Anti-Psychotics

Asenapine is a white to off-white powder.

SAPHRIS is supplied for sublingual administration in tablets containing 5-mg or 10-mg asenapine; inactive ingredients include gelatin and mannitol.

INDICATIONS AND USAGE
Schizophrenia
SAPHRIS is indicated for the treatment of schizophrenia. The efficacy of SAPHRIS was established in two 6-week trials and one maintenance trial in adults.

Bipolar Disorder
Monotherapy: SAPHRIS is indicated for the acute treatment of manic or mixed episodes associated with bipolar I disorder. Efficacy was established in two 3-week monotherapy trials in adults.

Adjunctive Therapy: SAPHRIS is indicated as adjunctive therapy with either lithium or valproate for the acute treatment of manic or mixed episodes associated with bipolar I disorder. Efficacy was established in one 3-week adjunctive trial in adults

DOSAGE AND ADMINISTRATION

Administration Instructions
SAPHRIS is a sublingual tablet. To ensure optimal absorption, patients should be instructed to place the tablet under the tongue and allow it to dissolve completely. The tablet will dissolve in saliva within seconds. SAPHRIS sublingual tablets should not be crushed, chewed, or swallowed. Patients should be instructed to not eat or drink for 10 minutes after administration .

Schizophrenia
Usual Dose for Acute Treatment in Adults: The recommended starting and target dose of SAPHRIS is 5 mg given twice daily. In short term controlled trials, there was no suggestion of added benefit with a 10 mg twice daily dose, but there was a clear increase in certain adverse reactions. The safety of doses above 10 mg twice daily has not been evaluated in clinical studies.

Maintenance Treatment: Efficacy was demonstrated with SAPHRIS in a maintenance trial in patients with schizophrenia. The starting dose in this study was 5 mg twice daily with an increase up to 10 mg twice daily after 1 week based on tolerability. While there is no body of evidence available to answer the question of how long the schizophrenic patient should remain on SAPHRIS, patients should be periodically reassessed to determine the need for maintenance treatment.

Bipolar Disorder
Usual Dose for Acute Treatment of Manic or Mixed Episodes Associated with Bipolar I Disorder in Adults:

Monotherapy: The recommended starting dose of SAPHRIS, and the dose maintained by 90% of the patients studied, is 10 mg twice daily. The dose can be decreased to 5 mg twice daily if warranted by adverse effects or based on individual tolerability.

In controlled monotherapy trials, the starting dose for SAPHRIS was 10 mg twice daily. On the second and subsequent days of the trials, the dose could be lowered to 5 mg twice daily, based on tolerability, but less than 10% of patients had their dose reduced. The safety of doses above 10 mg twice daily has not been evaluated in clinical trials.

Adjunctive Therapy: The recommended starting dose of SAPHRIS is 5 mg twice daily when administered as adjunctive therapy with either lithium or valproate. Depending on the clinical response and tolerability in the individual patient, the dose can be increased to 10 mg twice daily. The safety of doses above 10 mg twice daily as adjunctive therapy with lithium or valproate has not been evaluated in clinical trials.

Maintenance Treatment: While there is no body of evidence available to answer the question of how long the bipolar patient should remain on SAPHRIS, whether used as monotherapy or as adjunctive therapy with lithium or valproate, it is generally recommended that responding patients be continued beyond the acute response. If SAPHRIS is used for extended periods in bipolar disorder, the physician should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.

Dosage in Special Populations
In a study of subjects with hepatic impairment who were treated with a single dose of SAPHRIS 5 mg, there were increases in asenapine exposures (compared to subjects with normal hepatic function), that correlated with the degree of hepatic impairment. While the results indicated that no dosage adjustments are required in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment, there was a 7-fold increase (on average) in asenapine concentrations in subjects with severe hepatic impairment (Child-Pugh C) compared to the concentrations of those in subjects with normal hepatic function. Therefore, SAPHRIS is not recommended in patients with severe hepatic impairment. Dosage adjustments are not routinely required on the basis of age, gender, race, or renal impairment status [see Use in Specific Populations and Clinical Pharmacology].

