Dosage & Administration
Some patients with RA not receiving methotrexate may benefit from increasing the dosage to 40 mg every week or 80 mg every other week.
Pediatric Weight 2 Years of Age and Older | Recommended Dosage |
10 kg (22 lbs) to less than 15 kg (33 lbs) | 10 mg every other week |
15 kg (33 lbs) to less than 30 kg (66 lbs) | 20 mg every other week |
30 kg (66 lbs) and greater | 40 mg every other week |
Pediatric Weight | Recommended Dosage | |
Days 1 and 15 | ||
17 kg (37 lbs) to less than 40 kg (88 lbs) | Day 1: 80 mg Day 15: 40 mg | 20 mg every other week |
40 kg (88 lbs) and greater | Day 1: 160 mg (single dose or split over two consecutive days) Day 15: 80 mg | 40 mg every other week |
30 kg (66 lbs) to less than 60 kg (132 lbs) | Day 1: 80 mg Day 8 and subsequent doses: 40 mg every other week |
60 kg (132 lbs) and greater | Day 1: 160 mg (given in one day or split over two consecutive days) Day 15: 80 mg Day 29 and subsequent doses: 40 mg every week or 80 mg every other week |
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Hyrimoz Prescribing Information
- Patients treated with adalimumab products, including HYRIMOZ, are at increased risk for developing serious infections that may lead to hospitalization or death[see Warnings and Precautions (. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.)]
5.1 Serious InfectionsPatients treated with adalimumab products, including HYRIMOZ, are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis and tuberculosis have been reported with TNF blockers. Patients have frequently presented with disseminated rather than localized disease.
The concomitant use of a TNF blocker and abatacept or anakinra was associated with a higher risk of serious infections in patients with rheumatoid arthritis (RA); therefore, the concomitant use of HYRIMOZ and these biologic products is not recommended in the treatment of patients with RA
[see Warnings and Precautions and Drug Interactions ].Treatment with HYRIMOZ should not be initiated in patients with an active infection, including localized infections. Patients 65 years of age and older, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants (such as corticosteroids or methotrexate), may be at greater risk of infection. Consider the risks and benefits of treatment prior to initiating therapy in patients:
• with chronic or recurrent infection;• who have been exposed to tuberculosis;• with a history of an opportunistic infection;• who have resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis; or• with underlying conditions that may predispose them to infection.
TuberculosisCases of reactivation of tuberculosis and new onset tuberculosis infections have been reported in patients receiving adalimumab products, including patients who have previously received treatment for latent or active tuberculosis. Reports included cases of pulmonary and extrapulmonary (i.e., disseminated) tuberculosis. Evaluate patients for tuberculosis risk factors and test for latent infection prior to initiating HYRIMOZ and periodically during therapy.
Treatment of latent tuberculosis infection prior to therapy with TNF blocking agents has been shown to reduce the risk of tuberculosis reactivation during therapy. Prior to initiating HYRIMOZ, assess if treatment for latent tuberculosis is needed; and consider an induration of ≥ 5 mm a positive tuberculin skin test result, even for patients previously vaccinated with Bacille Calmette-Guerin (BCG).
Consider anti-tuberculosis therapy prior to initiation of HYRIMOZ in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Despite prophylactic treatment for tuberculosis, cases of reactivated tuberculosis have occurred in patients treated with adalimumab products. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision whether initiating anti-tuberculosis therapy is appropriate for an individual patient.
Strongly consider tuberculosis in the differential diagnosis in patients who develop a new infection during HYRIMOZ treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis.
MonitoringClosely monitor patients for the development of signs and symptoms of infection during and after treatment with HYRIMOZ, including the development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. Tests for latent tuberculosis infection may also be falsely negative while on therapy with HYRIMOZ.
Discontinue HYRIMOZ if a patient develops a serious infection or sepsis. For a patient who develops a new infection during treatment with HYRIMOZ, closely monitor them, perform a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and initiate appropriate antimicrobial therapy.
Invasive Fungal InfectionsIf patients develop a serious systemic illness and they reside or travel in regions where mycoses are endemic, consider invasive fungal infection in the differential diagnosis. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider appropriate empiric antifungal therapy, taking into account both the risk for severe fungal infection and the risks of antifungal therapy, while a diagnostic workup is being performed. To aid in the management of such patients, consider consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections.
- Discontinue HYRIMOZ if a patient develops a serious infection or sepsis.
• Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before HYRIMOZ use and during therapy. Initiate treatment for latent TB prior to HYRIMOZ use.• Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric anti-fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.• Bacterial, viral and other infections due to opportunistic pathogens, including Legionella and Listeria.
Patients treated with adalimumab products, including HYRIMOZ, are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis and tuberculosis have been reported with TNF blockers. Patients have frequently presented with disseminated rather than localized disease.
The concomitant use of a TNF blocker and abatacept or anakinra was associated with a higher risk of serious infections in patients with rheumatoid arthritis (RA); therefore, the concomitant use of HYRIMOZ and these biologic products is not recommended in the treatment of patients with RA
Treatment with HYRIMOZ should not be initiated in patients with an active infection, including localized infections. Patients 65 years of age and older, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants (such as corticosteroids or methotrexate), may be at greater risk of infection. Consider the risks and benefits of treatment prior to initiating therapy in patients:
• with chronic or recurrent infection;• who have been exposed to tuberculosis;• with a history of an opportunistic infection;• who have resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis; or• with underlying conditions that may predispose them to infection.
Cases of reactivation of tuberculosis and new onset tuberculosis infections have been reported in patients receiving adalimumab products, including patients who have previously received treatment for latent or active tuberculosis. Reports included cases of pulmonary and extrapulmonary (i.e., disseminated) tuberculosis. Evaluate patients for tuberculosis risk factors and test for latent infection prior to initiating HYRIMOZ and periodically during therapy.
Treatment of latent tuberculosis infection prior to therapy with TNF blocking agents has been shown to reduce the risk of tuberculosis reactivation during therapy. Prior to initiating HYRIMOZ, assess if treatment for latent tuberculosis is needed; and consider an induration of ≥ 5 mm a positive tuberculin skin test result, even for patients previously vaccinated with Bacille Calmette-Guerin (BCG).
Consider anti-tuberculosis therapy prior to initiation of HYRIMOZ in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Despite prophylactic treatment for tuberculosis, cases of reactivated tuberculosis have occurred in patients treated with adalimumab products. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision whether initiating anti-tuberculosis therapy is appropriate for an individual patient.
Strongly consider tuberculosis in the differential diagnosis in patients who develop a new infection during HYRIMOZ treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis.
Closely monitor patients for the development of signs and symptoms of infection during and after treatment with HYRIMOZ, including the development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. Tests for latent tuberculosis infection may also be falsely negative while on therapy with HYRIMOZ.
Discontinue HYRIMOZ if a patient develops a serious infection or sepsis. For a patient who develops a new infection during treatment with HYRIMOZ, closely monitor them, perform a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and initiate appropriate antimicrobial therapy.
