bedaquiline (Rx)

Brand and Other Names:Sirturo
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 20mg (functionally scored)
  • 100mg

Multidrug Resistant Pulmonary Tuberculosis

Diarylquinoline antimycobacterial indicated as part of combination therapy for pulmonary multidrug resistant tuberculosis (MDR-TB); reserve bedaquiline for when an effective treatment TB regimen cannot otherwise be provided

Only use 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, may be initiated in combination with at least 4 other drugs to which the patient’s MDR-TB isolate is likely to be susceptible

Weeks 1-2: 400 mg PO qDay for 2 weeks, THEN

Weeks 3-24: 200 mg 3 times/week with at least 48 hr between doses

CDC provisional guidelines

  • May be used off-label on a case-by-case basis in children, HIV-infected persons, pregnant women, persons with extrapulmonary MDR TB, and patients with comorbid conditions on concomitant medications when an effective treatment regimen cannot otherwise be provided
  • May be used on a case-by-case basis for durations longer than 24 weeks when an effective treatment regimen cannot be provided otherwise
  • Reference: MMWR Recommendations and Reports. October 25, 2013/62(rr9);1-12

Dosage Modifications

Renal impairment

  • Mild-to-moderate: No dosage adjustment required
  • Severe or end-stage renal disease requiring hemodialysis or peritoneal dialysis: Use with caution; if used, monitor for adverse reactions of bedaquiline

Hepatic impairment

  • Mild or moderate (Child-Pugh A or B): No dosage adjustment required
  • Severe (Child-Pugh C): Not studied; use only if benefits outweigh risks

Dosing Considerations

Limitations of use

  • Latent infection due to Mycobacterium tuberculosis
  • Drug-sensitive tuberculosis
  • Extra-pulmonary tuberculosis
  • Infections cause by nontuberculous mycobacteria

Nontuberculosis Mycobacteria Infection (Orphan)

Orphan designation for treatment of nontuberculosis mycobacteria infection

Orphan sponsor

  • Janssen Research & Development, LLC; 125 Trenton-Harbourton Road; Titusville, New Jersey 08560

Dosage Forms & Strengths

tablet

  • 20mg (functionally scored)
  • 100mg

Multidrug Resistant Pulmonary Tuberculosis

Diarylquinoline antimycobacterial indicated as part of combination therapy for pulmonary multidrug resistant tuberculosis (MDR-TB); reserve bedaquiline for when an effective treatment TB regimen cannot otherwise be provided

Only use 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, may be initiated in combination with at least 4 other drugs to which the patient’s MDR-TB isolate is likely to be susceptible

<5 years: Safety and efficacy not established

≥5 years

  • Weight ≥30 kg
    • Weeks 1-2: 400 mg PO qDay for 2 weeks, THEN
    • Weeks 3-24: 200 mg 3 times/week with at least 48 hr between doses
  • Weight 15 to <30 kg
    • Weeks 1-2: 200 mg PO qDay for 2 weeks, THEN
    • Weeks 3-24: 100 mg 3 times/week with at least 48 hr between doses

CDC provisional guidelines

  • May be used off-label on a case-by-case basis in children, HIV-infected persons, pregnant women, persons with extrapulmonary MDR TB, and patients with comorbid conditions on concomitant medications when an effective treatment regimen cannot otherwise be provided
  • May be used on a case-by-case basis for durations longer than 24 weeks when an effective treatment regimen cannot be provided otherwise
  • Reference: MMWR Recommendations and Reports. October 25, 2013/62(rr9);1-12

Dosage Modifications

Renal impairment

  • Mild-to-moderate: No dosage adjustment required
  • Severe or end-stage renal disease requiring hemodialysis or peritoneal dialysis: Use with caution; if used, monitor for adverse reactions of bedaquiline

Dosing Considerations

Limitations of use

  • Latent infection due to Mycobacterium tuberculosis
  • Drug-sensitive tuberculosis
  • Extra-pulmonary tuberculosis
  • Infections cause by nontuberculous mycobacteria
Next:

Interactions

Interaction Checker

and bedaquiline

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Due to system maintenance, the drug interactions feature you are attempting to access is temporarily unavailable. Please try again later.
            Previous
            Next:

            Adverse Effects

            >10%

            Adults

            • Nausea (38%)
            • Arthralgia (33%)
            • Headache (28%)
            • Chest pain (11%)

            Pediatrics

            • Arthralgia (40%)
            • Nausea (13%)
            • Abdominal pain (13%)

