Dosage & Administration
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Kevzara Prescribing Information
Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving immunosuppressive agents including KEVZARA. Among opportunistic infections, tuberculosis, candidiasis, and pneumocystis were reported with KEVZARA. Some patients presented with disseminated rather than localized disease and were often taking concomitant immunosuppressants such as methotrexate or corticosteroids. The most frequently observed serious infections with KEVZARA in RA patients included pneumonia and cellulitis
Avoid use of KEVZARA in patients with an active infection, including localized infections. Consider the risks and benefits of treatment prior to initiating KEVZARA in patients who have:
- chronic or recurrent infection;
- a history of serious or opportunistic infections;
- underlying conditions that may predispose them to infection;
- been exposed to tuberculosis; or
- lived in or traveled to areas of endemic tuberculosis or endemic mycoses.
Closely monitor patients for the development of signs and symptoms of infection during treatment with KEVZARA, as signs and symptoms of acute inflammation may be lessened due to suppression of the acute phase reactants
Hold treatment with KEVZARA if a patient develops a serious infection or an opportunistic infection.
Perform prompt and complete diagnostic testing appropriate for an immunocompromised patient who develops a new infection during treatment with KEVZARA; initiate appropriate antimicrobial therapy, and closely monitor the patient.
Evaluate patients for tuberculosis (TB) risk factors and test for latent infection prior to initiating treatment with KEVZARA. Treat patients with latent TB with standard antimycobacterial therapy before initiating KEVZARA. Consider anti-TB therapy prior to initiation of KEVZARA in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent TB but having risk factors for TB infection. When considering anti-TB therapy, consultation with a physician with expertise in TB may be appropriate.
Closely monitor patients for the development of signs and symptoms of TB including patients who tested negative for latent TB infection prior to initiating therapy.
Viral reactivation has been reported with immunosuppressive biologic therapies. Cases of herpes zoster were observed in clinical studies with KEVZARA
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
All patients in the safety data described below had moderately to severely active rheumatoid arthritis.
The safety of KEVZARA in combination with conventional DMARDs was evaluated based on data from seven studies, of which two were placebo-controlled, consisting of 2887 patients (long-term safety population). Of these, 2170 patients received KEVZARA for at least 24 weeks, 1546 for at least 48 weeks, 1020 for at least 96 weeks, and 624 for at least 144 weeks.
The pre-rescue placebo-controlled population includes patients from the two Phase 3 efficacy studies (Studies 1 and 2) from weeks 0 to 16 for Study 1 and weeks 0 to 12 for Study 2, and was used to assess common adverse reactions and laboratory abnormalities prior to patients being permitted to switch from placebo to KEVZARA. In this population, 582 patients, 579 patients, and 579 patients received KEVZARA 200 mg, KEVZARA 150 mg, or placebo once every two weeks, respectively, in combination with conventional DMARDs.
The 52-week placebo-controlled population includes patients from one Phase 2 study of 12-week duration and two Phase 3 efficacy studies (one of 24-week duration and the other of 52-week duration). This placebo-controlled population includes all subjects from the double-blind, placebo-controlled periods from each study and was analyzed under their original randomization assignment. In this population, 661 patients, 660 patients, and 661 patients received KEVZARA 200 mg, KEVZARA 150 mg, or placebo once every two weeks, respectively, in combination with conventional DMARDs.
Most safety data are described for the pre-rescue population. For rarer events, the 52-week placebo-controlled population is used.
The most common serious adverse reactions were infections
The most frequent adverse reactions (occurring in at least 3% of patients treated with KEVZARA in combination with DMARDs) observed with KEVZARA in the clinical studies were neutropenia, increased ALT, injection site erythema, upper respiratory infections, and urinary tract infections.
In the pre-rescue placebo-controlled population, premature discontinuation due to adverse reactions occurred in 8%, 6% and 3% of patients treated with KEVZARA 200 mg, KEVZARA 150 mg, and placebo, respectively.
The most common adverse reaction (greater than 1%) that resulted in discontinuation of therapy with KEVZARA was neutropenia.