If patients develop a serious systemic illness and they reside or travel in regions where mycoses are endemic, consider invasive fungal infection in the differential diagnosis. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider appropriate empiric antifungal therapy, taking into account both the risk for severe fungal infection and the risks of antifungal therapy, while a diagnostic workup is being performed. To aid in the management of such patients, consider consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections.
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.
The most common adverse reaction with adalimumab was injection site reactions. In placebo-controlled trials, 20% of subjects treated with adalimumab developed injection site reactions (erythema and/or itching, hemorrhage, pain or swelling), compared to 14% of subjects receiving placebo. Most injection site reactions were described as mild and generally did not necessitate drug discontinuation.
The proportion of subjects who discontinued treatment due to adverse reactions during the double-blind, placebo-controlled portion of studies in subjects with RA (i.e., Studies RA-I, RA-II, RA-III and RA-IV) was 7% for subjects taking adalimumab and 4% for placebo-treated subjects. The most common adverse reactions leading to discontinuation of adalimumab in these RA studies were clinical flare reaction (0.7%), rash (0.3%) and pneumonia (0.3%).
In the controlled portions of the 39 global adalimumab clinical trials in adult subjects with RA, PsA, AS, CD, UC, Ps, HS and UV, the rate of serious infections was 4.3 per 100 patient-years in 7973 adalimumab-treated subjects versus a rate of 2.9 per 100 patient-years in 4848 control-treated subjects. Serious infections observed included pneumonia, septic arthritis, prosthetic and post-surgical infections, erysipelas, cellulitis, diverticulitis, and pyelonephritis
In 52 global controlled and uncontrolled clinical trials in RA, PsA, AS, CD, UC, Ps, HS and UV that included 24,605 adalimumab treated subjects, the rate of reported active tuberculosis was 0.20 per 100 patient-years and the rate of positive PPD conversion was 0.09 per 100 patient-years. In a subgroup of 10,113 U.S. and Canadian adalimumab treated subjects, the rate of reported active TB was 0.05 per 100 patient-years and the rate of positive PPD conversion was 0.07 per 100 patient-years. These trials included reports of miliary, lymphatic, peritoneal, and pulmonary TB. Most of the TB cases occurred within the first eight months after initiation of therapy and may reflect recrudescence of latent disease. In these global clinical trials, cases of serious opportunistic infections have been reported at an overall rate of 0.05 per 100 patient-years. Some cases of serious opportunistic infections and TB have been fatal
In the rheumatoid arthritis controlled trials, 12% of subjects treated with adalimumab and 7% of placebo-treated subjects that had negative baseline ANA titers developed positive titers at Week 24. Two subjects out of 3046 treated with adalimumab developed clinical signs suggestive of new-onset lupus-like syndrome. The subjects improved following discontinuation of therapy. No subjects developed lupus nephritis or central nervous system symptoms. The impact of long-term treatment with adalimumab products on the development of autoimmune diseases is unknown.
There have been reports of severe hepatic reactions including acute liver failure in subjects receiving TNF-blockers. In controlled Phase 3 trials of adalimumab (40 mg SC every other week) in subjects with RA, PsA, and AS with control period duration ranging from 4 to 104 weeks, ALT elevations ≥ 3 x ULN occurred in 3.5% of adalimumab-treated subjects and 1.5% of control-treated subjects. Since many of these subjects in these trials were also taking medications that cause liver enzyme elevations (e.g., NSAIDs, MTX), the relationship between adalimumab and the liver enzyme elevations is not clear. In a controlled Phase 3 trial of adalimumab in subjects with polyarticular JIA who were 4 to 17 years, ALT elevations ≥ 3 x ULN occurred in 4.4% of adalimumab-treated subjects and 1.5% of control-treated subjects (ALT more common than AST); liver enzyme test elevations were more frequent among those treated with the combination of adalimumab and MTX than those treated with adalimumab alone. In general, these elevations did not lead to discontinuation of adalimumab treatment. No ALT elevations ≥ 3 x ULN occurred in the open-label study of adalimumab in subjects with polyarticular JIA who were 2 to <4 years.
In controlled Phase 3 trials of adalimumab (initial doses of 160 mg and 80 mg, or 80 mg and 40 mg on Days 1 and 15, respectively, followed by 40 mg every other week) in adult subjects with Crohn’s Disease with a control period duration ranging from 4 to 52 weeks, ALT elevations ≥ 3 x ULN occurred in 0.9% of adalimumab-treated subjects and 0.9% of control-treated subjects. In the Phase 3 trial of adalimumab in pediatric subjects with Crohn’s disease which evaluated efficacy and safety of two body weight based maintenance dose regimens following body weight based induction therapy up to 52 weeks of treatment, ALT elevations ≥ 3 x ULN occurred in 2.6% (5/192) of subjects, of whom 4 were receiving concomitant immunosuppressants at baseline; none of these subjects discontinued due to abnormalities in ALT tests.
In controlled Phase 3 trials of adalimumab (initial doses of 160 mg and 80 mg on Days 1 and 15 respectively, followed by 40 mg every other week) in adult subjects with UC with control period duration ranging from 1 to 52 weeks, ALT elevations ≥3 x ULN occurred in 1.5% of adalimumab-treated subjects and 1.0% of control-treated subjects. In controlled Phase 3 trials of adalimumab (initial dose of 80 mg then 40 mg every other week) in subjects with Ps with control period duration ranging from 12 to 24 weeks, ALT elevations ≥ 3 x ULN occurred in 1.8% of adalimumab-treated subjects and 1.8% of control-treated subjects.
In controlled trials of adalimumab (initial doses of 160 mg at Week 0 and 80 mg at Week 2, followed by 40 mg every week starting at Week 4), in subjects with HS with a control period duration ranging from 12 to 16 weeks, ALT elevations ≥ 3 x ULN occurred in 0.3% of adalimumab-treated subjects and 0.6% of control-treated subjects.
In controlled trials of adalimumab (initial doses of 80 mg at Week 0 followed by 40 mg every other week starting at Week 1) in adult subjects with uveitis with an exposure of 165.4 PYs and 119.8 PYs in adalimumab-treated and control-treated subjects, respectively, ALT elevations ≥ 3 x ULN occurred in 2.4% of adalimumab-treated subjects and 2.4% of control-treated subjects.
The data described below reflect exposure to adalimumab in 2468 subjects, including 2073 exposed for 6 months, 1497 exposed for greater than one year and 1380 in adequate and well-controlled studies (Studies RA-I, RA-II, RA-III, and RA-IV). Adalimumab was studied primarily in placebo-controlled trials and in long-term follow up studies for up to 36 months duration. The population had a mean age of 54 years, 77% were female, 91% were Caucasian and had moderately to severely active rheumatoid arthritis. Most subjects received 40 mg adalimumab every other week
Table 1 summarizes reactions reported at a rate of at least 5% in subjects treated with adalimumab 40 mg every other week compared to placebo and with an incidence higher than placebo. In Study RA-III, the types and frequencies of adverse reactions in the second year open-label extension were similar to those observed in the one-year double-blind portion.
