HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use TREMFYA™ safely and effectively. See full prescribing information for TREMFYA. TREMFYA (guselkumab) injection, for ...
These highlights do not include all the information needed to use TREMFYA™ safely and effectively. See full prescribing information for TREMFYA.
TREMFYA (guselkumab) injection, for subcutaneous use
Initial U.S. Approval: 2017
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. (1)
DOSAGE AND ADMINISTRATION
100 mg administered by subcutaneous injection at Week 0, Week 4 and every 8 weeks thereafter (2.1)
DOSAGE FORMS AND STRENGTHS
Injection: 100 mg/mL in a single-dose prefilled syringe. (3)
CONTRAINDICATIONS
None (4)
WARNINGS AND PRECAUTIONS
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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. (5.1)
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Tuberculosis (TB): eva luate for TB prior to initiating treatment with TREMFYA. (5.2)
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. (6)
To report SUSPECTED ADVERSE REACTIONS, contact Janssen Biotech, Inc. at 1-800-JANSSEN (1-800-526-7736) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Avoid use of live vaccines in patients treated with TREMFYA. (7.1)
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 7/2017
FULL PRESCRIBING INFORMATION: CONTENTS*
Table of Contents
1 INDICATIONS AND USAGE
TREMFYA™ is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
TREMFYA™ is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
2 DOSAGE AND ADMINISTRATION
2.1 Dosage - TREMFYA is administered by subcutaneous injection. The recommended dose is 100 mg at Week 0, Week 4, and every 8 weeks thereafter ...
2.1 Dosage
TREMFYA is administered by subcutaneous injection. The recommended dose is 100 mg at Week 0, Week 4, and every 8 weeks thereafter.
2.2 Tuberculosis Assessment Prior to Initiation of TREMFYA
eva luate patients for tuberculosis (TB) infection prior to initiating treatment with TREMFYA [see Warnings and Precautions (5.2)].
2.3 Important Administration Instructions
Administer TREMFYA subcutaneously. Each prefilled syringe is for single-dose only. Instruct patients to inject the full amount (1 mL), which provides 100 mg of TREMFYA.
Do not inject TREMFYA into areas where the skin is tender, bruised, red, hard, thick, scaly, or affected by psoriasis [see Instructions for Use].
TREMFYA is intended for use under the guidance and supervision of a physician. TREMFYA may be administered by a health care professional, or a patient may self-inject after proper training in subcutaneous injection technique.
The TREMFYA Instructions for Use contains more detailed patient instructions on the preparation and administration of TREMFYA [see Instructions for Use].
2.4 Preparation for Use of TREMFYA Prefilled Syringe
Before injection, remove TREMFYA prefilled syringe from the refrigerator and allow TREMFYA to reach room temperature (30 minutes) without removing the needle cap.
Inspect TREMFYA visually for particulate matter and discoloration prior to administration. TREMFYA is a clear and colorless to light yellow solution that may contain small translucent particles. Do not use if the liquid contains large particles, is discolored or cloudy. TREMFYA does not contain preservatives; therefore, discard any unused product remaining in the prefilled syringe.
3 DOSAGE FORMS AND STRENGTHS
Injection: 100 mg/mL in a single-dose prefilled syringe - TREMFYA is a clear and colorless to light yellow solution that may contain small translucent particles.
Injection: 100 mg/mL in a single-dose prefilled syringe
TREMFYA is a clear and colorless to light yellow solution that may contain small translucent particles.
4 CONTRAINDICATIONS
None.
None.
5 WARNINGS AND PRECAUTIONS
5.1 Infections - TREMFYA may increase the risk of infection. In clinical trials, infections occurred in 23% of subjects in the TREMFYA group versus 21% of subjects in ...
5.1 Infections
TREMFYA may increase the risk of infection. In clinical trials, infections occurred in 23% of subjects in the TREMFYA group versus 21% of subjects in the placebo group through 16 weeks of treatment. Upper respiratory tract infections, gastroenteritis, tinea infections, and herpes simplex infections occurred more frequently in the TREMFYA group than in the placebo group [see Adverse Reactions (6.1)]. The rate of serious infections for the TREMFYA group and the placebo group was ≤ 0.2%. Treatment with TREMFYA should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.
In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to prescribing TREMFYA. Instruct patients to seek medical help if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a clinically important or serious infection or is not responding to standard therapy, monitor the patient closely and discontinue TREMFYA until the infection resolves.
5.2 Pre-treatment eva luation for Tuberculosis
eva luate patients for tuberculosis (TB) infection prior to initiating treatment with TREMFYA. Initiate treatment of latent TB prior to administering TREMFYA. In clinical studies, 105 subjects with latent TB who were concurrently treated with TREMFYA and appropriate TB prophylaxis did not develop active TB (during the mean follow-up of 43 weeks). Monitor patients for signs and symptoms of active TB during and after TREMFYA treatment. Consider anti-TB therapy prior to initiating TREMFYA in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Do not administer TREMFYA to patients with active TB infection.
5.3 Immunizations
Prior to initiating therapy with TREMFYA, consider completion of all age appropriate immunizations according to current immunization guidelines. Avoid use of live vaccines in patients treated with TREMFYA. No data are available on the response to live or inactive vaccines.
6 ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of labeling: Infections [see Warnings and Precautions (5.1)] 6.1 ...
The following adverse reactions are discussed in greater detail in other sections of labeling:
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In clinical trials, a total of 1748 subjects with moderate-to-severe plaque psoriasis received TREMFYA. Of these, 1393 subjects were exposed to TREMFYA for at least 6 months and 728 subjects were exposed for at least 1 year.
