Central nervous system
CNS side effects include drowsiness, vertigo, headache, tremor, syncope, sleep disturbances, nightmares, restlessness, akinesia, agitation, seizures, rigidity, akathisia, confusion, fatigue, insomnia, hyperkinesia, weakness, lethargy, ataxia, slurred speech, depression, myoclonic jerks, and anxiety. Rarely seen are delusions, hallucinations, delirium, amnesia, libido increase or decrease, paranoia and irritability, abnormal EEG, worsening of psychosis, paresthesia, status epilepticus, and obsessive compulsive symptoms. Similar to other antipsychotics clozapine rarely has been known to cause neuroleptic malignant syndrome. Urinary incontinence
Clozapine is linked to urinary incontinence, though its appearance may be under-recognized. Withdrawal effects
Abrupt withdrawal may lead to cholinergic rebound effects, such as indigestion, diarrhea, nausea/vomiting, overabundance of saliva, profuse sweating, insomnia, and agitation. Abrupt withdrawal can also cause severe movement disorders, catatonia, and psychosis. Doctors have recommended that patients, families, and caregivers be made aware of the symptoms and risks of abrupt withdrawal of clozapine. When discontinuing clozapine, gradual dose reduction is recommended to reduce the intensity of withdrawal effects. Weight gain and diabetes
In addition to hyperglycemia, significant weight gain is frequently experienced by patients treated with clozapine. Impaired glucose metabolism and obesity have been shown to be constituents of the metabolic syndrome and may increase the risk of cardiovascular disease. The data suggest that clozapine may be more likely to cause adverse metabolic effects than some of the other atypical antipsychotics. Pneumonia
International adverse drug effect databases indicate that clozapine use is associated with a significantly increased incidence of and death from pneumonia and this may be one of the most significant adverse events.
Fludrocortisone, sold under the brand name Florinef, among others, is a corticosteroid used to treat adrenogenital syndrome, postural hypotension, and adrenal insufficiency. In adrenal insufficiency, it is generally taken together with hydrocortisone. Fludrocortisone is taken by mouth and is most commonly used in its acetate form.Common side effects of fludrocortisone include high blood pressure, swelling, heart failure, and low blood potassium. Other serious side effects can include low immune-system function, cataracts, muscle weakness, and mood changes. Whether use of fludrocortisone during pregnancy is safe for the fetus is unknown. Fludrocortisone is mostly a mineralocorticoid, but it also has glucocorticoid effects.Fludrocortisone was patented in 1953. It is on the World Health Organizations List of Essential Medicines. Medical uses
Fludrocortisone has been used in the treatment of cerebral salt-wasting syndrome. It is used primarily to replace the missing hormone aldosterone in various forms of adrenal insufficiency such as Addisons disease and the classic salt-wasting (21-hydroxylase deficiency) form of congenital adrenal hyperplasia. Due to its effects on increasing Na+ levels, and therefore blood volume, fludrocortisone is the first-line of treatment for orthostatic intolerance and postural orthostatic tachycardia syndrome (POTS). It can be used to treat low blood pressure.Fludrocortisone is also a confirmation test for diagnosing Conns syndrome (aldosterone-producing adrenal adenoma), the fludrocortisone suppression test. Loading the patient with fludrocortisone would suppress serum aldosterone level in a normal patient, whereas the level would remain elevated in a Conns patient. The fludrocortisone suppression test is an alternative to the NaCl challenge (which would use normal saline or salt tablets).