Spesolimab: Drug information

(For additional information see "Spesolimab: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

Brand Names: US

Spevigo

Brand Names: Canada

Spevigo

Pharmacologic Category

Interleukin-36 Receptor Antagonist;
Monoclonal Antibody

Dosing: Adult

Note: Screen for tuberculosis (TB) infection (latent TB) prior to initiating treatment. Avoid use in patients with TB disease (active TB) or other clinically significant active infection. Consider pretreatment with antituberculosis therapy in patients with TB infection.

Pustular psoriasis, generalized

Pustular psoriasis, generalized: IV: 900 mg once; if flare persists, an additional 900 mg may be given one week later (Ref).

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); however, the need for dosage adjustment is unlikely (not expected to undergo kidney elimination).

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); however, the need for dosage adjustment is unlikely (not expected to undergo hepatic elimination).

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions (Significant): Considerations

Infection

Spesolimab may increase the risk of infection. Infections reported in clinical trials include bacteremia, bacteriuria, cellulitis, herpes simplex dermatitis, oral herpes simplex infection, pustules, serious infection, upper respiratory tract infection, and urinary tract infection (Ref).

Onset: Rapid; onset occurred within 1 week of spesolimab administration.

Risk factors:

• History of recurrent or chronic infections

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.

>10%: Infection: Infection (14%; serious infection: 3%) (table 1)Infection

**Spesolimab: Adverse Reaction: Infection**
Drug (Spesolimab)	Placebo	Number of Patients (Spesolimab)	Number of Patients (Placebo)	Comments
14%	6%	35	18	N/A
3%	0%	35	18	Serious Infection

1% to 10%:

Dermatologic: Cellulitis (3%) (table 2)Cellulitis, herpes simplex dermatitis (≤3%) (table 3)Herpes Simplex Dermatitis, prurigo, pruritus, pustules (Bachelez 2021), urticaria

**Spesolimab: Adverse Reaction: Cellulitis**
Drug (Spesolimab)	Placebo	Number of Patients (Spesolimab)	Number of Patients (Placebo)
3%	0%	35	18

**Spesolimab: Adverse Reaction: Herpes Simplex Dermatitis**
Drug (Spesolimab)	Placebo	Number of Patients (Spesolimab)	Number of Patients (Placebo)	Comments
3%	0%	35	18	Combined term with oral herpes simplex infection

Gastrointestinal: Nausea and vomiting, oral herpes simplex infection (≤3%) (table 4)Oral Herpes Simplex Infection

**Spesolimab: Adverse Reaction: Oral Herpes Simplex Infection**
Drug (Spesolimab)	Placebo	Number of Patients (Spesolimab)	Number of Patients (Placebo)	Comments
3%	0%	35	18	Combined term with herpes simplex dermatitis

Genitourinary: Bacteriuria (3%) (table 5)Bacteriuria, urinary tract infection (6%) (table 6)Urinary Tract Infection

**Spesolimab: Adverse Reaction: Bacteriuria**
Drug (Spesolimab)	Placebo	Number of Patients (Spesolimab)	Number of Patients (Placebo)
3%	0%	35	18

**Spesolimab: Adverse Reaction: Urinary Tract Infection**
Drug (Spesolimab)	Placebo	Number of Patients (Spesolimab)	Number of Patients (Placebo)
6%	0%	35	18

Immunologic: Antibody development (Bachelez 2021)

Infection: Bacteremia (3%) (table 7)Bacteremia

**Spesolimab: Adverse Reaction: Bacteremia**
Drug (Spesolimab)	Placebo	Number of Patients (Spesolimab)	Number of Patients (Placebo)
3%	0%	35	18

Local: Injection-site reaction (including bruising at injection site, erythema at injection site, hematoma at injection site, induration at injection site, pain at injection site, swelling at injection site, warm sensation at injection site)

Nervous system: Asthenia, fatigue, headache

Ophthalmic: Periorbital edema

Respiratory: Dyspnea, upper respiratory tract infection (3%) (table 8)Upper Respiratory Tract Infection

**Spesolimab: Adverse Reaction: Upper Respiratory Tract Infection**
Drug (Spesolimab)	Placebo	Number of Patients (Spesolimab)	Number of Patients (Placebo)
3%	0%	35	18

Frequency not defined: Hypersensitivity: Drug reaction with eosinophilia and systemic symptoms

Contraindications

Severe or life-threatening hypersensitivity to spesolimab or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Guillain-Barre syndrome: Guillain-Barre syndrome has been reported in patients using spesolimab for unapproved indications.