Table 1. Adverse Reactions Reported by ≥5% of Subjects Treated with Adalimumab During Placebo-Controlled Period of Pooled RA Studies (Studies RA-I, RA-II, RA-III, and RA-IV)
Adalimumab 40 mg subcutaneous Every Other Week |
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* Laboratory test abnormalities were reported as adverse reactions in European trials. ** Does not include injection site erythema, itching, hemorrhage, pain or swelling. | ||
Other infrequent serious adverse reactions that do not appear in the Warnings and Precautions or Adverse Reaction sections that occurred at an incidence of less than 5% in adalimumab-treated subjects in RA studies (RA-I, RA-II, RA-III, and RA-IV) were:
In general, the adverse reactions in the adalimumab-treated subjects in the polyarticular juvenile idiopathic arthritis (JIA) trials (Studies JIA-I and JIA-II)
In Study JIA-I, adalimumab was studied in 171 subjects who were 4 to 17 years of age, with polyarticular JIA. Severe adverse reactions reported in the study included neutropenia, streptococcal pharyngitis, increased aminotransferases, herpes zoster, myositis, metrorrhagia, and appendicitis. Serious infections were observed in 4% of subjects within approximately 2 years of initiation of treatment with adalimumab and included cases of herpes simplex, pneumonia, urinary tract infection, pharyngitis, and herpes zoster.
In Study JIA-I, 45% of subjects experienced an infection while receiving adalimumab with or without concomitant MTX in the first 16 weeks of treatment. The types of infections reported in adalimumab-treated subjects were generally similar to those commonly seen in polyarticular JIA subjects who are not treated with TNF blockers. Upon initiation of treatment, the most common adverse reactions occurring in this population treated with adalimumab were injection site pain and injection site reaction (19% and 16%, respectively). A less commonly reported adverse event in subjects receiving adalimumab was granuloma annulare which did not lead to discontinuation of adalimumab treatment.
In the first 48 weeks of treatment in Study JIA-I, non-serious hypersensitivity reactions were seen in approximately 6% of subjects and included primarily localized allergic hypersensitivity reactions and allergic rash.
In Study JIA-I, 10% of subjects treated with adalimumab who had negative baseline anti-dsDNA antibodies developed positive titers after 48 weeks of treatment. No subject developed clinical signs of autoimmunity during the clinical trial.
Approximately 15% of subjects treated with adalimumab developed mild-to-moderate elevations of creatine phosphokinase (CPK) in Study JIA-I. Elevations exceeding 5 times the upper limit of normal were observed in several subjects. CPK concentrations decreased or returned to normal in all subjects. Most subjects were able to continue adalimumab without interruption.
In Study JIA-II, adalimumab was studied in 32 subjects who were 2 to <4 years of age or 4 years of age and older weighing <15 kg with polyarticular JIA. The safety profile for this population was similar to the safety profile seen in subjects 4 to 17 years of age with polyarticular JIA.
In Study JIA-II, 78% of subjects experienced an infection while receiving adalimumab. These included nasopharyngitis, bronchitis, upper respiratory tract infection, otitis media, and were mostly mild to moderate in severity. Serious infections were observed in 9% of subjects receiving adalimumab in the study and included dental caries, rotavirus gastroenteritis, and varicella.
In Study JIA-II, non-serious allergic reactions were observed in 6% of subjects and included intermittent urticaria and rash, which were all mild in severity.
Adalimumab has been studied in 395 subjects with psoriatic arthritis (PsA) in two placebo-controlled trials and in an open label study and in 393 subjects with ankylosing spondylitis (AS) in two placebo-controlled studies
Adults: The safety profile of adalimumab in 1478 adult subjects with Crohn’s disease from four placebo-controlled and two open-label extension studies
During the 4-week open label induction phase of Study PCD-I, the most common adverse reactions occurring in the pediatric population treated with adalimumab were injection site pain and injection site reaction (6% and 5%, respectively).
A total of 67% of children experienced an infection while receiving adalimumab in Study PCD-I. These included upper respiratory tract infection and nasopharyngitis.
A total of 5% of children experienced a serious infection while receiving adalimumab in Study PCD-I. These included viral infection, device related sepsis (catheter), gastroenteritis, H1N1 influenza, and disseminated histoplasmosis.
In Study PCD-I, allergic reactions were observed in 5% of children which were all non-serious and were primarily localized reactions.
Adalimumab has been studied in 1696 subjects with plaque psoriasis (Ps) in placebo-controlled and open-label extension studies [
Adalimumab has been studied in 727 subjects with hidradenitis suppurativa (HS) in three placebo-controlled studies and one open-label extension study [
Flare of HS, defined as ≥25% increase from baseline in abscesses and inflammatory nodule counts and with a minimum of 2 additional lesions, was documented in 22 (22%) of the 100 subjects who were withdrawn from adalimumab treatment following the primary efficacy timepoint in two studies.
Adalimumab has been studied in 464 adult subjects with uveitis (UV) in placebo-controlled and open-label extension studies and in 90 pediatric subjects with uveitis (Study PUV-I)
Consider the risks and benefits of TNF-blocker treatment including HYRIMOZ prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing a TNF-blocker in patients who develop a malignancy.
In the controlled portions of clinical trials of some TNF-blockers, including adalimumab products, more cases of malignancies have been observed among TNF-blocker-treated adult subjects compared to control-treated adult subjects. During the controlled portions of 39 global adalimumab clinical trials in adult patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn’s disease (CD), ulcerative colitis (UC), plaque psoriasis (Ps), hidradenitis suppurativa (HS) and uveitis (UV), malignancies, other than non-melanoma (basal cell and squamous cell) skin cancer, were observed at a rate (95% confidence interval) of 0.7 (0.48, 1.03) per 100 patient-years among 7973 adalimumab-treated subjects versus a rate of 0.7 (0.41, 1.17) per 100 patient-years among 4848 control-treated subjects (median duration of treatment of 4 months for adalimumab-treated subjects and 4 months for control-treated subjects). In 52 global controlled and uncontrolled clinical trials of adalimumab in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV, the most frequently observed malignancies, other than lymphoma and NMSC, were breast, colon, prostate, lung, and melanoma. The malignancies in adalimumab-treated subjects in the controlled and uncontrolled portions of the studies were similar in type and number to what would be expected in the general U.S. population according to the SEER database (adjusted for age, gender, and race).1
In controlled trials of other TNF blockers in adult patients at higher risk for malignancies (i.e., subjects with COPD with a significant smoking history and cyclophosphamide-treated patients with Wegener’s granulomatosis), a greater portion of malignancies occurred in the TNF blocker group compared to the control group.
During the controlled portions of 39 global adalimumab clinical trials in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV, the rate (95% confidence interval) of NMSC was 0.8 (0.52, 1.09) per 100 patient-years among adalimumab-treated subjects and 0.2 (0.10, 0.59) per 100 patient-years among control-treated subjects. Examine all patients, and in particular patients with a medical history of prior prolonged immunosuppressant therapy or psoriasis patients with a history of PUVA treatment for the presence of NMSC prior to and during treatment with HYRIMOZ.
