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Drug overview for ICLUSIG (ponatinib hcl):
Generic name: ponatinib HCl (poe-NA-ti-nib)
Drug class: Antineoplastic - Protein-Tyrosine Kinase Inhibitors
Therapeutic class: Antineoplastics
Ponatinib hydrochloride, an inhibitor of multiple tyrosine kinases, is an antineoplastic agent.
No enhanced Uses information available for this drug.
Generic name: ponatinib HCl (poe-NA-ti-nib)
Drug class: Antineoplastic - Protein-Tyrosine Kinase Inhibitors
Therapeutic class: Antineoplastics
Ponatinib hydrochloride, an inhibitor of multiple tyrosine kinases, is an antineoplastic agent.
No enhanced Uses information available for this drug.
DRUG IMAGES
ICLUSIG 15 MG TABLET
ICLUSIG 45 MG TABLET
The following indications for ICLUSIG (ponatinib hcl) have been approved by the FDA:
Indications:
Accelerated phase chronic myelocytic leukemia
Blastic phase chronic myeloid leukemia
Chronic phase chronic myeloid leukemia
Philadelphia chromosome positive acute lymphoblastic leukemia
Professional Synonyms:
Acute lymphoblastic leukemia, t(9;22)(q34;q11)
BCR/ABL positive acute lymphoblastic leukemia
Chronic granulocytic leukemia in accelerated phase
Chronic granulocytic leukemia in blast crisis phase
Chronic leukemic myelosis in accelerated phase
Chronic leukemic myelosis, blast crisis phase
Chronic myelogenic leukemia in accelerated phase
Chronic myelogenic leukemia in blast crisis phase
Chronic myelogenous leukemia chronic phase
Chronic myelogenous leukemia in accelerated phase
Chronic myelogenous leukemia in blast crisis phase
Chronic myeloid leukemia in accelerated phase
Chronic myeloid leukemia in blast crisis phase
CML Accelerated Phase
CML blast crisis phase
CML chronic phase
Indications:
Accelerated phase chronic myelocytic leukemia
Blastic phase chronic myeloid leukemia
Chronic phase chronic myeloid leukemia
Philadelphia chromosome positive acute lymphoblastic leukemia
Professional Synonyms:
Acute lymphoblastic leukemia, t(9;22)(q34;q11)
BCR/ABL positive acute lymphoblastic leukemia
Chronic granulocytic leukemia in accelerated phase
Chronic granulocytic leukemia in blast crisis phase
Chronic leukemic myelosis in accelerated phase
Chronic leukemic myelosis, blast crisis phase
Chronic myelogenic leukemia in accelerated phase
Chronic myelogenic leukemia in blast crisis phase
Chronic myelogenous leukemia chronic phase
Chronic myelogenous leukemia in accelerated phase
Chronic myelogenous leukemia in blast crisis phase
Chronic myeloid leukemia in accelerated phase
Chronic myeloid leukemia in blast crisis phase
CML Accelerated Phase
CML blast crisis phase
CML chronic phase
The following dosing information is available for ICLUSIG (ponatinib hcl):
Dosage of ponatinib hydrochloride is expressed in terms of ponatinib.
If adverse reactions occur, temporary interruption of therapy, dosage reduction, and/or discontinuance of ponatinib may be necessary. If dosage modification is required, reduce the dosage of ponatinib as described in Table 1. Permanently discontinue ponatinib in patients who are unable to tolerate the lowest dosage described in Table 1.
Table 1. Recommended Dosage Reduction for Ponatinib Toxicity.
Dosage Reduction Chronic Phase CML Accelerated Phase Newly Diagnosed or Blast Phase Ph+ ALL CML, or Ph+ ALL Monotherapy First 30 mg once daily 30 mg once daily 15 mg once daily Second 15 mg once daily 15 mg once daily 10 mg once daily Third 10 mg once daily Permanently Permanently discontinue if discontinue if patient is unable patient is unable to tolerate 15 mg to tolerate 10 mg once daily once daily Subsequent Permanently Permanently Permanently reduction discontinue if discontinue if discontinue if patient is unable patient is unable patient is unable to tolerate 10 mg to tolerate 15 mg to tolerate 10 mg once daily once daily once daily
If an adverse reaction occurs, reduce ponatinib dosage, or interrupt or permanently discontinue therapy as described in Table 2.
Table 2. Recommended Dosage Modification for Ponatinib Toxicity.
Adverse Reaction and Severity Modification Cardiovascular or Cerebrovascular Withhold ponatinib until resolved, Arterial Occlusive Event (Grade 1) then resume at the same dosage Cardiovascular or Cerebrovascular Withhold ponatinib until grade 0 or Arterial Occlusive Event (Grade 2) 1, then resume at the next lower dosage; discontinue ponatinib if event recurs Cardiovascular or Cerebrovascular Discontinue ponatinib Arterial Occlusive Event (Grade 3 or 4) Peripheral Vascular or Other Withhold ponatinib until resolved, Arterial Occlusive Event (Grade 1) then resume at the same dosage Peripheral Vascular or Other Withhold ponatinib until grade 0 or Arterial Occlusive Event (Grade 2) 1, then resume at the same dosage; if event recurs, withhold ponatinib until grade 0 or 1, then resume at the next lower dosage Peripheral Vascular or Other Withhold ponatinib until grade 0 or Arterial Occlusive Event (Grade 3) 1, then resume at the next lower dosage; discontinue ponatinib if event recurs Peripheral Vascular or Other Discontinue ponatinib Arterial Occlusive Event (Grade 4) Venous Thromboembolism (Grade 1) Withhold ponatinib until resolved, then resume at the same dosage Venous Thromboembolism (Grade 2) Withhold ponatinib until grade 0 or 1, then resume at the same dosage; if event recurs, withhold ponatinib until grade 0 or 1, then resume at the next lower dosage Venous Thromboembolism (Grade 3) Withhold ponatinib until grade 0 or 1, then resume at the next lower dosage; discontinue ponatinib if event recurs Venous Thromboembolism (Grade 4) Discontinue ponatinib Heart Failure (Grade 2 or 3) Withhold ponatinib until grade 0 or 1, then resume at the next lower dosage; discontinue ponatinib if event recurs Heart Failure (Grade 4) Discontinue ponatinib Hepatotoxicity (AST or ALT >3 times Withhold ponatinib until grade 0 or ULN) 1, then resume at the next lower dosage Hepatotoxicity (AST or ALT >=3 times Discontinue ponatinib ULN concurrent with bilirubin >2 times ULN and alkaline phosphatase <2 times ULN) Elevated Serum Lipase (Serum lipase Consider withholding ponatinib until >1 to 1.5 times ULN) resolution, then resume at same dosage Pancreatitis or Elevated Serum Withhold ponatinib until grade 0 or Lipase (Serum lipase >1.5 to 2 times 1 (<1.5 times ULN), then resume at ULN, serum lipase 2 to 5 times ULN next lower dosage and asymptomatic, or asymptomatic radiologic pancreatitis) Pancreatitis or Elevated Serum Withhold ponatinib until complete Lipase (Serum lipase >2 to 5 times resolution of symptoms and after ULN and symptomatic, symptomatic recovery of lipase elevation to grade 3 pancreatitis, or serum grade 0 or 1; then resume at the lipase >5 times ULN and next lower dosage asymptomatic) Symptomatic pancreatitis and serum Discontinue ponatinib lipase >5 times ULN Myelosuppression (ANC <1000/mm3 or Withhold ponatinib until ANC platelets <50,000/mm3) >=1500/mm3 and platelets >=75,000/mm3, then resume at the same dosage; if myelosuppression recurs, withhold ponatinib until resolution, then resume at the next lower dosage Other Non-Hematologic Adverse Events Withhold ponatinib until resolved, (Grade 1) then resume at the same dosage Other Non-Hematologic Adverse Events Withhold ponatinib until grade 0 or (Grade 2) 1, then resume at the same dosage; if event recurs, withhold ponatinib until grade 0 or 1, then resume at the next lower dosage Other Non-Hematologic Adverse Events Withhold ponatinib until grade 0 or (Grade 3 or 4) 1, then resume at the next lower dosage; if event recurs, discontinue ponatinib
Avoid concomitant use of ponatinib with strong inhibitors of cytochrome P-450 (CYP) 3A when possible. If concomitant use cannot be avoided, reduce the dosage of ponatinib as described in Table 3. After discontinuing a strong CYP3A inhibitor for 3-5 elimination half-lives, resume the dosage of ponatinib that was tolerated prior to initiating the strong CYP3A inhibitor.
Table 3. Recommended Dosage for Ponatinib Coadministered with Strong CYP3A Inhibitors.
