| Drug |
Dosage |
Remarks |
| Bedaquiline |
Week 1-2: 400 mg PO 24 hourly
Week 3-24: 200 mg PO 3x/week (with at least 48 hours between doses)
In combination with Pretomanid and Linezolid for XDR-TB, treatment-intolerant or non-responsive MDR-TB: 400 mg PO 24 hourly x 2 weeks, then 200 mg PO 3x/week for 24 weeks for a total of 26 weeks |
Adverse Reactions
- CNS effects (headache, dizziness); GI effects (nausea/vomiting); Other effects (arthralgia, chest pain, anorexia, increased transaminase, increased blood amylase, rash, hemoptysis)
Special Instructions
- Should be taken with food
- Use with caution in patients with QT prolongation or concomitantly taking medicinal products with known risk of QT prolongation, rare hereditary disease (eg galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption), severe renal and moderate to severe hepatic impairment
- Obtain electrocardiogram (ECG) prior to initiation of therapy or at least monthly after starting treatment
- Monitor LFTs, alkaline phosphatase and bilirubin levels at baseline, monthly during treatment duration and as needed
|
| Capreomycin |
Infants, children and adolescents:
15-30 mg/kg IM/IV 24 hourly 5x/week
Max dose: 1,000 mg/day
Adults:
1,000 mg deep IM/IV 24 hourly x 2-4 months, then 2-3x/week thereafter to complete 12-24 months treatment
Max dose: 20 mg/kg/day
|
Adverse Reactions
- Dermatologic effects (urticaria, maculopapular rash); Renal effects (elevation of serum creatinine or blood urea nitrogen, abnormal urine sediment, toxic nephritis, renal insufficiency, oliguria, acute tubular necrosis, electrolyte disturbance); Hematologic effects (decrease in bromsulphthalein excretion, leukocytosis, leukopenia, thrombocytopenia, excessive bleeding); Ototoxic effects (tinnitus, vertigo); Other effects (pain at injection site, sterile abscesses)
Special Instructions
- Use with caution in patients with renal insufficiency or pre-existing auditory impairment
- Audiometry, vestibular and renal function tests should be done at baseline and regularly while on treatment
- Monitor serum electrolytes and liver function frequently
|
| Cycloserine |
Children: 10-20 mg/kg PO 24 hourly
Adults: 250 mg PO 12 hourly x 2 weeks followed by 500-1,000 mg/day in divided doses
Max Dose: 1,000 mg/day
|
Adverse Reactions
- CNS effects (insanity, epilepsy-like seizures, hyperreflexia, headache, drowsiness, insomnia, memory loss/reduction, vertigo); Musculoskeletal effects (joint pain, tremor, hyperreflexia); Dermatologic effects (pruritus, exanthem); Other effects (GI disturbances, fever)
Special Instructions
- Contraindicated in patients with CNS disorders (eg epilepsy)
- Use with caution in patients with renal impairment
|
| Delamanid |
100 mg PO 12 hourly x 24 weeks |
Adverse Reactions
- Hematologic effects (reticulocytosis, anemia, eosinophilia); Metabolic effects (hypokalemia, hyperuricemia); CNS effects (dizziness, headache, paresthesia, tremor, insomnia, psychotic disorder, agitation, anxiety, depression, restlessness); Otologic effect (tinnitus); CV effects (palpitations, hypo- or hypertension); Respiratory effects (hemoptysis, cough, rhinorrhea); GI effects (upper abdominal pain, nausea/vomiting, diarrhea); Musculoskeletal effects (arthralgia, myalgia); Other effects (asthenia, decreased appetite)
Special Instructions
- Should be taken with food
- Use with caution in patients with known congenital prolongation of the QT interval or any clinical condition that prolongs the QT interval or w/ QT interval >500 millisecond, history of symptomatic cardiac arrhythmia or with clinically relevant bradycardia, any predisposing cardiac conditions for arrhythmia or congestive cardiac failure accompanied by reduced left ventricle ejection fraction and electrolyte disturbances