Switching from Other Antipsychotics
There are no systematically collected data to specifically address switching patients with schizophrenia or bipolar mania from other antipsychotics to SAPHRIS or concerning concomitant administration with other antipsychotics. While immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients with schizophrenia, more gradual discontinuation may be most appropriate for others. In all cases, the period of overlapping antipsychotic administration should be minimized

HOW SUPPLIED
SAPHRIS (asenapine) sublingual tablets are supplied as:

5-mg Tablets
Round, white to off-white sublingual tablets, with "5" on one side.
Child-resistant packaging
Box of 60 6 blisters with 10 tablets NDC 0052-0118-06
Hospital Unit Dose
Box of 100 10 blisters with 10 tablets NDC 0052-0118-90

10-mg Tablets
Round, white to off-white sublingual tablets, with "10" on one side.
Child-resistant packaging
Box of 60 6 blisters with 10 tablets NDC 0052-0119-06
Hospital Unit Dose
Box of 100 10 blisters with 10 tablets NDC 0052-0119-90

5-mg Tablets, black cherry flavor
Round, white to off-white sublingual tablets, with "5" on one side within a circle.
Child-resistant packaging
Box of 60 6 blisters with 10 tablets NDC 0052-2139-03
Hospital Unit Dose
Box of 100 10 blisters with 10 tablets NDC 0052-2139-04

10-mg Tablets, black cherry flavor
Round, white to off-white sublingual tablets, with "10" on one side within a circle.
Child-resistant packaging
Box of 60 6 blisters with 10 tablets NDC 0052-2142-03
Hospital Unit Dose
Box of 100 10 blisters with 10 tablets NDC 0052-2142-04

Storage
Store at 15°–30°C (59°–86°F) [see USP Controlled Room Temperature].

Schizophrenia: Oral: 10-15 mg once daily; may be increased to a maximum of 30 mg once daily (efficacy at dosages above 10-15 mg has not been shown to be increased). Dosage titration should not be more frequent than every 2 weeks.

Supplied: 5 mg, 10 mg, 15 mg, 20 mg, 30 mg tab. 1 mg/ml (150 ml) oral soln.

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Drug Updates:  ABILIFY MAINTENA ® (aripiprazole) for extended-release injectable suspension, for intramuscular use
[Drug information  /  PDF]  
Dosing:  Click (+) next to Dosage and Administration section (drug info link)

Initial U.S. Approval:  2013

Mechanism of Action: The mechanism of action of aripiprazole in the treatment of schizophrenia is unknown.

However, the efficacy of aripiprazole may be mediated through a combination of partial agonist activity at D2 and 5-HT1A receptors and antagonist activity at 5-HT2A receptors. Actions at receptors other than D2, 5-HT1A, and 5-HT2A may explain some of the other adverse reactions of aripiprazole (e.g., the orthostatic hypotension observed with aripiprazole may be explained by its antagonist activity at adrenergic alpha1 receptors).

INDICATIONS AND USAGE:  ABILIFY MAINTENA is an atypical antipsychotic indicated for the treatment of schizophrenia

HOW SUPPLIED:
For extended-release injectable suspension: 300 mg and 400 mg strength lyophilized powder for reconstitution in (3):
single-dose pre-filled dual chamber syringe
single-dose vial

Drug Updates:  ARISTADA™-- aripiprazole lauroxil injection, suspension

Warnings: 1) Significant hypotension may occur, particularly with parenteral administration. 2) Phenothiazines may cause anticholinergic effects (confusion, agitation, constipation, xerostomia, blurred vision, urinary retention). Therefore, they should be used with caution in patients with decreased gastrointestinal motility, urinary retention, BPH, xerostomia, or visual problems.

Supplied: Tablet: 10 mg, 25 mg, 50 mg, 100 mg, 200 mg. Injection: 25 mg/ml (1, 2 ml).

Reduce risk of suicidal behavior: Initial: 12.5 mg once or twice daily; increased, as tolerated, in increments of 25-50 mg/day to a target dose of 300-450 mg/day after 2-4 weeks; median dose is ~300 mg/day (range: 12.5-900 mg)

IMPORTANT
Termination of therapy: If dosing is interrupted for >/=48 hours, therapy must be reinitiated at 12.5-25 mg/day; may be increased more rapidly than with initial titration, unless cardiopulmonary arrest occurred during initial titration.
In the event of planned termination of clozapine, gradual reduction in dose over a 1- to 2-week period is recommended. If conditions warrant abrupt discontinuation (leukopenia), monitor patient for psychosis and cholinergic rebound (headache, nausea, vomiting, diarrhea).
Patients discontinued on clozapine therapy due to WBC <2000/mm3 or ANC <1000/mm3 should not be restarted on clozapine.

