ANTITUBERCULAR AGENT
arthralgia, nausea, abdominal pain.
Rx BEDAQUILINE FUMARATE
Oral: 100 mg tablet
Bedaquiline fumarate is diarylquinoline
antimycobacterial drug that inhibits mycobacterial
ATP
synthase, by binding to subunit c of the enzyme,
blocking the energy generation of M. tuberculosis.
Indication: Treatment of pulmonary multi-drug resistant
tuberculosis in combination with other drugs.
Contraindications: None.
Dose:
Note: Prior to treatment with Bedaquiline, obtain susceptibility
information against M. tuberculosis, ECG, serum electrolyte
concentrations and liver function tests.
Combination therapy, by mouth, ADULT (≥18 years), 400
mg once daily for the first 2 weeks, followed by 200
mg orally 3 times per week (at least 48 hours
between doses) for 22 weeks. The total duration of
therapy is 24 weeks.
Combination therapy, by mouth, CHILD (12 - 18 years,
≥30 kg body weight), 400 mg once daily for the first
2 weeks, followed by 200 mg orally 3 times per week
(at least 48 hours between doses) for 22 weeks. The
total duration of therapy is 24 weeks. (off label use
but dose recommendation from the WHO)
Dose Adjustment:
Lactation: Monitor infants for signs of hepatotoxicity.
Bedaquiline may be present in breast milk.
Pediatric: Safety and effectiveness of Bedaquiline have
not been established for those <12 years of age and
<30 kg body weight.
Hepatic: For severe impairment, use with caution and
monitor for adverse reactions.
Renal: Use with caution.
Precautions:
Resistance to Bedaquiline: Use only in combination with
other MDR-TB treatment.
WARNING: An INCREASED RISK OF DEATH was seen with
Bedaquiline use among adults. Only use Bedaquiline for
those ≥12 years of age when an effective treatment
regimen cannot be otherwise provided.
WARNING: Bedaquiline can PROLONG THE QT INTERVAL.
Avoid use with drugs that may cause additive QT
prolongation. Obtain and monitor ECG and serum
electrolytes. Discontinue if significant ventricular
arrhythmia or if QTcF interval prolongation of greater than
500 ms develops.
Hepatotoxicity: Monitor symptoms (fatigue, anorexia,
nausea, jaundice, dark urine, liver tenderness,
hepatomegaly) and liver function tests; test for viral
hepatitis; Discontinue other hepatotoxic drugs.
STORAGE AND STABILITY. Store at 25°C, excursions permitted
between 15°C and 30°C. Keep out of reach of children.
Adverse Drug Reactions:
Common:
Incidence ≥10%: ADULT, nausea, arthralgia,
headache, hemoptysis and chest pain, CHILD,
Less common:
Incidence <10%: Anorexia, increased transaminases,
rash, and increased blood amylase.
Drug Interactions:
Monitor closely with:
Increases AUC of Bedaquiline: Lopinavir/ritonavir
Avoid concomitant use with:
Reduces the therapeutic effect of Bedaquiline: Strong
CYP3A4 Inducers (rifampin, rifapentine, rifabutin),
moderate CYP3A4 Inducers (antiretroviral drugs:
efavirenz)
Increases risk of adverse or toxic effects of Bedaquiline:
CYP3A4 Inhibitors (ketoconazole, itraconazole), QT
Prolonging drugs (ketoconazole, clofazimine)
Administration: Take Bedaquiline with food. Administer
by directly observed therapy and used only in
combination with other anti-mycobacterial drugs.
Emphasize the need for compliance with full course
of therapy.
ATC Code: J04AK05
Rx DELAMANID
Inj.: 50 mg film-coated tablet
Delamanid is an antimycobacterial which can inhibit the
synthesis of mycobacterial cell wall components,
methoxy-mycolic and keto-mycolic acid.
Indications: Treatment of pulmonary multi-drug resistant
tuberculosis in combination with other drugs.
Contraindications: Hypersensitivity to Delamanid,
patients with serum albumin <2.8 g/dL.
Dose:
Combination therapy, by mouth, ADULT ≥18 years, 100
mg twice daily for 24 weeks. (no data in the elderly)
Precautions:
Resistance to Delamanid: Use only in combination with
other MDR-TB treatment.
QT Prolongation
Note: Monitor ECG and serum electrolytes.
Adverse Drug Reactions:
Common:
Incidence >10%: nausea, vomiting,
headache, insomnia, dizziness, tinnitus, hypokalemia,
gastritis, decreased appetite, and asthenia
Less Common: Anemia, eosinophilia,
hypertriglyceridemia, psychotic disorder, agitation,
anxiety and anxiety disorder, depression and depressed
mood, restlessness, neuropathy peripheral,
somnolence, hypoesthesia, dry eye, photophobia, ear
pain, low and high blood pressure, hematoma, hot flush,
dyspnea, cough, oropharyngeal pain, throat irritation,
dry throat, rhinorrhea, gastritis, constipation, abdominal
pain and discomfort, dyspepsia, dermatitis, urticaria,
rash, pruritus, hyperhidrosis, osteochondrosis, muscular
weakness, musculoskeletal pain, pain in extremity,
hematuria, pyrexia, chest pain, malaise, chest recommended if receiving HAART therapy with
discomfort, peripheral edema, increased blood cortisol. acceptable drug-drug interactions with rifapentine when
guided by physicians. See dose adjustment table for
Drug Interactions: latent tuberculosis dose adjustment according to BW.
Avoid concomitant use with:
Reduces the therapeutic effect of Delamanid: Strong Dose Adjustment:
inducers of CYP3A4 (rifampicin, carbamazepine) Recommended once weekly/once daily dosing for latent
tuberculosis in adults and children.
Increases the therapeutic effect of Delamanid:
Antiretroviral drugs (lopinavir/tenofovir) ADULTS (Latent Tuberculosis)
Weight Once Weight Once daily
Administration: For oral use. Delamanid should be taken weekly (1 month)
with food. Administer by directly observed therapy (12 weeks)
and used only in combination with other anti- 25.1-32 kg 600 mg <35 kg 300 mg
mycobacterial drugs. Emphasize the need for 32.1-50 kg 750 mg 35-45 kg 450 mg
compliance with full course of therapy. >50 kg 900 mg >45 kg 600 mg
Note: Delamanid must be given in combination with other drugs.
Treatment with an appropriate combination regimen should CHILDREN (Latent Tuberculosis)
continue after completion of the 24-week Delamanid treatment Weight Once weekly (12
period. weeks)
10-14 kg 300 mg
ATC Code: J04AK06
>14-25 kg 450 mg
>25-32 kg 600 mg
>32-50 kg 750 mg
Rx RIFAPENTINE >50 kg 900 mg