The use of KEVZARA as monotherapy was assessed in 132 patients, of which 67 received KEVZARA 200 mg and 65 patients received KEVZARA 150 mg without concomitant DMARDs. The safety profile was generally consistent with that in the population receiving concomitant DMARDs.
Overall Infections
In the pre-rescue placebo-controlled population, the rate of infections in the 200 mg and 150 mg KEVZARA + DMARD group was 110 and 105 events per 100 patient-years, respectively, compared to 81 events per 100 patient-years in the placebo + DMARD group. The most commonly reported infections (2% to 4% of patients) were upper respiratory tract infections, urinary tract infections, and nasopharyngitis.
In the 52-week placebo-controlled population, 0.8% of patients (5 patients) treated with KEVZARA 200 mg + DMARD, 0.6% (4 patients) treated with KEVZARA 150 mg + DMARD and 0.5% (3 patients) treated with placebo + DMARD had an event of herpes zoster
The overall rate of infections with KEVZARA + DMARD in the long-term safety population was consistent with rates in the controlled periods of the studies.
In the pre-rescue population, the rate of serious infections in the 200 mg and 150 mg KEVZARA + DMARD group was 3.8 and 4.4 events per 100 patient-years, respectively, compared to 2.5 events per 100 patient-years in the placebo + DMARD group. In the 52-week placebo-controlled population, the rate of serious infections in the 200 mg and 150 mg KEVZARA + DMARD group was 4.3 and 3.0 events per 100 patient-years, respectively, compared to 3.1 events per 100 patient-years in the placebo + DMARD group.
In the long-term safety population, the overall rate of serious infections was consistent with rates in the controlled periods of the studies. The most frequently observed serious infections included pneumonia and cellulitis. Cases of opportunistic infection have been reported
Gastrointestinal Perforation
In the 52-week placebo-controlled population, one patient on KEVZARA therapy experienced a gastrointestinal (GI) perforation (0.11 events per 100 patient-years).
In the long-term safety population, the overall rate of GI perforation was consistent with rates in the controlled periods of the studies. Reports of GI perforation were primarily reported as complications of diverticulitis including lower GI perforation and abscess. Most patients who developed GI perforations were taking concomitant nonsteroidal anti-inflammatory medications (NSAIDs) or corticosteroids. The contribution of these concomitant medications relative to KEVZARA in the development of GI perforations is not known
Hypersensitivity Reactions
In the pre-rescue placebo-controlled population, the proportion of patients who discontinued treatment due to hypersensitivity reactions was higher among those treated with KEVZARA (0.3% in 200 mg, 0.2% in 150 mg) than placebo (0%). The rate of discontinuations due to hypersensitivity in the long-term safety population was consistent with the placebo-controlled period.
Injection Site Reactions
In the pre-rescue placebo-controlled population, injection site reactions were reported in 7% of patients receiving KEVZARA 200 mg, 6% receiving KEVZARA 150 mg, and 1% receiving placebo. These injection site reactions (including erythema and pruritus) were mild in severity for the majority of patients and necessitated drug discontinuation in 2 (0.2%) patients receiving KEVZARA.
Laboratory Abnormalities
In the pre-rescue placebo-controlled population, decreases in neutrophil counts less than 1000 per mm3occurred in 6% and 4% of patients in the 200 mg KEVZARA + DMARD and 150 mg KEVZARA + DMARD group, respectively, compared to no patients in the placebo + DMARD groups. Decreases in neutrophil counts less than 500 per mm3occurred in 0.7% of patients in both the 200 mg KEVZARA + DMARD and 150 mg KEVZARA + DMARD groups. Decrease in ANC was not associated with the occurrence of infections, including seriou
In the long-term safety population, the observations on neutrophil counts were consistent with what was seen in the placebo-controlled clinical studies
In the pre-rescue placebo-controlled population, decreases in platelet counts less than 100,000 per mm3occurred in 1% and 0.7% of patients on 200 mg and 150 mg KEVZARA + DMARD, respectively, compared to no patients on placebo + DMARD, without associated bleeding events.