Dosage adjustment for toxicity:
Moderate leukopenia or granulocytopenia (WBC <3000/mm3 and ANC <1500/mm3): Discontinue therapy; may rechallenge patient when WBC >3500/mm3 and/or ANC >2000/mm3. Note: Patient is at greater risk for developing agranulocytosis.
Severe leukopenia or granulocytopenia (WBC <2000/mm3 and/or ANC <1000/mm3): Discontinue therapy and do not rechallenge patient.

Supplied: Tablet: 12.5 mg, 25 mg, 100 mg

Depot (Long-acting maintenance injections): IM, SQ (decanoate): 12.5 mg every 3 weeks. Conversion from hydrochloride to decanoate IM: 0.5 ml (12.5 mg) decanoate every 3 weeks is approximately equivalent to 10 mg hydrochloride/day.

Supplied: 1 mg, 2.5 mg, 5 mg, 10 mg tab. Oral concentrate: 5 mg/ml (120 ml). Injection (decanoate): 25 mg/ml (5 ml)

INDICATIONS
HALDOL (haloperidol) is indicated for use in the treatment of schizophrenia.
HALDOL is indicated for the control of tics and vocal utterances of Tourette's Disorder.

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DOSAGE AND ADMINISTRATION
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Dosing (Adults): Psychosis: Oral: 0.5-5 mg 2-3 times/day; usual maximum: 30 mg/day.
IM (as lactate): 2-5 mg every 4-8 hours as needed.

(Haldol decanoate): Initial: 10-20 times the daily oral dose administered at 4-week intervals. Maintenance dose: 10-15 times initial oral dose; used to stabilize psychiatric symptoms.

Unlabeled uses:
ICU- Delirium: 0.5mg - __? mg IV - may repeat bolus doses every 20-30 minutes until calm then administer 25% of the maximum dose every 6 hours. Monitor ECG and QTc interval.  HALDOL INJECTION IS NOT APPROVED FOR INTRAVENOUS ADMINISTRATION.

Rapid tranquilization:: Oral: 5-10 mg or IM: 5 mg. Average total dose (oral or IM) for tranquilization: 10-20 mg.

Elderly:  Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. HALDOL Injection is not approved for the treatment of patients with dementia-related psychosis.   START LOW (if indicated):  Patients over 65 years old generally should not receive >2 mg/24 hours.  If higher doses are given, (ECG) monitoring is recommended. Usual starting doses are 0.25 - 0.5 mg given no more than twice a day.

WARNINGS
Increased Mortality in Elderly Patients with Dementia-Related Psychosis
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. HALDOL Injection is not approved for the treatment of patients with dementia-related psychosis (see package insert for BOXED WARNING).

Cardiovascular Effects
Cases of sudden death, QT-prolongation, and Torsades de Pointes have been reported in patients receiving HALDOL. Higher than recommended doses of any formulation and intravenous administration of HALDOL appear to be associated with a higher risk of QT-prolongation and Torsades de Pointes. Although cases have been reported even in the absence of predisposing factors, particular caution is advised in treating patients with other QT-prolonging conditions (including electrolyte imbalance [particularly hypokalemia and hypomagnesemia], drugs known to prolong QT, underlying cardiac abnormalities, hypothyroidism, and familial long QT-syndrome). HALDOL INJECTION IS NOT APPROVED FOR INTRAVENOUS ADMINISTRATION. If HALDOL is administered intravenously, the ECG should be monitored for QT prolongation and arrhythmias.

Tardive Dyskinesia
A syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.

Both the risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses.

There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.

Given these considerations, antipsychotic drugs should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that, 1) is known to respond to antipsychotic drugs, and, 2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.

If signs and symptoms of tardive dyskinesia appear in a patient on antipsychotics, drug discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.

(For further information about the description of tardive dyskinesia and its clinical detection, please refer to ADVERSE REACTIONS - PACKAGE INSERT.)

Neuroleptic Malignant Syndrome (NMS)
A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status (including catatonic signs) and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure.

The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology.

The management of NMS should include 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.

If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.

