QMIIZ ODT: Package Insert and Label Information (Page 2 of 5)

5.7 Anaphylactic Reactions

Meloxicam has been associated with anaphylactic reactions in patients with and without known hypersensitivity to meloxicam and in patients with aspirin-sensitive asthma [see Contraindications (4) and Warnings and Precautions (5.8)].

Seek emergency help if an anaphylactic reaction occurs.

5.8 Exacerbation of Asthma Related to Aspirin Sensitivity

A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin- sensitive patients, QMIIZ ODT is contraindicated in patients with this form of aspirin sensitivity [see Contraindications (4) ]. When QMIIZ ODT is used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma.

5.9 Serious Skin Reactions

NSAIDs, including meloxicam, can cause serious skin adverse reactions 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 reactions, and to discontinue the use of QMIIZ ODT at the first appearance of skin rash or any other sign of hypersensitivity. QMIIZ ODT is contraindicated in patients with previous serious skin reactions to NSAIDs [see Contraindications (4) ].

5.10 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) has been reported in patients taking NSAIDs such as QMIIZ ODT. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling. Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. Sometimes symptoms of DRESS may resemble an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its presentation, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, discontinue QMIIZ ODT and evaluate the patient immediately.

5.11 Fetal Toxicity

Premature Closure of Fetal Ductus Arteriosus

Avoid use of NSAIDs, including QMIIZ ODT, in pregnant women at about 30 weeks gestation and later. NSAIDs, including QMIIZ ODT, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age.

Oligohydramnios/Neonatal Renal Impairment

Use of NSAIDs, including QMIIZ ODT, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation. Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.

If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit QMIIZ ODT use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if QMIIZ ODT treatment extends beyond 48 hours. Discontinue QMIIZ ODT if oligohydramnios occurs and follow up according to clinical practice [see Use in Specific Populations (8.1) ].

5.12 Hematologic Toxicity

Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. If a patient treated with QMIIZ ODT has any signs or symptoms of anemia, monitor hemoglobin or hematocrit.

NSAIDs, including QMIIZ ODT, may increase the risk of bleeding events. Co-morbid conditions such as coagulation disorders or concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. Monitor these patients for signs of bleeding [see Drug Interactions (7) ].

5.13 Patients with Phenylketonuria

QMIIZ ODT contains phenylalanine (a component of aspartame). The 7.5 mg and 15 mg orally disintegrating tablets contain 0.30 mg and 0.59 mg of phenylalanine, respectively. QMIIZ ODT is contraindicated in patients with phenylketonuria [see Contraindications (4) ].

5.14 Masking of Inflammation and Fever

The pharmacological activity of QMIIZ ODT in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections.

5.15 Laboratory Monitoring

Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a complete blood count (CBC) and a chemistry profile periodically [see Warnings and Precautions (5.2, 5.3, 5.6)].

6 ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the labeling:

  • Cardiovascular Thrombotic Events [see Boxed Warning and Warnings and Precautions (5.1)]
  • GI Bleeding, Ulceration, and Perforation [see Boxed Warning and Warnings and Precautions (5.2)]
  • Hepatotoxicity [see Warnings and Precautions (5.3) ]
  • Hypertension [see Warnings and Precautions (5.4) ]
  • Heart Failure and Edema [see Warnings and Precautions (5.5) ]
  • Renal Toxicity and Hyperkalemia [see Warnings and Precautions (5.6) ]
  • Anaphylactic Reactions [see Warnings and Precautions (5.7) ]
  • Serious Skin Reactions [see Warnings and Precautions (5.9) ]
  • Hematologic Toxicity [see Warnings and Precautions (5.12) ]

6.1 Clinical Trials Experience

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.

A total of 100 subjects entered four studies with QMIIZ ODT; 36 subjects entered two separate pilot bioavailability studies (BA); 32 subjects entered a bioequivalence (BE) study, and 32 subjects entered a food-effect study. The adverse reactions from the BA, BE, and food-effect studies are summarized in Table 1.