In the long-term safety population, the observations on platelet counts were consistent with what was seen in the placebo-controlled clinical studies
Liver enzyme elevations in the pre-rescue placebo-controlled population (KEVZARA + DMARD or placebo + DMARD) are summarized in Table 2. In patients experiencing liver enzyme elevation, modification of treatment regimen, such as interruption of KEVZARA or reduction in dose, resulted in decrease or normalization of liver enzymes
| Placebo + DMARD N=579 | KEVZARA 150 mg + DMARD N=579 | KEVZARA 200 mg + DMARD N=582 | |
|---|---|---|---|
| ULN = Upper Limit of Normal | |||
AST | |||
| Greater than ULN to 3 times ULN or less | 15% | 27% | 30% |
| Greater than 3 times ULN to 5 times ULN | 0% | 1% | 1% |
| Greater than 5 times ULN | 0% | 0.7% | 0.2% |
ALT | |||
| Greater than ULN to 3 times ULN or less | 25% | 38% | 43% |
| Greater than 3 times ULN to 5 times ULN | 1% | 4% | 3% |
| Greater than 5 times ULN | 0% | 1% | 0.7% |
Lipid parameters (LDL, HDL, and triglycerides) were first assessed at 4 weeks following initiation of KEVZARA + DMARDs in the placebo-controlled population. Increases were observed at this time point with no additional increases observed thereafter. Changes in lipid parameters from baseline to Week 4 are summarized below:
- Mean LDL increased by 12 mg/dL in the KEVZARA 150 mg every two weeks + DMARD group and 16 mg/dL in the KEVZARA 200 mg every two weeks + DMARD group.
- Mean triglycerides increased by 20 mg/dL in the KEVZARA 150 mg every two weeks + DMARD group and 27 mg/dL in the KEVZARA 200 mg every two weeks + DMARD group.
- Mean HDL increased by 3 mg/dL in both the KEVZARA 150 mg every two weeks + DMARD and KEVZARA 200 mg every two weeks + DMARD groups.
In the long-term safety population, the observations in lipid parameters were consistent with what was observed in the placebo-controlled clinical studies.
Malignancies
In the 52-week placebo-controlled population, 9 malignancies (exposure-adjusted event rate of 1.0 event per 100 patient-years) were diagnosed in patients receiving KEVZARA + DMARD compared to 4 malignancies in patients in the control group (exposure-adjusted event rate of 1.0 event per 100 patient-years).
In the long-term safety population, the rate of malignancies was consistent with the rate observed in the placebo-controlled period
Other Adverse Reactions
Adverse reactions occurring in 2% or more of patients on KEVZARA + DMARD and greater than those observed in patients on placebo + DMARD are summarized in Table 3.
| Adverse Reactions | Placebo + DMARD (N=579) | KEVZARA 150 mg + DMARD (N=579) | KEVZARA 200 mg + DMARD (N=582) |
|---|---|---|---|
| Neutropenia | 0.2% | 7% | 10% |
| Alanine aminotransferase increased | 2% | 5% | 5% |
| Injection site erythema | 0.9% | 5% | 4% |
| Injection site pruritus | 0.2% | 2% | 2% |
| Upper respiratory tract infection | 2% | 4% | 3% |
| Urinary tract infection | 2% | 3% | 3% |
| Hypertriglyceridemia | 0.5% | 3% | 1% |
| Leukopenia | 0% | 0.9% | 2% |
Medically relevant adverse reactions occurring at an incidence less than 2% in patients with rheumatoid arthritis treated with KEVZARA in controlled studies was oral herpes.
Safety has been studied in one Phase 3 study (Study 3) in 117 PMR patients of whom 59 received subcutaneous KEVZARA 200 mg
The common adverse reactions occurring in ≥5% of patients treated with KEVZARA were neutropenia (15.3%), leukopenia (6.8%), constipation (6.8%), rash pruritic (5.1%), myalgia (6.8%), fatigue (5.1%), and injection site pruritus (5.1%).
Serious adverse reactions of neutropenia occurred in 2 patients (3.4%) in the KEVZARA group compared to none in the placebo group. In both cases of neutropenia, the participants had a neutrophil count less than 500 per mm3without any infections and resolved following permanent discontinuation of study drug.