Current Ponatinib Dosage Recommended Ponatinib Dosage with a Strong CYP3A Inhibitor 45 mg once daily 30 mg once daily 30 mg once daily 15 mg once daily 15 mg once daily 10 mg once daily 10 mg once daily Avoid coadministration of ponatinib with a strong CYP3A inhibitor
If adverse reactions occur, temporary interruption of therapy, dosage reduction, and/or discontinuance of ponatinib may be necessary. If dosage modification is required, reduce the dosage of ponatinib as described in Table 1. Permanently discontinue ponatinib in patients who are unable to tolerate the lowest dosage described in Table 1.
Table 1. Recommended Dosage Reduction for Ponatinib Toxicity.
Dosage Reduction Chronic Phase CML Accelerated Phase Newly Diagnosed or Blast Phase Ph+ ALL CML, or Ph+ ALL Monotherapy First 30 mg once daily 30 mg once daily 15 mg once daily Second 15 mg once daily 15 mg once daily 10 mg once daily Third 10 mg once daily Permanently Permanently discontinue if discontinue if patient is unable patient is unable to tolerate 15 mg to tolerate 10 mg once daily once daily Subsequent Permanently Permanently Permanently reduction discontinue if discontinue if discontinue if patient is unable patient is unable patient is unable to tolerate 10 mg to tolerate 15 mg to tolerate 10 mg once daily once daily once daily
If an adverse reaction occurs, reduce ponatinib dosage, or interrupt or permanently discontinue therapy as described in Table 2.
Table 2. Recommended Dosage Modification for Ponatinib Toxicity.
Adverse Reaction and Severity Modification Cardiovascular or Cerebrovascular Withhold ponatinib until resolved, Arterial Occlusive Event (Grade 1) then resume at the same dosage Cardiovascular or Cerebrovascular Withhold ponatinib until grade 0 or Arterial Occlusive Event (Grade 2) 1, then resume at the next lower dosage; discontinue ponatinib if event recurs Cardiovascular or Cerebrovascular Discontinue ponatinib Arterial Occlusive Event (Grade 3 or 4) Peripheral Vascular or Other Withhold ponatinib until resolved, Arterial Occlusive Event (Grade 1) then resume at the same dosage Peripheral Vascular or Other Withhold ponatinib until grade 0 or Arterial Occlusive Event (Grade 2) 1, then resume at the same dosage; if event recurs, withhold ponatinib until grade 0 or 1, then resume at the next lower dosage Peripheral Vascular or Other Withhold ponatinib until grade 0 or Arterial Occlusive Event (Grade 3) 1, then resume at the next lower dosage; discontinue ponatinib if event recurs Peripheral Vascular or Other Discontinue ponatinib Arterial Occlusive Event (Grade 4) Venous Thromboembolism (Grade 1) Withhold ponatinib until resolved, then resume at the same dosage Venous Thromboembolism (Grade 2) Withhold ponatinib until grade 0 or 1, then resume at the same dosage; if event recurs, withhold ponatinib until grade 0 or 1, then resume at the next lower dosage Venous Thromboembolism (Grade 3) Withhold ponatinib until grade 0 or 1, then resume at the next lower dosage; discontinue ponatinib if event recurs Venous Thromboembolism (Grade 4) Discontinue ponatinib Heart Failure (Grade 2 or 3) Withhold ponatinib until grade 0 or 1, then resume at the next lower dosage; discontinue ponatinib if event recurs Heart Failure (Grade 4) Discontinue ponatinib Hepatotoxicity (AST or ALT >3 times Withhold ponatinib until grade 0 or ULN) 1, then resume at the next lower dosage Hepatotoxicity (AST or ALT >=3 times Discontinue ponatinib ULN concurrent with bilirubin >2 times ULN and alkaline phosphatase <2 times ULN) Elevated Serum Lipase (Serum lipase Consider withholding ponatinib until >1 to 1.5 times ULN) resolution, then resume at same dosage Pancreatitis or Elevated Serum Withhold ponatinib until grade 0 or Lipase (Serum lipase >1.5 to 2 times 1 (<1.5 times ULN), then resume at ULN, serum lipase 2 to 5 times ULN next lower dosage and asymptomatic, or asymptomatic radiologic pancreatitis) Pancreatitis or Elevated Serum Withhold ponatinib until complete Lipase (Serum lipase >2 to 5 times resolution of symptoms and after ULN and symptomatic, symptomatic recovery of lipase elevation to grade 3 pancreatitis, or serum grade 0 or 1; then resume at the lipase >5 times ULN and next lower dosage asymptomatic) Symptomatic pancreatitis and serum Discontinue ponatinib lipase >5 times ULN Myelosuppression (ANC <1000/mm3 or Withhold ponatinib until ANC platelets <50,000/mm3) >=1500/mm3 and platelets >=75,000/mm3, then resume at the same dosage; if myelosuppression recurs, withhold ponatinib until resolution, then resume at the next lower dosage Other Non-Hematologic Adverse Events Withhold ponatinib until resolved, (Grade 1) then resume at the same dosage Other Non-Hematologic Adverse Events Withhold ponatinib until grade 0 or (Grade 2) 1, then resume at the same dosage; if event recurs, withhold ponatinib until grade 0 or 1, then resume at the next lower dosage Other Non-Hematologic Adverse Events Withhold ponatinib until grade 0 or (Grade 3 or 4) 1, then resume at the next lower dosage; if event recurs, discontinue ponatinib
Avoid concomitant use of ponatinib with strong inhibitors of cytochrome P-450 (CYP) 3A when possible. If concomitant use cannot be avoided, reduce the dosage of ponatinib as described in Table 3. After discontinuing a strong CYP3A inhibitor for 3-5 elimination half-lives, resume the dosage of ponatinib that was tolerated prior to initiating the strong CYP3A inhibitor.
Table 3. Recommended Dosage for Ponatinib Coadministered with Strong CYP3A Inhibitors.
Current Ponatinib Dosage Recommended Ponatinib Dosage with a Strong CYP3A Inhibitor 45 mg once daily 30 mg once daily 30 mg once daily 15 mg once daily 15 mg once daily 10 mg once daily 10 mg once daily Avoid coadministration of ponatinib with a strong CYP3A inhibitor
Ponatinib hydrochloride is administered orally once daily without regard to food. The tablets should be swallowed whole and should not be crushed, broken, cut, or chewed. If a dose is missed, the next dose should be taken at the regularly scheduled time the next day.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| ICLUSIG 30 MG TABLET | Maintenance | Adults take 1 tablet (30 mg) by oral route once daily swallowing whole. Do not break, crush, dissolve and/or chew. |
| ICLUSIG 45 MG TABLET | Maintenance | Adults take 1 tablet (45 mg) by oral route once daily swallowing whole. Do not break, crush, dissolve and/or chew. |
| ICLUSIG 15 MG TABLET | Maintenance | Adults take 2 tablets (30 mg) by oral route once daily swallowing whole. Do not break, crush, dissolve and/or chew. |
| ICLUSIG 10 MG TABLET | Maintenance | Adults take 1 tablet (10 mg) by oral route once daily swallowing whole. Do not break, crush, dissolve and/or chew. |
No generic dosing information available.
