IDH2 Inhibitor Pregnancy: Based on animal embryo-fetal toxicity studies, enasidenib can cause fetal harm when given to a pregnant woman; there are no data in pregnant women. In animals, oral administration during organogenesis was associated with embryo-fetal mortality and altered growth from 0.1 times the steady-state clinical exposure at the recommended human dose. Advise pregnant women of the potential risk to a fetus and use effective contraception.

Enasidenib

Brand names: Idhifa

Enasidenib is an orally active inhibitor of mutant isocitrate dehydrogenase 2 (IDH2) used in the treatment of acute myeloid leukaemia carrying an IDH2 mutation.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 100 mg

Route: Oral — swallow tablets whole with or without food; do not chew, split or crush. Available as 50 mg and 100 mg tablets.

Frequency: Once daily at about the same time each day, until disease progression or unacceptable toxicity; in patients without disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for clinical response

INDICATION AND PATIENT SELECTION: acute myeloid leukaemia — select patients on the basis of an IDH2 mutation in blood or bone marrow using an approved test. MISSED OR VOMITED DOSE: give the dose as soon as possible on the same day and return to the normal schedule the following day. MONITORING: assess blood counts and blood chemistries for leukocytosis and tumour lysis syndrome before starting and at least every 2 weeks for at least the first 3 months of treatment. DOSE MODIFICATIONS FOR TOXICITY — Differentiation syndrome: if suspected, give systemic corticosteroids (e.g. dexamethasone 10 mg every 12 hours) and start haemodynamic monitoring; interrupt enasidenib if severe pulmonary symptoms requiring intubation or ventilator support and/or renal dysfunction persist for more than 48 hours after starting corticosteroids; resume when signs and symptoms improve to Grade 2 or lower, and taper corticosteroids only after symptoms resolve. Non-infectious leukocytosis (white cell count above 30 x 10^9/L): start hydroxyurea per institutional practice; interrupt enasidenib if leukocytosis does not improve with hydroxyurea, then resume at 100 mg daily when the white cell count is below 30 x 10^9/L. Bilirubin more than 3 times the upper limit of normal sustained for 2 weeks or more without elevated transaminases or other hepatic disorder: reduce to 50 mg daily, and resume 100 mg daily if the bilirubin elevation resolves to less than 2 times the upper limit of normal. Other Grade 3 or higher treatment-related toxicity including tumour lysis syndrome: interrupt until toxicity resolves to Grade 2 or lower, then resume at 50 mg daily, increasing to 100 mg daily if toxicities resolve to Grade 1 or lower; discontinue if Grade 3 or higher toxicity recurs. GERIATRIC: no dosage adjustment is required based on age. PAEDIATRIC: safety and effectiveness in paediatric patients have not been established. SOURCE: no UK SPC was fetched in this bundle — this draft is distilled from the US IDHIFA prescribing information and must be verified against UK labelling.

Dose auto-extracted from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

None — the US label section 4 Contraindications reads 'None'

Side effects

Nausea and vomiting (most common, at least 20%)
Diarrhoea (most common, at least 20%)
Elevated bilirubin (most common, at least 20%)
Decreased appetite (most common, at least 20%)
Differentiation syndrome — occurred in 14% of patients and may be life-threatening or fatal if untreated; onset from 1 day to 5 months after starting; features included acute respiratory distress with dyspnoea and/or hypoxia (68%), need for supplemental oxygen (76%), pulmonary infiltrates (73%), renal impairment (70%), pleural effusion (45%), fever (36%), lymphadenopathy (33%), bone pain (27%), peripheral oedema with rapid weight gain (21%) and pericardial effusion (18%)
Serious adverse reactions were reported in 77.1% of patients; the most frequent (at least 2%) were leukocytosis (10%), differentiation syndrome (8%), diarrhoea (6%), nausea (5%), tumour lysis syndrome (5%), vomiting (3%) and decreased appetite (3%)

Interactions

Certain CYP1A2 substrates — avoid concomitant use unless otherwise recommended in their prescribing information where minimal concentration changes may lead to serious adverse reactions; enasidenib is a CYP1A2 inhibitor and increases their exposure. Consider reducing caffeine intake during treatment
Certain CYP2C19 substrates — avoid concomitant use unless otherwise recommended in their prescribing information; enasidenib is a CYP2C19 inhibitor and increases their exposure
Certain CYP3A substrates — avoid concomitant use unless otherwise recommended in their prescribing information
Certain OATP1B1, OATP1B3 and BCRP substrates — avoid concomitant use unless otherwise recommended in their prescribing information

Clinical monograph

How it works

It inhibits the mutant IDH2 enzyme, reducing production of the oncometabolite 2-hydroxyglutarate and promoting differentiation of the leukaemic cells.

Prescribing in practice

It can cause differentiation syndrome, which may be life-threatening, so clinicians and patients must recognise its features early and start corticosteroids promptly.
Treatment is restricted to patients with a confirmed IDH2 mutation and should be supervised by clinicians experienced in leukaemia therapy.
It can raise bilirubin and prolong the QT interval, so relevant biochemistry and the ECG should be checked.

Monitoring

Monitor the full blood count, liver biochemistry and electrolytes, and watch closely for signs of differentiation syndrome.

Counselling the patient

Report fever, breathlessness, rapid weight gain or swelling without delay, as these may indicate differentiation syndrome.
Do not stop the medicine on your own; discuss any troublesome effects with your team.

Evidence & guidelines

Mutant IDH2 inhibition is used in IDH2-mutated acute myeloid leukaemia in line with its licensed indication and supporting clinical trial evidence.

Reference: AG221-C-001 trial (Stein et al. Blood 2017); MHRA SPC Idhifa; NICE assessment; Stein et al. NEJM 2020 (AML IDH2); Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways