Names and pronunciation
(pree-toh′mah-nid) Pretomanid* *Both trade and generic the same name
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Individual generic drug information
Extracted information for pretomanid only.
(pree-toh′mah-nid) Pretomanid* *Both trade and generic the same name
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Func. class.: Antimycobacterial
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Chem. class.: Nitroimidazooxazine
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ACTION: Kills actively replicating tuberculosis by Mycobacterium inhibiting mycolic acid biosynthesis, thereby blocking cell wall production
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USES: Drug-resistant TB
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Extracted information for pretomanid only.
CONTRAINDICATIONS Hypersensitivity to this product, bedaqui- line, linezolid (used in combination) PRECAUTIONS Breastfeeding, hepatic disease, myelosup- pression, pregnancy, QT prolongation, infertility
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SIDE EFFECTS CNS: Peripheral neuropathy, headache, insomnia CV: QT prolongation, hypertension GI: Nausea, vomiting, anorexia, abdomi- nal pain, weight loss, diarrhea, constipa- tion, gastritis, dyspepsia INTEG: Acne, rash, pruritus, dry skin RESP: Lower respiratory tract infection, cough, pleuritic pain HEMA: Thrombocytopenia, neutropenia, anemia META: Hypoglycemia MS: MS pain EENT: Visual impairment, increased hyper- amylasemia hemoptysis, hyperlipasemia
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INTERACTIONS Decreased: pretomanid effect—strong or moderate CYP3A4 inducers (rifAMPin, efavirenz); avoid using together Increased: effect of OAT3 substrates— monitor for adverse reactions; dosage reduction for OAT3 substrate drugs may be needed Drug/Lab Increased: AST/ALT, bilirubin, γ-glutamyltransferase
Source page 1083
Extracted information for pretomanid only.
DOSAGE AND ROUTES • Adult PO Pretomanid Tablet 200 mg daily × 26 wk; bedaquiline 400 mg PO daily × 2 wk, then 200 mg 3 times per wk, with at least 48 hr between doses, × 24 weeks (total of 26 wk); linezolid 1,200 mg PO daily × 26 wk, with adjustments to 600 mg daily and further reduction to 300 mg daily or interruption of dosing for known linezolid adverse reactions of my- elosuppression, peripheral neuropathy, and optic neuropathy
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Available forms: Tablets 200 mg
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Administer: • Take the combination with food, swallow whole with water • If the combination is interrupted for safety reasons, missed doses can be made up at the end of the treatment; doses of line- zolid alone missed because of linezolid ad- verse reactions should not be made up • Combination may be extended beyond 26 wk if needed
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Extracted information for pretomanid only.
Assess: • Hepatotoxicity: assess for fatigue, an- orexia, nausea, jaundice, clay-colored stools, dark urine, liver tenderness, and hepato- megaly; obtain LFTs baseline, at 2 wk, monthly; if new or worsening hepatic dys- function occurs, test for viral hepatitis and discontinue other hepatotoxic medications; interrupt treatment with the entire regimen if ALT/AST are accompanied by total bilirubin elevation >2× ULN or ALT/AST >8× ULN or ALT/AST >5× ULN and continue >2 wk • Myelosuppression: assess for anemia (may be fatal), leukopenia, thrombocyto- penia, pancytopenia; monitor CBC base- line, 2 wk, monthly; decreasing or inter- rupting dosing may be needed in worsening myelosuppression • Peripheral/optic neuropathy, peripheral neuropathy: monitor visual function; if an P impairment occurs, interrupt dosing and obtain ophthalmologic testing • QT prolongation: obtain an ECG base- line, and ≤2, 12, 24 wk; obtain serum po- tassium, calcium, and magnesium at baseline and correct if abnormal; con- tinue to monitor if QT prolongation occurs; may occur more often in a history of tors- ades de pointes, congenital long QT syn- drome, hypothyroidism, bradydysrhyth- mia, uncompensated HF or serum calcium, magnesium, or potassium levels less than lower limits of normal • Lactic acidosis: assess for recurrent nausea or vomiting; if this occurs, evalu- ate immediately bicarbonate and lactic acid levels and possible interruption of combination
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Evaluate: Therapeutic response: TB cultures negative
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To report fatigue, vomiting, anorexia, nausea, jaundice, clay-colored stools, dark urine, liver tenderness, and visual impairment immediately • To swallow whole with water; that all products must be taken as a combination regimen • Pregnancy/breastfeeding: to report if pregnancy is planned or suspected: not to be used in pregnancy or breastfeeding
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Extracted information for pretomanid only.
PHARMACOKINETICS Protein binding 86.4%, metabolized by multiple reductive and oxidative path- ways; 53% excreted in urine, 38% in feces, as metabolites; half-life 16.9-17.4 hr; CYP3A4 is responsible for 20% of the metabolism; pretomanid significantly inhibits organic anion transporter-3 (OAT3) transporter
Source page 1083
Filter the extracted dose blocks for this individual drug.
• Adult PO Pretomanid Tablet 200 mg daily × 26 wk; bedaquiline 400 mg PO daily × 2 wk, then 200 mg 3 times per wk, with at least 48 hr between doses, × 24 weeks (total of 26 wk); linezolid 1,200 mg PO daily × 26 wk, with adjustments to 600 mg daily and further reduction to 300 mg daily or interruption of dosing for known linezolid adverse reactions of my- elosuppression, peripheral neuropathy, and optic neuropathy
Candidate age grouping · source pages 1082, 1083