Meloxicam Information
Meloxicam () . Dosage And Administration
Carefully consider the potential benefits and risks of Meloxicam () tablets and other treatment options before deciding to use Meloxicam () tablets. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals [see
After observing the response to initial therapy with Meloxicam () tablets, adjust the dose to suit an individual patient's needs.
In adults, the maximum recommended daily oral dose of Meloxicam () tablets are 15 mg regardless of formulation. In patients with hemodialysis, a maximum daily dosage of 7.5 mg is recommended [see
Meloxicam () may be taken without regard to timing of meals.
Meloxicam () . Warnings And Precautions
Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years’ duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, 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.
Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke [see
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 does increase the risk of serious GI events [see
NSAIDs, including Meloxicam () , 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 3-6 months, and in about 2-4% 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 therapyHowever, even short-term therapy is not without risk.
Prescribe NSAIDs, including Meloxicam () , 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 an NSAID, use the lowest effective dose for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during Meloxicam () therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of Meloxicam () until a serious GI adverse event is ruled out. For high-risk patients, consider alternate therapies that do not involve NSAIDs.
Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including Meloxicam () . 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 [see
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 () . If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), discontinue Meloxicam () [see
NSAIDs, including Meloxicam () , can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. NSAIDs, including Meloxicam () , 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.
Patients taking ACE inhibitors, thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs.
Long-term administration of NSAIDs, including Meloxicam () , can result in renal papillary necrosis, renal insufficiency, acute renal failure, and other renal injury. Renal toxicity has also been seen in patients in whom 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-dependent 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, ACE-inhibitors, and angiotensin II receptor antagonists, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
A pharmacokinetic study in patients with mild and moderate renal impairment revealed that no dosage adjustments in these patient populations are required. Patients with severe renal impairment have not been studied. The use of Meloxicam () in patients with severe renal impairment with CrCl less than 20 mL/min is not recommended. A study performed in patients on hemodialysis revealed that although overall C was diminished in this population, the proportion of free drug not bound to plasma was increased. Therefore it is recommended that Meloxicam () dosage in this population not exceed 7.5 mg per day. Closely monitor the renal function of patients with impaired renal function who are taking Meloxicam () [see
Use caution when initiating treatment with Meloxicam () in patients with considerable dehydration. It is advisable to rehydrate patients first and then start therapy with Meloxicam () . Caution is also recommended in patients with pre-existing kidney disease.
The extent to which metabolites may accumulate in patients with renal impairment has not been studied with Meloxicam () . Because some Meloxicam () metabolites are excreted by the kidney, monitor patients with significant renal impairment closely.
Anemia may occur in patients receiving NSAIDs, including Meloxicam () . 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 () , should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.
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. Carefully monitor patients treated with Meloxicam () who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants.
Meloxicam () . Adverse Reactions
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The following serious adverse reactions are discussed elsewhere in the labeling:
Adults
Osteoarthritis and Rheumatoid Arthritis
The Meloxicam () Phase 2/3 clinical trial database includes 10,122 OA patients and 1012 RA patients treated with Meloxicam () 7.5 mg/day, 3,505 OA patients and 1351 RA patients treated with Meloxicam () 15 mg/day. Meloxicam () at these doses was administered to 661 patients for at least 6 months and to 312 patients for at least one year. Approximately 10,500 of these patients were treated in ten placebo- and/or active-controlled osteoarthritis trials and 2363 of these patients were treated in ten placebo- and/or active-controlled rheumatoid arthritis trials. Gastrointestinal (GI) adverse events were the most frequently reported adverse events in all treatment groups across Meloxicam () trials.
A 12-week multicenter, double-blind, randomized trial was conducted in patients with osteoarthritis of the knee or hip to compare the efficacy and safety of Meloxicam () with placebo and with an active control. Two 12-week multicenter, double-blind, randomized trials were conducted in patients with rheumatoid arthritis to compare the efficacy and safety of Meloxicam () with placebo.
Table 1a depicts adverse events that occurred in ≥2% of the Meloxicam () treatment groups in a 12-week placebo- and active-controlled osteoarthritis trial.
Table 1b depicts adverse events that occurred in ≥2% of the Meloxicam () treatment groups in two 12-week placebo- controlled rheumatoid arthritis trials.
The adverse events that occurred with Meloxicam () in ≥2% of patients treated short-term (4-6 weeks) and long-term (6 months) in active-controlled osteoarthritis trials are presented in Table 2
Higher doses of Meloxicam () (22.5 mg and greater) have been associated with an increased risk of serious GI events; therefore, the daily dose of Meloxicam () should not exceed 15 mg.
The following is a list of adverse drug reactions occurring in
Meloxicam () . Drug Interactions
When Meloxicam () is administered with aspirin (1000 mg three times daily) to healthy volunteers, an increase the AUC (10%) and C (24%) of Meloxicam () was noted. The clinical significance of this interaction is not known; however, as with other NSAIDs concomitant administration of Meloxicam () and aspirin is not generally recommended because of the potential for increased adverse effects.
Concomitant administration of low-dose aspirin with Meloxicam () may result in an increased rate of GI ulceration or other complications, compared to use of Meloxicam () alone. Meloxicam () is not a substitute for aspirin for cardiovascular prophylaxis.
The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone.
Monitor anticoagulant activity, particularly in the first few days after initiating or changing Meloxicam () therapy in patients receiving warfarin or similar agents, since these patients are at an increased risk of bleeding than with the use of either drug alone. Use caution when administering Meloxicam () with warfarin since patients on warfarin may experience changes in INR and an increased risk of bleeding complications when a new medication is introduced [see
Meloxicam () . Use In Specific Populations
Pregnancy Category C; Category D starting 30 weeks gestation.
