Dasatinib instructions

1. Generic name: dasatinib, Dasatinib

Product name:Sprycel, Starcel

2. Indications:

1. Dasatinib is suitable for adult patients:

(1) Newly diagnosed chronic phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML);

(2) Chronic, accelerated, or myeloid or lymphoblastic stage Ph+CML, resistant or intolerant to previous treatments including imatinib.

(3) Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL), resistant or intolerant to previous treatments.

2. Dasatinib is suitable for the treatment of pediatric patients 1 year old and above:

(1) Chronic phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML);

(2)Newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) combined with chemotherapy.

3. Usage and dosage:

1. Recommended dosage:

(1) Adult patients: The recommended starting dose for chronic phase CML is 100 mg orally once daily; for accelerated phase CML, myeloid or lymphoblastic phase CML, or Ph+ ALL, the recommended starting dose is 140 mg orally once daily. Dasatinib can be taken in the morning or evening with or without food.

(2) Pediatric patients: The recommended starting dose is based on body weight and the recommended dose should be taken orally once daily with or without food. The dose for patients weighing ≥10 to <20 kg is 40 mg; for patients weighing ≥20 to <30 kg, the dose is 60 mg; for patients weighing ≥30 to <45 kg, the dose is 70 mg; and for patients weighing at least ≥45 kg, the dose is 100 mg. Based on changes in body weight, the dose is recalculated every 3 months or more frequently if necessary.

For pediatric patients withPh+ ALL, initiate dasatinib treatment on or before day 15 of induction chemotherapy, when diagnosis is confirmed, and continue for 2 years. Tablets are not recommended for patients weighing <10kg.

2. Dose escalation: For adult patients with CML and Ph+ ALL who do not achieve a hematological or cytogenetic response at the recommended starting dose, a dose increase to 140 mg/day (chronic phase CML) or 180 mg/day (advanced CML and Ph+ ALL) may be considered. For pediatric patients with chronic myelogenous leukemia, consider increasing the dose to 120 mg once daily. Dose escalation is not recommended in pediatric patients with Ph+ ALL, in which case dasatinib is given concomitantly with chemotherapy.

3. Duration of treatment: In clinical studies, adult and pediatric patients with chronic phase CML continue to be treated with dasatinib until the disease progresses or the patient no longer tolerates it. The impact of discontinuing treatment after achieving cytogenetic response (including complete cytogenetic response [CCyR]) or major molecular response (MMR and MR4.5) on long-term disease outcomes has not been determined. In clinical studies, the maximum duration of treatment with dasatinib in pediatric patients with Ph+ ALL was 2 years.

4. Adverse reactions:

The most common adverse reactions in clinical studies of dasatinib were infection, bone marrow suppression, headache, bleeding, pleural effusion, dyspnea, diarrhea, vomiting, nausea, abdominal pain, rash, musculoskeletal pain, fatigue, leg and arm and facial swelling, and fever. After dasatinib was put on the market, adverse events such as hepatitis B virus reactivation, atrial fibrillation/atrial flutter, interstitial lung disease, Stevens-Johnson syndrome, nephrotic syndrome, thrombotic microangiopathy, and hepatotoxicity also occurred.

5. Storage:

Dasatinib is a tablet and should be stored20°C to 25°C (68°F to 77°F); tolerances allowed are between 15°C and 30°C (59°F and 86°F). Pregnant persons should avoid contact with crushed or broken tablets. Dasatinib tablets consist of a tablet core and a film coating to protect healthcare professionals from exposure to the active substance. When handling tablets that have been inadvertently crushed or broken, appropriate handling using latex or nitrile gloves is recommended to minimize the risk of skin contact.

6. Special groups:

1. Breastfeeding: Since dasatinib has potentially serious adverse reactions in nursing children, it is not recommended to breastfeed during drug treatment and within 2 weeks after the last dose; and pregnant women should be informed of the potential risks to the fetus.

2. Contraception: Based on animal data, dasatinib may damage reproductive tissue in both women and men. Therefore, it is recommended that women of reproductive potential and men who are partners of a female of reproductive potential use effective contraception during drug treatment and for 30 days after the last dose.

7. Mechanism of action:

Nanomolar concentrations of dasatinib inhibit the following kinases:BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2 and PDGFRβ. Based on modeling studies, dasatinib is expected to bind to multiple conformations of ABL kinase. In vitro, dasatinib is active in leukemia cell lines representing imatinib mesylate-sensitive and -resistant disease variants.

Dasatinib inhibits the growth of chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL. Under experimental conditions, dasatinib can overcome imatinib resistance caused by mutations in the BCR-ABL kinase domain, activation of alternative signaling pathways involving SRC family kinases (LYN, HCK), and overexpression of multidrug resistance genes.

The original drug of dasatinib has been launched in China and is included in the medical insurance. Currently, reimbursement is only available to eligible patients. Common specifications The price of each box of 50mg*60 tablets may be around RMB 10,000. The original drug overseas is even more expensive. Dasatinib generics are also sold overseas. The ingredients of the drug are basically the same as those sold domestically and abroad, but the price is cheap. For example, the price of a box of 50mg*60 tablets produced by an Indian pharmaceutical factory may be several hundred yuan (the price may fluctuate due to exchange rates).