Daurismo

Daurismo is a prescription medicine that is used with the medicine cytarabine to treat adults with newly-diagnosed acute myeloid leukemia (AML). 

Daurismo belongs to a group of anticancer drugs called hedgehog pathway inhibitors. These work by stopping a protein responsible for cell growth signal transduction. In cancer, the signaling pathway is constantly on, leading to tumor growth. Daurismo allows this signaling to be blocked and stops cancer growth.

This medication comes in tablet form and is taken once daily, with or without food. Do not chew, divide, or break Daurismo tablets. Swallow tablets whole.

Common side effects include low red blood cell and platelet counts, shortness of breath and bleeding. Daurismo can cause extreme tiredness. Do not drive or operate heavy machinery until you know how Daurismo affects you.

Daurismo is a prescription medicine that is used with the medicine cytarabine to treat newly-diagnosed acute myeloid leukemia (AML) in adults who:

• are 75 years of age or older, or
• have other medical conditions that prevent the use of standard chemotherapy

Daurismo has not been studied in people with severe kidney problems or moderate-to-severe liver problems.
It is not known if Daurismo is safe and effective in children.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with Daurismo. See the “Daurismo Precautions” section.

Common side effects of Daurismo include the following:

• low red blood cell count (anemia)
• tiredness
• bleeding
• fever with low white blood cell count
• muscle pain
• nausea
• swelling of arms or legs
• low platelet count
• shortness of breath
• decreased appetite
• changes in taste
• pain or sores in your mouth or throat
• constipation
• rash

Daurismo can cause severe tiredness and dizziness. Do not drive or operate heavy machinery until you know how Daurismo affects you.

This is not a complete list of Dauirsmo side effects. Ask your doctor or pharmacist for more information. Tell your doctor if you have any side effects that bother you or that do not go away. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• Medications that block a protein in the body (CYP3A4) such as some macrolide antibiotics (clarithromycin, telithromycin), some HIV protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir), some HCV protease inhibitors (boceprevir, telaprevir), some azole antifungals (ketoconazole, itraconazole, posaconazole, voriconazole), delavirdine (Rescriptor), and nefazodone

• Medications that increase the activity of the enzyme CYP3A4 such as carbamazepine (Tegretol, Equetro, Carbatrol), phenobarbital, phenytoin (Dilantin), rifampin (Rifadin), and St John's wort

• Drugs that can cause an arrhythmia called Torsades des Point such as

  • Certain anti-arrhythmia medications including

    • procainamide, sotalol (Betapace), quinidine, dofetilide (Tikosyn), amiodarone (Nexterone, Pacerone, Cordarone), ibutilide (Corvert)

  • Certain fluoroquinolone antibiotics including

    • levofloxacin (Levaquin), ciprofloxacin (Cipro), gatifloxacin (Zymar), moxifloxacin (Avelox)

  • Certain macrolide antibiotics including

    • clarithromycin (Biaxin), erythromycin (EES, others)

  • Certain azole antifungals including

    • ketoconazole (Nizoral), itraconazole (Sporanox, Onmel)

  • Certain antidepressants including

    • amitriptyline, desipramine (Norpramin), imipramine (Tofranil), doxepin (Silenor), fluoxetine (Prozac, Sarafem, Symbyax), sertraline (Zoloft), venlafaxine (Effexor XR)

  • Certain antipsychotics including

    • haloperidol (Haldol), droperidol (Inapsine), quetiapine (Seroquel XR), thioridazine, ziprasidone (Geodon)

  • And other medications including

    • cisapride, sumatriptan (Treximet, Imitrex, Alsuma, Zecuity), zolmitriptan (Zomig, arsenic trioxide (Trisenox), dolasetron (Anzemet), and methadone (Methadone, Dolophine)

This is not a complete list of Daurismo drug interactions. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with Daurismo including the following:

• QT prolongation. This is a condition when changes in the electrical activity of your heart occur, causing irregular heartbeats that can be life threatening. Talk to your healthcare provider about other medicines you are taking before you start taking Daurismo. Tell your healthcare provider right away if you have any signs or symptoms of QT prolongation:

  • feeling faint

  • lightheadedness

  • dizziness

  • feeling like your heart is beating irregularly or quickly

• Harm to unborn baby. Daurismo used in pregnant women can cause babies be born with problems. Tell your doctor if you are pregnant or plan to become pregnant. See "Pregnancy" section.

