Meclofenamate

Mechanism of Action

Nonsteroidal anti-inflammatory drug (NSAID) that elicits anti-inflammatory, analgesic, and antipyretic activity

Inhibits synthesis of prostaglandins in body tissues by inhibiting at least 2 cyclo-oxygenase (COX) isoenzymes, COX-1 and COX-2

May inhibit chemotaxis, alter lymphocyte activity, decrease proinflammatory cytokine activity, and inhibit neutrophil aggregation; these effects may contribute to anti-inflammatory activity

Absorption

Peak plasma time: 0.5-2 hr

Peak plasma concentration: 4.8 mcg/mL

Food decreases rate and extent of absorption (bioavailability decreased by 26%; Cmax decreased 4-fold; time to Cmax delayed by 3 hr)

Distribution

Vd: 23.3 L

Metabolism

Extensively metabolized to an active metabolite (Metabolite I; 3-hydroxymethyl metabolite of meclofenamic acid) and at least 6 other less well-characterized minor metabolites

Elimination

Half-life: 0.8-5.3 hr (single-dose); 0.8-2.1 hr (TID x14 days); 15 hr (Metabolite I)

Clearance: 206 mL/min

Excretion: 70% urine; ~30% feces via biliary excretion

• Rheumatoid Arthritis (RA)

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© Meclofenamate Patient Information is supplied by Cerner Multum, Inc. and Meclofenamate Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

Meclofenamate is a nonsteroidal anti-inflammatory drug (NSAID). Meclofenamate works by reducing hormones that cause inflammation and pain in the body.

Meclofenamate is used to treat fever or mild to moderate pain in adults. Meclofenamate is also used to relieve symptoms of osteoarthritis or rheumatoid arthritis in adults, and juvenile arthritis in children who are at least 14 years old.

Meclofenamate is also used to treat menstrual pain or heavy menstrual bleeding.

Meclofenamate is sometimes used long-term to treat symptoms of ankylosing spondylitis, gouty arthritis, or shoulder pain caused by bursitis or tendinitis.

Meclofenamate may also be used for purposes not listed in this medication guide.

Meclofenamate can increase your risk of fatal heart attack or stroke, especially if you use it long term or take high doses, or if you have heart disease. Do not use this medicine just before or after heart bypass surgery (coronary artery bypass graft, or CABG).

Meclofenamate may also cause stomach or intestinal bleeding, which can be fatal. These conditions can occur without warning while you are using meclofenamate, especially in older adults.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include decreased urination, confusion, behavior changes, agitation, or seizure (convulsions).

Get emergency medical help if you have signs of an allergic reaction: sneezing, runny or stuffy nose; wheezing or trouble breathing; hives; swelling of your face, lips, tongue, or throat.

Get emergency medical help if you have signs of a heart attack or stroke: chest pain spreading to your jaw or shoulder, sudden numbness or weakness on one side of the body, slurred speech, feeling short of breath.

Stop using meclofenamate and call your doctor at once if you have:

• the first sign of any skin rash, no matter how mild;

• shortness of breath (even with mild exertion);

• swelling or rapid weight gain;

• signs of stomach bleeding--bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds;

• liver problems--nausea, upper stomach pain, itching, tired feeling, flu-like symptoms, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

• kidney problems--little or no urinating, painful or difficult urination, swelling in your feet or ankles, feeling tired or short of breath;

• low red blood cells (anemia)--pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating; or

• severe skin reaction--fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Older adults may be more likely to have symptoms of stomach bleeding.

Common side effects may include:

• nausea, stomach pain; or

• diarrhea.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take meclofenamate or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to meclofenamate. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Incidence Greater Than 1%

The following adverse reactions were observed in clinical trials and included observations from more than 2,700 patients, 594 of whom were treated for one year and 248 for at least 2 years.

The most frequently reported adverse reactions associated with Meclofenamate sodium involve the gastrointestinal system. In controlled studies of up to 6 months duration, these disturbances occurred in the following decreasing order of frequency with the approximate incidences in parentheses: diarrhea (10% to 33%), nausea with or without vomiting (11%), other gastrointestinal disorders (10%), and abdominal pain*. In long-term uncontrolled studies of up to 4 years duration, one third of the patients had at least one episode of diarrhea some time during Meclofenamate sodium therapy.

In approximately 4% of the patients in controlled studies, diarrhea was severe enough to require discontinuation of Meclofenamate sodium. The occurrence of diarrhea is dose related, generally subsides with dose reduction, and clears with termination of therapy. The incidence of diarrhea in patients with osteoarthritis is generally lower than that reported in patients with rheumatoid arthritis.

Other reactions less frequently reported were pyrosis*, flatulence*, anorexia, constipation, stomatitis, and peptic ulcer. The majority of the patients with peptic ulcer had either a history of ulcer disease or were receiving concomitant anti-inflammatory drugs, including corticosteroids which are known to produce peptic ulceration.