            1-10%

            Adults

            • Anorexia (9%)
            • Rash (8%)

            Adults or children

            • Transaminases increased (9%)
            • Blood amylase increased (3%)

            Frequency Not Defined

            QT prolongation

            Previous
            Next:

            Warnings

            Black Box Warnings

            An increased risk of death was seen in the bedaquiline treatment group (9/79, 11.4%) compared to the placebo treatment group (2/81, 2.5%) in 1 clinical trial

            Only use when an effective treatment regimen cannot otherwise be provided

            QT prolongation can occur; coadministration with drugs that prolong the QT interval may cause additive QT prolongation

            Contraindications

            None

            Cautions

            Increased risk of death in bedaquiline treatment group

            Administered by directly observed therapy (DOT)

            Potential for development of resistance to bedaquiline in M tuberculosis exists; must only be used in an appropriate combination regimen fo treatment of pulmonary MDR-TB to reduce risk of developing resistance

            Hepatotoxicity

            • Hepatic-related adverse effects increased when bedaquiline added to multidrug regimen; avoid alcohol and other hepatotoxic drugs, especially in patients with hepatic impairment
            • Monitor symptoms (eg, fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, 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
            • Monitor ALT, AST, Alkaline phosphatase, and bilirubin at baseline, and monthly while on treatment
            • Discontinue if
              • Aminotransferase increases are accompanied by total bilirubin elevation >2x ULN
              • Aminotransferase elevations >8x ULN
              • Aminotransferase elevations persist beyond 2 weeks

            QT prolongation

            • Prolongs QT interval; obtain ECG before initiating treatment and at least 2, 12, and 24 weeks after starting treatment
            • Obtain baseline serum levels for potassium, calcium, and magnesium and correct if abnormal; follow-up electrolyte monitoring if QT prolongation detected
            • Increased risk for QT prolongation with
            • Coadministration with QT prolonging drugs (eg, fluoroquinolones, macrolides, clofazimine)
            • History of Torsade de Pointes, congenital long-QT syndrome, uncompensated heart failure, or hypothyroidism with bradyarrhythmias
            • Discontinue bedaquiline and other QT prolonging drugs if the following develops
            • Clinically significant ventricular arrhythmia
            • QTcF interval >500 ms
            • Monitor ECG to confirm QT interval returned to baseline
            • If syncope occurs, obtain ECG

            Drug interaction overview

            • May prolong QT interval; assess thoroughly and if possible, avoid coadministration with other drugs that prolong QT interval
            • Metabolized by CYP3A4; avoid strong CYP3A4 inducers (eg, rifampin, rifapentine, rifabutin) and antiretroviral drugs that are moderate inducers (eg, efavirenz) that may reduce bedaquiline’s effect
            • Coadministration with CYP3A4 inhibitors may increase systemic exposure and result in adverse effects; avoid coadministration with strong CYP3A4 inhibitors >14 consecutive days, unless the benefit of treatment outweighs the risk
            • Use bedaquiline with caution when coadministered with lopinavir/ritonavir and only if the benefit outweighs the risk
            • There are no clinical data on the combined use of antiretroviral agents and bedaquiline in HIV/MDR-TB coinfected patients and only limited clinical data on use in HIV/MDR-TB coinfected patients not receiving antiretroviral therapy
            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy

            Available data from published literature of use in pregnant women are insufficient to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

            Clinical considerations

            • Active tuberculosis in pregnancy is associated with adverse maternal and neonatal outcomes including, maternal anemia, caesarean delivery, preterm birth, low birth weight, birth asphyxia, and perinatal infant death

            Animal studies

            • Reproduction studies in rats and rabbits revealed no evidence of harm to fetuses of pregnant rats and rabbits during organogenesis at exposures up to 6x the clinical dose based on AUC comparisons

            Lactation

            No data are available regarding presence in human milk

            Monitor infants exposed for signs of bedaquiline-related adverse reactions (eg, hepatotoxicity)

            Animal studies

            • Bedaquiline concentrations in rat milk were 6-fold to 12-fold higher than the maximum concentration observed in maternal plasma at exposures 1-2x the clinical exposure (based on AUC comparisons)

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

            Previous
            Next:

            Pharmacology

            Mechanism of Action

            Diarylquinoline; inhibits mycobacterial adenosine 5'-triphosphate (ATP) synthase, an enzyme essential for the generation of energy in Mycobacterium tuberculosis