Oral: 150 mg film-coated tablet
Rifapentine is a rifamycin antibacterial that is used, with
other antimycobacterials, for the treatment of
tuberculosis. It is under investigation for the
treatment and prophylaxis of Mycobacterium avium
complex infections in patients with AIDS.
Indications: indicated in adults and children 12 years and
older for the treatment of active pulmonary
tuberculosis (TB) caused by Mycobacterium
tuberculosis.For the treatment of latent tuberculosis
infection (LTBI)
Contraindications: Hypersensitivity to rifapentine, other
rifamycins, or any component of the formulation
Dose:
Tuberculosis (active), initial phase, by mouth, ADULT,
600 mg twice weekly with an interval >72 hours
between doses by directly observed therapy (DOT) for
2 months as part of multidrug regimen; continuation
phase, by mouth, 600 mg once weekly by DOT for 4
months as part of multidrug regimen; initial phase, by
mouth, CHILDREN >12 years, 600 mg twice weekly
with an interval >72 hours between doses by DOT for
2 months; continuation phase, by mouth, 600 mg
once weekly by DOT for 4 months in combination with
isoniazid (INH) or another appropriate agent for
susceptible organisms
NOTE: Drug-susceptible TB guidelines recommend
against once-weekly therapy; use should only be
considered in rare situations in certain HIV-uninfected
individuals with no cavitation on chest x-ray; for children,
initial phase should include a 3- to 4- drug regimen
Tuberculosis (latent), by mouth, ADULT, once-weekly
regimen, administer for 12 weeks in combination
with INH; once-daily regimen, administer for 1 month
in combination with INH; CHILDREN, once-weekly
regimen, administer for 12 weeks in combination
with INH
NOTE: For HIV-positive patients, including those with
AIDS, rifapentine in combination with INH is
Note: Use with caution for patients with renal
impairment; pharmacokinetics in adult patients with
varying degrees of hepatic impairment were similar
to those in healthy volunteers.
Precautions:
Hypersensitivity reactions, including anaphylaxis, may
occur.
Patients with abnormal liver tests and/or liver disease
should only be given rifapentine when absolutely
necessary and under strict medical supervision.
Patients with cavitary pulmonary lesions and/or positive
sputum cultures after initial treatment phase and
patients with bilateral pulmonary disease have higher
relapse rates
Not recommended in patients with porphyria; may
experience exacerbation due to enzyme-inducing
properties
Should not be used during the continuation phase of
treatment in HIV-seropositive patients
Red/orange discoloration in urine, feces, saliva, sweat,
tears, skin, teeth and tongue
May discolor breast milk red-orange
NOTE: Compliance with drug regimen is absolutely
necessary; permanent staining may occur in patients
wearing soft contact lenses during therapy, and in
patients with dentures
Adverse Drug Reactions:
Common: hyperuricemia; pyuria, hematuria, urinary
tract infection; neutropenia, lymphocytopenia,
anemia
Less Common: chest pain; pain, headache, dizziness,
fatigue; diaphoresis, acne vulgaris, pruritis,
maculopapular rash; hypoglycemia, hyperglycemia,
increased nonprotein nitrogen, gout,
hyperphosphatemia; anorexia, nausea, constipation,
dyspepsia, abdominal pain, diarrhea, vomiting,
hemorrhoids; casts in urine; leukopenia,
thrombocytosis, leukocytosis, neutrophilia,
thrombocythemia, polycythemia, lymphadenopathy;
increased serum ALT, increased serum AST,
 hepatotoxicity; hypersensitivity reaction; influenza,
herpes zoster, infection; back pain, arthralgia,
osteoarthrosis, tremor; conjunctivitis; hemoptysis,
cough, bronchitis, pharyngitis, epistaxis, pleurisy;
accidental injury, fever

Drug Interactions:
Avoid concomitant use with:
Enhances therapeutic effect of the following drugs:

Decreases therapeutic effects of the following drugs:

BCG vaccine
Cholera vaccine
Lactobacillus and estriol
Sodium picosulfate
Typhoid vaccine

Increases risk of adverse or toxic effects of Rifapentin:

Prolonged use (superinfection)

Increases risk of adverse or toxic effects of the following

drugs:
Isoniazid (hepatotoxic effect)

Administration: Orally administer with meals; for

patients who cannot swallow tablets, may be crushed
and added to a small amount of semi-solid food and
consumed immediately

Pregnancy Category: C

ATC Code: J04AB05