The following drug interaction information is available for ICLUSIG (ponatinib hcl):
There are 4 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Efalizumab; Natalizumab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Natalizumab,(1-3) efalizumab,(4) immunosuppressives, and immunomodulators all suppress the immune system. CLINICAL EFFECTS: Concurrent use of natalizumab(1-3) or efalizumab(4) with immunosuppressives or immunomodulators may result in an increased risk of infections, including progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV). PREDISPOSING FACTORS: Previous JCV infection, longer duration of natalizumab treatment - especially if greater than 2 years, and prior or concomitant treatment with immunosuppressant medication are all independent risk factors which increase the risk for PML.(1,5) The FDA has estimated PML incidence stratified by risk factors: If anti-JCV antibody positive, no prior immunosuppressant use and natalizumab treatment less than 25 months, incidence <1/1,000. If anti-JCV antibody positive, history of prior immunosuppressant use and natalizumab treatment less than 25 months, incidence 2/1,000 If anti-JCV antibody positive, no prior immunosuppressant use and natalizumab treatment 25-48 months, incidence 4/1,000 If anti-JCV antibody positive, history of prior immunosuppressant use and natalizumab treatment 25-48 months, incidence 11/1,000. PATIENT MANAGEMENT: The US manufacturer of natalizumab states patients with Crohn's disease should not receive concurrent immunosuppressants, with the exception of limited overlap of corticosteroids, due to the increased risk for PML. For new natalizumab patients currently receiving chronic oral corticosteroids for Crohn's Disease, begin corticosteroid taper when therapeutic response to natalizumab has occurred. If corticosteroids cannot be discontinued within six months of starting natalizumab, discontinue natalizumab.(3) The US manufacturer of natalizumab states that natalizumab should not ordinarily be used in multiple sclerosis patients receiving immunosuppressants or immunomodulators due to the increased risk for PML. Immunosuppressives include, but are not limited to azathioprine, cyclophosphamide, cyclosporine, mercaptopurine, methotrexate, mitoxantrone, mycophenolate, and corticosteroids.(3,6) The UK manufacturer of natalizumab states that concurrent use with immunosuppressives or antineoplastic agents is contraindicated.(1) The Canadian manufacturer of natalizumab states that natalizumab should not be used with immunosuppressive or immunomodulatory agents.(2) The US manufacturer of certolizumab states that concurrent therapy with natalizumab is not recommended.(7) DISCUSSION: Progressive multifocal leukoencephalopathy has been reported in patients receiving concurrent natalizumab were recently or concomitantly taking immunomodulators or immunosuppressants.(1-5,8,9) In a retrospective cohort study of multiple sclerosis patients newly initiated on a disease-modifying therapy, use of high-efficacy agents (alemtuzumab, natalizumab, or ocrelizumab) resulted in the same risk of overall infections as moderate-efficacy agents, but there was an elevated risk of serious infections (adjusted hazard ratio [aHR] = 1.24, 95% confidence interval (CI) = 1.06-1.44) and UTIs (aHR = 1.21, 95% CI = 1.14-1.30).(10) |
TYSABRI |
| Live Vaccines; Live BCG/Selected Immunosuppressive Agents SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: A variety of disease modifying agents suppress the immune system. Immunocompromised patients may be at increased risk for uninhibited replication after administration of live, attenuated vaccines or intravesicular BCG. Immune response to vaccines may be decreased during periods of immunocompromise.(1) CLINICAL EFFECTS: The expected serum antibody response may not be obtained and/or the vaccine may result in illness.(1) After instillation of intravesicular BCG, immunosuppression may interfere with local immune response, or increase the severity of mycobacterial infection following inadvertent systemic exposure.(2) PREDISPOSING FACTORS: Immunosuppressive diseases (e.g. hematologic malignancies, HIV disease), treatments (e.g. radiation) and drugs may all increase the magnitude of immunodeficiency. PATIENT MANAGEMENT: The Centers for Disease Control(CDC) Advisory Committee on Immunization Practices (ACIP) states that live-virus and live, attenuated vaccines should not be administered to patients who are immunocompromised. The magnitude of immunocompromise and associated risks should be determined by a physician.(1) For patients scheduled to receive chemotherapy, vaccination should ideally precede the initiation of chemotherapy by 14 days. Patients vaccinated while on immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated at least 3 months after discontinuation of therapy.(1) Patients who receive anti-B cell therapies should not receive live vaccines for at least 6 months after such therapies due to a prolonged duration of immunosuppression. An exception is the Zoster vaccine, which can be given at least 1 month after receipt of anti-B cell therapies.(1) The US manufacturer of abatacept states live vaccines should not be given during or for up to 3 months after discontinuation of abatacept.(2) The US manufacturer of live BCG for intravesicular treatment of bladder cancer states use is contraindicated in immunosuppressed patients.(3) The US manufacturer of daclizumab states live vaccines are not recommended during and for up to 4 months after discontinuation of treatment.(4) The US manufacturer of guselkumab states that live vaccines should be avoided during treatment with guselkumab.(5) The US manufacturer of inebilizumab-cdon states that live vaccines are not recommended during treatment and after discontinuation until B-cell repletion. Administer all live vaccinations at least 4 weeks prior to initiation of inebilizumab-cdon.(6) The US manufacturer of ocrelizumab states that live vaccines are not recommended during treatment and until B-cell repletion occurs after discontinuation of therapy. Administer all live vaccines at least 4 weeks prior to initiation of ocrelizumab.(7) The US manufacturer of ozanimod states that live vaccines should be avoided during and for up to 3 months after discontinuation of ozanimod.(8) The US manufacturer of siponimod states that live vaccines are not recommended during treatment and for up to 4 weeks after discontinuation of treatment.(9) The US manufacturer of ustekinumab states BCG vaccines should not be given in the year prior to, during, or the year after ustekinumab therapy.(10) The US manufacturer of satralizumab-mwge states that live vaccines are not recommended during treatment and should be administered at least four weeks prior to initiation of satralizumab-mwge.(11) The US manufacturer of ublituximab-xiiy states that live vaccines are not recommended during treatment and until B-cell recovery. Live vaccines should be administered at least 4 weeks prior to initiation of ublituximab-xiiy.(12) The US manufacturer of etrasimod states that live vaccines should be avoided during and for 5 weeks after treatment. Live vaccines should be administered at least 4 weeks prior to initiation of etrasimod.(13) The US manufacturer of emapalumab-lzsg states that live vaccines should not be administered to patients receiving emapalumab-lzsg and for at least 4 weeks after the last dose of emapalumab-lzsg. The safety of immunization with live vaccines during or following emapalumab-lzsg therapy has not been studied.(14) DISCUSSION: Killed or inactivated vaccines do not pose a danger to immunocompromised patients.(1) Patients with a history of leukemia who are in remission and have not received chemotherapy for at least 3 months are not considered to be immunocompromised.(1) |
ACAM2000 (NATIONAL STOCKPILE), ADENOVIRUS TYPE 4, ADENOVIRUS TYPE 4 AND TYPE 7, ADENOVIRUS TYPE 7, BCG (TICE STRAIN), BCG VACCINE (TICE STRAIN), DENGVAXIA, ERVEBO (NATIONAL STOCKPILE), FLUMIST 2025-2026, FLUMIST HOME 2025-2026, IXCHIQ, M-M-R II VACCINE, PRIORIX, PROQUAD, ROTARIX, ROTATEQ, STAMARIL, VARIVAX VACCINE, VAXCHORA ACTIVE COMPONENT, VAXCHORA VACCINE, VIVOTIF, YF-VAX |
| Talimogene laherparepvec/Selected Immunosuppressants SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Talimogene laherparepvec is a live, attenuated herpes simplex virus.(1) CLINICAL EFFECTS: Concurrent use of talimogene laherparepvec in patients receiving immunosuppressive therapy may cause a life-threatening disseminated herpetic infection.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Talimogene laherparepvec is contraindicated in immunosuppressed patients.(1) The magnitude of immunocompromise and associated risks due to immunosuppressant drugs should be determined by a physician. DISCUSSION: Concurrent use of talimogene laherparepvec in patients receiving immunosuppressive therapy may cause a life-threatening disseminated herpetic infection.(1) |
IMLYGIC |
| Nadofaragene Firadenovec/Selected Immunosuppressants SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Nadofaragene firadenovec may contain low levels of replication-competent adenovirus.(1) CLINICAL EFFECTS: Concurrent use of nadofaragene firadenovec in patients receiving immunosuppressive therapy may cause disseminated adenovirus infection.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Individuals who are immunosuppressed or immune-deficient should not receive nadofaragene firadenovec.(1) DISCUSSION: Nadofaragene firadenovec is a non-replicating adenoviral vector-based gene therapy but may contain low levels of replication-competent adenovirus. Immunocompromised persons, including those receiving immunosuppressant therapy, may be at risk for disseminated adenovirus infection.(1) |
ADSTILADRIN |
