Dosing & Uses
Dosage Forms & Strengths
tablet
- 10mg
- 15mg
- 30mg
- 45mg
Chronic Myeloid Leukemia
Chronic phase (CP) chronic myeloid leukemia (CML)
- Indicated for patients with CP-CML with resistance or intolerance to at least 2 prior kinase inhibitors
- 45 mg PO qDay initially
- Reduce to 15 mg PO qDay upon achievement of ≤1% BCR-ABL1IS
- Re-escalate dose to previously tolerated dosage of 30 mg or 45 mg PO qDay in patients with loss of response
- Continue until loss of response at the re-escalated dose or unacceptable toxicity
- Consider discontinuing treatment if response has not occurred by 3 months
Accelerated phase (AP) or blast phase (BP) CML
- Indicated for AP-CML or BP-CML for whom no other kinase inhibitors are indicated, and for T315I-postive CML (CP, AP, BP)
- Optimal dose not identified
- 45 mg PO qDay
- Consider reducing dose for AP-CML in patients who have achieved a major cytogenetic response
- Continue until loss of response or unacceptable toxicity
- Consider discontinuing treatment if response has not occurred by 3 months
Acute Lymphoblastic Leukemia
Indicated for patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) for whom no other kinase inhibitors are indicated
Also indicated for T315I-postive Ph+ ALL
Optimal dose not identified
45 mg PO qDay initially
Continue until loss of response or unacceptable toxicity
Consider discontinuing treatment if response has not occurred by 3 months
Dosage Modifications
Dose reductions for adverse reactions
-
CP-CML
- First reduction: 30 mg PO qDay
- Second reduction: 15 mg PO qDay
- Third reduction: 10 mg PO qDay
- Unable to tolerate 10 mg/day: Permanently discontinue
-
AP-CML, BP-CML, and Ph+ ALL
- First reduction: 30 mg PO qDay
- Second reduction: 15 mg PO qDay
- Unable to tolerate 15 mg/day: Permanently discontinue
Arterial occlusive events (cardiovascular or cerebrovascular)
- Grade 1: Interrupt therapy until resolved, then resume at same dose
- Grade 2: Interrupt therapy until Grade ≤1, then resume at next lower dose
- Grade 2 recurs or Grade 3 or 4: Discontinue treatment
Arterial occlusive events (peripheral vascular and other or venous thromboembolism [VTE])
- Grade 1 or 2: Interrupt therapy until resolved, then resume at same dose
- Grade 2 recurs or Grade 3: Interrupt therapy until Grade ≤1, then resume at next lower dose
- Grade 3 recurs or 4: Discontinue treatment
Heart failure
- Grade 2 or 3: Interrupt therapy until Grade ≤1, then resume at next lower dose
- Grade 2 or 3 recurs or Grade 4: Discontinue treatment
Hepatotoxicity
- AST or ALT >3x ULN: Interrupt therapy until Grade ≤1, then resume at next lower dose
- AST or ALT ≥3x ULN with bilirubin >2x ULN and alkaline phosphatase <2x ULN: Discontinue treatment
Pancreatitis and elevated lipase
- Serum lipase >1 to 1.5x ULN: Consider interrupting therapy until resolution then resume at same dose
- Serum lipase >1.5 to 2x ULN, 2 to 5x ULN and asymptomatic, or asymptomatic radiologic pancreatitis: Interrupt therapy until Grade ≤1 (defined as <1.5x ULN) then resume at next lower dose
- Serum lipase >2 to 5x ULN and symptomatic, symptomatic Grade 3 pancreatitis, or serum lipase >5x ULN and asymptomatic: Interrupt therapy until complete resolution of symptoms and after recovery of lipase elevation Grade ≤1, then resume at next lower dose
- Symptomatic pancreatitis and serum lipase >5x ULN: Discontinue therapy
Myelosuppression
- ANC <1 x 109/L or platelets <50 x 109/L: Interrupt therapy until ANC at least 1.5 x 109/L and platelet at least 75 x 109/L, then resume at same dose
- If recurrence, interrupt therapy until resolution, then resume at next lower dose
Other nonhematologic adverse reactions
- Grade 1: Interrupt therapy until resolved, then resume at same dose
- Grade 2: Interrupt therapy until Grade ≤1, then resume at same dose
- Grade 2 recurs or Grade 3 or 4: Interrupt therapy until Grade ≤1, then resume at next lower dose
- Grade 3 or 4 recurs: Discontinue therapy
Strong CYP3A4 inhibitors
- Avoid coadministration with strong CYP3A inhibitors
- If unavoidable, reduce dosage as recommended
- After strong CYP3A inhibitor has been discontinued for 3-5 elimination half-lives, resume dosage that was tolerated before initiating the strong CYP3A
-
Recommended dose for coadministration of strong CYP3A inhibitors
- Current ponatinib dose is 45 mg qDay: Reduce ponatinib to 30 mg qDay
- Current ponatinib dose is 30 mg qDay: Reduce ponatinib to 15 mg qDay
- Current ponatinib dose is 15 mg qDay: Reduce ponatinib to 10 mg qDay
- Current ponatinib dose is 10 mg qDay: Avoid coadministration
Renal impairment
- Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment required
- Severe (CrCl <30 mL/min): Not studied
Hepatic impairment
- Pre-existing hepatic impairment (Child-Pugh A, B, or C): Reduce starting dose from 45 mg qDay to 30 mg qDay
Dosing Considerations
Verify pregnancy status of females of reproductive potential before initiation
Limitation of use
- Not indicated and is not recommended for patients with newly diagnosed CP-CML
Gastrointestinal Stromal Tumors (Orphan)
Orphan designation for treatment of gastrointestinal stromal tumors (GIST)
Sponsor
- ARIAD Pharmaceuticals, Inc; 26 Landsdowne Street; Cambridge, MA 02339-4234
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (73)
- afatinib
ponatinib increases levels of afatinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Reduce afatinib daily dose by 10 mg if not tolerated when coadministered with P-gp inhibitors.
