Prescription Drug Information: NALFON

NALFON- fenoprofen calcium tablet, film coated
Xspire Pharma, LLC

Cardiovascular Thrombotic Events

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use (see WARNINGSand PRECAUTIONS).
  • Fenoprofen calcium tablets are contraindicated in the setting of coronary artery bypass graft (CABG) surgery (see CONTRAINDICATIONSand WARNINGS).

Gastrointestinal Risk

  • NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration and perforation of stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events (see WARNINGS).

DESCRIPTION

NALFON ® (fenoprofen calcium tablets) USP is a nonsteroidal, anti-inflammatory, antiarthritic drug. Chemically, fenoprofen calcium is an arylacetic acid derivative. The structural formula is as follows:

FStruct-1
(click image for full-size original)

Benzeneacetic acid, α-methyl-3-phenoxy-, calcium salt (2:1)-(±)-, dihydrate

Fenoprofen calcium, USP is a white crystalline powder, soluble in alcohol (95%) to the extent of approximately 15 mg/mL at 25°C, slightly soluble in water and insoluble in benzene.

The pKa of fenoprofen calcium is 4.5 at 25°C.

Film-coated NALFON tablets for oral administration are available containing fenoprofen calcium as the dihydrate equivalent to 600 mg of fenoprofen and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, pregelatinized starch, sodium lauryl sulfate, titanium dioxide and FD&C Yellow No. 6 Aluminum Lake.

CLINICAL PHARMACOLOGY

NALFON ® tablets 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, aspirin and indomethacin were each compared with those of a placebo. All three drugs demonstrated antierythemic activity.

In all patients with rheumatoid arthritis, the anti-inflammatory action of NALFON 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 NALFON has also been evidenced by increased mobility (i.e., a decrease in the number of joints having limited motion).

The use of NALFON 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 NALFON to maintenance therapy with gold salts or steroids. Whether or not NALFON 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 NALFON 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 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 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 NALFON 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 is rapidly absorbed and peak plasma levels of 50 mcg/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’ hydroxy-fenoprofen 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 NALFON.

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 NALFON tablets, USP and other treatment options before deciding to use NALFON tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).

NALFON tablets are 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

NALFON tablets are contraindicated in patients who have shown hypersensitivity to fenoprofen calcium.

NALFON tablets 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).

NALFON is contraindicated in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).

NALFON 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 3 years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.

To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, 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, such as NALFON, increases the risk of serious gastrointestinal (GI) events (see GI WARNINGS).

Status Post Coronary Artery Bypass Graft (CABG) Surgery

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

Post-MI Patients

Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and all-cause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next 4 years of follow-up.

Avoid the use of NALFON tablets in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If NALFON tablets are used in patients with a recent MI, monitor patients for signs of cardiac ischemia.

Hypertension

NSAIDs, including NALFON, can lead to onset of new hypertension or worsening of preexisting 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 NALFON, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.

Heart Failure and Edema

The Coxib and traditional NSAID Trialists’ Collaboration meta-analysis of randomized controlled trials demonstrated an approximately 2-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.

Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of fenoprofen calcium may blunt the CV effects of several therapeutic agents used to treat these medical conditions [e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers (ARBs)] (see Drug Interactions).

Avoid the use of NALFON tablets in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If NALFON tablets are used in patients with severe heart failure, monitor patients for signs of worsening heart failure.

Gastrointestinal Effects

Risk of Ulceration, Bleeding and Perforation

NSAIDs, including NALFON tablets, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration and perforation of the stomach, small intestine or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy, is symptomatic. Upper GI ulcers, gross bleeding or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3 to 6 months, and in about 2% to 4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short-term therapy is not without risk.

NSAIDs should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population.

To minimize the potential risk for an adverse GI event in patients treated with a NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.

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