Stelara

Drug overview for STELARA (ustekinumab):

Generic name: USTEKINUMAB (US-te-KIN-ue-mab)
Drug class: Antipsoriatics
Therapeutic class: Dermatological

Ustekinumab and ustekinumab-auub, human immunoglobulin G1 kappa (IgG1) monoclonal antibodies directed against the p40 subunit of interleukin-12 (IL-12) and interleukin-23 (IL-23), are immunosuppressive agents. Ustekinumab-auub is biosimilar to ustekinumab (Stelara(R)). FDA defines a biosimilar as a biological product that is highly similar toan FDA-licensed reference biological with the exception of minor differences in clinicallyinactive components and for which there are no clinically meaningful differences in safety,purity, or potency.

The claim of biosimilarity is based on a totality-of-evidenceapproach, which includes consideration of data from analytical, animal, and clinical studies(e.g., human pharmacokinetic and pharmacodynamic studies, clinical immunogenicity assessment, additional comparative clinical studies). Therefore, biosimilarity may be established even when there are formulation or minor structural differences as long as thesedifferences are not clinically meaningful. Biosimilars are approved through an abbreviatedlicensure pathway that establishes biosimilarity between the proposed biological and thereference biological but does not independently establish safety and effectiveness of theproposed biological.

In order to be considered an interchangeable biosimilar, a biologicalproduct must meet additional requirements beyond demonstrating biosimilarity to its referenceproduct; these requirements include demonstrating that the biological product can be expectedto produce the same clinical results as the reference product in any given patient and, for abiological product that is administered more than once to an individual, the risk in terms ofsafety or diminished efficacy of alternating or switching between use of the biological productand the reference product is no greater than the risk of using the reference product withoutsuch alternation or switch. Biosimilar products that are interchangeable can be substituted for the reference product without the intervention of the healthcare provider who prescribed the reference product. The currently available evidence demonstrates that the ustekinumab biosimilar (Wezlana(R)) is interchangeable with Stelera(R) at the pharmacy level. In this monograph, unless otherwise stated, the term ''ustekinumab products'' refers to ustekinumab(the reference drug) and its biosimilar (ustekinumab-auub).

No enhanced Uses information available for this drug.

DRUG IMAGES

STELARA 45 MG/0.5 ML VIAL
STELARA 90 MG/ML SYRINGE
STELARA 45 MG/0.5 ML SYRINGE
STELARA 130 MG/26 ML VIAL

The following indications for STELARA (ustekinumab) have been approved by the FDA:

Indications:
Crohn's disease
Moderate to severe plaque psoriasis
Psoriatic arthritis
Ulcerative colitis

Professional Synonyms:
Colitis ulcerativa
Psoriasis arthropica
Psoriatic arthropathy
Regional enteritis
Regional ileocolitis

The following drug interaction information is available for STELARA (ustekinumab):

Contraindicated
Severe
Moderate

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)	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 TRIVALENT 2024-2025, IXCHIQ, JYNNEOS, JYNNEOS (NATIONAL STOCKPILE), 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 9 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
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
IgG Antibodies and Derivatives/Efgartigimod-alfa SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3) DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod alfa may decrease concentrations of compounds that bind to the human FcRn.(3)	VYVGART, VYVGART HYTRULO
Anifrolumab/Biologic Therapies SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of anifrolumab with other biologic therapies may result in additive or synergistic effects on the immune system.(1) CLINICAL EFFECTS: Concurrent use of anifrolumab with other biologic therapies may increase the risk of serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The concurrent use of anifrolumab with other biologic therapies is not recommended.(1) DISCUSSION: The combination of anifrolumab with other biologic therapies has not been studied and is not recommended.(1)	SAPHNELO
Pozelimab/IgG Antibodies and Derivatives SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Pozelimab is an IgG4P antibody. Concurrent use of immunoglobulins and other IgG-based antibodies that bind to FcRn may interfere with the FcRn recycling mechanism of pozelimab and decrease systemic exposure of pozelimab.(3) CLINICAL EFFECTS: The levels and effectiveness of pozelimab may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of pozelimab states that concomitant use of intravenous immunoglobulin should avoided with pozelimab. If concomitant use cannot be avoided, monitor patients for worsening signs and symptoms of CD55-deficient protein-losing enteropathy.(3) DISCUSSION: Clinical drug interaction studies with pozelimab have not been performed. Immunoglobulins may interfere with the endosomal FcRn recycling mechanism of monoclonal antibodies like pozelimab and decrease concentrations of pozelimab.(3)	VEOPOZ
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

