of Meclofenamic acid include the following

• Common side effects

Diarrhea, constipation, gas, sores in the mouth, headache, ringing in the ears,

• Rare side effects

Blurred vision, unexplained weight gain, fever, blisters, rash, itching, hives, swelling of the eyes, face, lips, tongue, throat, arms, hands, feet, ankles, or lower legs, hoarseness, difficulty breathing or swallowing, yellowing of the skin or eyes, excessive tiredness, unusual bleeding or bruising, lack of energy, nausea, loss of appetite, pain in the upper right part of the stomach, flu-like symptoms, pale skin, fast heartbeat, cloudy, discolored, or bloody urine, back pain, difficult or painful urination.

• Pregnancy

Pregnancy Category C

Meclofenamate sodium, like aspirin and other non-steroidal anti-inflammatory drugs, causes fetotoxicity, minor skeletal malformations, e.g., supernumerary ribs, and delayed ossification in rodent reproduction trials, but no major teratogenicity. Similarly, it prolongs gestation and interferes with parturition and with normal development of young before weaning. Meclofenamate sodium is not recommended for use during pregnancy, particularly in the 1st and 3rd trimesters based on these animal findings. There are, however, no adequate and well controlled studies in pregnant women.

• Nursing Mothers

Trace amounts of meclofenamic acid are excreted in human milk. Because of the possible adverse effects of prostaglandin-inhibiting drugs on neonates, meclofenamate sodium is not recommended for nursing women.

• Pediatric Use

Safety and effectiveness in children below the age of 14 have not been established.

• Pharmacodynamic

Meclofenamic acid is a nonsteroidal agent which has demonstrated anti-inflammatory, analgesic, and antipyretic activity.

• Pharmacokinetics

Absorption

Meclofenamic acid is rapidly absorbed after oral administration.

Distribution

Apparent volume of distribution of Meclofenamic acid is 9.1 to 43.2 L. Meclofenamic acid is Greater than 99% bound to plasma proteins over a wide drug concentration range.

Metabolism and Excretion

Meclofenamate acid is Primarily excreted via urine (70%; primarily as metabolites); feces (30%)

• https://www.rxlist.com/meclofenamate-drug.htm#overdosage
• https://reference.medscape.com/drug/meclofenamate-1000133
• https://medlineplus.gov/druginfo/meds/a682287.html#:~:text=Meclofenamate is used to relieve,the lining of the joints
• https://go.drugbank.com/drugs/DB00939
• https://www.drugs.com/mtm/meclofenamate.html
• https://www.uptodate.com/contents/meclofenamate-drug-information?search=meclofenamate&source=panel_search_result&selectedTitle=1~6&usage_type=panel&kp_tab=drug_general&display_rank=1