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
Orudis Side Effects, and Drug Interactions - Ketoprofen
Orudis Side Effects, and Drug Interactions - Ketoprofen
SIDE EFFECTS
The incidence of
common adverse reactions (above 1%) was obtained from a population
of 835 Orudis-treated patients in double-blind trials lasting from
4 to 54 weeks and in 622 Oruvail-treated (200 mg/day) patients in
trials lasting from 4 to 16 weeks.
Minor gastrointestinal
side effects predominated;
upper gastrointestinal symptoms were more common than lower gastrointestinal
symptoms. In crossover trials
in 321 patients with rheumatoid
arthritis or osteoarthritis,
there was no difference in
either upper or lower gastrointestinal
symptoms between patients treated with 200 mg
of Oruvail once a day or 75 mg
of Orudis TID (225 mg/day). Peptic ulcer
or GI bleeding
occurred in controlled clinical trials in less than 1% of 1,076
patients; however, in open
label continuation studies
in 1,292 patients the rate
was greater than 2%. The incidence
of peptic ulceration
in patients on NSAIDs
is dependent on many risk
factors including age, sex,
smoking, alcohol use,
diet, stress, concomitant
drugs such as aspirin
and corticosteroids, as well as the dose
and duration of treatment
with NSAIDs (see WARNINGS).
Gastrointestinal reactions were followed in frequency
by central nervous system
side effects, such
as headache, dizziness,
or drowsiness. The incidence of some adverse reactions appears to
be dose-related (see DOSAGE AND
ADMINISTRATION). Rare adverse reactions (incidence less
than 1%) were collected from foreign reports to manufacturers and
regulatory agencies, publications, and U. S. clinical
trials.
Reactions are listed below under body
system, then by incidence
or number of cases in decreasing incidence.
INCIDENCE GREATER THAN
1% (PROBABLE CAUSAL RELATIONSHIP)
Digestive: Dyspepsia (1196), nausea*, abdominal
pain*, diarrhea, constipation,
flatulence, anorexia,
vomiting, stomatitis.
Nervous System: Headache, dizziness,
CNS inhibition
(i. e., pooled reports of somnolence,
malaise, depression,
etc.) or excitation (i. e., insomnia,
nervousness, dreams, etc.)*.
Special Senses: Tinnitus, visual
disturbance.
Skin and Appendages: Rash.
Urogenital: Impairment of renal
function (edema, increased
BUN)*, signs or symptoms of urinary-tract irritation.
*Adverse events occurring in 3 to 9% of patients.
INCIDENCE LESS THAN
1% (PROBABLE CAUSAL RELATIONSHIP)
Body as a Whole: Chills, facial
edema, infection,
pain, allergic reaction,
anaphylaxis.
Cardiovascular: Hypertension, palpitation,
tachycardia, congestive heart
failure, peripheral
vascular disease,
vasodilation.
Digestive: Appetite increased, dry mouth,
eructation, gastritis, rectal
hemorrhage, melena,
fecal occult blood,
salivation, peptic
ulcer, gastrointestinal
perforation, hematemesis,
intestinal ulceration.
Hemic: Hypocoagulability, agranulocytosis,
anemia, hemolysis, purpura,
thrombocytopenia.
Metabolic and Nutritional: Thirst, weight
gain, weight loss, hepatic
dysfunction, hyponatremia.
Musculoskeletal: Myalgia.
Nervous System: Amnesia, confusion,
impotence, migraine,
paresthesia, vertigo.
Respiratory: Dyspnea, hemoptysis,
epistaxis, pharyngitis,
rhinitis, bronchospasm,
laryngeal edema.
Skin and Appendages: Alopecia, eczema, pruritus,
purpuric rash, sweating, urticaria,
bullous rash,
exfoliative dermatitis,
photosensitivity, skin discoloration, onycholysis.
Special Senses: Conjunctivitis, conjunctivitis
sicca, eye pain, hearing
impairment, retinal
hemorrhage and pigmentation
change, taste perversion.