There are 4 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)	ABECMA, ABRAXANE, ABRILADA(CF), ABRILADA(CF) PEN, ACTEMRA, ACTEMRA ACTPEN, ACTIMMUNE, ADALIMUMAB-AACF(CF), ADALIMUMAB-AACF(CF) PEN, ADALIMUMAB-AACF(CF) PEN CROHNS, ADALIMUMAB-AACF(CF) PEN PS-UV, ADALIMUMAB-AATY(CF), ADALIMUMAB-AATY(CF) AUTOINJECT, ADALIMUMAB-ADAZ(CF), ADALIMUMAB-ADAZ(CF) PEN, ADALIMUMAB-ADBM(CF), ADALIMUMAB-ADBM(CF) PEN, ADALIMUMAB-ADBM(CF) PEN CROHNS, ADALIMUMAB-ADBM(CF) PEN PS-UV, ADALIMUMAB-ADBM(CF)PEN, ADALIMUMAB-FKJP(CF), ADALIMUMAB-FKJP(CF) PEN, ADALIMUMAB-RYVK(CF), ADALIMUMAB-RYVK(CF) AUTOINJECT, ADCETRIS, ADRIAMYCIN, ADRUCIL, AFINITOR, AFINITOR DISPERZ, AKEEGA, ALFERON N, ALIMTA, ALIQOPA, ALKERAN, ALUNBRIG, ALYMSYS, AMJEVITA(CF), AMJEVITA(CF) AUTOINJECTOR, AMTAGVI, ARAVA, ARCALYST, ARRANON, ARSENIC TRIOXIDE, ARZERRA, ASPARLAS, ASTAGRAF XL, AUBAGIO, AUGTYRO, AVASTIN, AVONEX, AVONEX PEN, AVSOLA, AZACITIDINE, AZELAIC ACID, BAFIERTAM, BAVENCIO, BELEODAQ, BELRAPZO, BENDAMUSTINE HCL, BENDEKA, BESPONSA, BESREMI, BETASERON, BEXAROTENE, BICNU, BIMZELX, BIMZELX AUTOINJECTOR, BLEOMYCIN SULFATE, BLINCYTO, BORTEZOMIB, BOSULIF, BRAFTOVI, BREYANZI, BREYANZI CD4 COMPONENT, BREYANZI CD8 COMPONENT, BRIUMVI, BRUKINSA, BUSULFAN, BUSULFEX, CAELYX, CALQUENCE, CAMPATH, CAMPTOSAR, CAPECITABINE, CARBOPLATIN, CARMUSTINE, CARVYKTI, CELLCEPT, CIBINQO, CIMZIA, CISPLATIN, CLADRIBINE, CLOFARABINE, COLUMVI, COPAXONE, COPIKTRA, COSENTYX, COSENTYX (2 SYRINGES), COSENTYX SENSOREADY (2 PENS), COSENTYX SENSOREADY PEN, COSENTYX SYRINGE, COSENTYX UNOREADY PEN, COSMEGEN, CYCLOPHOSPHAMIDE, CYCLOSPORINE, CYCLOSPORINE MODIFIED, CYLTEZO(CF), CYLTEZO(CF) PEN, CYLTEZO(CF) PEN CROHN'S-UC-HS, CYLTEZO(CF) PEN PSORIASIS-UV, CYTARABINE, DACARBAZINE, DACOGEN, DACTINOMYCIN, DANYELZA, DARAPRIM, DARZALEX, DARZALEX FASPRO, DASATINIB, DAUNORUBICIN HCL, DAURISMO, DECITABINE, DEXRAZOXANE, DIMETHYL FUMARATE, DOCETAXEL, DOCIVYX, DOXIL, DOXORUBICIN HCL, DOXORUBICIN HCL LIPOSOME, DROXIA, EFLORNITHINE HCL, ELAHERE, ELLENCE, ELREXFIO, ENBREL, ENBREL MINI, ENBREL SURECLICK, ENHERTU, ENSPRYNG, ENTYVIO, ENTYVIO PEN, ENVARSUS XR, EPIRUBICIN HCL, EPKINLY, ERBITUX, ERLOTINIB HCL, ERWINASE, ETOPOPHOS, ETOPOSIDE, EVEROLIMUS, EVOMELA, FARYDAK, FLOXURIDINE, FLUDARABINE