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IDH1 Inhibitor Pregnancy: Contraindicated — embryotoxic; effective contraception required during and for 1 month after treatment

Ivosidenib

Brand names: Tibsovo

Adult dose

Dose: 500 mg once daily
Route: Oral
Frequency: Once daily
Max: 500 mg/day
AML with IDH1 mutation (R132); newly diagnosed (unfit for intensive chemotherapy) or relapsed/refractory; IDH1 mutation testing mandatory before initiation

Paediatric dose

Dose: Not established N/A/kg
Route: N/A
Frequency: N/A
Max: N/A
Not licensed in paediatrics

Dose adjustments

Renal

No dose adjustment required for mild-moderate renal impairment; limited data in severe

Hepatic

Mild-moderate: no adjustment; severe: limited data — use with caution

Paediatric weight-based calculator

Not licensed in paediatrics

Clinical pearls

  • AGILE trial (Montesinos et al. NEJM 2022): ivosidenib + azacitidine significantly improved event-free survival and OS vs azacitidine alone in newly diagnosed IDH1-mutated AML (24-month OS 24.4% vs 7.9%)
  • Differentiation syndrome (DS): occurs when IDH1 inhibition triggers differentiation of leukaemic blasts — can be fatal; early recognition critical — treat immediately with dexamethasone 10 mg BD and hold ivosidenib if severe
  • MHRA 2021 approved; NICE TA751 for R/R IDH1-mutated AML; IDH1 mutation prevalence ~6–10% of AML — companion diagnostic (Abbott RealTime IDH1) mandatory
  • QTc prolongation: obtain ECG baseline and monitor; correct electrolytes (K+, Mg²⁺) before starting; hold if QTc >500 ms
  • Unlike conventional chemotherapy, ivosidenib induces terminal differentiation of IDH1-mutant blasts into functioning neutrophils — patients may develop leucocytosis as part of treatment response, not disease progression

Contraindications

  • No IDH1 mutation on diagnostic testing
  • Known long QT syndrome without correction
  • Known hypersensitivity

Side effects

  • Differentiation syndrome (life-threatening — fever, dyspnoea, pleural/pericardial effusion, pulmonary infiltrates)
  • QTc prolongation
  • Nausea
  • Fatigue
  • Arthralgia
  • Leucocytosis
  • Diarrhoea

Interactions

  • QTc-prolonging drugs — additive QTc risk; avoid combination or monitor ECG closely
  • Strong CYP3A4 inhibitors — increase ivosidenib exposure; reduce dose to 250 mg if unavoidable
  • Strong CYP3A4 inducers — significantly reduce ivosidenib; avoid

Monitoring

  • ECG (baseline, weekly ×4, then monthly)
  • FBC and differential (weekly ×4 then monthly — watch for leucocytosis indicating DS)
  • LFTs
  • Uric acid (tumour lysis)
  • Signs/symptoms of differentiation syndrome daily

Reference: BNFc; BNF 90; AGILE trial (Montesinos et al. NEJM 2022); NICE TA751; MHRA SPC Tibsovo; AG120-C-001 phase I (DiNardo et al. NEJM 2018). Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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