A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Nalfon Warnings, Precautions, Pregnancy, Nursing, Abuse - Fenoprofen
Nalfon Warnings, Precautions, Pregnancy, Nursing, Abuse - Fenoprofen
WARNINGS
Risk of GI Ulceration, Bleeding, and Perforation with NSAID Therapy
Serious gastrointestinal toxicity, such as bleeding, ulceration, and perforation,
can occur at any time, with or without warning symptoms, in patients treated
chronically with NSAID therapy. Although minor upper gastrointestinal problems,
such as dyspepsia, are common, usually developing early in therapy, physicians
should remain alert for ulceration and bleeding in patients treated chronically
with NSAIDs, even in the absence of previous GI tract symptoms. In patients
observed in clinical trials of several months to 2 years duration, symptomatic
upper GI ulcers, gross bleeding, or perforation appear to occur in approximately
1% of patients treated for 3 to 6 months, and in about 2% to 4% of patients
treated for 1 year. Physicians should inform patients about the signs and/or
symptoms of serious GI toxicity and what steps to take if they occur.
Studies to date have not identified any subset of patients not at risk of developing
peptic ulceration and bleeding. Except for a prior history of serious GI events
and other risk factors known to be associated with peptic ulcer disease, such
as alcoholism, smoking, etc, no risk factors (eg, age, sex) have been associated
with increased risk. Elderly or debilitated patients seem to tolerate ulceration
or bleeding less well than other individuals and most spontaneous reports of
fatal GI events are in this population. Studies to date are inconclusive concerning
the relative risk of various NSAIDs in causing such reactions. High doses of
any NSAID probably carry a greater risk of these reactions, although controlled
clinical trials showing this do not exist in most cases. In considering the
use of relatively large doses (within the recommended dosage range), sufficient
benefit should be anticipated to offset the potential increased risk of GI toxicity.
Since Nalfon has been marketed, there have been reports of genitourinary tract
problems in patients taking it. The most frequently reported problems have been
episodes of dysuria, cystitis, hematuria, interstitial nephritis, and nephrotic
syndrome. This syndrome may be preceded by the appearance of fever, rash, arthralgia,
oliguria, and azotemia and may progress to anuria. There may also be substantial
proteinuria, and, on renal biopsy, electron microscopy has shown foot process
fusion and T-lymphocyte infiltration in the renal interstitium. Early recognition
of the syndrome and withdrawal of the drug have been followed by rapid recovery.
Administration of steroids and the use of dialysis have also been included in
the treatment. Because a syndrome with some of these characteristics has also
been reported with other nonsteroidal anti-inflammatory drugs, it is recommended
that patients who have had these reactions with other such drugs not be treated
with Nalfon. In patients with possibly compromised renal function, periodic
renal function examinations should be done.
PRECAUTIONS
General Renal Effects There have been reports of acute
interstitial nephritis and nephrotic syndrome ( see Contraindications
and WARNINGS
).
A second form of renal toxicity has been seen in patients with prerenal conditions
leading to a reduction in renal blood flow or blood volume, in which renal prostaglandins
play a supportive role in the maintenance of renal perfusion. In these patients,
administration of an NSAID may cause a dose-dependent reduction in prostaglandin
formation and may precipitate overt renal decompensation at any time. Patients
at greatest risk for this reaction are those with impaired renal function, heart
failure, liver dysfunction, those taking diuretics, and the elderly. Discontinuation
of NSAID therapy is typically followed by recovery to the pretreatment state.
Since Nalfon is primarily eliminated by the kidneys, patients with possibly
compromised renal function (such as the elderly) should be monitored periodically,
especially during long-term therapy. For such patients, it may be anticipated
that a lower daily dosage will avoid excessive drug accumulation.
Miscellaneous Peripheral edema has been observed in some patients
taking Nalfon; therefore, Nalfon should be used with caution in patients with
compromised cardiac function or hypertension. The possibility of renal involvement
should be considered.
Studies to date have not shown changes in the eyes attributable to the administration
of Nalfon. However, adverse ocular effects have been observed with other anti-inflammatory
drugs. Eye examinations, therefore, should be performed if visual disturbances
occur in patients taking Nalfon.
Caution should be exercised by patients whose activities require alertness
if they experience CNS side effects while taking Nalfon.
Since the safety of Nalfon has not been established in patients with impaired
hearing, these patients should have periodic tests of auditory function during
prolonged therapy with Nalfon.
Information for Patients Nalfon, like other drugs of its class,
is not free of side effects. The side effects of these drugs can cause discomfort
and, rarely, there are more serious side effects, such as gastrointestinal bleeding,
which may result in hospitalization and even fatal outcomes.
NSAIDs (Nonsteroidal Anti-Inflammatory Drugs) are often essential agents in
the management of arthritis and have a major role in the treatment of pain,
but they also may be commonly employed for conditions which are less serious.
