A-Z Drug Facts > Dasatinib

Dasatinib

Pronouncation: (da-SA-ti-nib)
Class: Protein-tyrosine kinase inhibitor

Trade Names:
Sprycel
- Tablets 20 mg
- Tablets 50 mg
- Tablets 70 mg

Pharmacology

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Inhibits growth of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines that overexpress the kinase BCR-ABL.

Pharmacokinetics

Absorption

T _max is between 0.5 and 6 h.

Distribution

Vd is 2,505 L, suggesting extensive distribution in extravascular space. Protein binding 96%; active metabolite 93%.

Metabolism

Extensively metabolized by CYP3A4 to an active metabolite, which is equipotent to dasatinib. Also metabolized by flavin-containing monooxygenase-3 and uridine diphosphate-glucuronosyltransferase enzymes.

Elimination

Terminal t _½ is 3 to 5 h. Excretion is primarily fecal (85%) and 4% in urine.

Special Populations

Renal/Hepatic function impairment

No clinical studies conducted.

Indications and Usage

Treatment of adults with chronic, accelerated or myeloid, or lymphoid blast phase CML with resistance or intolerance to prior therapy including imatinib; treatment of adults with Philadelphia chromosome–positive (Ph+) ALL with resistance or intolerance to prior therapy.

Contraindications

None known.

Dosage and Administration

Adults

PO 70 mg twice daily, once in the morning and evening. Consider dose increases or reductions of 20 mg increments per dose based on safety and tolerability. If a severe nonhematologic adverse reaction occurs, treatment must be withheld until the reaction resolves or improves. Then, resume treatment as appropriate at a reduced dose, depending on severity of the reaction.

Dose Adjustments for Coadministration with Strong CYP3A4 Inhibitors
Adults

PO If a strong CYP3A4 inhibitor must be coadministered, consider decreasing the dasatinib dosage to 20 to 40 mg daily.

Dose Adjustments for Neutropenia and Thrombocytopenia
Adults Chronic phase CML

PO Starting dosage 70 mg twice daily. If absolute neutrophil count (ANC) is less than 0.5 × 10 ⁹ /L and/or platelet count is less than 50 × 10 ⁹ /L, stop dasatinib until ANC is at least 1 × 10 ⁹ /L and platelets at least 50 × 10 ⁹ /L. Then, resume treatment at the original starting dose. If platelets are less than 25 × 10 ⁹ /L and/or recurrence of ANC less than 0.5 × 10 ⁹ /L for more than 7 days, stop dasatinib until ANC is at least 1 × 10 ⁹ /L and platelets at least 50 × 10 ⁹ /L. Then, resume treatment at 50 mg twice daily (second episode) or 40 mg twice daily (third episode).

Accelerated phase CML, blast phase CML and Ph+ ALL

PO Starting dosage 70 mg twice daily. If ANC is less than 0.5 × 10 ⁹ /L and/or platelet count is less than 10 × 10 ⁹ /L, check if cytopenia is related to leukemia. If unrelated to leukemia, stop dasatinib until ANC is at least 1 × 10 ⁹ /L and platelets at least 20 × 10 ⁹ /L. Then, resume treatment at the original starting dose. If recurrence of cytopenia, check if cytopenia is related to leukemia, and resume dasatinib at a dosage of 50 mg twice daily (second episode) or 40 mg twice daily (third episode). If cytopenia is related to leukemia, consider escalating the dasatinib dosage to 100 mg twice daily.

General Advice

• May be given without respect to meals.
• Tablets should be swallowed whole. Do not crush or cut.

Storage/Stability

Store between 59° and 86°F.

Drug Interactions

Antacids

Based on nonclinical data, if antacid therapy cannot be avoided, administer the antacid at least 2 h before or after dasatinib.

CYP3A4 inducers (eg, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin, St. John's wort)

May reduce dasatinib plasma levels, decreasing the therapeutic effect. When possible, use alternative therapy.

CYP3A4 inhibitors (eg, atazanavir, clarithromycin, erythromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin)

May elevate dasatinib plasma concentrations, increasing the risk of adverse reactions.

CYP3A4 substrates (eg, alfentanil, astemizole, cisapride, cyclosporine, ergot alkaloids, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, terfenadine)

Plasma levels may be altered by dasatinib; therefore, use with caution.

