Ponatinib Brand Name– Iclusig
What is Ponatinib
Ponatinib is an oral multi-kinase inhibitor.
It works by inhibiting ABL and T315I mutant ABL in addition to other tyrosine kinase proteins (e.g., VEGFR, PDGFR, FGFR, EPH, Src family kinases, KIT, RET, FLT-3, and TIE-2) that promote the growth and development of cancer cells.
Ponatinib is indicated for the treatment of T315I-positive chronic phase (CP), accelerated phase (AP), or blast phase (BP) chronic myeloid leukemia (CML) or T315I-positive Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL), or for the treatment of patients with CP, AP, or BP CML or Ph+ALL for whom no other tyrosine kinase inhibitor is indicated.
It is not recommended for use in patients with newly diagnosed, chronic phase CML based on data from a randomized, phase III (EPIC) trial that was stopped early when serious adverse reactions were reported in this patient population.
Ponatinib was evaluated in adult patients with CP (n = 267), AP (n = 83), or BP (n = 62) CML whose disease was resistant or intolerant to prior tyrosine kinase inhibitor therapy with dasatinib or nilotinib or had a T315I-positive mutation in a multi-national, open-label, phase II trial (PACE trial).
The major cytogenic response at 12 months (primary endpoint) was 56% in CP-CML patients.
Additionally, treatment with ponatinib resulted in major hematologic response rates at 6 months (primary endpoint) of 55%, 31%, and 41% in patients with AP-CML, BP-CML, and Ph+ALL, respectively.
Ponatinib was approved by the FDA in December 2012, and subsequently withdrawn by the manufacturer in October 2013 at the request of the FDA due to the risk of life-threatening blood clots and severe narrowing of blood vessels.
In December 2013, after implementing new FDA requirements for safety measures addressing the risk of life-threatening blood clots and severe narrowing of blood vessels, the manufacturer once again began marketing ponatinib to appropriate patients.
Indications
- acute lymphocytic leukemia (ALL)
- chronic myelogenous leukemia (CML)
For the treatment of chronic myelogenous leukemia (CML)
for the treatment of T315I-positive CML in chronic phase, accelerated phase, or blast phase
Side Effects
- abdominal pain
- abdominal pain
- alopecia
- anemia
- anorexia
- anorexia
- aortic dissection
- arthralgia
- arthralgia
- ascites
- asthenia
- asthenia
- atrial fibrillation
- atrial flutter
- atrial tachycardia
- AV block
- avascular necrosis
- back pain
- back pain
- bleeding
- bleeding
- blurred vision
- bone pain
- bone pain
- bradycardia
- cardiac arrest
- cataracts
- cerebral edema
- chest pain (unspecified)
- chills
- chills
- conjunctivitis
- constipation
- constipation
- corneal erosion
- cough
- dehydration
- diarrhea
- diarrhea
- dizziness
- dysgeusia
- dysgeusia
- dyspnea
- dyspnea
- elevated hepatic enzymes
- elevated hepatic enzymes
- erythema
- erythema
- erythema multiforme
- fatigue
- fatigue
- fever
- fever
- fluid retention
- fluid retention
- gastrointestinal fistula
- GI bleeding
- GI perforation
- headache
- headache
- heart failure
- hematemesis
- hepatic failure
- hepatotoxicity
- hyperamylasemia
- hyperamylasemia
- hyperbilirubinemia
- hyperbilirubinemia
- hypercalcemia
- hyperemia
- hyperesthesia
- hyperglycemia
- hyperglycemia
- hyperkalemia
- hyperkalemia
- hypernatremia
- hypernatremia
- hypertension
- hypertensive crisis
- hyperthyroidism
- hypertriglyceridemia
- hypertriglyceridemia
- hyperuricemia
- hypoalbuminemia
- hypoalbuminemia
- hypocalcemia
- hypocalcemia
- hypoesthesia
- hypoglycemia
- hypokalemia
- hypokalemia
- hyponatremia
- hyponatremia
- hypophosphatemia
- hypophosphatemia
- hypothyroidism
- hypotonia
- hypotonia
- impaired wound healing
- infection
- infection
- insomnia
- intracranial bleeding
- iritis
- keratitis
- leukoencephalopathy
- leukopenia
- lymphopenia
- macular edema
- melena
- metabolic acidosis
- metabolic acidosis
- muscle cramps
- musculoskeletal pain
- musculoskeletal pain
- myalgia
- myalgia
- myocardial infarction
- nausea
- nausea
- nephrotoxicity
- nephrotoxicity
- neutropenia
- ocular irritation
- ocular pain
- oral ulceration
- oral ulceration
- pancreatitis
- paresthesias
- pericardial effusion