- alpelisib
ponatinib will increase the level or effect of alpelisib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of alpelisib (BCRP substrate) with a BCRP inhibitor may increase alpelisib concentration, which may increase the risk of toxicities. If unable to avoid or use alternant drugs, closely monitor for increased adverse reactions.
- aluminum hydroxide
aluminum hydroxide decreases levels of ponatinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.
- aluminum hydroxide/magnesium carbonate
aluminum hydroxide/magnesium carbonate decreases levels of ponatinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.
- aluminum hydroxide/magnesium trisilicate
aluminum hydroxide/magnesium trisilicate decreases levels of ponatinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.
- apalutamide
apalutamide will decrease the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
- atazanavir
atazanavir increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- bosentan
bosentan decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.
- calcium carbonate
calcium carbonate decreases levels of ponatinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.
- carbamazepine
carbamazepine decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.
- ceritinib
ceritinib will increase the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- chloramphenicol
chloramphenicol will increase the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent use cannot be avoided, reduce ponatinib dose to next lower dose level (45 mg to 30 mg; 30 mg to 15 mg; 15 mg to 10 mg); if patient is taking ponatinib 10 mg once daily prior to concurrent use, avoid use of chloramphenicol and consider alternative therapy; after chloramphenicol discontinued for 3 to 5 half-lives, resume dose of ponatinib tolerated prior to starting chloramphenicol
- cimetidine
cimetidine decreases levels of ponatinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.
- citric acid/sodium bicarbonate
citric acid/sodium bicarbonate decreases levels of ponatinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.
- clarithromycin
clarithromycin increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- cobicistat
cobicistat will increase the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- conivaptan
conivaptan increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- darunavir
darunavir increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- deferiprone
deferiprone, ponatinib. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis; if an alternative is not possible, monitor absolute neutrophil count more frequently.
- dexamethasone
dexamethasone decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.
- edoxaban
ponatinib will increase the level or effect of edoxaban by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Dose adjustment may be required with strong P-gp inhibitors. DVT/PE treatment: Decrease dose to 30 mg PO once daily. NVAF: No dose reduction recommended
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- enzalutamide
enzalutamide decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.
- eslicarbazepine acetate
eslicarbazepine acetate will decrease the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy
- etravirine
etravirine decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.
- famotidine
famotidine decreases levels of ponatinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.
- fexinidazole
fexinidazole will increase the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.
- fosamprenavir
fosamprenavir increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- fosphenytoin
fosphenytoin decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.
- grapefruit
grapefruit increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- ibuprofen/famotidine
ibuprofen/famotidine decreases levels of ponatinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.
- idelalisib
idelalisib will increase the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates
- imatinib
imatinib increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- indinavir
indinavir increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- isoniazid
isoniazid increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- ivosidenib
ivosidenib will decrease the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
- ketoconazole
ketoconazole increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- levoketoconazole
levoketoconazole increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- lopinavir
lopinavir increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- magnesium hydroxide
magnesium hydroxide decreases levels of ponatinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.
- magnesium oxide
magnesium oxide decreases levels of ponatinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.
- mifepristone
mifepristone will increase the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- nafcillin
nafcillin decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.
- nefazodone
nefazodone increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- nelfinavir
nelfinavir increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- nevirapine
nevirapine decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.
- nicardipine
nicardipine increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- nizatidine
nizatidine decreases levels of ponatinib by increasing gastric pH. Applies only to oral form of both agents. Avoid or Use Alternate Drug.
- oxcarbazepine
oxcarbazepine decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.
