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Fazaclo (Clozapine) - Indications and Dosage

 
 



INDICATIONS AND USAGE

Treatment-Resistant Schizophrenia

FAZACLO is 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 its use, FAZACLO 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 in treatment-resistant schizophrenia was demonstrated in a 6-week, randomized, double-blind, active-controlled study comparing clozapine 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

FAZACLO is 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 in reducing the risk of recurrent suicidal behavior was demonstrated over a two-year treatment period in the InterSePT™ trial [see Clinical Studies].

DOSAGE AND ADMINISTRATION

2.1 Required Laboratory Testing Prior to Initiation and During Therapy

Prior to initiating treatment with FAZACLO, 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].

Important Administration Instructions

FAZACLO orally disintegrating tablets should be immediately placed in the mouth after removing the tablet from the blister pack or bottle. The tablet disintegrates rapidly after placement in the mouth. The tablets can be allowed to disintegrate, or they may be chewed. They may be swallowed with saliva. No water is necessary for administration.

The orally disintegrating tablets in a blister pack should be left in the unopened blister until the time of use. Just prior to use, peel the foil from the blister and gently remove the orally disintegrating tablet. Do not push the tablets through the foil, because this could damage the tablet.

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].

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

Maintenance Treatment

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

Discontinuation of Treatment

In the event of planned termination of FAZACLO 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 FAZACLO in patients who have discontinued FAZACLO (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]. If that dose is well tolerated, the dose may be increased to the previously therapeutic dose more quickly than recommended for initial treatment.

2.7 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: Dosage Adjustments in Patients Taking Concomitant Medications

Co-Medications

Scenarios

Initiating FAZACLO while taking a

co-medication

Adding a

co-medication

while taking FAZACLO

Discontinuing a

co-medication

while continuing FAZACLO

Strong CYP1A2 Inhibitors

Use one third of the FAZACLO dose.

Increase FAZACLO dose based on clinical response.

Moderate or Weak CYP1A2 Inhibitors

Monitor for adverse reactions. Consider reducing the FAZACLO dose if necessary.

Monitor for lack of effectiveness. Consider increasing FAZACLO 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 FAZACLO dose. Monitor for decreased effectiveness.

Reduce FAZACLO dose based on clinical response.

Moderate or Weak CYP1A2 or CYP3A4 Inducers

Monitor for decreased effectiveness. Consider increasing the FAZACLO dose if necessary.

Monitor for adverse reactions. Consider reducing the FAZACLO dose if necessary.

Renal or Hepatic Impairment or CYP2D6 Poor Metabolizers

It may be necessary to reduce the FAZACLO 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

FAZACLO is available as 12.5 mg, 25 mg, 100 mg, 150 mg, and 200 mg round, yellow, orally disintegrating tablets.

HOW SUPPLIED/STORAGE AND HANDLING

How Supplied

12.5 mg

1/4-inch diameter round, yellow tablet debossed with “A05” on one side.

  •  Bottles of 100: 100 tablets in an HDPE bottle with child-resistant cap … NDC No. 18860-101-10

25 mg

5/16-inch diameter round, yellow tablet debossed with “A06” on one side.

  •  Bottles of 100: 100 tablets in an HDPE bottle with child-resistant cap … NDC No. 18860-102-10

  •  Cartons of 48 for Institutional Use Only: 8 cards, 6 non child-resistant
    blisters per card ……………………………………………………...… NDC No. 18860-102-01

100 mg

1/2-inch diameter round, yellow tablet debossed with “A08” on one side.

  •  Bottles of 100: 100 tablets in an HDPE bottle with child-resistant cap … NDC No. 18860-104-10

  •  Cartons of 48 for Institutional Use Only: 8 cards, 6 non child-resistant
    blisters per card ……………………………..…………………….….… NDC No. 18860-104-01

150 mg

9/16-inch diameter round, yellow tablet debossed with “A09” on one side.

  •  Bottles of 100: 100 tablets in an HDPE bottle with child-resistant cap … NDC No. 18860-105-10

  •  Cartons of 48 for Institutional Use Only: 8 cards, 6 non child-resistant
    blisters per card ………………………………….………………………NDC No. 18860-105-01

200 mg

5/8-inch diameter round, yellow tablet debossed with “A10” on one side.

  •  Bottles of 100: 100 tablets in an HDPE bottle with child-resistant cap … NDC No. 18860-106-10

  •  Cartons of 48 for Institutional Use Only: 8 cards, 6 non child-resistant
    blisters per card …………………………………………..…………..… NDC No. 18860-106-01

Storage and Handling

Store FAZACLO at 20°C to 25°C (68° to 77°F); excursions permitted to 15°C to 30°C (59° to 86°F). (See USP Controlled Room Temperature.) Protect from moisture.

KEEP OUT OF REACH OF CHILDREN.

FAZACLO tablets must remain in the original package until used by the patient.

Drug dispensing should not ordinarily exceed a weekly supply. If a patient is eligible for WBC count and ANC testing every 2 weeks, then a 2-week supply of FAZACLO can be dispensed. If a patient is eligible for WBC count and ANC testing every 4 weeks, then a 4-week supply of FAZACLO can be dispensed. Dispensing should be contingent upon the WBC count and ANC testing results.

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