DRUG INTERACTIONS

­ Avoid use of live vaccines in patients treated with TREMFYA.

TREMFYA is an interleukin-23 blocker indicated for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

ADVERSE REACTIONS

­ Most common (=1%) adverse reactions associated with TREMFYA

include upper respiratory infections, headache, injection site reactions, arthralgia, diarrhea, gastroenteritis, tinea infections, and herpes simplex infections.

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CONTRAINDICATIONS

­ None 

WARNINGS AND PRECAUTIONS

­ • Infections: TREMFYA may increase the risk of infection. Instruct patients to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a serious infection develops, discontinue TREMFYA until the infection resolves.

• Tuberculosis (TB): Evaluate for TB prior to initiating treatment with TREMFYA. 

INDICATIONS AND USAGE

­ TREMFYA is an interleukin-23 blocker indicated for the treatment of adult patients with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

DOSAGE AND ADMINISTRATION

­ 100 mg administered by subcutaneous injection at Week 0, Week 4 and every 8 weeks thereafter 

DOSAGE FORMS AND STRENGTHS

­ Injection: 100 mg/mL in a single-dose prefilled syringe.

 Storage and Handling

TREMFYA is sterile and preservative-free. Discard any unused portion. • Store in a refrigerator at 2ºC to 8ºC (36ºF to 46ºF) • Store in original carton until time of use • Protect from light until use. • Do not freeze. • Do not shake

 PATIENT COUNSELING INFORMATION

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use) before starting TREMFYA therapy,           and each time the prescription is renewed, as there may be new information they need to know.

Infections

Instruct patients of the importance of communicating any history of infections to the healthcare provider and contacting their healthcare provider if they develop any symptoms of an infection [see Warnings and Precautions (5.1)].

Instruction on Injection Technique

Instruct the patient or caregivers to perform the first self-injection under the supervision and guidance of a qualified healthcare professional for proper training in subcutaneous injection 

Technique.

Instruct patients who are self-administering to inject the full dose of TREMFYA [see Medication Guide and Instructions for Use]. Instruct patients or caregivers in the technique of proper needle and syringe disposal.

Needles and syringes should be disposed of in a puncture-resistant container. Advise patients and caregivers not to reuse needles or syringes.

Remind patients if they forget to take their dose of TREMFYA to inject their dose as soon as they remember. They should then take their next dose at the appropriate scheduled time.

Product of USA Manufactured by: Janssen Biot

CLNICAL PHARMACOLOGY

1 Mechanism of Action

Guselkumab is a human monoclonal IgG1? antibody that selectively binds to the p19 subunit of interleukin 23 (IL-23) and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in normal inflammatory and immune responses.

Guselkumab inhibits the release of proinflammatory cytokines and chemokines.

Pharmacodynamics

Guselkumab reduced serum levels of IL-17A, IL-17F and IL-22 relative to pretreatment levels in evaluated subjects with psoriasis based on exploratory analysis of the pharmacodynamic markers.

The relationship between these pharmacodynamic markers and the mechanism(s) by which guselkumab exerts its clinical effects is not fully understood. 

Pharmacokinetics

Guselkumab exhibited linear pharmacokinetics in healthy subjects and subjects with psoriasis following subcutaneous injections. In subjects with psoriasis, following subcutaneous administration of 100 mg of TREMFYA at Weeks 0 and 4, and every 8 weeks thereafter, mean steady-state trough serum guselkumab concentration was approximately 1.2 mcg/mL.

Absorption

Following a single 100 mg subcutaneous injection in healthy subjects, guselkumab reached a mean (± SD) maximum serum concentration of 8.09 ± 3.68 mcg/mL by approximately 5.5 days post dose.

The absolute bioavailability of guselkumab following a single 100 mg subcutaneous injection was estimated to be approximately 49% in healthy subjects.

Distribution

In subjects with plaque psoriasis, apparent volume of distribution was 13.5 L. Elimination Apparent clearance in subjects with plaque psoriasis was 0.516 L/day. Mean half-life of guselkumab was approximately 15 to 18 days in subjects with plaque psoriasis across studies.

Metabolism

The exact pathway through which guselkumab is metabolized has not been characterized. As a human IgG monoclonal antibody, guselkumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.

USE IN SPECIFIC POPULATIONS

1 Pregnancy Risk Summary

There are no available data on TREMFYA use in pregnant women to inform a drug associated risk of adverse developmental outcomes. Human IgG antibodies are known to cross the placental barrier; therefore, TREMFYA may be transmitted from the mother to the developing fetus.

In a combined embryofetal development and pre- and post-natal development study, no adverse developmental effects were observed in infants born to pregnant monkeys after subcutaneous administration of guselkumab during organogenesis through parturition at doses up to 30 times the maximum recommended human dose (MRHD).

Neonatal deaths were observed at 6- to 30-times the MRHD (see Data). The clinical significance of these nonclinical findings is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data- Animal Data In a combined embryofetal development and pre- and post-natal development study, pregnant cynomolgus monkeys were administered weekly subcutaneous doses of guselkumab up to Reference ID: 4123919 6 50 mg/kg (30 times the MRHD based on a mg/kg comparison) from the beginning of organogenesis to parturition.

Neonatal deaths occurred in the offspring of one control monkey, three monkeys administered guselkumab at 10 mg/kg/week (6 times the MRHD based on a mg/kg comparison) and three monkeys administered guselkumab at 50 mg/kg/week (30 times the MRHD based on a mg/kg comparison). The clinical significance of these findings is unknown. No guselkumab-related effects on functional or immunological development were observed in the infants from birth through 6 months of age.

2. Lactation Risk Summary

There are no data on the presence of guselkumab in human milk, the effects on the breastfed infant, or the effects on milk production. Guselkumab was not detected in the milk of lactating cynomolgus monkeys. Maternal IgG is known to be present in human milk. 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 infant from TREMFYA or from the underlying maternal condition. 8.4

3.Pediatric use-

The safety and efficacy of TREMFYA in pediatric patients (less than 18 years of age) have not been established.

4. Geriatric Use

Of the 1748 subjects with plaque psoriasis exposed to TREMFYA, a total of 93 subjects were 65 years or older, and 4 subjects were 75 years or older. No overall differences in safety or effectiveness were observed between older and younger subjects who received TREMFYA. However, the number of subjects aged 65 years and older was not sufficient to determine whether they respond differently from younger subjects [see Clinical Pharmacology (12.3)].

5. OVERDOSAGE

In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and administer appropriate symptomatic treatment immediately.