- ozanimod
ponatinib increases toxicity of ozanimod by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of ozanimod (a BCRP substrate) with BCRP inhibitors increases the exposure of the minor (RP101988, RP101075) and major active metabolites (CC112273, CC1084037) of ozanimod, which may increase the risk of ozanimod adverse reactions. .
- palifermin
palifermin increases toxicity of ponatinib by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.
- pentobarbital
pentobarbital decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.
- phenobarbital
phenobarbital decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.
- phenytoin
phenytoin decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.
- pomalidomide
ponatinib increases levels of pomalidomide by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- posaconazole
posaconazole increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- primidone
primidone decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.
- quinidine
quinidine increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- ribociclib
ribociclib will increase the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- rifabutin
rifabutin decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.
- rifampin
rifampin decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.
- rifapentine
rifapentine decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.
- rimegepant
ponatinib will increase the level or effect of rimegepant by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
ponatinib will increase the level or effect of rimegepant by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of rimegepant (a BCRP substrate) with inhibitors of BCRP. - riociguat
ponatinib will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed
ponatinib will increase the level or effect of riociguat by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Coadministration of riociguat (P-gp substrate) with strong P-gp inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed - ritonavir
ritonavir increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- ropeginterferon alfa 2b
ropeginterferon alfa 2b, ponatinib. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Myelosuppressive agents can produce additive myelosuppression. Avoid use and monitor patients receiving the combination for effects of excessive myelosuppression.
- saquinavir
saquinavir increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- talazoparib
ponatinib will increase the level or effect of talazoparib by Other (see comment). Avoid or Use Alternate Drug. BCRP inhibitors may increase systemic exposure of talazoparib (a BCRP substrate). If coadministration cannot be avoided, monitor for potential adverse reactions.
- tipranavir
tipranavir increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- tucatinib
tucatinib will increase the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.
- venetoclax
ponatinib will increase the level or effect of venetoclax by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If a P-gp inhibitor must be used, reduce the venetoclax dose by at least 50%. Monitor more closely for signs of venetoclax toxicities.
- voriconazole
voriconazole increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Decrease ponatinib starting dose to 30 mg qDay if coadministration with strong CYP3A4 inhibitors cannot be avoided.
- voxelotor
voxelotor will increase the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.
Monitor Closely (119)
- aliskiren
ponatinib increases levels of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- alvimopan
ponatinib increases levels of alvimopan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ambrisentan
ponatinib increases levels of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- amiodarone
ponatinib increases levels of amiodarone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- amitriptyline
ponatinib increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- armodafinil
armodafinil decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- atorvastatin
ponatinib increases levels of atorvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
ponatinib increases toxicity of atorvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy. - bendamustine
ponatinib increases levels of bendamustine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- berotralstat
ponatinib increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.
ponatinib increases levels of berotralstat by Other (see comment). Modify Therapy/Monitor Closely. Comment: Reduced dose of berotralstat (a BCRP substrate) to 110 mg/day when coadministered with BCRP inhibitors. - betrixaban
ponatinib increases levels of betrixaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Decrease betrixaban dose to 80 mg PO once, then 40 mg PO qDay if coadministered with a P-gp inhibitor.
- budesonide
ponatinib increases levels of budesonide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- carvedilol
ponatinib increases levels of carvedilol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- cenobamate
cenobamate will decrease the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
- ceritinib
ponatinib increases levels of ceritinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- cetirizine
ponatinib increases levels of cetirizine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- chlorothiazide
ponatinib increases levels of chlorothiazide by Other (see comment). Use Caution/Monitor.
- cimetidine
ponatinib increases levels of cimetidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
ponatinib increases levels of cimetidine by Other (see comment). Use Caution/Monitor. - ciprofloxacin
ponatinib increases levels of ciprofloxacin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- clobazam
clobazam decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- crofelemer
crofelemer increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.
- cyclosporine
ponatinib increases levels of cyclosporine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- dabigatran
ponatinib will increase the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Atrial fibrillation: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <30 mL/min. DVT/PE treatment: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <50 mL/min
- dabrafenib
dabrafenib will decrease the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
- daunorubicin
ponatinib increases levels of daunorubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
ponatinib increases levels of daunorubicin by Other (see comment). Use Caution/Monitor. - desloratadine
ponatinib increases levels of desloratadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- dexamethasone
ponatinib increases levels of dexamethasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- dichlorphenamide
dichlorphenamide and ponatinib both decrease serum potassium. Use Caution/Monitor.
dichlorphenamide, ponatinib. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Both drugs can cause metabolic acidosis. - digoxin
ponatinib increases levels of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- dipyridamole
ponatinib increases levels of dipyridamole by Other (see comment). Use Caution/Monitor.
