DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Clozapine (Clozapine) - Indications and Dosage

 
 



INDICATIONS AND USAGE

Treatment Resistant Schizophrenia

Clozapine tablets USP are indicated for the treatment of severely ill patients with schizophrenia who fail to respond adequately to standard antipsychotic treatment. Because of the significant risk of agranulocytosis and seizure associated with their use, clozapine tablets USP should be used only in patients who have failed to respond adequately to standard antipsychotic treatment [see Warnings and Precautions (5.1, 5.4)].

The effectiveness of clozapine tablets USP in treatment-resistant schizophrenia was demonstrated in a 6 week, randomized, double-blind, active-controlled study comparing clozapine tablets USP and chlorpromazine in patients who had failed other antipsychotics [see Clinical Studies ].

Reduction in the Risk of Recurrent Suicidal Behavior in Schizophrenia or Schizoaffective Disorder

Clozapine tablets USP are indicated for reducing the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder who are judged to be at chronic risk for re-experiencing suicidal behavior, based on history and recent clinical state. Suicidal behavior refers to actions by a patient that put him/herself at risk for death.

The effectiveness of clozapine tablets USP in reducing the risk of recurrent suicidal behavior was demonstrated over a two-year treatment period in the InterSePT™ trial [see Clinical Studies (14.2) ].

DOSAGE AND ADMINISTRATION

Required Laboratory Testing Prior to Initiation and During Therapy

Prior to initiating treatment with clozapine tablets, obtain a complete blood count (CBC) with differential. The absolute neutrophil count (ANC) must be greater than or equal to 2000/mm3 and the WBC must be greater than or equal to 3500 mm3 in order to initiate treatment. To continue treatment, the ANC and WBC must be monitored regularly [see Warnings and Precautions ].

Dosing Information

The starting dose is 12.5 mg once daily or twice daily. The total daily dose can be increased in increments of 25 mg to 50 mg per day, if well-tolerated, to achieve a target dose of 300 mg to 450 mg per day (administered in divided doses) by the end of 2 weeks. Subsequently, the dose can be increased once weekly or twice weekly, in increments of up to 100 mg. The maximum dose is 900 mg per day. To minimize the risk of orthostatic hypotension, bradycardia, and syncope, it is necessary to use this low starting dose, gradual titration schedule, and divided dosages [see Warnings and Precautions].

Clozapine tablets can be taken with or without food [see Pharmacokinetics ].

Maintenance Treatment

Generally, it is recommended that patients responding to clozapine tablets continue maintenance treatment on their effective dose beyond the acute episode.

Discontinuation of Treatment

In the event of planned termination of clozapine tablets therapy, reduce the dose gradually over a period of 1 to 2 weeks. If abrupt discontinuation is necessary (because of agranulocytosis or another medical condition, for example), monitor carefully for the recurrence of psychotic symptoms and symptoms related to cholinergic rebound such as profuse sweating, headache, nausea, vomiting, and diarrhea.

Re-Initiation of Treatment

When restarting clozapine tablets in patients who have discontinued clozapine tablets (i.e., 2 days or more since the last dose), re-initiate with 12.5 mg once daily or twice daily. This is necessary to minimize the risk of hypotension, bradycardia, and syncope [see Warnings and Precautions (5.3).] If that dose is well tolerated, the dose may be increased to the previously therapeutic dose more quickly than recommended for initial treatment.

Dosage Adjustments with Concomitant use of CYP1A2, CYP2D6, CYP3A4 Inhibitors or CYP1A2, CYP3A4 Inducers

Dose adjustments may be necessary in patients with concomitant use of: strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin, or enoxacin); moderate or weak CYP1A2 inhibitors (e.g., oral contraceptives, or caffeine); CYP2D6 or CYP3A4 inhibitors (e.g., cimetidine, escitalopram, erythromycin, paroxetine, bupropion, fluoxetine, quinidine, duloxetine, terbinafine, or sertraline); CYP3A4 inducers (e.g., phenytoin, carbamazepine, St. John’s wort, and rifampin); or CYP1A2 inducers (e.g., tobacco smoking) (Table 1) [See Drug Interactions (7)].  

Table 1: Dose Adjustment in Patients Taking Concomitant Medications

Co-medications

Scenarios

Initiating clozapine tablets while taking a co-medication

Adding a co-medication while taking clozapine tablets

Discontinuing a co-medication while continuing clozapine tablets

Strong CYP1A2 Inhibitors

Use one third of the clozapine tablets dose.

Increase clozapine tablets dose based on clinical response.

Moderate or Weak CYP1A2 Inhibitors

Monitor for adverse reactions. Consider reducing the clozapine tablets dose if necessary.

Monitor for lack of effectiveness. Consider increasing clozapine tablets dose if necessary.

CYP2D6 or CYP3A4 Inhibitors

Strong CYP3A4 Inducers

Concomitant use is not recommended. However, if the inducer is necessary, it

may be necessary to increase the clozapine tablets dose. Monitor for decreased effectiveness.

Reduce clozapine tablets dose based on

clinical response.

Moderate or weak CYP1A2 or CYP3A4 Inducers

Monitor for decreased effectiveness. Consider increasing the clozapine tablets dose if necessary.

Monitor for adverse reactions. Consider reducing the clozapine tablets dose if necessary.

Renal or Hepatic Impairment or CYP2D6 Poor Metabolizers

It may be necessary to reduce the clozapine tablets dose in patients with significant renal or hepatic impairment, or in CYP2D6 poor metabolizers [see Use in Specific Populations (8.6, 8.7)].

DOSAGE FORMS AND STRENGTHS

Clozapine tablets are available as 25 mg, 50 mg, 100 mg, and 200 mg pale-yellow tablets with a score on one side.

HOW SUPPLIED/STORAGE AND HANDLING

How Supplied

Clozapine Tablets USP are available as pale yellow, round tablets, debossed

and “4359" on one side and "25" and a bisect on the other side, containing 25 mg clozapine, USP packaged in bottles of 100 and 500 tablets and unit-dose boxes of 100 tablets.

Clozapine Tablets USP are available as pale yellow, round, flat-faced, beveled-edge tablets, debossed

and “4404" on one side and "50" and a bisect on the other side, containing 50 mg clozapine, USP packaged in bottles of 100 and 500 tablets and unit-dose boxes of 100 tablets.

Clozapine Tablets USP are available as pale yellow, round, flat-faced, beveled-edge tablets, debossed

and “7772" on one side and "100" and a bisect on the other side, containing 100 mg clozapine, USP packaged in bottles of 100 and 500 tablets and unit-dose boxes of 100 tablets.

Clozapine Tablets USP are available as pale yellow, oval-shaped, biconvex tablets, debossed

and “4405” on one side and “200” and a deep bisect on the other side, containing 200 mg clozapine, USP packaged in bottles of 100 and 500 tablets and unit-dose boxes of 100 tablets.

Storage and Handling

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Dispense in a tight container as defined in the USP, with a child-resistant closure (as required).

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2015