- Contraindicated in patients with serum albumin <2.8 g/dL, moderate to severe hepatic impairment and those taking strong inducers of CYP3A (eg Carbamazepine)
- ECG should be obtained before initiation of treatment and monthly during the full course of treatment
|
| Ethambutol (E) |
Infants, children and adolescents:
15-25 mg/kg PO 24 hourly
Max dose: 1,600 mg/day
Adults: 15 mg/kg PO 24 hourly
Max dose: 1,500 mg/day
Retreatment: 25 mg/kg PO 24 hourly x 2 months then reduce to
15 mg/kg PO 24 hourly
Max dose: 2,500 mg/day
|
Adverse Reactions
- GI effects (nausea/vomiting, anorexia, abdominal pain); CNS effects (headache, dizziness, confusion, disorientation, hallucination); Hypersensitivity effects (rash, pruritus); Other effects (jaundice or transient liver dysfunction, peripheral neuropathy, thrombocytopenia, dose-related retrobulbar neuritis)
Special Instructions
- Use with caution in patients with renal impairment
- Contraindicated in patients with optic and retrobulbar neuritis
- Monitor visual acuity, liver and renal function prior to initiation of treatment and during treatment
- Discontinue treatment immediately should changes in vision, color blindness or visual defects occur
- Monthly testing of visual acuity and color discrimination is recommended for patients taking doses >15-25 mg/kg, taking for >2 months and patients with renal insufficiency
|
| Ethionamide |
Infants, children and adolescents:
15-20 mg/kg PO divided 8-24 hourly
Max dose: 1,000 mg/day
Adults:
15-20 mg/kg PO divided 12-24 hourly or
250-500 mg PO divided 12-24 hourly
Max dose: 1,000 mg/day
|
Adverse Reactions
- GI effects (anorexia, increased salivation, metallic taste, nausea/vomiting, abdominal pain, diarrhea); CNS effects (depression, anxiety, psychosis, peripheral neuritis); Hepatic effects (jaundice, hepatitis); Other effects (thrombocytopenia, rashes, stomatitis, optic neuritis, postural hypotension, gynecomastia, impotence)
Special Instructions
- Should be taken with food
- Contraindicated in patients with severe hepatic impairment
- Use with caution in patients with DM, thyroid dysfunction or psychiatric illness
- Monitor LFTs, blood glucose, thyroid and visual acuity regularly
|
| Isoniazid (H)1 |
Children:
5-20 mg/kg PO 24 hourly
Max dose: 300 mg or
20-40 mg/kg PO 24 hourly 2-3x/week
Max dose: 900 mg/day
Adults:
5-10 mg/kg PO 24 hourly
May shift to 15 mg/kg PO 24 hourly 2x/week after 2 months of daily dosing or
300 mg PO 24 hourly
or 100 mg PO 6-8 hourly
Max dose: 900 mg/day
|
Adverse Reactions
- Hepatic effects (asymptomatic elevation of aminotransferases, clinical or sometimes fatal hepatitis); CNS effects (dizziness, depression, encephalopathy, seizures, lethargy, slurred speech); CV effects (hypertension, palpitation, tachycardia); GI effects (nausea/vomiting, anorexia, dry mouth, constipation); Other effects (flushing, rash, anemia, peripheral neuropathy)
Special Instructions
- Pyridoxine supplementation is recommended to prevent peripheral neuropathy
- If flushing occurs with intake of foods and beverages that have high monoamine content (eg cheese, wine), instruct patients to avoid concomitant intake of these with Isoniazid
- Use with caution in patients with chronic alcoholism, diabetics, chronic liver disease or severe renal dysfunction
|
| Para-aminosalicylic acid |
Infants, children and adolescents:
200-300 mg/kg PO divided 6-12 hourly
Adults:
150 mg/kg PO divided 6-8 hourly or
8-12 g/day PO divided 8-12 hourly
|
Adverse Reactions
