Yuflyma

/ Padagis Israel Agencies Ltd

After proper training in injection technique, patients may self-inject with this medical treatment if their physician determines that it is appropriate and with medical follow-up as necessary.
Rheumatoid arthritis
The recommended dose for adult patients with rheumatoid arthritis is 40 mg adalimumab administered every other week as a single dose via subcutaneous injection.
Psoriasis
The recommended dose for adult patients is an initial dose of 80 mg administered subcutaneously, followed by 40 mg subcutaneously given every other week starting one week after the initial dose.
Hidradenitis suppurativa
The recommended dose regimen for adult patients with hidradenitis suppurativa (HS) is 160 mg initially at Day 1 (in one day or for two consecutive days), followed by 80 mg two weeks later at Day 15 (in one day). Two weeks later (Day 29) continue with a dose of 40 mg every week or 80 mg every other week. Antibiotics may be continued during treatment if necessary. It is recommended that the patient should use a topical antiseptic wash on their HS lesions on a daily basis during treatment.
Crohn’s disease
The recommended Yuflyma induction dose regimen for adult patients with moderately to severely active Crohn’s disease is 160 mg at Week 0 (in one day or two consecutive days), followed by 80 mg at Week 2 (in one day), followed by a maintenance dose of 40 mg every other week via subcutaneous injection beginning at Week 4.
Ulcerative colitis
The recommended induction dose regimen for adult patients with moderate to severe ulcerative colitis is 160 mg at Week 0 (in one day or two consecutive days) and 80 mg at Week 2 (in one day). After induction treatment, the recommended dose is 40 mg every other week via subcutaneous injection.
Uveitis
The recommended dose of for adult patients with uveitis is an initial dose of 80 mg, followed by 40 mg given every other week starting one week after the initial dose. There is limited experience in the initiation of treatment with adalimumab alone. Treatment can be initiated in combination with corticosteroids and/or with other non-biologic immunomodulatory agents. Concomitant corticosteroids may be tapered in accordance with clinical practice starting two weeks after initiating treatment.
Intestinal Behcet’s disease
The initial dose for adult intestinal Behcet’s disease patients is 160 mg as subcutaneous injection. The initial dose is followed by 80 mg two weeks later. From four weeks after the initial dose, 40 mg is administered every other week.

Rheumatoid arthritis
Adalimumab in combination with methotrexate is indicated for:
* Moderate to severe, active rheumatoid arthritis in adult patients when the response to disease-modifying anti-rheumatic drugs including methotrexate has been inadequate.
* Severe, active and progressive rheumatoid arthritis in adults not previously treated with methotrexate.
This medical product can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.
Juvenile idiopathic arthritis
Polyarticular juvenile idiopathic arthritis
In combination with methotrexate is indicated for the treatment of active polyarticular juvenile idiopathic arthritis, in patients from the age of 2 years who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs). This medical product can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.
Enthesitis-related arthritis
Active enthesitis-related arthritis in patients, 6 years of age and older, who have had an inadequate response to, or who are intolerant of, conventional therapy.
Axial spondyloarthritis
Ankylosing spondylitis (AS)
Adults with severe active ankylosing spondylitis who have had an inadequate response to conventional therapy.
Axial spondyloarthritis without radiographic evidence of AS
Adults with severe axial spondyloarthritis without radiographic evidence of AS, but with objective signs of inflammation by radiological and/or laboratory tests including MRI and serum CRP levels, who have had an inadequate response to, or are intolerant to, non – steroidal anti-inflammatory drugs (NSAIDs).
Psoriatic arthritis
Active and progressive psoriatic arthritis in adults when the response to previous disease-modifying anti-rheumatic drug therapy has been inadequate. Adalimumab has been shown to reduce the rate of progression of peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of the disease and to improve physical function.
Psoriasis
Moderate to severe chronic plaque psoriasis in adult patients who are candidates for systemic therapy.
Paediatric plaque psoriasis
Severe chronic plaque psoriasis in children and adolescents from 4 years of age who have had an inadequate response to or are inappropriate candidates for topical therapy and phototherapies.
Hidradenitis suppurativa (HS)
Active moderate to severe hidradenitis suppurativa (acne inversa) in adults and adolescents from 12 years of age with an inadequate response to conventional systemic HS therapy.
Crohn’s disease
Adult patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy. For reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.
Paediatric Crohn’s disease
Moderately to severely active Crohn’s disease in paediatric patients (from 6 years of age), who have had an inadequate response to conventional therapy including primary nutrition therapy and corticosteroid, and/or an immunomodulator, or who are intolerant to or have contraindications for such therapies.
Ulcerative colitis
Moderately to severely active ulcerative colitis in adult patients who have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies.
Paediatric ulcerative colitis
Moderately to severely active ulcerative colitis in paediatric patients (from 6 years of age) who have had an inadequate response to conventional therapy including corticosteroids and/or 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies.
Uveitis
Non-infectious intermediate, posterior and panuveitis in adult patients who have had an inadequate response to corticosteroids, in patients in need of corticosteroid-sparing, or in whom corticosteroid treatment is inappropriate.
Paediatric Uveitis
Chronic non-infectious uveitis in paediatric patients from 2 years of age who have had an inadequate response to or are intolerant to conventional therapy, or in whom conventional therapy is inappropriate.
Intestinal Behcet’s disease
Intestinal Behcet’s disease in patients who have had an inadequate response to conventional therapy.

