Prescription Drug Information: Meloxicam (Page 2 of 6)

5.4 Hypertension

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.

5.5 Congestive Heart Failure and Edema

Fluid retention and edema have been observed in some patients taking NSAIDs. Use meloxicam with caution in patients with fluid retention, hypertension, or heart failure.

5.6 Renal Effects

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 max 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 Dosage and Administration ( 2.1), Use in Specific Populations ( 8.7), and Clinical Pharmacology ( 12.3) ].

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.

5.7 Anaphylactoid Reactions

As with other NSAIDs, anaphylactoid reactions have occurred in patients without known prior exposure to meloxicam. Meloxicam 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 ( 4.1) and Warnings and Precautions ( 5.12) ]. Seek emergency help in cases where an anaphylactoid reaction occurs.

5.8 Adverse Skin Reactions

NSAIDs, including meloxicam, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin manifestations and discontinue use of the drug at the first appearance of skin rash or any other sign of hypersensitivity.

5.9 Pregnancy

Starting at 30 weeks gestation, avoid the use of meloxicam because it may cause premature closure of the ductus arteriosus [ see Use in Specific Populations ( 8.1) and Patient Counseling Information ( 17.8) ].

5.10 Corticosteroid Treatment

Meloxicam cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Slowly taper patients on prolonged corticosteroid therapy if a decision is made to discontinue corticosteroids.

5.11 Masking of Inflammation and Fever

The pharmacological activity of meloxicam in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

5.12 Hematological Effects

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.

5.13 Use in Patients with Pre-existing 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 NSAIDs has been reported in such aspirin-sensitive patients, meloxicam should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with pre-existing asthma.

5.14 Monitoring

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 should be discontinued.

6 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:

  • Cardiovascular thrombotic events [ see Boxed Warning and Warnings and Precautions ( 5.1)]
  • Gastrointestinal effects – risk of GI ulceration, bleeding, and perforation [ see Boxed Warning and Warnings and Precautions ( 5.2) ]
  • Hepatic effects [see Warnings and Precautions ( 5.3)]
  • Hypertension [see Warnings and Precautions ( 5.4)]
  • Congestive heart failure and edema [see Warnings and Precautions ( 5.5)]
  • Renal effects [see Warnings and Precautions ( 5.6)]
  • Anaphylactoid reactions [ see Warnings and Precautions ( 5.7)]
  • Adverse skin reactions [see Warnings and Precautions ( 5.8)]

6.1 Clinical Trials Experience

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, 3505 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.

Table 1a Adverse Events (%) Occurring in ≥2% of Meloxicam Patients in a 12-Week Osteoarthritis Placebo- and Active-Controlled Trial
Placebo Meloxicam 7.5 mg daily Meloxicam 15 mg daily Diclofenac 100 mg daily
No. of Patients 157 154 156 153
Gastrointestinal 17.2 20.1 17.3 28.1
Abdominal Pain 2.5 1.9 2.6 1.3
Diarrhea 3.8 7.8 3.2 9.2
Dyspepsia 4.5 4.5 4.5 6.5
Flatulence 4.5 3.2 3.2 3.9
Nausea 3.2 3.9 3.8 7.2
Body as a Whole
Accident Household 1.9 4.5 3.2 2.6
Edema 1 2.5 1.9 4.5 3.3
Fall 0.6 2.6 0.0 1.3
Influenza-Like Symptoms 5.1 4.5 5.8 2.6
Central and Peripheral Nervous System
Dizziness 3.2 2.6 3.8 2.0
Headache 10.2 7.8 8.3 5.9
Respiratory
Pharyngitis 1.3 0.6 3.2 1.3
Upper Respiratory Tract Infection 1.9 3.2 1.9 3.3
Skin
Rash 2 2.5 2.6 0.6 2.0

1 WHO preferred terms edema, edema dependent, edema peripheral and edema legs combined 2 WHO preferred terms rash, rash erythematous and rash maculo-papular combined