- Hepatic effects (asymptomatic elevation of aminotransferases, clinical or sometimes fatal hepatitis); CNS effects (dizziness, depression, encephalopathy, seizures, lethargy, slurred speech, peripheral neuropathy); CV effects (hypertension, palpitation, tachycardia); GI effects (nausea/vomiting, anorexia, diarrhea, abdominal pain); Hematologic effects (agranulocytosis, hemolytic anemia, leukopenia, thrombocytopenia); Other effects (flushing, rash, fever)
Special Instructions
- Ingest with acidic food (eg yogurt, orange juice)
- Use with caution in patients with liver and renal impairment, gastric ulcer
- Contraindicated in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency and severe renal disease
- Monitor patients closely for the first 3 months of therapy
|
| Pretomanid |
XDR-TB, treatment-intolerant or non-responsive MDR-TB in combination with Bedaquiline and Linezolid:
200 mg PO 24 hourly x 26 weeks |
Adverse Reactions
- Hepatic effects (increased transaminases, hyperamylasemia, increased gamma-glutamyltransferase); GI effects (nausea/vomiting, abdominal pain, dyspepsia, diarrhea); Dermatologic effects (acne, rash, pruritus); Respiratory effects (pleuritic pain, cough, hemoptysis, lower respiratory tract infection); Other effects (peripheral neuropathy, anemia, headache, back pain, visual impairment, hypoglycemia, abnormal weight loss, decreased appetite)
Special Instructions
- Swallow tablet whole with water
- Take combination regimen with food
- Use with caution in patients with QT prolongation, hepatic and/or renal impairment, visual impairment, myelosuppression
- Monitor ECG, LFTs, visual function
|
Protionamide
(Prothionamide) |
Children: 10-20 mg/kg PO 24 hourly
Max dose: 750 mg/day
Adults: 15-20 mg/kg PO 24 hourly
Max dose: 1,000 mg/day
|
Adverse Reactions
- CNS effects (psychiatric disturbances [depression, anxiety, psychosis]); GI effects (metallic taste, excessive salivation, nausea/vomiting, abdominal pain, diarrhea, jaundice, hepatitis); Other effects (anorexia, peripheral and/or optic neuritis, postural hypotension, thrombocytopenia, rash, stomatitis, gynecomastia)
Special Instructions
- Contraindicated in patients with severe hepatic dysfunction, psychoses, porphyria, alcoholism, epilepsy
- Use with caution in patients with overt liver damage, marked confusion
- Monitor LFTs before and during treatment
|
| Pyrazinamide (Z) |
Children: 20-35 mg/kg PO divided 6-8 hourly
Max dose: 3,000 mg/day
Adults: 20-35 mg/kg PO divided 6-8 hourly
Max dose: 3,000 mg/day
or 50 mg/kg PO divided 6-8 hourly 3x/week or 75 mg/kg PO divided 6-8 hourly 2x/week
|
Adverse Reactions
- Hepatic effect (hepatotoxicity); GI effects (nausea/vomiting, anorexia); Musculoskeletal effects (arthralgia, myalgia); Other effects (rash, fever, photosensitivity, hyperuricemia)
Special Instructions
- Use with caution in patients with liver impairment, renal failure, porphyria, DM, history of chronic alcoholism, gout
- Contraindicated in patients with severe hepatic impairment
- Monitor LFTs in patients with underlying liver disease or when using with Rifampicin
|
| Rifabutin |
150-450 mg PO 24 hourly or
5 mg/kg PO 24 hourly |
Adverse Reactions
- Hematologic effect (neutropenia); GI effects (nausea, abdominal pain, dyspepsia); Dermatologic effect (rash); Hepatic effect (asymptomatic elevation of liver enzymes); Other effects (myalgia, flu-like syndrome, uveitis, orange discoloration of body fluids)
Special Instructions
- Use with caution in patients with renal and hepatic impairment
- Advise patient that soft contact lenses and clothing may be permanently stained orange