The most common adverse reactions that resulted in permanent discontinuation of therapy with KEVZARA were neutropenia in 3 patients (5.1%) and infection in 3 separate patients (5.1%), including COVID-19 (n=1), intervertebral discitis (n=1), and pneumonia (n=1).
Overall Infections
In Study 3, the proportion of patients with infections was lower in the KEVZARA group (37.3%) compared to the placebo group (50.0%). Two patients (3.2%) in the KEVZARA group and 1 patient (1.7%) in the placebo group had an event of herpes zoster.
In Study 3, the proportion of patients with serious infections was similar in the KEVZARA group (5.1%) compared to the placebo group (5.2%).
Injection Site Reactions
In Study 3, three patients (5.1%) in the KEVZARA group experienced injection site reactions of pruritus which were mild in severity. No patient in the placebo group experienced injection site reactions.
Laboratory Abnormalities
In Study 3, decreases in neutrophil counts less than 1,000 per mm3occurred in 12% of the KEVZARA treated group and no patient in the placebo treated group. Decreases in neutrophil counts less than 500 per mm3occurred in 3.4% of patients in KEVZARA treated group compared to no patient in the placebo treated group.
In Study 3, decreases in platelet counts between 75,000 to 100,000 per mm3occurred in two patients (3.4%) in the KEVZARA group, compared to no patient in the placebo treated group. These platelet count decreases were transient and not associated with bleeding events.
In Study 3, no KEVZARA treated patients had an ALT or AST greater than 3 times the upper limit of normal (ULN). In the placebo treated group, 2 patients had ALT elevations greater than 3 times the ULN.
In Study 3, cholesterol levels ≥299.27 mg/dL were observed in 8/58 (13.8%) patients in the KEVZARA group compared to 4/58 (6.9%) patients in the placebo group. Triglycerides ≥407.4 mg/dL were observed in 3/58 (5.2%) patients in the KEVZARA group compared to 1/58 (1.7%) in the placebo group.
No significant differences in mean HDL between KEVZARA group and placebo group were observed. At Week 52, mean increase from baseline for LDL and triglycerides levels were observed in the KEVZARA group though both remained within the normal range.
The safety of KEVZARA was studied in patients 2 to 17 years of age with pJIA who have had an inadequate response to current therapy (Study 4)
The overall median duration of study treatment for the recommended dose was 672 days. The cumulative exposure to treatment for patients who received the recommended dose at any time during the study was 184.1 patient-years.
The most common adverse drug reactions were nasopharyngitis, neutropenia, upper respiratory tract infection, and injection site erythema.
The most common adverse drug reaction that resulted in permanent discontinuation of therapy with KEVZARA was neutropenia (5.4%).
No new adverse reactions and safety concerns were identified in the pJIA population compared to the RA population.
Infections
In Study 4, the rate of infections was 146.6 events per 100 patient-years. The most common infections observed were nasopharyngitis (36.6%) and upper respiratory tract infections (URTI) (14.0%).
Injection Site Reactions
In Study 4, injection site reactions (ISRs) occurred in 13 (14.0%) patients and the most commonly reported ISR was injection site erythema (9.7%). The majority of these events were mild and none of the ISRs required patient withdrawal from treatment or dose interruption.
Laboratory Abnormalities
In Study 4, decreases in neutrophil counts less than 1000 per mm3occurred in 10/52 (19.2%) patients weighing in ≥30 kg and 20/41 (48.8%) patients weighing 10 to <30 kg. The frequency of decreased neutrophil count was higher until Week 12. Decrease in ANC was not associated with an occurrence of infections, including serious infections.
In Study 4, decrease in monocyte counts occurred in 4 (4.3%) patients and were mild in severity and non-serious.
In Study 4, nine (9.7%) patients had ALT increases, including one (1.1%) patient who had ALT >3 times upper limit of normal (ULN) and up to ≤5 times ULN, and two (2.2%) patients who had ALT increases >5 times ULN and up to ≤10 times ULN that resulted in permanent discontinuation. All patients recovered.