* Hypersensitivity to the active substance or to any of the excipients.
* Active tuberculosis or other severe infections such as sepsis, and opportunistic infections.
* Moderate to severe heart failure (NYHA class III/IV).

Infections
Patients taking TNF-antagonists are more susceptible to serious infections. Impaired lung function may increase the risk for developing infections. Patients must therefore be monitored closely for infections, including tuberculosis, before, during and after treatment. Because the elimination of adalimumab may take up to four months, monitoring should be continued throughout this period. Patients who develop a new infection while undergoing treatment should be monitored closely and undergo a complete diagnostic evaluation. Administration of this medical product should be discontinued if a patient develops a new serious infection or sepsis, and appropriate antimicrobial or antifungal therapy should be initiated until the infection is controlled.
Serious infections
Serious infections, including sepsis, due to bacterial, mycobacterial, invasive fungal, parasitic, viral, or other opportunistic infections such as listeriosis, legionellosis and pneumocystis have been reported in patients receiving adalimumab.
Other serious infections seen in clinical trials include pneumonia, pyelonephritis, septic arthritis and septicaemia. Hospitalisation or fatal outcomes associated with infections have been reported.
Tuberculosis
Tuberculosis, including reactivation and new onset of tuberculosis, has been reported in patients receiving adalimumab. Reports included cases of pulmonary and extra-pulmonary (i.e., disseminated) tuberculosis. Before initiation of therapy, all patients must be evaluated for both active or inactive (“latent”) tuberculosis infection. This evaluation should include a detailed medical assessment of patient history of tuberculosis or possible previous exposure to people with active tuberculosis and previous and/or current immunosuppressive therapy.
If active tuberculosis is diagnosed, adalimumab therapy must not be initiated.
Other opportunistic infections
Opportunistic infections, including invasive fungal infections have been observed in patients receiving adalimumab. For patients who develop the signs and symptoms such as fever, malaise, weight loss, sweats, cough, dyspnoea, and/or pulmonary infiltrates or other serious systemic illness with or without concomitant shock an invasive fungal infection should be suspected and administration should be promptly discontinued. Diagnosis and administration of empiric antifungal therapy in these patients should be made in consultation with a physician with expertise in the care of patients with invasive fungal infections.
Hepatitis B reactivation
Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including adalimumab, who are chronic carriers of this virus (i.e. surface antigen positive). Some cases have had a fatal outcome. Patients should be tested for HBV infection before initiating treatment. Carriers of HBV who require treatment with adalimumab should be closely monitored for signs and symptoms of active HBV infection throughout therapy and for several months following termination of therapy. In patients who develop HBV reactivation, Adalimumab should be stopped and effective anti-viral therapy with appropriate supportive treatment should be initiated.
Neurological events
TNF-antagonists including adalimumab have been associated in rare instances with new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease including multiple sclerosis and optic neuritis, and peripheral demyelinating disease, including Guillain-Barré syndrome. Exercise caution in considering the use of adalimumab in patients with pre-existing or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of adalimumab should be considered if any of these disorders develop. There is a known association between intermediate uveitis and central demyelinating disorders. Neurologic evaluation should be performed in patients with non-infectious intermediate uveitis prior to the initiation of therapy and regularly during treatment to assess for pre- existing or developing central demyelinating disorders.
Allergic reactions
Serious allergic reactions associated with adalimumab were rare during clinical trials. Non-serious allergic reactions associated with adalimumab were uncommon during clinical trials. Reports of serious allergic reactions including anaphylaxis have been received following adalimumab administration. If an anaphylactic reaction or other serious allergic reaction occurs, administration should be discontinued immediately and appropriate therapy initiated.
Immunosuppression