Table 1b Adverse Events (%) Occurring in ≥2% of Meloxicam Patients in two 12-Week Rheumatoid Arthritis Placebo-Controlled Trials
Placebo

Meloxicam

7.5 mg daily

Meloxicam

15 mg

No. of Patients 469 481 477
Gastrointestinal Disorders 14.1 18.9 16.8
Abdominal Pain NOS 2 0.6 2.9 2.3
Dyspeptic signs and symptoms 1 3.8 5.8 4.0
Nausea 2 2.6 3.3 3.8
General Disorders and Administration Site Conditions
Influenza like illness 2 2.1 2.9 2.3
Infection and Infestations
Upper respiratory tract infections-pathogen class unspecified 1 4.1 7.0 6.5
Musculoskeletal and Connective Tissue Disorders
Joint related signs and symptoms 1 1.9 1.5 2.3
Nervous System Disorders
Headaches NOS 2 6.4 6.4 5.5
Skin and Subcutaneous Tissue Disorders
Rash NOS 2 1.7 1.0 2.1

1 MedDRA high level term (preferred terms): dyspeptic signs and symptoms (dyspepsia, dyspepsia aggravated, eructation, gastrointestinal irritation), upper respiratory tract infections-pathogen unspecified (laryngitis NOS, pharyngitis NOS, sinusitis NOS), joint related signs and symptoms (arthralgia, arthralgia aggravated, joint crepitation, joint effusion, joint swelling) 2 MedDRA preferred term: nausea, abdominal pain NOS, influenza-like illness, headaches NOS, and rash NOS

The adverse events that occurred with meloxicam in ≥2% of patients treated short-term (4 to 6 weeks) and long-term (6 months) in active-controlled osteoarthritis trials are presented in Table 2.

Table 2 Adverse Events (%) Occurring in ≥2% of Meloxicam Patients in 4 to 6 Weeks and 6 Month Active-Controlled Osteoarthritis Trials
4 to 6 Weeks Controlled Trials 6 month Controlled Trials

Meloxicam

7.5 mg daily

Meloxicam

15 mg daily

Meloxicam

7.5 mg daily

Meloxicam

15 mg daily

No. of Patients 8955 256 169 306
Gastrointestinal 11.8 18.0 26.6 24.2
Abdominal Pain 2.7 2.3 4.7 2.9
Constipation 0.8 1.2 1.8 2.6
Diarrhea 1.9 2.7 5.9 2.6
Dyspepsia 3.8 7.4 8.9 9.5
Flatulence 0.5 0.4 3.0 2.6
Nausea 2.4 4.7 4.7 7.2
Vomiting 0.6 0.8 1.8 2.6
Body as a Whole
Accident Household 0.0 0.0 0.6 2.9
Edema 1 0.6 2.0 2.4 1.6
Pain 0.9 2.0 3.6 5.2
Central and Peripheral Nervous System
Dizziness 1.1 1.6 2.4 2.6
Headache 2.4 2.7 3.6 2.6
Hematologic
Anemia 0.1 0.0 4.1 2.9
Musculoskeletal
Arthralgia 0.5 0.0 5.3 1.3
Back Pain 0.5 0.4 3.0 0.7
Psychiatric
Insomnia 0.4 0.0 3.6 1.6
Respiratory
Coughing 0.2 0.8 2.4 1.0
Upper Respiratory Tract Infection 0.2 0.0 8.3 7.5
Skin
Pruritus 0.4 1.2 2.4 0.0
Rash 2 0.3 1.2 3.0 1.3
Urinary
Micturition Frequency 0.1 0.4 2.4 1.3
Urinary Tract Infection 0.3 0.4 4.7 6.9

1 WHO preferred terms edema, edema dependent, edema peripheral and edema legs combined 2 WHO preferred terms rash, rash erythematous and rash maculo-papular combined

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.

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