Vanflyta

Vanflyta (quizartinib) is an oral targeted treatment called a kinase inhibitor that may be used to treat newly diagnosed acute myeloid leukemia (AML) in adults that is FLT3-ITD positive, in combination with standard chemotherapy treatments (cytarabine and anthracycline).

• Your healthcare provider will perform a test to make sure that Vanflyta is right for you.
• Vanflyta is not for use alone as maintenance therapy after a hematopoietic stem cell transplant.

Vanflyta works by specifically targeting FLT3 mutations, which block the multiplication and growth of leukemic cells, slowing the progression of AML, and improving overall survival. FLT3 mutations are the most common gene mutations identified in AML, with approximately 80% identified as FLT3-ITD (internal tandem duplications) mutations. These patients typically have a poor prognosis with an increased risk of relapse and a shorter overall survival.

• Research has shown that Vanflyta improves overall survival compared with chemotherapy alone, reducing the risk of death by 22%, and increasing the length of time in remission (median 38.6 months [Vanflyta + chemotherapy] compared to 12.4 months [chemotherapy alone]).

Vanflyta was FDA-approved on 20 July 2023.

Take Vanflyta exactly as your healthcare provider tells you to. Do not change your dose or stop taking Vanflyta unless your healthcare provider tells you to.

• Take Vanflyta by mouth 1 time a day at approximately the same time each day.
• Vanflyta may be taken with or without food.
• Swallow the tablets whole. Do not cut, crush, or chew.

Do not take Vanflyta if you are allergic to Vanflyta, quizartinib, or any of the inactive ingredients in the tablet.

Vanflyta should not be used in patients with very low potassium, very low magnesium, long QT syndrome (QTcF >450ms), or ventricular arrhythmias or torsades de pointes.

To make sure Vanflyta is safe for you, tell your doctor if you have ever had:

• heart problems.
• low blood levels of potassium or magnesium.
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed.

Certain medications may affect the concentration of Vanflyta. Tell your healthcare provider about all the medications you take.

It is not known if Vanflyta is safe and effective in children.

Pregnancy

Vanflyta can harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment.

If you can become pregnant, your healthcare provider will perform a pregnancy test 7 days before you start treatment with Vanflyta. Females who can become pregnant should use effective birth control (contraception) during treatment and for 7 months after the last dose.

Males with female partners who can become pregnant should use effective birth control during treatment and for 4 months after the last dose.

Talk to your healthcare provider about birth control methods you can use during this time.

Breastfeeding

It is not known if Vanflyta passes into breast milk. Do not breastfeed during treatment and for 1 month after the last dose.

Fertility

Vanflyta may cause fertility problems in females and males, which may affect your ability to have children. Talk to your healthcare provider if you have concerns about fertility.

The most common side effects of Vanflyta include:

• low white blood cell counts
• changes in levels of electrolytes in the blood
• changes in liver function tests
• low white blood cell counts with fever
• diarrhea
• mouth sores
• nausea
• stomach (abdominal) pain
• serious infection throughout the body and organs (sepsis)
• headache
• vomiting
• upper respiratory tract infections
• low platelet counts
• decreased appetite
• fungal infections
• nosebleeds
• herpesvirus infections
• trouble sleeping
• abnormal electrocardiogram (QT prolongation)
• upset stomach
• low red blood cell counts (anemia)
• eye irritation.

Serious side effects and warnings

Vanflyta carries a Boxed Warning for QT interval prolongation, torsades de pointes, and cardiac arrest.

Vanflyta can cause changes in the electrical activity of your heart, such as QT prolongation, torsades de pointes, and irregular heartbeats. These can be fatal. Your healthcare provider will check the electrical activity of your heart with a test called an electrocardiogram (ECG) and will also do blood tests to check your potassium and magnesium levels before and during treatment with Vanflyta. Tell your healthcare provider right away if you have an irregular heartbeat or feel dizzy, lightheaded, faint, or have diarrhea or vomiting.

Vanflyta may harm an unborn baby. Females who can become pregnant should use effective birth control during treatment with Vanflyta and for 7 months after the last dose. Males with female partners who can become pregnant should use effective birth control during treatment and for 4 months after the last dose.

You will receive a Patient Wallet Card from your healthcare provider. Carry it with you at all times and show it to all of your healthcare providers. Get medical help right away if you develop any of the signs and symptoms of QT prolongation and torsades de pointes listed on the card. You may need to be treated in a hospital.

These are not all the possible side effects of Vanflyta. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Vanflyta is only available only through a restricted program called the Vanflyta Risk Evaluation and Mitigation Strategy (Vanflyta REMS) due to the risk of QT prolongation, torsades de pointes, and cardiac arrest. For healthcare providers to be eligible to prescribe Vanflyta they must:

• Enrol and complete training in Vanflyta REMS
• Counsel patients receiving Vanflyta about the risk of QT prolongation, torsades de pointes, and cardiac arrest, and provide patients with a Patient Wallet Card.

Pharmacies that dispense Vanflyta must be certified with the Vanflyta REMS and must verify prescribers are certified through the Vanflyta REMS.

Further information about the Vanflyta REMS is available at www.VANFLYTAREMS.com or by telephone at 1-855-212-6670.

The usual dose of Vanflyta is 35.4mg once a day.

• The dosage may need to be reduced or increased depending on the person taking Vanflyta's QTcF interval.

How long Vanflyta is taken depends on the phase. Typically:

• Induction phase: 2 weeks in each cycle (Days 8 to 21)
• Consolidation: 2 weeks in each cycle (Days 6 to 19)
• Maintenance: once daily with no break for up to 36 cycles.

If you miss a dose of Vanflyta, take your dose as soon as you remember, if it is still the same day. Take your next dose at your usual time on the next day. If it is already the next day, do not take 2 doses on the same day to make up for a missed dose.

If you vomit after taking a dose of Vanflyta, do not take another dose. Take your next dose at your usual time the next day.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Several medicines may interact with Vanflyta. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Tell your doctor about all your other medicines, especially:

• QT interval prolonging drugs, such as haloperidol, amiodarone, amitriptyline, ondansetron, citalopram, methadone, sumatriptan, fluoroquinolones
• Strong CYP3A Inhibitors, such as clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, or tipranavir. The dosage of Vanflyta needs to be reduced.
• Strong or Moderate CYP3A inducers such as apalutamide, carbamazepine, enzalutamide, fosphenytoin, lumacaftor, phenobarbital, phenytoin, rifampin (rifampicin), dexamethasone, efavirenz. Avoid.
• St John’s Wort.

This list is not complete. Other drugs may interact with Vanflyta, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.

Store your Vanflyta tablets at room temperature between 68°F and 77°F (20°C and 25°C).

Keep out of the reach of children.

Active ingredient: quizartinib 17.7 mg or 26.5 mg.

Inactive ingredients:

Tablet core: hydroxypropyl betadex, microcrystalline cellulose, and magnesium stearate.

Tablet coating: hypromellose, talc, triacetin, and titanium dioxide. The 26.5 mg tablet coating also contains ferric oxide.

Tablets are available in Vanflyta 17.7 mg and 26.5 mg strengths.

Daiichi Sankyo Company, Ltd., makes Vanflyta.