TREMFYA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TREMFYA (TREMFYA).
Guselkumab is a human monoclonal antibody that selectively binds to the p19 subunit of interleukin-23 (IL-23) and inhibits its interaction with the IL-23 receptor, thereby blocking IL-23-mediated signaling and the downstream activation of Th17 cells and production of proinflammatory cytokines.
| Metabolism | Guselkumab is a monoclonal antibody, expected to be degraded into small peptides and amino acids via catabolic pathways, not metabolized by cytochrome P450 enzymes. |
| Excretion | Primarily degraded into small peptides and amino acids via general protein catabolism; no significant renal or hepatic elimination. Fecal excretion of intact drug is negligible. |
| Half-life | Terminal elimination half-life approximately 23-31 days (mean ~27 days), supporting subcutaneous dosing every 8 weeks after initial loading. |
| Protein binding | Bound to plasma proteins, primarily to immunoglobulin G (IgG) receptors; no specific binding to albumin or alpha-1 acid glycoprotein quantified; typical monoclonal antibody binding >90%. |
| Volume of Distribution | Approximately 4.5-6.5 L (in patients with psoriasis), indicating limited distribution primarily in vascular and interstitial spaces; not extensively into tissues. |
| Bioavailability | SC: Approximately 49-57% (absolute bioavailability) after subcutaneous administration; IM/IV not approved. |
| Onset of Action | SC: Clinical response (PASI 75) observed as early as Week 4, peak efficacy typically by Week 16. |
| Duration of Action | Sustained response with every 8-week dosing; therapeutic levels maintained throughout interval. Missed doses may require re-initiation. |
Subcutaneous injection: 100 mg at week 0, week 4, then every 8 weeks thereafter.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment. |
| Liver impairment | No dose adjustment required for hepatic impairment. |
| Pediatric use | Not approved for pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended; limited data in patients ≥65 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TREMFYA (TREMFYA).
| Breastfeeding | It is not known whether guselkumab is excreted in human milk or absorbed systemically after ingestion. Because human IgG is present in breast milk, it is likely that guselkumab will be present in breast milk. The M/P ratio is unknown. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for TREMFYA and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. |
| Teratogenic Risk | TREMFYA (guselkumab) is a human IgG1 monoclonal antibody. Based on its mechanism of action, it may cross the placenta, particularly during the second and third trimesters. Animal studies have not shown direct or indirect harmful effects with respect to reproductive toxicity, but there are no adequate and well-controlled studies in pregnant women. Therefore, it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. There is no known teratogenic risk in the first trimester; however, due to Fc-receptor mediated placental transfer, fetal exposure is higher in the second and third trimesters, potentially affecting immune responses. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Severe hypersensitivity to guselkumab or any excipients","Active serious infection"]
| Precautions | ["Infections: increased risk of serious infections; avoid use during active infections","Hypersensitivity reactions: angioedema, urticaria, etc.; discontinue if occurs","Tuberculosis: evaluate for latent TB prior to initiation; treat latent TB before starting","Immunizations: avoid live vaccines during treatment"] |
Loading safety data…
| Fetal Monitoring | No specific maternal or fetal monitoring requirements are established for guselkumab use during pregnancy. However, as with other biologic agents, monitoring for infusion reactions at administration and for infections in the mother and infant postnatally is prudent. For women of childbearing potential, pregnancy testing before initiating therapy is recommended per routine clinical practice. |
| Fertility Effects | No dedicated fertility studies in humans have been conducted with guselkumab. Animal studies did not reveal impairment of male or female fertility at doses up to 200 mg/kg in cynomolgus monkeys (approximately 35 times the human exposure at the recommended dose). However, the clinical relevance of this finding is unknown. It is not expected to have a significant effect on fertility based on its mechanism of action. |