PHOSPHATE, FLUOROURACIL, FOLOTYN, FYARRO, GAMIFANT, GAVRETO, GAZYVA, GEFITINIB, GEMCITABINE HCL, GENGRAF, GLATIRAMER ACETATE, GLATOPA, GLEEVEC, GLEOSTINE, GLIADEL, HADLIMA, HADLIMA PUSHTOUCH, HADLIMA(CF), HADLIMA(CF) PUSHTOUCH, HEPZATO, HERCEPTIN, HERCEPTIN HYLECTA, HERZUMA, HULIO(CF), HULIO(CF) PEN, HUMIRA, HUMIRA PEN, HUMIRA(CF), HUMIRA(CF) PEN, HUMIRA(CF) PEN CROHN'S-UC-HS, HUMIRA(CF) PEN PEDIATRIC UC, HUMIRA(CF) PEN PSOR-UV-ADOL HS, HYCAMTIN, HYDREA, HYDROXYUREA, HYRIMOZ, HYRIMOZ PEN, HYRIMOZ(CF), HYRIMOZ(CF) PEDIATRIC CROHN'S, HYRIMOZ(CF) PEN, HYRIMOZ(CF) PEN CROHN-UC START, HYRIMOZ(CF) PEN PSORIASIS, IBRANCE, ICLUSIG, IDACIO(CF), IDACIO(CF) PEN, IDACIO(CF) PEN CROHN'S-UC, IDACIO(CF) PEN PSORIASIS, IDAMYCIN PFS, IDARUBICIN HCL, IFEX, IFOSFAMIDE, ILARIS, IMATINIB MESYLATE, IMBRUVICA, IMDELLTRA, IMFINZI, INFLECTRA, INFLIXIMAB, INFUGEM, INQOVI, INREBIC, IRESSA, IRINOTECAN HCL, ISTODAX, IWILFIN, IXEMPRA, JAKAFI, JAYPIRCA, JEMPERLI, JEVTANA, JOENJA, JYLAMVO, KADCYLA, KANJINTI, KEMOPLAT, KESIMPTA PEN, KEVZARA, KEYTRUDA, KINERET, KISQALI, KYMRIAH, LAPATINIB, LEFLUNICLO, LEFLUNOMIDE, LEMTRADA, LENALIDOMIDE, LEUKERAN, LITFULO, LONSURF, LUNSUMIO, LUTATHERA, LYNPARZA, MATULANE, MAVENCLAD, MEKINIST, MEKTOVI, MELPHALAN HCL, METHOTREXATE, METHOTREXATE SODIUM, MITOMYCIN, MITOXANTRONE HCL, MONJUVI, MUTAMYCIN, MVASI, MYCOPHENOLATE MOFETIL, MYCOPHENOLIC ACID, MYFORTIC, MYHIBBIN, MYLERAN, NELARABINE, NEORAL, NIPENT, NULOJIX, OCREVUS, OCREVUS ZUNOVO, OGIVRI, OJJAARA, OLUMIANT, ONCASPAR, ONIVYDE, ONTRUZANT, ONUREG, OPDIVO, OPDUALAG, ORENCIA, ORENCIA CLICKJECT, OXALIPLATIN, PACLITAXEL, PACLITAXEL PROTEIN-BOUND, PADCEV, PARAPLATIN, PAZOPANIB HCL, PEGASYS, PEMETREXED, PEMETREXED DISODIUM, PEMFEXY, PEMRYDI RTU, PERJETA, PHESGO, PHOTOFRIN, PLEGRIDY, PLEGRIDY PEN, PLUVICTO, POLIVY, POMALYST, POTELIGEO, PRALATREXATE, PROCARBAZINE HCL, PROGRAF, PROLEUKIN, PROVENGE, PYRIMETHAMINE, REBIF, REBIF REBIDOSE, REMICADE, RENFLEXIS, REVLIMID, REZUROCK, RIABNI, RINVOQ, RINVOQ LQ, RITUXAN, RITUXAN HYCELA, ROMIDEPSIN, RUBRACA, RUXIENCE, RYDAPT, RYLAZE, RYTELO, SANDIMMUNE, SARCLISA, SCEMBLIX, SIKLOS, SIMLANDI(CF) AUTOINJECTOR, SIMPONI, SIMPONI ARIA, SIMULECT, SIROLIMUS, SODIUM IODIDE I-123, SOTYKTU, SPRYCEL, STRONTIUM-89 CHLORIDE, SUNITINIB MALATE, SUTENT, TABLOID, TACROLIMUS, TACROLIMUS