DICLOTREX II (diclofenac sodium/menthol/camphor)

There are 3 contraindications. Absolute contraindication.

Contraindication List
Aspirin exacerbated respiratory disease
Post-operative from CABG surgery
Pregnancy

There are 15 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Acute myocardial infarction
Alcohol use disorder
Burns
Cerebrovascular accident
Chronic heart failure
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Debilitation
Disease of liver
Gastrointestinal hemorrhage
Gastrointestinal ulcer
Increased risk of bleeding
Peptic ulcer
Systemic mastocytosis
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
Edema
Hypertension

There are 29 severe adverse reactions.

More Frequent	Less Frequent
None.	None.

Rare/Very Rare

Abnormal hepatic function tests Acute eruptions of skin Acute myocardial infarction Allergic dermatitis Anaphylaxis Anemia Asthma Body fluid retention Bullous dermatitis Burns Cerebrovascular accident DRESS syndrome Exfoliative dermatitis Gastric ulcer Gastroenteritis Gastrointestinal hemorrhage Gastrointestinal perforation Gastrointestinal ulcer Heart failure Hepatic failure Hepatic necrosis Hepatitis Jaundice Platelet aggregation inhibition Rectal bleeding Renal papillary necrosis Stevens-johnson syndrome Tongue swelling Toxic epidermal necrolysis

There are 35 less severe adverse reactions.

More Frequent	Less Frequent
Dry skin Pruritus of skin	Bruising Contact dermatitis Drowsy Dysgeusia Dyspepsia Edema Headache disorder Nausea Paresthesia Skin inflammation Skin rash Skin ulcer Stinging of skin Treatment site sequelae

Rare/Very Rare
Cataracts Cramps in legs Depression Diarrhea Dizziness Eczema Gastritis Halitosis Hyperkinesis Hypertension Hypoesthesia Localized edema Myalgia Palpitations Sinusitis Urinary tract infection Urticaria Visual changes 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.