Dosage and Administration

Important Administration Instructions

Administer SIRTURO^® by directly observed therapy (DOT).
Only use SIRTURO^® in combination with at least 3 other drugs to which the patient's MDR-TB isolate has been shown to be susceptible in vitro. If in vitro testing results are unavailable, SIRTURO^® treatment may be initiated in combination with at least 4 other drugs to which the patient's MDR-TB isolate is likely to be susceptible. Refer to the prescribing information of the drugs used in combination with SIRTURO^® for further information.
SIRTURO^® (20 mg and 100 mg) must be taken with food.
SIRTURO^® 20 mg are functionally scored tablets which can be split at the scored lines into two equal halves of 10 mg each to provide doses less than 20 mg.
As an alternative method of administration, SIRTURO^® 20 mg tablets can be dispersed in water and administered, or dispersed in water and further mixed with a beverage of soft food, or crushed and mixed with soft food, or administered through a feeding tube.
Emphasize the need for compliance with the full course of therapy.

Required Testing Prior to Administration
Prior to treatment with SIRTURO^®, obtain the following:

Susceptibility information for the background regimen against M. tuberculosis isolate if possible.
ECG
Serum potassium, calcium, and magnesium concentrations
Liver enzymes

Recommended Dosage in Adult Patients

The recommended dosage of SIRTURO^® in adult patients is:

Adult Patients: Recommended Dosage of SIRTURO^®
Dosage Recommendation
Weeks 1 and 2	Weeks 3 to 24^a
400 mg (4 of the 100 mg tablets OR 20 of the 20 mg tablets) orally once daily		200 mg (2 of the 100 mg tablets OR 10 of the 20 mg tablets) orally 3 times per week
a=At least 48 hours between doses

The total duration of treatment with SIRTURO^® in adults is 24 weeks. Administer SIRTURO^® tablets with food.

Recommended Dosage in Pediatric Patients (5 years and older and weighing at least 15 kg)

The recommended dosage of SIRTURO^® in pediatric patients (5 years and older and weighing at least 15 kg) is based on body weight:

Pediatric Patients: Recommended Dosage of SIRTURO^® in Pediatric Patients (5 years and older and weighing at least 15 kg)
Body Weight	Dosage Recommendation
Body Weight	Weeks 1 and 2	Weeks 3 to 24^a
15 kg to less than 30 kg	200 mg (2 of the 100 mg tablets OR 10 of the 20 mg tablets) orally once daily	100 mg (1 of the 100 mg tablets OR 5 of the 20 mg tablets) orally 3 times per week
Greater than or equal to 30 kg	400 mg (4 of the 100 mg tablets OR 20 of the 20 mg tablets) orally once daily	200 mg (2 of the 100 mg tablets OR 10 of the 20 mg tablets) orally 3 times per week
a=At least 48 hours between doses

The total duration of treatment with SIRTURO^® in pediatric patients is 24 weeks. Administer SIRTURO^® tablets with food.

Missed Dose

If a dose is missed during the first 2 weeks of treatment, do not administer the missed dose (skip the dose and then continue the daily dosing regimen). From Week 3 onwards, if a dose is missed, administer the missed dose as soon as possible, and then resume the 3 times a week dosing regimen. The total dose of SIRTURO^® during a 7-day period should not exceed the recommended weekly dose (with at least 24 hours between each intake).

Method of Administration

There is one method of administration of SIRTURO^® 100 mg tablet and 4 different methods of administration of SIRTURO^® 20 mg tablet as follows:

For SIRTURO^® 100 mg tablet, administer the tablet whole with water. Take with food.
For SIRTURO^® 20 mg tablet, the 4 different methods of administration are outlined below.

Each administration method requires SIRTURO^® to be taken with food.

Methods of Administration of SIRTURO^® 20 mg Tablet

Administration of 20 mg Tablets to Patients who Can Swallow Intact Tablets:

Administer SIRTURO^® 20 mg tablet whole or divided in half along the functional score line into 2 equal halves of 10 mg each. Administer SIRTURO^® 20 mg tablet with water. Take with food.

Administration of 20 mg Tablets to Patients who Cannot Swallow Intact Tablets:

Dispersed in Water and Administered with Beverage or Soft Food

For patients who have difficulty swallowing intact tablets, SIRTURO^® 20 mg tablet can be dispersed in water and administered. To aid with administration, the dispersion can be further mixed with a beverage (e.g., water, milk products, apple juice, orange juice, cranberry juice or carbonated beverage) or soft food (e.g., yogurt, apple sauce, mashed banana or porridge) as follows:

Disperse tablets in water (maximum of 5 tablets in 5 mL of water) in a drinking cup.
Mix the contents of the cup well until the tablets are completely dispersed and then orally administer the contents of the cup immediately with food. To aid with administration, the dispersed mixture in water can be further mixed with at least 5 mL of beverage or 1 teaspoonful of soft food and then orally administer the contents of the cup immediately.
If the total dose requires more than 5 tablets, repeat the above preparation steps with the appropriate number of additional tablets until the desired dose is reached.
Ensure no tablet residue is left in the cup, rinse with beverage or add more soft food and orally administer the contents of the cup immediately.

Crushed and Mixed with Soft Food

SIRTURO^® 20 mg tablet can be crushed and mixed with soft food (e.g., yogurt, apple sauce, mashed banana or porridge) immediately prior to use and administered orally. Ensure no tablet residue is left in container, add more soft food if necessary and administer the contents immediately.

Administration Through a Feeding Tube

SIRTURO^® 20 mg tablet can be administered through a feeding tube (8 French or greater) as follows:

Disperse 5 tablets or less in 50 mL of non-carbonated water and mix well. Mixture should be white to almost white with visible particles expected.
Administer through the feeding tube immediately.
Repeat with additional tablets until desired dose is reached.
Rinse and flush with 25 mL of additional water to ensure no tablet residue is left in materials used for preparation or the feeding tube.