XL, TALTZ AUTOINJECTOR, TALTZ AUTOINJECTOR (2 PACK), TALTZ AUTOINJECTOR (3 PACK), TALTZ SYRINGE, TALVEY, TALZENNA, TARCEVA, TARGRETIN, TASIGNA, TECARTUS, TECELRA, TECENTRIQ, TECENTRIQ HYBREZA, TECFIDERA, TECVAYLI, TEMODAR, TEMOZOLOMIDE, TEMSIROLIMUS, TEPADINA, TERIFLUNOMIDE, TEVIMBRA, THIOTEPA, TOFACITINIB CITRATE, TOFIDENCE, TOPOTECAN HCL, TORISEL, TORPENZ, TOTECT, TRAMETINIB, TRAZIMERA, TREANDA, TRETINOIN, TREXALL, TRISENOX, TRODELVY, TRUQAP, TRUXIMA, TYENNE, TYENNE AUTOINJECTOR, TYKERB, TZIELD, UNITUXIN, UPLIZNA, UVADEX, VANFLYTA, VECTIBIX, VEGZELMA, VELCADE, VENCLEXTA, VENCLEXTA STARTING PACK, VERZENIO, VIDAZA, VINBLASTINE SULFATE, VINCASAR PFS, VINCRISTINE SULFATE, VINORELBINE TARTRATE, VITRAKVI, VIVIMUSTA, VONJO, VOTRIENT, VUMERITY, XALKORI, XATMEP, XELJANZ, XELJANZ XR, XELODA, XOFIGO, XPOVIO, YESCARTA, YONDELIS, YUFLYMA(CF), YUFLYMA(CF) AI CROHN'S-UC-HS, YUFLYMA(CF) AUTOINJECT (2 PCK), YUFLYMA(CF) AUTOINJECTOR, YUSIMRY(CF) PEN, ZANOSAR, ZEJULA, ZEPZELCA, ZEVALIN, ZIRABEV, ZOLINZA, ZORTRESS, ZYDELIG, ZYMFENTRA, ZYNLONTA, ZYNYZ
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
Belimumab/Biologic Therapies SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concurrent use of belimumab with other biologic therapies may result in additive or synergistic effects on the immune system.(1) CLINICAL EFFECTS: Concurrent use of belimumab with other biologic therapies may increase the risk of serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The concurrent use of belimumab with other biologic therapies should be approached with caution.(1) DISCUSSION: In a randomized, double-blind, placebo-controlled trial, more patients who received belimumab and rituximab experienced serious adverse events, serious infections, and post-injection systemic reactions (22.2%, 9%, and 13.2%, respectively) than patients who received belimumab with placebo (13.9%, 2.8%, 9.7%) or standard therapy (19.7%, 5.3%, 5.3%).(1) The combination of belimumab with other biologic therapies has not been studied and should be used cautiously.(1)	BENLYSTA
IgG Antibodies and Derivatives/Rozanolixizumab-noli SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3) DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3)	RYSTIGGO