For males:

• It is not known if Daurismo is present in semen. Do not donate semen during treatment with Daurismo and for at least 30 days after your last dose. 
• You should always use effective birth control, including a condom, even if you have had a vasectomy, during sex with female partners who are pregnant or who are able to become pregnant, during treatment with Daurismo and for at least 30 days after your last dose to protect your female partner from being exposed to Daurismo.
• Tell your healthcare provider right away if your partner becomes pregnant or thinks she is pregnant while you are taking Daurismo.

Daurismo can cause severe tiredness and dizziness. Do not drive or operate heavy machinery until you know how Daurismo affects you.

Do not take Daurismo if you are allergic to Daurismo or to any of its ingredients.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Daurismo, there are no specific foods that you must exclude from your diet when receiving this medication.

Before taking Daurismo, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to Daurismo or to any of its ingredients
• have heart problems, including a condition called long QT syndrome.
• have abnormal blood salt (electrolytes) levels.
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Tell your doctor if you are pregnant or plan to become pregnant. Daurismo can cause your baby to die before it is born (be stillborn) or cause your baby to have severe birth defects.

In animal studies, pregnant animals were given this medication and had some babies born with problems. No well-controlled studies have been done in humans. The use of Daurismo in pregnant women can caused some babies to be born with problems. Do not use Daurismo during pregnancy. Talk doctor about any questions pregnancy risks with Daurismo.

For females who can become pregnant:

• You should talk to your healthcare provider about the risks of Daurismo to your unborn child.
• Your healthcare provider will do a pregnancy test within 7 days before you start taking Daurismo. 
• You should not use Daurismo during pregnancy.
• You should use effective birth control during treatment and for at least 30 days after your last dose of Daurismo. Talk with your healthcare provider about what birth control method is right for you during this time.
• Talk to your healthcare provider right away if you have unprotected sex or if you think that your birth control has failed. 
• Tell your healthcare provider right away if you become pregnant or think that you may be pregnant.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if Daurismo crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, women should not breastfeed while on and at least 30 days after last dose of Daurismo. Your doctor and you will decide if the benefits outweigh the risk of using this medication.

• Take Daurismo with the medicine cytarabine exactly as your healthcare provider tells you.
• Take Daurismo 1 time each day, at about the same time each day. 
• Take Daurismo with or without food. 
• Do not chew, split or crush Daurismo tablets.
• If you miss a dose, take it as soon as you remember. If it is less than 12 hours before your next dose, just skip the missed dose and take your next dose at your regular time. Do not take 2 doses of Daurismo within 12 hours.
• If you vomit after taking a dose of Daurismo, do not take an extra dose, just take your next dose at your regular time.
• Your healthcare provider will perform certain tests to check you for side effects before and during treatment with Daurismo. 
• Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with Daurismo if you have certain side effects. Do not change your dose or stop taking Daurismo unless your healthcare provider tells you.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated

• other medical conditions you have

• other medications you are taking

• how you respond to this medication

The recommended dose of Daurismo (glasdegib) for the treatment of treat acute myeloid leukemia (AML) is 100 mg once daily on days 1 to 28 in combination with cytarabine 20 mg subcutaneously twice daily on days 1 to 10 of each 28-day cycle. Dose of either drug may be adjusted depending on side effects or toxicities experienced.  

If you take too much Daurismo, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

• Store Daurismo at room temperature between 68°F to 77°F (20°C to 25°C).

• Keep this and all medicines out of the reach of children.

Warning: Embryo-Fetal Toxicity

See full prescribing information for complete boxed warning.

• Daurismo can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. Daurismo is embryotoxic, fetotoxic, and teratogenic in animals.

• Conduct pregnancy testing in females of reproductive potential prior to initiation of Daurismo treatment. Advise females of reproductive potential to use effective contraception during treatment with Daurismo and for at least 30 days after the last dose.

• Advise males of the potential risk of exposure through semen and to use condoms with a pregnant partner or a female partner of reproductive potential during treatment with Daurismo and for at least 30 days after the last dose to avoid potential drug exposure.