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Iclusig: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on Jan 5, 2023.

1. How it works

  • Iclusig is a brand (trade) name for ponatinib which may be used to treat certain types of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL).
  • Iclusig (ponatinib) works by inhibiting multiple tyrosine kinases depending on its concentration. At low concentration levels, Iclusig inhibits the tyrosine kinase activity of ABL and T315I mutant ABL, and at high concentrations, it inhibits the activity of VEGFR, PDGFR, FGFR, EPH receptors, and SRC families of kinases, the KIT protein (c-KIT), RET, TIE2, and FLT3. By targeting these enzymes and receptors, Iclusig inhibits the viability of cells expressing native or mutant BCR-ABL, including T315I. This reduces tumor size.
  • Iclusig belongs to the class of medicines known as BCR-ABL tyrosine kinase inhibitors (TKIs). It may also be called a multikinase inhibitor or a VEGF/VEGFR inhibitor.

2. Upsides

  • May be used to treat chronic phase (CP) chronic myeloid leukemia (CML) in adults with resistance or intolerance to at least two prior kinase inhibitors. May also be used to treat accelerated phase (AP) or blast phase (BP) CML for whom no other kinase inhibitors are indicated, or for T315I-positive CML (chronic phase, accelerated phase, or blast phase).
  • Consider for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) for whom no other kinase inhibitors are indicated. or T315I-positive Ph+ ALL.
  • Available as 10mg, 15mg, 30mg, and 45mg tablets.
  • Usually started at a dose of 45mg daily which is then reduced upon achievement of 1% or less BCR-ABL1 (CP-CML) or with a major cytogenic response (AP-CML).
  • Inhibits multiple conformations of the ABL kinase.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Rash and other skin reactions, joint pain, abdominal pain, headache, constipation, dry skin, high blood pressure, fatigue, anemia, nausea, fever, myelosuppression, cardiac arrhythmias, fluid retention, hemorrhage, or neuropathy are the most common side effects reported.
  • Can cause serious side effects, such as arterial occlusive events, venous thromboembolic events, heart failure, and hepatotoxicity, and there are boxed warnings about these in the product information.
  • Arterial occlusive events, including myocardial infarctions (heart attack), stroke, brain stenosis, and severe peripheral vascular disease, some of which have been fatal, have been reported with Iclusig use. Has occurred in people young or old, regardless of preexisting cardiovascular disease. Venous thromboembolic events have also occurred. Monitor for cardiovascular or adverse thromboembolic events and discontinue or withhold based on severity.
  • Heart failure, including fatalities, has occurred in Iclusig treated patients. Monitor for heart failure and treat it as necessary. Discontinue or withhold for new or worsening heart failure.
  • Has caused hepatotoxicity, liver failure, and death. Monitor liver function tests and discontinue or withhold Iclusig if tests are significantly abnormal. People with liver impairment are more at risk of adverse effects.
  • Severe pancreatitis has occurred in people receiving Iclusig. Most resolved on discontinuation of Iclusig.
  • Do NOT use for newly diagnosed chronic phase CML. Research has shown these patients are at increased risk of serious adverse reactions compared to starting with another TKI such as imatinib (Gleevec).
  • The dosage of Iclusig may need withholding if serious adverse events, such as arterial occlusive events, venous thromboembolic events, heart failure, hepatotoxicity, pancreatitis, elevated lipase, or myelosuppression occur. Restarting at a lower dosage may be considered depending on the event. See product information.
  • Avoid administration of Iclusig with strong CYP3A inhibitors. If it cannot be avoided, reduce the dosage of Iclusig. 3 to 5 elimination half-lives after discontinuation of the strong CYP3A4 inhibitor, increase the dosage of Iclusig back up to the usual recommended dosage for that patient and their condition.
  • For people with liver disease, reduce the starting dosage of Iclusig from 45mg once daily to 30mg once daily.
  • May increase the risk of bleeding and bruising because it can reduce the number of platelets in the blood. Monitor for any unexplained bruising or bleeding and consider a platelet transfusion if necessary. Fatal and serious hemorrhage events have been reported.
  • May cause visual disturbances or blurred vision which may affect a person's ability to drive or operate machinery. Blindness and retinal toxicities have also been reported.
  • Tumor lysis syndrome has been reported in people receiving Iclusig. Correct dehydration and treat high uric acid levels before Iclusig initiation.
  • May cause abnormalities in laboratory tests such as decreases in platelets, neutrophils, white blood cells, lymphocytes, and hemoglobin. Increases in blood glucose, creatinine, and potassium may also occur. Increases in lipase and amylase have also been reported as well as decreases in bicarbonate, calcium, sodium, and phosphate.
  • Reversible posterior leukoencephalopathy syndrome (RPLS) has been reported in patients who received Iclusig, symptoms include high blood pressure, seizures, headache, decreased alertness, altered mental functioning, vision loss, and other visual and neurological disturbances. Withhold Iclusig and perform an MRI to confirm the diagnosis.
  • Iclusig may delay the ability of wounds to heal and Iclusig should be withheld for at least 1 week before elective surgery. Do not administer for at least 2 weeks following major surgery. Gastrointestinal perforation has also been reported and Iclusig should be permanently discontinued if this happens.
  • May cause hepatitis B reactivation. Ensure a person's vaccination status is up to date before administering Iclusig. Do not administer any live vaccines during treatment.
  • May increase the risk of infection, such as upper respiratory tract infections or the flu because it can reduce the number of white blood cells in your blood (called neutropenia). Regular blood cell counts are required.
  • Iclusig may harm a developing fetus and should not be given to pregnant women. Females of reproductive potential should use effective contraception during treatment with Iclusig and for at least 3 weeks after the last dose. Breastfeeding is not advised during treatment with Iclusig and for 6 days after the final dose. May impair fertility in females.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