The following contraindication information is available for STELARA (ustekinumab):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

*History of clinically important hypersensitivity to the drug or any ingredient in the formulation.

There are 0 contraindications.

There are 7 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Cholecystitis
Diverticulitis of gastrointestinal tract
Inactive tuberculosis
Infection
Infectious gastroenteritis
Malignancy
Urinary tract infection

There are 1 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Exfoliative dermatitis

The following adverse reaction information is available for STELARA (ustekinumab):

Overview
Severe
Less Severe

Adverse reaction overview.

Adverse effects reported in >=3% of patients with psoriasis receiving ustekinumab productsin clinical studies include nasopharyngitis, upper respiratory tract infection, headache, and fatigue. Adverse effects in patients with psoriatic arthritis are similar to those in patients with psoriasis. Adverse effects reported in >=3% of patients with Crohn disease receiving ustekinumab productsin clinical studies include vomiting during induction therapy and nasopharyngitis, injection site erythema, vulvovaginal candidiasis/mycotic infection, bronchitis, pruritus, urinary tract infection, and sinusitis during maintenance therapy. Adverse effects reported in >=3% of patients with ulcerative colitis receiving ustekinumab productsin clinical studies include nasopharyngitis during induction therapy and nasopharyngitis, headache, abdominal pain, influenza, fever, diarrhea, sinusitis, fatigue, and nausea during maintenance therapy.

There are 28 severe adverse reactions.

More Frequent	Less Frequent
Infection	Influenza

Rare/Very Rare
Anaphylaxis Angioedema Appendicitis Bacterial sepsis Bronchiolitis obliterans with organizing pneumonia Bullous pemphigoid Cellulitis Cholecystitis Diverticulitis of gastrointestinal tract Eosinophilic pneumonia Erythrodermic psoriasis Exfoliative dermatitis Gastroenteritis Herpes zoster ophthalmicus Interstitial pneumonitis Listeriosis Lower respiratory infection Malignancy Malignant neoplasm of skin Osteomyelitis Pneumonia Posterior reversible encephalopathy syndrome Pustular psoriasis Sepsis Squamous cell carcinoma of skin Vasculitis

Rare/Very Rare

Anaphylaxis
Angioedema
Appendicitis
Bacterial sepsis
Bronchiolitis obliterans with organizing pneumonia
Bullous pemphigoid
Cellulitis
Cholecystitis
Diverticulitis of gastrointestinal tract
Eosinophilic pneumonia
Erythrodermic psoriasis
Exfoliative dermatitis
Gastroenteritis
Herpes zoster ophthalmicus
Interstitial pneumonitis
Listeriosis
Lower respiratory infection
Malignancy
Malignant neoplasm of skin
Osteomyelitis
Pneumonia
Posterior reversible encephalopathy syndrome
Pustular psoriasis
Sepsis
Squamous cell carcinoma of skin
Vasculitis

There are 16 less severe adverse reactions.

More Frequent	Less Frequent
Fatigue Headache disorder Pharyngitis Upper respiratory infection Vomiting	Influenza

Rare/Very Rare
Urticaria

The following precautions are available for STELARA (ustekinumab):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy of ustekinumab and its biosimilar (ustekinumab-auub)have been established in pediatric patients 6-17 years of age with moderate to severe plaque psoriasis. Use of ustekinumab in adolescent patients 12-17 years of age is based on evidence from a randomized clinical trial in this age group. Use of ustekinumab in pediatric patients 6-11 years of age with moderate to severe plaque psoriasis is based on evidence from an open-label, single-arm, efficacy, safety, and pharmacokinetics study.

The safety profile of ustekinumab productsin pediatric patients with psoriasis is similar to that in adults with psoriasis. Safety and efficacy of ustekinumab and its biosimilar (ustekinumab-auub) have been established in pediatric patients 6-17 years of age with psoriatic arthritis. Use of ustekinumab in this age group is based on evidence fromrandomized clinical trialsin adults with psoriasis and psoriatic arthritis, pharmacokinetic data from adults and pediatric patients with psoriasis, pharmacokinetic data from adults with psoriatic arthritis, and safety data from two clinical studies in 44 pediatric patients 6-11 years of age with psoriasis and 110 pediatric patients 12-17 years of age with psoriasis.

