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
Ponstel Warnings, Precautions, Pregnancy, Nursing, Abuse - Mefenamic Acid
Ponstel Warnings, Precautions, Pregnancy, Nursing, Abuse - Mefenamic Acid
WARNINGS
Gastrointestinal (GI) Effects - Risk of GI Ulceration, Bleeding, and
Perforation
Serious gastrointestinal toxicity, such as inflammation, bleeding, ulceration,
and perforation of the stomach, small intestine or large intestine, can
occur at any time, with or without warning symptoms, in patients treated
with nonsteroidal anti-inflammatory drugs (NSAIDs). Minor upper gastrointestinal
problems, such as dyspepsia, are common and may also occur at any time
during NSAID therapy. Therefore, physicians and patients should remain
alert for ulceration and bleeding, even in the absence of previous GI
tract symptoms. Patients should be informed about the signs and/or symptoms
of serious GI toxicity and the steps to take if they occur. The utility
of periodic laboratory monitoring has not been demonstrated, nor has it
been adequately assessed. Only one in five patients, who develop a serious
upper GI adverse event on NSAID therapy, is symptomatic. It has been demonstrated
that upper GI ulcers, gross bleeding or perforation, caused by NSAIDs,
appear to occur in approximately 1% of patients treated for 3-6 months,
and in about 2-4% of patients treated for one year. These trends continue,
thus 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. 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, the lowest effective
dose should be used for the shortest possible duration. For high risk
patients, alternate therapies that do not involve NSAIDs should be considered.
Studies have shown that patients with a prior history of peptic ulcer
disease and/or gastrointestinal bleeding and who use NSAIDs, have
a greater than 10-fold risk for developing a GI bleed than patients with
neither of these risk factors. In addition to a past history of ulcer
disease, pharmacoepidemiological studies have identified several other
cotherapies or comorbid conditions that may increase the risk for GI bleeding
such as: treatment with oral corticosteroids, treatment with anticoagulants,
longer duration of NSAID therapy, smoking, alcoholism, older age, and
poor general health status.
Anaphylactoid REACTIONS
As with other NSAIDs, anaphylactoid reactions may occur in patients without
known prior exposure to Ponstel. Ponstel should not be given to patients
with the aspirin triad. This symptom complex typically occurs in asthmatic
patients who experience rhinitis with or without nasal polyps, or who
exhibit severe potentially fatal bronchospasm after taking aspirin or
other NSAIDs (see CONTRAINDICATIONS
and PRECAUTIONS
: Preexisting Asthma). Emergency
help should be sought in cases where an anaphylactoid reaction occurs.
Advanced Renal Disease
In cases with pre- existing advanced kidney disease, treatment with Ponstel
is not recommended (see CONTRAINDICATIONS).
Pregnancy
In late pregnancy, as with other NSAIDs, Ponstel should be avoided because
it may cause premature closure of the ductus arteriosus.
PRECAUTIONS
General
Ponstel cannot be expected to substitute for corticosteroids or to treat
corticosteroid insufficiency. Abrupt discontinuation of corticosteroids
may lead to disease exacerbation. Patients on prolonged corticosteroid
therapy should have their therapy tapered slowly if a decision is made
to discontinue corticosteroids.
Because Ponstel reduces inflammation, it may diminish the diagnostic
signs for detecting complications of presumed noninfectious, painful conditions.
Hepatic Effects
Borderline elevations of one or more liver function tests may occur in
up to 15% of patients taking NSAIDs, including Ponstel. These laboratory
abnormalities may progress, may remain unchanged, or may be transient
with continuing therapy. Notable elevations of ALT or AST (approximately
three or more times the upper limit of normal) have been reported in approximately
1% of patients in clinical trials with NSAIDs. In addition, rare cases
of severe hepatic reactions, including jaundice and fatal fulminant hepatitis,
liver necrosis and hepatic failure, some of them with fatal outcomes have
been reported.
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 a more severe hepatic reaction while on therapy
with Ponstel. If clinical signs and symptoms consistent with liver disease
develop, or if systemic manifestations occur (e.g., eosinophilia, rash,
etc.), Ponstel should be discontinued.
Renal Effects
Caution should be used when initiating treatment with Ponstel in patients
with considerable dehydration. It is advisable to rehydrate patients first
and then start therapy with Ponstel. Ponstel is not recommended in patients
with pre-existing kidney disease (see CONTRAINDICATIONS).