- docetaxel
ponatinib increases levels of docetaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- doxorubicin
ponatinib increases levels of doxorubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
ponatinib increases levels of doxorubicin by Other (see comment). Use Caution/Monitor. - doxorubicin liposomal
ponatinib increases levels of doxorubicin liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
ponatinib increases levels of doxorubicin liposomal by Other (see comment). Use Caution/Monitor. - duvelisib
ponatinib will increase the level or effect of duvelisib by Other (see comment). Use Caution/Monitor. Coadministration of duvelisib (a BCRP substrate) with a BCRP transport inhibitor may increase levels or effects of duvelisib.
- elagolix
elagolix decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.
- eletriptan
ponatinib increases levels of eletriptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- encorafenib
encorafenib, ponatinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.
- erythromycin base
ponatinib increases levels of erythromycin base by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- erythromycin ethylsuccinate
ponatinib increases levels of erythromycin ethylsuccinate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- erythromycin lactobionate
ponatinib increases levels of erythromycin lactobionate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- erythromycin stearate
ponatinib increases levels of erythromycin stearate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- estradiol
ponatinib increases levels of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- etoposide
ponatinib increases levels of etoposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- everolimus
ponatinib increases levels of everolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- fexofenadine
ponatinib increases levels of fexofenadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- fluvastatin
ponatinib increases toxicity of fluvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.
- fosamprenavir
ponatinib increases levels of fosamprenavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- glecaprevir/pibrentasvir
ponatinib will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with P-gp/BCRP inhibitors.
- glyburide
ponatinib increases levels of glyburide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
ponatinib increases levels of glyburide by Other (see comment). Use Caution/Monitor. - hydrocortisone
ponatinib increases levels of hydrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- iloperidone
iloperidone increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.
- imatinib
ponatinib increases levels of imatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
ponatinib increases levels of imatinib by Other (see comment). Use Caution/Monitor. - indinavir
ponatinib increases levels of indinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- irinotecan
ponatinib increases levels of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
ponatinib increases levels of irinotecan by Other (see comment). Use Caution/Monitor. - irinotecan liposomal
ponatinib increases levels of irinotecan liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
ponatinib increases levels of irinotecan liposomal by Other (see comment). Use Caution/Monitor. - istradefylline
istradefylline will increase the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
- itraconazole
itraconazole increases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease ponatinib starting dose to 30 mg qDay if concomitantly used with strong CYP3A4 inhibitors.
- ivermectin
ponatinib increases levels of ivermectin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- lapatinib
ponatinib increases levels of lapatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
ponatinib increases levels of lapatinib by Other (see comment). Use Caution/Monitor. - leflunomide
ponatinib increases levels of leflunomide by Other (see comment). Use Caution/Monitor.
- lenacapavir
lenacapavir will increase the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lidocaine
ponatinib increases levels of lidocaine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- loperamide
ponatinib increases levels of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- loratadine
ponatinib increases levels of loratadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- lorlatinib
lorlatinib will decrease the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lovastatin
ponatinib increases levels of lovastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- maraviroc
ponatinib increases levels of maraviroc by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- mefloquine
ponatinib increases levels of mefloquine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- methotrexate
ponatinib increases levels of methotrexate by Other (see comment). Use Caution/Monitor.
- methylprednisolone
ponatinib increases levels of methylprednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- mitomycin
ponatinib increases levels of mitomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- mitotane
mitotane decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.
- mitoxantrone
ponatinib increases levels of mitoxantrone by Other (see comment). Use Caution/Monitor.
- morphine
ponatinib increases levels of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- naldemedine
ponatinib increases levels of naldemedine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with P-gp inhibitors.
- nelfinavir
ponatinib increases levels of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- nilotinib
ponatinib increases levels of nilotinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- nintedanib
ponatinib increases levels of nintedanib by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. If nintedanib adverse effects occur, management may require interruption, dose reduction, or discontinuation of therapy .
- nitrofurantoin
ponatinib increases levels of nitrofurantoin by Other (see comment). Use Caution/Monitor.
- ondansetron
ponatinib increases levels of ondansetron by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- paclitaxel
ponatinib increases levels of paclitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- paclitaxel protein bound
ponatinib increases levels of paclitaxel protein bound by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- pazopanib
ponatinib increases levels of pazopanib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- pioglitazone
pioglitazone increases toxicity of ponatinib by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.
- pitavastatin
ponatinib increases toxicity of pitavastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.
- ponesimod
ponesimod and ponatinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- posaconazole
ponatinib increases levels of posaconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- pravastatin
ponatinib increases levels of pravastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
ponatinib increases toxicity of pravastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy. - prednisone
ponatinib increases levels of prednisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- quinidine
ponatinib increases levels of quinidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ranolazine
ponatinib increases levels of ranolazine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
ponatinib increases toxicity of ranolazine by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy. - rifampin
ponatinib increases levels of rifampin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- rifaximin
ponatinib increases levels of rifaximin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- risperidone
ponatinib increases levels of risperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ritonavir
ponatinib increases levels of ritonavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- rosuvastatin
ponatinib increases toxicity of rosuvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.