In the controlled portions of clinical trials of all the TNF-blockers in adults, more cases of lymphoma have been observed among TNF-blocker-treated subjects compared to control-treated subjects. In the controlled portions of 39 global adalimumab clinical trials in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV, 2 lymphomas occurred among 7973 adalimumab-treated subjects versus 1 among 4848 control-treated subjects. In 52 global controlled and uncontrolled clinical trials of adalimumab in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV with a median duration of approximately 0.7 years, including 24,605 subjects and over 40,215 patient-years of adalimumab, the observed rate of lymphomas was approximately 0.11 per 100 patient-years. This is approximately 3-fold higher than expected in the general U.S. population according to the SEER database (adjusted for age, gender, and race).1Rates of lymphoma in clinical trials of adalimumab cannot be compared to rates of lymphoma in clinical trials of other TNF blockers and may not predict the rates observed in a broader patient population. Patients with RA and other chronic inflammatory diseases, particularly those with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to several fold) than the general population for the development of lymphoma, even in the absence of TNF blockers. Post-marketing cases of acute and chronic leukemia have been reported in association with TNF-blocker use in RA and other indications. Even in the absence of TNF-blocker therapy, patients with RA may be at a higher risk (approximately 2-fold) than the general population for the development of leukemia.
Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blockers (initiation of therapy ≤ 18 years of age), of which HYRIMOZ is a member. Approximately half the cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months of therapy (range 1 to 84 months). Most of the patients were receiving concomitant immunosuppressants. These cases were reported post-marketing and are derived from a variety of sources including registries and spontaneous postmarketing reports.
Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including adalimumab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn's disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with the immunosuppressants azathioprine or 6-mercaptopurine (6–MP) concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants. The potential risk with the combination of azathioprine or 6-mercaptopurine and HYRIMOZ should be carefully considered.
Consider the risks and benefits of TNF-blocker treatment including HYRIMOZ prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing a TNF-blocker in patients who develop a malignancy.
In the controlled portions of clinical trials of some TNF-blockers, including adalimumab products, more cases of malignancies have been observed among TNF-blocker-treated adult subjects compared to control-treated adult subjects. During the controlled portions of 39 global adalimumab clinical trials in adult patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn’s disease (CD), ulcerative colitis (UC), plaque psoriasis (Ps), hidradenitis suppurativa (HS) and uveitis (UV), malignancies, other than non-melanoma (basal cell and squamous cell) skin cancer, were observed at a rate (95% confidence interval) of 0.7 (0.48, 1.03) per 100 patient-years among 7973 adalimumab-treated subjects versus a rate of 0.7 (0.41, 1.17) per 100 patient-years among 4848 control-treated subjects (median duration of treatment of 4 months for adalimumab-treated subjects and 4 months for control-treated subjects). In 52 global controlled and uncontrolled clinical trials of adalimumab in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV, the most frequently observed malignancies, other than lymphoma and NMSC, were breast, colon, prostate, lung, and melanoma. The malignancies in adalimumab-treated subjects in the controlled and uncontrolled portions of the studies were similar in type and number to what would be expected in the general U.S. population according to the SEER database (adjusted for age, gender, and race).1
In controlled trials of other TNF blockers in adult patients at higher risk for malignancies (i.e., subjects with COPD with a significant smoking history and cyclophosphamide-treated patients with Wegener’s granulomatosis), a greater portion of malignancies occurred in the TNF blocker group compared to the control group.
During the controlled portions of 39 global adalimumab clinical trials in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV, the rate (95% confidence interval) of NMSC was 0.8 (0.52, 1.09) per 100 patient-years among adalimumab-treated subjects and 0.2 (0.10, 0.59) per 100 patient-years among control-treated subjects. Examine all patients, and in particular patients with a medical history of prior prolonged immunosuppressant therapy or psoriasis patients with a history of PUVA treatment for the presence of NMSC prior to and during treatment with HYRIMOZ.
In the controlled portions of clinical trials of all the TNF-blockers in adults, more cases of lymphoma have been observed among TNF-blocker-treated subjects compared to control-treated subjects. In the controlled portions of 39 global adalimumab clinical trials in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV, 2 lymphomas occurred among 7973 adalimumab-treated subjects versus 1 among 4848 control-treated subjects. In 52 global controlled and uncontrolled clinical trials of adalimumab in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV with a median duration of approximately 0.7 years, including 24,605 subjects and over 40,215 patient-years of adalimumab, the observed rate of lymphomas was approximately 0.11 per 100 patient-years. This is approximately 3-fold higher than expected in the general U.S. population according to the SEER database (adjusted for age, gender, and race).1Rates of lymphoma in clinical trials of adalimumab cannot be compared to rates of lymphoma in clinical trials of other TNF blockers and may not predict the rates observed in a broader patient population. Patients with RA and other chronic inflammatory diseases, particularly those with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to several fold) than the general population for the development of lymphoma, even in the absence of TNF blockers. Post-marketing cases of acute and chronic leukemia have been reported in association with TNF-blocker use in RA and other indications. Even in the absence of TNF-blocker therapy, patients with RA may be at a higher risk (approximately 2-fold) than the general population for the development of leukemia.
Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blockers (initiation of therapy ≤ 18 years of age), of which HYRIMOZ is a member. Approximately half the cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months of therapy (range 1 to 84 months). Most of the patients were receiving concomitant immunosuppressants. These cases were reported post-marketing and are derived from a variety of sources including registries and spontaneous postmarketing reports.
Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including adalimumab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn's disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with the immunosuppressants azathioprine or 6-mercaptopurine (6–MP) concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants. The potential risk with the combination of azathioprine or 6-mercaptopurine and HYRIMOZ should be carefully considered.
Indications and Usage, Hidradenitis Suppurativa (
Indications and Usage, Uveitis (
Dosage and Administration, Uveitis (
Pediatric Weight (2 Years of Age and older) | Recommended Dosage |
10 kg (22 lbs) to less than 15 kg (33 lbs) | 10 mg every other week |
15 kg (33 lbs) to less than 30 kg (66 lbs) | 20 mg every other week |
30 kg (66 lbs) and greater | 40 mg every other week |
Dosage and Administration, Hidradenitis Suppurativa (
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Warnings and Precautions, Autoimmunity (
HYRIMOZ is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. HYRIMOZ should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician
• Serious infections:Do not start HYRIMOZ during an active infection. If an infection develops, monitor carefully, and stop HYRIMOZ if infection becomes serious. (5.1)• Invasive fungal infections:For patients who develop a systemic illness on HYRIMOZ, consider empiric antifungal therapy for those who reside or travel to regions where mycoses are endemic. (5.1)• Malignancies:Incidence of malignancies was greater in adalimumab-treated patients than in controls. (5.2)• Anaphylaxis or serious hypersensitivity reactionsmay occur. (5.3)• Hepatitis B virus reactivation:Monitor HBV carriers during and several months after therapy. If reactivation occurs, stop HYRIMOZ and begin anti-viral therapy. (5.4)• Demyelinating disease:Exacerbation or new onset, may occur. (5.5)• Cytopenias, pancytopenia:Advise patients to seek immediate medical attention if symptoms develop, and consider stopping HYRIMOZ. (5.6)• Heart failure:Worsening or new onset, may occur. (5.8)• Autoimmunity:Stop HYRIMOZ if lupus-like syndrome or autoimmune hepatitis develop. (5.9)
Patients treated with adalimumab products, including HYRIMOZ, are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis and tuberculosis have been reported with TNF blockers. Patients have frequently presented with disseminated rather than localized disease.
