fenoprofen (Rx)

>10%

Dyspepsia (10.3%)

Somnolence

Increased LFT

1-10%

Abdominal pain

Anemia

Diarrhea

Dizziness

Edema

Headache

Constipation

Confusion

Tremor

Sweating

Tinnitus

Blurred vision

Palpitations

Nervousness

Fatigue

Rash

Nausea

Vomiting

GI bleeding, ulceration, perforation

Frequency Not Defined

Insomnia

Asthenia

Paresthesia

Muscle weakness

Decreased hearing

Purpura, bruising, hemorrhage

Thrombocytopenia, hemolytic anemia, aplastic anemia, agranulocytosis, pancytopenia, slight decreases in hemoglobin concentration & hematocrit

Dysuria, cystitis, hematuria

Nephrotic syndrome, renal failure, oliguria, anuria, azotemia, allergic nephritis, nephrosis, papillary necrosis

Jaundice

Cholestatic hepatitis

Contraindications

Absolute: ASA allergy

Relative: bleeding disorders, duodenal/gastric/peptic ulcer, renal impairment, stomatitis, SLE, ulcerative colitis, upper GI disease, late pregnancy (may cause premature closure of ductus arteriosus)

Cautions

Use caution in asthma (bronchial), cardiac disease, CHF, hepatic impairment, HTN

Long-term administration of NSAIDs may result in renal papillary necrosis and other renal injury; patients at greatest risk include the elderly, or those with impaired renal function, hypovolemia, heart failure, liver dysfunction, salt depletion, and individuals taking diuretics, ACE inhibitors, or ARBs

Drug reaction with eosinophilia and systemic symptoms (DRESS)

• Drug Reaction reported in patients taking NSAIDs; some of these events have been fatal or life-threatening; DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling
• Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis; sometimes symptoms of DRESS may resemble an acute viral infection
• Eosinophilia is often present; because this disorder is variable in its presentation, other organ systems not noted here may be involved
• Early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident; if such signs or symptoms are present, discontinue therapy and evaluate the patient immediately

Heart Failure (HF) risk

• NSAIDS have the potential to trigger HF by prostaglandin inhibition that leads to sodium and water retention, increased systemic vascular resistance, and blunted response to diuretics
• NSAIDS should be avoided or withdrawn whenever possible
• AHA/ACC Heart Failure Guidelines; Circulation. 2016; 134

Pregnancy

Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive

In animal reproduction studies, embryo-fetal lethality and skeletal abnormalities were noted in offspring of pregnant rabbits following oral administration of fenoprofen during organogenesis at 0.6 times the maximum human daily dose of 3200 mg/day

However, there were no major malformations noted following oral administration of fenoprofen calcium to pregnant rats and rabbits during organogenesis at exposures up to 0.3 and 0.6 times the maximum human daily dose of 3200 mg/day

Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization

In animal studies, administration of prostaglandin synthesis inhibitors such as fenoprofen, resulted in increased pre- and post-implantation loss

Prostaglandins also have been shown to have an important role in fetal kidney development. In published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses

Fetal toxicity

• NSAIDs can cause premature closure of fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment
• Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment
• If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit use to lowest effective dose and shortest duration possible; if treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios; if oligohydramnios occurs, discontinue therapy and follow up according to clinical practice
• Use of NSAIDs at about 30 weeks gestation or later in pregnancy increases risk of premature closure of the fetal ductus arteriosus
• Because of these risks, limit dose and duration of use between about 20 and 30 weeks of gestation, and avoid use at about 30 weeks of gestation and later in pregnancy

Labor or Delivery

• There are no studies on the effects of NALFON during labor or delivery; in animal studies, NSAIDS, including fenoprofen, inhibit prostaglandin synthesis, cause delayed parturition, and increase incidence of stillbirth

Reproductive potential

• Females

  • Based on mechanism of action, the use of prostaglandin mediated NSAIDs may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women
  • Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation
  • Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation; consider withdrawal of NSAIDs, in women who have difficulties conceiving or who are undergoing investigation of infertility

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

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

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

Pharmacokinetics

Onset: 2-4hr

Duration: 4-6 hr

Peak Plasma Time: 2 hr

Peak Plasma Concentration: 50 mcg/mL

Protein Bound: 99% (albumin)

Metabolism: Liver

Metabolites: 4'-hydroxyfenoprofen, glucuronic acid conjugates

Enzymes inhibited: cyclooxygenase-1 (COX-1) & -2 (COX-2), prostaglandin synthesis

Half-life: 2.5-3 hr

Clearance: within 24 hr

Excretion: urine (primarily); feces