Long-term administration of Ponstel has resulted in renal papillary necrosis
and other renal medullary changes. Renal toxicity has also been seen in
patients in which renal prostaglandins have a compensatory role in the
maintenance of renal perfusion. In these patients, administration of a
nonsteroidal anti-inflammatory drug may cause a dose-dependant reduction
in prostaglandin formation and, secondarily, in renal blood flow, which
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 ACE inhibitors, and the
elderly. Discontinuation of nonsteroidal anti-inflammatory drug therapy
is usually followed by recovery to the pretreatment state.
Ponstel metabolites are eliminated primarily by the kidneys. The extent
to which the metabolites may accumulate in patients with renal failure
has not been studied.
Hematological Effects
Anemia is sometimes seen in patients receiving NSAIDs, including Ponstel.
This may be due to fluid retention, GI loss, or an effect upon erythropoiesis.
Patients on long-term treatment with NSAIDs, including Ponstel, should
have their hemoglobin or hematocrit checked if they exhibit any signs
or symptoms of anemia.
All drugs which inhibit the biosynthesis of prostaglandins may interfere
to some extent with platelet function and vascular responses to bleeding.
NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding
time in some patients. Unlike aspirin, their effect on platelet function
is quantitatively less, or shorter duration, and reversible. Ponstel does
not generally affect platelet counts, or partial thromboplastin time (PTT),
but may prolong prothrombin time (PT). Patients receiving Ponstel who
may be adversely affected by alterations in platelet function, such as
those with coagulation disorders or patients receiving anticoagulants,
should be carefully monitored.
Fluid Retention and Edema
Fluid retention and edema have been observed in some patients taking
NSAIDs. Therefore, as with other NSAIDs, Ponstel should be used with caution
in patients with fluid retention, hypertension, or heart failure.
Preexisting Asthma
Patients with asthma may have aspirin-sensitive asthma. The use of aspirin
in patients with aspirin-sensitive asthma has been associated with severe
bronchospasm which can be fatal. Since cross reactivity, including bronchospasm,
between aspirin and other nonsteroidal anti-inflammatory drugs has been
reported in such aspirin-sensitive patients, Ponstel should not be administered
to patients with this form of aspirin sensitivity and should be used with
caution in patients with preexisting asthma.
Information for Patients
See PATIENT INFORMATION section.
Laboratory Tests
Patients on long-term treatment with NSAIDs should have their CBC and
a chemistry profile checked periodically. If clinical signs and symptoms
consistent with liver or renal disease develop, systemic manifestations
occur (e.g.. eosinophilia, rash, etc.) or if abnormal liver tests persist
or worsen, Ponstel should be discontinued.
Drug Interactions
See DRUG INTERATIONS section.
Drug/Laboratory Test Interactions
Ponstel may prolong prothrombin time.4
Therefore, when the drug is administered to patients receiving oral anticoagulant
drugs, frequent monitoring of prothrombin time is necessary.
A false-positive reaction for urinary bile, using the diazo tablet test,
may result after mefenamic acid administration. If biliuria is suspected,
other diagnostic procedures, such as the Harrison spot test, should be
performed.
Pregnancy
Teratogenic Effects
Pregnancy Category C. Reproduction studies have been performed
in rats, rabbits, and dogs. Rats given up to 10 times the human dose showed
decreased fertility, delay in parturition, and a decreased rate of survival
to weaning. Rabbits at 2.5 times the human dose showed an increase in
the number of resorptions. There were no fetal anomalies observed in these
studies nor in dogs at up to 10 times the human dose.4
However, animal reproduction studies are not always predictive of human
response. There are no adequate and well-controlled studies in pregnant
women. Ponstel should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus.
Nonteratogenic Effects
Because of the known effects of nonsteroidal anti-inflammatory drugs
on the fetal cardiovascular system (closure of ductus arteriosus), use
during pregnancy (particularly late pregnancy) should be avoided.
Labor and Delivery
In rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin
synthesis, an increased incidence of dystocia, delayed parturition, and
decreased pup survival occurred. The effects of Ponstel on labor and delivery
in pregnant women are unknown.
Nursing Mothers
Trace amounts of Ponstel may be present in breast milk and transmitted
to the nursing infant.7 Because of the
potential for serious adverse reactions in nursing infants from Ponstel
a decision should be made whether to discontinue nursing or to discontinue
the drug, taking into account the importance of the drug to the mother.
Pediatric Use
Safety and effectiveness in pediatric patients below the age of 14 have
not been established.
Geriatric Use
As with any NSAID, caution should be exercised in treating the elderly
(65 years and older).
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