- rucaparib
rucaparib will increase the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
- saquinavir
ponatinib increases levels of saquinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- saxagliptin
ponatinib increases levels of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- selexipag
ponatinib will increase the level or effect of selexipag by Other (see comment). Use Caution/Monitor. Selexipag is a ABCG2 (BCRP) substrate. Monitor selexipag for increased pharmacologic or adverse effects when coadministered with ABCG2 (BCRP) inhibitors.
- silodosin
ponatinib increases levels of silodosin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- simvastatin
ponatinib increases levels of simvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
ponatinib increases levels of simvastatin by Other (see comment). Use Caution/Monitor. - siponimod
siponimod and ponatinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- sirolimus
ponatinib increases levels of sirolimus by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.
- sitagliptin
ponatinib increases levels of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- sodium zirconium cyclosilicate
sodium zirconium cyclosilicate will decrease the level or effect of ponatinib by increasing gastric pH. Applies only to oral form of both agents. Modify Therapy/Monitor Closely. Check specific recommendations for drugs that exhibit pH-dependent solubility that may affect their systemic exposure and efficacy. In general, administer drugs at least 2 hr before or after sodium zirconium cyclosilicate.
- stiripentol
stiripentol, ponatinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
- sulfasalazine
ponatinib increases levels of sulfasalazine by Other (see comment). Use Caution/Monitor.
- tacrolimus
ponatinib increases levels of tacrolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- tazemetostat
tazemetostat will decrease the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tecovirimat
tecovirimat will decrease the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
- temsirolimus
ponatinib increases levels of temsirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- teniposide
ponatinib increases levels of teniposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- testosterone
ponatinib increases levels of testosterone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- tolvaptan
ponatinib increases levels of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- topotecan
ponatinib increases levels of topotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
ponatinib increases levels of topotecan by Other (see comment). Use Caution/Monitor. - verapamil
ponatinib increases levels of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- vinblastine
ponatinib increases levels of vinblastine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- vincristine
ponatinib increases levels of vincristine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- vincristine liposomal
ponatinib increases levels of vincristine liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
Minor (11)
- acetazolamide
acetazolamide will increase the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- dexlansoprazole
dexlansoprazole decreases levels of ponatinib by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown.
- efavirenz
efavirenz decreases levels of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown. Avoid unless the coadministration outweighs the possible risk of ponatinib underexposure; monitor for signs of reduced efficacy.
- esomeprazole
esomeprazole decreases levels of ponatinib by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown.
- lansoprazole
lansoprazole decreases levels of ponatinib by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of ponatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- omeprazole
omeprazole decreases levels of ponatinib by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown.
- pantoprazole
pantoprazole decreases levels of ponatinib by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown.
- rabeprazole
rabeprazole decreases levels of ponatinib by increasing gastric pH. Applies only to oral form of both agents. Minor/Significance Unknown.
Adverse Effects
>10%
Hypertension (53-71%)
Neutropenia (24-63%)
Leukopenia (14-63%)
Anemia (9-55%)
Thrombocytopenia (36-57%)
Rash (34-54%)
Abdominal pain (34-49%)
Constipation (24-47%)
Fatigue or asthenia (31-39%)
Headache (25-39%)
Dry skin (24-39%)
Lymphopenia (10-37%)
Pyrexia (23-32%)
Nausea (22-32%)
Arthralgia (13-31%)
Decreased appetite (8-31%)
Diarrhea (13-26%)
Febrile neutropenia (1-25%)
Vomiting (13-24%)
Oral mucositis (9-23%)
Edema, peripheral (13-22%)
Myalgia (6-22%)
Sepsis (1-22%)
Dyspnea (7-21%)
Pleural effusion (3-19%)
Cough (6-18%)
Pain in extremity (9-17%)
Back pain (11-16%)
Pain (6-16%)
Cardiac failure (6-15%)
Chills (7-13%)
Peripheral neuropathy (6-13%)
Muscle spasms (5-13%)
Weight decreased (5-13%)
Arterial ischemia (3-13%)
Pneumonia (3-13%)
Bone pain (9-12%)
Urinary tract infection (7-12%)
Insomnia (7-12%)
Nasopharyngitis (3-12%)
Upper respiratory tract infection (8-11%)
Dizziness (3-11%)
GI hemorrhage (2-11%)
Cellulitis (2-11%)
1-10%
Arterial ischemic event (8%)
MI (5%)