The observed pre-dose (trough) concentrations aregenerally comparable between adult patients with psoriasis and psoriatic arthritis and pediatric patients with psoriasis, and the pharmacokinetic exposure is expected to becomparable between adult and pediatric patients with psoriatic arthritis. Safety and efficacy of ustekinumab products have not been established in pediatric patients Crohn disease or ulcerative colitis or in pediatric patients <6 years of age with psoriasis or psoriatic arthritis.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

Ustekinumab

1 Day – 6 Years

Safety and efficacy not established age < 6 years,

Reproductive and developmental toxicity studies in monkeys at ustekinumab exposure levels of more than 100 times the human exposure at the maximum recommended subcutaneous dosage revealed no evidence of adverse developmental effects on fetuses or neonatal offspring. Limited data regarding use of ustekinumab productsin pregnant women are insufficient to inform a drug-associated risk.

Drug/Drug Class	Severity	Precaution Description	Pregnancy Category Description
Ustekinumab	2	Insufficient human data avail; animal data do not sug dev tox	No fda rating but may have precautions or warnings; may have animal and/or human studies or pre or post marketing information.

It is not known whether ustekinumab is distributed into human milk or affects breast-fed infants or milk production. Ustekinumab is distributed into milk in lactating monkeys, and maternal immunoglobulin G (IgG) is distributed into human milk. If ustekinumab is distributed into human milk, the effects on the infant from local exposure in the GI tract are unknown.

Systemic exposure to ustekinumab in breast-fed infants is expected to be low since the drug is a large molecule and is degraded in the GI tract. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for theustekinumab productand any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Precaution Exists
Precaution exists. (No data or inconclusive human data.) Use of this drug by breast feeding mothers should be evaluated carefully.

Drug Name	Excretion Potential	Effect on Infant	Notes
Ustekinumab	Excreted.This drug is known to be excreted in human breast milk.	It is not known whether this drug has an adverse effect on the nursing infant. (No data or inconclusive human data)	Detectable at low levels in human milk, no known adv reaction

In clinical trials evaluating ustekinumab in patients with psoriasis, psoriatic arthritis, Crohn disease, or ulcerative colitis, approximately 5.1% of patients receiving ustekinumab were >=65 years of age and about 0.6% were >=75 years of age.

Although no differences in safety and efficacy relative to younger adults were observed, the number of patients >=65 years of age is insufficient to determine whether they respond differently than younger adults. About 5.5% of patients with psoriasis included in a population pharmacokinetic analysis of ustekinumab were >= 65 years of age; there were no apparent changes in pharmacokinetic parameters (clearance and volume of distribution) in those >=65 years of age.

The following icd codes are available for STELARA (ustekinumab)'s list of indications:

Crohn's disease
K50	Crohn's disease [regional enteritis]
K50.0	Crohn's disease of small intestine
K50.00	Crohn's disease of small intestine without complications
K50.01	Crohn's disease of small intestine with complications
K50.011	Crohn's disease of small intestine with rectal bleeding
K50.012	Crohn's disease of small intestine with intestinal obstruction
K50.013	Crohn's disease of small intestine with fistula
K50.014	Crohn's disease of small intestine with abscess
K50.018	Crohn's disease of small intestine with other complication
K50.019	Crohn's disease of small intestine with unspecified complications
K50.1	Crohn's disease of large intestine
K50.10	Crohn's disease of large intestine without complications
K50.11	Crohn's disease of large intestine with complications
K50.111	Crohn's disease of large intestine with rectal bleeding
K50.112	Crohn's disease of large intestine with intestinal obstruction
K50.113	Crohn's disease of large intestine with fistula
K50.114	Crohn's disease of large intestine with abscess
K50.118	Crohn's disease of large intestine with other complication
K50.119	Crohn's disease of large intestine with unspecified complications
K50.8	Crohn's disease of both small and large intestine
K50.80	Crohn's disease of both small and large intestine without complications
K50.81	Crohn's disease of both small and large intestine with complications
K50.811	Crohn's disease of both small and large intestine with rectal bleeding
K50.812	Crohn's disease of both small and large intestine with intestinal obstruction
K50.813	Crohn's disease of both small and large intestine with fistula
K50.814	Crohn's disease of both small and large intestine with abscess
K50.818	Crohn's disease of both small and large intestine with other complication
K50.819	Crohn's disease of both small and large intestine with unspecified complications
K50.9	Crohn's disease, unspecified
K50.90	Crohn's disease, unspecified, without complications
K50.91	Crohn's disease, unspecified, with complications
K50.911	Crohn's disease, unspecified, with rectal bleeding
K50.912	Crohn's disease, unspecified, with intestinal obstruction
K50.913	Crohn's disease, unspecified, with fistula
K50.914	Crohn's disease, unspecified, with abscess
K50.918	Crohn's disease, unspecified, with other complication
K50.919	Crohn's disease, unspecified, with unspecified complications
Moderate to severe plaque psoriasis
L40.0	Psoriasis vulgaris
L40.8	Other psoriasis
L40.9	Psoriasis, unspecified
Psoriatic arthritis
L40.5	Arthropathic psoriasis
L40.50	Arthropathic psoriasis, unspecified
L40.51	Distal interphalangeal psoriatic arthropathy
L40.52	Psoriatic arthritis mutilans
L40.53	Psoriatic spondylitis
L40.54	Psoriatic juvenile arthropathy
L40.59	Other psoriatic arthropathy
Ulcerative colitis
K51	Ulcerative colitis
K51.0	Ulcerative (chronic) pancolitis
K51.00	Ulcerative (chronic) pancolitis without complications
K51.01	Ulcerative (chronic) pancolitis with complications
K51.011	Ulcerative (chronic) pancolitis with rectal bleeding
K51.012	Ulcerative (chronic) pancolitis with intestinal obstruction
K51.013	Ulcerative (chronic) pancolitis with fistula
K51.014	Ulcerative (chronic) pancolitis with abscess
K51.018	Ulcerative (chronic) pancolitis with other complication
K51.019	Ulcerative (chronic) pancolitis with unspecified complications
K51.2	Ulcerative (chronic) proctitis
K51.20	Ulcerative (chronic) proctitis without complications
K51.21	Ulcerative (chronic) proctitis with complications
K51.211	Ulcerative (chronic) proctitis with rectal bleeding
K51.212	Ulcerative (chronic) proctitis with intestinal obstruction
K51.213	Ulcerative (chronic) proctitis with fistula
K51.214	Ulcerative (chronic) proctitis with abscess
K51.218	Ulcerative (chronic) proctitis with other complication
K51.219	Ulcerative (chronic) proctitis with unspecified complications
K51.3	Ulcerative (chronic) rectosigmoiditis
K51.30	Ulcerative (chronic) rectosigmoiditis without complications
K51.31	Ulcerative (chronic) rectosigmoiditis with complications
K51.311	Ulcerative (chronic) rectosigmoiditis with rectal bleeding
K51.312	Ulcerative (chronic) rectosigmoiditis with intestinal obstruction
K51.313	Ulcerative (chronic) rectosigmoiditis with fistula
K51.314	Ulcerative (chronic) rectosigmoiditis with abscess
K51.318	Ulcerative (chronic) rectosigmoiditis with other complication
K51.319	Ulcerative (chronic) rectosigmoiditis with unspecified complications
K51.5	Left sided colitis
K51.50	Left sided colitis without complications
K51.51	Left sided colitis with complications
K51.511	Left sided colitis with rectal bleeding
K51.512	Left sided colitis with intestinal obstruction
K51.513	Left sided colitis with fistula
K51.514	Left sided colitis with abscess
K51.518	Left sided colitis with other complication
K51.519	Left sided colitis with unspecified complications
K51.8	Other ulcerative colitis
K51.80	Other ulcerative colitis without complications
K51.81	Other ulcerative colitis with complications
K51.811	Other ulcerative colitis with rectal bleeding
K51.812	Other ulcerative colitis with intestinal obstruction
K51.813	Other ulcerative colitis with fistula
K51.814	Other ulcerative colitis with abscess
K51.818	Other ulcerative colitis with other complication
K51.819	Other ulcerative colitis with unspecified complications
K51.9	Ulcerative colitis, unspecified
K51.90	Ulcerative colitis, unspecified, without complications
K51.91	Ulcerative colitis, unspecified, with complications
K51.911	Ulcerative colitis, unspecified with rectal bleeding
K51.912	Ulcerative colitis, unspecified with intestinal obstruction
K51.913	Ulcerative colitis, unspecified with fistula
K51.914	Ulcerative colitis, unspecified with abscess
K51.918	Ulcerative colitis, unspecified with other complication
K51.919	Ulcerative colitis, unspecified with unspecified complications