The concomitant use of a TNF blocker and abatacept or anakinra was associated with a higher risk of serious infections in patients with rheumatoid arthritis (RA); therefore, the concomitant use of HYRIMOZ and these biologic products is not recommended in the treatment of patients with RA
Treatment with HYRIMOZ should not be initiated in patients with an active infection, including localized infections. Patients 65 years of age and older, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants (such as corticosteroids or methotrexate), may be at greater risk of infection. Consider the risks and benefits of treatment prior to initiating therapy in patients:
• with chronic or recurrent infection;• who have been exposed to tuberculosis;• with a history of an opportunistic infection;• who have resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis; or• with underlying conditions that may predispose them to infection.
Cases of reactivation of tuberculosis and new onset tuberculosis infections have been reported in patients receiving adalimumab products, including patients who have previously received treatment for latent or active tuberculosis. Reports included cases of pulmonary and extrapulmonary (i.e., disseminated) tuberculosis. Evaluate patients for tuberculosis risk factors and test for latent infection prior to initiating HYRIMOZ and periodically during therapy.
Treatment of latent tuberculosis infection prior to therapy with TNF blocking agents has been shown to reduce the risk of tuberculosis reactivation during therapy. Prior to initiating HYRIMOZ, assess if treatment for latent tuberculosis is needed; and consider an induration of ≥ 5 mm a positive tuberculin skin test result, even for patients previously vaccinated with Bacille Calmette-Guerin (BCG).
Consider anti-tuberculosis therapy prior to initiation of HYRIMOZ in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Despite prophylactic treatment for tuberculosis, cases of reactivated tuberculosis have occurred in patients treated with adalimumab products. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision whether initiating anti-tuberculosis therapy is appropriate for an individual patient.
Strongly consider tuberculosis in the differential diagnosis in patients who develop a new infection during HYRIMOZ treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis.
Closely monitor patients for the development of signs and symptoms of infection during and after treatment with HYRIMOZ, including the development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. Tests for latent tuberculosis infection may also be falsely negative while on therapy with HYRIMOZ.
Discontinue HYRIMOZ if a patient develops a serious infection or sepsis. For a patient who develops a new infection during treatment with HYRIMOZ, closely monitor them, perform a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and initiate appropriate antimicrobial therapy.
If patients develop a serious systemic illness and they reside or travel in regions where mycoses are endemic, consider invasive fungal infection in the differential diagnosis. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider appropriate empiric antifungal therapy, taking into account both the risk for severe fungal infection and the risks of antifungal therapy, while a diagnostic workup is being performed. To aid in the management of such patients, consider consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections.
Consider the risks and benefits of TNF-blocker treatment including HYRIMOZ prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing a TNF-blocker in patients who develop a malignancy.
In the controlled portions of clinical trials of some TNF-blockers, including adalimumab products, more cases of malignancies have been observed among TNF-blocker-treated adult subjects compared to control-treated adult subjects. During the controlled portions of 39 global adalimumab clinical trials in adult patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn’s disease (CD), ulcerative colitis (UC), plaque psoriasis (Ps), hidradenitis suppurativa (HS) and uveitis (UV), malignancies, other than non-melanoma (basal cell and squamous cell) skin cancer, were observed at a rate (95% confidence interval) of 0.7 (0.48, 1.03) per 100 patient-years among 7973 adalimumab-treated subjects versus a rate of 0.7 (0.41, 1.17) per 100 patient-years among 4848 control-treated subjects (median duration of treatment of 4 months for adalimumab-treated subjects and 4 months for control-treated subjects). In 52 global controlled and uncontrolled clinical trials of adalimumab in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV, the most frequently observed malignancies, other than lymphoma and NMSC, were breast, colon, prostate, lung, and melanoma. The malignancies in adalimumab-treated subjects in the controlled and uncontrolled portions of the studies were similar in type and number to what would be expected in the general U.S. population according to the SEER database (adjusted for age, gender, and race).1
In controlled trials of other TNF blockers in adult patients at higher risk for malignancies (i.e., subjects with COPD with a significant smoking history and cyclophosphamide-treated patients with Wegener’s granulomatosis), a greater portion of malignancies occurred in the TNF blocker group compared to the control group.
During the controlled portions of 39 global adalimumab clinical trials in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV, the rate (95% confidence interval) of NMSC was 0.8 (0.52, 1.09) per 100 patient-years among adalimumab-treated subjects and 0.2 (0.10, 0.59) per 100 patient-years among control-treated subjects. Examine all patients, and in particular patients with a medical history of prior prolonged immunosuppressant therapy or psoriasis patients with a history of PUVA treatment for the presence of NMSC prior to and during treatment with HYRIMOZ.
In the controlled portions of clinical trials of all the TNF-blockers in adults, more cases of lymphoma have been observed among TNF-blocker-treated subjects compared to control-treated subjects. In the controlled portions of 39 global adalimumab clinical trials in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV, 2 lymphomas occurred among 7973 adalimumab-treated subjects versus 1 among 4848 control-treated subjects. In 52 global controlled and uncontrolled clinical trials of adalimumab in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV with a median duration of approximately 0.7 years, including 24,605 subjects and over 40,215 patient-years of adalimumab, the observed rate of lymphomas was approximately 0.11 per 100 patient-years. This is approximately 3-fold higher than expected in the general U.S. population according to the SEER database (adjusted for age, gender, and race).1Rates of lymphoma in clinical trials of adalimumab cannot be compared to rates of lymphoma in clinical trials of other TNF blockers and may not predict the rates observed in a broader patient population. Patients with RA and other chronic inflammatory diseases, particularly those with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to several fold) than the general population for the development of lymphoma, even in the absence of TNF blockers. Post-marketing cases of acute and chronic leukemia have been reported in association with TNF-blocker use in RA and other indications. Even in the absence of TNF-blocker therapy, patients with RA may be at a higher risk (approximately 2-fold) than the general population for the development of leukemia.
Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blockers (initiation of therapy ≤ 18 years of age), of which HYRIMOZ is a member. Approximately half the cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months of therapy (range 1 to 84 months). Most of the patients were receiving concomitant immunosuppressants. These cases were reported post-marketing and are derived from a variety of sources including registries and spontaneous postmarketing reports.
Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including adalimumab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn's disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with the immunosuppressants azathioprine or 6-mercaptopurine (6–MP) concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants. The potential risk with the combination of azathioprine or 6-mercaptopurine and HYRIMOZ should be carefully considered.
Anaphylaxis and angioneurotic edema have been reported following administration of adalimumab products. If an anaphylactic or other serious allergic reaction occurs, immediately discontinue administration of HYRIMOZ and institute appropriate therapy. In clinical trials of adalimumab, hypersensitivity reactions (e.g., rash, anaphylactoid reaction, fixed drug reaction, non-specified drug reaction, urticaria) have been observed.
Use of TNF blockers, including HYRIMOZ, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of this virus. In some instances, HBV reactivation occurring in conjunction with TNF blocker therapy has been fatal. The majority of these reports have occurred in patients concomitantly receiving other medications that suppress the immune system, which may also contribute to HBV reactivation. Evaluate patients at risk for HBV infection for prior evidence of HBV infection before initiating TNF blocker therapy. Exercise caution in prescribing TNF blockers for patients identified as carriers of HBV. Adequate data are not available on the safety or efficacy of treating patients who are carriers of HBV with anti-viral therapy in conjunction with TNF blocker therapy to prevent HBV reactivation. For patients who are carriers of HBV and require treatment with TNF blockers, closely monitor such patients for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy. In patients who develop HBV reactivation, stop HYRIMOZ and initiate effective anti-viral therapy with appropriate supportive treatment. The safety of resuming TNF blocker therapy after HBV reactivation is controlled is not known. Therefore, exercise caution when considering resumption of HYRIMOZ therapy in this situation and monitor patients closely.
Use of TNF blocking agents, including adalimumab products, has been associated with rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease, including multiple sclerosis (MS) and optic neuritis, and peripheral demyelinating disease, including Guillain-Barré syndrome. Exercise caution in considering the use of HYRIMOZ in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of HYRIMOZ should be considered if any of these disorders develop. There is a known association between intermediate uveitis and central demyelinating disorders.
Rare reports of pancytopenia including aplastic anemia have been reported with TNF blocking agents. Adverse reactions of the hematologic system, including medically significant cytopenia (e.g., thrombocytopenia, leukopenia) have been infrequently reported with adalimumab products. The causal relationship of these reports to adalimumab products remains unclear. Advise all patients to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever, bruising, bleeding, pallor) while on HYRIMOZ. Consider discontinuation of HYRIMOZ therapy in patients with confirmed significant hematologic abnormalities.
Concurrent use of anakinra (an interleukin-1 antagonist) and another TNF-blocker, was associated with a greater proportion of serious infections and neutropenia and no added benefit compared with the TNF-blocker alone in patients with RA. Therefore, the combination of HYRIMOZ and anakinra is not recommended
Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers. Cases of worsening CHF have also been observed with adalimumab products. Adalimumab products have not been formally studied in patients with CHF; however, in clinical trials of another TNF blocker, a higher rate of serious CHF-related adverse reactions was observed. Exercise caution when using HYRIMOZ in patients who have heart failure and monitor them carefully.
In a placebo-controlled clinical trial of patients with RA, no difference was detected in anti-pneumococcal antibody response between adalimumab and placebo treatment groups when the pneumococcal polysaccharide vaccine and influenza vaccine were administered concurrently with adalimumab. Similar proportions of subjects developed protective levels of anti-influenza antibodies between adalimumab and placebo treatment groups; however, titers in aggregate to influenza antigens were moderately lower in patients receiving adalimumab. The clinical significance of this is unknown. Patients on HYRIMOZ may receive concurrent vaccinations, except for live vaccines. No data are available on the secondary transmission of infection by live vaccines in patients receiving adalimumab products.
It is recommended that pediatric patients, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating HYRIMOZ therapy. Patients on HYRIMOZ may receive concurrent vaccinations, except for live vaccines.
The safety of administering live or live-attenuated vaccines in infants exposed to adalimumab products
In controlled trials, the concurrent administration of TNF-blockers and abatacept was associated with a greater proportion of serious infections than the use of a TNF-blocker alone; the combination therapy, compared to the use of a TNF-blocker alone, has not demonstrated improved clinical benefit in the treatment of RA. Therefore, the combination of abatacept with TNF-blockers including HYRIMOZ is not recommended
• Administer by subcutaneous injection2 DOSAGE AND ADMINISTRATION• Administer by subcutaneous injection (2)
Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis (2.2):• Adults:40 mg every other week.
Some patients with RA not receiving methotrexate may benefit from increasing the dosage to 40 mg every week or 80 mg every other week.
Juvenile Idiopathic Arthritis or Pediatric Uveitis (2.3):Pediatric Weight2 Years of Age and OlderRecommended Dosage10 kg (22 lbs) to less than 15 kg (33 lbs)
10 mg every other week
15 kg (33 lbs) to less than 30 kg (66 lbs)
20 mg every other week
30 kg (66 lbs) and greater
40 mg every other week
Crohn's Disease (2.4):• Adults:160 mg on Day 1 (given in one day or split over two consecutive days); 80 mg on Day 15; and 40 mgevery other week starting on Day 29. • Pediatric Patients 6 Years of Age and Older:
Pediatric WeightRecommended DosageDays 1 and 15- Starting on Day 29
17 kg (37 lbs) to less than 40 kg (88 lbs)
Day 1: 80 mg
Day 15: 40 mg
20 mg every other week
40 kg (88 lbs) and greater
Day 1: 160 mg (single dose or split over two consecutive days)
Day 15: 80 mg
40 mg every other week
Ulcerative Colitis (2.5):• Adults: 160 mg on Day 1 (given in one day or split over two consecutive days), 80 mg on Day 15 and 40 mg every other week starting on Day 29.Discontinue in patients without evidence of clinical remission by eight weeks (Day 57).
Plaque Psoriasis or Adult Uveitis (2.6):• Adults: 80 mg initial dose, followed by 40 mg every other week starting one week after initial dose.
