Adverse reactions associated with ARTHROTEC
Adverse reaction information for ARTHROTEC is derived from Phase III
multinational controlled clinical trials in over 2,000 patients, receiving
ARTHROTEC 50 or ARTHROTEC 75, as well as from blinded, controlled trials
of Voltaren® Delayed-Release Tablets (diclofenac)
and Cytotec® Tablets (misoprostol).
Gastrointestinal
GI disorders had the highest reported incidence of adverse events for patients
receiving ARTHROTEC. These events were generally minor, but led to discontinuation
of therapy in 9% of patients on ARTHROTEC and 5% of patients on diclofenac.
For GI ulcer rates, see CLINICAL STUDIES—Upper gastrointestinal safety.
| GI disorder |
ARTHROTEC |
Diclofenac |
| Abdominal pain |
21% |
15% |
| Diarrhea |
19% |
11% |
| Dyspepsia |
14% |
11% |
| Nausea |
11% |
6% |
| Flatulence |
9% |
4% |
ARTHROTEC can cause more abdominal pain, diarrhea and other GI symptoms
than diclofenac alone.
Diarrhea and abdominal pain developed early in the course of therapy,
and were usually self-limited (resolved after 2 to 7 days). Rare instances
of profound diarrhea leading to severe dehydration have been reported in
patients receiving misoprostol. Patients with an underlying condition such
as inflammatory bowel disease, or those in whom dehydration, were it to
occur, would be dangerous, should be monitored carefully if ARTHROTEC is
prescribed. The incidence of diarrhea can be minimized by administering
ARTHROTEC with food and by avoiding coadministration with magnesium-containing
antacids.
Gynecological
Gynecological disorders previously reported with misoprostol use have
also been reported for women receiving ARTHROTEC (see below). Postmenopausal
vaginal bleeding may be related to administration of ARTHROTEC. If it occurs,
diagnostic workup should be undertaken to rule out gynecological pathology
(see boxed CONTRAINDICATIONS AND WARNINGS).
Elderly
Overall, there were no significant differences in the safety profile
of ARTHROTEC in over 500 patients 65 years of age or older compared with
younger patients.
Other adverse experiences reported occasionally or rarely with ARTHROTEC,
diclofenac or other NSAIDs, or misoprostol are:
Body as a whole: Asthenia, death, fatigue, fever, infection,
malaise, sepsis, chills.
Cardiovascular system: Arrhythmia, atrial fibrillation,
congestive heart failure, hypertension, hypotension, increased CPK, increased
LDH, myocardial infarction, palpitations, phlebitis, premature ventricular
contractions, syncope, tachycardia, vasculitis.
Central and peripheral nervous system: Coma, convulsions,
dizziness, drowsiness, headache, hyperesthesia, hypertonia, hypoesthesia,
insomnia, meningitis, migraine, neuralgia, paresthesia, somnolence, tremor,
vertigo.
Digestive: Anorexia, appetite changes, constipation, dry
mouth, dysphagia, enteritis, esophageal ulceration, esophagitis, eructation,
gastritis, gastroesophageal reflux, GI bleeding, GI neoplasm benign, glossitis,
heartburn, hematemesis, hemorrhoids, intestinal perforation, peptic ulcer,
stomatitis and ulcerative stomatitis, tenesmus, vomiting.
Female reproductive disorders: Breast pain, dysmenorrhea,
intermenstrual bleeding, leukorrhea, menstrual disorder, menorrhagia, vaginal
hemorrhage.
Hemic and lymphatic system: Agranulocytosis, anemia, aplastic
anemia, coagulation time increased, ecchymosis, eosinophilia, epistaxis,
hemolytic anemia, leukocytosis, leukopenia, lymphadenopathy, melena, pancytopenia,
pulmonary embolism, purpura, rectal bleeding, thrombocythemia, thrombocytopenia.
Hypersensitivity: Angioedema, laryngeal/pharyngeal edema,
urticaria.
Liver and biliary system: Abnormal hepatic function, bilirubinemia,
hepatitis, jaundice, liver failure, pancreatitis.
Male reproductive disorders: Impotence, perineal pain.
Metabolic and nutritional: Alkaline phosphatase increased,
BUN increased, dehydration, glycosuria, gout, hypercholesterolemia, hyperglycemia,
hyperuricemia, hypoglycemia, hyponatremia, periorbital edema, porphyria,
weight changes.
Musculoskeletal system: Arthralgia, myalgia.
Psychiatric: Anxiety, concentration impaired, confusion,
depression, disorientation, dream abnormalities, hallucinations, irritability,
nervousness, paranoia, psychotic reaction.
Respiratory system: Asthma, coughing, dyspnea, hyperventilation,
pneumonia, respiratory depression.
Skin and appendages: Acne, alopecia, bruising, eczema,
erythema multiforme, exfoliative dermatitis, pemphigoid reaction, photosensitivity,
pruritus, pruritus ani, rash, skin ulceration, Stevens-Johnson syndrome,
sweating increased, toxic epidermal necrolysis.
Special senses: Hearing impairment, taste loss, taste perversion,
tinnitus.
Urinary system: Cystitis, dysuria, hematuria, interstitial
nephritis, micturition frequency, nocturia, nephrotic syndrome, oliguria/polyuria,
papillary necrosis, proteinuria, renal failure, urinary tract infection.
Vision: Amblyopia, blurred vision, conjunctivitis, diplopia,
glaucoma, iritis, lacrimation abnormal, night blindness, vision abnormal.