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
Feldene Warnings, Precautions, Pregnancy, Nursing, Abuse - Piroxicam
Feldene Warnings, Precautions, Pregnancy, Nursing, Abuse - Piroxicam
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 two 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 one
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 (e.g., 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.
PRECAUTIONS
Renal Effects: As
with other nonsteroidal anti-inflammatory
drugs, long-term administration
of piroxicam to animals has resulted in renal papillary necrosis
and other abnormal
renal pathology. In
humans, there have been reports of acute
interstitial nephritis
with hematuria, proteinuria,
and occasionally, nephrotic
syndrome.
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, where the renal
prostaglandins have 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. Patients at greatest risk
of 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.
Because of extensive renal
excretion of piroxicam
and its biotransformation products (less than 5% of the daily dose
excreted unchanged, see CLINICAL
PHARMACOLOGY), lower doses of piroxicam should be anticipated
in patients with impaired renal
function, and they should be carefully monitored.
Although other nonsteroidal anti-inflammatory
drugs do not have the same direct effects on platelets that aspirin
does, all drugs inhibiting prostaglandin biosynthesis
do interfere with platelet
function to some degree;
therefore, patients who may be adversely affected by such
an action should be carefully observed when FELDENE is administered.
Because of reports of adverse eye
findings with nonsteroidal anti-inflammatory agents, it is recommended
that patients who develop visual
complaints during treatment with FELDENE have ophthalmic
evaluation.
As with other nonsteroidal anti-inflammatory
drugs, borderline
elevations of one 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 (three 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
reaction while on therapy
with FELDENE. Severe hepatic
reactions, including jaundice and cases of fatal
hepatitis, have been
reported with FELDENE. Although such reactions are rare, if abnormal
liver tests persist or
worsen, if clinical signs and symptoms consistent with liver
disease develop, or
if systemic manifestations occur (e.g., eosinophilia,
rash, etc.), FELDENE should
be discontinued. (See also ADVERSE
REACTIONS.)
Although at the recommended dose
of 20 mg/day of FELDENE increased fecal blood loss
due to gastrointestinal
irritation did not
occur (see CLINICAL PHARMACOLOGY),
in about 4% of the patients treated with FELDENE alone or concomitantly
with aspirin, reductions in hemoglobin
and hematocrit values were observed. Therefore, these values should
be determined if signs or symptoms of anemia
occur.
Peripheral edema has
been observed in approximately 2% of the patients treated with FELDENE.
Therefore, as with other nonsteroidal anti-inflammatory drugs, FELDENE
should be used with caution in patients with heart
failure, hypertension or other conditions predisposing
to fluid retention,
since its usage may be associated with a worsening of these conditions.
A combination of dermatological and/or allergic
signs and symptoms suggestive of serum
sickness have occasionally
occurred in conjunction with the use of FELDENE. These include arthralgias,
pruritus, fever,
fatigue, and rash including
vesiculo bullous reactions
and exfoliative dermatitis.
Information for Patients
FELDENE, 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,
but they also may be commonly employed for conditions which are
less serious.
Physicians may w.s. 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
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 Ulceration,
Bleeding and Perforation with NSAID
Therapy).
Drug Interactions
FELDENE is highly protein
bound, and
therefore, might be expected to displace other protein-bound drugs.
Although this has not occurred in in vitro studies with coumarin-type
anticoagulants, interactions with coumarin-type anticoagulants have
been reported with FELDENE since marketing, therefore, physicians
should closely monitor
patients for a change in dosage requirements when administering
FELDENE to patients on coumarin-type anticoagulants and other highly
protein-bound drugs.
Plasma levels of piroxicam are depressed
to approximately 80% of their normal values when FELDENE is administered
in conjunction with aspirin (3900 mg/day), but concomitant
administration
of antacids has no effect
on piroxicam plasma levels
(see CLINICAL PHARMACOLOGY).
Nonsteroidal anti-inflammatory
agents, including FELDENE, have been reported to increase steady
state plasma
lithium levels. It is
recommended that plasma
lithium levels be monitored
when initiating, adjusting and discontinuing FELDENE.
Carcinogenesis, Chronic Animal Toxicity and Impairment of Fertility
Subacute and chronic
toxicity studies have
been carried out in rats, mice, dogs, and monkeys.
The pathology most
often seen was that characteristically associated with the animal
toxicology of anti-inflammatory
agents: renal papillary
necrosis (see PRECAUTIONS
) and gastrointestinal
lesions.
In classical studies in laboratory
animals piroxicam did not show
any teratogenic potential.
Reproductive studies revealed no
impairment of fertility
in animals.
Pregnancy and Nursing Mothers
Like other drugs that inhibit the synthesis
and release of prostaglandins,
piroxicam increased the incidence
of dystocia and delayed
parturition in pregnant
animals when piroxicam administration
was continued late into pregnancy. Gastrointestinal tract
toxicity was increased
in pregnant females
in the last trimester
of pregnancy compared
to non-pregnant females or females in earlier trimesters of pregnancy.
FELDENE is not recommended for use in nursing
mothers or in pregnant women because of the animal
findings and since safety for such
use has not been established in humans.
Use in Children
Dosage recommendations and indications for use in children
have not been established.
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