In Study 4, triglyceride levels of ≥150 mg/dL (1 × ULN) were observed in one (1.1%) patient. Three (3.2%) patients overall had elevation in triglycerides, and all were mild in severity and non-serious. No significant changes in mean LDL, HDL or total cholesterol were observed during the entire 156-week treatment period.
- Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients should be tested for latent tuberculosis before KEVZARA use and during therapy. Treatment for latent infection should be initiated prior to KEVZARA use.
- Invasive fungal infections, such as candidiasis, and pneumocystis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease.
- Bacterial, viral and other infections due to opportunistic pathogens.
Indications and Usage (KEVZARA®is an interleukin-6 (IL-6) receptor antagonist indicated for treatment of:
KEVZARA®is indicated for treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). KEVZARA is indicated for treatment of adult patients with polymyalgia rheumatica who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper. 1.3 Polyarticular Juvenile Idiopathic Arthritis (pJIA) KEVZARA is indicated for treatment of active polyarticular juvenile idiopathic arthritis (pJIA) in patients who weigh 63 kg or greater. | 6/2024 | ||||||||||||||||||||||||||||
Dosage and Administration (General Considerations for Administration
Recommended Dosage in RA
Recommended Dosage in PMR
Recommended Dosage in pJIA
Dosage Modifications for Cytopenias, Abnormal Liver Enzymes, Infections
Not Recommended for Concomitant Use with Biological DMARDS The concurrent use of KEVZARA with biological DMARDs such as tumor necrosis factor (TNF) antagonists, IL-1R antagonists, anti-CD20 monoclonal antibodies and selective co-stimulation modulators has not been studied. Avoid using KEVZARA with biological DMARDs because of the possibility of increased immunosuppression and increased risk of infection. Recommended Evaluations Prior to Treatment
The recommended dosage of KEVZARA is 200 mg once every two weeks given as a subcutaneous injection [see Dosage and Administration (2.1)]. KEVZARA may be used as monotherapy or in combination with methotrexate (MTX) or other conventional DMARDs. Modify the dosage as recommended in Table 1 if the patient develops neutropenia, thrombocytopenia, or liver enzyme abnormalities [see Dosage and Administration (2.6), Warnings and Precautions (5.2)and Adverse Reactions (6.1)]. The recommended dosage of KEVZARA is 200 mg once every two weeks given as a subcutaneous injection, in combination with a tapering course of systemic corticosteroids [see Dosage and Administration (2.1)] . KEVZARA can be used as monotherapy following discontinuation of corticosteroids.Discontinue KEVZARA if the patient develops neutropenia (using ANC results obtained at the end of the dosing interval), thrombocytopenia, or liver enzyme abnormalities [see Dosage and Administration (2.6), Warnings and Precautions (5.2)and Adverse Reactions (6.1)]. 2.4 Recommended Dosage for Polyarticular Juvenile Idiopathic Arthritis The recommended dosage of KEVZARA for patients who weigh 63 kg and greater is 200 mg once every two weeks given as a subcutaneous injection (maximum dose 200 mg). Dosage in this patient population can be achieved by administering the 200 mg/1.14 mL pre-filled syringe. The pre-filled pen is not intended for use in pediatric patients [see Dosage and Administration (2.6), Warnings and Precautions (5.2)and Adverse Reactions (6.1)]. KEVZARA is not approved in pediatric patients weighing less than 63 kg because of the lack of an appropriate dosage form.In patients with pJIA, KEVZARA can be used alone or in combination with conventional DMARDs. 2.5 Preparation and Administration Instructions Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. KEVZARA solution should be clear and colorless to pale yellow. Do not use if the solution is cloudy, discolored or contains particles, or if any part of the pre-filled syringe or pre-filled pen appears to be damaged. Rotate injection sites with each injection. Do not inject into skin that is tender, damaged, or has bruises or scars. Pre-filled Pen and Pre-filled Syringe
Dosage Modifications for Patients with Rheumatoid Arthritis
Dosage Modifications for Patients with Polymyalgia Rheumatica
Dosage Modification for Patients with Polyarticular Juvenile Idiopathic Arthritis Dose reduction of KEVZARA has not been studied in the pJIA population. Discontinue KEVZARA if ALT >5 ULN, platelet count ≤50,000 cells/mm3, neutrophil count <500 cells/mm3associated with infection. Hold KEVZARA dosing for ALT >3 to ≤5 ULN, platelet count >50,000 to ≤100,000 cells/mm3, and neutrophil count ≥500 to <1000 cells/mm3, and until the clinical condition has been evaluated. The decision to discontinue KEVZARA should be based upon the medical assessment of the individual patient. If appropriate, the dose of concomitant methotrexate and/or other medications should be modified or discontinued. | 6/2024 | ||||||||||||||||||||||||||||
KEVZARA® is an interleukin-6 (IL-6) receptor antagonist indicated for treatment of:
- adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). ()
