Sprycel

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

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

GENERIC AVAILABLE: No

The blood concentration of dasatinib may be increased by several drugs that reduce its break down by liver enzymes. Increased blood concentrations of dasatinib may increase the occurrence of adverse effects. Examples include ketoconazole, itraconazole (Sporanox), clarithromycin (Biaxin), atazanavir (Reyataz), indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir), saquinavir (Invirase), telithromycin (Ketek), voriconazole (Vfend), and grapefruit juice. A dose reduction should be considered if there are no alternative medications that will not interact with dasatinib, for example a reduction in dose from 100 mg to 20 mg or 140 mg to 40 mg daily.

Certain drugs decrease the concentration of dasatinib resulting in decreased blood levels and possibly reduced effect. Examples include dexamethasone, carbamazepine, phenobarbital, rifampin, phenobarbital, and St John's Wort. A dose increase should be considered if dasatinib is combined with such drugs.

Drugs that reduce production of acid in the stomach reduce the absorption of dasatinib. Examples include proton pump inhibitors (PPIs) such as omeprazole (Prilosec) and H2 blocking drugs such as famotidine (Pepcid). Antacids used 2 hours before or after administration of dasatinib are reasonable alternatives to drugs that reduce the production of acid in the stomach.

Dasatinib increases the blood concentration of simvastatin (Zocor) by reducing the activity of enzymes that break down simvastatin in the liver. This may increase the side effects of simvastatin. Dasatinib may interact with other drugs that are broken down in a similar way as simvastatin.

>10%

Fluid retention, incl CHF, pulm edema, pleural effusion (50%)

Diarrhea (49%)

Headache (40%)

Hemorrhage (40%)

Fatigue (39%)

Pyrexia (39%)

Skin rash (35%)

Infection (34%)

Nausea (34%)

Dyspnea (32%)

Cough (28%)

Pain (26%)

Abdominal pain (25%)

Vomiting (22%)

Anorexia (19%)

Arthralgia (19%)

Asthenia (19%)

Constipation (14%)

Dizziness (14%)

Musculoskeletal pain (14%)

Weight loss (14%)

Chest pain (13%)

Neuropathy (13%)

Myalgia (12%)

Abdominal distention (11%)

Arrhythmia (11%)

Chills (11%)

Pneumonia (11%)

Pruritus (11%)

Weight gain (11%)

1-10% (selected)

Anemia

Febrile neutropenia

Thrombocytopenia

Mucosal inflammation

Postmarketing Reports

Cardiac disorders: Atrial fibrillation/atrial flutter

Vascular disorders: Thrombosis/embolism (including pulmonary embolism, deep vein thrombosis)

Respiratory, thoracic, and mediastinal disorders: Interstitial lung disease, pulmonary arterial hypertension

Dermatologic reactions: Stevens-Johnson syndrome, erythema multiforme

Infections: Hepatitis B virus reactivation

Renal and urinary disorders: Nephrotic syndrome

Antineoplastic agent; a kinase inhibitor.1 2 3

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Dasatinib is used to treat different types of leukemia. Leukemia is a type of cancer where the body makes too many abnormal white blood cells. It belongs to the general group of medicines known as antineoplastics or cancer medicines. Dasatinib interferes with the growth of cancer cells, which are eventually destroyed by the body.

This medicine is available only with your doctor's prescription.

