Ponatinib Dosage

Medically reviewed by Drugs.com. Last updated on Apr 12, 2021.

Usual Adult Dose for Chronic Myelogenous Leukemia

Chronic phase chronic myeloid leukemia (CP-CML):
-Initial Dose: 45 mg orally once a day
-Upon achievement of 1% BCR-ABL1 or less (standardized according to International Scale): 15 mg orally once a day
-For loss of response: Re-escalate to a previously tolerated dosage of 30 mg or 45 mg orally once a day

Accelerated phase chronic myeloid leukemia (AP-CML), blast phase chronic myeloid leukemia (BP-CML) or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL):
-Initial dose: 45 mg orally once a day

Comments:
-The optimal dose has not been identified for AP-CML, BP-CML, and Ph+ ALL.
-Consider dose reduction for AP-CML patients who have achieved major cytogenic response.
-Continue treatment until loss of response or unacceptable toxicity.
-Drug discontinuation should be considered if patient response has not occurred by 3 months (90 days).
-This drug is not indicated and is not recommended for the treatment of patients with newly diagnosed chronic phase chronic myeloid leukemia (CP-CML).

Uses:
-For the treatment of adult patients with CP-CML with resistance or intolerance to at least two prior kinase inhibitors
-For the treatment of adult patients with AP-CML, or BP-CML or Ph+ ALL for whom no other kinase inhibitors are indicated
-For the treatment of adult patients with T315I-positive CML (chronic phase, accelerated phase, or blast phase) or T315I-positive Ph+ ALL

Usual Adult Dose for Acute Lymphoblastic Leukemia

Chronic phase chronic myeloid leukemia (CP-CML):
-Initial Dose: 45 mg orally once a day
-Upon achievement of 1% BCR-ABL1 or less (standardized according to International Scale): 15 mg orally once a day
-For loss of response: Re-escalate to a previously tolerated dosage of 30 mg or 45 mg orally once a day

Accelerated phase chronic myeloid leukemia (AP-CML), blast phase chronic myeloid leukemia (BP-CML) or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL):
-Initial dose: 45 mg orally once a day

Comments:
-The optimal dose has not been identified for AP-CML, BP-CML, and Ph+ ALL.
-Consider dose reduction for AP-CML patients who have achieved major cytogenic response.
-Continue treatment until loss of response or unacceptable toxicity.
-Drug discontinuation should be considered if patient response has not occurred by 3 months (90 days).
-This drug is not indicated and is not recommended for the treatment of patients with newly diagnosed chronic phase chronic myeloid leukemia (CP-CML).

Uses:
-For the treatment of adult patients with CP-CML with resistance or intolerance to at least two prior kinase inhibitors
-For the treatment of adult patients with AP-CML, or BP-CML or Ph+ ALL for whom no other kinase inhibitors are indicated
-For the treatment of adult patients with T315I-positive CML (chronic phase, accelerated phase, or blast phase) or T315I-positive Ph+ ALL

Renal Dose Adjustments

Data not available.

Liver Dose Adjustments

ANY LEVEL OF LIVER DYSFUNCTION (CHILD-PUGH A, B, OR C):
-Reduce the initial dose to 30 mg once a day in patients with preexisting liver dysfunction (Child-Pugh A, B, or C) and monitor for adverse reactions.
-The safety of multiple doses, or doses higher than 30 mg have not been studied in patients with hepatic impairment.

IF HEPATOTOXICITY DEVELOPS DURING TREATMENT:
Elevation of liver transaminase greater than 3 times the upper limit of normal (ULN) and if:
-Occurrence at 45 mg: Interrupt dosing and monitor hepatic function; and resume treatment at 30 mg after recovery to Grade 1 or less (less than 3 x ULN)
-AST or ALT at least 3 times ULN with an elevation of bilirubin greater than 2 times ULN and alkaline phosphatase less than 2 times ULN: Discontinue treatment

Dose Adjustments

-Patients with chronic phase myeloid leukemia who have achieved a 1% BCR-ABL1 or less (standardized according to International Scale) or patients with accelerated phase chronic myeloid leukemia who achieve a major cytogenetic response: Consider reducing the dose
-If response to treatment has not occurred by 3 months: Consider treatment discontinuation

