Drug reference

Ponatinib

BNF 80 (2020–2021)

Source: BNF 80 (2020–2021)
PDF pages: 1074, 1075

Review source pages for extracted sections and age labels. BNF dose snippets show only their first line.

Overview

Indications And Dose

Treatment of chronic, accelerated, or blast phase chronic myeloid leukaemia in patients who have the T315I mutation or who have resistance to or intolerance of dasatinib or nilotinib, and for whom subsequent treatment with imatinib is not clinically appropriate | Treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia in patients who have the T315I mutation or who have resistance to or intolerance of dasatinib, and for whom subsequent treatment with imatinib is not clinically appropriate ▶BY MOUTH ▶Adult: 45 mg once daily, for dose adjustments due to side-effects or dose reduction due to risk of vascular occlusive events, consult product literature

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Dose Adjustments

DUE TO INTERACTIONS ▶Manufacturer advises consider a reduced initial dose of 30 mg daily with concurrent use of potent inhibitors of CYP3A4.

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Cautions

Alcohol abuse—increased risk of pancreatitis. current severe hypertriglyceridaemia—increased risk of pancreatitis. discontinue treatment if a complete haematologic response has not occurred within 3 months. hepatitis B infection. history of myocardial infarction—do not use unless potential beneﬁt outweighs potential risk. history of pancreatitis. history of stroke—do not use unless potential beneﬁt outweighs potential risk. hypertension—medically control during treatment and interrupt treatment if uncontrolled CAUTIONS, FURTHER INFORMATION ▶Cardiovascular status Assess cardiovascular status before treatment—manage cardiovascular risk factors before and during treatment. ▶Hepatitis B infection The MHRA advises that patients who are carriers of hepatitis B virus should be closely monitored for signs and symptoms of active infection throughout treatment and for several months after stopping treatment; expert advice should be sought for patients who test positive for hepatitis B virus and in those with active infection.

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National Funding Access Decisions

NICE decisions ▶Ponatinib for treating chronic myeloid leukaemia and acute lymphoblastic leukaemia (June 2017) NICE TA451 Ponatinib is recommended, within its marketing authorisation, as an option for treating chronic-, accelerated- or blast-phase chronic myeloid leukaemia in adults when: . the disease is resistant to dasatinib or nilotinib or . they cannot tolerate dasatinib or nilotinib and for whom subsequent treatment with imatinib is not clinically appropriate or . the T315I gene mutation is present. Ponatinib is recommended, within its marketing authorisation, as an option for treating Philadelphia- chromosome-positive acute lymphoblastic leukaemia in adults when: . the disease is resistant to dasatinib or . they cannot tolerate dasatinib and for whom subsequent treatment with imatinib is not clinically appropriate or . the T315I gene mutation is present. Ponatinib is recommended only if the company provides the drug with the discount agreed in the patient access scheme. www.nice.org.uk/guidance/ta451

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Safety

Important Safety Information

MHRA/CHM ADVICE: PONATINIB: RISK OF VASCULAR OCCLUSIVE EVENTS—UPDATED ADVICE ON POSSIBLE DOSE REDUCTION (UPDATED APRIL 2017) The beneﬁts and risks of ponatinib were reviewed by the European Medicines Agency’s Committee on Medicinal Products for Human Use in 2014, which recommended that strengthened warnings should be added to the product information aimed at minimising the risk of blood clots and blockages in the arteries. Additional long-term follow-up data are now available that supports new advice on dose modiﬁcation to reduce this risk. The MHRA advise that although the recommended starting dose of ponatinib remains unchanged, prescribers should consider reducing the dose for patients with chronic phase chronic myeloid leukaemia (CP-CML) who have achieved a major cytogenetic response while on treatment. The following factors should be taken into account in the individual patient assessment: . cardiovascular risk; . side-effects of ponatinib therapy (including cardiovascular and other dose-related toxicity); . time to cytogenetic response; . BCR-ABL transcript levels. The MHRA recommends close monitoring of response, if dose reduction is undertaken. MHRA/CHM ADVICE: RISK OF HEPATITIS B VIRUS REACTIVATION WITH BCR-ABL TYROSINE KINASE INHIBITORS (MAY 2016) An EU wide review has concluded that ponatinib can cause hepatitis B reactivation; the MHRA recommends establishing hepatitis B virus status in all patients before initiation of treatment. MHRA/CHM ADVICE: PONATINIB (ICLUSIG ®): REPORTS OF POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (OCTOBER 2018) Post-marketing cases of posterior reversible encephalopathy syndrome (PRES) have been reported in patients receiving ponatinib. Treatment should be interrupted if PRES is conﬁrmed and resumed only once the event is resolved and if the beneﬁt of continued treatment outweighs the risk. Patients should be advised to contact their healthcare professional immediately if they develop sudden-onset severe headache, confusion, seizures, or vision changes. RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES See Cytotoxic drugs p. 938.

