Sprycel

Sprycel (Dasatinib): A Comprehensive Overview

Introduction

Sprycel, known generically as dasatinib, is a targeted cancer therapy used primarily in the treatment of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). It belongs to the class of drugs known as tyrosine kinase inhibitors (TKIs), which work by blocking specific enzymes involved in the growth and proliferation of cancer cells. Sprycel is a second-generation TKI, offering improved efficacy and a broader spectrum of activity compared to earlier treatments like imatinib (Gleevec). This article provides an in-depth look at Sprycel, including its mechanism of action, indications, pharmacokinetics, side effects, contraindications, and important considerations for use.

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Mechanism of Action

Dasatinib is a multi-targeted tyrosine kinase inhibitor that works by inhibiting several key enzymes involved in cancer cell growth and survival. These enzymes include:

1. BCR-ABL Tyrosine Kinase: Dasatinib is highly effective against the BCR-ABL fusion protein, which is the hallmark of chronic myeloid leukemia (CML). This abnormal protein results from the Philadelphia chromosome translocation (t(9;22)) and drives the uncontrolled proliferation of leukemic cells.

2. SRC Family Kinases: Dasatinib also inhibits SRC family kinases (e.g., SRC, LCK, YES, FYN), which play a role in cell signaling, survival, and proliferation.

3. Other Tyrosine Kinases: Dasatinib targets additional kinases, including KIT, EPHA2, and PDGFRβ, which may contribute to its efficacy in certain cancers.

By inhibiting these kinases, dasatinib disrupts downstream signaling pathways, leading to reduced proliferation, increased apoptosis (programmed cell death), and inhibition of tumor growth.

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Indications and Uses

Sprycel is approved for the treatment of the following conditions:

1. Chronic Myeloid Leukemia (CML):

   • Newly Diagnosed Chronic Phase CML: Sprycel is indicated as a first-line treatment for adults with newly diagnosed Philadelphia chromosome-positive (Ph+) CML in the chronic phase.

   • Resistant or Intolerant CML: It is also used for patients with chronic, accelerated, or blast phase CML who are resistant or intolerant to prior therapy, including imatinib.

2. Acute Lymphoblastic Leukemia (ALL):

   • Philadelphia Chromosome-Positive ALL (Ph+ ALL): Sprycel is indicated for the treatment of adults with Ph+ ALL who are resistant or intolerant to prior therapy.

3. Investigational Uses:

   • Dasatinib is being studied in other cancers, including solid tumors and other hematologic malignancies, due to its broad kinase inhibition profile.

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Pharmacokinetics

1. Absorption:

   • Dasatinib is administered orally and is rapidly absorbed after ingestion. Its bioavailability is approximately 34%, and absorption is not significantly affected by food.

2. Distribution:

   • Dasatinib is widely distributed in the body and is highly protein-bound (96%). It has a large volume of distribution, indicating extensive tissue penetration.

3. Metabolism:

   • Dasatinib is primarily metabolized in the liver by the cytochrome P450 enzyme system, particularly CYP3A4. It is converted into active and inactive metabolites.

4. Excretion:

   • The drug is primarily excreted in the feces (85%), with a small portion (4%) eliminated in the urine. The elimination half-life of dasatinib is approximately 3-5 hours, necessitating twice-daily dosing in most cases.

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Dosage and Administration

The dosage of Sprycel varies depending on the indication, patient response, and tolerability. Common dosing regimens include:

• Chronic Phase CML: 100 mg once daily or 50 mg twice daily.

• Accelerated or Blast Phase CML/Ph+ ALL: 140 mg once daily or 70 mg twice daily.

Dose adjustments may be necessary for patients with hepatic impairment or those experiencing significant side effects. Sprycel should be taken with or without food, but grapefruit juice should be avoided as it can increase dasatinib levels.

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Side Effects

Sprycel is generally well-tolerated, but it can cause a range of side effects, some of which may be severe. Common side effects include:

1. Hematologic:

   • Myelosuppression, including neutropenia, thrombocytopenia, and anemia. Regular blood counts are required to monitor for these effects.

2. Gastrointestinal:

   • Nausea, vomiting, diarrhea, abdominal pain, and gastrointestinal bleeding.

3. Fluid Retention:

   • Pleural effusion, pericardial effusion, and peripheral edema. Patients should be monitored for signs of fluid retention, such as shortness of breath or swelling.

4. Cardiovascular:

   • QT prolongation, arrhythmias, and congestive heart failure (CHF). Cardiac function should be monitored in patients at risk.

5. Dermatological:

   • Rash, pruritus, and skin reactions.

6. Other:

   • Fatigue, headache, musculoskeletal pain, and increased risk of infections.