Cardiovascular: edema

Dermatologic: rash*, urticaria, pruritus

Central Nervous System: headache*, dizziness*

Special Senses: tinnitus

* Incidence between 3% and 9%. Those reactions occurring in 1% to 3% of patients are not marked with an asterisk.

Incidence Less Than 1%Probably Causally Related

The following adverse reactions were reported less frequently than 1% during controlled clinical trials and through voluntary reports since marketing. The probability of a causal relationship exists between the drug and these adverse reactions.

Gastrointestinal: bleeding and/or perforation with or without obvious ulcer formation, colitis, cholestatic jaundice

Renal: renal failure

Hematologic: neutropenia, thrombocytopenic purpura, leukopenia, agranulocytosis, hemolytic anemia, eosinophilia, decrease in hemoglobin and/or hematocrit

Dermatologic: erythema multiforme, Stevens-Johnson Syndrome, exfoliative dermatitis

Hepatic: alteration of liver function tests

Allergic: lupus and serum sickness-like symptoms

Incidence Less Than 1%Causal Relationship Unknown

Other reactions have been reported but under conditions where a causal relationship could not be established. However, in these rarely reported events, that possibility cannot be excluded. Therefore, these observations are listed to alert physicians.

Cardiovascular: palpitations

Central Nervous System: malaise, fatigue, paresthesia, insomnia, depression

Special Senses: blurred vision, taste disturbances, decreased visual acuity, temporary loss of vision, reversible loss of color vision, retinal changes including macular fibrosis, macular and perimacular edema, conjunctivitis, iritis

Renal: nocturia

Gastrointestinal: paralytic ileus

Dermatologic: erythema nodosum, hair loss

2 to 4 hours

Half-Life Elimination

Meclofenamate sodium: 0.8 to 2.1 hours; Metabolite I: ~15 hours

Protein Binding

>99%

Refer to adult dosing. Use with caution; initiate dose at lower end of the dosing range.

Concerns related to adverse effects:

• 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 NSAID or aspirin therapy.

• Cardiovascular events: [US Boxed Warning]: NSAIDs cause an increased risk of serious (and potentially fatal) adverse cardiovascular thrombotic events, including MI and stroke. Risk may occur early during treatment and may increase with duration of use. 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 blood pressure; 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 (ACCF/AHA [Yancy 2013]). 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).

• GI events: [US Boxed Warning]: NSAIDs cause increased risk of serious GI inflammation, ulceration, bleeding, and perforation (may be fatal); elderly patients and patients with history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events. These events may occur at any time during therapy and without warning. 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 (Strate 2016). 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 (Bhatt 2008).

• 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 exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); may occur without warning; discontinue use at first appearance of skin rash (or any other hypersensitivity).

Disease-related concerns:

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

• Coronary artery bypass graft surgery: [US Boxed Warning]: Use is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Risk of MI and stroke may be increased with use following CABG surgery.

• Hepatic impairment: Use with caution in patients with hepatic impairment. Patients with advanced hepatic disease are at an increased risk of GI bleeding with NSAIDs.

• Renal impairment: Use with caution in patients with renal impairment. Avoid use in patients with advanced renal disease; monitor renal function closely if therapy must be initiated. Discontinue use if clinical signs and symptoms renal impairment develop or if systemic manifestations occur.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Elderly patients are at greater risk for serious GI, cardiovascular, and/or renal adverse events. Use with caution; initiate dose at the lower end of the dosing range.

Other warnings/precautions:

• Surgical/dental procedures: Withhold for at least 4 to 6 half-lives prior to surgical or dental procedures.

Consult your pharmacist.

How to use Meclofenamate Powder

Consult your pharmacist.

Consult your pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Consult your pharmacist.

200 mg to 400 mg orally per day in 3 to 4 divided doses
Maximum dose: 400 mg/day

Comments:
-Initiate therapy at a lower dose and increase as necessary to improve clinical response.
-Dosages should be individualized for each patient based on the severity of symptoms and clinical response.
-Improvement may be seen within a few days of beginning therapy, however, 2 to 3 weeks of treatment may be needed to obtain optimum therapeutic benefit.

Use: For the relief of signs and symptoms of osteoarthritis and rheumatoid arthritis

-Renal dysfunction: Use with caution.
-Advanced renal disease: Not recommended; if treatment is necessary, close monitoring of renal function is advised.

Data not available

Summary of Use during Lactation

Because no information is available on the use of meclofenamate during breastfeeding, other agents may be preferred, especially while nursing a newborn or preterm infant.

Drug Levels

Maternal Levels. Relevant published information was not found as of the revision date.

Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

Acetaminophen, Celecoxib, Flurbiprofen, Ibuprofen, Indomethacin, Naproxen, Piroxicam

References