In a study of 64 patients with rheumatoid arthritis that were treated with adalimumab, there was no evidence of depression of delayed-type hypersensitivity, depression of immunoglobulin levels, or change in enumeration of effector T-, B-, NK-cells, monocyte/macrophages, and neutrophils.
Malignancies and lymphoproliferative disorders
In the controlled portions of clinical trials of TNF-antagonists, more cases of malignancies including lymphoma have been observed among patients receiving a TNF-antagonist compared with control patients. However, the occurrence was rare. In the post marketing setting, cases of leukaemia have been reported in patients treated with a TNF-antagonist. With the current knowledge, a possible risk for the development of lymphomas, leukaemia, and other malignancies in patients treated with a TNF-antagonist cannot be excluded.
With current data it is not known if adalimumab treatment influences the risk for developing dysplasia or colon cancer. All patients with ulcerative colitis who are at increased risk for dysplasia or colon carcinoma (for example, patients with long-standing ulcerative colitis or primary sclerosing cholangitis), or who had a prior history of dysplasia or colon carcinoma should be screened for
dysplasia at regular intervals before therapy and throughout their disease course. This evaluation should include colonoscopy and biopsies per local recommendations.
Haematologic reactions
Adverse events of the haematologic system, including medically significant cytopenia (e.g., thrombocytopenia, leukopenia) have been reported with adalimumab. All patients should be advised to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias (e.g., persistent fever, bruising, bleeding, pallor). Discontinuation of therapy should be considered in patients with confirmed significant haematologic abnormalities.
Vaccinations
Similar antibody responses to the standard 23-valent pneumococcal vaccine and the influenza trivalent virus vaccination were observed in a study in 226 adult subjects with rheumatoid arthritis who were treated with adalimumab or placebo. No data are available on the secondary transmission of infection by live vaccines in patients receiving adalimumab.
It is recommended that paediatric patients, if possible, be brought up to date with all immunisations in agreement with current immunisation guidelines prior to initiating Yuflyma therapy.
Patients on Yuflyma may receive concurrent vaccinations, except for live vaccines. Administration of live vaccines (e.g., BCG vaccine) to infants exposed to adalimumab in utero is not recommended for 5 months following the mother’s last adalimumab injection during pregnancy.
Congestive heart failure
In a clinical trial with another TNF-antagonist worsening congestive heart failure and increased mortality due to congestive heart failure have been observed. Cases of worsening congestive heart failure have also been reported in patients receiving adalimumab. This medical product should be used with caution in patients with mild heart failure (NYHA class I/II). This medical product is contraindicated in moderate to severe heart failure. Treatment with adalimumab must be discontinued in patients who develop new or worsening symptoms of congestive heart failure.
Autoimmune processes
Treatment with adalimumab may result in the formation of autoimmune antibodies. The impact of long- term treatment with adalimumab on the development of autoimmune diseases is unknown. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with adalimumab and is positive for antibodies against double-stranded DNA, further treatment with should not be given.
Concurrent administration of biologic DMARDS or TNF-antagonists
Concomitant administration of adalimumab with other biologic DMARDS (e.g, anakinra and abatacept) or other TNF-antagonists is not recommended based upon the possible increased risk for infections, including serious infections and other potential pharmacological interactions.
Surgery
There is limited safety experience of surgical procedures in patients treated with adalimumab. The long half-life of adalimumab should be taken into consideration if a surgical procedure is planned. A patient who requires surgery while on adalimumab should be closely monitored for infections and appropriate actions should be taken. There is limited safety experience in patients undergoing arthroplasty while receiving adalimumab.
Elderly
The frequency of serious infections among adalimumab treated subjects over 65 years of age (3.7%) was higher than for those under 65 years of age (1.5%). Some of those had a fatal outcome. Particular attention regarding the risk for infection should be paid when treating the elderly.
See prescribing information for full details.

