Fenoprofen

FENOPROFEN- fenoprofen calcium capsule
Bryant Ranch Prepack

Rx only

DESCRIPTION

Fenoprofen Calcium capsules, USP is a nonsteroidal, anti-inflammatory, antiarthritic drug. Fenoprofen Calcium capsules contain fenoprofen calcium as the dihydrate in an amount equivalent to 200 mg (0.826 mmol) or 400 mg (1.65 mmol) of fenoprofen. The 200 mg capsules contain cellulose, gelatin, iron oxides, silicone, titanium dioxide and other inactive ingredients. The 400 mg capsules contain crospovidone, FD&C Blue 1, FD&C Red 40, gelatin, iron oxide yellow, magnesium stearate, sodium lauryl sulfate, talc, and titanium dioxide. Chemically, Fenoprofen Calcium is an arylacetic acid derivative.

The structural formula is as follows:

Benzeneacetic acid, α-methyl-3-phenoxy-,calcium salt dihydrate, (±)-

Fenoprofen Calcium is a white crystalline powder that has the structural formula C₃₀ H₂₆ CaO₆ •2H₂ O representing a molecular weight of 558.65. At 25°C, it dissolves to a 15 mg/mL solution in alcohol (95%). It is slightly soluble in water and insoluble in benzene.

CLINICAL PHARMACOLOGY

Fenoprofen Calcium is a nonsteroidal, anti-inflammatory, antiarthritic drug that also possesses analgesic and antipyretic activities. Its exact mode of action is unknown, but it is thought that prostaglandin synthetase inhibition is involved.

Results in humans demonstrate that fenoprofen has both anti-inflammatory and analgesic actions. The emergence and degree of erythemic response were measured in adult male volunteers exposed to ultraviolet irradiation. The effects of Fenoprofen Calcium, aspirin, and indomethacin were each compared with those of a placebo. All 3 drugs demonstrated antierythemic activity.

In all patients with rheumatoid arthritis, the anti-inflammatory action of Fenoprofen Calcium has been evidenced by relief of pain, increase in grip strength, and reductions in joint swelling, duration of morning stiffness, and disease activity (as assessed by both the investigator and the patient). The anti-inflammatory action of Fenoprofen Calcium has also been evidenced by increased mobility (i.e., a decrease in the number of joints having limited motion).

The use of Fenoprofen Calcium in combination with gold salts or corticosteroids has been studied in patients with rheumatoid arthritis. The studies, however, were inadequate in demonstrating whether further improvement is obtained by adding Fenoprofen Calcium to maintenance therapy with gold salts or steroids. Whether or not Fenoprofen Calcium used in conjunction with partially effective doses of a corticosteroid has a “steroid-sparing” effect is unknown.

In patients with osteoarthritis, the anti-inflammatory and analgesic effects of Fenoprofen Calcium have been demonstrated by reduction in tenderness as a response to pressure and reductions in night pain, stiffness, swelling, and overall disease activity (as assessed by both the patient and the investigator). These effects have also been demonstrated by relief of pain with motion and at rest and increased range of motion in involved joints.

In patients with rheumatoid arthritis and osteoarthritis, clinical studies have shown Fenoprofen Calcium to be comparable to aspirin in controlling the aforementioned measures of disease activity, but mild gastrointestinal reactions (nausea, dyspepsia) and tinnitus occurred less frequently in patients treated with Fenoprofen Calcium than in aspirin-treated patients. It is not known whether Fenoprofen Calcium causes less peptic ulceration than does aspirin.

In patients with pain, the analgesic action of Fenoprofen Calcium has produced a reduction in pain intensity, an increase in pain relief, improvement in total analgesia scores, and a sustained analgesic effect.

Under fasting conditions, Fenoprofen Calcium is rapidly absorbed, and peak plasma levels of 50 μg/mL are achieved within 2 hours after oral administration of 600 mg doses. Good dose proportionality was observed between 200 mg and 600 mg doses in fasting male volunteers. The plasma half-life is approximately 3 hours. About 90% of a single oral dose is eliminated within 24 hours as fenoprofen glucuronide and 4′-hydroxyfenoprofen glucuronide, the major urinary metabolites of fenoprofen. Fenoprofen is highly bound (99%) to albumin.

The concomitant administration of antacid (containing both aluminum and magnesium hydroxide) does not interfere with absorption of Fenoprofen Calcium.

There is less suppression of collagen-induced platelet aggregation with single doses of Fenoprofen Calcium than there is with aspirin.

INDICATIONS AND USAGE

Carefully consider the potential benefits and risks of Fenoprofen Calcium and other treatment options before deciding to use Fenoprofen Calcium. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

Fenoprofen Calcium is indicated:

• For relief of mild to moderate pain in adults.
• For relief of the signs and symptoms of rheumatoid arthritis.
• For relief of the signs and symptoms of osteoarthritis.

CONTRAINDICATIONS

Fenoprofen Calcium is contraindicated in patients who have shown hypersensitivity to fenoprofen calcium.

Fenoprofen Calcium should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients (see WARNINGS – Anaphylactoid Reactions, and PRECAUTIONS – Preexisting Asthma).

Fenoprofen Calcium is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).

Fenoprofen Calcium is contraindicated in patients with a history of significantly impaired renal function (see WARNINGS – Advanced Renal Disease).

WARNINGS

CARDIOVASCULAR EFFECTS

Cardiovascular Thrombotic Events

Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may give a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur.

There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious GI events (see WARNINGS — Gastrointestinal Effects).

Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS).

Hypertension

NSAIDs, including Fenoprofen Calcium, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including Fenoprofen Calcium, should be used with caution in patients with hypertension. Blood pressure should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.