  • Iclusig is an oral multikinase inhibitor that may be used to treat Chronic CML or PH+ALL that is resistant or intolerant to other kinase inhibitors. It is more likely to cause side effects when compared with imatinib (Gleevec), such as arterial and venous thrombosis, cardiac failure, myelosuppression, pancreatitis, liver toxicity, high blood pressure, and skin reactions.

5. Tips

  • Iclusig may be taken once daily with or without food, either in the morning or at night. Do not stop taking Iclusig without talking to your doctor.
  • Swallow Iclusig tablets whole with a glass of water. They should not be chewed, cut, dissolved, or crushed. Take them at the same time every day. If you find it hard to swallow the tablets, tell your doctor, nurse, or pharmacist.
  • If you miss a dose of Iclusig, take the next dose at the regularly scheduled time the next day. Do not take a double dose unless your doctor tells you to.
  • Tell your doctor immediately if you experience 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.
  • Iclusig may cause heart failure and an abnormally slow or fast heartbeat. Contact your healthcare provider if you experience symptoms such as shortness of breath, chest pain, palpitations, dizziness, or fainting. Also call your doctor if you experience confusion, headache, dizziness, chest pain, abdominal discomfort, nausea or vomiting, tingling or pain in your hands or feet, weight gain, fever, or any other unusual or worrying side effects.
  • Liver toxicity and bleeding can occur with Iclusig. Tell your doctor if you develop yellow skin or eyes, weight loss, or unusual bleeding or bruising. Eye problems, such as blurred vision, dry eye, or eye pain are also side effects of Iclusig that should be reported.
  • Stay hydrated while taking Iclusig because of the risk of tumor lysis syndrome.
  • If you have any planned surgery, tell your doctor because Iclusig may need to be temporarily stopped because it can delay wound healing.
  • Do not take Iclusig with grapefruit or grapefruit juice or products because this may increase its side effects.
  • Talk to your doctor if you are experiencing any severe or troublesome side effects such as tingling, burning, or weakness in your hands or feet.
  • During treatment, you will regularly see a hematologist (a doctor who treats blood cancers) or a cancer doctor, a specialist nurse, or a specialist pharmacist, and have your blood monitored regularly. Keep these appointments.
  • Iclusig can increase your risk of developing an infection that may become serious. Contact the hospital straight away on the 24-hour contact number you have been given if your temperature goes over 37.5°C (99.5°F), you suddenly feel unwell, even with a normal temperature, you have symptoms of an infection (fever, pain, difficulty breathing, feeling shivery and shaking, a sore throat, a cough, diarrhea, needing to pee a lot, or pain while peeing), or your temperature goes below 36°C (96.8°F).
  • Iclusig can make you bruise or bleed more easily. Talk to your doctor if you have any unexplained bruising or bleeding including nosebleeds, bleeding gums, heavy periods, blood in your urine (pee) or stools (poo), or tiny red or purple spots on the skin that may look like a rash.
  • Tell your doctor if you develop any other side effects of concern, including rapid weight gain. This may indicate fluid build-up. If you have a severe rash or any blistering or peeling contact your doctor immediately.
  • Iclusig can cause visual defects or blurred vision which may affect your ability to drive or operate machinery.
  • Talk to your doctor or pharmacist before taking any other medicines with Iclusig including vitamins, herbal drugs, or complementary therapies.
  • All your vaccinations should be up to date before starting Iclusig. While taking Iclusig you will not be allowed to have any live vaccines. Doctors usually recommend that people with cancer have a flu vaccination and a coronavirus vaccination. These are both inactivated vaccinations that can help reduce the risk of infection. If you have had Hepatitis B (a liver infection) in the past, this treatment can make it active again.
  • Tell your doctor if you are pregnant, intending to become pregnant, or breastfeeding because Iclusig may not be suitable for you.