Data from two placebo- and active-controlled trials (VOYAGE 1 and VOYAGE 2) in 1441 subjects (mean age 44 years; 70% males; 82% white) were pooled to eva luate the safety of TREMFYA (100 mg administered subcutaneously at Weeks 0 and 4, followed by every 8 weeks).
Weeks 0 to 16
In the 16-week placebo-controlled period of the pooled clinical trials (VOYAGE 1 and VOYAGE 2), adverse events occurred in 49% of subjects in the TREMFYA group compared to 47% of subjects in the placebo group and 49% of subjects in the U.S. licensed adalimumab group. Serious adverse events occurred in 1.9% of the TREMFYA group (6.3 events per 100 subject-years of follow-up) compared to 1.4% of the placebo group (4.7 events per 100 subject-years of follow-up), and in 2.6% of U.S. licensed adalimumab group (9.9 events per 100 subject-years of follow-up).
Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the TREMFYA group than in the placebo group during the 16-week placebo-controlled period.
Adverse reactions that occurred in < 1% but > 0.1% of subjects in the TREMFYA group and at a higher rate than in the placebo group through Week 16 in VOYAGE 1 and VOYAGE 2 were migraine, candida infections, and urticaria.
Specific Adverse Reactions
Infections
Infections occurred in 23% of the TREMFYA group compared to 21% of the placebo group.
The most common (≥ 1%) infections were upper respiratory infections, gastroenteritis, tinea infections, and herpes simplex infections; all cases were mild to moderate in severity and did not lead to discontinuation of TREMFYA.
Elevated Liver Enzymes
Elevated liver enzymes were reported more frequently in the TREMFYA group (2.6%) than in the placebo group (1.9%). Of the 21 subjects who were reported to have elevated liver enzymes in the TREMFYA group, all events except one were mild to moderate in severity and none of the events led to discontinuation of TREMFYA.
Safety through Week 48
Through Week 48, no new adverse reactions were identified with TREMFYA use and the frequency of the adverse reactions was similar to the safety profile observed during the first 16 weeks of treatment.
6.2 Immunogenicity
As with all therapeutic proteins, there is the potential for immunogenicity with TREMFYA. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to guselkumab with the incidences of antibodies to other products may be misleading.
Up to Week 52, approximately 6% of subjects treated with TREMFYA developed antidrug antibodies. Of the subjects who developed antidrug antibodies, approximately 7% had antibodies that were classified as neutralizing antibodies. Among the 46 subjects who developed antibodies to guselkumab and had eva luable data, 21 subjects exhibited lower trough levels of guselkumab, including one subject who experienced loss of efficacy after developing high antibody titers. However, antibodies to guselkumab were generally not associated with changes in clinical response or development of injection-site reactions.
7 DRUG INTERACTIONS
7.1 Live Vaccinations - Avoid use of live vaccines in patients treated with TREMFYA [see Warnings and Precautions (5.3)]. 7.2 CYP450 ...
7.2 CYP450 Substrates
The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNFα, interferon) during chronic inflammation.
Results from an exploratory drug-drug interaction study in subjects with moderate-to-severe psoriasis suggested a low potential for clinically relevant drug interactions for drugs metabolized by CYP3A4, CYP2C9, CYP2C19 and CYP1A2 but the interaction potential cannot be ruled out for drugs metabolized by CYP2D6. However, the results were highly variable because of the limited number of subjects in the study.
Upon initiation of TREMFYA in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect or drug concentration and consider dosage adjustment as needed [see Clinical Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy - Risk Summary There are no available data on TREMFYA use in pregnant women to inform a drug associated risk of adverse ...
8.1 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 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.
8.2 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 Pediatric Use
The safety and efficacy of TREMFYA in pediatric patients (less than 18 years of age) have not been established.
8.5 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)].
10 OVERDOSAGE
In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and administer appropriate symptomatic treatment immediately.
In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and administer appropriate symptomatic treatment immediately.
11 DESCRIPTION
Guselkumab, an interleukin-23 blocker, is a human immunoglobulin G1 lambda (IgG1λ) monoclonal antibody. Guselkumab is produced in a mammalian cell line using recombinant DNA technology ...
Guselkumab, an interleukin-23 blocker, is a human immunoglobulin G1 lambda (IgG1λ) monoclonal antibody. Guselkumab is produced in a mammalian cell line using recombinant DNA technology.
TREMFYA (guselkumab) Injection is a sterile, preservative free, clear, colorless to light yellow solution that may contain small translucent particles. Each single-dose prefilled syringe for subcutaneous use contains 100 mg of guselkumab in 1 mL. TREMFYA is supplied as a single-dose solution in a 1 mL glass syringe with a 27G, half inch fixed needle assembled in a passive needle guard delivery system.
Each TREMFYA prefilled syringe delivers 1 mL of solution containing guselkumab (100 mg), L-histidine (0.6 mg), L-histidine monohydrochloride monohydrate (1.5 mg), polysorbate 80 (0.5 mg), sucrose (79 mg) and water for injection at pH 5.8.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action - Guselkumab is a human monoclonal IgG1λ antibody that selectively binds to the p19 subunit of interleukin 23 (IL-23) and inhibits its ...
12.1 Mechanism of Action
Guselkumab is a human monoclonal IgG1λ 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.
12.2 Pharmacodynamics
Guselkumab reduced serum levels of IL-17A, IL-17F and IL-22 relative to pretreatment levels in eva luated subjects with psoriasis based on exploratory analysis of the pharmacodynami