Histamine type 2 blockers (eg, famotidine), proton pump inhibitors (eg, omeprazole)

May reduce dasatinib plasma levels, decreasing the therapeutic effect.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Arrhythmia (11%); CHF/cardiac dysfunction (4%); angina pectoris, cardiomegaly, flushing, hypertension, hypotension, MI, palpitations (less than 10%).

CNS

Headache (40%); fatigue (39%); asthenia (19%); constipation, dizziness (14%); neuropathy (13%); CNS bleeding (2%); affect liability, anxiety, confusional states, convulsions, depression, dysgeusia, insomnia, malaise, somnolence, syncope, tremor (less than 10%).

Dermatologic

Skin rash (35%); pruritus (11%); acne, alopecia, dermatitis including eczema, dry skin, hyperhidrosis, nail disorder, photosensitivity, pigmentation disorder, urticaria (less than 10%).

EENT

Conjunctivitis, dry eye, tinnitus, vertigo (less than 10%).

GI

Diarrhea (49%); nausea (34%); vomiting (22%); anorexia (19%); GI bleeding (14%); abdominal distention (11%); anal fissure, colitis, dyspepsia, dysphagia, gastritis, oral soft tissue disorder (less than 10%).

Genitourinary

Gynecomastia, renal failure, urinary frequency (less than 10%).

Hematologic-Lymphatic

Febrile neutropenia (9%); anemia, neutropenia, pancytopenia, thrombocytopenia (less than 10%).

Lab Tests

Elevated bilirubin and transaminases, hypocalcemia, hypophosphatemia, increased blood CPK, increased troponin (less than 10%).

Metabolic-Nutritional

Decreased weight (14%); increased weight (11%); appetite disturbances, hyperuricemia (less than 10%).

Musculoskeletal

Musculoskeletal pain (39%); arthralgia (19%); myalgia (12%); muscle inflammation, muscular weakness, musculoskeletal stiffness (less than 10%).

Respiratory

Dyspnea (32%); cough (28%); upper respiratory tract infection/inflammation (26%); pneumonia (11%); pulmonary edema (4%); asthma, lung infiltration, pneumonitis (less than 10%).

Miscellaneous

Fever (39%); superficial edema (36%); infection including bacterial, fungal, viral, and nonspecific (34%); abdominal pain (25%); pleural effusion (22%); mucosal inflammation (16%); chest pain (13%); chills (11%); generalized edema (5%); pericardial effusion (4%); ascites, pulmonary hypertension (1%); contusion, enterocolitis infection, herpes virus infection, sepsis, tumor lysis syndrome (less than 10%).

Precautions

Monitor Monitor CBC weekly for the first 2 mo, then monthly thereafter, or as clinically indicated.

Pregnancy

Category D .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Bleeding

Severe hemorrhage may occur. Use with caution in patients receiving anticoagulants or medications that may inhibit platelet function.

Fluid retention

Fluid retention, possibly severe (eg, pleural and pericardial effusion), may occur.

Lactose content

A daily dose contains lactose 189 mg.

Myelosuppression

Severe thrombocytopenia, neutropenia, and anemia may occur and can usually be managed by withholding treatment or reducing the dose.

QTc prolongation

QTc prolongation has been reported; therefore, use with caution in patients who have or may develop QTc prolongation, including patients with hypokalemia or hypomagnesemia, congenital QT syndrome, or patients taking high-dose anthracycline therapy, antiarrhythmic agents, or other medicines that prolong the QT interval. Correct hypokalemia or hypomagnesemia before administering dasatinib.

Overdosage

Symptoms

No symptoms were reported with an accidental overdose of 200 mg.

Patient Information

• Advise patient to read the patient information leaflet before using product the first time and with each refill.
• Advise men to employ birth control methods if sexually active.
• Advise patient to inform health care provider of lactose intolerance, or heart or liver problems.
• Advise patient to swallow the tablet whole and not to break, cut, or crush the tablet.
• Advise patient to take this medication twice daily, once in the morning and evening, with or without a meal.
• Instruct patient to take exactly as prescribed and not to change the dose or discontinue therapy unless advised by health care provider.
• Advise patient that if a dose is missed to take the next scheduled dose at the regular time and not to take 2 doses at the same time.
• Inform patient to contact health care provider if more than the prescribed dose is accidentally taken.
• Instruct patient regarding how to store, administer, and dispose of outdated medication.

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