An atypical antipsychotic - It is used to treat schizophrenia, psychotic disorders, and bipolar diso... more
FDA Alerts
Special Alerts:
[Posted 05/02/2007] FDA notified healthcare professionals that the Agency proposed that makers of all antidepressant medications update the existing black box warning on the prescribing information for their products to include warnings about the increased risks of suicidal thinking and behavior in young adults ages 18 to 24 years old during the first one to two months of treatment. The proposed labeling changes also state that scientific data did not show this increased risk in adults older than 24 years of age and that adults 65 years of age and older taking antidepressants have a decreased risk of suicidality. The proposed updates apply to the entire category of antidepressants. Individuals currently taking prescribed antidepressant medications should not stop taking them and should notify their healthcare professional if they have concerns. Manufacturers of antidepressant medications will have 30 days to submit their revised product labeling and revised Medication Guides to FDA for review. See the FDA press release for the list of products affected by the proposed antidepressant product labeling changes. For more information visit the FDA website at: http://www.fda.gov/medwatch/safety/2007/safety07.htm#Antidepressant, http://www.fda.gov/bbs/topics/NEWS/2007/NEW01624.html and http://www.fda.gov/cder/drug/antidepressants/default.htm.
[Posted 07/19/2006] FDA notified healthcare professionals and consumers of important information from two recent studies that should be considered when making treatment decisions in pregnant women who take antidepressants. The studies included pregnant women who were treated with selective serotonin reuptake inhibitors (SSRIs), or in a few cases, other antidepressant medications.
One study illustrated the potential risk of relapsed depression after stopping antidepressant medication during pregnancy. In this study, women who stopped their medicine were five times more likely to have a relapse of depression during their pregnancy than were women who continued to take their antidepressant medicine while pregnant.
The second study suggests there may be additional, though rare, risks of taking SSRI medications during pregnancy. This study focused on newborn babies with persistent pulmonary hypertension (PPHN), which is a serious and life-threatening lung condition that occurs soon after birth. Babies born with PPHN have high pressure in their lung blood vessels and are not able to get enough oxygen into their bloodstream. In this study, PPHN was six times more common in babies whose mothers took an SSRI antidepressant after the 20th week of pregnancy compared to babies whose mothers did not take an antidepressant. The study was too small to compare the risk of one drug compared to another. The finding of PPHN in babies of mothers who used a SSRI antidepressant in the second half of pregnancy adds to concerns from previous reports that infants of mothers taking SSRIs late in pregnancy may experience difficulties such as irritability, difficulty feeding and in very rare cases, difficulty breathing.
Additionally, the labeling for paroxetine (Paxil) was recently changed to add information about findings in an epidemiologic study that suggests that exposure to the drug in the first trimester of pregnancy may be associated with an increased risk of cardiac birth defects.
Women who are pregnant or thinking about becoming pregnant should not stop any antidepressant medication without first consulting their physician. The FDA is seeking additional information about the possible risk of PPHN in newborn babies of mothers who took SSRI antidepressants in pregnancy. FDA has asked the sponsors of all SSRIs to change prescribing information to describe the potential risk for PPHN. For more information visit the FDA website at: http://www.fda.gov/medwatch/safety/2006/safety06.htm#SSRIpreg and http://www.fda.gov/cder/drug/advisory/SSRI_PPHN200607.htm.
[Posted 07/19/2006] FDA notified healthcare professionals and consumers of new safety information regarding taking medications used to treat migraine headaches (triptans) together with certain types of antidepressant and mood disorder medications (selective serotonin reuptake inhibitors (SSRIs) and selective serotonin/norepinephrine reuptake inhibitors (SNRIs). A life-threatening condition called serotonin syndrome may occur when triptans are used together with a SSRI or a SNRI.
Serotonin syndrome occurs when the body has too much of a chemical found in the nervous system (serotonin). Each of the above medications (triptans, SSRIs, and SNRIs), cause an increase in serotonin levels. Symptoms of serotonin syndrome may include restlessness, hallucinations, loss of coordination, fast heart beat, rapid changes in blood pressure, increased body temperature, overactive reflexes, nausea, vomiting, and diarrhea.
Healthcare professionals prescribing a triptan, SSRI or SNRI should keep in mind that triptans are often used intermittently and either the triptan, SSRI or SNRI may be prescribed by a different physician; weigh the potential risk of serotonin syndrome with the expected benefit of using the above combination; discuss the possibility of serotonin syndrome with patients if a triptan and an SSRI or SNRI will be used together; and follow patients closely during treatment if a triptan and an SSRI or SNRI are used together.
Patients taking a triptan along with an SSRI or SNRI should talk to their doctor before stopping their medication and should immediately seek medical attention if they experience any of the above symptoms. FDA requested that all manufacturers of triptans, SSRIs and SNRIs update their prescribing information to warn of the possibility of serotonin syndrome when these medications are taken together. For more information visit the FDA website at: http://www.fda.gov/medwatch/safety/2006/safety06.htm#Triptans and http://www.fda.gov/cder/drug/advisory/SSRI_SS200607.htm.
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
IM for management of acute agitation in patients with schizophrenia for whom treatment with olanzapine is appropriate and who require an IM antipsychotic agent for rapid control of behaviors that interfere with diagnosis and care.
