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
Celebrex Side Effects, and Drug Interactions - Celecoxib
Celebrex Side Effects, and Drug Interactions - Celecoxib
SIDE EFFECTS
Of the CELEBREX treated patients in controlled trials, approximately
4,250 were patients with OA, approximately 2,100 were patients with
RA, and approximately 1,050 were patients with post-surgical pain.
More than 8,500 patients have received a total daily dose
of CELEBREX of 200 mg (100
mg BID or 200 mg QD) or more,
including more than 400 treated at 800 mg (400 mg
BID). Approximately 3,900 patients have received CELEBREX at these
doses for 6 months or more; approximately 2,300 of these have received
it for 1 year or more and 124 of these have received it for 2 years
or more.
Adverse events from controlled trials: Table 4 lists all
adverse events, regardless of causality, occurring in ³2%
of patients receiving CELEBREX from 12 controlled studies conducted
in patients with OA or RA that included a placebo
and/or a positive control
group.
|
Table 4
Adverse Events Occurring in ³
2% Of Celebrex Patients
|
|
Celebrex
(100-200mg
BID)
and
(200mg QD)
|
Placebo
|
Naproxen
500 mg
BID
|
Ibuprofen
800 mg
TID
|
Diclofenac
75 mg
BID
|
| |
(N=4146)
|
(N=1864)
|
(N=1366)
|
(N=387)
|
(N=345)
|
| Gastrointestinal
|
| Abdominal pain
|
4.1%
|
2.8%
|
7.7%
|
9.0%
|
9.0%
|
| Diarrhea |
5.6%
|
3.8%
|
5.3%
|
9.3%
|
5.8%
|
| Dyspepsia |
8.8%
|
6.2%
|
12.2%
|
10.9%
|
12.8%
|
| Flatulence |
2.2%
|
1.0%
|
3.6%
|
4.1%
|
3.5%
|
| Nausea |
3.5%
|
4.2%
|
6.0%
|
3.4%
|
6.7%
|
| Body as a whole
|
| Back Pain |
2.8%
|
3.6%
|
2.2%
|
2.6%
|
0.9%
|
| Peripheral edema
|
2.1%
|
1.1%
|
2.1%
|
1.0%
|
3.5%
|
| Injury-accidental
|
2.9%
|
2.3%
|
3.0%
|
2.6%
|
3.2%
|
| Central and peripheral
nervous system |
| Dizziness |
2.0%
|
1.7%
|
2.6%
|
1.3%
|
2.3%
|
| Headache |
15.8%
|
20.2%
|
14.5%
|
15.5%
|
15.4%
|
| Psychiatric
|
| Insomnia |
2.3%
|
2.3%
|
2.9%
|
1.3%
|
1.4%
|
| Respiratory
|
| Pharyngitis |
2.3%
|
1.1%
|
1.7%
|
1.6%
|
2.6%
|
| Rhinitis |
2.0%
|
1.3%
|
2.4%
|
2.3%
|
0.6%
|
| Sinusitis |
5.0%
|
4.3%
|
4.0%
|
5.4%
|
5.8%
|
| Upper resp. tract
Infection |
8.1%
|
6.7%
|
9.9%
|
9.8%
|
9.9%
|
| Skin |
| Rash |
2.2%
|
2.1%
|
2.1%
|
1.3%
|
1.2%
|
In placebo- or active-controlled clinical
trials, the discontinuation rate due to adverse events was 7.1%
for patients receiving CELEBREX and 6.1% for patients receiving
placebo. Among the most common reasons for discontinuation due to
adverse events in the CELEBREX treatment
groups were dyspepsia
and abdominal pain
(cited as reasons for discontinuation in 0.8% and 0.7% of CELEBREX
patients, respectively). Among patients receiving placebo, 0.6%
discontinued due to dyspepsia
and 0.6% withdrew due to abdominal pain.
The following adverse events occurred in 0.1 - 1.9% of patients
regardless of causality.