Hyperpyrexia and heat stroke, not associated with the above symptom complex, have also been reported with HALDOL.

[SEE PACKAGE INSERT FOR ADDITIONAL COMMENTS]

Supplied: Tablet: 0.5 mg, 1 mg, 2 mg, 5 mg, 10 mg, 20 mg. Oral concentrate: 2 mg/ml (15 ml, 120 ml). Injection (decanoate): 50 mg/ml (1 ml, 5 ml); 100 mg/ml (1 ml, 5 ml). Injection (lactate): 5 mg/ml (1 ml, 10 ml).

DRUG INTERACTIONS
The dose of FANAPT should be reduced in patients co-administered a strong CYP2D6 or CYP3A4 inhibitor.

DOSAGE AND ADMINISTRATION
DOSAGE AND ADMINISTRATION (summary):
The recommended target dosage of FANAPT tablets is 12 to 24 mg/day administered twice daily. This target dosage range is achieved by daily dosage adjustments, alerting patients to symptoms of orthostatic hypotension, starting at a dose of 1 mg twice daily, then moving to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg twice daily on days 2, 3, 4, 5, 6, and 7 respectively, to reach the 12 mg/day to 24 mg/day dose range. FANAPT can be administered without regard to meals.

Usual Dose
FANAPT must be titrated slowly from a low starting dose to avoid orthostatic hypotension due to its alpha-adrenergic blocking properties. The recommended starting dose for FANAPT tablets is 1 mg twice daily. Increases to reach the target dose range of 6-12 mg twice daily may be made with daily dosage adjustments to 2 mg twice daily, 4 mg twice daily, 6 mg twice daily, 8 mg twice daily, 10 mg twice daily, and 12 mg twice daily on days 2, 3, 4, 5, 6, and 7, respectively. Efficacy was demonstrated with FANAPT in a dose range of 6 to 12 mg twice daily. Prescribers should be mindful of the fact that patients need to be titrated to an effective dose of FANAPT. Thus, control of symptoms may be delayed during the first 1 to 2 weeks of treatment compared to some other antipsychotic drugs that do not require similar titration. Prescribers should also be aware that some adverse effects associated with FANAPT use are dose related.

The maximum recommended dose is 12 mg twice daily (24 mg/day); FANAPT doses above 24 mg/day have not been systematically evaluated in the clinical trials.

FANAPT can be administered without regard to meals.

Dosage in Special Populations
Dosage adjustments are not routinely indicated on the basis of age, gender, race, or renal impairment status.

Dosage adjustment for patients taking FANAPT concomitantly with potential CYP2D6 inhibitors: FANAPT dose should be reduced by one-half when administered concomitantly with strong CYP2D6 inhibitors such as fluoxetine or paroxetine. When the CYP2D6 inhibitor is withdrawn from the combination therapy, FANAPT dose should then be increased to where it was before.

Dosage adjustment for patients taking FANAPT concomitantly with potential CYP3A4 inhibitors: FANAPT dose should be reduced by one-half when administered concomitantly with strong CYP3A4 inhibitors such as ketoconazole or clarithromycin. When the CYP3A4 inhibitor is withdrawn from the combination therapy, FANAPT dose should be increased to where it was before.

Dosage adjustment for patients taking FANAPT who are poor metabolizers of CYP2D6: FANAPT dose should be reduced by one-half for poor metabolizers of CYP2D6.

Hepatic Impairment: FANAPT is not recommended for patients with hepatic impairment.

Maintenance Treatment
Although there is no body of evidence available to answer the question of how long the patient treated with FANAPT should be maintained, it is generally recommended that responding patients be continued beyond the acute response. Patients should be periodically reassessed to determine the need for maintenance treatment.

Reinitiation of Treatment in Patients Previously Discontinued
Although there are no data to specifically address re-initiation of treatment, it is recommended that the initiation titration schedule be followed whenever patients have had an interval off FANAPT of more than 3 days.

Switching from Other Antipsychotics
There are no specific data to address how patients with schizophrenia can be switched from other antipsychotics to FANAPT or how FANAPT can be used concomitantly with other antipsychotics. Although immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients with schizophrenia, more gradual discontinuation may be most appropriate for others. In all cases, the period of overlapping antipsychotic administration should be minimized.

