Bedaquiline

Renal Impairment SIRTURO has mainly been studied in adult patients with normal renal function. Renal excretion of unchanged bedaquiline is not substantial (less than or equal to 0.001%). No dose adjustment is required in patients with mild or moderate renal impairment. In patients with severe renal impairment or end stage renal disease requiring hemodialysis or peritoneal dialysis, SIRTURO should be used with caution [see Clinical Pharmacology ] .

Monitor adult and pediatric patients for adverse reactions of SIRTURO when administered to patients with severe renal impairment or end stage renal disease requiring hemodialysis or peritoneal dialysis.

Hepatic Impairment The pharmacokinetics of bedaquiline were assessed after single-dose administration to adult patients with moderate hepatic impairment (Child-Pugh B) [see Clinical Pharmacology ] . Based on these results, no dose adjustment is necessary for SIRTURO in patients with mild or moderate hepatic impairment. SIRTURO has not been studied in patients with severe hepatic impairment and should be used with caution in these patients only when the benefits outweigh the risks.

Clinical monitoring for SIRTURO-related adverse reactions is recommended [see Warnings and Precautions ] .

Important Administration Instructions Administer SIRTURO by directly observed therapy (DOT). Only use SIRTURO in combination with at least three other drugs to which the patient's 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 four other drugs to which the patient's 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 [see Dosage and Administration ].

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 or soft food, or crushed and mixed with soft food, or administered through a feeding tube [see Dosage and Administration ]. 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 [see Dosage and Administration ] ECG [see Warnings and Precautions ] Serum potassium, calcium, and magnesium concentrations [see Warnings and Precautions ] Liver enzymes [see Warnings and Precautions ]

Method of Administration There is one method of administration of SIRTURO 100 mg tablet and four different methods of administration of SIRTURO 20 mg tablet as follows, each of which must be taken with food: For SIRTURO 100 mg tablet, administer the tablet whole with water. Take with food. For SIRTURO 20 mg tablet, the four different methods of administration are outlined below.

Each administration method requires SIRTURO to be taken with food in addition to any soft food or beverage used to administer SIRTURO by the different methods for patients who cannot swallow intact SIRTURO 20 mg tablets. 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 split in half along the functional score line into two 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 Mixed with Beverage or Soft Food For patients who have difficulty swallowing intact tablets, SIRTURO 20 mg tablet can be dispersed in water prior to administration with food.

If needed to aid with administration, the dispersed mixture in water 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. If needed to aid with oral 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. Take with food in addition to any beverage or soft food used to aid in administration.

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. To ensure no tablet residue is left in the container, add more soft food and administer the contents immediately. Take with food in addition to any beverage or soft food used to aid in administration.

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. Administer with food.