regimen-monograph

PNAT

Cancer Type

Hematologic, Leukemia - Chronic Myeloid (CML)

Intent

Palliative

Regimen Category

Evidence-Informed

Funding Program

Exceptional Access Program

Drugs Used

ponatinib

A - Regimen Name

PNAT Regimen

Ponatinib

Disease Site

Hematologic

Leukemia - Chronic Myeloid (CML)

Intent

Palliative

Regimen Category

Evidence-Informed :

Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR). Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.

Rationale and Uses

For the treatment of patients with Philadelphia chromosome positive (Ph+) chronic phase (CP), accelerated phase (AP) or blast phase (BP) chronic myeloid leukemia (CML), with documented T315i mutation, or where there is resistance, disease progression, or intolerance to at least 2 prior tyrosine kinase inhibitors.

(Refer to EAP criteria.)

Supplementary Public Funding

ponatinib
Exceptional Access Program (ponatinib - For the treatment of Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia, according to specific criteria) (EAP Website)

B - Drug Regimen

ponatinib

45 mg

Daily

Consider reducing ponatinib dose for patients with CP-CML (from 45 mg to 15 mg daily) upon achieving molecular response (≤ 1% BCR-ABL1^IS). Patients with loss of response can re-escalate to a previously tolerated dose of 30 mg or 45 mg daily

Consider reducing ponatinib dose for patients with AP-CML who have achieved a MCyR (major cytogenetic response).

C - Cycle Frequency

CONTINUOUS TREATMENT

Until disease progression or unacceptable toxicity.

Consider discontinuation if a hematologic response has not been achieved by 3 months.

D - Premedication and Supportive Measures

Antiemetic Regimen:

Minimal – No routine prophylaxis; PRN recommended

Also refer to CCO Antiemetic Recommendations.

Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.

Ensure adequate hydration and correct hyperuricemia before starting ponatinib.
Patients' cardiovascular status should be assessed and risk factors managed prior to starting treatment and monitored during treatment.

E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated.

Consider temporary hold of ponatinib prior to undergoing major surgery.

Dosage with toxicity

Dose Level	Ponatinib Dose (mg/day)
0	45
-1	30
-2	15
-3	Discontinue

Toxicity	Severity	Action/Ponatinib Dose
Myelosuppression	ANC < 1 x 10⁹/L or platelets < 50 x 10⁹/L (unrelated to disease)	Hold* until recovery, restart at the same dose. If recurs, hold* until recovery, restart at ↓ 1 dose level from previous dose.
Hemorrhage	Grade 3 or 4	Hold and investigate. Consider the risk vs. benefit of restarting.
LFTs	AST or ALT > 3 x ULN	Hold until recovery to ≤ grade 1, restart at ↓ 1 dose level from previous dose.
LFTs	AST or ALT ≥ 3 x ULN AND total bilirubin > 2 x ULN AND ALP < 2 x ULN	Discontinue.
Pancreatitis and elevation of amylase / lipase	Asymptomatic grade 2 pancreatitis and/or amylase/lipase > 1.5 to 2 x ULN, or >2 to 5 x ULN and asymptomatic	Consider hold until resolution then restart at same dose level.
	Amylase/lipase > 5 x ULN and asymptomatic	Hold until amylase/lipase ≤ 1.5 x ULN, then restart at ↓ 1 dose level from previous dose.
	Grade 3 pancreatitis or amylase/lipase > 2 to 5 x ULN and symptomatic	Hold until resolution of symptoms and recovery of amylase/lipase to ≤ 1.5 x ULN, then restart at ↓ 1 dose level from previous dose.
	Grade 4 pancreatitis or amylase/lipase > 5 x ULN and symptomatic	Discontinue.
Hypertriglyceridemia	Grade 3 or 4	Manage patient appropriately to reduce pancreatitis risk.
Arterial Occlusive Events (AOE): cardiovascular or cerebrovascular	Grade 1	Hold until resolution, then restart at same dose level.
	Grade 2	Hold until ≤ grade 1, then restart by ↓ 1 dose level from previous dose. Discontinue at recurrence.
	Grade 3 or 4	Discontinue.
AOE: peripheral or other or VTE	Grade 1	Hold until resolution, then restart at same dose level.
	Grade 2	Hold until ≤ grade 1, then restart at same dose level. If recurrence, hold until ≤ grade 1, then restart by ↓ 1 dose level from previous dose.
	Grade 3	Hold until ≤ grade 1, then restart by ↓ 1 dose level from previous dose. Discontinue at recurrence.
	Grade 4	Discontinue.
Heart failure	Grade 2 or 3	Hold until ≤ grade 1, then restart by ↓ 1 dose level from previous dose. Discontinue at recurrence.
Heart failure	Grade 4	Discontinue.
Hypertension	Any	Treat to normalize blood pressure. Hold, reduce dose, or discontinue (as clinically indicated) if not medically controlled, and evaluate for renal artery stenosis.
Fluid retention	Any	Hold, reduce or discontinue ponatinib as clinically indicated.
PRES	Any	Hold if suspected. Discontinue if confirmed. or Restart if resolved and only if benefits outweigh risks.
Other non-hematologic toxicity	Grade 2	Hold until ≤ grade 1, then restart at same dose level. If recurrence, hold until ≤ grade 1, then restart by ↓ 1 dose level from previous dose.
Other non-hematologic toxicity	Grade 3 or 4	Hold until recovery. Restart at ↓ 1 dose level from previous dose. If grade 4, consider discontinuation. Discontinue at recurrence.
*Restart once ANC ≥ 1.5 x 10⁹/L and platelets ≥ 75 x 10⁹/L.