HOW SUPPLIED
FANAPT tablets are available in the following strengths: 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg and 12 mg. The tablets are white, round, flat, beveled-edged and identified with a logo “” debossed on one side and tablet strength “1”, “2”, “4”, “6”, “8”, “10”, or “12” debossed on the other side.

Supplied: 5 mg, 10 mg, 25 mg, 50 mg cap.

Mechanism of Action: The mechanism of action of loxapine in the treatment of agitation associated with schizophrenia is unknown. However, its efficacy could be mediated through a combination of antagonism of central dopamine D2 and serotonin 5-HT2A receptors. The mechanism of action of loxapine in the treatment of agitation associated with bipolar I disorder is unknown.

INDICATIONS AND USAGE
ADASUVE is a typical antipsychotic indicated for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults.

Efficacy was demonstrated in 2 trials in acute agitation: one in schizophrenia and one in bipolar I disorder (1, 14)

Limitations of Use:
ADASUVE must be administered only in an enrolled healthcare facility (1)
DOSAGE AND ADMINISTRATION
Must be administered only by a healthcare professional ( 2.1)
10 mg by oral inhalation using an inhaler ( 2.1)
Administer only a single dose within any 24-hour period ( 2.1)
Prior to administering, screen all patients for a history of pulmonary disease, and examine patients (including chest auscultation) for respiratory abnormalities (e.g. wheezing) ( 2.2)
Refer to Full Prescribing Information for important instructions on use of the ADASUVE inhaler ( 2.3)
After administration, monitor patients for signs and symptoms of bronchospasm at least every 15 minutes for at least one hour ( 2.4)

DOSAGE FORMS AND STRENGTHS
Inhalation powder: 10 mg unit in a single-use inhaler ( 3)

CONTRAINDICATIONS
Current diagnosis or history of asthma, chronic obstructive pulmonary disease (COPD), or other lung disease associated with bronchospasm.
Acute respiratory signs/symptoms (e.g., wheezing) .
Current use of medications to treat airways disease, such as asthma or COPD.
History of bronchospasm following ADASUVE treatment.
Known hypersensitivity to loxapine or amoxapine.

WARNINGS AND PRECAUTIONS
Neuroleptic Malignant Syndrome: May develop in patients treated with antipsychotic drugs. Discontinue treatment ( 5.4)
Hypotension and Syncope: Use with caution in patients with known cardiovascular or cerebrovascular disease ( 5.5)
Seizure: Use with caution in patients with a history of seizures or with conditions that lower the seizure threshold ( 5.6)
Potential for Cognitive and Motor Impairment: Use caution when driving or operating machinery ( 5.7)
Cerebrovascular Adverse Reactions: Increased incidence of stroke and transient ischemic attack in elderly patients with dementia-related psychosis treated with antipsychotic drugs ( 5.8)

The efficacy of LATUDA in schizophrenia was established in four 6-week controlled studies of adult patients with schizophrenia.

The effectiveness of LATUDA for longer-term use, that is, for more than 6 weeks, has not been established in controlled studies. Therefore, the physician who elects to use LATUDA for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient [see Dosage and Administration].

DOSAGE AND ADMINISTRATION
Schizophrenia
The recommended starting dose of LATUDA is 40 mg once daily. Initial dose titration is not required. LATUDA has been shown to be effective in a dose range of 40 mg/day to 120 mg/day. In the 6-week controlled trials, there was no suggestion of added benefit with the 120 mg/day dose, but there was a dose-related increase in certain adverse reactions. Therefore, the maximum recommended dose is 80 mg/day.

Administration Instructions
LATUDA should be taken with food (at least 350 calories).

Dosage in Special Populations
Dosage adjustments are not recommended on the basis of age, gender, and race.

Dose adjustment is recommended in moderate and severe renal impairment patients. The dose in these patients should not exceed 40 mg/day.

Dose adjustment is recommended in moderate and severe hepatic impairment patients. The dose in these patients should not exceed 40 mg/day.

Dosing recommendation for patients taking LATUDA concomitantly with potential CYP3A4 inhibitors: When coadministration of LATUDA with a moderate CYP3A4 inhibitor such as diltiazem is considered, the dose should not exceed 40 mg/day. LATUDA should not be used in combination with a strong CYP3A4 inhibitor (e.g., ketoconazole).