Pancreatitis (5%)
Abdominal pain (4%)
Hemorrhage (4%)
Cardiac failure (4%)
Pneumonia, severe (4%)
Effusions (3%)
Febrile neutropenia (3%)
Thrombocytopenia, severe (3%)
Pyrexia, severe (3%)
Sepsis, severe (2%)
Anemia, severe (2%)
Atrial fibrillation (2%)
Venous thromboembolism (2%)
Hypertension (2%)
Stroke or TIA (2%)
Peripheral arterial disease (2%)
CNS hemorrhage (2%)
GI hemorrhage (2%)
Postmarketing Reports
Vascular occlusion
Arterial occlusion
Venous thromboembolism
Thrombotic microangiopathy
Reversible posterior leukoencephalopathy syndrome (RPLS) – also known as Posterior Reversible Encephalopathy Syndrome - PRES)
Metabolism and nutrition disorders: Dehydration
Skin and subcutaneous tissue disorders: Severe cutaneous reaction (e.g. Erythema multiforme, Stevens-Johnson syndrome)
Gastrointestinal perforation, fistula
Endocrine disorders: Hyperthyroidism
Vascular disorders: Arterial (including aortic) aneurysms, dissections, and rupture
Warnings
Black Box Warnings
Arterial occlusive events
- Arterial occlusive events (AOEs), including fatalities, have occurred
- AOEs included fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures
- Patients with and without cardiovascular risk factors, including patients age ≤50 years, experienced these events
- Monitor for evidence of AOEs
- Interrupt or discontinue treatment based on severity
- Consider benefit-risk to guide a decision to restart therapy
Thromboembolism
- Monitor for evidence of thromboembolism, interrupt or stop ponatinib
- Consider dose modification or discontinuation in patients who develop serious venous thromboembolism
- Thrombotic events reported include deep venous thrombosis, pulmonary embolism, superficial thrombophlebitis, and retinal vein thrombosis with vision loss
Heart failure
- Heart failure, including fatalities, occurred in 9% of treated patients
- Monitor cardiac function; interrupt or stop ponatinib for new or worsening heart failure
Hepatotoxicity
- Hepatotoxicity, liver failure, and death reported
- Monitor hepatic function before and during treatment Interrupt and then reduce or discontinue for hepatotoxicity (see Dosage Modifications)
Contraindications
None
Cautions
Arterial occlusive events, including fatalities, have occurred
Serious or severe VTEs have occurred
Fatal, serious or severe heart failure events reported
May cause hepatotoxicity, including liver failure and death; hepatotoxic events reported, include elevations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and gamma-glutamyl transferase (GGT)
Serious or severe pancreatitis has occurred
Peripheral and cranial neuropathy reported; monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness; interrupt, then resume at same or reduced dose or discontinue drug based on recurrence/severity
Serious ocular toxicities leading to blindness or blurred vision reported; conjunctival irritation, corneal erosion or abrasion, dry eye, conjunctivitis, conjunctival hemorrhage, hyperemias and edema or eye pain cataracts, periorbital edema, blepharitis, glaucoma, eyelid edema, ocular hyperemia, iritis, iridocyclitis, and ulcerative keratitis; conduct comprehensive eye exams at baseline and periodically during treatment
Fatal and serious hemorrhage events have occurred; interrupt dose for serious or severe hemorrhage
Severe myelosuppression (Grade 3 or 4) was observed early, with a median onset time of 1 month (range less than 1-40 months)
Monitor for fluid retention; interrupt, reduce, or discontinue
Monitor for symptoms of arrhythmias; monitor for signs and symptoms suggestive of slow heart rate (fainting, dizziness) or rapid heart rate (chest pain, palpitations, or dizziness) and manage patients as clinically indicated; interrupt, then resume at same or reduced dose or discontinue drug based on recurrence/severity; symptomatic bradycardia and supraventricular tachycardia reported
Thrombocytopenia, neutropenia, and anemia may require dose interruption, or reduction; monitor CBC q2weeks x 3 months and then monthly and as clinically indicated; interrupt for ANC <1000/mm3 or thrombocytopenia <50,000/mm3
Serious tumor lysis syndrome developed and hyperuricemia occurred; ensure adequate hydration and correct high uric acid levels before initiating therapy to decrease risk for tumor lysis syndrome
May compromise wound healing or increase risk for GI perforation; temporarily interrupt therapy in patients undergoing major surgical procedures
Monitor serum lipase every 2 weeks for first 2 months and then monthly thereafter or as clinically indicated; consider additional serum lipase monitoring in patients with a history of pancreatitis or alcohol abuse; interrupt, then resume at same or reduced dose or discontinue drug based on severity; evaluate for pancreatitis when lipase elevation is accompanied by abdominal symptoms
Can cause fetal harm; advise women of potential risk to a fetus
Revere posterior leukoencephalopathy syndrome
- Reversible posterior leukoencephalopathy syndrome (RPLS; also known as posterior reversible encephalopathy syndrome) has been reported; symptoms include hypertension, seizure, headache, decreased alertness, altered mental functioning, vision loss, and other visual and neurological disturbances
