How it is administered

Ivosidenib is available as a film-coated 250 mg tablet for oral administration. The recommended dose is 500 mg taken orally once daily, with or without food, but it should not be taken with a high-fat meal. Tablets should be swallowed whole and not split, crushed, or chewed. If a dose is missed or vomited, do not take an extra dose; take the next dose as scheduled.

How it works

Ivosidenib is a targeted therapy that works by inhibiting the mutant isocitrate dehydrogenase 1 (IDH1) enzyme. In certain blood cancers like acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), mutations in the IDH1 gene cause the enzyme to produce an abnormal metabolite called 2-hydroxyglutarate (2-HG). This metabolite interferes with normal cell differentiation, leading to the accumulation of immature blood cells (blasts) in the bone marrow and blood.

By blocking the mutant IDH1 enzyme, ivosidenib reduces the production of 2-HG, which helps restore normal cell differentiation and reduces the number of leukemia cells. This allows the bone marrow to produce healthier blood cells. Ivosidenib is specifically effective in patients whose cancer cells have a susceptible IDH1 mutation, as confirmed by an FDA-approved test.

Who Should take it

Ivosidenib is indicated for adults with blood cancers that have a susceptible IDH1 mutation. It is used in:

• Newly diagnosed acute myeloid leukemia (AML) in adults 75 years or older, or those with comorbidities that prevent intensive chemotherapy, either alone or in combination with azacitidine.
• Adults with relapsed or refractory AML (disease that has returned or did not respond to previous treatment).
• Adults with relapsed or refractory myelodysplastic syndromes (MDS).

Before starting ivosidenib, patients must have their cancer tested for the IDH1 mutation using an FDA-approved test. It is not indicated for patients whose cancers do not have this mutation.

Who should not take it

There are no absolute contraindications listed for ivosidenib. However, it should not be used in patients who have experienced serious allergic reactions to the drug or any of its components.

Caution is advised in patients with a history of long QT syndrome, uncontrolled or significant cardiovascular disease, or those taking medications that can prolong the QT interval, as ivosidenib can increase the risk of heart rhythm problems. It should also be avoided in pregnant women, as it may cause harm to the fetus, and in women who are breastfeeding. The safety and effectiveness in children have not been established.

Commonly used with

Ivosidenib is often used in combination with azacitidine, especially for newly diagnosed AML in adults who cannot receive intensive chemotherapy. In other situations, it may be used as a single agent.

Supportive care medications, such as anti-nausea drugs, antibiotics, and medications to manage side effects, may also be used alongside ivosidenib.

Commonly tested with

Ivosidenib has been tested in combination with azacitidine for newly diagnosed AML. It has also been studied as a single agent in relapsed or refractory AML and MDS.

Other supportive medications, such as hydroxyurea (for high white blood cell counts) and corticosteroids (for differentiation syndrome), may be used during clinical trials or in clinical practice to manage side effects or complications.