Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
BOXED WARNING - updated/truncated to show changes
WARNING: SEVERE NEUTROPENIA; ORTHOSTATIC HYPOTENSION, BRADYCARDIA, AND SYNCOPE; SEIZURE; MYOCARDITIS AND CARDIOMYOPATHY; INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS
- Clozaril treatment has caused severe neutropenia, defined as an absolute neutrophil count (ANC) less than 500/µL. Severe neutropenia can lead to serious infection and death. Prior to initiating treatment with Clozaril a baseline ANC must be at least 1500/ µL for the general population; and must be at least 1000/µL for patients with documented Benign Ethnic Neutropenia (BEN). During treatment, patients must have regular ANC monitoring. Advise patients to immediately report symptoms consistent with severe neutropenia or infection (e.g., fever, weakness, lethargy, or sore throat). Because of the risk of severe neutropenia, Clozaril is available only through a restricted program under a Risk Evaluation Mitigation Strategy (REMS) called the Clozapine REMS Program…
- Clozaril is contraindicated in patients with a history of serious hypersensitivity to clozapine (e.g., photosensitivity, vasculitis, erythema multiforme, or Stevens-Johnson Syndrome) or any other component of Clozaril
WARNINGS AND PRECAUTIONS
- * update the neutropenia monitoring algorithms and associated Clozaril (clozapine) treatment recommendations; and to accommodate for Clozaril (clozapine) treatment for patients with benign ethnic neutropenia
Clozapine REMS Program
ADVERSE REACTIONS – Postmarketing Experience
- … and retrograde ejaculation.
- For hospice patients (i.e., terminally ill patients with an estimated life expectancy of six months or less), the prescriber may reduce the ANC monitoring frequency to once every 6 months, after a discussion with the patient and his/her caregiver. Individual treatment decisions should weigh the importance of monitoring ANC in the context of the need to control psychiatric symptoms and the patient’s terminal illness.
6 ADVERSE REACTIONS
6.2 Postmarketing Experience
- added ..... colitis.
Immune System Disorders
- Angioedema, leukocytoclastic vasculitis.
Skin and Subcutaneous Tissue Disorders
- added ..... skin pigmentation disorder
Musculoskeletal System and Connective Tissue Disorders
- Myasthenic syndrome, rhabdomyolysis, and systemic lupus erythematosus.
Cerebrovascular adverse events
- An increased risk of cerebrovascular adverse events has been observed in dementia patients treated with some atypical antipsychotics. The mechanism for this increased risk is not known. An increased risk cannot be excluded for dementia patients or other patients treated with Clozaril. Clozaril should be used with caution in patients with dementia or risk factors for stroke.
- Pharmacokinetic-Related Interactions: Concomitant administration of drugs known to induce cytochrome P450 enzymes may decrease
the plasma levels of clozapine...tobacco smoke
Postmarketing Clinical Experience
- Central Nervous System: obsessive compulsive symptoms
- Metabolic and Nutritional Disorders: new onset diabetes
- Respiratory System: pneumonia and lower respiratory tract infection which may be fatal