Hepatic Impairment

The recommended starting dose is 30 mg once daily in patients with hepatic impairment (Child-Pugh classes A, B or C); use caution in these patients. There was an increase in adverse effects in patients with severe hepatic impairment. The safety of multiple ponatinib doses, or doses > 30 mg, has not been studied in patients with hepatic impairment.

Renal Impairment

Renal excretion is not a major route of elimination. There are no specific recommendations for dosage adjustment. Ponatinib has not been studied in patients with CrCl < 30 mL/min or end-stage renal disease; exercise caution if ponatinib is administered to these patients.

Dosage in the Elderly

Patients aged 65 and older (with chronic phase CML) are more likely to experience adverse effects and reduced efficacy compared to younger patients. Patients ≥ 65 years of age are more likely to experience adverse effects including vascular occlusion, decreased platelet count, peripheral edema, increased lipase, dyspnea, asthenia, muscle spasms, and decreased appetite.

F - Adverse Effects

Refer to ponatinib drug monograph(s) for additional details of adverse effects.

Common (25-49%)

Less common (10-24%)

Uncommon (< 10%),

but may be severe or life-threatening

Rash (may be severe)
Myelosuppression ± infection, bleeding (may be severe)
Fluid retention (including effusions)
Eye disorders (may be severe including retinal vascular disorders)
Abdominal pain
↑ Amylase / lipase (may be severe)
Headache

Hypertension (may be severe)
Constipation
Fatigue
Peripheral neuropathy
Musculoskeletal pain
Nausea, vomiting
↑ LFTs (may be severe)
Arterial thromboembolism (may be severe)

Cardiotoxicity
Arrhythmia
Venous thromboembolism
Diarrhea
Artery aneurysm / dissection
Peripheral ischemia
Tumour lysis syndrome
GI perforation
Pancreatitis
Atypical infections (including HBV reactivation)
Pulmonary hypertension
PRES
Cranial neuropathy

G - Interactions

Refer to ponatinib drug monograph(s) for additional details.

Avoid strong CYP3A4 inhibitors. Reduce ponatinib dose if given concomitantly with strong CYP3A4 inhibitors. Refer to "Ponatinib Dosage with Strong CYP3A4 Inhibitors" table below.
Avoid strong CYP3A4 inducers if possible. Caution and monitor for reduced ponatinib efficacy if used together.

