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TREATMENT-EMERGENT EXTRAPYRAMIDAL SYMPTOMS ASSESSED BY RATING SCALES INCIDENCE IN A FIXED DOSAGE RANGE, PLACEBO-CONTROLLED CLINICAL TRIAL — ACUTE PHASE* Percentage of Patients Reporting Event Olanzapine Olanzapine Olanzapine Placebo 5 ± 2.5 mg/ day 10 ± 2.5 mg/ day 15 ± 2.5 mg/ day
Parkinsonism 1 15 14 12 14 Akathisia 2 23 16 19 27
* No statistically significant differences. 1 Percentage of patients with a Simpson-Angus Scale total score >3.
2 Percentage of patients with a Barnes Akathisia Scale global score 2. The following table enumerates the percentage of patients with treatment-emergent extrapyramidal symptoms as assessed by spontaneously reported adverse events during acute therapy in the same controlled clinical trial comparing olanzapine at 3 fixed doses with placebo in the treatment of schizophrenia. Text Continues Below
TREATMENT-EMERGENT EXTRAPYRAMIDAL SYMPTOMS ASSESSED BY ADVERSE EVENTS INCIDENCE IN A FIXED DOSAGE RANGE, PLACEBO-CONTROLLED CLINICAL TRIAL — ACUTE PHASE Percentage of Patients Reporting Event Olanzapine Olanzapine Olanzapine Placebo 5 ± 2.5 mg/ day 10 ± 2.5 mg/ day 15 ± 2.5 mg/ day (N= 68) (N= 65) (N= 64) (N= 69) Dystonic events 1 1 3 2 3
Parkinsonism events 2 10 8 14 20 Akathisia events 3 1 5 11* 10*
Dyskinetic events 4 4 0 2 1 Residual events 5 1 2 5 1
Any extrapyramidal event 16 15 25 32* * Statistically significantly different from placebo. 1 Patients with the following COSTART terms were counted in this category: dystonia, generalized spasm, neck rigidity, oculogyric crisis, opisthotonos, torticollis. 2 Patients with the following COSTART terms were counted in this category: akinesia, cogwheel rigidity, extrapyramidal syndrome, hypertonia, hypokinesia, masked facies, tremor. 3 Patients with the following COSTART terms were counted in this category: akathisia, hyperkinesia. 4 Patients with the following COSTART terms were counted in this category: buccoglossal syndrome, choreoathetosis, dyskinesia, tardive dyskinesia. 5 Patients with the following COSTART terms were counted in this category: movement disorder, myoclonus, twitching. Other Adverse Events — The following table addresses dose relatedness for other adverse events using data from a schizophrenia trial involving fixed dosage ranges. It enumerates the percentage of patients with treatment-emergent adverse events for the three fixed-dose range groups and placebo. The data were analyzed using the Cochran-Armitage test, excluding the placebo group, and the table includes only those adverse events for which there was a statistically significant trend. Percentage of Patients Reporting Event Olanzapine Olanzapine Olanzapine
Adverse Event Placebo 5 ± 2.5 mg/ day 10 ± 2.5 mg/ day 15 ± 2.5 mg/ day (N= 68) (N= 65) (N= 64) (N= 69)
Asthenia 15 8 9 20 Dry mouth 4 3 5 13
Nausea 9 0 2 9 Somnolence 16 20 30 39
Tremor 3 0 5 7 Vital Sign Changes — Olanzapine is associated with orthostatic hypotension and tachycardia (see PRECAUTIONS). Weight Gain — In placebo-controlled, 6-week studies, weight gain was reported in 5.6% of olanzapine patients compared to 0.8% of placebo patients. Olanzapine patients gained an average of 2.8 kg, compared to an average 0.4 kg weight loss in placebo patients; 29% of olanzapine patients gained greater than 7% of their baseline weight, compared to 3% of placebo patients. A categorization of patients at baseline on the basis of body mass index (BMI) revealed a significantly greater effect in patients with low BMI compared to normal or overweight patients; nevertheless, weight gain was greater in all 3 olanzapine groups compared to the placebo group. During long-term continuation therapy with olanzapine (238 median days of exposure), 56% of olanzapine patients met the criterion for having gained greater than 7% of their baseline weight. Average weight gain during long-term therapy was 5.4 kg. Laboratory Changes — An assessment of the premarketing experience for olanzapine revealed an association with asymptomatic increases in SGPT, SGOT, and GGT (see PRECAUTIONS).