• Hypersensitivity reactions: Hypersensitivity reactions have been reported, and may include immediate (eg, anaphylaxis) or delayed (eg, drug reaction with eosinophilia and systemic symptoms) reactions. Discontinue treatment if anaphylaxis or other serious allergic reaction occurs; ensure availability of medications for the treatment of hypersensitivity reactions during administration.

Disease-related concerns:

• Tuberculosis: Safety has not been established in patients who are positive for tuberculosis.

Concurrent drug therapy issues:

• Immunizations: Avoid use of live vaccines in patients treated with spesolimab. Patients who recently received a live vaccine were excluded from the clinical trial (Bachelez 2021).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Spevigo: Spesolimab-sbzo 450 mg/7.5 mL (60 mg/mL) (7.5 mL)

Generic Equivalent Available: US

Pricing: US

Solution (Spevigo Intravenous)

450 mg/7.5 mL (per mL): $4,172.45

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Spevigo: Spesolimab-sbzo 450 mg/7.5 mL (60 mg/mL) (7.5 mL)

Administration: Adult

IV: For IV use only. Must be diluted prior to administration. Flush IV line with NS before and after infusion. Administer by IV infusion over 90 minutes using a sterile, nonpyrogenic, low protein binding in-line filter (0.2 micron). Do not administer other medications through the same line during the spesolimab infusion. If an infusion related reaction occurs, stop the infusion immediately. For mild to moderate reactions, once symptoms resolve may resume infusion at a slower rate and gradually increase to complete the infusion; the total infusion time (including stop time) should not exceed 180 minutes.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761244s000lbl.pdf#page=11, must be dispensed with this medication.

Use: Labeled Indications

Pustular psoriasis, generalized: Treatment of generalized pustular psoriasis flares in adults.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Chikungunya Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider therapy modification

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination

Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification

Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Rabies Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification

Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid combination

Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Pregnancy Considerations

Spesolimab is a humanized monoclonal antibody (IgG1). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).

Breastfeeding Considerations

It is not known if spesolimab is present in breast milk.

Spesolimab is a humanized monoclonal antibody (IgG₁). Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Anderson 2021).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.

Monitoring Parameters

Infusion related reactions (eg, hematoma, bruising), signs and symptoms of hypersensitivity/anaphylaxis or infection during and after the infusion.

Mechanism of Action

Spesolimab, a humanized monoclonal antibody, binds to interleukin-36 (IL36) receptor and prevents binding of endogenous IL36 which prevents activation of proinflammatory and profibrotic pathways by endogenous IL36. The precise role of reduced IL36 receptor activity in generalized pustular psoriasis is unknown.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: 6.4 L at steady state.

Half-life elimination: 25.5 days (median).

Anderson PO. Monoclonal antibodies during breastfeeding. Breastfeed Med. 2021;16(8):591-593. doi:10.1089/bfm.2021.0110 [PubMed 33956488]
Bachelez H, Choon SE, Marrakchi S, et al. Trial of spesolimab for generalized pustular psoriasis. N Engl J Med. 2021;385(26):2431-2440. doi:10.1056/NEJMoa2111563 [PubMed 34936739]
Clements T, Rice TF, Vamvakas G, et al. Update on transplacental transfer of IgG subclasses: impact of maternal and fetal factors. Front Immunol. 2020;11:1920. doi:10.3389/fimmu.2020.01920 [PubMed 33013843]
Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. 2012;2012:985646. doi:10.1155/2012/985646 [PubMed 22235228]
Pentsuk N, van der Laan JW. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol. 2009;86(4):328-344. doi:10.1002/bdrb.20201 [PubMed 19626656]
Refer to manufacturer's labeling.
Spevigo (spesolimab) [prescribing information]. Ridgefield, Connecticut: Boehringer Ingelheim Pharmaceuticals Inc; September 2022.

Topic 139549 Version 41.0

خرید پکیج

Spesolimab: Drug information