- Confirm diagnosis with a MRI
- Interrupt therapy until resolution; safety of resumption in patients upon resolution of RPLS is unknown
Hypertension
- Serious or severe hypertension, including hypertensive crisis, has occurred
- Urgent clinical intervention may be required for hypertension associated with confusion, headache, chest pain, or shortness of breath
- Monitor blood pressure at baseline and as clinically indicated and manage hypertension as clinically indicated
- Interrupt, dose reduce, or stop therapy if hypertension is not medically controlled
- For significant worsening, labile or treatment-resistant hypertension, interrupt therapy and consider evaluating for renal artery stenosis
Increased toxicity in newly diagnosed CP-CML
- Study showed ponatinib-treated patients with CP-CML had 2-fold increased risk of serious adverse reaction compared with imatinib
- Median exposure to treatment was <6 months
- Arterial and venous thrombosis and occlusions occurred at least twice as frequently with ponatinib compared with imatinib; ponatinib-treated patients also exhibited greater incidence of myelosuppression, hepatotoxicity, cardiac failure, hypertension, and skin and subcutaneous tissue disorders
- Ponatinib is not indicated nor recommended for newly diagnosed CP-CML
Drug interaction overview
- CYP3A4 substrate
- Inhibits P-gp, BCRP, and bile salt export pump
-
Strong CYP3A inhibitors
- Avoid coadministration
- Strong CYP3A inhibitors increase ponatinib plasma concentrations and toxicities; if unable to avoid, reduce ponatinib dose
-
Strong CYP3A4 inducers
- Avoid coadministration unless benefits outweighs risks; monitor for reduced efficacy of ponatinib
- Strong CYP3A inducers decrease ponatinib plasma concentrations
Pregnancy & Lactation
Pregnancy
Based on findings in animals and its mechanism of action, fetal harm when administered to pregnant females
No data available on use in pregnant females
Verify pregnancy status of females of reproductive potential before initiation
Contraception
- Females of reproductive potential: Use effective contraception during treatment and for 3 weeks after final dose
Infertility
- Based on animal data, impair fertility in females of reproductive potential may occur
- Unknown whether these effects on fertility are reversible
Animal data
- Oral administration to pregnant rats during organogenesis caused adverse developmental effects at doses lower than human exposures at the recommended human dose
- Advise pregnant females of potential risk to a fetus
Lactation
There is no data on drug presence in human milk or the effects on breastfed children, or on milk production
Advise females not to breastfeed during treatment and for 6 days following last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Kinase inhibitor; inhibits activity of ABL and T315I mutant ABL; inhibits additional kinases including BEGFR, PDGFR, FGFR, EPH receptors and SRC families of kinases, and KIT, RET, TIE2, and FLT3
Absorption
Bioavailability: Unknown
Peak plasma time: 6 hr Peak
Peak plasma concentration: 73 ng/mL(45 mg/day)
AUC: 1253 mcg•h/mL (45 mg/day)
Aqueous solubility is pH dependent, with higher pH resulting in lower solubility
Distribution
Protein bound: >99%
Vd: 1223 L (steady-state at day 28)
Metabolism
Metabolized predominantly by CYP3A4, and to a lesser extent CYP2C8, CYP2D6, and CYP3A5
Also metabolized by esterases and/or amidases P-gp substrate (weak)
Elimination
Half-life: 24 hr (range: 12-66 hr)
Excretion: 87% feces, 5% urine
Pharmacogenomics
Inhibited the in vitro viability of cells expressing native or mutant BCR-ABL, including T315I
Administration
Oral Administration
May take with or without food
Swallow tablets whole; do not crush, break, cut, or chew tablets
Missed dose: Take next dose at regularly scheduled time the next day
Storage
Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Iclusig oral - | 15 mg tablet |  | |
| Iclusig oral - | 45 mg tablet |  |
Copyright © 2010 First DataBank, Inc.
Patient Handout
ponatinib oral
PONATINIB - ORAL
(poe-NA-ti-nib)
COMMON BRAND NAME(S): Iclusig
WARNING: Ponatinib has caused serious (sometimes fatal) blood clots (such as heart attack, stroke, pulmonary embolus-PE, deep vein thrombosis-DVT). Talk to your doctor about the risks and benefits of this medication. Get medical help right away if you develop symptoms of a blood clot, including chest/jaw/left arm pain, confusion, trouble speaking, weakness on one side of the body, severe headache, severe dizziness, sudden vision changes, trouble breathing, pain/swelling/redness of arms/legs.This medication can cause very serious (possibly fatal) heart failure. Tell your doctor right away if you develop symptoms of heart failure, including shortness of breath, swelling ankles/feet, unusual tiredness, unusual/sudden weight gain.Ponatinib can also rarely cause very serious (possibly fatal) liver disease. Your doctor will order blood tests to check your liver before you start and while you are taking ponatinib. Tell your doctor right away if you develop symptoms of liver disease, including nausea/vomiting that doesn't stop, stomach/abdominal pain, dark urine, yellowing eyes/skin. Your doctor may need to change your dosage or discontinue the drug.