There are 20 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Deferiprone/Selected Myelosuppressive Agents SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis may increase the frequency or risk for severe toxicity.(1) CLINICAL EFFECTS: Concurrent use of deferiprone and myelosuppressive agents may result in severe neutropenia or agranulocytosis, which may be fatal. PREDISPOSING FACTORS: Agranulocytosis may be less common in patients receiving deferiprone for thalassemia, and more common in patients treated for other systemic iron overload conditions (e.g. myelodysplastic syndromes, sickle cell disease).(2,3) Inadequate monitoring appears to increase the risk for severe outcomes. Manufacturer post market surveillance found that in all fatal cases of agranulocytosis reported between 1999 and 2005, data on weekly white blood count (WBC) monitoring was missing. In three fatal cases, deferiprone was continued for two to seven days after the detection of neutropenia or agranulocytosis.(2) PATIENT MANAGEMENT: If possible, discontinue one of the drugs associated with risk for neutropenia or agranulocytosis. If alternative therapy is not available, documentation and adherence to the deferiprone monitoring protocol is essential. Baseline absolute neutrophil count (ANC) must be at least 1,500/uL prior to starting deferiprone. Monitor ANC weekly during therapy. If infection develops, interrupt deferiprone therapy and monitor ANC more frequently. If ANC is less than 1,500/uL but greater than 500/uL, discontinue deferiprone and any other drugs possibly associated with neutropenia. Initiate ANC and platelet counts daily until recovery (i.e. ANC at least 1,500/uL). If ANC is less than 500/uL, discontinue deferiprone, evaluate patient and hospitalize if appropriate. Do not resume deferiprone unless potential benefits outweigh potential risks.(1) DISCUSSION: Drugs linked to this monograph have an FDA Boxed Warning for risk of neutropenia, agranulocytosis, or pancytopenia, or have > 5% risk for neutropenia and/or warnings describing risk for myelosuppression in manufacturer prescribing information.(1-25) In pooled clinical studies submitted to the FDA, 6.1% of deferiprone patients met criteria for neutropenia and 1.7% of patients developed agranulocytosis.(1) The time to onset of agranulocytosis was highly variable with a range of 65 days to 9.2 years (median, 161 days).(3) |
DEFERIPRONE, DEFERIPRONE (3 TIMES A DAY), FERRIPROX, FERRIPROX (2 TIMES A DAY), FERRIPROX (3 TIMES A DAY) |
| Ponatinib/Strong CYP3A4 Inducers; Rifabutin SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong inducers of CYP3A4 and rifabutin may induce the metabolism of ponatinib via this pathway.(1-3) CLINICAL EFFECTS: Concurrent or recent use of strong CYP3A4 inducers or rifabutin may reduce the clinical effectiveness of ponatinib.(1-3) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid the concurrent use of ponatinib with strong CYP3A4 inducers.(1-3) The Canadian and UK manufacturers of ponatinib include rifabutin in their list of CYP3A4 inducers that should be avoided.(2-3) When possible, select alternative agents in place of the strong CYP3A4 inducer. Monitor patients receiving concurrent therapy for reduced efficacy. DISCUSSION: Coadministration of a single ponatinib 45 mg dose with rifampin 600 mg daily in 19 healthy volunteers resulted in a decrease in ponatinib area-under-the-curve (AUC) and maximum concentration (Cmax) by 62% and 42%, respectively. (1) Strong CYP3A4 inducers linked to this monograph are: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine and St John's Wort.(4,5) |
ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, BRAFTOVI, BUTALB-ACETAMINOPH-CAFF-CODEIN, BUTALBITAL, BUTALBITAL-ACETAMINOPHEN, BUTALBITAL-ACETAMINOPHEN-CAFFE, BUTALBITAL-ASPIRIN-CAFFEINE, CARBAMAZEPINE, CARBAMAZEPINE ER, CARBATROL, CEREBYX, DILANTIN, DILANTIN-125, DONNATAL, EPITOL, EQUETRO, ERLEADA, FIORICET, FIORICET WITH CODEINE, FOSPHENYTOIN SODIUM, LYSODREN, MITOTANE, MYSOLINE, ORKAMBI, PENTOBARBITAL SODIUM, PHENOBARBITAL, PHENOBARBITAL SODIUM, PHENOBARBITAL-BELLADONNA, PHENOBARBITAL-HYOSC-ATROP-SCOP, PHENOHYTRO, PHENYTEK, PHENYTOIN, PHENYTOIN SODIUM, PHENYTOIN SODIUM EXTENDED, PRIFTIN, PRIMIDONE, RIFABUTIN, RIFADIN, RIFAMPIN, SEZABY, TALICIA, TEGRETOL, TEGRETOL XR, TENCON, TIBSOVO, XTANDI |
| Tofacitinib/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of tofacitinib and azathioprine, other biologic disease-modifying antirheumatic drugs (DMARDs), or potent immunosuppressants may result in additive or synergistic effects on the immune system.(1) CLINICAL EFFECTS: Concurrent use of tofacitinib and azathioprine, other biologic DMARDs, or potent immunosuppressants use may increase the risk of serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Tofacitinib should not be used concurrently with azathioprine, other biologic DMARDs, or cyclosporine.(1) Patient should be monitored for decreases in lymphocytes and neutrophils. Therapy should be adjusted based on the indication. - For all indications: If absolute neutrophil count (ANC) or lymphocyte count is less than 500 cells/mm3, discontinue tofacitinib. - For rheumatoid arthritis or psoriatic arthritis and absolute neutrophil count (ANC) 500 to 1000 cells/mm3: interrupt dosing. When ANC is greater than 1000 cells/mm3, resume Xeljanz 5 mg twice daily or Xeljanz XR 11 mg once daily. - For ulcerative colitis and ANC 500 to 1000 cells/mm3: -If taking Xeljanz 10 mg twice daily, decrease to 5 mg twice daily. When ANC is greater than 1000 cells/mm3, increase to 10 mg twice daily based on clinical response. -If taking Xeljanz 5 mg twice daily, interrupt dosing. When ANC is greater than 1000 cells/mm3, resume 5 mg twice daily. -If taking Xeljanz XR 22 mg once daily, decrease to 11 mg once daily. When ANC is greater than 1000 cells/mm3, increase to 22 mg once daily based on clinical response. -If taking Xeljanz XR 11 mg once daily, interrupt dosing. When ANC is greater than 1000 cells/mm3, resume 11 mg once daily. - For polyarticular course juvenile idiopathic arthritis (pcJIA) and ANC 500 to 1000 cells/mm3: interrupt dosing until ANC is greater than 1000 cells/mm3.(1) DISCUSSION: Concurrent use of tofacitinib and azathioprine, other biologic DMARDs, or potent immunosuppressants may increase the risk of infection.(1) |
TOFACITINIB CITRATE, XELJANZ, XELJANZ XR |
| Clozapine/Selected Myelosuppressive Agents SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Clozapine and other myelosuppressive agents may be associated with neutropenia or agranulocytosis.(2) CLINICAL EFFECTS: Moderate neutropenia, even if due to combination therapy, may require abrupt discontinuation of clozapine resulting in decompensation of the patient's psychiatric disorder (e.g. schizophrenia). The disease treated by the myelosuppressive agent may be compromised if myelosuppression requires dose reduction, delay, or discontinuation of the myelosuppressive agent. Undetected severe neutropenia or agranulocytosis may be fatal. PREDISPOSING FACTORS: Low white blood counts prior to initiation of the myelosuppressive agent may increase risk for clinically significant neutropenia. PATIENT MANAGEMENT: If a patient stabilized on clozapine therapy requires treatment with a myelosuppressive agent, the clozapine prescriber should consult with prescriber of the myelosuppressive agent (e.g. oncologist) to discuss treatment and monitoring options.(2) More frequent ANC monitoring or treatment alternatives secondary to neutropenic episodes may need to be considered. Clozapine is only available through a restricted distribution system which requires documentation of the absolute neutrophil count (ANC) prior to dispensing.(1-2) For most clozapine patients, clozapine treatment must be interrupted for a suspected clozapine-induced ANC < 1000 cells/microliter. For patients with benign ethnic neutropenia (BEN), treatment must be interrupted for suspected clozapine-induced neutropenia < 500 cells/microliter.(2) DISCUSSION: Clozapine is only available through a restricted distribution system which requires documentation of the ANC prior to dispensing.(1) Agents linked to this interaction generally have > 5% risk for neutropenia and/or warnings describing risk for myelosuppression in manufacturer prescribing information.(3-26) |
CLOZAPINE, CLOZAPINE ODT, CLOZARIL, VERSACLOZ |
| Selected Multiple Sclerosis Agents/Immunosuppressants; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ocrelizumab or ofatumumab in combination with immunosuppressives and immune-modulators all suppress the immune system.(1,2) CLINICAL EFFECTS: Concurrent use of ocrelizumab or ofatumumab with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1,2) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: The ocrelizumab US prescribing information states: - Ocrelizumab and other immune-modulating or immunosuppressive therapies, (including immunosuppressant doses of corticosteroids) are expected to increase the risk of immunosuppression, and the risk of additive immune system effects must be considered if these therapies are coadministered with ocrelizumab. When switching from drugs with prolonged immune effects, such as daclizumab, fingolimod, natalizumab, teriflunomide, or mitoxantrone, the duration and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects when initiating ocrelizumab.(1) The ofatumumab US prescribing information states: - Ofatumumab and other immunosuppressive therapies (including systemic corticosteroids) may have the potential for increased immunosuppressive effects and increase the risk of infection. When switching between therapies, the duration and mechanism of action of each therapy should be considered due to the potential for additive immunosuppressive effects. Ofatumumab for MS therapy has not been studied in combination with other MS agents that suppress the immune system.(2) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1,2) In a retrospective cohort study of multiple sclerosis patients newly initiated on a disease-modifying therapy, use of high-efficacy agents (alemtuzumab, natalizumab, or ocrelizumab) resulted in the same risk of overall infections as moderate-efficacy agents, but there was an elevated risk of serious infections (adjusted hazard ratio [aHR] = 1.24, 95% confidence interval (CI) = 1.06-1.44) and UTIs (aHR = 1.21, 95% CI = 1.14-1.30).(3) |
KESIMPTA PEN, OCREVUS, OCREVUS ZUNOVO |
| Upadacitinib/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Upadacitinib, immunosuppressives, and immunomodulators all suppress the immune system. CLINICAL EFFECTS: Concurrent use of upadacitinib with immunosuppressives or immunomodulators may result in an increased risk of serious infections. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of upadacitinib states that concurrent use of upadacitinib with immunosuppressives or immunomodulators is not recommended. DISCUSSION: Serious infections have been reported in patients receiving upadacitinib. Reported infections included pneumonia, cellulitis, tuberculosis, multidermatomal herpes zoster, oral/esophageal candidiasis, cryptococcosis. Reports of viral reactivation, including herpes virus reactivation and hepatitis B reactivation, were reported in clinical studies with upadacitinib.(1) |