1.1 Rheumatoid Arthritis (RA)KEVZARA®is indicated for treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs).
- adult patients with polymyalgia rheumatica (PMR) who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper. ()
1.2 Polymyalgia Rheumatica (PMR)KEVZARA is indicated for treatment of adult patients with polymyalgia rheumatica who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper.
- patients who weigh 63 kg or greater with active polyarticular juvenile idiopathic arthritis (pJIA). ()1.3 Polyarticular Juvenile Idiopathic Arthritis (pJIA)KEVZARA is indicated for treatment of active polyarticular juvenile idiopathic arthritis (pJIA) in patients who weigh 63 kg or greater.
- KEVZARA initiation is not recommended in patients with ANC less than 2,000/mm3, platelets less than 150,000/mm3 or liver transaminases above 1.5 times ULN. See Full Prescribing Information (FPI) for complete information. ()
2.1 General Considerations Prior to AdministrationNot Recommended for Concomitant Use with Biological DMARDSThe concurrent use of KEVZARA with biological DMARDs such as tumor necrosis factor (TNF) antagonists, IL-1R antagonists, anti-CD20 monoclonal antibodies and selective co-stimulation modulators has not been studied. Avoid using KEVZARA with biological DMARDs because of the possibility of increased immunosuppression and increased risk of infection.
Recommended Evaluations Prior to Treatment- Complete blood count (CBC): Treatment initiation with KEVZARA is not recommended in patients with an absolute neutrophil count (ANC) below 2000 per mm3, or platelet count below 150,000 per mm3. Monitor laboratory parameters[see Warnings and Precautions (5.2)].
- Liver function tests (LFT): Treatment initiation with KEVZARA is not recommended in patients with or who have alanine transaminase (ALT) or aspartate aminotransferase (AST) above 1.5 times the upper limit of normal (ULN). Monitor laboratory parameters[see Dosage and Administration (2.6)and Warnings and Precautions (5.2)].
- Lipid parameters (total cholesterol, LDL cholesterol, HDL cholesterol and/or triglycerides): Assess lipid parameters at baseline. Monitor laboratory parameters[see Warnings and Precautions (5.2)].
- Active and latent tuberculosis infection evaluation: Prior to initiating KEVZARA, test patients for active and latent tuberculosis (TB). KEVZARA should not be administered to patients with active TB. If positive for latent infection, consider treating for TB prior to KEVZARA use[see Warnings and Precautions (5.1)].
- Evaluate for infections: Avoid KEVZARA use in patients with active infections[see Warnings and Precautions (5.1)].
- Complete blood count (CBC): Treatment initiation with KEVZARA is not recommended in patients with an absolute neutrophil count (ANC) below 2000 per mm3, or platelet count below 150,000 per mm3. Monitor laboratory parameters
- The recommended dosage is 200 mg subcutaneously, once every 2 weeks. ()
2.2 Recommended Dosage for Rheumatoid ArthritisThe recommended dosage of KEVZARA is 200 mg once every two weeks given as a subcutaneous injection
[see Dosage and Administration (2.1)].KEVZARA may be used as monotherapy or in combination with methotrexate (MTX) or other conventional DMARDs.