Dosing recommendation for patients taking LATUDA concomitantly with potential CYP3A4 inducers: LATUDA should not be used in combination with a strong CYP3A4 inducer (e.g., rifampin).

HOW SUPPLIED
LATUDA tablets are available in the following shape and color (Table 1) with respective one-sided debossing: 40 mg (white to off-white, round, 'L40'), or 80 mg (pale green, oval, 'L80').

Supplied: 5 mg, 10 mg, 25 mg, 50 mg tab.

Acute mania associated with bipolar disorder: Oral: Mono- therapy: Usual starting dose: 10-15 mg once daily - increase by 5 mg/day at intervals of not less than 24 hours. Maintenance: 5-20 mg/day. Maximum dose: 20 mg/day. Combination therapy (with lithium or valproate): Initial: 10 mg once daily; dosing range: 5-20 mg/day.

Agitation (acute, associated with bipolar disorder or schizophrenia): IM: Initial dose: 5-10 mg (a lower dose of 2.5 mg may be considered when clinical factors warrant); additional doses (2.5-10 mg) may be considered; however, 2-4 hours should be allowed between doses to evaluate response (maximum total daily dose: 30 mg, per manufacturer's recommendation).

Supplied: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg tablet. Orally-disintegrating tab (Zydis®): 5, 10, 15, 20 mg. Injection: 10 mg (powder for reconstitution)

Manufacturer:
ZYPREXA® Zydis® (Olanzapine) Orally Disintegrating Tablets
ZYPREXA Zydis, an alternative formulation that dissolves quickly in the mouth, is available in 5, 10, 15, and 20 mg tablets.

* Rapidly dissolves in mouth
* Can be taken with or without water
* Same indications as ZYPREXA tablet
* For use where clinically indicated (for example, patients who have difficulty swallowing pills, those who cheek or spit their medication)
* Bioequivalent to ZYPREXA tablets

ZYPREXA® IntraMuscular
ZYPREXA IntraMuscular is approved for the treatment of agitation associated with schizophrenia and bipolar mania.

Follow the steps below to reconstitute and use ZYPREXA IntraMuscular:

1. Inject 2.1 mL of Sterile Water for Injection into single-packaged vial for up to 10-mg dose.
2. Dissolve contents of vial completely; resulting solution should be clear and yellow.
3. Use solution within 1 hour; discard any unused portion.
4. Refer to table for injection volumes and corresponding doses of ZYPREXA IntraMuscular.
5. Immediately after use, dispose of syringe in approved sharps box.

Recommended dose for agitation in schizophrenia or bipolar mania is 10 mg. If clinically warranted, subsequent doses up to 10 mg may be given to agitated patients with schizophrenia or bipolar mania. However, the efficacy of repeated doses has not been systematically evaluated in controlled clinical trials. The safety of total daily doses greater than 30 mg or of 10 mg injections given more frequently than 2 hours after the initial dose and 4 hours after the second dose has not been evaluated in clinical trials. Maximal dosing (three 10-mg doses administered 2-4 hours apart) may be associated with substantial occurrence of significant orthostatic hypotension; it is recommended that patients requiring subsequent intramuscular injections be assessed for orthostatic hypotension prior to the administration of any subsequent doses. The administration of an additional dose to a patient with a clinically significant postural change in systolic blood pressure is not recommended.

Patients should remain recumbent if drowsy or dizzy after injection until examination has indicated that they are not experiencing postural hypotension and/or bradycardia.

Recommended dose for agitation in special populations is 2.5mg - 5mg.
A dose of  5 mg per injection should be considered for geriatric patients or when other clinical factors warrant. A lower dose of 2.5mg per injection should be considered for patients who otherwise might be debilitated, be predisposed to hypotensive reactions, or be pharmacodynamically sensitive to olanzapine.

Supplied: 2 mg, 4 mg, 8 mg, 16 mg tab.

Evidence supporting approval of pimozide for use in Tourette's Disorder was obtained in two controlled clinical investigations which enrolled patients between the ages of 8 and 53 years. Most subjects in the two trials were 12 or older.

Dosing (Adults): Tourette's: In general, treatment with ORAP should be initiated with a dose of 1 to 2 mg a day in divided doses. The dose may be increased thereafter every other day. Most patients are maintained at less than 0.2 mg/kg per day, or 10 mg/day, whichever is less. Doses greater than 0.2 mg/kg/day or 10 mg/day are not recommended.  Note: Sudden unexpected deaths have occurred in patients taking doses >10 mg. Note: An ECG should be performed baseline and periodically thereafter, especially during dosage adjustment.

