Tasigna 150mg capsules are described as an orally bioavailable aminopyrimidine derivative which is contains as Bcr-Abl tyrosine kinase prohibitor containing anti-tumor activity. To overwhelmed Imatinib resistance, nilotinib which is an active substance of Tasigna 150mg capsules binds to and balance the inactive configuration of kinase domain of Abl protein of Bcr-Abl merging protein, concluding as prohibition of multiplication of Philadelphia chromosome positive advanced myeloid leukemia which is mediated by Bcr-Abl.
Tasigna 150mg prescribed for
The prescribing information of Tasigna 150mg capsules for both pediatric and adult patients is given as follows;
Patients with newly diagnosed Philadelphia chromosome positive CML-CP; patients suffered with resistance or intolerance Philadelphia positive CML-CP & CML-AP mainly in adults; & patients with resistance or intolerance Philadelphia positive CML-CP majorly in pediatric patients.
For all these conditions, Tasigna 150mg capsules are indicated for both adults and pediatric with the age of greater than or equal to 1 year. Tasigna is used only after resistance occurred with prior tyrosine kinase inhibitor therapy.
Mechanism of Tasigna
Tasigna containing Nilotinib is pharmacologically classified as Bcr-Abl tyrosine kinase inhibitor.
Tasigna is used to overthrow the Imatinib resistance in advanced myelogenous leukemia condition.
Nilotinib is involved in the inhibition of Bcr-Abl interceded multiplication of murine leukemia cells lines and human cell lines obtained from patients with Philadelphia positive CML.
The mean bioavailability of Nilotinib is reaches as 50% after drug intake. The maximum plasma concentration time of Nilotinib reaches within 3 hours after oral administration.
Nilotinibis highly bound to the human plasma protein with the range of 98%.
The metabolism of Tasigna 150mg is mediated by CYP3A4 with minor extent by CYP2C8. Nilotinib is the vital component circulating majorly in the blood stream; no metabolites are contributing in pharmacological action.
After single dose of Tasigna, the excretion is occurring within 7 days of administration with more than 90% range; 93% in feces. Half-life period: 17 hours at 69% Creatinine clearance: 29L/hr.
Dosage and administration of Tasigna
For newly commenced ph+ CML-CP:
The prescribed dose of Tasigna is 300mg should be administered orally as two times a day.
For resistance or intolerance ph.+ CML-CP or CML-AP:
The prescribed dose of Tasigna is 400mg should be administered as orally as two times day.
For newly commenced or resistance ph+ CML-CP:
The prescribed dose of Tasigna for pediatrics is, 230mg/m2 should be administered orally as two times a day around 50mg dose and maximum dose should be 400mg single dose.
Depending on body surface area the dose should be considered;
Up to 0.32m2: 50mg for single dose; 100mg for total daily dose
0.33 to 0.54m2: 100mg for single dose; 200mg for total daily dose
0.55 to 0.76m2: 150mg for single dose; 300mg for daily dose
0.77 to 0.97m2: 200mg as single dose; 400mg as total daily dose
0.98 to 1.19m2: 250mg as single dose; 500mg as total daily dose
1.20 to 1.41m2: 300mg as a single dose; 600mg as total daily dose
1.42 to 1.63m2: 350mg as single dose; 700mg as total dose
> Or equal to 1.64m2: 400mg as a single dose; 800mg as total daily dose.
Interrupt or discontinue the therapy in the patients who are having hematological toxicities. Patient with increased serum amylase or lipase, bilirubin, AST; the therapy should be interrupt and monitor the levels. Continue the therapy with 400mg of Tasigna as single dose. In pediatric the dose should be 230mg/m2 as a single dose.
In liver damage patients:
Newly commenced ph+ CML in advanced phase; mild to moderate or severe: The dose of Tasigna reduced to 200mg as two times a day, elevates the dose as 300mg for two times a day.
In resistance CML ph+ in either accelerated or chronic phase:
For mild, moderate: The reduced dose is 300mg as two times a day; resume to increase as 400mg as two times a day. For severe: Reduced to 200mg as twice daily, increased to 300mg as twice daily and then resume at 400mg two times a day. For concurrent use of Tasigna with strong CYP3A4 inhibitors: The dose of Tasigna reduced to 300mg as a single dose in patients with intolerant ph+ CML or 200mg of Tasigna capsules as a single dose in patients with newly raised ph+ CML-CP. Patient is necessary to need strong CYP3A4 inhibitors, must be investigated by monitoring QT intervals frequently. Tasigna capsules should be administered on an empty stomach. Food should not be taken for at least 2 hours earlier the dose and for at least 1 hour after the dose.
Tasigna side effects
The serious adverse reactions like; Myelosuppression, QT extension, Sudden death, Arterial vascular occlusive events, Pancreatitis, Increasing serum lipase, Hepatotoxicity, Abnormal in electrolytes, Hemorrhage, Fluid retention
The most common side effects
Rash, Pruritus, Alopecia, Dry skin, Nausea, vomiting, Constipation or diarrhea, Abdominal pain, dyspepsia, Headache, dizziness, Fatigue, Myalgia, Arthralgia, Muscle spasms, Back pain, Cough, Oropharyngeal pain, Dyspnea, Nasopharyngitis, Respiratory tract infection, Flu like syndromes, Gastroenteritis, Eyelid edema, Insomnia, Hypertension this are the most common tasigna side effects.
To overcome this problem, patient may monitor frequently by testing blood counts before or after the therapy.
Monitor ECG frequently Avoid concomitant use of Tasigna 150mg with anti-arrhythmia agents Provide supportive measures
In patients with CML may leads to sudden mortality. Tasigna 150mg is produce ventricular repolarization which may contributed for sudden death
Pancreatitis & increased lipase
Patient with pancreatitis may have increase in serum lipase levels, this may cause abdominal symptoms and to reduce the problems, treatment should be postponed & undergone with appropriate diagnostics Test serum lipase value periodically.
Increased bilirubin, AST, ALT leads to liver injury. To avoid this condition, patient should be monitor with hepatic function test.
This may contraindicate to Tasigna 150mg treatment. Electrolytes should be in balanced state.
Tumor lysis syndrome
Maintain with sufficient hydration Maintain the uric acid level before starting the treatment
Reduce the dose of Tasigna Provide alternative treatment Reduce the exposure of Tasigna
Embryo fetal damage
Tasigna 150mg causes fetal damage while using this in pregnancy or lactation period. Investigate the patients properly who are discontinue the Tasigna 150mg therapy, the range of Bcr-Abl transcripts level.