6. Response and effectiveness

  • Consider discontinuing if a response has not occurred by 3 months.
  • The molecular response rate (overall % BCR-ABL1 rate) in patients with CP-CML administered Iclusig 45mg (which reduced to 15mg) was 42% at 12 months. The rate in patients with or without T315I mutation was also 42%. The cytogenetic response (MCyR) was 49% by 12 months in patients with CP-CML and 50% in those with T315I mutation and 48% in those without T315I mutation.
  • In CP, AP, BP CML, and Ph+ ALL, the overall MCyR was 55% and the CCyR was 46%; 40% experienced a major molecular response. In patients who received an MCyR or MMR the median time to response was 3 months and 6 months respectively.

7. Interactions

Medicines that interact with Iclusig may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Iclusig. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Iclusig interacts with over 490 drugs. Most of these interactions are considered major or moderate. Common medications that may interact with Iclusig include:

  • alteplase
  • antiandrogens, such as apalutamide and enzalutamide
  • antipsychotics, such as clozapine
  • aspirin or other NSAIDs such as diclofenac
  • azathioprine
  • black cohosh or brewer's yeast
  • chemotherapy agents such as mitotane
  • colchicine
  • corticosteroids, such as dexamethasone
  • CYP450 3A4 inducers, such as carbamazepine, fosphenytoin, phenobarbital, phenytoin, and rifampin (may reduce the effectiveness of Iclusig)
  • CYP450 3A4 inhibitors, such as clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, goldenseal, and grapefruit (may increase plasma concentrations of Iclusig)
  • dabigatran
  • digoxin
  • enoxaparin
  • erythromycin
  • etanercept
  • etodolac
  • fingolimod
  • gastric acid-reducing agents, such as lansoprazole
  • grapefruit juice
  • griseofulvin
  • heparin
  • high cholesterol treatments such as simvastatin
  • HIV medications such as atazanavir or cobicistat
  • interferon
  • ketoconazole or itraconazole
  • live vaccines and some other vaccines, such as BCG, cholera, Covid-19 vaccines, measles, hepatitis b vaccines, yellow fever, or live influenza vaccines (Iclusig reduces the immune response to vaccination. Administer live or live-attenuated vaccines at least 4 weeks before Iclusig initiation, and non-live vaccines at least 2 weeks before)
  • rifampin or rifabutin
  • SSRIs such as fluoxetine, paroxetine, or sertraline
  • St. John's Wort
  • targeted treatments such as brigatinib and dabrafenib
  • TNF inhibitors such as adalimumab
  • warfarin.

Iclusig does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A, or CYP2D6 enzymes and does not induce CYP1A2, CYP2B6, or CYP3A enzymes. Iclusig inhibits P-gp, BCRP, and the bile salt export pump (BSEP) but does not inhibit OATP1B1, OATP1B3, OCT1, OCT2, or the organic anion transporters OAT1 and OAT3.

Note that this list is not all-inclusive and includes only common medications that may interact with Iclusig. You should refer to the prescribing information for Iclusig for a complete list of interactions.

References

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Iclusig only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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