Hidradenitis Suppurativa (2.7):• Adults:o Day 1: 160 mg (given in one day or split over two consecutive days)o Day 15: 80 mgo Day 29 and subsequent doses: 40 mg every week or 80 mg every other week
• Adolescents 12 years of age and older:
- Adolescent Weight
- Recommended Dosage
30 kg (66 lbs) to less than 60 kg (132 lbs)
Day 1: 80 mg
Day 8 and subsequent doses: 40 mg every other week
60 kg (132 lbs) and greater
Day 1: 160 mg (given in one day or split over two consecutive days)
Day 15: 80 mg
Day 29 and subsequent doses: 40 mg every week or 80 mg every other week
2.1 Recommended Tuberculosis EvaluationPrior to initiating HYRIMOZ and periodically during therapy, evaluate patients for active tuberculosis and test for latent infection
[see Warnings and Precautions ].2.2 Recommended Dosage in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing SpondylitisThe recommended subcutaneous dosage of HYRIMOZ for adult patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS)
[see Indication and Usage ]is 40 mg administered every other week. Methotrexate (MTX), other non-biologic DMARDs, glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs), and/or analgesics may be continued during treatment with HYRIMOZ. In the treatment of RA, some patients not taking concomitant MTX may derive additional benefit from increasing the dosage of HYRIMOZ to 40 mg every week or 80 mg every other week.2.3 Recommended Dosage in Juvenile Idiopathic Arthritis or Pediatric Patients with UveitisThe recommended subcutaneous dosage of HYRIMOZ for pediatric patients 2 years of age and older with polyarticular juvenile idiopathic arthritis (JIA) or pediatric uveitis[see Indications and Usage , ],based on weight, is shown below. MTX, glucocorticoids, NSAIDs, and/or analgesics may be continued during treatment with HYRIMOZ.Pediatric Weight
(2 Years of Age and older)Recommended Dosage10 kg (22 lbs) to less than 15 kg (33 lbs)10 mg every other week15 kg (33 lbs) to less than 30 kg (66 lbs)20 mg every other week30 kg (66 lbs) and greater40 mg every other weekAdalimumab products have not been studied in patients with polyarticular JIA or pediatric uveitis less than 2 years of age or in patients with a weight below 10 kg.2.4 Recommended Dosage in Crohn’s DiseaseSubcutaneous Adult Dosage RegimenThe recommended subcutaneous dosage of HYRIMOZ for adult patients with moderately to severely active Crohn’s disease (CD) is 160 mg initially on Day 1 (given in one day or split over two consecutive days), followed by 80 mg two weeks later (Day 15). Two weeks later (Day 29) begin a dosage of 40 mg every other week. Aminosalicylates and/or corticosteroids may be continued during treatment with HYRIMOZ. Azathioprine, 6-mercaptopurine (6-MP)
[see Warnings and Precautions (5.2)]or MTX may be continued during treatment with HYRIMOZ if necessary.Subcutaneous Pediatric Dosage RegimenThe recommended subcutaneous dosage of HYRIMOZ for pediatric patients 6 years of age and older with moderately to severely active Crohn’s disease (CD), based on body weight, is shown below:
Pediatric Weight
Recommended Dosage
Days 1 through 15
Starting on Day 29
17 kg (37 lbs) to less than 40 kg (88 lbs)
Day 1: 80 mg
Day 15: 40 mg
20 mg every other week
40 kg (88 lbs) and greater
Day 1: 160 mg (single dose or split over two consecutive days)
Day 15: 80 mg
40 mg every other week
2.5 Recommended Dosage in Ulcerative ColitisSubcutaneous Adult Dosage RegimenThe recommended subcutaneous dosage of HYRIMOZ for adult patients with moderately to severely active ulcerative colitis is 160 mg initially on Day 1 (given in one day or split over two consecutive days), followed by 80 mg two weeks later (Day 15). Two weeks later (Day 29) continue with a dosage of 40 mg every other week.
Discontinue HYRIMOZ in adult patients without evidence of clinical remission by eight weeks (Day 57) of therapy. Aminosalicylates and/or corticosteroids may be continued during treatment with HYRIMOZ. Azathioprine and 6-mercaptopurine (6-MP)
[see Warnings and Precautions (5.2)]may be continued during treatment with HYRIMOZ if necessary.2.6 Recommended Dosage in Plaque Psoriasis or Adults with UveitisThe recommended subcutaneous dosage of HYRIMOZ for adult patients with plaque psoriasis (Ps) or uveitis (UV)
[see Indications and Usage ]is an initial dose of 80 mg, followed by 40 mg given every other week starting one week after the initial dose. The use of adalimumab products in moderate to severe chronic Ps beyond one year has not been evaluated in controlled clinical studies.2.7 Recommended Dosage in Hidradenitis SuppurativaSubcutaneous Adult Dosage RegimenThe recommended subcutaneous dosage of HYRIMOZ for adult patients with moderate to severe hidradenitis suppurativa (HS) is an initial dose of 160 mg (given in one day or split over two consecutive days), followed by 80 mg two weeks later (Day 15). Begin 40 mg weekly or 80 mg every other week dosing two weeks later (Day 29).Subcutaneous Pediatric Dosage RegimenThe recommended subcutaneous dosage of HYRIMOZ for pediatric patients 12 years of age and older weighing at least 30 kg with moderate to severe hidradenitis suppurativa (HS), based on body weight, is shown below[see Use in Specific Populations and Clinical Pharmacology ]:- Body Weight of Pediatric Patients (12 years of age and older)
- Recommended Dosage
- 30 kg (66 lbs) to less than 60 kg (132 lbs)
• Day 1: 80 mg• Day 8 and subsequent doses: 40 mg every other week
- 60 kg (132 lbs) and greater
• Day 1: 160 mg (given in one day or split over two consecutive days);• Day 15: 80 mg• Day 29 and subsequent doses: 40 mg every week or 80 mg every other week
2.8 General Considerations for AdministrationHYRIMOZ is intended for use under the guidance and supervision of a physician. A patient may self-inject HYRIMOZ or a caregiver may inject HYRIMOZ using either the HYRIMOZ single-dose prefilled Sensoready Pen or the HYRIMOZ single-dose prefilled syringe if a physician determines that it is appropriate, and with medical follow-up, as necessary, after proper training in subcutaneous injection technique.
HYRIMOZ can be taken out of the refrigerator for 15 to 30 minutes before injecting to allow the liquid to come to room temperature. Do not remove the cap while allowing it to reach room temperature. Carefully inspect the solution in the HYRIMOZ single-dose prefilled Sensoready Pen or HYRIMOZ single-dose prefilled syringe for particulate matter and discoloration prior to subcutaneous administration. The solution should be clear, colorless or slightly yellowish. Do not use a prefilled syringe or prefilled Sensoready Pen if the solution is cloudy, discolored, or has flakes or particles in it. HYRIMOZ does not contain preservatives; therefore, discard unused portions of drug remaining from the syringe.
Instruct patients using the HYRIMOZ single-dose prefilled Sensoready Pen and the HYRIMOZ single-dose prefilled syringe to inject the full amount according to the directions provided in the Instructions for Use [
seeInstructions for Use].Injections should occur at separate sites in the thigh or abdomen. Rotate injection sites and do not give injections into areas where the skin is tender, bruised, red or hard.
If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.
• Adults:40 mg every other week.
Some patients with RA not receiving methotrexate may benefit from increasing the dosage to 40 mg every week or 80 mg every other week.
