Mobic (Meloxicam) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

Adults

Osteoarthritis and Rheumatoid Arthritis

The MOBIC Phase 2/3 clinical trial database includes 10,122 OA patients and 1012 RA patients treated with MOBIC 7.5 mg/day, 3,505 OA patients and 1351 RA patients treated with MOBIC 15 mg/day. MOBIC 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 MOBIC 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 MOBIC 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 MOBIC with placebo.

Table 2a depicts adverse events that occurred in ≥ 2% of the MOBIC treatment groups in a 12-week placebo and active-controlled osteoarthritis trial.

Table 2b depicts adverse events that occurred in ≥ 2% of the MOBIC treatment groups in two 12-week placebo controlled rheumatoid arthritis trials.

Table 2a Adverse Events (%) Occurring in ≥ 2% of MOBIC Patients in a 12-Week Osteoarthritis Placebo and Active-Controlled Trial

	Placebo	MOBIC 7.5 mg daily	MOBIC 15 mg daily	Diclofenac 100 mg daily
No. of Patients	157	154	156	153
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
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
Edema1	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
Rash2	2.5	2.6	0.6	2.0

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

	Placebo	MOBIC 7.5 mg daily	MOBIC 15 mg daily
No. of Patients	469	481	477
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),, and musculoskeletal and connective tissue signs and symptoms NEC (back pain, back pain aggravated, muscle spasms, musculoskeletal pain)
2 MedDRA preferred term: diarrhea NOS, nausea, abdominal pain NOS, influenza like illness, headaches NOS, dizziness (excl vertigo), and rash NOS
Gastrointestinal disorders	14.1	18.9	16.8
Abdominal pain NOS2	0.6	2.9	2.3
Diarrhea NOS2	5.1	4.8	3.4
Dyspeptic signs and symptoms1	3.8	5.8	4.0
Nausea2	2.6	3.3	3.8
General disorders and administration site conditions
Influenza like illness2	2.1	2.9	2.3
Infection and infestations
Upper respiratory tract infections-pathogen     class unspecified1	4.1	7.0	6.5
Musculoskeletal and connective tissue disorders
Joint related signs and symptoms1	1.9	1.5	2.3
Musculoskeletal and connective tissue     signs and symptoms NEC1	3.8	1.7	2.9
Nervous system disorders
Headaches NOS2	6.4	6.4	5.5
Dizziness (excl vertigo)2	3.0	2.3	0.4
Skin and subcutaneous tissue disorders
Rash NOS2	1.7	1.0	2.1

The adverse events that occurred with MOBIC in ≥ 2% of patients treated short-term (4-6 weeks) and long-term (6 months) in active-controlled osteoarthritis trials are presented in Table 3.

Table 3 Adverse Events (%) Occurring in ≥ 2% of MOBIC Patients in 4 to 6 Weeks and 6 Month Active-Controlled Osteoarthritis Trials

	4-6 Weeks Controlled Trials		6 Month Controlled Trials
	MOBIC 7.5 mg daily	MOBIC 15 mg daily	MOBIC 7.5 mg daily	MOBIC 15 mg daily
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
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
Edema1	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
Rash2	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

Higher doses of MOBIC (22.5 mg and greater) have been associated with an increased risk of serious GI events; therefore the daily dose of MOBIC should not exceed 15 mg.

Pediatrics

Pauciarticular and Polyarticular Course Juvenile Rheumatoid Arthritis (JRA)

Three hundred and eighty-seven patients with pauciarticular and polyarticular course JRA were exposed to MOBIC with doses ranging from 0.125 to 0.375 mg/kg per day in three clinical trials. These studies consisted of two 12-week multicenter, double-blind, randomized trials (one with a 12-week open-label extension and one with a 40-week extension) and one 1-year open-label PK study. The adverse events observed in these pediatric studies with MOBIC were similar in nature to the adult clinical trial experience, although there were differences in frequency. In particular, the following most common adverse events, abdominal pain, vomiting, diarrhea, headache, and pyrexia, were more common in the pediatric than in the adult trials. Rash was reported in seven (<2%) patients receiving MOBIC. No unexpected adverse events were identified during the course of the trials. The adverse events did not demonstrate an age or gender-specific subgroup effect.

The following is a list of adverse drug reactions occurring in < 2% of patients receiving MOBIC in clinical trials involving approximately 16,200 patients. Adverse reactions reported only in worldwide post-marketing experience or the literature are shown in italics and are considered rare (< 0.1%).

Body as a Whole	allergic reaction, anaphylactoid reactions including shock, face edema, fatigue, fever, hot flushes, malaise, syncope, weight decrease, weight increase
Cardiovascular	angina pectoris, cardiac failure, hypertension, hypotension, myocardial infarction, vasculitis
Central and Peripheral Nervous System	convulsions, paresthesia, tremor, vertigo
Gastrointestinal	colitis, dry mouth, duodenal ulcer, eructation, esophagitis, gastric ulcer, gastritis, gastroesophageal reflux, gastrointestinal hemorrhage, hematemesis, hemorrhagic duodenal ulcer, hemorrhagic gastric ulcer, intestinal perforation, melena, pancreatitis, perforated duodenal ulcer, perforated gastric ulcer, stomatitis ulcerative
Heart Rate and Rhythm	arrhythmia, palpitation, tachycardia
Hematologic	agranulocytosis, leukopenia, purpura, thrombocytopenia
Liver and Biliary System	ALT increased, AST increased, bilirubinemia, GGT increased, hepatitis, jaundice, liver failure
Metabolic and Nutritional	dehydration
Psychiatric Disorders	abnormal dreaming, anxiety, appetite increased, confusion, depression, nervousness, somnolence
Respiratory	asthma, bronchospasm, dyspnea
Skin and Appendages	alopecia, angioedema, bullous eruption, erythema multiforme, photosensitivity reaction, pruritus, exfoliative dermatitis, Stevens-Johnson syndrome, sweating increased, toxic epidermal necrolysis, urticaria
Special Senses	abnormal vision, conjunctivitis, taste perversion, tinnitus
Urinary System	acute urinary retention, albuminuria, BUN increased, creatinine increased, hematuria, interstitial nephritis, renal failure