Drug information of gilteritinib

gilteritinib


Gilteritinib is used to treat acute myeloid leukemia (AML) in adults with an abnormal FLT3 gene. Your doctor will test you for this gene.

Gilteritinib is given after other cancer treatments did not work or have stopped working.

Mechanism of effect

Gilteritinib is a tyrosine kinase inhibitor which inhibits multiple tyrosine kinases, such as FMS-like tyrosine kinase 3 (FLT3). Gilteritinib inhibits FLT3 receptor signaling and proliferation in cells expressing FLT3 (including FLT3-ITD), tyrosine kinase domain mutations (TKD) FLT3-D835Y and FLT3-ITD-D835Y; it induces apoptosis in FLT3-ITD-expressing leukemia cells.

Pharmacokinetics

Distribution

Central: 1,092 L; Peripheral: 1,100 L

Metabolism

Primarily hepatic via CYP3A4; primary human metabolites include M17 (formed via N-dealkylation and oxidation), M16 and M10 (both formed via N-dealkylation), none of which exceed 10% of overall parent exposure

Excretion

Feces: 64.5%; Urine: 16.4% as unchanged drug and metabolites

Onset of Action

Inhibition of FLT3 phosphorylation: Rapid (within 24 hours after the initial dose)

Time to Peak

~4 to 6 hours

Half-Life Elimination

113 hours

Protein Binding

~94% to human plasma proteins

 

Drug indications

Acute myeloid leukemia, relapsed or refractory: Treatment of relapsed or refractory acute myeloid leukemia (AML) in adult patients with an FMS-like tyrosine kinase 3 (FLT3) mutation as detected by an approved test.

Dosage

Acute myeloid leukemia, relapsed or refractory, FLT3-positive: Oral: 120 mg once daily for a minimum of 6 months (to allow time for a clinical response) or until disease progression or unacceptable toxicity.

Missed doses: If a dose is missed, administer the missed dose as soon as possible on the same day (and at least 12 hours prior to the next scheduled dose). Return to the normal dosing schedule the following day; do not administer 2 doses within 12 hours.

Drug contraindications

Hypersensitivity to gilteritinib or any component of the formulation

Side effects

Along with its needed effects, gilteritinib may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking gilteritinib:

More common

  • Bloody urine
  • blurred vision
  • chest pain
  • chills
  • confusion
  • cough
  • decreased frequency or amount of urine
  • dizziness
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • fainting
  • fast or irregular heartbeat
  • fever
  • headache
  • increased thirst
  • lightheadedness
  • loss of appetite
  • lower back or side pain
  • nausea
  • nervousness
  • pounding in the ears
  • rapid, shallow breathing
  • recurrent fainting
  • slow heartbeat
  • sneezing
  • sore throat
  • stomach pain
  • sweating
  • swelling of the face, fingers, or lower legs
  • tightness in the chest
  • troubled breathing
  • unusual tiredness or weakness
  • vomiting
  • weight gain

Less common

  • Anxiety
  • blue or pale skin
  • chest discomfort
  • chest pain, possibly moving to the left arm, neck, or shoulder
  • difficulty swallowing
  • dilated neck veins
  • extreme tiredness or weakness
  • hives, itching, skin rash
  • irregular breathing
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • seizures
  • unusual drowsiness
  • vision problems

Some side effects of gilteritinib may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  • Change in taste
  • constipation
  • decreased appetite
  • diarrhea
  • loss of taste
  • muscle or joint pain
  • swelling or inflammation of the mouth
  • trouble sleeping

Alerts

Concerns related to adverse effects:

-  Differentiation syndrome: [US Boxed Warning]: Patients treated with gilteritinib have experienced symptoms of differentiation syndrome (rapid proliferation and differentiation of myeloid cells), which can be fatal or life-threatening if not treated. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, or renal dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution. Concomitant acute febrile neutrophilic dermatosis has been observed in some cases. The onset of differentiation syndrome (with or without concomitant leukocytosis) ranged from 2 to 75 days after gilteritinib initiation; the majority of patients who experienced this syndrome recovered after treatment or therapy interruption. If differentiation syndrome is suspected, administer dexamethasone 10 mg IV every 12 hours (or equivalent oral/IV corticosteroid) and monitor hemodynamics until improvement. Administer corticosteroids for a minimum of 3 days; once symptoms resolve, taper corticosteroid. Differentiation syndrome symptoms may recur if corticosteroids are discontinued early. If severe signs/symptoms of differentiation syndrome continue for more than 48 hours after corticosteroid initiation, interrupt gilteritinib therapy until symptoms are no longer severe.

- Gilteritinib can cause a condition called differentiation syndrome, which affects blood cells and can be fatal if not treated. This condition may occur within 2 days to 3 months after you start taking gilteritinib.

- Seek medical help right away if you have symptoms of differentiation syndrome: fever, cough, trouble breathing, bone pain, rapid weight gain, or swelling in your arms, legs, underarms, groin, or neck.

Before taking this medicine

You should not use gilteritinib if you are allergic to it.

Tell your doctor if you have ever had:

  • heart problems;
  • long QT syndrome (in you or a family member); or
  • an electrolyte imbalance (such as low levels of potassium or magnesium in your blood).

Before you take gilteritinib, your heart function may need to be checked using an electrocardiograph or ECG (sometimes called an EKG).

Points of recommendation

Gilteritinib can harm an unborn baby or cause birth defects if the mother or the father is using this medicine.

If you are a woman, do not use gilteritinib if you are pregnant. You may need to have a negative pregnancy test before starting this treatment. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 6 months after your last dose.

If you are a man, use effective birth control if your sex partner is able to get pregnant. Keep using birth control for at least 4 months after your last dose.

Tell your doctor right away if a pregnancy occurs while either the mother or the father is using gilteritinib.

Do not breastfeed while using this medicine, and for at least 2 months after your last dose.

Gilteritinib is usually given once per day. Take this medicine with a full glass of water, at the same time each day.

You may take gilteritinib with or without food.

Take the missed dose on the same day you remember it. Skip the missed dose if your next dose is due in less than 12 hours. Do not use two doses within a 12-hour period.

Oral: Administer with or without food at approximately the same time each day. Do not break or crush the tablets.

Storage

Store at 20ºC to 25ºC (68°F to 77°F); excursions permitted between 15ºC to 30ºC (59°F to 86°F). Store in original container until dispensed. Protect from light, moisture, and humidity.

Pregnancy level

HAVE NOT BEEN ESTABLISHED

Use should be avoided.

US FDA pregnancy category: Not assigned.

Breast feeding warning

Use should be avoided.

Excreted into human milk: Unknown
Excreted into animal milk: Data not available

Comments:
-Following administration of this drug to lactating animals, milk concentrations of radioactivity were higher than radioactivity in maternal plasma at 4 and 24 hours post-dose.
-Because of the potential for serious adverse reactions in a breastfed child, women should not breastfeed during therapy and for 2 months after.

Based on the mechanism of action and information from animal reproductions studies, gilteritinib may cause fetal harm following maternal use during pregnancy.

Drug forms

Xospata

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