Pediatric Weight 2 Years of Age and Older | Recommended Dosage |
10 kg (22 lbs) to less than 15 kg (33 lbs) | 10 mg every other week |
15 kg (33 lbs) to less than 30 kg (66 lbs) | 20 mg every other week |
30 kg (66 lbs) and greater | 40 mg every other week |
• Adults:160 mg on Day 1 (given in one day or split over two consecutive days); 80 mg on Day 15; and 40 mg• Pediatric Patients 6 Years of Age and Older:
Pediatric Weight | Recommended Dosage | |
Days 1 and 15 |
| |
17 kg (37 lbs) to less than 40 kg (88 lbs) | Day 1: 80 mg Day 15: 40 mg | 20 mg every other week |
40 kg (88 lbs) and greater | Day 1: 160 mg (single dose or split over two consecutive days) Day 15: 80 mg | 40 mg every other week |
• Adults: 160 mg on Day 1 (given in one day or split over two consecutive days), 80 mg on Day 15 and 40 mg every other week starting on Day 29.
• Adults: 80 mg initial dose, followed by 40 mg every other week starting one week after initial dose.
• Adults:o Day 1: 160 mg (given in one day or split over two consecutive days)o Day 15: 80 mgo Day 29 and subsequent doses: 40 mg every week or 80 mg every other week
• Adolescents 12 years of age and older:
|
|
30 kg (66 lbs) to less than 60 kg (132 lbs) | Day 1: 80 mg Day 8 and subsequent doses: 40 mg every other week |
60 kg (132 lbs) and greater | Day 1: 160 mg (given in one day or split over two consecutive days) Day 15: 80 mg Day 29 and subsequent doses: 40 mg every week or 80 mg every other week |
• Pen (Sensoready Pen)• Prefilled Syringe with BD UltraSafe Passive™ Needle Guard• Prefilled Syringe
Available studies with use of adalimumab during pregnancy do not reliably establish an association between adalimumab and major birth defects. Clinical data are available from the Organization of Teratology Information Specialists (OTIS)/MotherToBaby Pregnancy Registry in pregnant women with rheumatoid arthritis (RA) or Crohn’s disease (CD) treated with adalimumab. Registry results showed a rate of 10% for major birth defects with first trimester use of adalimumab in pregnant women with RA or CD and a rate of 7.5% for major birth defects in the disease-matched comparison cohort. The lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects (
Adalimumab is actively transferred across the placenta during the third trimester of pregnancy and may affect immune response in the
The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Published data suggest that the risk of adverse pregnancy outcomes in women with RA or inflammatory bowel disease (IBD) is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth.
Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester (
The safety and effectiveness of HYRIMOZ have not been established in pediatric patients with psoriatic arthritis, ankylosing spondylitis, or plaque psoriasis.
The safety and effectiveness of HYRIMOZ have been established for:
• reducing signs and symptoms of moderately to severely active polyarticular JIA in pediatric patients 2 years of age and older.• the treatment of moderately to severely active Crohn’s disease in pediatric patients 6 years of age and older.• the treatment of moderate to severe hidradenitis suppurativa in patients 12 years of age and older.• the treatment of non-infectious intermediate, posterior, and panuveitis in pediatric patients 2 years of age and older.
Due to their inhibition of TNFα, adalimumab products administered during pregnancy could affect immune response in the in utero-exposed newborn and infant. Data from eight infants exposed to adalimumab in utero suggest adalimumab crosses the placenta
Post-marketing cases of lymphoma, including hepatosplenic T-cell lymphoma and other malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blockers including adalimumab products
The safety and effectiveness of HYRIMOZ for the treatment of moderately to severely active polyarticular JIA have been established in pediatric patients 2 years of age and older. Use for this indication is supported by evidence from an adequate and well-controlled study (Study JIA) of adalimumab in patients 4 to 17 years of age
The safety of adalimumab in pediatric patients in the polyarticular JIA trials was generally similar to that observed in adults with certain exceptions
The safety and effectiveness of HYRIMOZ have not been established in pediatric patients with JIA less than 2 years of age.
The safety and effectiveness of HYRIMOZ for the treatment of moderately to severely active Crohn’s disease have been established in pediatric patients 6 years of age and older. Use of HYRIMOZ for this indication is supported by evidence from adequate and well-controlled studies in adults with additional data from a randomized, double-blind, 52-week clinical study of two dose concentrations of adalimumab in 192 pediatric patients (6 years to 17 years of age) [
The safety and effectiveness of HYRIMOZ have not been established in pediatric patients with Crohn’s disease less than 6 years of age.
The safety and effectiveness of HYRIMOZ for the treatment of non-infectious, intermediate, posterior, and panuveitis have been established in pediatric patients 2 years of age and older. Use of HYRIMOZ for this indication is supported by evidence from adequate and well-controlled studies of adalimumab in adults and a 2:1 randomized, controlled clinical study of adalimumab in 90 pediatric patients
Use of HYRIMOZ in pediatric patients 12 years of age and older for the treatment of moderate to severe HS is supported by evidence from adequate and well-controlled studies of adalimumab in adult HS patients. Additional population pharmacokinetic modeling and simulation predicted that weight-based dosing of adalimumab in pediatric patients 12 years of age and older can provide generally similar exposure to adult HS patients. The course of HS is sufficiently similar in adult and adolescent patients to allow extrapolation of data from adult to adolescent patients. The recommended dosage in pediatric patients 12 years of age or older is based on body weight
The safety and effectiveness of HYRIMOZ have not been established in patients less than 12 years of age with HS.
A prospective cohort pregnancy exposure registry conducted by OTIS/MotherToBaby in the U.S. and Canada between 2004 and 2016 compared the risk of major birth defects in live-born infants of 221 women (69 RA, 152 CD) treated with adalimumab during the first trimester and 106 women (74 RA, 32 CD) not treated with adalimumab.
The proportion of major birth defects among live-born infants in the adalimumab-treated and untreated cohorts was 10% (8.7% RA, 10.5% CD) and 7.5% (6.8% RA, 9.4% CD), respectively. The lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects. This study cannot reliably establish whether there is an association between adalimumab and major birth defects because of methodological limitations of the registry, including small sample size, the voluntary nature of the study, and the non-randomized design.
In an independent clinical study conducted in ten pregnant women with IBD treated with adalimumab, adalimumab concentrations were measured in maternal serum as well as in cord blood (n=10) and infant serum (n=8) on the day of birth. The last dose of adalimumab was given between 1 and 56 days prior to delivery. Adalimumab concentrations were 0.16 to 19.7 mcg/mL in cord blood, 4.28 to 17.7 mcg/mL in infant serum, and 0 to 16.1 mcg/mL in maternal serum. In all but one case, the cord blood concentration of adalimumab was higher than the maternal serum concentration, suggesting adalimumab actively crosses the placenta. In addition, one infant had serum concentrations at each of the following: 6 weeks (1.94 mcg/mL), 7 weeks (1.31 mcg/mL), 8 weeks (0.93 mcg/mL), and 11 weeks (0.53 mcg/mL), suggesting adalimumab can be detected in the serum of infants exposed in utero for at least 3 months from birth.
In an embryo-fetal perinatal development study, pregnant cynomolgus monkeys received adalimumab from gestation days 20 to 97 at doses that produced exposures up to 373 times that achieved with the MRHD without methotrexate (on an AUC basis with maternal IV doses up to 100 mg/kg/week). Adalimumab did not elicit harm to the fetuses or malformations.