Very common: Respiratory tract infections (including lower and upper respiratory tract infection, pneumonia, sinusitis, pharyngitis, nasopharyngitis and pneumonia herpes viral), Leukopenia (including neutropenia and agranulocytosis), anaemia, Lipids increased, Headache, Abdominal pain, nausea and vomiting, Elevated liver enzymes, Rash (including exfoliative rash), Musculoskeletal pain, Injection site reaction (including injection site erythema).
Common: Systemic infections (including sepsis, candidiasis and influenza), intestinal infections (including gastroenteritis viral), skin and soft tissue infections (including paronychia, cellulitis, impetigo, necrotising fasciitis and herpes zoster), ear infections, oral infections (including herpes simplex, oral herpes and tooth infections), reproductive tract infections (including vulvovaginal mycotic infection), urinary tract infections (including pyelonephritis), fungal infections, joint infections, skin cancer excluding melanoma (including basal cell carcinoma and squamous cell carcinoma),
benign neoplasm, leucocytosis, thrombocytopenia, hypersensitivity, allergies (including seasonal allergy), hypokalaemia, uric acid increased, blood sodium abnormal, hypocalcaemia, hyperglycaemia, hypophosphatemia, dehydration, mood alterations (including depression), anxiety, insomnia, paraesthesias (including hypoesthesia), migraine, nerve root compression, Visual impairment, conjunctivitis, blepharitis, eye swelling, vertigo, tachycardia, hypertension, flushing, haematoma, asthma, dyspnoea, cough, GI haemorrhage, dyspepsia, gastroesophageal reflux disease, sicca syndrome, worsening or new onset of psoriasis (including palmoplantar pustular psoriasis) , urticaria, bruising (including purpura), dermatitis (including eczema), onychoclasis, hyperhidrosis, alopecia1), pruritus, muscle spasms (including blood creatine phosphokinase increased), renal impairment, haematuria, chest pain, oedema, pyrexia, coagulation and bleeding disorders (including activated partial
thromboplastin time prolonged), autoantibody test positive (including double stranded DNA antibody), blood lactate dehydrogenase increased, impaired healing.

Adalimumab has been studied in rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and psoriatic arthritis patients taking adalimumab as monotherapy and those taking concomitant methotrexate. Antibody formation was lower when adalimumab was given together with methotrexate in comparison with use as monotherapy.
Administration of adalimumab without methotrexate resulted in increased formation of antibodies, increased clearance and reduced efficacy of adalimumab.
See prescribing information for full details.

Pregnancy: A large number (approximately 2100) of prospectively collected pregnancies exposed to adalimumab resulting in live birth with known outcomes, including more than 1500 exposed during the first trimester, does not indicate an increase in the rate of malformation in the newborn. Due to its inhibition of TNFα, adalimumab administered during pregnancy could
affect normal immune responses in the newborn. Adalimumab should only be
used during pregnancy if clearly needed.
Adalimumab may cross the placenta into the serum of infants born to women
treated with adalimumab during pregnancy. Consequently, these infants may be at increased risk for infection. Administration of live vaccines (e.g., BCG vaccine) to infants exposed to adalimumab in utero is not recommended for 5 months following the mother’s last adalimumab injection during pregnancy.
Lactation: Limited information from the published literature indicates that adalimumab is excreted in breast milk at very low concentrations with the presence of adalimumab in human milk at concentrations of 0.1% to 1% of the maternal serum level. Given orally, immunoglobulin G proteins undergo intestinal proteolysis and have poor bioavailability. No effects on the breastfed newborns/infants are anticipated. Consequently, this medical product can be used during breastfeeding.
See prescribing information for full details.

No dose-limiting toxicity was observed during clinical trials. The highest dose level evaluated has been multiple intravenous doses of 10 mg/kg, which is approximately 15 times the recommended dose.