DOSAGE MODIFICATION FOR COADMINISTRATION OF STRONG CYP450 3A INHIBITORS/INDUCERS:
-Concomitant use of strong CYP450 3A inducer: Avoid unless the benefit outweighs the risk and monitor for reduced efficacy; select a concomitant medication with no or minimal CYP450 3A induction potential if possible
-Concomitant use of strong CYP450 3A inhibitors:
-If current dose 45 mg once a day: Reduce dose to 30 mg once a day
-If current dose 30 mg once a day: Reduce dose to 15 mg once a day
-If current dose is 15 mg once a day: Reduce dose to 10 mg once a day
-If current dose is 10 mg once a day: Avoid use
-Resume the dosage that was tolerated prior to initiating the strong CYP450 3A inhibitor after the strong CYP450 3A inhibitor has been discontinued for 3 to 5 elimination half-lives.

RECOMMENDED DOSE REDUCTION FOR ADVERSE REACTIONS:
-First Reduction: 30 mg orally once a day for CP-CML, AP-CML, BP-CML, and Ph+ ALL
-Second Reduction: 15 mg orally once a day for CP-CML, AP-CML, BP-CML, and Ph+ ALL
-Third reduction: 10 mg orally once a day for CP-CML and permanently discontinue for AP-CML, BP-CML, and Ph+ ALL patients unable to tolerate the second dose reduction
-Subsequent reduction: Permanently discontinue treatment for CP-CML, AP-CML, BP-CML, and Ph+ ALL

HEPATOTOXICITY:
Elevation of liver transaminase greater than 3 times the upper limit of normal (ULN) and if:
-Occurrence at 45 mg: Interrupt dosing and monitor hepatic function; and resume treatment at 30 mg after recovery to Grade 1 or less (less than 3 x ULN)
-AST or ALT at least 3 times ULN with an elevation of bilirubin greater than 2 times ULN and alkaline phosphatase less than 2 times ULN: Discontinue treatment

ELEVATED LIPASE/PANCREATITIS:
-Serum lipase greater than 1 to 1.5 x ULN: Consider treatment interruption until resolution and then resume at same dose
-Serum lipase greater than 1.5 to 2 times ULN, 2 to 5 times ULN and asymptomatic, or asymptomatic radiologic pancreatitis: Interrupt until Grade 0 or 1 (less than 1.5 times ULN) and then resume at next lower dose
-Serum lipase greater than 2 to 5 times ULN and symptomatic, symptomatic Grade 3 pancreatitis, or serum lipase greater than 5 times ULN and asymptomatic: Interrupt until complete resolution of symptoms and after recovery of lipase elevation Grade 0 or 1, then resume at next lower dose
-Symptomatic pancreatitis and serum lipase greater than 5 times ULN: Discontinue treatment

MYELOSUPPRESSION:
-ANC less than 1 x 10(9)/L or platelets less than 50 x 10(9)/L and if:
-First Occurrence: Interrupt treatment and resume at same dose after recovery to ANC 1.5 x 10(9)/L or greater and platelets 75 x 10(9)/L or greater
-Recurrence: Interrupt treatment until resolution and then resume at next lower dose

ARTERIAL OCCLUSIVE EVENTS:
Cardiovascular or Cerebrovascular:
-Grade 1: Interrupt treatment until resolved, then resume at same dose
-Grade 2: Interrupt treatment until Grade 0 or 1, then resume at next lower dose and discontinue if recurrence
-Grade 3 or 4: Discontinue treatment

Peripheral vascular and other or venous thromboembolic events:
-Grade 1: Interrupt treatment until resolved, resume at same dose
-Grade 2: Interrupt treatment until Grade 0 or 1, then resume at same dose and if recurrence, interrupt treatment until Grade 0 or 1, then resume at next lower dose
-Grade 3: Interrupt treatment until Grade 0 or 1, then resume at next lower dose and discontinue if recurrence
-Grade 4: Discontinue treatment

