Meloxicam tablets 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.
The pharmacological activity of meloxicam tablets in reducing
fever and inflammation may diminish the utility of these diagnostic signs in
detecting complications of presumed noninfectious, painful conditions.
Borderline elevations of one or more liver tests may
occur in up to 15% of patients taking NSAIDs including meloxicam tablets. 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 meloxicam tablets. If clinical signs and symptoms
consistent with liver disease develop, or if systemic manifestations occur
(e.g., eosinophilia, rash, etc.), meloxicam tablets should be discontinued.
Caution should be used when initiating treatment with
meloxicam tablets in patients with considerable dehydration. It is advisable to
rehydrate patients first and then start therapy with meloxicam tablets. Caution
is also recommended in patients with pre-existing kidney disease (see
WARNINGS, Renal Effects, and Advanced Renal Disease).
The extent to which metabolites may accumulate in
patients with renal failure has not been studied with meloxicam tablets.
Because some meloxicam tablets metabolites are excreted by the kidney, patients
with significantly impaired renal function should be more closely monitored.
Anemia is sometimes seen in patients receiving NSAIDs,
including meloxicam tablets. This may be due to fluid retention, occult or
gross GI blood loss, or an incompletely described effect upon erythropoiesis.
Patients on long-term treatment with NSAIDs, including meloxicam tablets,
should have their hemoglobin or hematocrit checked if they exhibit any signs or
symptoms of anemia.
Drugs which inhibit the biosynthesis of prostaglandins
may interfere to some extent with platelet function and vascular responses to
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, of shorter duration, and reversible.
Patients receiving meloxicam tablets who may be adversely affected by
alterations in platelet function, such as those with coagulation disorders or
patients receiving anticoagulants, should be carefully monitored.
Patients with asthma may have aspirin-sensitive asthma.
The use of aspirin in patients with aspirinsensitive asthma has been associated
with severe bronchospasm which can be fatal. Since cross reactivity, including
bronchospasm, between aspirin and other NSAIDs has been reported in such
aspirin-sensitive patients, meloxicam tablets should not be administered to
patients with this form of aspirin sensitivity and should be used with caution
in patients with pre-existing asthma.
Information For Patients
Patients should be informed of the following
information before initiating therapy with an NSAID and periodically during the
course of ongoing therapy. Patients should also be encouraged to read the NSAID
Medication Guide that accompanies each prescription dispensed.
Meloxicam tablets, like other NSAIDs, may cause serious
CV side effects, such as MI or stroke, which may result in hospitalization and
even death. Although serious CV events can occur without warning symptoms,
patients should be alert for the signs and symptoms of chest pain, shortness of
breath, weakness, slurring of speech, and should ask for medical advice when
observing any indicative sign or symptoms. Patients should be apprised of the
importance of this follow-up (see WARNINGS, Cardiovascular Effects).
Meloxicam tablets, like other NSAIDs, can cause GI
discomfort and, rarely, serious GI side effects, such as ulcers and bleeding,
which may result in hospitalization and even death. Although serious GI tract
ulcerations and bleeding can occur without warning symptoms, patients should be
alert for the signs and symptoms of ulcerations and bleeding, and should ask
for medical advice when observing any indicative sign or symptoms including
epigastric pain, dyspepsia, melena, and hematemesis. Patients should be
apprised of the importance of this follow-up (see WARNINGS, Gastrointestinal
(GI) Effects - Risk of GI Ulceration, Bleeding, and Perforation).
Meloxicam tablets, like other NSAIDs, can cause serious
skin side effects such as exfoliative dermatitis, SJS, and TEN, which may
result in hospitalizations and even death. Although serious skin reactions may
occur without warning, patients should be alert for the signs and symptoms of
skin rash and blisters, fever, or other signs of hypersensitivity such as
itching, and should ask for medical advice when observing any indicative signs
or symptoms. Patients should be advised to stop the drug immediately if they
develop any type of rash and contact their physicians as soon as possible.
Patients should promptly report signs or symptoms of
unexplained weight gain or edema to their physicians.
Patients should be informed of the warning signs and
symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus,
jaundice, right upper quadrant tenderness, and “flu-like” symptoms).