Olanzapine administration was also associated with increases in serum prolactin (see PRECAUTIONS), with an asymptomatic elevation of the eosinophil count in 0.3% of patients, and with an increase in CPK. Given the concern about neutropenia associated with other psychotropic compounds and the finding of leukopenia associated with the administration of olanzapine in several animal models (see ANIMAL TOXICOLOGY), careful attention was given to examination of hematologic parameters in premarketing studies with olanzapine. There was no indication of a risk of clinically significant neutropenia associated with olanzapine treatment in the premarketing database for this drug. ECG Changes — Between-group comparisons for pooled placebo-controlled trials revealed no statistically significant olanzapine/ placebo differences in the proportions of patients experiencing potentially important changes in ECG parameters, including QT, QTc, and PR intervals. Olanzapine use was associated with a mean increase in heart rate of 2.4 beats per minute compared to no change among placebo patients. This slight tendency to tachycardia may be related to olanzapine's potential for inducing orthostatic changes (see PRECAUTIONS). Other Adverse Events Observed During the Clinical Trial Evaluation of Olanzapine Following is a list of terms that reflect treatment-emergent adverse events reported by patients treated with olanzapine (at multiple doses 1 mg/ day) in clinical trials (8661 patients, 4165 patient-years of exposure). This listing does not include those events already listed in previous tables or elsewhere in labeling, those events for which a drug cause was remote, those event terms which were so general as to be uninformative, and those events reported only once or twice which did not have a substantial probability of being acutely life-threatening. Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring in at least 1/ 100 patients (only those not already listed in the tabulated results from placebo-controlled trials appear in this listing); infrequent adverse events are those occurring in 1/ 100 to 1/ 1000 patients; rare events are those occurring in fewer than 1/ 1000 patients. Body as a Whole —
Frequent: dental pain and flu syndrome;
Infrequent: abdomen enlarged, chills, face edema, intentional injury, malaise, moniliasis, neck pain, neck rigidity, pelvic pain, photosensitivity reaction, and suicide attempt;
Rare: chills and fever, hangover effect, and sudden death. Cardiovascular System —
Frequent: hypotension;
Infrequent: atrial fibrillation, bradycardia, cerebrovascular accident, congestive heart failure, heart arrest, hemorrhage, migraine, pallor, palpitation, vasodilatation, and ventricular extrasystoles;
Rare: arteritis, heart failure, and pulmonary embolus. Digestive System —
Frequent: flatulence, increased salivation, and thirst;
Infrequent: dysphagia, esophagitis, fecal impaction, fecal incontinence, gastritis, gastroenteritis, gingivitis, hepatitis, melena, mouth ulceration, nausea and vomiting, oral moniliasis, periodontal abscess, rectal hemorrhage, stomatitis, tongue edema, and tooth caries;
Rare: aphthous stomatitis, enteritis, eructation, esophageal ulcer, glossitis, ileus, intestinal obstruction, liver fatty deposit, and tongue discoloration. Endocrine System —
Infrequent: diabetes mellitus;
Rare: diabetic acidosis and goiter. Hemic and Lymphatic System —
Infrequent: anemia, cyanosis, leukocytosis, leukopenia, lymphadenopathy, and thrombocytopenia;
Rare: normocytic anemia and thrombocythemia. Metabolic and Nutritional Disorders —
Infrequent: acidosis, alkaline phosphatase increased, bilirubinemia, dehydration, hypercholesteremia, hyperglycemia, hyperlipemia, hyperuricemia, hypoglycemia, hypokalemia, hyponatremia, lower extremity edema, and upper extremity edema;
Rare: gout, hyperkalemia, hypernatremia, hypoproteinemia, ketosis, and water intoxication. Musculoskeletal System —
Frequent: joint stiffness and twitching;
Infrequent: arthritis, arthrosis, leg cramps, and myasthenia;
Rare: bone pain, bursitis, myopathy, osteoporosis, and rheumatoid arthritis. Nervous System —
Frequent: abnormal dreams, amnesia, delusions, emotional lability, euphoria, manic reaction, paresthesia, and schizophrenic reaction; Infrequent: akinesia, alcohol misuse, antisocial reaction, ataxia, CNS stimulation, cogwheel rigidity, delirium, dementia, depersonalization, dysarthria, facial paralysis, hypesthesia, hypokinesia, hypotonia, incoordination, libido decreased, libido increased, obsessive compulsive symptoms, phobias, somatization, stimulant misuse, stupor, stuttering, tardive dyskinesia, vertigo, and withdrawal
syndrome;
Rare: circumoral paresthesia, coma, encephalopathy, neuralgia, neuropathy, nystagmus, paralysis, subarachnoid hemorrhage, and tobacco misuse. Respiratory System —
Frequent: dyspnea;
Infrequent: apnea, asthma, epistaxis, hemoptysis, hyperventilation, hypoxia, laryngitis, and voice alteration;
Rare: atelectasis, hiccup, hypoventilation, lung edema, and stridor. Skin and Appendages —
Frequent: sweating;
Infrequent: alopecia, contact dermatitis, dry skin, eczema, maculopapular rash, pruritus, seborrhea, skin discoloration, skin ulcer, urticaria, and vesiculobullous rash;
Rare: hirsutism and pustular rash. Special Senses —
Frequent: conjunctivitis; Infrequent: abnormality of accommodation, blepharitis, cataract, deafness, diplopia, dry eyes, ear pain, eye hemorrhage, eye inflammation, eye pain, ocular muscle abnormality, taste perversion, and tinnitus;
Rare: corneal lesion, glaucoma, keratoconjunctivitis, macular hypopigmentation, miosis, mydriasis, and pigment deposits lens. Urogenital System —
Frequent: vaginitis*;
Infrequent: abnormal ejaculation*, amenorrhea*, breast pain, cystitis, decreased menstruation*, dysuria, female lactation*, glycosuria, gynecomastia, hematuria, impotence*, increased menstruation*, menorrhagia*, metrorrhagia*, polyuria, premenstrual syndrome*, pyuria, urinary frequency, urinary retention, urinary urgency, urination impaired, uterine fibroids enlarged*, and vaginal hemorrhage*;
Rare: albuminuria, breast enlargement, mastitis, and oliguria. *Adjusted for gender. Postintroduction Reports Adverse events reported since market introduction which were temporally (but not necessarily causally) related to ZYPREXA therapy include the following: allergic reaction (e. g., anaphylactoid reaction, angioedema, pruritus or urticaria), diabetic coma, pancreatitis, and priapism. Page: << Prev | 1 | 2 | 3 | 4 | 5
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