Modify the dosage as recommended in Table 1 if the patient develops neutropenia, thrombocytopenia, or liver enzyme abnormalities
[see Dosage and Administration (2.6), Warnings and Precautions (5.2)and Adverse Reactions (6.1)]. - For RA, KEVZARA may be used as monotherapy or in combination with methotrexate (MTX) or other conventional DMARDs. ()
2.2 Recommended Dosage for Rheumatoid ArthritisThe recommended dosage of KEVZARA is 200 mg once every two weeks given as a subcutaneous injection
[see Dosage and Administration (2.1)].KEVZARA may be used as monotherapy or in combination with methotrexate (MTX) or other conventional DMARDs.
Modify the dosage as recommended in Table 1 if the patient develops neutropenia, thrombocytopenia, or liver enzyme abnormalities
[see Dosage and Administration (2.6), Warnings and Precautions (5.2)and Adverse Reactions (6.1)].
- The recommended dosage is 200 mg subcutaneously, once every two weeks in combination with a tapering course of corticosteroids. ()
2.3 Recommended Dosage for Polymyalgia RheumaticaThe recommended dosage of KEVZARA is 200 mg once every two weeks given as a subcutaneous injection, in combination with a tapering course of systemic corticosteroids
[see Dosage and Administration (2.1)]. KEVZARA can be used as monotherapy following discontinuation of corticosteroids.Discontinue KEVZARA if the patient develops neutropenia (using ANC results obtained at the end of the dosing interval), thrombocytopenia, or liver enzyme abnormalities
[see Dosage and Administration (2.6), Warnings and Precautions (5.2)and Adverse Reactions (6.1)]. - For PMR, KEVZARA can be used as monotherapy following discontinuation of corticosteroids. ()
2.3 Recommended Dosage for Polymyalgia RheumaticaThe recommended dosage of KEVZARA is 200 mg once every two weeks given as a subcutaneous injection, in combination with a tapering course of systemic corticosteroids
[see Dosage and Administration (2.1)]. KEVZARA can be used as monotherapy following discontinuation of corticosteroids.Discontinue KEVZARA if the patient develops neutropenia (using ANC results obtained at the end of the dosing interval), thrombocytopenia, or liver enzyme abnormalities
[see Dosage and Administration (2.6), Warnings and Precautions (5.2)and Adverse Reactions (6.1)].
- The recommended dosage is 200 mg given subcutaneously once every 2 weeks for pJIA patients who weigh 63 kg or greater using the 200 mg/1.14 mL pre-filled syringe. ()2.4 Recommended Dosage for Polyarticular Juvenile Idiopathic ArthritisThe recommended dosage of KEVZARA for patients who weigh 63 kg and greater is 200 mg once every two weeks given as a subcutaneous injection (maximum dose 200 mg). Dosage in this patient population can be achieved by administering the 200 mg/1.14 mL pre-filled syringe. The pre-filled pen is not intended for use in pediatric patients[see Dosage and Administration (2.6), Warnings and Precautions (5.2)and Adverse Reactions (6.1)].KEVZARA is not approved in pediatric patients weighing less than 63 kg because of the lack of an appropriate dosage form.In patients with pJIA, KEVZARA can be used alone or in combination with conventional DMARDs.
- For pJIA, KEVZARA can be used as monotherapy or in combination with conventional DMARDs. ()2.4 Recommended Dosage for Polyarticular Juvenile Idiopathic ArthritisThe recommended dosage of KEVZARA for patients who weigh 63 kg and greater is 200 mg once every two weeks given as a subcutaneous injection (maximum dose 200 mg). Dosage in this patient population can be achieved by administering the 200 mg/1.14 mL pre-filled syringe. The pre-filled pen is not intended for use in pediatric patients[see Dosage and Administration (2.6), Warnings and Precautions (5.2)and Adverse Reactions (6.1)].KEVZARA is not approved in pediatric patients weighing less than 63 kg because of the lack of an appropriate dosage form.In patients with pJIA, KEVZARA can be used alone or in combination with conventional DMARDs.
- See FPI for complete information. ()
2.6 Dosage Modifications for Cytopenias, Abnormal Liver Enzymes, or InfectionsDosage Modifications for Patients with Rheumatoid Arthritis- Laboratory Abnormalities: Modify dosage in case of neutropenia, thrombocytopenia, or liver enzyme elevations as shown in Table 1[see Warnings and Precautions (5.2)and Clinical Pharmacology (12.2)]. For treatment initiation criteria, refer to the dosage recommendations for RA[see Dosage and Administration (2.1, 2.2)].