- Clinical and laboratory monitoring in patients with underlying liver disease should be increased
- Monitor serum concentrations of drugs taken concomitantly
|
Rifampicin (R)
(Rifampin) |
10mg/kg PO 24 hourly
Max dose: 600 mg/day
|
Adverse Reactions
- GI effects (glossitis, anorexia, nausea/vomiting, epigastric discomfort, abdominal spasm, diarrhea); Dermatologic effects (urticaria, rash, pruritus); Hematologic effects (eosinophilia, leukopenia, thrombocytopenia, hemolytic anemia, hemolysis); Renal effects (hemoglobinuria, hematuria, renal failure); CNS effects (drowsiness, headache, lightheadedness, dizziness); Other effects (edema, tiredness, fever)
Special Instructions
- Use with caution in patients with history of alcoholism, impaired hepatic function, DM, porphyria
- Contraindicated in patients with severe hepatic impairment
- Advise patient that soft contact lenses and clothing may be permanently stained orange or reddish
- Clinical and laboratory monitoring in patients with underlying liver disease should be increased
|
| Rifapentine |
Initial phase:
600 mg PO 2x/week x 2 months with an interval of ≥72 hours between doses
Continuation phase:
600 mg PO weekly x 4 months
Latent TB Infection (in combination with Isoniazid x
12 weeks)
10-14 kg: 300 mg PO weekly
14.1-25 kg: 450 mg PO weekly
25.1-32 kg: 600 mg PO weekly
32.1-50 kg: 750 mg PO weekly
>50 kg: 900 mg PO weekly
|
Adverse Reactions
- Dermatologic effects (urticaria, skin discoloration); GI effects (constipation, esophagitis, gastritis, pancreatitis); Hepatic effects (bilirubinemia, hepatitis); Hematologic effects (thrombocytopenia, neutrophilia, leukocytosis, purpura, hematoma); Psychiatric effect (aggressive reaction); Metabolic effects (hyperkalemia, hypovolemia, increased alkaline phosphatase, increased lactate dehydrogenase); Musculoskeletal effects (gout, arthrosis); Other effects (peripheral edema, fatigue)
Special Instructions
- Advise patient that soft contact lenses and clothing may be permanently stained orange
- Concomitant administration of Pyridoxine (Vitamin B6) is recommended in malnourished patients and those who are predisposed to neuropathy (eg alcoholics and diabetics) and in adolescents
- May cause many drug interactions and this may necessitate regular measurements of serum concentrations of drugs taken concomitantly
- Patients with drug-resistant organisms may require longer duration of treatment with other drug regimens
|
| Streptomycin |
Children: 20-40 mg/kg IM 24 hourly
Max dose: 1,000 mg
or 25-30 mg/kg IM 2-3x/week
Max dose: 1,500 mg/day
Adults: 15 mg/kg IM/IV 24 hourly
Max dose: 1,000 mg
or 25-30 mg/kg IM/IV 3x/week
Max dose: 1,500 mg/day
or 1,000 mg IM 24 hourly daily or 2-3x/week or 750 mg IM 3x/week or 1,500 mg IM 2x/week
|
Adverse Reactions
- GI effects (nausea/vomiting); CNS effect (paresthesia of the face); Dermatologic effects (rash, urticaria); Other effects (vestibular ototoxicity, angioneurotic edema, eosinophilia, urine output without renal function changes is indicative of renal toxicity)
Special Instructions
- Use with caution in patients with renal function impairment, pre-existing vertigo, tinnitus or hearing loss and in those with neuromuscular disorders
- Give drug after dialysis to avoid premature removal of the drug
- Regular monthly assessments of renal and auditory/vestibular function
|
*Fixed dose combinations of antituberculosis drugs are available. Please see the latest MIMS for specific formulations and prescribing information.
1Combination with Pyridoxine is available. Please see the latest MIMS for specific formulations and prescribing information. |
