A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Mobic Side Effects, and Drug Interactions - Meloxicam
Mobic Side Effects, and Drug Interactions - Meloxicam
SIDE EFFECTS
The MOBIC phase 2/3 clinical trial database includes 10,122 patients
treated with MOBIC 7.5 mg/day and 3,505 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. 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. Table 2 depicts
adverse events that occurred in ³ 2% of
the MOBIC treatment groups.
| Table 2 Adverse Events (%) Occurring
in ³ 2% of MOBIC Patients in
a 12-Week Osteoarthritis Placebo and Active-Controlled Trial |
Body System /
Adverse Event |
Placebo |
MOBIC
7.5 mg daily |
MOBIC
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 |
1.9 |
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 |
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
The adverse events that occurred with MOBIC in ³
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 ³ 2% of MOBIC Patients in
4 to 6 Weeks and 6 Month Active-Controlled Osteoarthritis Trials |
Body System /
Adverse Event |
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 |
| 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
|
| 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 |
| Musculo-Skeletal |
| 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 |
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
As with other NSAIDs, higher doses of MOBIC (e.g., chronic daily 30 mg
dose) were associated with an increased risk of serious GI events, therefore
the daily dose of MOBIC should not exceed 15 mg.
The following is a list of adverse drug reactions occurring in < 2%
of patients receiving MOBIC in clinical trials involving approximately
15,400 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,
bilirubinema, 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,
Stevens-Johnson syndrome, sweating
increased, toxic epidermal
necrolysis, urticaria |
| Special Senses: |
abnormal vision, conjunctivitis,
taste perversion, tinnitus |
| Urinary System: |
albuminuria, BUN increased, creatinine
increased, hematuria, interstitial
nephritis, renal failure |
DRUG INTERACTIONS
ACE inhibitors
Reports suggest that NSAIDs may diminish the antihypertensive effect
of angiotensin-converting enzyme (ACE) inhibitors. This interaction should
be given consideration in patients taking NSAIDs concomitantly with ACE
inhibitors.
Aspirin
Concomitant administration of aspirin (1000 mg TID) to healthy volunteers
tended to increase the AUC (10%) and Cmax (24%) of meloxicam.
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 MOBIC may
result in an increased rate of GI ulceration or other complications, compared
to use of MOBIC alone. MOBIC is not a substitute for aspirin for cardiovascular
prophylaxis.
Cholestyramine
Pretreatment for four days with cholestyramine significantly increased
the clearance of meloxicam by 50%. This resulted in a decrease in t1/2,
from 19.2 hours to 12.5 hours, and a 35% reduction in AUC. This suggests
the existence of a recirculation pathway for meloxicam in the gastrointestinal
tract. The clinical relevance of this interaction has not been established.
Cimetidine
Concomitant administration of 200 mg cimetidine QID did not alter the
single-dose pharmacokinetics of 30 mg meloxicam.
Digoxin
Meloxicam 15 mg once daily for 7 days did not alter the plasma concentration
profile of digoxin after b-acetyldigoxin
administration for 7 days at clinical doses. In vitro testing found
no protein binding drug interaction between digoxin and meloxicam.
Furosemide
Clinical studies, as well as post-marketing observations, have shown
that NSAIDs can reduce the natriuretic effect of furosemide and thiazide
diuretics in some patients. This effect has been attributed to inhibition
of renal prostaglandin synthesis. Studies with furosemide agents and meloxicam
have not demonstrated a reduction in natriuretic effect. Furosemide single
and multiple dose pharmacodynamics and pharmacokinetics are not affected
by multiple doses of meloxicam. Nevertheless, during concomitant therapy
with furosemide and MOBIC, patients should be observed closely for signs
of declining renal function (see PRECAUTIONS,
Renal Effects), as well as to assure diuretic efficacy.
Lithium
In clinical trials, NSAIDs have produced an elevation of plasma lithium
levels and a reduction in renal lithium clearance. In a study conducted
in healthy subjects, mean pre-dose lithium concentration and AUC were
increased by 21% in subjects receiving lithium doses ranging from 804
to 1072 mg BID with meloxicam 15 mg QD as compared to subjects receiving
lithium alone. These effects have been attributed to inhibition of renal
prostaglandin synthesis by MOBIC. Patients on lithium treatment should
be closely monitored when MOBIC is introduced or withdrawn.
Methotrexate
A study in 13 rheumatoid arthritis (RA) patients evaluated the effects
of multiple doses of meloxicam on the pharmacokinetics of methotrexate
taken once weekly. Meloxicam did not have a significant effect on the
pharmacokinetics of single doses of methotrexate. In vitro, methotrexate
did not displace meloxicam from its human serum binding sites.
Warfarin
Anticoagulant activity should be monitored, particularly in the first
few days after initiating or changing MOBIC therapy in patients receiving
warfarin or similar agents, since these patients are at an increased risk
of bleeding. The effect of meloxicam on the anticoagulant effect of warfarin
was studied in a group of healthy subjects receiving daily doses of warfarin
that produced an INR (International Normalized Ratio) between 1.2 and
1.8. In these subjects, meloxicam did not alter warfarin pharmacokinetics
and the average anticoagulant effect of warfarin as determined by prothrombin
time. However, one subject showed an increase in INR from 1.5 to 2.1.
Caution should be used when administering MOBIC with warfarin since patients
on warfarin may experience changes in INR and an increased risk of bleeding
complications when a new medication is introduced.
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