RINVOQ, RINVOQ LQ |
| Inebilizumab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inebilizumab, immunosuppressives, and immunomodulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of inebilizumab with immunosuppressive or immunomodulating agents may result in myelosuppression including neutropenia resulting in an increased risk for serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of inebilizumab states that the concurrent use of inebilizumab with immunosuppressive agents, including systemic corticosteroids, may increase the risk of infection. If concurrent therapy is warranted, consider the risk of additive immune suppression and monitor based on prescribing information for both agents.(1) DISCUSSION: Inebilizumab has not been studied in combination with other immunosuppressants. If concurrent therapy is warranted, consider the potential for increased immunosuppressive risks from both agents. The most common infections reported by inebilizumab treated patients in the randomized and open-label clinical trial periods included urinary tract infections (20%), nasopharyngitis (13%), upper respiratory tract infections (8%), and influenza (7%). Although there been no cases of Hepatitis B virus reactivation or progressive multifocal leukoencephalopathy reported in patients taking inebilizumab, these infections have been observed in patients taking other B-cell-depleting antibodies.(1) |
UPLIZNA |
| Baricitinib/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of baricitinib with other biologic disease-modifying antirheumatic drugs (DMARDs) or potent immunosuppressants such as azathioprine or cyclosporine may result in additive or synergistic effects on the immune system. CLINICAL EFFECTS: Concurrent use of baricitinib with other biologic DMARDs or potent immunosuppressants such as azathioprine or cyclosporine may increase the risk of serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of baricitinib states that concurrent use of baricitinib with biologic DMARDs or potent immunosuppressants is not recommended.(1) DISCUSSION: Most patients who developed serious infections while being treated with baricitinib were on concomitant immunosuppressants like methotrexate and corticosteroids. The combination of baricitinib with other biologic DMARDs has not been studied.(1) |
OLUMIANT |
| Ponatinib/Strong CYP3A4 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Agents that inhibit the CYP3A4 isoenzyme may inhibit the metabolism of ponatinib.(1) CLINICAL EFFECTS: Concurrent use of strong CYP3A4 inhibitors may increase levels of and effects from ponatinib, including thromboembolic events, hepatotoxicity, heart failure, hypertension, pancreatitis, neuropathy, ocular toxicity, hemorrhage, myelosuppression, or tumor lysis syndrome.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid the use of strong CYP3A4 inhibitors in patients undergoing therapy with ponatinib.(1) Consider alternatives with no or minimal enzyme inhibition. If concurrent administration with ponatinib is warranted, the recommended ponatinib dose should be reduced based on current daily dose during concomitant treatment:(1) -If current daily dose is 45 mg, reduce to 30 mg daily. -If current daily dose is 30 mg, reduce to 15 mg daily. -If current daily dose is 15 mg, reduce to 10 mg daily. -If current daily dose is 10 mg, avoid concurrent use with strong CYP3A4 inhibitors. Even with the dose reduction, patients receiving concomitant therapy may be at increased risk for adverse reactions. Assure recommended monitoring (e.g. complete blood counts, liver function, lipase, blood pressure measurement) is scheduled and patient is aware of signs of thrombosis (e.g. symptoms of myocardial infarction or stroke). If the ponatinib dose has been reduced due to coadministration of a CYP3A4 inhibitor, and the inhibitor is subsequently discontinued, reevaluate ponatinib efficacy and safety to determine if a dose increase is appropriate.(1) DISCUSSION: In 22 healthy volunteers, ketoconazole (400 mg once daily) increased the concentration maximum (Cmax) and area-under-curve (AUC) of a single 15 mg dose of ponatinib by 47% and 78%, respectively.(1) Strong inhibitors of CYP3A4 include: adagrasib, boceprevir, ceritinib, clarithromycin, cobicistat, idelalisib, indinavir, itraconazole, josamycin, ketoconazole, lonafarnib, lopinavir, mibefradil, mifepristone, nefazodone, nelfinavir, nirmatrelvir/ritonavir, paritaprevir, posaconazole, ribociclib, saquinavir, telaprevir, telithromycin, tipranavir, troleandomycin, tucatinib, or voriconazole.(2,3) |
APTIVUS, CLARITHROMYCIN, CLARITHROMYCIN ER, EVOTAZ, GENVOYA, ITRACONAZOLE, ITRACONAZOLE MICRONIZED, KALETRA, KETOCONAZOLE, KISQALI, KORLYM, KRAZATI, LANSOPRAZOL-AMOXICIL-CLARITHRO, LOPINAVIR-RITONAVIR, MIFEPREX, MIFEPRISTONE, NEFAZODONE HCL, NOXAFIL, OMECLAMOX-PAK, PAXLOVID, POSACONAZOLE, PREZCOBIX, RECORLEV, SPORANOX, STRIBILD, SYMTUZA, TOLSURA, TUKYSA, TYBOST, VFEND, VFEND IV, VIRACEPT, VOQUEZNA TRIPLE PAK, VORICONAZOLE, ZOKINVY, ZYDELIG, ZYKADIA |
| Leflunomide; Teriflunomide/Selected Immunosuppressants SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of leflunomide or teriflunomide and potent immunosuppressants may result in additive or synergistic effects on the immune system.(1,2) Leflunomide is a prodrug and is converted to its active metabolite teriflunomide.(1) CLINICAL EFFECTS: Concurrent use of leflunomide or teriflunomide with immunosuppressants may result in an increased risk of serious infections, including opportunistic infections, especially Pneumocystis jiroveci pneumonia, tuberculosis (including extra-pulmonary tuberculosis), and aspergillosis. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If leflunomide or teriflunomide is used concurrently with immunosuppressive agents, chronic CBC monitoring should be performed more frequently, every month instead of every 6 to 8 weeks. If bone marrow suppression or a serious infection occurs, leflunomide or teriflunomide should be stopped and rapid drug elimination procedure should be performed.(1,2) DISCUSSION: Pancytopenia, agranulocytosis and thrombocytopenia have been reported in patients receiving leflunomide or teriflunomide alone, but most frequently in patients taking concurrent immunosuppressants.(1,2) Severe and potentially fatal infections, including sepsis, have been reported in patients receiving leflunomide or teriflunomide, especially Pneumocystis jiroveci pneumonia and aspergillosis. Tuberculosis has also been reported.(1,2) |
ARAVA, AUBAGIO, LEFLUNICLO, LEFLUNOMIDE, TERIFLUNOMIDE |
| Ponesimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ponesimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of ponesimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection, cryptococcal infection, or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: The ponesimod US prescribing information states ponesimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Caution should be used during concomitant administration because of the risk of additive immune effects during therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects. Initiating treatment with ponesimod after alemtuzumab is not recommended. However, ponesimod can generally be started immediately after discontinuation of beta interferon or glatiramer acetate.(1) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections, cryptococcal meningitis, disseminated cryptococcal infections, and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1) |
PONVORY |
| Sodium Iodide I 131/Myelosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1) DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1) |
HICON, SODIUM IODIDE I-131 |
| Fingolimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Fingolimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1-3) CLINICAL EFFECTS: Concurrent use of fingolimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1-3) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: Recommendations for fingolimod regarding this interaction differ between regulatory approving agencies. The fingolimod US prescribing information states: - Antineoplastic, immune-modulating, or immunosuppressive therapies, (including corticosteroids) are expected to increase the risk of immunosuppression, and the risk of additive immune system effects must be considered if these therapies are coadministered with fingolimod. When switching from drugs with prolonged immune effects, such as natalizumab, teriflunomide or mitoxantrone, the duration and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects when initiating fingolimod.(1) The fingolimod Canadian prescribing information states: - Concurrent use with immunosuppressive or immunomodulatory agents is contraindicated due to the risk of additive immune system effects. However, co-administration of a short course of corticosteroids (up to 5 days) did not increase the overall rate of infection in patients participating Phase III clinical trials.(2) The fingolimod UK specific product characteristics states: - Fingolimod is contraindicated in patients currently receiving immunosuppressive therapies or those immunocompromised by prior therapies. When switching patients from another disease modifying therapy to Gilenya, the half-life and mode of action of the other therapy must be considered in order to avoid an additive immune effect whilst at the same time minimizing the risk of disease activation.(3) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1-3) |
FINGOLIMOD, GILENYA, TASCENSO ODT |
| Ozanimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ozanimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of ozanimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: The ozanimod US prescribing information state this information regarding this interaction: -Ozanimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Caution should be used during concomitant administration because of the risk of additive immune effects during therapy and in the week following administration. When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects. Initiating treatment with ozanimod after alemtuzumab is not recommended. However, ozanimod can generally be started immediately after discontinuation of beta interferon or glatiramer acetate.(1) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1) |
ZEPOSIA |
| Siponimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Siponimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of siponimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: The siponimod US prescribing information state this information regarding this interaction: -Siponimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Caution should be used during concomitant administration because of the risk of additive immune effects during therapy and in the week following administration. When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects. Initiating treatment with siponimod after alemtuzumab is not recommended. However, siponimod can generally be started immediately after discontinuation of beta interferon or glatiramer acetate.(1) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1) |
MAYZENT |
| Cladribine/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Cladribine in combination with immunosuppressives and immune-modulators all suppress the immune system.(1-2) CLINICAL EFFECTS: Concurrent use of cladribine with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1-2) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: Recommendations for cladribine regarding this interaction differ between regulatory approving agencies. The cladribine US prescribing information states: -Concomitant use with myelosuppressive or other immunosuppressive drugs is not recommended. Acute short-term therapy with corticosteroids can be administered. In patients who have previously been treated with immunomodulatory or immunosuppressive drugs, consider potential additive effect, the mode of action, and duration of effect of the other drugs prior to initiation of cladribine.(1) The cladribine Canadian prescribing information states: -Use of cladribine in immunocompromised patients is contraindicated because of a risk of additive effects on the immune system. Acute short-term therapy with corticosteroids can be administered during cladribine treatment.(2) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1-2) |
CLADRIBINE, MAVENCLAD |
| Ritlecitinib/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ritlecitinib, immunosuppressives, and immunomodulators all suppress the immune system. CLINICAL EFFECTS: Concurrent use of ritlecitinib with immunosuppressives or immunomodulators may result in an increased risk of serious infections. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of ritlecitinib states that concurrent use of ritlecitinib with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants is not recommended.(1) DISCUSSION: Serious infections have been reported in patients receiving ritlecitinib. Reported infections included appendicitis, COVID-19 infection (including pneumonia), and sepsis. Reports of viral reactivation, including herpes virus reactivation was reported in clinical studies with ritlecitinib.(1) |
LITFULO |
| Etrasimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Etrasimod causes reversible sequestration of lymphocytes in lymphoid tissues, resulting in a mean 55% decrease in peripheral blood lymphocyte count at 52 weeks.(1) Other immunosuppressives and immune-modulators also suppress the immune system. CLINICAL EFFECTS: Concurrent use of etrasimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious and fatal infections, such as disseminated herpetic infection, cryptococcal infection, or progressive multifocal leukoencephalopathy (PML).(1) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications increases the risk of adverse effects. PATIENT MANAGEMENT: The etrasimod US prescribing information states etrasimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Concomitant administration of these therapies with etrasimod should be avoided because of the risk of additive immune effects during therapy and in the weeks following administration. Etrasimod's effect on peripheral lymphocytes may persist for up to 5 weeks after discontinuation.(1) When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects.(1) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections, cryptococcal meningitis, disseminated cryptococcal infections, and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients treated with other sphingosine-1 phosphate receptor modulators.(1) |
VELSIPITY |
| Ropeginterferon alfa-2b/Slt Immunosuppress; Immunomodulator SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ropeginterferon alfa-2b and immunosuppressives both suppress the immune system. CLINICAL EFFECTS: Concurrent use of ropeginterferon alfa-2b with immunosuppressives may result in an increased risk of serious infections. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid concurrent use of myelosuppressive agents.(1-2) If concurrent use cannot be avoided, monitor for effects of excessive immunosuppression. DISCUSSION: In clinical trials, 20% of patients experienced leukopenia. Interferon alfa products may cause fatal or life-threatening infections.(1-2) |
BESREMI |
| Deuruxolitinib/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Deuruxolitinib, immunosuppressives, and immunomodulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of deuruxolitinib and potent immunosuppressants may increase the risk of serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of deuruxolitinib states that concurrent use of deuruxolitinib with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants is not recommended.(1) If concurrent use cannot be avoided, patients should be monitored for signs and symptoms of infection. If a patient develops a serious or opportunistic infection, interrupt deuruxolitinib treatment until the infection is controlled. DISCUSSION: Serious infections have been reported in patients receiving treatment with deuruxolitinib.(1) |
LEQSELVI |
There are 5 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Ustekinumab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Ustekinumab, immunosuppressives, and immunomodulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of ustekinumab with immunosuppressive or immunomodulating agents may result in an increased risk for serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of ustekinumab recommends caution because the concurrent use of ustekinumab with immunosuppressive agents may increase the risk of infection. If concurrent therapy is warranted, consider the risk of additive immune suppression and monitor based on prescribing information for both agents.(1) DISCUSSION: Ustekinumab has not been studied in combination with other immunosuppressants in psoriasis studies. In psoriatic arthritis studies, concomitant methotrexate use did not appear to influence the safety or efficacy of ustekinumab. In Crohn's disease and ulcerative colitis studies, concomitant use of immunosuppressants or corticosteroids did not appear to influence the safety or efficacy of ustekinumab. If concurrent therapy is warranted, consider the potential for increased immunosuppressive risks from both agents.(1) The most common infections reported by ustekinumab treated patients in the clinical trial periods included nasopharyngitis(8%) and upper respiratory tract infection(5%). Serious bacterial, mycobacterial, fungal, and viral infections were observed in patients receiving ustekinumab. Cases of interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia resulting in respiratory failure or prolonged hospitalization have been reported in patients receiving ustekinumab.(1) |
IMULDOSA, OTULFI, PYZCHIVA, SELARSDI, STELARA, STEQEYMA, USTEKINUMAB, USTEKINUMAB-AEKN, USTEKINUMAB-TTWE, WEZLANA, YESINTEK |
| COVID-19 Vaccines/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Immunosuppressants and immunomodulators may prevent the immune system from properly responding to the COVID-19 vaccine.(1,2) CLINICAL EFFECTS: Administration of a COVID-19 vaccine with immunosuppressants or immunomodulators may interfere with vaccine-induced immune response and impair the efficacy of the vaccine. However, patients should be offered and given a COVID-19 vaccine even if the use and timing of immunosuppressive agents cannot be adjusted.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: In an effort to optimize COVID-19 vaccine response, the American College of Rheumatology (ACR) published conditional recommendations for administration of COVID-19 vaccines with immunosuppressants and immunomodulators.(1) The CDC also provides clinical considerations for COVID-19 vaccination in patients on immunosuppressants.(2) The CDC states that all immunocompromised patients over 6 months of age should receive at least 1 dose of COVID-19 vaccine if eligible. See the CDC's Interim Clinical Considerations for Use of COVID-19 Vaccines for specific recommendations based on age, vaccination history, and vaccine manufacturer.(2) The ACR states that in general, immunosuppressants and immunomodulators should be held for 1-2 weeks after each vaccine dose. See below for specific recommendations for certain agents.(1) The CDC advises planning for vaccination at least 2 weeks before starting or resuming immunosuppressive therapy.(2) Patients should be offered and given a COVID-19 vaccine even if the use and timing of immunosuppressive agents cannot be adjusted.(1,2) B-cell depleting agents, including rituximab: The ACR recommends consulting with the rheumatologist to determine optimal timing of COVID-19 vaccination. Measuring CD19 B cells may be considered to determine need for a booster vaccine dose. If B cell levels are not measured, a supplemental vaccine dose 2-4 weeks before the next scheduled dose of rituximab is recommended.(1) The CDC states that the utility of B-cell quantification to guide clinical care is not known and is not recommended. Patients who receive B-cell depleting therapy should receive COVID-19 vaccines about 4 weeks before the next scheduled dose. For patients who received 1 or more doses of COVID-19 vaccine during treatment with B-cell-depleting therapies that were administered over a limited period (e.g., as part of a treatment regimen for certain malignancies), revaccination may be considered. The suggested interval to start revaccination is about 6 months after completion of the B-cell-depleting therapy.(2) Abatacept: - Subcutaneous abatacept should be withheld for 1-2 weeks after each vaccine dose, as disease activity allows. - For intravenous abatacept, time administration so that vaccination will occur 1 week before the next abatacept infusion.(1) Cyclophosphamide: When feasible, administer cyclophosphamide one week after each COVID-19 vaccine dose.