Urogenital: Menometrorrhagia, hematuria,
renal failure, interstitial
nephritis, nephrotic
syndrome.
INCIDENCE LESS THAN
1% (CAUSAL RELATIONSHIP UNKNOWN)
The following rare adverse reactions, whose causal relationship
to ketoprofen is uncertain, are being listed to serve as alerting
information to the physician.
Body as a Whole: Septicemia, shock.
Cardiovascular: Arrhythmias, myocardial
infarction.
Digestive: Buccal necrosis,
ulcerative colitis,
microvesicular steatosis, jaundice,
pancreatitis.
Endocrine: Diabetes mellitus (aggravated).
Nervous System: Dysphoria, hallucination,
libido disturbance, nightmares,
personality disorder,
aseptic meningitis.
Urogenital: Acute tubulopathy, gynecomastia.
DRUG INTERACTIONS
The following drug interactions
were studied with ketoprofen doses of 200 mg/day. The possibility
of increased interaction should be kept in mind when Orudis doses
greater than 50 mg as a single
dose or 200 mg
of ketoprofen per day are
used concomitantly with highly bound
drugs.
1. Antacids: Concomitant administration
of magnesium hydroxide
and aluminum hydroxide
does not interfere with the rate
or extent of the absorption of ketoprofen administered as Orudis.
2. Aspirin: Ketoprofen does not alter aspirin
absorption; however, in a study of 12 normal
subjects, concurrent administration
of aspirin decreased ketoprofen protein
binding and increased ketoprofen plasma clearance from 0.07 L/kg/h
without aspirin to 0.11
L/kg/h with aspirin. The clinical
significance of these changes has not been adequately studied. Therefore,
concurrent use of aspirin
and ketoprofen is not recommended.
3. Diuretic: Hydrochlorothiazide, given concomitantly
with ketoprofen, produces a reduction
in urinary potassium
and chloride excretion compared to hydrochlorothiazide
alone. Patients taking diuretics are at a greater risk
of developing renal failure
secondary to a decrease
in renal blood
flow caused by prostaglandin
inhibition (see PRECAUTIONS).
4. Digoxin: In a study in 12 patients with
congestive heart failure
where ketoprofen and digoxin
were concomitantly administered, ketoprofen did not alter the serum
levels of digoxin.
5. Warfarin: In
a short-term controlled study in 14 normal volunteers, ketoprofen
did not significantly interfere with the effect of warfarin on prothrombin
time. Bleeding from a number
of sites may be a complication
of warfarin treatment
and GI bleeding
a complication
of ketoprofen treatment. Because prostaglandina play
an important role in hemostasis
and ketoprofen has an effect
on platelet function
as well (see DRUG/LABORATORY TEST
INTERACTIONS below), concurent therapy
with ketoprofen and warfarin requires close monitoring of patients
on both drugs.
6. Probenecid: Probenecid increases both free and
bound ketoprofen by reducing the plasma
clearance of ketoprofen
to about one-third, as well as decreasing its protein
binding. Therefore, the combination of ketoprofen and probenecid
is not recommended.
7. Methotrexate: Ketoprofen, like other NSAIDs, may
cause changes in the elimination
of methotrexate
leading to elevated serum
levels of the drug and
increased toxicity.
8. Lithium: Nonsteroidal anti-inflammatory
agents have been reported to increase steadystate plasma
lithium levels. It is
recommended that plasma
lithium levels be monitored
when ketoprofen is coadministered with lithium.
DRUG/LABORATORY TEST
INTERACTIONS: EFFECT ON BLOOD
COAGULATION
Ketoprofen decreases platelet
adhesion and aggregation.
Therefore, it can prolong bleeding
time by approximately 3
to 4 minutes from baseline values. There is no
significant change
in platelet count,
prothrombin time,
partial thromboplastin
time, or thrombin time.
top