Table 1: Dosage Modifications due to Neutropenia, Thrombocytopenia, or Elevated Liver Enzymes in Patients with Rheumatoid Arthritis Low Absolute Neutrophil Count (ANC)Lab Value (cells/mm3)RecommendationANC greater than 1,000 Maintain current dosage of KEVZARA. ANC 500 to 1,000 Hold treatment with KEVZARA until ANC greater than 1,000.
KEVZARA can then be resumed at 150 mg every two weeks and increased to 200 mg every two weeks as clinically appropriate.ANC less than 500 Discontinue KEVZARA. Low Platelet CountLab Value (cells/mm3)Recommendation50,000 to 100,000 Hold treatment with KEVZARA until platelets greater than 100,000.
KEVZARA can then be resumed at 150 mg every two weeks and increased to 200 mg every two weeks as clinically appropriate.Less than 50,000 If confirmed by repeat testing, discontinue KEVZARA. Liver Enzyme AbnormalitiesLab ValueRecommendationALT or AST greater than ULN to 3 times ULN Consider dosage modification of concomitant DMARDs as clinically appropriate. ALT or AST greater than 3 times ULN to 5 times ULN Hold treatment with KEVZARA until ALT or AST less than 3 times ULN.
KEVZARA can then be resumed at 150 mg every two weeks and increased to 200 mg every two weeks as clinically appropriate.ALT or AST greater than 5 times ULN Discontinue KEVZARA. - Infections:If a patient with RA develops a serious infection or an opportunistic infection, hold treatment with KEVZARA until the infection is controlled[see Warnings and Precautions (5.1)].
Dosage Modifications for Patients with Polymyalgia Rheumatica- Laboratory Abnormalities: Discontinue KEVZARA in patients with PMR who develop the following laboratory abnormalities[see Warnings and Precautions (5.2)and Clinical Pharmacology (12.2)]:
- neutropenia (ANC below 1,000 per mm3at the end of the dosing interval)
- thrombocytopenia (platelet count below 100,000 per mm3)
- AST or ALT elevations 3 times above the ULN
Dosage modifications have not been studied in patients with PMR with these conditions. For treatment initiation criteria, refer to the dosage recommendations for PMR[see Dosage and Administration (2.1, 2.3)]. - Infections: If a patient with PMR develops a serious infection or an opportunistic infection, hold treatment with KEVZARA until the infection is controlled[see Warnings and Precautions (5.1)].
Dosage Modification for Patients with Polyarticular Juvenile Idiopathic ArthritisDose reduction of KEVZARA has not been studied in the pJIA population. Discontinue KEVZARA if ALT >5 ULN, platelet count ≤50,000 cells/mm3, neutrophil count <500 cells/mm3associated with infection. Hold KEVZARA dosing for ALT >3 to ≤5 ULN, platelet count >50,000 to ≤100,000 cells/mm3, and neutrophil count ≥500 to <1000 cells/mm3, and until the clinical condition has been evaluated. The decision to discontinue KEVZARA should be based upon the medical assessment of the individual patient. If appropriate, the dose of concomitant methotrexate and/or other medications should be modified or discontinued.
Injection: 150 mg/1.14 mL and 200 mg/1.14 mL clear and colorless to pale-yellow solution in a single-dose pre-filled syringe.
Injection: 150 mg/1.14 mL and 200 mg/1.14 mL clear and colorless to pale-yellow solution in a single-dose pre-filled pen.
- Lactation: Discontinue drug or nursing taking into consideration importance of drug to mother. ()
8.2 LactationRisk SummaryNo information is available on the presence of sarilumab in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Maternal IgG is present in human milk. If sarilumab is transferred into human milk, the effects of local exposure in the gastrointestinal tract and potential limited systemic exposure in the infant to sarilumab are unknown. The lack of clinical data during lactation precludes clear determination of the risk of KEVZARA to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for KEVZARA and the potential adverse effects on the breastfed child from KEVZARA or from the underlying maternal condition.