USES: Ponatinib is used to treat certain types of blood cancer (chronic myelogenous leukemia-CML, acute lymphoblastic leukemia-ALL). It works by slowing or stopping the growth of cancer cells. It belongs to a class of drugs known as kinase inhibitors.
HOW TO USE: Read the Medication Guide provided by your pharmacist before you start taking ponatinib and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with or without food as directed by your doctor, usually once daily. Swallow the tablets whole. Do not crush, break, cut, chew, or dissolve the tablets. Drink plenty of fluids unless otherwise directed by your doctor. The dosage is based on your medical condition, lab results, response to treatment, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Do not increase your dose or take this medication more often than directed. Your condition will not improve any faster, and your risk of side effects will increase.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day.Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor or pharmacist says you may do so safely. Grapefruit can increase the chance of side effects with this medicine. Ask your doctor or pharmacist for more details.Acid-lowering medications for indigestion, heartburn, or ulcers (such as proton pump inhibitors/PPIs, H2 blockers, antacids) may prevent ponatinib from working. Consult your doctor or pharmacist if you are taking any of these medications.Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets.
SIDE EFFECTS: See also Warning section.Headache, dizziness, constipation, or loss of appetite may occur. If any of these effects last or get worse, tell your doctor or pharmacist immediately.People using this medication may have serious side effects. However, you have been prescribed this drug because your doctor has judged that the benefit to you is greater than the risk of side effects. Careful monitoring by your doctor may decrease your risk.Tell your doctor right away if you have any serious side effects, including: weight gain, numb/tingling skin, pain/numbness/burning feeling in fingers/toes, fainting, fast/slow/irregular/pounding heartbeat, eye pain/swelling/irritation, slow wound healing, sudden severe headache, blurred vision/vision problems, problems thinking.Ponatinib sometimes causes side effects due to the rapid destruction of cancer cells (tumor lysis syndrome). To lower your risk, your doctor may add a medication and tell you to drink plenty of fluids. Tell your doctor right away if you have symptoms such as: signs of kidney problems (such as painful urination, pink/bloody urine, change in the amount of urine), muscle spasms/weakness.Get medical help right away if you have any very serious side effects, including: sudden/severe back pain, unusual bleeding/bruising, black/bloody stools, vomit that contains blood or looks like coffee grounds, shortness of breath, seizures.This medication may raise your blood pressure. Check your blood pressure regularly and tell your doctor if the results are high. Your doctor may control your blood pressure with medication.This medication may lower your ability to fight infections. This may make you more likely to get a serious infection or make any infection you have worse. Tell your doctor right away if have any signs of infection (such as sore throat that doesn't go away, fever, chills, cough).A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Before taking ponatinib, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, heart problems (such as history of heart attack, angina, high blood pressure), previous stroke or "mini-stroke" (transient ischemic attack), blood vessel problems (such as an aneurysm or a tear/break in the aorta or other blood vessels), diabetes, high cholesterol, tobacco use.This drug may make you dizzy or blur your vision. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness or clear vision until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).This medication may cause wounds to heal slowly or poorly. Your doctor or dentist may tell you to temporarily stop treatment with this medication at least 1 week before surgery or a dental procedure. Ask your doctor or dentist for specific instructions about when to stop and when to restart treatment with this medication. Tell your doctor/dentist right away if you have wounds that are not healing well.Tell your health care professional that you are using ponatinib before having any immunizations/vaccinations. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose).To lower the chance of getting cut, bruised, or injured, use caution with sharp objects like razors and nail cutters, and avoid activities such as contact sports.Older adults may be more sensitive to the side effects of this drug, especially unusual bleeding/bruising, blood clots, swollen legs/ankles, muscle spasms, weakness, loss of appetite.Tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while taking ponatinib. Ponatinib may harm an unborn baby. Your doctor should order a pregnancy test before you start this medication. Ask about reliable forms of birth control while taking this medication and for 3 weeks after the last dose. If you become pregnant, talk to your doctor right away about the risks and benefits of this medication.It is unknown if this medication passes into breast milk. Because of the possible risk to the infant, breast-feeding while using this drug and for 6 days after stopping treatment is not recommended. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: See also How to Use section.Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Other medications can affect the removal of ponatinib from your body, which may affect how ponatinib works. Examples include azole antifungals (such as itraconazole), macrolide antibiotics (such as erythromycin), HIV protease inhibitors (such as lopinavir), rifamycins (such as rifabutin), ritonavir, drugs for seizures (such as phenytoin), St. John's wort, among others. .
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: Do not share this medication with others.Lab and/or medical tests (such as blood pressure, eye exam, liver function, complete blood counts, lipase, uric acid) should be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.
MISSED DOSE: If you miss a dose, skip the missed dose. Take your next dose at the regular time the next day. Do not double the dose to catch up.
STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).
Information last revised February 2023. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