Physicians may wish to discuss with their patients the potential risks ( see
WARNINGS
, Precautions, and Adverse REACTIONS sections) and likely
benefits of NSAID treatment, particularly when the drugs are used for less serious
conditions where treatment without NSAIDs may represent an acceptable alternative
to both the patient and physician.
Laboratory Tests In chronic studies in rats, high doses of Nalfon
caused elevation of serum transaminase and hepatocellular hypertrophy. In clinical
trials, some patients developed elevation of serum transaminase, LDH, and alkaline
phosphatase that persisted for some months and usually, but not always, declined
despite continuation of the drug. The significance of this is unknown. It is
recommended, therefore, that Nalfon be discontinued if any significant liver
abnormality occurs.
As with other nonsteroidal anti-inflammatory drugs, borderline elevations in
1 or more liver tests may occur in up to 15% of patients. These abnormalities
may progress, may remain essentially unchanged, or may be transient with continued
therapy. The SGPT (ALT) test is probably the most sensitive indicator of liver
dysfunction. Meaningful (ie, 3 times the upper limit of normal) elevations of
SGPT or SGOT (AST) occurred in controlled clinical trials in less than 1% of
patients. A patient with symptoms and/or signs suggesting liver dysfunction,
or in whom an abnormal liver test has occurred, should be evaluated for evidence
of the development of more severe hepatic reactions while using Nalfon.
Severe hepatic reactions, including jaundice and cases of fatal hepatitis,
have been reported with Nalfon, as with other nonsteroidal anti-inflammatory
drugs. As a result, during long-term therapy, liver function tests should be
monitored periodically. Although such reactions are rare, if liver tests continue
to be abnormal or worsen, if clinical signs and symptoms consistent with liver
disease develop, or if systemic manifestations occur (eg, eosinophilia and rash),
Nalfon should be discontinued. If this drug is to be used in the presence of
impaired liver function, it must be done under strict observation.
Patients with initial low hemoglobin values who are receiving long-term therapy
with Nalfon should have a hemoglobin determination made at reasonable intervals.
Nalfon decreases platelet aggregation and may prolong bleeding time. Patients
who may be adversely affected by prolongation of the bleeding time should be
carefully observed when Nalfon is administered.
Because serious GI tract ulceration and bleeding can occur without warning
symptoms, physicians should follow chronically treated patients for the signs
and symptoms of ulceration and bleeding and should inform them of the importance
of this follow-up ( see Risk of GI Ulcerations, Bleeding and Perforation
with NSAID Therapy under WARNINGS
).
Laboratory Test Interactions Amerlex-M kit assay values of total
and free triiodothyronine in patients receiving Nalfon have been reported as
falsely elevated on the basis of a chemical cross-reaction that directly interferes
with the assay. Thyroid-stimulating hormone, total thyroxine, and thyrotropin-releasing
hormone response are not affected.
Drug Interactions The coadministration of aspirin decreases
the biologic half-life of fenoprofen because of an increase in metabolic clearance
that results in a greater amount of hydroxylated fenoprofen in the urine. Although
the mechanism of interaction between fenoprofen and aspirin is not totally known,
enzyme induction and displacement of fenoprofen from plasma albumin binding
sites are possibilities. Because Nalfon has not been shown to produce any additional
effect beyond that obtained with aspirin alone and because aspirin increases
the rate of excretion of Nalfon, the concomitant use of Nalfon and salicylates
is not recommended.
Chronic administration of phenobarbital, a known enzyme inducer, may be associated
with a decrease in the plasma half-life of fenoprofen. When phenobarbital is
added to or withdrawn from treatment, dosage adjustment of Nalfon may be required.
In vitro studies have shown that fenoprofen, because of its affinity for albumin,
may displace from their binding sites other drugs that are also albumin bound,
and this may lead to drug interaction. Theoretically, fenoprofen could likewise
be displaced. Patients receiving hydantoins, sulfonamides, or sulfonylureas
should be observed for increased activity of these drugs and, therefore, signs
of toxicity from these drugs. In patients receiving coumarin-type anticoagulants,
the addition of Nalfon to therapy could prolong the prothrombin time. Patients
receiving both drugs should be under careful observation. Patients treated with
Nalfon may be resistant to the effects of loop diuretics.
In patients receiving Nalfon and a steroid concomitantly, any reduction in
steroid dosage should be gradual in order to avoid the possible complications
of sudden steroid withdrawal.
Usage in Pregnancy Safe use of Nalfon during pregnancy and lactation
has not been established; therefore, administration to pregnant patients and
nursing mothers is not recommended. Reproduction studies have been performed
in rats and rabbits. When fenoprofen was given to rats during pregnancy and
continued until the time of labor, parturition was prolonged. Similar results
have been found with other nonsteroidal anti-inflammatory drugs that inhibit
prostaglandin synthetase.
Usage in Pediatric Patients Safety and effectiveness in pediatric
patients have not been established.
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