(1) Recipients of hematopoietic cell transplant or CAR-T-cell therapy who received one or more doses of COVID-19 vaccine prior to or during treatment should undergo revaccination following the current CDC recommendations for unvaccinated patients. Revaccination should start at least 3 months (12 weeks) after transplant or CAR-T-cell therapy.(2) TNF-alpha inhibitors and cytokine inhibitors: The ACR was not able to reach consensus on whether to modify dosing or timing of these agents with COVID-19 vaccination.(1) The CDC includes these agents in their general recommendation to hold therapy for at least 2 weeks following vaccination.(2) DISCUSSION: The ACR convened a COVID-19 Vaccine Guidance Task Force to provide guidance on optimal use of COVID-19 vaccines in rheumatology patients. These recommendations are based on limited clinical evidence of COVID-19 vaccines in patients without rheumatic and musculoskeletal disorders and evidence of other vaccines in this patient population.(1) The ACR recommendation for rituximab is based on studies of humoral immunity following receipt of other vaccines. These studies have uncertain generalizability to vaccination against COVID-19, as it is unknown if efficacy is attributable to induction of host T cells versus B cell (antibody-based) immunity.(1) The ACR recommendation for mycophenolate is based on preexisting data of mycophenolate on non-COVID-19 vaccine immunogenicity. Emerging data suggests that mycophenolate may impair SARS-CoV-2 vaccine response in rheumatic and musculoskeletal disease and transplant patients.(1) The ACR recommendation for methotrexate is based on data from influenza vaccines and pneumococcal vaccines with methotrexate.(1) The ACR recommendation for JAK inhibitors is based on concerns related to the effects of JAK inhibitors on interferon signaling that may result in a diminished vaccine response.(1) The ACR recommendation for subcutaneous abatacept is based on several studies suggesting a negative effect of abatacept on vaccine immunogenicity. The first vaccine dose primes naive T cells, naive T cell priming is inhibited by CTLA-4, and abatacept is a CTLA-4Ig construct. CTLA-4 should not inhibit boosts of already primed T cells at the time of the second vaccine dose.(1) |
COMIRNATY 2024-2025, MODERNA COVID 24-25(6M-11Y)EUA, NOVAVAX COVID 2024-2025 (EUA), PFIZER COVID 2024-25(5-11Y)EUA, PFIZER COVID 2024-25(6M-4Y)EUA, SPIKEVAX 2024-2025 |
| Sarilumab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Sarilumab, immunosuppressives, and immunomodulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of sarilumab with immunosuppressive or immunomodulating agents may result in an increased risk for serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of sarilumab recommends caution because the concurrent use of sarilumab with immunosuppressive agents may increase the risk of infection. If concurrent therapy is warranted, consider the risk of additive immune suppression and monitor based on prescribing information for both agents.(1) DISCUSSION: Sarilumab was studied as monotherapy and in combination with methotrexate or conventional disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis studies. Sarilumab has not been studied with biological DMARDs and concurrent use should be avoided. If concurrent therapy is warranted, consider the potential for increased immunosuppressive risks from both agents.(1) The most common infections reported by sarilumab treated patients in the clinical trial periods included pneumonia and cellulitis. Serious bacterial, mycobacterial, fungal, and viral infections were observed in patients receiving sarilumab. Cases of tuberculosis, candidiasis, and pneumocystis with sarilumab have been reported.(1) |
KEVZARA |
| Ublituximab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Ublituximab, immunosuppressives, and immunomodulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of ublituximab with immunosuppressive or immunomodulating agents may result in an increased risk for serious infections.(1) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: The US manufacturer of ublituximab recommends caution because the concurrent use of ublituximab with immunomodulating or immunosuppressive agents, including immunosuppressant doses of corticosteroids, may increase the risk of infection.(1) If concurrent therapy is warranted, consider the risk of additive immune suppression and monitor based on prescribing information for both agents. When switching from agents with immune effects, the half-life and mechanism of action of these drugs must be taken into consideration in order to prevent additive immunosuppressive effects.(1) DISCUSSION: The most common infections reported by ublituximab-treated patients in the clinical trial periods included upper respiratory tract infections and urinary tract infections. Serious, including life-threatening or fatal, bacterial and viral infections were observed in patients receiving ublituximab.(1) Serious and/or fatal bacterial, fungal, and new or reactivated viral infections have been associated with other anti-CD20 B-cell depleting therapies. There were no cases of progressive multifocal leukoencephalopathy (PML) reported during the clinical trials; however, there have been reports of PML during or following completion of other anti-CD20 B-cell depleting therapies.(1) |
BRIUMVI |
| Tocilizumab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Tocilizumab, immunosuppressives, and immunomodulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of tocilizumab with immunosuppressive or immunomodulating agents may result in an increased risk for serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of tocilizumab recommends caution because the concurrent use of tocilizumab with immunosuppressive agents may increase the risk of infection. If concurrent therapy is warranted, consider the risk of additive immune suppression and monitor based on prescribing information for both agents.(1) DISCUSSION: Tocilizumab was studied as monotherapy and in combination with methotrexate, non-biologic DMARDs or corticosteroids, depending on the indication. Tocilizumab has not been studied with biological DMARDs and concurrent use should be avoided. If concurrent therapy is warranted, consider the potential for increased immunosuppressive risks from both agents.(1) The most common infections reported by tocilizumab treated patients in the clinical trial periods included pneumonia, urinary tract infection, cellulitis, herpes zoster, gastroenteritis, diverticulitis, sepsis and bacterial arthritis. Serious bacterial, mycobacterial, fungal, and viral infections were observed in patients receiving tocilizumab. Cases of tuberculosis, cryptococcus, aspergillosis, candidiasis, and pneumocystosis have been reported.(1) |
ACTEMRA, ACTEMRA ACTPEN, TOFIDENCE, TYENNE, TYENNE AUTOINJECTOR |
The following contraindication information is available for ICLUSIG (ponatinib hcl):
Drug contraindication overview.
*None.
*None.
There are 3 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Arterial aneurysm |
| Arterial dissection |
| Lactation |
There are 23 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Acute coronary arterial thrombosis |
| Acute decompensated heart failure |
| Acute myocardial infarction |
| Anemia |
| Arterial thrombosis |
| Cerebrovascular accident |
| Chronic heart failure |
| Coronary artery disease |
| Disease of liver |
| Gastrointestinal perforation |
| Hemorrhage |
| Hypertension |
| Intracranial bleeding |
| Invasive surgical procedure |
| Neutropenic disorder |
| Occlusive vascular disease |
| Pancreatitis |
| Peripheral vascular disease |
| Posterior reversible encephalopathy syndrome |
| Pregnancy |
| Thrombocytopenic disorder |
| Thromboembolic disorder |
| Venous thrombosis |
There are 6 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Bradycardia |
| Edema |
| Impaired wound healing |
| Peripheral neuropathy |
| Supraventricular arrhythmias |
| Viral hepatitis B |
The following adverse reaction information is available for ICLUSIG (ponatinib hcl):
Adverse reaction overview.
The most common adverse reactions reported in >20% of patients receiving ponatinib as monotherapy include rash and related conditions, arthralgia, abdominal pain, headache, constipation, dry skin, hypertension, fatigue, fluid retention and edema, pyrexia, nausea, pancreatitis/lipase elevation, hemorrhage, anemia, hepatic dysfunction, and arterial occlusive events. Grade 3 or 4 laboratory abnormalities reported in more than 20% of patients include decreased platelet count, decreased neutrophil count, and decreased white blood cell count. The most common adverse reactions reported in patients receiving ponatinib in combination with chemotherapy include hepatic dysfunction, arthralgia, rash and related conditions, headache, pyrexia, abdominal pain, constipation, fatigue, nausea, oral mucositis, hypertension, pancreatitis/lipase elevation, peripheral neuropathy, hemorrhage, febrile neutropenia, fluid retention and edema, vomiting, paresthesia, and cardiac arrhythmias. Grade 3 or 4 laboratory abnormalities reported in more than 20% of patients include decreased white blood cell count, decreased neutrophil count, decreased platelet count, decreased lymphocytes, decreased hemoglobin, increased lipase, and increased ALT.
The most common adverse reactions reported in >20% of patients receiving ponatinib as monotherapy include rash and related conditions, arthralgia, abdominal pain, headache, constipation, dry skin, hypertension, fatigue, fluid retention and edema, pyrexia, nausea, pancreatitis/lipase elevation, hemorrhage, anemia, hepatic dysfunction, and arterial occlusive events. Grade 3 or 4 laboratory abnormalities reported in more than 20% of patients include decreased platelet count, decreased neutrophil count, and decreased white blood cell count. The most common adverse reactions reported in patients receiving ponatinib in combination with chemotherapy include hepatic dysfunction, arthralgia, rash and related conditions, headache, pyrexia, abdominal pain, constipation, fatigue, nausea, oral mucositis, hypertension, pancreatitis/lipase elevation, peripheral neuropathy, hemorrhage, febrile neutropenia, fluid retention and edema, vomiting, paresthesia, and cardiac arrhythmias. Grade 3 or 4 laboratory abnormalities reported in more than 20% of patients include decreased white blood cell count, decreased neutrophil count, decreased platelet count, decreased lymphocytes, decreased hemoglobin, increased lipase, and increased ALT.
