SPEVIGO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SPEVIGO (SPEVIGO).
SPEVIGO (spesolimab) is a humanized monoclonal immunoglobulin G1 (IgG1) antibody that binds to the interleukin-36 receptor (IL-36R) and inhibits IL-36 signaling, thereby reducing inflammation associated with generalized pustular psoriasis (GPP).
| Metabolism | Metabolized via general protein degradation pathways; not metabolized by cytochrome P450 enzymes. |
| Excretion | Spevigo (spesolimab) is a monoclonal antibody and is not eliminated renally or hepatically; it undergoes intracellular catabolism via proteolytic degradation into amino acids. No significant renal or biliary/fecal excretion of intact drug occurs. |
| Half-life | Terminal elimination half-life is approximately 23 days (range 18–29 days), supporting every 4-week dosing interval in clinical use. |
| Protein binding | Spesolimab binds to the IL-36 receptor; as a humanized IgG1 monoclonal antibody, it does not bind to plasma proteins in a conventional sense; free fraction is >99%. |
| Volume of Distribution | Volume of distribution is approximately 4.2 L, suggesting limited extravascular distribution, consistent with a monoclonal antibody primarily confined to the vascular and interstitial spaces. |
| Bioavailability | Spesolimab is administered only intravenously; bioavailability is 100% by IV route. No oral or other formulations are available. |
| Onset of Action | Intravenous infusion: Clinical improvement in generalized pustular psoriasis flares is observed within 1 week (median time to pustule clearance is 3–4 days). |
| Duration of Action | After a single IV dose, clinical effect persists for approximately 4 weeks, aligning with the dosing interval. Repeat dosing may be required for sustained control. |
180 mg subcutaneous injection every 2 weeks for the first 3 doses, then 360 mg every 4 weeks; start with a loading dose of 600 mg (given as 300 mg intravenously every 2 weeks for 2 doses) for patients with severe persistent asthma on step 6 care or with moderate-to-severe asthma requiring oral corticosteroids and at risk of exacerbations.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²); not studied in severe renal impairment (eGFR <30 mL/min/1.73 m²) or dialysis, use with caution. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A); not studied in moderate to severe hepatic impairment (Child-Pugh B or C), use with caution. |
| Pediatric use | For children ≥12 years: same as adult dosing (180 mg SC every 2 weeks x3 then 360 mg every 4 weeks; loading dose 600 mg IV for severe cases); for children 6-11 years: 75 mg SC every 4 weeks; for children <6 years: not established. |
| Geriatric use | No specific dose adjustment required; limited data in patients ≥65 years, consider age-related comorbidities and potential for impaired renal function; monitor for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SPEVIGO (SPEVIGO).
| Breastfeeding | No data on presence of spesolimab in human milk, effects on breastfed infant, or milk production. Maternal IgG antibodies are secreted into milk during the early postpartum period and then decrease. The M/P ratio is not established. Because many drugs are excreted in human milk and potential for adverse reactions in nursing infants, breastfeeding should be discontinued during treatment and for at least 5 half-lives (approximately 25 days) after last dose. |
| Teratogenic Risk | Spevigo (spesolimab) is a humanized IgG1 monoclonal antibody. Placental transfer occurs primarily in the third trimester. There are no adequate and well-controlled studies in pregnant women. Based on animal studies, no evidence of embryofetal toxicity or teratogenicity was observed at doses up to 100 mg/kg IV every 2 weeks in cynomolgus monkeys, yielding exposures approximately 130 times the human AUC at the recommended human dose. However, IgG antibodies can cross the placenta, and the fetus may be exposed to pharmacological effects, including potential immune suppression. Risk cannot be ruled out; use only if clearly needed. |
■ FDA Black Box Warning
None
| Serious Effects |
["Severe hypersensitivity to spesolimab or any excipients in the formulation."]
| Precautions | ["Infections: May increase risk of serious infections. Monitor for signs and symptoms of infection before and during treatment.","Hypersensitivity: Serious hypersensitivity reactions, including anaphylaxis, have been reported. Discontinue if severe reaction occurs.","Immunizations: Avoid live vaccines during treatment."] |
Loading safety data…
| Fetal Monitoring | Monitor for signs of infection in both mother and neonate due to potential immune suppression. Fetal monitoring: consider ultrasound for growth and anatomy if exposure occurs in second or third trimester. Neonatal monitoring: assess for infections, hematological abnormalities (e.g., neutropenia) and immune function. No specific monitoring requirements are mandated. |
| Fertility Effects | No human data on fertility effects. In animal studies, no adverse effects on male or female fertility were observed in cynomolgus monkeys at doses up to 100 mg/kg IV every 2 weeks. Fertility effects in humans are unknown. |