Ponatinib Dosage with Strong CYP3A4 Inhibitors

Current Ponatinib Dose (mg daily)	Ponatinib Dose^† (mg daily) with a Strong CYP3A4 Inhibitor
45	30
30	15
15	Discontinue

^†Resume previous dose after the inhibitor has been discontinued for 3 to 5 elimination half-lives.

H - Drug Administration and Special Precautions

Refer to ponatinib drug monograph(s) for additional details.

Administration:

Ponatinib should be swallowed whole with or without food.
Tablets should not be crushed, chewed or dissolved.
Grapefruit, starfruit, pomegranate, Seville oranges, their juices or products should be avoided during ponatinib treatment.
If a dose is missed, an additional dose should not be taken. Patients should take the next dose at the usual time.
Store at room temperature (15^oC to 30^oC) in the original package.

Contraindications:

Patients who have a hypersensitivity to this drug or any of its components
Patients who have uncontrolled hypertension or other unmanaged cardiac risk factors
Patients with dehydration or untreated hyperuricemia

Warnings/Precautions:

Ponatinib should not be used in patients with a history of myocardial infarction, prior revascularization or stroke, unless the potential benefit outweighs the risk.
Use with caution and consider benefits vs risks in patients with a prior history of ischemia, hypertension, congestive heart failure or conditions that may impair left ventricular function, diabetes or hyperlipidemia.
Use with caution in patients at risk of bleeding, those receiving antiplatelets and/or anticoagulants.
Use with caution in patients with a history of pancreatitis or alcohol abuse.
Contains lactose; patients with hereditary galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption should not take ponatinib.
Use caution when driving or operating a vehicle or potentially dangerous machinery as dizziness, mental status changes and vision problems have been reported.

Pregnancy/Lactation:

This regimen is not recommended for use in pregnancy. Adequate contraception should be used by patients and their partners while on treatment and after the last treatment dose. Recommended methods and duration of contraception may differ depending on the treatment. Refer to the drug monograph(s) for more information.
It is unknown whether ponatinib affects the effectiveness of oral contraceptives. An alternative or additional method of contraception should be used.
Breastfeeding is not recommended during treatment and after the last treatment dose. Refer to the drug monograph(s) for recommendations after the last treatment dose (if available).
Effects on fertility: Documented in studies with female animals.

I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.

Recommended Clinical Monitoring

Blood pressure; Baseline and as clinically indicated; ensure hypertension is controlled to minimize risk of arterial thromboembolism
CBC; Baseline, every 2 weeks for the first 3 months, and then monthly or as clinically indicated
Liver function tests; Baseline, at least monthly or as clinically indicated
Lipase, amylase; Baseline, every 2 weeks for the first 2 months, and then periodically or as clinically indicated
LVEF; Baseline, 3 months after treatment initiation, and as clinically indicated
Calcium, phosphate; Baseline and as clinically indicated
Eye exam and fundoscopy; Baseline, with blurred vision and as clinically indicated
Clinical toxicity assessment for bleeding, infection, arterial or venous thromboembolism, fluid retention (including regular weight monitoring), hypertension, cardiac and GI effects, tumour lysis syndrome, ocular, wound healing, and neurologic effects; Baseline and at each visit
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

J - Administrative Information

Outpatient prescription for home administration

K - References

Cortes JE, Kim DW, Pinilla-Ibarz J, et al. Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. Blood 2018;132(4):393-404.

Cortes JE, Kim DW, Pinilla-Ibarz J, et al; PACE Investigators. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 2013 Nov 7;369(19):1783-96.

Ponatinib drug monograph, Ontario Health (Cancer Care Ontario).

June 2026 Updated Supportive Care, Dose Modifications, Adverse Effects, Interactions, Administration/Special precautions, and Monitoring sections

M - Disclaimer

Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph. Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
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Last Updated: July 21, 2026

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