Ten (10) adverse reactions were reported after receiving QMIIZ ODT and ten (10) adverse reactions were reported after receiving meloxicam tablets.

Table 1 Adverse Reactions in BA, BE, and Food-Effect Study in ≥ 2% of Subjects

1 N = number of subjects that reported adverse reactions

2 N = % of subjects that reported adverse reactions

Adverse Reaction QMIIZ ODT N 1 (%) 2 Meloxicam N 1 (%) 2
Alanine aminotransferase increased 0 (0.0) 2 (2.0)
Blood pressure decreased 2 (2.0) 3 (3.0)
Headache 2 (2.0) 1 (1.0)

The most frequently reported adverse reactions associated with QMIIZ ODT were: blood pressure decreased (2 subjects, 2.0%) and headache (2 subjects, 2.0%). The most frequently reported adverse reactions associated with meloxicam tablets were: blood pressure decreased (3 subjects, 3.0%) and alanine aminotransferase increased (2 subjects, 2.0%).

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 2 depicts adverse events that occurred in ≥2% of the meloxicam treatment groups in a 12-week placebo- and active-controlled osteoarthritis trial.
  • Table 3 depicts adverse events that occurred in ≥2% of the meloxicam treatment groups in two 12-week placebo-controlled rheumatoid arthritis trials.
Table 2 Adverse Events (%) Occurring in ≥ 2% of Meloxicam Patients in a 12-Week Osteoarthritis Placebo- and Active-Controlled Trial

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

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
Edema1 2.5 1.6 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 3 Adverse Events (%) Occurring in ≥ 2% of Meloxicam Patients in two 12-Week Rheumatoid Arthritis Placebo-Controlled Trials

1 MedDRA high level term, (preferred terms): dyspeptic signs and symptoms (dyspepsia, dyspepsia aggravated, eructation, gastrointestinal irritation), upper respiratory tract infections-pathogens unspecified (laryngitis NOS, sinusitis NOS) joint related signs and symptoms (arthralgia, arthralgia aggravated, joint crepitation, joint effusion joint swelling),

2 MedDRA preferred terms: nausea, abdominal pain NOS, influenza-like illness, headaches NOS, and rash NOS

Placebo Meloxicam 7.5 mg daily Meloxicam 15 mg daily
No. of Patients 469 481 477
Gastrointestinal Disorders 14.1 18.9 16.8
Abdominal pain NOS2 0.6 2.9 2.3
Dyspeptic signs and symptoms1 3.8 5.8 4.0
Nausea 2.6 3.3 3.8
General Disorders and Administrative 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
Nervous System Disorders
Headaches NOS2 6.4 6.4 5.5
Skin and Subcutaneous Tissue Disorders
Rash NOS2 1.7 1.0 2.1

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 4.

Table 4 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

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 meloxicam (22.5 mg and greater) have been associated with an increased risk of serious GI events; therefore, the daily dose of QMIIZ ODT 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 meloxicam 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 meloxicam 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 meloxicam. 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 meloxicam in clinical trials involving approximately 16,200 patients.

Body as a Whole allergic reaction, 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 leukopenia, purpura, thrombocytopenia
Liver and Biliary System ALT increased, AST increased, bilirubinemia, gamma-glutamyl transferase (GGT) increased, hepatitis
Metabolic and Nutritional dehydration
Psychiatric abnormal dreaming, anxiety, appetite increased, confusion, depression, nervousness, somnolence
Respiratory asthma, bronchospasm, dyspnea
Skin and Appendages alopecia, angioedema, bullous eruption, photosensitivity reaction, pruritus, sweating increased, urticaria
Special Senses abnormal vision, conjunctivitis, taste perversion, tinnitus
Urinary System albuminuria, blood urea nitrogen (BUN) increased, creatinine increased, hematuria, renal failure

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