FLANAX (naproxen sodium)

There are 8 contraindications. Absolute contraindication.

Contraindication List
Aspirin exacerbated respiratory disease
Cerebrovascular accident
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
Renal transplant

There are 19 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Acute myocardial infarction
Alcohol use disorder
Anemia
Burns
Chronic heart failure
Disease of liver
Edema
Esophageal dysmotility
Gastrointestinal hemorrhage
Gastrointestinal perforation
Gastrointestinal ulcer
History of kidney donation
Hypertension
Increased risk of bleeding
Kidney disease with likely reduction in glomerular filtration rate (GFr)
Nephrectomy
Systemic mastocytosis
Thrombotic disorder
Tobacco smoker

There are 1 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Increased risk of bleeding due to coagulation disorder

There are 99 severe adverse reactions.

More Frequent	Less Frequent
Abnormal hepatic function tests Body fluid retention Skin rash Tinnitus Urticaria	Blurred vision Bruising Ecchymosis Hemorrhage Polydipsia Purpura Visual changes

Rare/Very Rare

Acute cognitive impairment Acute eruptions of skin Acute myocardial infarction Acute pancreatitis Agranulocytosis Allergic dermatitis Anaphylaxis Anemia Angioedema Aplastic anemia Bacterial sepsis Bloody vomit Bronchospastic pulmonary disease Bullous dermatitis Burns Cardiac arrhythmia Cerebrovascular accident Chest tightness Chronic heart failure Colitis Coma Corneal opacity Cystitis Depression Dyspnea Eosinophilia Eosinophilic pneumonia Erythema multiforme Exfoliative dermatitis Facial edema Fever Gastric ulcer Gastrointestinal hemorrhage Gastrointestinal obstruction Gastrointestinal perforation Gastrointestinal ulcer Glomerulonephritis Heart failure Hematuria Hemolytic anemia Hepatic failure Hepatitis Hyperglycemia Hyperkalemia Hypersensitivity drug reaction Hypertension Hypoglycemic disorder Hypotension Interstitial nephritis Jaundice Kidney disease with reduction in glomerular filtration rate (GFr) Leukopenia Loffler syndrome Lupus-like syndrome Lymphadenopathy Myalgia Nephrotic syndrome Non-infective meningitis Optic neuritis Pancytopenia Peptic ulcer Periorbital edema Pharyngeal edema Pneumonia Polyuria Proteinuria Pruritus of skin Pulmonary edema Rectal bleeding Renal failure Renal papillary necrosis Renal tubular necrosis Respiratory depression Seizure disorder Severe burns Skin ulcer Stevens-johnson syndrome Superficial skin ulcer Syncope Tachycardia Throat constriction Thrombocytopenic disorder Thrombotic disorder Toxic epidermal necrolysis Urticaria Vasculitis Wheezing

There are 60 less severe adverse reactions.

More Frequent	Less Frequent
Blistering skin Constipation Contact dermatitis Dizziness Drowsy Edema Headache disorder Heartburn Nausea Stinging of skin	Acute pain at drug application site Diarrhea Dry skin Dyspepsia Erythema Hearing loss Hyperhidrosis Palpitations Pruritus of skin Skin irritation Stinging of skin Upper abdominal pain Vertigo

Rare/Very Rare

Alopecia Appetite changes Black tarry stools Concentration difficulty Conjunctivitis Cough Dysgeusia Dysuria Eructation Erythema nodosum Esophagitis Fatigue Gastritis General weakness Glossitis Hallucinations Headache disorder Insomnia Lichen planus Menstrual disorder Muscle weakness Nervousness Ocular pain Oliguria Papilledema Paresthesia Pruritus of skin Reduced sensation of skin Skin photosensitivity Stinging of skin Stomatitis Symptoms of anxiety Tremor Vomiting Weight gain Weight loss Xerostomia

Maternal use of capsaicin 8% patches is not expected to result in fetal exposure; systemic absorption of the drug following topical administration is negligible. In animal reproductive studies, no evidence of malformations were observedwhen capsaicin was administered daily by the topical route to pregnant rats and rabbitsduring the period of organogenesis at doses of up to 11- and 37-times, respectively, themaximum recommended human dose (MRHD) at 716 mg capsaicin perday (4 topical systems containing 179 mg/topical systems). In a peri- and postnataldevelopment study, no adverse effects were observed when capsaicin was administereddaily by the topical route to rats during implantation to weaning at doses of up to 11-times the MRHD.

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 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 naproxen, 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.

Reproduction studies of naproxen in rats at 20 mg/kg daily (125 mg/m2, 0.23 times the human systemic exposure), rabbits at 20 mg/kg daily (220 mg/m2, 0.27 times the human systemic exposure), and mice at 170 mg/kg daily (510 mg/m2, 0.28 times the human systemic exposure) have not revealed evidence of harm to the fetus. Severe hypoxemia due to persistent pulmonary hypertension has occurred in infants whose mothers received naproxen to delay parturition. Neonatal death also has been reported when the drug was used to prevent preterm labor; autopsy of a neonate showed brain hemorrhage, multiple gastric ulcers, extensive GI bleeding, and an adverse cardiovascular effect known to be associated with use of NSAIAs.

In addition, severe hyponatremia, water retention, cerebral irritation, and paralytic ileus was reported in a neonate whose mother ingested 5 g of naproxen 8 hours before delivery; it has been suggested that naproxen adversely affected renal function. Renal dysfunction and abnormal prostaglandin E concentrations in premature infants also have been reported. Effects of naproxen during labor or delivery have not been studied. In animal studies, NSAIAs, including naproxen, inhibited prostaglandin synthesis, delayed parturition, and increased the incidence of stillbirth.

Breastfeeding is not expected to result in fetal exposure of capsaicin; systemic absorption from topical application of capsaicin 8% patch is negligible. There are no data on the effects of capsaicin on human milk production. To minimize potential direct exposure of capsaicin to the breastfed infant, avoid applying the patches directly to the nipple andareola.

Consider the developmental and health benefits of breastfeeding along withthe mother's clinical need for capsaicin and any potential adverse effects on thebreastfed infant from the drug or from the underlying maternal condition. Naproxen is distributed into milk at concentrations of approximately 1% of peak plasma concentrations of the drug. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for naproxen and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

In controlled clinical trials of capsaicin 8% patch in patients with postherpeticneuralgia, 75% of patients were 65 years of age and older and 43% of patients were 75 yearsof age and older. The safety and effectiveness were similar in geriatric patients and youngerpatients.