            Absorption

            Bioavailability: Increased 2-fold when taken with standard meal compared with fasted conditions

            Peak plasma time

            • Adults: 5 hr
            • Age 14-18 years: 4 hr

            Plasma concentrations

            • Peak
              • Adults: 1659 ng/mL
              • Age 14-18 years: 1800 ng/mL
            • Minimum
              • Adults: 654 ng/mL
              • Age 14-18 years: 544 ng/mL

            AUC

            Adults: 25,863 ng⋅hr/mL

            Age 14-18 years: 26,300 ng⋅hr/mL

            Distribution

            Protein Bound: >99.9%

            Vd: 164 L

            Metabolism

            Metabolized primarily by CYP3A4 to form N-monodesmethyl metabolite (M2) which is 4- to 6-times less active

            Elimination

            Half-life: 5.5 months (mean terminal half-life of bedaquiline and the M2 metabolite from peripheral tissues)

            Renal clearance: <0.001%

            Excretion: Mainly in feces

            Previous
            Next:

            Administration

            Oral Administration

            Administer by directly observed therapy (DOT)

            Only use in combination with at least 3 other drugs to which the patient’s MDR-TB isolate has been shown to be susceptible in vitro

            Must take with food

            Swallow 100-mg tablets whole with water

            20-mg tablets: Functionally scored tablets that can be split into 2 equal halves of 10 mg each

            Missed dose

            • During first 2 weeks of treatment: Do not make up the missed dose but continue the usual dosing schedule
            • From week 3 onwards: If dose is missed, patients should take the missed dose as soon as possible, and then resume the 3 times/week regimen
            • Total dose during a 7-day period should not exceed the recommended weekly dose (with at least 24 hr between each dose)

            Patients unable to swallow 20-mg tablet(s)

            • Disperse in water and administer with beverage or soft food
              • Disperse tablets in water (maximum of 5 tablets in 5 mL of water) in a drinking cup
              • Mix contents well until tablets are completely dispersed and then orally administer immediately with food To aid with administration, dispersed mixture can be further mixed with at least 5 mL of beverage (eg, water, milk products, apple juice, orange juice, cranberry juice, carbonated beverage) or 1 teaspoonful of soft food (eg, yogurt, apple sauce, mashed banana, porridge) and then orally administer the contents of the cup immediately
              • If total dose requires >5 tablets, repeat above preparation steps with appropriate number of additional tablets until the desired dose is reached
              • Ensure no tablet residue is left in cup, rinse with beverage or add more soft food and orally administer contents immediately
            • Crush and mix with soft food
              • 20-mg tablet can be crushed and mixed with soft food (eg, yogurt, apple sauce, mashed banana, porridge) immediately before administration
              • Ensure no tablet residue is left in container, add more soft food and administer the contents immediately
            • Administration via NG tube (8 French or greater)
              • Disperse <5 tablets in 50-mL of noncarbonated water and mix well
              • Mixture should be white to almost white with visible particles expected
              • Administer through the nasogastric 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 nasogastric tube

            Storage

            Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF)

            Protect from light and moisture

            Keep container tightly closed

            20-mg tablets: Store in original container; bottle contains desiccant (do not discard)

            100-mg tablets: Dispense in original container; store tablets dispensed outside the original container in a tight light-resistant container with an expiration date not to exceed 3 months

            Previous
            Next:

            Images

            No images available for this drug.
            Previous
            Next:

            Patient Handout

            Patient Education
            bedaquiline oral

            BEDAQUILINE - ORAL

            (bed-AK-wi-leen)

            COMMON BRAND NAME(S): Sirturo

            WARNING: This medication may increase the risk of death. It should only be used when other treatments have not worked.Bedaquiline may cause a condition that affects the heart rhythm (QT prolongation). The risk of QT prolongation may be increased if you are taking other drugs that may cause QT prolongation. (See also Precautions section).

            USES: This medication must be used with other medications to treat active multi-drug-resistant tuberculosis (TB) of the lungs in people with limited treatment options. Bedaquiline belongs to a class of drugs known as antibiotics. It works by stopping the growth of the bacteria that causes TB.This antibiotic treats only bacterial infections. It will not work for viral infections (such as common cold, flu). Using any antibiotic when it is not needed can cause it to not work for future infections.