• Tell all of your health care providers that you take Sprycel. This includes your doctors, nurses, pharmacists, and dentists.
• You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
• If you have upset stomach, throwing up, loose stools (diarrhea), or are not hungry, talk with your doctor. There may be ways to lower these side effects.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Do not take antacids within 2 hours of this medicine.
• If you are allergic to lactose or have lactose intolerance, talk with your doctor.
• Avoid grapefruit and grapefruit juice.
• You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor. Rarely, some bleeding problems have been deadly.
• Call your doctor right away if you have any signs of bleeding problems, like bruising; black, tarry, or bloody stools; bleeding gums; blood in the urine; coughing up blood; cuts that take a long time to stop bleeding; feel dizzy; feeling very tired or weak; nosebleeds; pain or swelling; throwing up blood or throw up that looks like coffee grounds; or very bad headache.
• Very bad heart problems like heart failure and deadly heart attack have happened with Sprycel. Talk with your doctor.
• This medicine may raise the chance of a very bad lung problem (pulmonary arterial hypertension). This may happen any time after starting this drug, even after more than 1 year of taking it. Talk with your doctor.
• Have your heart and lung function checked. Talk with your doctor.
• This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking this medicine with your other drugs.
• If you are 65 or older, use Sprycel with care. You could have more side effects.
• This medicine may affect fertility. Fertility problems may lead to not being able to get pregnant or father a child. Talk with the doctor.
• Pregnant women must not handle crushed or broken tablets. Talk with the doctor.
• This medicine may cause harm to the unborn baby if you take it while you are pregnant.
• Use birth control that you can trust to prevent pregnancy while taking this medicine and for 1 month after stopping Sprycel.
• If you get pregnant while taking this medicine or within 1 month after your last dose, call your doctor right away.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Drugs That May Increase Dasatinib Plasma Concentrations

CYP3A4 Inhibitors: Dasatinib is a CYP3A4 substrate. In a trial of 18 patients with solid tumors, 20-mg Sprycel once daily coadministered with 200 mg of ketoconazole twice daily increased the dasatinib Cmax and AUC by four- and five-fold, respectively. Concomitant use of Sprycel and drugs that inhibit CYP3A4 may increase exposure to dasatinib and should be avoided. In patients receiving treatment with Sprycel, close monitoring for toxicity and a Sprycel dose reduction should be considered if systemic administration of a potent CYP3A4 inhibitor cannot be avoided [see Dosage and Administration (2.1)].

Drugs That May Decrease Dasatinib Plasma Concentrations

CYP3A4 Inducers: When a single morning dose of Sprycel was administered following 8 days of continuous evening administration of 600 mg of rifampin, a potent CYP3A4 inducer, the mean Cmax and AUC of dasatinib were decreased by 81% and 82%, respectively. Alternative agents with less enzyme induction potential should be considered. If Sprycel must be administered with a CYP3A4 inducer, a dose increase in Sprycel should be considered [see Dosage and Administration (2.1)].

Antacids: Nonclinical data demonstrate that the solubility of dasatinib is pH dependent. In a trial of 24 healthy subjects, administration of 30 mL of aluminum hydroxide/magnesium hydroxide 2 hours prior to a single 50-mg dose of Sprycel was associated with no relevant change in dasatinib AUC; however, the dasatinib Cmax increased 26%. When 30 mL of aluminum hydroxide/magnesium hydroxide was administered to the same subjects concomitantly with a 50-mg dose of Sprycel, a 55% reduction in dasatinib AUC and a 58% reduction in Cmax were observed. Simultaneous administration of Sprycel with antacids should be avoided. If antacid therapy is needed, the antacid dose should be administered at least 2 hours prior to or 2 hours after the dose of Sprycel.

H2 Antagonists/Proton Pump Inhibitors: Long-term suppression of gastric acid secretion by H2 antagonists or proton pump inhibitors (e.g., famotidine and omeprazole) is likely to reduce dasatinib exposure. In a trial of 24 healthy subjects, administration of a single 50-mg dose of Sprycel 10 hours following famotidine reduced the AUC and Cmax of dasatinib by 61% and 63%, respectively. In a trial of 14 healthy subjects, administration of a single 100-mg dose of Sprycel 22 hours following a 40-mg omeprazole dose at steady state reduced the AUC and Cmax of dasatinib by 43% and 42%, respectively. The concomitant use of H2 antagonists or proton pump inhibitors with Sprycel is not recommended. The use of antacids (at least 2 hours prior to or 2 hours after the dose of Sprycel) should be considered in place of H2 antagonists or proton pump inhibitors in patients receiving Sprycel therapy.