There are 60 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Anemia Arterial thrombosis Bone marrow depression Hypertension Increased alanine transaminase Increased alkaline phosphatase Increased aspartate transaminase Infection Leukopenia Lymphopenia Neutropenic disorder Pleural effusions Thrombocytopenic disorder Thromboembolic disorder |
Acute myocardial infarction Atrial fibrillation Cerebrovascular accident Chronic heart failure Gastrointestinal hemorrhage Hemorrhage Hypothyroidism Intracerebral hemorrhage Pancreatitis Peripheral vascular disease Pneumonia Retinal hemorrhage Retinal vascular occlusion Supraventricular arrhythmias Supraventricular tachycardia |
| Rare/Very Rare |
|---|
|
Abnormal hepatic function tests Acute cerebral infarction Arterial aneurysm Arterial dissection Bradycardia Cataracts Corneal ulcer Cranial nerve disorder Dehydration Disseminated intravascular coagulation Drug-induced hepatitis Erythema multiforme Gastrointestinal fistula Gastrointestinal perforation Heart block Hepatic failure Hypertensive crisis Hyperthyroidism Impaired wound healing Iridocyclitis Iritis Mesenteric artery thrombosis Peripheral ischemia Posterior reversible encephalopathy syndrome Reactivation of hepatitis B Retinal thrombosis Stevens-johnson syndrome Subdural intracranial hemorrhage Thrombosis of retinal vein Thrombotic thrombocytopenic purpura Tumor lysis syndrome |
There are 44 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Acute abdominal pain Anorexia Arthralgia Constipation Cough Diarrhea Dry skin Dyspnea Elevated serum lipase Fatigue Fever Headache disorder Myalgia Nausea Pain Pain in extremities Peripheral neuropathy Skin rash Stomatitis Vomiting |
Back pain Blurred vision Body fluid retention Bone pain Chills Dizziness Dry eye Elevated serum amylase Hyperesthesia Hypoesthesia Insomnia Macular retinal edema Muscle spasm Ocular pain Paresthesia Periorbital edema Peripheral edema Skin pigmentation enhancement Weight loss |
| Rare/Very Rare |
|---|
|
Acquired melanocytic nevus Glaucoma Muscle rigidity Panniculitis Squamous cell carcinoma of skin |
The following precautions are available for ICLUSIG (ponatinib hcl):
Safety and efficacy have not been established in pediatric patients younger than 18 years of age.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Based on its mechanism of action and findings from animal studies, ponatinib may cause fetal harm. In animal reproduction studies, oral administration of ponatinib to pregnant rats during organogenesis caused adverse developmental effects at doses lower than human exposures at the recommended human dose. There are no available data in human pregnancy.
Verify the pregnancy status of females of reproductive potential prior to initiating ponatinib. If used during pregnancy or if the patient becomes pregnant while receiving ponatinib, apprise the patient of the potential fetal hazard.
Verify the pregnancy status of females of reproductive potential prior to initiating ponatinib. If used during pregnancy or if the patient becomes pregnant while receiving ponatinib, apprise the patient of the potential fetal hazard.
There are no data on the presence of ponatinib in human milk or the effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions to ponatinib in breastfed children, advise patients to avoid breastfeeding during ponatinib treatment and for 1 week following the last dose.
Because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly, caution is advised in dose selection for geriatric patients. Of the 94 patients in the OPTIC trial who received ponatinib 45 mg daily as their initial dosage, 17% were 65 years of age or older and 2.1% were 75 years of age or older.
Patients 65 years of age or older had lower rates of BCR-ABL1IS <=1% at 12 months compared to younger patients (27% versus 47%). Patients 65 years of age or older were also more likely to experience arterial occlusive events compared to younger patients (38% versus 9%). In the PACE trial, 35% of patients were 65 years of age or older and 8% were 75 years of age or older.
In patients with chronic phase CML, the major cytogenetic response rate was 40% in those 65 years of age and older compared with 65% in those younger than 65 years of age. In patients with accelerated or blast phase CML or with Ph+ ALL, the major hematologic response rate was 45% in those 65 years of age and older compared with 44% in those younger than 65 years of age. Arterial occlusive events occurred in 35% of patients 65 years of age or older and 21% of patients younger than 65 years of age.
In the PhALLCON trial, 21% of patients were 65 years of age or older and 7% were 75 years of age or older. No differences in efficacy were seen in patients 65 years of age or older and younger patients. Arterial occlusive events occurred more frequently in patients 65 years of age and older as compared to those less than 65 years of age (21% versus 2.3%).
Adverse reactions associated with ponatinib therapy (e.g., vascular occlusion, thrombocytopenia, peripheral edema, elevated serum lipase concentration, dyspnea, asthenia, muscle spasm, decreased appetite) may occur more frequently in patients 65 years of age or older. Because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly, caution is advised in dose selection for geriatric patients.
Patients 65 years of age or older had lower rates of BCR-ABL1IS <=1% at 12 months compared to younger patients (27% versus 47%). Patients 65 years of age or older were also more likely to experience arterial occlusive events compared to younger patients (38% versus 9%). In the PACE trial, 35% of patients were 65 years of age or older and 8% were 75 years of age or older.
In patients with chronic phase CML, the major cytogenetic response rate was 40% in those 65 years of age and older compared with 65% in those younger than 65 years of age. In patients with accelerated or blast phase CML or with Ph+ ALL, the major hematologic response rate was 45% in those 65 years of age and older compared with 44% in those younger than 65 years of age. Arterial occlusive events occurred in 35% of patients 65 years of age or older and 21% of patients younger than 65 years of age.
In the PhALLCON trial, 21% of patients were 65 years of age or older and 7% were 75 years of age or older. No differences in efficacy were seen in patients 65 years of age or older and younger patients. Arterial occlusive events occurred more frequently in patients 65 years of age and older as compared to those less than 65 years of age (21% versus 2.3%).
Adverse reactions associated with ponatinib therapy (e.g., vascular occlusion, thrombocytopenia, peripheral edema, elevated serum lipase concentration, dyspnea, asthenia, muscle spasm, decreased appetite) may occur more frequently in patients 65 years of age or older. Because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly, caution is advised in dose selection for geriatric patients.
The following prioritized warning is available for ICLUSIG (ponatinib hcl):
WARNING: Ponatinib has caused serious (sometimes fatal) problems from blood clots (such as heart attack, stroke, blood clots in the lungs or legs). Get medical help right away if you have: chest/jaw/left arm pain, unusual sweating, confusion, trouble speaking, weakness on one side of the body, sudden/severe headaches, sudden dizziness/fainting, sudden vision changes, shortness of breath/rapid breathing, pain/swelling/warmth in the groin/calf. 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.
WARNING: Ponatinib has caused serious (sometimes fatal) problems from blood clots (such as heart attack, stroke, blood clots in the lungs or legs). Get medical help right away if you have: chest/jaw/left arm pain, unusual sweating, confusion, trouble speaking, weakness on one side of the body, sudden/severe headaches, sudden dizziness/fainting, sudden vision changes, shortness of breath/rapid breathing, pain/swelling/warmth in the groin/calf. 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.
The following icd codes are available for ICLUSIG (ponatinib hcl)'s list of indications:
| Accelerated phase chronic myelocytic leukemia | |
| C92.1 | Chronic myeloid leukemia, BCr/ABl-positive |
| C92.10 | Chronic myeloid leukemia, BCr/ABl-positive, not having achieved remission |
| C92.12 | Chronic myeloid leukemia, BCr/ABl-positive, in relapse |
| C92.2 | Atypical chronic myeloid leukemia, BCr/ABl-negative |
| C92.20 | Atypical chronic myeloid leukemia, BCr/ABl-negative, not having achieved remission |
| C92.22 | Atypical chronic myeloid leukemia, BCr/ABl-negative, in relapse |
| Blastic phase chronic myeloid leukemia | |
| C92.1 | Chronic myeloid leukemia, BCr/ABl-positive |
| C92.10 | Chronic myeloid leukemia, BCr/ABl-positive, not having achieved remission |
| C92.12 | Chronic myeloid leukemia, BCr/ABl-positive, in relapse |
| C92.2 | Atypical chronic myeloid leukemia, BCr/ABl-negative |
| C92.20 | Atypical chronic myeloid leukemia, BCr/ABl-negative, not having achieved remission |
| C92.22 | Atypical chronic myeloid leukemia, BCr/ABl-negative, in relapse |
| Chronic phase chronic myeloid leukemia | |
| C92.1 | Chronic myeloid leukemia, BCr/ABl-positive |
| C92.10 | Chronic myeloid leukemia, BCr/ABl-positive, not having achieved remission |
| C92.2 | Atypical chronic myeloid leukemia, BCr/ABl-negative |
| C92.20 | Atypical chronic myeloid leukemia, BCr/ABl-negative, not having achieved remission |
| Philadelphia chromosome positive ALL | |
| C91.0 | Acute lymphoblastic leukemia [ALl] |
| C91.00 | Acute lymphoblastic leukemia not having achieved remission |
| C91.02 | Acute lymphoblastic leukemia, in relapse |
Formulary Reference Tool