There are no adequate and well-controlled studies in pregnant women. Meloxicam () crosses the placental barrier. Prior to 30 weeks gestation, use Meloxicam () during pregnancy only if the potential benefit justifies the potential risk to the fetus. Starting at 30 weeks gestation, avoid Meloxicam () and other NSAIDs, in pregnant women as premature closure of the ductus arteriosus in the fetus may occur. If this drug is used during this time period in pregnancy, inform the patient of the potential hazard to a fetus [see
Teratogenic Effects
Meloxicam () was not teratogenic when administered to pregnant rats during fetal organogenesis at oral doses up to 4 mg/kg/day (2.6-fold greater than the maximum recommended human daily dose [MRHD] based on body surface area [BSA] comparison). Administration of Meloxicam () to pregnant rabbits throughout embryogenesis produced an increased incidence of septal defects of the heart at an oral dose of 60 mg/kg/day. The no effect level was 20 mg/kg/day (26-fold greater than the MRHD based on BSA conversion).
Nonteratogenic Effects
In rats and rabbits, embryolethality occurred at oral Meloxicam () doses of 1 mg/kg/day and 5 mg/kg/day, respectively (0.65-and 6.5-fold greater, respectively, than the MRHD based on BSA comparison) when administered throughout organogenesis.
As with any NSAID, caution should be exercised in treating the elderly (65 years and older).
Of the total number of subjects in clinical studies, 5157 were age 65 and over (4044 in OA studies and 1113 in RA studies). No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Meloxicam () . Overdosage
There is limited experience with Meloxicam () overdose. Four cases have taken 6 to 11 times the highest recommended dose; all recovered. Cholestyramine is known to accelerate the clearance of Meloxicam () .
Symptoms following acute NSAID overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain, which are generally reversible with supportive care. Gastrointestinal bleeding can occur. Severe poisoning may result in hypertension, acute renal failure, hepatic dysfunction, respiratory depression, coma, convulsions, cardiovascular collapse, and cardiac arrest. Anaphylactoid reactions have been reported with therapeutic ingestion of NSAIDs, and may occur following an overdose.
Patients should be managed with symptomatic and supportive care following an NSAID overdose. Administration of activated charcoal is recommended for patients who present 1-2 hours after overdose. For substantial overdose or severely symptomatic patients, activated charcoal may be administered repeatedly. Accelerated removal of Meloxicam () by 4 gm oral doses of cholestyramine given three times a day was demonstrated in a clinical trial. Administration of cholestyramine may be useful following an overdose. Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion may not be useful due to high protein binding.
For additional information about overdose treatment, call a poison control center (1-800-222-1222).
Meloxicam () . Description
Meloxicam () , an oxicam derivative, is a member of the enolic acid group of nonsteroidal anti-inflammatory drugs (NSAIDs). Each yellow Meloxicam () tablet contains 7.5 mg or 15 mg Meloxicam () for oral administration. Meloxicam () is chemically designated as 4-hydroxy-2-methyl--(5-methyl-2-thiazolyl)--1,2-benzothiazine-3carboxamide-1,1-dioxide. The molecular weight is 351.4. Its empirical formula is CHNOS and it has the following structural formula.
Meloxicam () is a pale yellow powder, practically insoluble in water, slightly soluble in acetone, soluble in dimethylformamide, very slightly soluble in ethanol (96 %) and in methanol. Meloxicam () has an apparent partition coefficient (log P) = 0.1 in -octanol/buffer pH 7.4. Meloxicam () has pKa values of 1.1 and 4.2.
Each Meloxicam () tablet intended for oral administration contains 7.5 mg or 15 mg of Meloxicam () . In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, crospovidone, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone and sodium citrate dihydrate.
Meloxicam () . How Supplied/storage And Handling
Meloxicam () Tablets, 7.5 mg are yellow, round-shaped, flat beveled edge, uncoated tablets debossed with ‘ZC’ and ‘25’ on one side and plain on other side and are supplied as follows:
NDC 65841-050-16 in bottles of 90 tablets
NDC 65841-050-01 in bottles of 100 tablets
NDC 65841-050-05 in bottles of 500 tablets
NDC 65841-050-31 in unit-of-use packages of 30 tablets
Meloxicam () Tablets, 15 mg are yellow, round-shaped, flat beveled edge, uncoated tablet debossed with ‘ZC’ and ‘26’ on one side and plain on other side and are supplied as follows:
NDC 65841-051-16 in bottles of 90 tablets
NDC 65841-051-01 in bottles of 100 tablets
NDC 65841-051-05 in bottles of 500 tablets
NDC 65841-051-31 in unit-of-use packages of 30 tablets
Store at 20° to 25° C (68° to 77° F) [see USP Controlled Room Temperature]. Keep Meloxicam () tablets in a dry place.
Dispense tablets in a tight container.
Keep this and all medications out of the reach of children.
Meloxicam ()
Meloxicam ()
Meloxicam ()
Meloxicam () Package Label.principal Display Panel
NDC 65841-050-01 in bottle of 100 tablets
Meloxicam () Tablets, 7.5 mg
Ronly
100 tablets
ZYDUS
NDC 65841-051-01 in bottle of 100 tablets
Meloxicam () Tablets, 15 mg
Ronly
100 tablets
ZYDUS