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Contraindications and Precautions

1. Contraindications:

   • Sprycel is contraindicated in patients with known hypersensitivity to dasatinib or any of its components.

2. Precautions:

   • Hematologic Toxicity: Regular monitoring of blood counts is essential to detect and manage myelosuppression.

   • Fluid Retention: Patients should be monitored for signs of fluid retention, and dose adjustments or diuretics may be necessary.

   • Cardiac Toxicity: Sprycel can cause QT prolongation and cardiac dysfunction. Electrocardiograms (ECGs) and cardiac monitoring may be required.

   • Hepatic Impairment: Dose adjustments may be necessary for patients with liver dysfunction.

   • Pregnancy and Lactation: Sprycel is classified as a Category D drug in pregnancy, meaning it can cause fetal harm. It should be used only if the potential benefits outweigh the risks. Breastfeeding is not recommended during treatment.

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Drug Interactions

Dasatinib has a high potential for drug interactions due to its metabolism by CYP3A4 and its effects on drug transporters. Some notable interactions include:

1. CYP3A4 Inhibitors: Drugs like ketoconazole, itraconazole, and clarithromycin can increase dasatinib levels, increasing the risk of toxicity.

2. CYP3A4 Inducers: Drugs like rifampin, phenytoin, and carbamazepine can decrease dasatinib levels, reducing its efficacy.

3. Antacids and H2 Blockers: These can reduce the absorption of dasatinib. It is recommended to administer dasatinib at least 2 hours before or after these medications.

4. QT-Prolonging Drugs: Concomitant use with other QT-prolonging drugs (e.g., amiodarone, ciprofloxacin) may increase the risk of arrhythmias.

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Conclusion

Sprycel (dasatinib) is a highly effective targeted therapy for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Its ability to inhibit multiple tyrosine kinases, including BCR-ABL and SRC family kinases, makes it a valuable option for patients who are resistant or intolerant to other therapies. However, its use requires careful monitoring for side effects, particularly hematologic toxicity, fluid retention, and cardiac complications.

Patients should be educated about the importance of adherence to prescribed regimens and the need for regular follow-up. With proper use, Sprycel can significantly improve outcomes for patients with CML and Ph+ ALL, offering hope for long-term remission and improved quality of life.