            HOW TO USE: Read the Medication Guide provided by your pharmacist before you start taking bedaquiline and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with food as directed by your doctor, usually once daily for the first 2 weeks, followed by 3 times a week for the next 22 weeks. The dosage is based on your medical condition, age, and response to treatment. Children's dosage is also based on weight.The manufacturer directs to swallow the 100-milligram tablets whole. However, many similar drugs (immediate-release tablets) can be split/crushed. Follow your doctor's direction on how to take this medication.If you are using the 20-milligram tablets and do not have trouble swallowing tablets, swallow the tablets (whole or split) with water.If you are using the 20-milligram tablets and have trouble swallowing tablets, you may take your dose 2 different ways: (1) Add your dose (up to 5 tablets) to 1 teaspoonful (5 milliliters) of water in a cup and mix well. You can then either swallow the mixture right away, or you can add the mixture to at least 1 teaspoonful (5 milliliters) of beverage or soft food and take right away. Examples of beverages you can take this with include water, milk products, apple juice, orange juice, cranberry juice, or carbonated beverages. Soft foods such as yogurt, apple sauce, mashed banana, or porridge may also be used. Make sure to take all of your dose by rinsing the cup with beverage or soft food and swallowing right away. (2) Crush tablets and mix with soft food. Soft foods such as yogurt, apple sauce, mashed banana, or porridge may be used. Mix well and take all of the mixture right away. Make sure to take all of your dose by adding more soft food and swallowing right away. Do not prepare a mixed dose ahead of time.The 20-milligram tablets may also be given through a feeding tube. For specific directions, ask your health care professional.For the best effect, take this antibiotic at evenly spaced times. If you are taking this medication daily, take it at the same time each day. If you are taking this medication 3 times a week, take it at least 48 hours apart on the same days of the week (for example, Mondays, Wednesdays, and Fridays) at the same time of day. Mark the days on the calendar when you need to take the medication.Continue to take this medication (and other TB medications) until the full prescribed amount is finished, even if symptoms disappear after a few days. Stopping the medication too early or skipping doses may allow bacteria to continue to grow, which may result in a return of the infection.Tell your doctor if your condition lasts or gets worse.

            SIDE EFFECTS: See also Warning section.Nausea, joint pain, and headache may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: symptoms of liver damage (such as nausea/vomiting that doesn't stop, loss of appetite, dark urine, stomach/abdominal pain, yellowing eyes/skin).Get medical help right away if you have any very serious side effects, including: coughing up blood, chest pain, fast/irregular heartbeat, severe dizziness, fainting.Bedaquiline can commonly cause a rash that is usually not serious. However, you may not be able to tell it apart from a rare rash that could be a sign of a severe reaction. Tell your doctor right away if you develop any rash.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking bedaquiline, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease.Bedaquiline may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can rarely cause serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using bedaquiline, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using bedaquiline safely.Alcohol may increase the risk of liver disease. Avoid alcoholic beverages while using this medication.Bedaquiline may cause live bacterial vaccines (such as typhoid vaccine) to not work well. Tell your health care professional that you are using bedaquiline before having any immunizations/vaccinations.Older adults may be more sensitive to the side effects of this drug, especially QT prolongation (see above).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is unknown if this drug passes into breast milk. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Other medications can affect the removal of bedaquiline from your body, which may affect how bedaquiline works. Examples include efavirenz, rifamycins (such as rifampin, rifapentine), among others.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

            NOTES: Do not share this medication with others.This medication has been prescribed for your current condition only. Do not use it later for another infection unless your doctor tells you to.Lab and/or medical tests (such as liver function, EKG, potassium/calcium/magnesium levels) should be done before you start taking this medication and while you are taking it. Keep all medical and lab appointments. Consult your doctor for more details.

            MISSED DOSE: If you miss a daily dose during the first 2 weeks of treatment, skip the missed dose. Take your next dose at the regular time.If you miss a dose from week 3 onward, take it as soon as you remember, then go back to your usual 3-times-a-week dosing schedule. Make sure that there is at least 24 hours between your doses and that you do not take more than the weekly dose in a 7-day period. If you are unsure of what to do after a missed dose, talk to your doctor or pharmacist.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Store the 20-milligram tablets in the original container. Keep the desiccant (drying agent) in the bottle and close the bottle tightly after each use to protect from moisture.Store the 100-milligram tablets in the original container. If necessary, the 100-milligram tablets may be stored in another container for up to 3 months. Close the bottle tightly after each use to protect from light.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            Information last revised December 2022. Copyright(c) 2022 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.