Drugs That May Have Their Plasma Concentration Altered By Dasatinib

CYP3A4 Substrates: Single-dose data from a trial of 54 healthy subjects indicate that the mean Cmax and AUC of simvastatin, a CYP3A4 substrate, were increased by 37% and 20%, respectively, when simvastatin was administered in combination with a single 100-mg dose of Sprycel. Therefore, CYP3A4 substrates known to have a narrow therapeutic index such as alfentanil, astemizole, terfenadine, cisapride, cyclosporine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, or ergot alkaloids (ergotamine, dihydroergotamine) should be administered with caution in patients receiving Sprycel.

Sprycel (dasatinib) is a kinase inhibitor. The chemical name for dasatinib is N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide, monohydrate. The molecular formula is C22H26ClN7O2S • H2O, which corresponds to a formula weight of 506.02 (monohydrate). The anhydrous free base has a molecular weight of 488.01. Dasatinib has the following chemical structure:

Dasatinib is a white to off-white powder. The drug substance is insoluble in water and slightly soluble in ethanol and methanol. Sprycel tablets are white to off-white, biconvex, film-coated tablets containing dasatinib, with the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, hydroxypropyl cellulose, and magnesium stearate. The tablet coating consists of hypromellose, titanium dioxide, and polyethylene glycol.

How Supplied

Sprycel® (dasatinib) tablets are available as described in Table 13.

Storage

Sprycel tablets should be stored at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].

Handling and Disposal

Sprycel is an antineoplastic product. Follow special handling and disposal procedures.

Sprycel tablets consist of a core tablet (containing the active drug substance), surrounded by a film coating to prevent exposure of pharmacy and clinical personnel to the active drug substance. However, if tablets are inadvertently crushed or broken, pharmacy and clinical personnel should wear disposable chemotherapy gloves. Personnel who are pregnant should avoid exposure to crushed or broken tablets.

Take Sprycel exactly as prescribed by your doctor. Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

You may take the medicine with or without food. Take the medicine at the same time each day.

Do not crush, chew, or break a Sprycel tablet. Swallow it whole.

Do not use a pill that has been accidentally broken. The medicine from a crushed or broken pill can be dangerous if it gets in your eyes, mouth, or nose, or on your skin. If this occurs, wash your skin with soap and water or rinse your eyes with water. Ask your doctor or pharmacist how to safely handle and dispose of a broken tablet or capsule.

Sprycel can lower blood cells that help your body fight infections and help your blood to clot. Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests.

Do not change your dose or stop using Sprycel without your doctor's advice.

Store at room temperature away from moisture and heat.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Grapefruit and grapefruit juice may interact with dasatinib and lead to unwanted side effects. Avoid the use of grapefruit products while taking Sprycel.

Avoid taking an antacid within 2 hours before or after you take Sprycel. Some antacids can make it harder for your body to absorb dasatinib.

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Dasatinib can pass into body fluids (urine, feces, vomit). Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash ands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Get emergency medical help if you have signs of an allergic reaction to Sprycel: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor right away if you have any symptoms of pulmonary arterial hypertension (PAH), such as:

• feeling tired or short of breath (even with mild exertion);

• swelling in your feet or lower legs;

• blue-colored lips and skin; and

• a light-headed feeling, like you might pass out.

Call your doctor at once if you have:

• pain when you breathe, rapid heart rate, feeling short of breath (especially when lying down);

• pain in your chest, on your left side, or behind your breastbone;

• rapid weight gain (especially in your face and midsection);

• low platelets or red blood cells - pale skin, feeling light-headed, easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;

• low white blood cell counts - fever, swollen gums, painful mouth sores, pain when swallowing, skin sores, cold or flu symptoms, cough; or

• other signs of bleeding - bloody or tarry stools, coughing up blood or vomit that looks like coffee grounds, confusion, headache, problems with speech, extreme weakness or drowsiness.

Common Sprycel side effects may include:

• swelling, bleeding, blood cell disorders;

• breathing problems;

• headache, tiredness;

• nausea, diarrhea; or

• mild skin rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.