HEART FAILURE:
-Grade 2 or 3: Interrupt treatment until Grade 0 or 1, then resume at next lower dose and discontinue if recurrence
-Grade 4: Discontinue treatment

OTHER NON-HEMATOLOGIC ADVERSE REACTIONS:
-Grade 1: Interrupt treatment until resolved, then resume at same dose
-Grade 2: Interrupt treatment until Grade 0 or 1, then resume at same dose, and if recurrence, interrupt until Grade 0 or 1, then resume at next lower dose
-Grade 3 or 4: Interrupt treatment until Grade 0 or 1, then resume at next lower dose and discontinue if recurrence

Precautions

US BOXED WARNING:
ARTERIAL OCCLUSION, VENOUS THROMBOEMBOLISM, HEART FAILURE, AND HEPATOTOXICITY:
-Arterial occlusions, venous thromboembolism, heart failure, and hepatotoxicity/liver failure have occurred.
-There were fatalities among the reported arterial occlusion, heart failure, and hepatotoxic cases.
-Monitor for heart failure, hepatic function, and for evidence of arterial occlusion and venous thromboembolism.
-Dose modification, interruption, or discontinuation of treatment should be considered.
-A benefit-risk consideration should guide a decision to restart therapy.

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available.

Other Comments

Administration Advice:
-This drug may be taken with or without food, and at the same approximate time each day.
-Swallow tablets whole; do not crush, break, cut, chew, or dissolve the tablets.
-If a dose is missed, take the next dose at the regularly scheduled time the next day.
-Do not take 2 doses at the same time to make up for a missed dose.
-This drug contains lactose monohydrate, care and close monitoring is recommended for intolerant patients.

Storage Requirements:
-Store at 68F to 77F (20C to 25C)
-Excursion permitted to 59F to 86F (15C to 30C)

Monitoring:
-Monitor for evidence of arterial occlusive events and venous thromboembolic events.
-Monitor for heart failure.
-Monitor liver function tests at baseline, then at least monthly or as clinically indicated.
-Monitor blood pressure at baseline and as clinically in indicated.
-Monitor serum lipase every 2 weeks for the first 2 months and then monthly thereafter or as clinically indicated.
-Monitor for symptoms of peripheral and cranial neuropathy.
-Monitor for vision at baseline and periodically during treatment.
-Monitor for hemorrhage.
-Monitor for fluid retention.
-Monitor for signs and symptoms of arrhythmias.
-Monitor blood counts every 2 weeks for the first 3 months and then monthly or as indicated for myelosuppression.

Patient Advice:
-Advise the patient to read the approved patient labeling (Medication Guide).
-Advise females of the potential risk to a fetus and inform their healthcare provider of a known or suspected pregnancy.
-Advice females of reproductive potential to use effective contraception during treatment and for at least 3 weeks after the last dose.
-Advise females of the potential for reduced fertility.
-Advise not to breastfeed during treatment and for 6 days after the last dose.
-Advise patients to inform of any planned surgical procedure.
-Advise patients to immediately report any symptoms suggestive of a blood clot such as chest pain, shortness of breath, weakness on one side of the body, speech problems, leg pain, or leg swelling.
-Advise patients to report any signs and symptoms suggestive of hemorrhage such as unusual bleeding or easy bruising.
-Advise patients to report symptoms suggestive of heart complications such as chest pain, shortness of breath, hypertension, palpitations, dizziness, or fainting.
-Advise patients to report any symptoms suggestive of pancreatitis such as nausea, vomiting, abdominal pain, or abdominal discomfort.
-Advise patients to report any developing fluid retention such as leg swelling, abdominal swelling, weight gain, or shortness of breath.
-Advice patients to report fever, infection, headache, seizure, altered mental status, and neurological disturbances.
-Advise patients to report symptoms of liver problems such as jaundice, anorexia, bleeding or bruising.
-Advise patients to avoid drinking grapefruit juice or eating grapefruit during treatment.
-Inform patients that the tablets contain lactose monohydrate.
-Advise patients to report symptoms of neuropathy such as hypo- and hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness.
-Advise patients to report symptoms of ocular toxicity such as blurred vision, dry eye, or eye pain.

Further information

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