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Interactions

→Appendix 1: ponatinib

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Side Effects

▶Common or very common Acute coronary syndrome. alopecia. anaemia. appetite decreased. arrhythmias. arthralgia. asthenia. cerebrovascular insufﬁciency. chills. constipation. cough. diarrhoea. dizziness. dry eye. dry mouth. dysphonia. dyspnoea. electrolyte imbalance. embolism and thrombosis. erectile dysfunction. eye inﬂammation. febrile neutropenia. fever. ﬂuid imbalance . gastrointestinal discomfort. gastrooesophageal reﬂux disease. haemorrhage. headaches. heart failure. hyperglycaemia. hypertension. hypertriglyceridaemia. hyperuricaemia. hypothyroidism. increased risk of infection. inﬂuenza like illness. insomnia. ischaemic heart disease. lethargy. mass. muscle complaints. nausea . oedema. pain. pancreatitis. pancytopenia. pericardial effusion. peripheral neuropathy. peripheral vascular disease. pleural effusion. pulmonary hypertension. sensation abnormal. sepsis. skin reactions. stomatitis. sweat changes. vasodilation. vision disorders. vomiting. weight decreased ▶Uncommon Cardiac discomfort. cardiomyopathy ischaemic. coronary vasospasm. hepatic disorders. hepatic failure (including fatal cases). intracranial haemorrhage. left ventricular dysfunction. posterior reversible encephalopathy syndrome (PRES). renal artery stenosis. splenic infarction. tumour lysis syndrome

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Conception And Contraception

Ensure effective contraception during treatment in men and women; effectiveness of hormonal contraception unknown— alternative or additional methods of contraception should be used.

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Pregnancy

Avoid—toxicity in animal studies. See also Pregnancy and reproductive function in Cytotoxic drugs p. 938.

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Breast Feeding

Manufacturer advises discontinue breastfeeding—no information available.

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Hepatic Impairment

Manufacturer advises caution.

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Renal Impairment

No information available— manufacturer advises caution if creatinine clearance less than 50 mL/minute.

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Monitoring Requirements

▶Manufacturer advises monitor serum lipase every 2 weeks for the ﬁrst 2 months and periodically thereafter— withhold treatment if lipase elevated and abdominal symptoms occur. ▶Manufacturer advises a full blood count every 2 weeks for the ﬁrst 3 months and then monthly thereafter or as clinically indicated. ▶Manufacturer advises monitor liver function periodically. ▶Manufacturer advises monitor for vascular occlusion or thromboembolism—interrupt treatment immediately if this occurs.

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Dose and formulations

Medicinal Forms

There can be variation in the licensing of different medicines containing the same drug. Tablet CAUTIONARY AND ADVISORY LABELS 3, 25 ▶Iclusig (Incyte Biosciences UK Ltd) A Ponatinib (as Ponatinib hydrochloride) 15 mg Iclusig 15mg tablets | 30 tablet P £2,525.00 Ponatinib (as Ponatinib hydrochloride) 30 mg Iclusig 30mg tablets | 30 tablet P £5,050.00 Ponatinib (as Ponatinib hydrochloride) 45 mg Iclusig 45mg tablets | 30 tablet P £5,050.00

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Dose text by age group

Adult

45 mg once daily, for dose adjustments due to

First-line fragment. Read the complete Indications and Dose section above.

PDF page 1074

Age labels are extracted for navigation. Check the complete source section and current local guidance before clinical use.

Drug reference

Ponatinib

BNF 80 (2020–2021)

Source: BNF 80 (2020–2021)
PDF pages: 1074, 1075

Review source pages for extracted sections and age labels. BNF dose snippets show only their first line.

Overview

Indications And Dose

PDF page 1074

Dose Adjustments

DUE TO INTERACTIONS ▶Manufacturer advises consider a reduced initial dose of 30 mg daily with concurrent use of potent inhibitors of CYP3A4.

PDF page 1074

Cautions

PDF page 1074

National Funding Access Decisions

PDF page 1075

Safety

Important Safety Information

PDF page 1074

Interactions

→Appendix 1: ponatinib

PDF page 1074

Side Effects

PDF page 1074

Conception And Contraception

Ensure effective contraception during treatment in men and women; effectiveness of hormonal contraception unknown— alternative or additional methods of contraception should be used.

PDF page 1074

Pregnancy

Avoid—toxicity in animal studies. See also Pregnancy and reproductive function in Cytotoxic drugs p. 938.

PDF page 1074

Breast Feeding

Manufacturer advises discontinue breastfeeding—no information available.

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Hepatic Impairment

Manufacturer advises caution.

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Renal Impairment

No information available— manufacturer advises caution if creatinine clearance less than 50 mL/minute.

PDF page 1075

Monitoring Requirements

PDF page 1075

Dose and formulations

Medicinal Forms

PDF page 1075

Dose text by age group

Adult

45 mg once daily, for dose adjustments due to

First-line fragment. Read the complete Indications and Dose section above.

PDF page 1074

Age labels are extracted for navigation. Check the complete source section and current local guidance before clinical use.