SIRTURO® Appropriate Use

INDICATIONS AND USAGE

SIRTURO® (bedaquiline) is a diarylquinoline antimycobacterial drug indicated as part of combination therapy in the treatment of adults (≥18 years) with pulmonary multi drug resistant tuberculosis (MDR TB). Reserve SIRTURO® for use when an effective treatment regimen cannot otherwise be provided. Administer SIRTURO® by directly observed therapy (DOT).

This indication is approved under accelerated approval based on time to sputum culture conversion. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials

Limitations of Use

Do not use SIRTURO® for the treatment of:

  • Latent infection due to Mycobacterium tuberculosis
  • Drug-sensitive tuberculosis
  • Extra-pulmonary tuberculosis
  • Infections caused by non-tuberculous mycobacteria

The safety and efficacy of SIRTURO® in the treatment of HIV-infected patients with MDR-TB have not been established as clinical data are limited.

SIRTURO® Patient Access

Janssen Therapeutics, Division of Janssen Products, LP, is committed to appropriate and responsible access to SIRTURO®. SIRTURO® is available by prescription from healthcare professionals associated with qualified centers for the evaluation, diagnoses, and treatment of TB, including pulmonary MDR-TB. Qualified centers include public health departments, clinics that treat TB, and hospitals and institutions with a TB concentration.

If you have questions regarding access to SIRTURO®, please contact Metro Medical at 1-855-691-0963.

Patient Counseling

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Patients should be advised that the following serious side effects can occur with SIRTURO®: death, heart rhythm abnormalities, and/or hepatitis. In addition, patients should also be advised about other potential side effects: nausea, joint pain, headache, increased blood amylase, hemoptysis, chest pain, anorexia, and/or rash. Additional testing may be needed to monitor or reduce the likelihood of adverse effects.

Advise patients to take SIRTURO® in combination with other antimycobacterial drugs as prescribed. Emphasize compliance with the full course of therapy. Advise  patients that skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the treatment and (2) increase the likelihood that their mycobacterium may develop resistance and the disease will not be treatable by SIRTURO® or other antibacterial drugs in the future.

If a dose is missed during the first 2 weeks of treatment advise patients not to make up the missed dose but to continue the usual dosing schedule. From Week 3 onwards, if a 200-mg dose is missed, advise patients to take the missed dose as soon as possible, and then resume the 3 times a week regimen.

  • Patients should be informed to take SIRTURO® with food.
  • Patients should be advised to abstain from alcohol, hepatotoxic medications, or herbal products.
  • Patients should be advised to discuss with their physician the other medications they are taking and other medical conditions before starting treatment with SIRTURO®.

Print out this helpful information on treating with SIRTURO® for your patients.

CDC TB Treatment Guidelines

The Centers for Disease Control and Prevention (CDC) has established guidelines for the treatment of TB, including drug-resistant pulmonary TB.

Prescribing physicians are responsible for not only prescribing an appropriate regimen but also for successful completion of therapy. Access the CDC Treatment Guidelines for TB here.

IMPORTANT SAFETY INFORMATION

WARNINGS: INCREASED MORTALITY; QT PROLONGATION

    Increased Mortality
  • An increased risk of death was seen in the SIRTURO® treatment group (9/79, 11.4%) compared to the placebo treatment group (2/81, 2.5%) in one placebo-controlled trial. Only use SIRTURO® when an effective treatment regimen cannot otherwise be provided.
    QT Prolongation
  • QT prolongation can occur with SIRTURO®. Use with drugs that prolong the QT interval may cause additive QT prolongation. Monitor ECGs. Discontinue SIRTURO® if significant ventricular arrhythmia or if QTcF interval prolongation of greater than 500 ms develops.

Warnings and Precautions

Increased Mortality

An increased risk of death was seen in the SIRTURO® treatment group. The imbalance in deaths is unexplained. No discernible pattern between death and sputum culture conversion, relapse, sensitivity to other drugs used to treat tuberculosis, HIV status, or severity of disease could be observed. Only use SIRTURO® when an effective treatment regimen cannot otherwise be provided.

QT Prolongation

SIRTURO® prolongs the QT interval. Obtain an ECG before initiation of treatment, and at least 2, 12, and 24 weeks after starting treatment with SIRTURO®. Obtain serum potassium, calcium, and magnesium at baseline and correct if abnormal. Monitor electrolytes if QT prolongation is detected.

SIRTURO® has not been studied in patients with ventricular arrhythmias or recent myocardial infarction.

The following may increase the risk for QT prolongation when patients are receiving SIRTURO®: use with other QT prolonging drugs including fluoroquinolones and macrolide antibacterial drugs and the antimycobacterial drug, clofazimine; a history of Torsade de Pointes; a history of congenital long QT syndrome; a history of or ongoing hypothyroidism; a history of or ongoing bradyarrhythmias; a history of uncompensated heart failure; serum calcium, magnesium, or potassium levels below the lower limits of normal

If necessary, bedaquiline treatment initiation could be considered in these patients after a favorable benefit risk assessment and with frequent ECG monitoring.

Discontinue SIRTURO® and all other QT prolonging drugs if the patient develops clinically significant ventricular arrhythmia or a QTcF interval of greater than 500 ms (confirmed by repeat ECG).

If syncope occurs, obtain an ECG to detect QT prolongation.

Hepatotoxicity

More hepatic-related adverse drug reactions were reported with the use of SIRTURO® plus other drugs to treat tuberculosis compared to other drugs used to treat tuberculosis without the addition of SIRTURO®. Alcohol and other hepatotoxic drugs should be avoided while on SIRTURO®, especially in patients with impaired hepatic function.

Monitor symptoms (such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, and hepatomegaly) and laboratory tests (ALT, AST, alkaline phosphatase, and bilirubin) at baseline, monthly while on treatment, and as needed. Test for viral hepatitis and discontinue other hepatotoxic medications if evidence of new or worsening liver dysfunction occurs. Discontinue SIRTURO® if:

  • aminotransferase elevations are accompanied by total bilirubin elevation greater than two times the upper limit of normal
  • aminotransferase elevations are greater than eight times the upper limit of normal
  • aminotransferase elevations are greater than five times the upper limit of normal and persist beyond two weeks

Drug Interactions

CYP3A4 Inducers/Inhibitors: Bedaquiline is metabolized by CYP3A4 and its systemic exposure and therapeutic effect may therefore be reduced during co-administration with inducers of CYP3A4. Avoid coadministration of strong CYP3A4 inducers such as rifamycins (i.e., rifampin, rifapentine, and rifabutin) or moderate CYP3A4 inducers such as efavirenz. Co-administration of SIRTURO® with strong CYP3A4 inhibitors may increase the systemic exposure to bedaquiline, which could potentially increase the risk of adverse reactions. Therefore, avoid the use of strong CYP3A4 inhibitors used for more than 14 consecutive days while on SIRTURO®, unless the benefit of treatment with the drug combination outweighs the risk. Appropriate clinical monitoring for SIRTURO®-related adverse reactions is recommended.

Adverse Reactions

Adverse reactions that occurred more frequently than placebo during treatment with SIRTURO® included: nausea (38% vs. 32%), arthralgia (33% vs. 22%), headache (28% vs. 12%), hemoptysis (18% vs. 11%), chest pain (11% vs. 7%), anorexia (9% vs. 4%), transaminases increased (9% vs. 1%), rash (8% vs. 4%), and blood amylase increased (3% vs. 1%).

Please see full Prescribing Information, including Boxed Warnings and Medication Guide, for more details.