Supplied: 1 mg, 2 mg tab.

Mania: Oral: Initial: 50 mg twice daily on day 1, increase dose in increments of 100 mg/day to 200 mg twice daily on day 4; may increase to a target dose of 800 mg/day by day 6 at increments of </= 200 mg/day. Usual dosage range: 400-800 mg/day.

Supplied: 25 mg, 100 mg, 200 mg, 300 mg tab.

Supplied: Tablet: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg. Oral solution: 1 mg/ml (30 ml). Oral disintegrating tablets (Risperdal M-Tabs): 0.5 mg, 1 mg , 2 mg. Injection (Risperdal® Consta): 25 mg, 37.5 mg, 50 mg.

Depressive disorders, dementia: Oral: Initial: 25 mg 3 times/day; maintenance dose: 20 to 200 mg/day.

Supplied: 10 mg, 15 mg, 25 mg, 50 mg, 100 mg, 150 mg, 200 mg tablet.

Severe psychosis: Initial: 5 mg 2 times/day, may increase gradually, if necessary; maximum: 60 mg/day.

Rapid tranquilization (administered every 30 to 60 minutes): Oral: 5-10 mg; average total dose for tranquilization: 15-30 mg

Supplied: 1 mg, 2 mg, 5 mg, 10 mg cap.

Supplied: 1 mg, 2 mg, 5 mg, 10 mg tab.

Supplied: 20 mg, 40 mg, 60 mg, 80 mg cap.  20 mg - injection (powder for reconstitution).

Dosage forms: Lithium is a monovalent cation

Lithium carbonate
Tablet or capsule:
300 mg (8.12 mEq lithium)
600 mg (16.24 mEq lithium)

Extended release capsule:
300 mg (8.12 mEq lithium)
450 mg (12.18 mEq lithium)

Lithium citrate
Oral solution: 8 mEq (of lithium) /5 mL

Other:
1) No clinically significant differences exist between lithium-immediate-release capsules and tablets.
2) Both formulations are 95-100% absorbed.
3) Switching among the citrate, capsule, and tablet dosage forms should not result in significantly different 12-hr steady-state levels.
4) Sustained-release formulations were developed to decrease the adverse effects associated with peak and rapidly rising serum lithium concentrations. This difference is restricted to a minority of patients.
5) Switch patients between the immediate-release and sustained-release products on a mg-for-mg basis.

Usual dosage:
900-2000 mg/day (acute mania) with normal renal function.
600 mg/day (prophylaxis).

Literature-Based Dosing vs Kinetic-Based Dosing
Based on kinetic population parameters and modified according to clinical experience
-initial doses = 900-1200mg/day; increased by 300-600mg Q 2-3 days. if decreased renal function, use above guidelines. Test Dose Methods for Inital Dosage (Single Point Method) .
Monitor serum lithium every 4 to 5 days during initial therapy. Drawing Levels: obtain trough level just before next dose (8-12 hours after previous dose). Levels should be obtained twice weekly until both patient's clinical status and levels are stable then levels may be obtained every 1-3 months. Target levels:  Acute mania: 0.6-1.2 mEq/L (SI: 0.6-1.2 mmol/L)
Protection against future episodes in most patients with bipolar disorder: 0.8-1 mEq/L (SI: 0.8-1.0 mmol/L); a higher rate of relapse is described in subjects who are maintained at <0.4 mEq/L (SI: 0.4 mmol/L). Elderly patients can usually be maintained at lower end of therapeutic range (0.6-0.8 mEq/L)

Toxic concentration: >1.5 mEq/L (SI: >2 mmol/L). Adverse effect levels: GI complaints/tremor: 1.5-2 mEq/L.  Confusion/somnolence: 2-2.5 mEq/L. Seizures/death: >2.5 mEq/L

Renal Dosing:
CrCl 10-50 mL/minute: Administer 50-75% of normal dose
CrCl < 10 mL/minute: Administer 25-50% of normal dose
Hemodialysis: 50-100% dialyzable - administer after each dialysis treatment.
Most patients tolerate BID dosing.