If these occur, patients should be instructed to stop therapy and seek
immediate medical therapy.
Patients should be informed of the signs of an
anaphylactoid reaction (e.g., difficulty breathing, swelling of the face or
throat). If these occur, patients should be instructed to seek immediate emergency
help (see WARNINGS).
In late pregnancy, as with other NSAIDs, meloxicam
tablets should be avoided because it will cause premature closure of the ductus
Because serious GI tract ulcerations and bleeding can
occur without warning symptoms, physicians should monitor for signs or symptoms
of GI bleeding. 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, meloxicam tablets should be discontinued.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
No carcinogenic effect of meloxicam was observed in rats
given oral doses up to 0.8 mg/kg/day (approximately 0.4-fold the human dose at
15 mg/day for a 50 kg adult based on body surface area conversion) for 104
weeks or in mice given oral doses up to 8.0 mg/kg/day (approximately 2.2-fold
the human dose, as noted above) for 99 weeks.
Meloxicam was not mutagenic in an Ames assay, or
clastogenic in a chromosome aberration assay with human lymphocytes and an in
vivo micronucleus test in mouse bone marrow.
Meloxicam did not impair male and female fertility in
rats at oral doses up to 9 and 5 mg/kg/day, respectively (4.9-fold and 2.5-fold
the human dose, as noted above). However, an increased incidence of
embryolethality at oral doses ≥ 1
mg/kg/day (0.5-fold the human dose, as noted above) was observed in rats when
dams were given meloxicam 2 weeks prior to mating and during early embryonic development.
Pregnancy Category C.
Meloxicam caused an increased incidence of septal defect
of the heart, a rare event, at an oral dose of 60 mg/kg/day (64.5-fold the
human dose at 15 mg/day for a 50 kg adult based on body surface area conversion)
and embryolethality at oral doses ≥ 5 mg/kg/day (5.4-fold the human dose,
as noted above) when rabbits were treated throughout organogenesis. Meloxicam
was not teratogenic in rats up to an oral dose of 4 mg/kg/day (approximately
2.2-fold the human dose, as noted above) throughout organogenesis. An increased
incidence of stillbirths was observed when rats were given oral doses ≥ 1
mg/kg/day throughout organogenesis. Meloxicam crosses the placental barrier.
There are no adequate and well-controlled studies in pregnant women. Meloxicam
tablets should be used during pregnancy only if the potential benefit justifies
the potential risk to the fetus.
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.
Meloxicam caused a reduction in birth index, live births,
and neonatal survival at oral doses ≥ 0.125 mg/kg/day (approximately
0.07-fold the human dose at 15 mg/day for a 50 kg adult based on body surface
area conversion) when rats were treated during the late gestation and lactation
period. No studies have been conducted to evaluate the effect of meloxicam on
the closure of the ductus arteriosus in humans; use of meloxicam during the
third trimester of pregnancy should be avoided.
Labor And Delivery
Studies in rats with meloxicam, as with other drugs known
to inhibit prostaglandin synthesis, showed an increased incidence of
stillbirths, prolonged delivery, and delayed parturition at oral dosages ≥ 1
mg/kg/day (approximately 0.5-fold the human dose at 15 mg/day for a 50 kg adult
based on body surface area conversion), and decreased pup survival at an oral
dose of 4 mg/kg/day (approximately 2.1-fold the human dose, as noted above)
throughout organogenesis. Similar findings were observed in rats receiving oral
dosages ≥ 0.125
mg/kg/day (approximately 0.07-fold the human dose, as noted above) during late
gestation and the lactation period. The effects of meloxicam tablets on labor
and delivery in pregnant women are unknown.
It is not known whether this drug is excreted in human milk
however, meloxicam was excreted in the milk of lactating rats at concentrations
higher than those in plasma.
Because many drugs are excreted in human milk and because
of the potential for serious adverse reactions in nursing infants from
meloxicam tablets, a decision should be made whether to discontinue nursing or
to discontinue the drug, taking into account the importance of the drug to the
Use of this drug product for a pediatric indication is
protected by marketing exclusivity.
As with any NSAID, caution should be exercised in
treating the elderly (65 years and older).