Versacloz Dosage

Absolute Neutrophil Count Testing Prior to VERSACLOZ Initiation

Prior to initiating VERSACLOZ treatment, obtain a baseline absolute neutrophil count (ANC). VERSACLOZ initiation is not recommended in patients with an ANC less than 1500/µL.

For patients with documented Benign Ethnic Neutropenia (BEN) (also known as Duffy-null associated neutrophil count)), obtain at least two baseline ANC levels. VERSACLOZ initiation is not recommended in patients with BEN with an ANC less than 1000/µL.

For dosage modifications based on ANC results, see Dosage and Administration(2.4, 2.5).

Recommended Dosage

To reduce the risk of orthostatic hypotension, bradycardia, and syncope, the recommended starting dosage is much lower than the target dosage.

The recommended starting oral dosage of VERSACLOZ is 12.5 mg once or twice daily. If well-tolerated, increase the total daily dose in increments of 25 mg to 50 mg per day to achieve a target dosage of 150 mg to 225 mg twice per day by the end of two weeks. Subsequently, may increase the dosage in increments of up to 100 mg once weekly or twice weekly. The maximum recommended VERSACLOZ oral dosage is 450 mg twice daily.

Important Administration Instructions

Educate patients and caregivers on how to administer VERSACLOZ ( see the Instructions for Use). VERSACLOZ can be taken with or without food [ see Clinical Pharmacology (12.3)].

The following are important administration instructions:

• Administer VERSACLOZ orally using the provided oral syringes (1 mL or 9 mL).
• After shaking the VERSACLOZ bottle for 10 seconds, press the syringe adaptor on top of the bottle.
• Insert the oral syringe (1 mL or 9 mL) filled with air into the adapter, dispel the air into the bottle, and then turn the bottle upside down.
• Draw the prescribed amount of the oral suspension from the bottle and immediately dispense directly to the mouth after preparation. Do not store a dose in the syringe for later use.

After use, may wash the oral syringe with warm water and then dry the oral syringe for the next use. The bottle may be closed with the same cap without removing the bottle adapter.

Dosage Modification Based on ANC Results

Table 1 provides recommended VERSACLOZ dosage modifications based on ANC results. For dosage modifications based on ANC results for patients with Benign Ethnic Neutropenia (BEN) (also known as Duffy-null associated neutrophil count), see Table 2.

Table 1: VERSACLOZ Dosage Modifications Based on ANC Results and Frequency of ANC Testing

1Confirm all initial reports of ANC less than 1500/μL with a repeat ANC measurement within 24 hours

Dosage Modifications Based on ANC Results for Patients with Benign Ethnic Neutropenia

Table 2 provides recommended VERSACLOZ dosage modifications based on ANC results for patients with Benign Ethnic Neutropenia (BEN) (also known as Duffy-null associated neutrophil count).. For dosage modifications based on ANC results for patients without BEN, see Table 1.

Table 2: Dosage Modifications Based on ANC Results and Frequency of ANC Testing in Patients with Benign Ethnic Neutropenia 1

1Benign Ethnic Neutropenia (BEN) is also known as Duffy-null associated neutrophil count.

2Confirm all initial reports of ANC less than 1500/μL with a repeat ANC measurement within 24 hours

Discontinuation of VERSACLOZ Treatment

If discontinuing VERSACLOZ in patients with:

• Moderate or severe neutropenia, see Table 1.
• Normal or mild neutropenia, reduce the dosage gradually over a period of 1 to 2 weeks, and continue monitoring ANC levels until their ANC is ≥1500/μL.

If discontinuing VERSACLOZ in patients with Benign Ethnic Neutropenia (BEN) (also known as Duffy-null associated neutrophil count) with:

• Neutropenia, see Table 2.
• ANC within their normal range of ANC reduce the dosage gradually over a period of 1 to 2 weeks.

When discontinuing VERSACLOZ, monitor patients for the symptoms related to psychotic recurrence and cholinergic rebound (e.g., profuse sweating, headache, nausea, vomiting, diarrhea).

Restarting VERSACLOZ Treatment After Interrupting VERSACLOZ

When restarting VERSACLOZ in patients who have interrupted VERSACLOZ treatment, use a lower dosage to minimize the risk of hypotension, bradycardia, and syncope.

• If one day’s dosage is missed, resume VERSACLOZ treatment at 40% to 50% of the previous dosage.
• If two days of dosing is missed, resume VERSACLOZ treatment at approximately 25% of the previous dosage.
• For longer interruptions, restart VERSACLOZ treatment with a dosage of 12.5 mg once or twice daily. If this dosage is well-tolerated, may increase the dosage to the previous dosage more quickly than recommended than for initial VERSACLOZ treatment.

Dosage Modifications for Drug Interactions

See Table 3 for recommended dosage modifications to reduce the risk of VERSACLOZ associated adverse reactions or reduce the risk of lower effectiveness.

Table 3: VERSACLOZ Dosage Modifications for Drug Interactions

Dosage Recommendations in Patients with Renal or Hepatic Impairment, or CYP2D6 Poor Metabolizers

It may be necessary to reduce the VERSACLOZ dosage in patients with significant renal impairment or hepatic impairment, or in CYP2D6 poor metabolizers.