Tablets of Sprycel. What is dasatinib? A drug called dasatinib is used to treat cancer, and it works by inhibiting the development and spread of cancer cells within the body. Dasatinib is effective in the treatment of Philadelphia chromosome-positive chronic myelogenous leukemia in both adults and children. This form of blood cancer can occur at any age (CML). Dasatinib is also utilized in the treatment of acute lymphoblastic leukemia (ALL) in both adults and children when the Philadelphia chromosome is present. Warnings A medicine called dasatinib is used to treat cancer, and it works by inhibiting the development and spread of cancer cells within the body. Dasatinib can reduce the number of blood cells that assist your body in warding off infections and in clotting your blood. You run the risk of getting an infection and will likely bleed more easily. Make an appointment with your primary care provider if you see any unusual bruising, bleeding, or indications of infection (fever, chills, body aches). Dasatinib use has been linked to the development of pulmonary arterial hypertension, a disease that is extremely uncommon but extremely dangerous (PAH). If treatment for PAH is delayed for an extended period of time, there is a chance that the condition will become irreversible. Have a discussion with your primary care physician about the likelihood of you acquiring PAH. Before beginning to use this medication Dasatinib use has been linked to the development of pulmonary arterial hypertension, a disease that is extremely uncommon but extremely dangerous (PAH). PAH is caused when there is a rise in blood pressure inside the arteries that are found in the lungs. Because of this, it is more difficult for your heart to pump blood through your lungs, which also has the effect of weakening the muscles in your heart. If treatment for PAH is delayed for an extended period of time, there is a chance that the condition will become irreversible. Have a discussion with your primary care physician about the likelihood of you acquiring PAH. If you have ever experienced any of the following, you should let your doctor know so that dasatinib can be prescribed to you with confidence: a compromised immune system (which can be brought on by illness or by taking certain medications); gastrointestinal or intestinal hemorrhaging; illness of the liver; coronary artery disease; a potassium or magnesium deficiency, as measured by your blood levels; long QT syndrome (whether you have it or a member of your family does); lung disease; or lactose intolerance. Dasatinib may damage an unborn infant. While you are taking dasatinib and for at least 30 days following your last dosage, you should use an effective method of birth control to prevent becoming pregnant. If you get pregnant, you should contact your physician as soon as possible. Both men and women are at risk of experiencing decreased fertility (inability to have children) if they take dasatinib. Dasatinib might be harmful to the fetus if it is used during pregnancy; thus, it is essential to take birth control to avoid becoming pregnant in the first place. When you are taking dasatinib and for at least two weeks following your final dosage, you should avoid breastfeeding your child. What is the correct way to take dasatinib? Dasatinib should be taken in the manner specified by your physician. Read all of the medication guides or instruction papers that come with your medicine, and make sure to follow all of the guidelines that are included on the prescription label. Your physician may decide to adjust your dosage every so often. Dasatinib can be taken with or without food according on your preference. Always remember to take your medication at the same time each day. Do not crush, chew, or break the pill; it should be swallowed in its whole. Do not take a medication that has been shattered because it was dropped accidently. If the medication from a tablet that has been crushed or broken goes into your eyes, mouth, or nose, or if it gets on your skin, it can be extremely harmful. In the event that this does place, you should either cleanse your skin with some soap and water or rinse your eyes with some water. When handling a pill or capsule that has been shattered, always use gloves made of rubber. Ask your healthcare provider or pharmacist how to dispose of the broken pill in a secure manner. It is not safe for a pregnant woman to handle a pill that has been broken. Dasatinib can reduce the number of blood cells that assist your body in warding off infections and in clotting your blood. There will likely be frequent tests done on your blood. The outcomes of these tests might cause a delay in the administration of cancer therapy to the patient. Dasatinib should not have its dose adjusted or its use discontinued without first seeing your physician. Keep at room temperature and away from heat and moisture when storing. While I am on dasatinib, what should I try not to do? Dasatinib may cause undesirable side effects in patients if grapefruit and grapefruit juice are taken at the same time. When you are on this medication, you should stay away from anything that contains grapefruit. Dasatinib should not be used with an antacid within two hours before or after taking the medication. It's possible that using certain antacids will make it more difficult for your body to absorb dasatinib. Steer clear of ill persons and anyone who could be carrying diseases. If you see any symptoms of infection, you should contact your physician as soon as possible. Dasatinib side effects You should seek immediate medical attention if you have symptoms of an allergic response to dasatinib, such as hives, difficulty breathing, or swelling in the face or throat. Also get assistance if you experience a severe skin reaction (fever, sore throat, burning in your eyes, skin pain, red or purple skin rash that spreads and causes blistering and peeling). Make an appointment with your primary care provider as soon as you can if you see any of the following signs of pulmonary arterial hypertension (PAH): discomfort in the chest, feelings of fatigue or shortness of breath (even with very light activity); you may have swelling in your feet, lower legs, or abdomen; a skin tone and lip color resembling blue; and a sensation of being light-headed and on the verge of passing out. In addition, contact your physician without delay if you have: persistent and severe nausea and vomiting as well as diarrhea; headaches of a severe kind, acute weariness, discomfort in the muscles or joints; a painful sensation when you breathe and shortness of breath, particularly when you lie down; edema, fast weight gain; discomfort in the chest, rapid heartbeats, or a feeling of fluttering in the chest; a propensity to bruise easily, unusual bleeding (from the nose, mouth, vagina, or rectum), tiny areas of purple or red beneath the skin; Other symptoms of internal bleeding include blood in the urine, bloody or tarry stools, spitting up blood or vomit that looks like coffee grounds, disorientation, headaches, and difficulties communicating; signs of low blood cell counts, including fever, chills, fatigue, symptoms similar to the flu, mouth sores, skin sores, pale complexion, chilly hands and feet, feeling lightheaded; or alternatively, Cramps in the muscles, nausea, vomiting, weakness, swelling, feeling short of breath, or seizures are all indicators that tumor cells are breaking down. There is a possibility that dasatinib will stunt children's growth. Talk to your child's physician if you see that they are not growing at a typical rate while they are on this medication. The following are examples of common dasatinib adverse effects that may occur: vomiting, diarrhoea, and abdominal discomfort; aches and pains in your head, shoulders, legs, hands, and foot; issues with breathing; skin rash; or feeling exhausted. What other medications could have an impact on dasatinib? It is possible that using certain drugs at the same time might have adverse effects. Some medications have the potential to alter the blood levels of other medications that you take, which may result in an increase in adverse effects or a reduction in the efficacy of the prescriptions. Dasatinib may raise your risk of bleeding that is severe or even deadly, particularly if you are also taking a blood thinner or any other prescription that prevents blood clots from forming. There are several medicines that have the potential to interact with dasatinib, and certain drugs should not be used at the same time as dasatinib. Talk to your primary care physician about any and all medications you are currently taking, as well as any medications you decide to start or stop taking. This include both prescription and over-the-counter medications, in addition to herbal and vitamin supplements. This does not include all of the conceivable combinations of factors.