|
Celebrex
(100 - 200 mg BID
or 200 mg QD)
|
| Gastrointestinal |
Constipation,
diverticulitis, dysphagia, eructation,
esophagitis,
gastritis, gastroenteritis,
gastroesophageal reflux, hemorrhoids, hiatal hernia,
melena, stomatitis,
tooth disorder,
vomiting |
| Cardiovascular |
Aggravated hypertension,
dry mouth, glaucoma,
tenesmus |
| General |
Allergy
aggravated, allergic reaction,
asthenia, chest
pain, cyst
NOS, Edema generalized, face edema, fatigue,
fever, hot
flushes, influenza-like symptoms, pain,
peripheral pain |
| Resistance
Mechanism Disorders |
Herpes
simplex, herpes zoster, infection
bacterial, infection
Fungal, infection
soft tissue,
infection viral, moniliasis, moniliasis
genital, otitis
media |
| Central,
peripheral nervous system |
Leg cramps,
hypertonia, hypoesthesia, migraine,
neuralgia, neuropathy,
Paresthesia, vertigo |
| Female reproductive |
Breast fibroadenosis,
breast neoplasm, breast
pain, dysmenorrhea,
menstrual disorder, vaginal
hemorrhage, vaginitis |
| Male reproductive
|
Prostatic disorder
|
| Hearing
and vestibular |
Deafness,
ear abnormality, earache,
tinnitus |
| Heart rate
and rhythm |
Angina pectoris,
coronary artery
disorder, myocardial
infarction, palpitation,
tachycardia
|
| Liver
and biliary system |
Hepatic
function abnormal,
SGOT increased, SGPT
increased |
| Metabolic
and nutritional |
BUN increased,
CPK increased, diabetes
mellitus, hypercholesterolemia,
Hyperglycemia, hypokalemia, NPN increase, creatinine
increased,Alkaline phosphatase
increased, weight increase |
| Musculoskeletal |
Arthralgia,
arthrosis, bone disorder, fracture
accidental, myalgia,
neck stiffness, synovitis,
tendinitis |
| Platelets
(bleeding or clotting) |
Ecchymosis,
epistaxis, thrombocythemia |
| Psychiatric
|
Anorexia, anxiety,
appetite increased, depression,
nervousness, somnolence |
| Hemic |
Anemia |
| Respiratory
|
Bronchitis,
bronchospasm, bronchospasm aggravated, coughing, dyspnea,
Laryngitis, pneumonia
|
| Skin and appendages
|
Alopecia, dermatitis,
nail disorder, photosensitivity
reaction, pruritus,
rash erythematous,
rash maculopapular,
skin disorder, skin
dry, sweating
increased, urticaria |
| Application
site disorders |
Cellulitis, dermatitis
contact, injection site
reaction, skin
nodule |
| Special senses
|
Taste perversion
|
| Urinary
system |
Albuminuria,
cystitis, dysuria, hematuria,
micturition
frequency, renal
calculus, urinary
incontinence, urinary tract
infection |
| Vision |
Blurred vision,
cataract, conjunctivitis, eye pain
|
Other serious adverse reactions which occur rarely (£0.1%),
regardless of causality: The following serious adverse
events have occurred rarely in patients, taking CELEBREX.
| Cardiovascular:
|
Syncope, congestive
heart failure, ventricular
fibrillation,
pulmonary embolism,
cerebrovascular
accident, peripheral gangrene, thrombophlebitis |
| Gastrointestinal:
|
Intestinal obstruction,
intestinal perforation, gastrointestinal
bleeding, colitis
with bleeding,
esophageal perforation, pancreatitis,
cholelithiasis,
ileus |
| Hemic and lymphatic: |
Thrombocytopenia |
| Nervous system: |
Ataxia |
| Renal: |
Acute renal
failure |
| General: |
Sepsis, sudden death |
DRUG INTERACTIONS
General: Significant interactions may occur when
celecoxib is administered together with drugs that inhibit P450
2C9. Celecoxib metabolism is predominantly mediated via
cytochrome P450 2C9
in the liver. Co-administration of celecoxib
with drugs that are known to inhibit 2C9 should be done with caution.
In vitro studies indicate that celecoxib
is not an inhibitor of cytochrome
P450 2C9, 2C19 or 3A4. In vitro studies also indicate that
celecoxib, although not a substrate,
is an inhibitor of
cytochrome P450 2D6. Therefore, there is a potential
for an in vivo drug interaction with drugs that are metabolized
by P450 2D6.
Clinical studies with celecoxib
have identified potentially significant interactions with fluconazole
and lithium. Experience with nonsteroidal anti-inflammatory drugs
(NSAIDs) suggests the potential
for interactions with furosemide
and ACE inhibitors. The
effects celecoxib
on the pharmacokinetics and/or pharmacodynamics
of glyburide, ketoconazole, methotrexate, phenytoin, tolbutamide,
and warfarin have been studied in vivo and clinically important
interactions have not been found.
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 CELEBREX concomitantly with ACE-inhibitors.
Furosemide: Clinical studies, as well as post
marketing observations, have shown that NSAIDs
can reduce the natriuretic
effect of furosemide
and thiazides in some patients. This response
has been attributed to inhibition
of renal prostaglandin
synthesis.
Aspirin: CELEBREX can be used with low dose
aspirin. However, concomitant administration
of aspirin with CELEBREX
may result in an increased rate of GI
ulceration or other
complications, compared to use of CELEBREX alone (see CLINICAL
PHARMACOLOGY - CLINICAL STUDIES:
Special Studies - Gastrointestinal). Because of its lack
of platelet effects,
CELEBREX is not a substitute
for aspirin for cardiovascular
prophylaxis.
Fluconazole: Concomitant administration
of fluconazole at 200 mg
QD resulted in a two-fold increase in celecoxib
plasma concentration.
This increase is due to the inhibition
of celecoxib metabolism
via P450 2C9 by fluconazole
(see CLINICAL PHARMACOLOGY
- Pharmacokinetics: Metabolism). CELEBREX should be introduced
at the lowest recommended dose
in patients receiving fluconazole.
Lithium: In a study conducted in healthy
subjects, mean steady-state lithium
plasma levels increased
approximately 17% in subjects receiving lithium
450 mg BID with CELEBREX
200 mg BID as compared to
subjects receiving lithium
alone. Patients on lithium
treatment should be
closely monitored when CELEBREX is introduced or withdrawn.
Methotrexate: In an interaction study of rheumatoid
arthritis patients taking methotrexate, CELEBREX did not have a
significant effect
on the pharmacokinetics
of methotrexate.
Warfarin: The effect
of celecoxib on the
anti-coagulant effect of warfarin was studied in a group
of healthy subjects
receiving daily doses of 2-5 mg
of warfarin. In these subjects,
celecoxib did not
alter the anticoagulant
effect of warfarin as
determined by prothrombin time. However, caution should be used
when administering CELEBREX with warfarin since these patients are
at increased risk of bleeding
complications.
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