DICLOFENAC SODIUM ER (diclofenac sodium)

There are 7 contraindications. Absolute contraindication.

Contraindication List
Aspirin exacerbated respiratory disease
Cerebrovascular accident
Drug-induced hepatitis
History of roux-en-Y gastric bypass
Post-operative from CABG surgery
Pregnancy
Renal transplant

There are 20 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Acute myocardial infarction
Alcohol use disorder
Chronic heart failure
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Disease of liver
Gastrointestinal hemorrhage
Gastrointestinal perforation
Gastrointestinal ulcer
Hepatic porphyria
History of kidney donation
Hypertension
Increased risk of bleeding
Increased risk of bleeding due to coagulation disorder
Kidney disease with likely reduction in glomerular filtration rate (GFr)
Nephrectomy
Non-infective meningitis
Systemic mastocytosis
Thrombotic disorder
Tobacco smoker

There are 4 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Anemia
Asthma
Dehydration
Edema

There are 68 severe adverse reactions.

More Frequent	Less Frequent
None.	Body fluid retention Edema Esophageal ulcer Gastrointestinal ulcer Increased alanine transaminase Peptic ulcer Skin rash Tinnitus

Rare/Very Rare

Abnormal hepatic function tests Abnormal vaginal bleeding Acute eruptions of skin Acute myocardial infarction Acute pancreatitis Agranulocytosis Allergic dermatitis Anaphylaxis Anemia Angioedema Aplastic anemia Black tarry stools Bloody stools Bloody vomit Bronchospastic pulmonary disease Bullous dermatitis Cerebrovascular accident Colitis Cystitis DRESS syndrome Dyspnea Eosinophilia Epistaxis Erythema multiforme Esophagitis Exfoliative dermatitis Gastric ulcer Gastrointestinal hemorrhage Gastrointestinal perforation Heart failure Hematuria Hemolytic anemia Hemorrhage Hepatic failure Hepatic necrosis Hepatitis Hyperkalemia Hypertension Infection Interstitial nephritis Jaundice Kidney disease with reduction in glomerular filtration rate (GFr) Leukopenia Memory impairment Nephrotic syndrome Nephrotoxicity Non-infective meningitis Oliguria Pancytopenia Pneumonia Proteinuria Renal failure Renal papillary necrosis Respiratory depression Seizure disorder Stevens-johnson syndrome Thrombocytopenic disorder Thrombotic disorder Toxic epidermal necrolysis Urticaria

There are 41 less severe adverse reactions.

More Frequent	Less Frequent
Acute abdominal pain Constipation Diarrhea Dizziness Drowsy Dyspepsia Headache disorder Hyperhidrosis Insomnia Nausea Pruritus of skin Vomiting	Flatulence Heartburn

Rare/Very Rare
Acute cognitive impairment Alopecia Appetite changes Asthma Conjunctivitis Depression Dream disorder Ecchymosis Eructation Fever Flushing General weakness Hearing loss Hyperglycemia Irritability Lymphadenopathy Medication overuse headache Palpitations Purpura Skin photosensitivity Stomatitis Symptoms of anxiety Syncope Tachycardia Tremor Weight loss Xerostomia

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. Diclofenac crosses the placenta in mice, rats, and humans.

Reproduction studies in rabbits, rats, and mice receiving oral diclofenac sodium dosages up to 10, 10, and 20 mg/kg daily, respectively, have not revealed evidence of teratogenicity; however, these dosages produced maternal (e.g., dystocia, prolonged gestation) and fetal (e.g., reduced weight, growth, and survival) toxicity. 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 diclofenac, 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 diclofenac on labor and delivery in humans currently are not known.

In animal studies, NSAIAs, including diclofenac, inhibit prostaglandin synthesis, delay parturition, and increase the incidence of stillbirth. Diclofenac sodium in fixed combination with misoprostol is contraindicated in women who are pregnant because misoprostol exhibits abortifacient activity and can cause serious fetal harm. In addition, it is recommended that diclofenac in fixed combination with misoprostol be used in women of childbearing potential only if they require NSAIA therapy and are considered at high risk of complications resulting from NSAIA-induced gastric or duodenal ulceration or at high risk of developing gastric or duodenal ulceration.

(See Cautions: Pregnancy, Fertility, and Lactation, in Misoprostol 56:28.28.)

Diclofenac may be distributed into milk. While diclofenac was not detectable in breast milk in 12 women who received diclofenac 100 mg orally daily for 7 days or a single 50-mg IM dose administered in the immediate postpartum period, the drug was detected in breast milk at a concentration of 100 mcg/L (equivalent to an infant dose of about 0.03 mg/kg daily) in one woman receiving a diclofenac salt at a dosage of 150 mg daily. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for diclofenac and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

No enhanced Geriatric Use information available for this drug.