Bipolar Disorder
Short-term management (alone or in combination with lithium or divalproex sodium [e.g., valproate sodium, valproic acid]) of acute mixed or manic episodes and maintenance of treatment response in patients with bipolar I disorder.
Management (in fixed-combination with fluoxetine) of acute depressive episodes in patients with bipolar depression (bipolar disorder, depressed).
IM for management of acute agitation in patients with bipolar I disorder for whom treatment with olanzapine is appropriate and who require an IM antipsychotic agent for rapid control of behaviors that interfere with diagnosis and care.
Dosage and Administration
Administration
Administer orally or by deep IM injection. (See Possible Prescribing and Dispensing Errors under Cautions.)
Oral Administration
Administer orally as conventional tablets, orally disintegrating tablets, or capsules (in fixed combination with fluoxetine) once daily without regard to meals. Administer fixed-combination olanzapine and fluoxetine capsules in the evening.
Just prior to administration, gently remove orally disintegrating tablet from blister packet; do not push tablet through foil. With dry hands, peel open blister package, place tablet on tongue to dissolve, and swallow with or without liquid.
IM Administration
Administer by IM injection slowly and deeply into the muscle mass. Do not administer IV or sub-Q.
Reconstitution
Reconstitute by adding 2.1 mL of sterile water for injection to vial containing 10 mg of olanzapine to provide a solution containing approximately 5 mg/mL.
Following reconstitution, use immediately (within 1 hour). Discard any unused portion.
Dosage
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Adults
Schizophrenia
Oral
Initially, 5–10 mg, usually as a single daily dose. Within several days, may increase by 5 mg daily, to a target dosage of 10 mg daily.
Make subsequent dosage adjustments at intervals of not less than 7 days, usually in increments or decrements of 5 mg once daily.
Increasing dosage beyond 10 mg daily usually does not result in greater efficacy; such increases generally should occur only after assessment of the patient’s clinical status.
Optimum duration of therapy currently is not known, but maintenance therapy with antipsychotic agents is well established. In responsive patients, continue as long as clinically necessary and tolerated, but at lowest possible effective dosage; reassess need for continued therapy periodically.
Bipolar Disorder
Acute Mania: Monotherapy
Oral
Initially, 10–15 mg once daily. Make dosage adjustments in increments or decrements of 5 mg daily, at intervals of not less than 24 hours.
Effective dosage in clinical studies generally ranged from 5–20 mg daily.
If elect to use olanzapine for extended periods, periodically reevaluate the long-term usefulness for the individual patient.
Acute Mania: Combination Therapy
Oral
Initially, 10 mg once daily when administered with lithium or divalproex sodium.
Effective dosage of olanzapine in clinical studies generally ranged from 5–20 mg daily.
No dosage adjustment for lithium or divalproex sodium is required when used in combination with olanzapine.
Acute Depression: Combination Therapy
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Oral
Initially, 6 mg in fixed combination with 25 mg of fluoxetine (Symbyax® 6/25) once daily in the evening.
Increase dosage according to patient response and tolerance as indicated.
In clinical trials, antidepressive efficacy was demonstrated at olanzapine dosages ranging from 6–12 mg daily and fluoxetine dosages ranging from 25–50 mg daily.
If elect to use combined olanzapine and fluoxetine for extended periods, periodically reevaluate the long-term risks and benefits for the individual patient.
Acute Agitation in Schizophrenia and Bipolar Mania
IM
Initially, 10 mg. Consider lower doses (2.5, 5, or 7.5 mg) when clinically warranted.
In clinical trials, efficacy of IM olanzapine for controlling agitation in patients with schizophrenia or bipolar mania was demonstrated in a dosage range of 2.5–10 mg.
If agitation persists, may administer subsequent single doses of up to 10 mg. However, efficacy of repeated doses was not systematically evaluated in controlled trials.
Assess patients for orthostatic hypotension prior to administration of any subsequent IM doses. (See Cardiovascular Effects under Cautions.)
Oral therapy should replace IM therapy as soon as possible.
Prescribing Limits
Adults
Schizophrenia
Oral
Safety of dosages >20 mg daily not established.
Bipolar Disorder
Oral
Safety of dosages >20 mg daily not established.
Dosages >18 mg of olanzapine and 75 mg of fluoxetine in fixed-combination for acute depressive episodes not evaluated in clinical studies.
Acute Agitation in Schizophrenia and Bipolar Mania
IM
Safety of dosages >30 mg daily or of 10-mg IM doses given more frequently than 2 hours after the initial dose and 4 hours after the second dose not established.
Special Populations
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Initially, 5 mg orally daily or 2.5 mg IM in debilitated patients, in those predisposed to hypotension, in those who may be particularly sensitive to the effects of olanzapine, or in those who might metabolize olanzapine slowly (e.g., nonsmoking women ≥65 years of age); when indicated, adjust dosage with caution.
In fixed combination with fluoxetine for acute depressive episodes in bipolar disorder, an oral dosage of 6 mg of olanzapine and 25 mg of fluoxetine (Symbyax® 6/25) is recommended for initial and maintenance therapy in patients predisposed to hypotension, in those with hepatic impairment, or those who might metabolize the drugs(s) slowly (e.g., female gender, geriatric age, nonsmoking status); when indicated, adjust dosage with caution.
Geriatric Patients
Careful dosage titration of oral olanzapine recommended in patients >65 years of age; initiate therapy at low end of dosage range.
FDA Alerts
Media Gallery