- peripheral edema
- peripheral edema
- peripheral neuropathy
- peripheral neuropathy
- pharyngitis
- phlebitis
- pleural effusion
- pruritus
- pruritus
- pulmonary edema
- pulmonary embolism
- QT prolongation
- rash
- rash
- respiratory arrest
- restless legs syndrome (RLS)
- restless legs syndrome (RLS)
- retinal hemorrhage
- retinal thrombosis
- sinus tachycardia
- Stevens-Johnson syndrome
- stomatitis
- stomatitis
- stroke
- subdural hematoma
- supraventricular tachycardia (SVT)
- syncope
- thrombocytopenia
- thromboembolism
- thrombosis
- thrombotic microangiopathy
- tumor lysis syndrome (TLS)
- ventricular tachycardia
- vomiting
- vomiting
- weakness
- weakness
- weight loss
- weight loss
- xerophthalmia
- xerosis
- xerosis
Monitoring Parameters
- CBC with differential
- LFTs
- ophthalmologic exam
- pregnancy testing
- serum lipase
- serum uric acid
Contraindications
- alcoholism
- anemia
- ascites
- atrial fibrillation
- atrial flutter
- AV block
- bleeding
- bone marrow suppression
- bradycardia
- breast-feeding
- cardiac arrhythmias
- cardiac disease
- contraception requirements
- diabetes mellitus
- edema
- geriatric
- GI bleeding
- heart failure
- hepatic disease
- hepatotoxicity
- hyperlipidemia
- hypertension
- hyperuricemia
- impaired wound healing
- infertility
- intracranial bleeding
- leukopenia
- myocardial infarction
- neurotoxicity
- neutropenia
- pancreatitis
- pericardial effusion
- peripheral neuropathy
- peripheral vascular disease
- pleural effusion
- pregnancy
- pregnancy testing
- QT prolongation
- renal artery stenosis
- reproductive risk
- stroke
- surgery
- tachycardia
- thrombocytopenia
- thromboembolism
- tumor lysis syndrome (TLS)
- visual disturbance
Interactions
- Afatinib
- Aliskiren
- Aliskiren; Amlodipine
- Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ
- Aliskiren; Hydrochlorothiazide, HCTZ
- Aliskiren; Valsartan
- Alpelisib
- Aluminum Hydroxide
- Aluminum Hydroxide; Magnesium Carbonate
- Aluminum Hydroxide; Magnesium Hydroxide
- Aluminum Hydroxide; Magnesium Hydroxide; Simethicone
- Aluminum Hydroxide; Magnesium Trisilicate
- Amoxicillin; Clarithromycin; Lansoprazole
- Amoxicillin; Clarithromycin; Omeprazole
- Antacids
- Apalutamide
- Aspirin, ASA; Citric Acid; Sodium Bicarbonate
- Aspirin, ASA; Omeprazole
- Atazanavir; Cobicistat
- Atropine; Hyoscyamine; Phenobarbital; Scopolamine
- Belladonna Alkaloids; Ergotamine; Phenobarbital
- Betrixaban
- Boceprevir
- Calcium Carbonate
- Calcium Carbonate; Magnesium Hydroxide
- Calcium Carbonate; Risedronate
- Calcium Carbonate; Simethicone
- Carbamazepine
- Ceritinib
- Chloroquine
- Clarithromycin
- Clozapine
- Cobicistat
- Colchicine
- Colchicine; Probenecid
- Conivaptan
- Dabigatran
- Dapagliflozin; Saxagliptin
- Darunavir; Cobicistat
- Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
- Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
- Delavirdine
- Dexlansoprazole
- Dichlorphenamide
- Digoxin
- Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
- Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
- Enzalutamide
- Esomeprazole
- Esomeprazole; Naproxen
- Everolimus
- Fexofenadine
- Fexofenadine; Pseudoephedrine
- Fosphenytoin
- grapefruit juice
- H2-blockers
- Imatinib
- Indinavir
- Isoniazid, INH; Pyrazinamide, PZA; Rifampin
- Isoniazid, INH; Rifampin
- Itraconazole
- Ketoconazole
- Lansoprazole
- Lansoprazole; Naproxen
- Lapatinib
- Lefamulin
- Letermovir
- Loperamide
- Loperamide; Simethicone
- Lopinavir; Ritonavir
- Magnesium Hydroxide
- Maraviroc
- Metformin; Saxagliptin
- Metformin; Sitagliptin
- Methotrexate
- Mitoxantrone
- Nefazodone
- Nelfinavir
- Ombitasvir; Paritaprevir; Ritonavir
- Omeprazole
- Omeprazole; Amoxicillin; Rifabutin
- Omeprazole; Sodium Bicarbonate
- Ozanimod
- Pantoprazole
- Phenobarbital
- Phenytoin
- Posaconazole
- Rabeprazole
- Ranolazine
- Ribociclib
- Ribociclib; Letrozole
- Rifampin
- Rimegepant
- Ritonavir
- Rosuvastatin
- Saquinavir
- Saxagliptin
- Simvastatin; Sitagliptin
- Sirolimus
- Sitagliptin
- Sodium Bicarbonate
- St. John’s Wort, Hypericum perforatum
- Sulfasalazine
- Talazoparib
- Telaprevir
- Telithromycin
- Temsirolimus
- Tolvaptan
- Topotecan
- Tucatinib
- Ubrogepant
- Venetoclax
- Voriconazole