MECLOFENAMATE SODIUM (meclofenamate sodium)

There are 6 contraindications. Absolute contraindication.

Contraindication List
Aspirin exacerbated respiratory disease
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
History of roux-en-Y gastric bypass
Post-operative from CABG surgery
Pregnancy

There are 9 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Acute myocardial infarction
Alcohol use disorder
Gastrointestinal hemorrhage
Gastrointestinal ulcer
Increased risk of bleeding
Kidney disease with likely reduction in glomerular filtration rate (GFr)
Peptic ulcer
Systemic mastocytosis
Tobacco smoker

There are 5 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Anemia
Chronic heart failure
Disease of liver
Hypertension
Peripheral edema

There are 51 severe adverse reactions.

More Frequent	Less Frequent
Allergic dermatitis Skin rash	Aphthous stomatitis Body fluid retention Edema Esophageal ulcer Gastric ulcer Gastrointestinal ulcer Peptic ulcer Pruritus of skin Tinnitus Urticaria

Rare/Very Rare

Abnormal hepatic function tests Acute myocardial infarction Agranulocytosis Altered mental status Anaphylaxis Anemia Bloody stools Bloody vomit Blurred vision Cerebrovascular accident Colitis Conjunctivitis Depression Diplopia Drug-induced hepatitis Dry eye Eosinophilia Erythema multiforme Erythema nodosum Exfoliative dermatitis Gastrointestinal hemorrhage Gastrointestinal perforation Hemolytic anemia Hepatitis Hyperkalemia Hypertension Jaundice Kidney disease with reduction in glomerular filtration rate (GFr) Leukopenia Lupus-like syndrome Mood changes Nephrotoxicity Neutropenic disorder Peripheral neuropathy Renal failure Stevens-johnson syndrome Thrombocytopenic disorder Toxic epidermal necrolysis Visual changes

There are 16 less severe adverse reactions.

More Frequent	Less Frequent
Diarrhea Dizziness Flatulence Headache disorder Heartburn Nausea	Anorexia Constipation Gastric acid hypersecretory conditions Mouth irritation Xerostomia

Rare/Very Rare
Acute abdominal pain Dysgeusia Fatigue Insomnia Palpitations

Use of NSAIAs during pregnancy at about 30 weeks of gestation or later can cause premature closure of the fetal ductus arteriosus, and use at about 20 weeks of gestation or later has been associated with fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, use of NSAIAs should be avoided in pregnant women at about 30 weeks of gestation or later; if NSAIA therapy is necessary between about 20 and 30 weeks of gestation, the lowest effective dosage and shortest possible duration of treatment should be used. Monitoring of amniotic fluid volume via ultrasound examination should be considered if the duration of NSAIA treatment exceeds 48 hours; if oligohydramnios occurs, the drug should be discontinued and follow-up instituted according to clinical practice.

Pregnant women should be advised to avoid use of NSAIAs beginning at 20 weeks' gestation unless otherwise advised by a clinician; they should be informed that NSAIAs should be avoided beginning at 30 weeks' gestation because of the risk of premature closure of the fetal ductus arteriosus and that monitoring for oligohydramnios may be necessary if NSAIA therapy is required for longer than 48 hours' duration between about 20 and 30 weeks of gestation. Known effects of NSAIAs on the human fetus during the third trimester of pregnancy include prenatal constriction of the ductus arteriosus, tricuspid incompetence, and pulmonary hypertension; nonclosure of the ductus arteriosus during the postnatal period (which may be resistant to medical management); and myocardial degenerative changes, platelet dysfunction with resultant bleeding, intracranial bleeding, renal dysfunction or renal failure, renal injury or dysgenesis potentially resulting in prolonged or permanent renal failure, oligohydramnios, GI bleeding or perforation, and increased risk of necrotizing enterocolitis. Fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment has been observed, on average, following days to weeks of maternal NSAIA use, although oligohydramnios has been observed infrequently as early as 48 hours after initiation of NSAIA therapy.

Oligohydramnios is often, but not always, reversible (generally within 3-6 days) following discontinuance of NSAIA therapy. Complications of prolonged oligohydramnios may include limb contracture and delayed lung maturation. A limited number of case reports have described maternal NSAIA use and neonatal renal dysfunction, in some cases irreversible, without oligohydramnios.

Some cases of neonatal renal dysfunction have required treatment with invasive procedures such as exchange transfusion or dialysis. Deaths associated with neonatal renal failure have been reported. Methodologic limitations of these postmarketing studies and case reports include lack of a control group; limited information regarding dosage, duration, and timing of drug exposure; and concomitant use of other drugs.

These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAIA use. Available data on neonatal outcomes generally involved preterm infants, and the extent to which certain reported risks can be generalized to full-term infants is uncertain. Animal reproduction studies in rats and rabbits have not demonstrated evidence of developmental abnormalities with meclofenamate.

Animal data indicate that prostaglandins have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, inhibitors of prostaglandin synthesis, such as meclofenamate, were associated with increased pre- and post-implantation losses. Prostaglandins also have an important role in fetal kidney development.

In animal studies, inhibitors of prostaglandin synthesis impaired kidney development at clinically relevant doses. The effects of meclofenamate sodium on labor and delivery are unknown. In studies in rats, drugs that inhibit prostaglandin synthesis, including NSAIAs, increased the incidence of dystocia, delayed parturition, and decreased pup survival.

Meclofenamic acid is distributed in trace amounts into human milk. In suckling rodents, the drug interferes with normal development before weaning. Because of its effect in rodents and possible adverse effects secondary to inhibition of prostaglandin synthesis in neonates, the manufacturers recommend that meclofenamate sodium not be used in nursing women and a decision should be made to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

No enhanced Geriatric Use information available for this drug.