Adalimumab

Registered South African indications: 

• Rheumatoid arthritis
• Psoriatic arthritis
• Axial spondyloarthritis
• Ankylosing spondylitis
• Crohns disease
• Ulcerative colitis
• Hidradenitis suppurativa
• Psoriasis
  - Plaque psoriasis
  - Nail psoriasis
• Uveitis
• Polyarticular juvenile idiopathic arthritis

Patients treated with adalimumab are at increased risk for developing serious infections that may lead to hospitalisation or death. Adalimumab should be discontinued if a patient develops a serious infection or sepsis

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Moderate to severe cardiac failure (NHYA class III/IV)
• Active tuberculosis or other severe infections
• Concomitant use with live vaccines

Contraindications registered in other jurisdictions

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

• Pregnancy 
• Breastfeeding 
• Renal impairment 
• Hepatic impairment
• Elderly 
• Impaired respiratory function
• Active infections
• Previous exposure to tuberculosis
• Active or latent tuberculosis 
• Previous travel in areas of high risk of tuberculosis or endemic mycoses
• History of recurring infection
• Underlying conditions which may predispose patients to infections
• Previous or current immunosuppressive therapy
• Psoriasis patients with a history of psoralen and ultraviolet A therapy
• Non-melanoma skin cancer
• Hepatitis B carriers
• Central or peripheral nervous system demyelinating disorders
• Children
• Adolescents 
• Moderate to severe chronic obstructive pulmonary disease
• Significant smoking history 
• Ulcerative colitis with risk factors for dysplasia or colon carcinoma
• Mild heart failure (NYHA I/II)
• Surgery
• Small bowel obstruction

Forms avail. in SA and covered in this monograph: inj, pfp, pfs

South African registered indications and dosages

Treatment should be initiated and supervised by specialist medical practitioner experienced in the diagnosis and treatment of conditions for which adalimumab is indicated

Rheumatoid arthritis (RA)
- For the treatment of moderate to severe rheumatoid arthritis in adult patients, including recently diagnosed patients who have not been previously treated with methotrexate (MTX)

• SC: 40mg, admin. as a single dose, every other week

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Adalimumab has been shown to induce clinical remission, reduces the rate of progression of structural damage as measured by X-ray and improves physical function, when given in combination with methotrexate

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Adalimumab can be used in combination with methotrexate or given as monotherapy in the case of intolerance to methotrexate or when continued treatment with methotrexate is deemed inappropriate
Methotrexate, glucocorticoids, salicylates, nonsteroidal anti-inflammatory medicines, analgesics or other DMARD’s may be continued during treatment with adalimumab

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In monotherapy, some patients who experience decrease in their response may benefit from an increase in dose intensity to 40mg of adalimumab every week. Available data suggest that the clinical response is usually achieved within 12 weeks of treatment. Continued therapy should be carefully reconsidered in a patient not responding within this time period

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Psoriatic arthritis (PsA)
- For reducing signs and symptoms of psoriatic arthritis

• SC: 40mg, admin. as a single dose, every other week

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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 improves physical function. Adalimumab can be used alone or in combination with disease modifying anti-rheumatic medicines (DMARDs). Glucocorticoids, salicylates, nonsteroidal anti inflammatory medicines, analgesics or disease modifying anti-rheumatic drugs can be continued during treatment with adalimumab

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Psoriasis
- For the treatment of moderate to severe chronic plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy when other systemic therapies are medically less appropriate

• SC: Initial: 80mg, admin. as a single dose; Followed by: 40mg, every other week starting one week after the initial dose; Beyond 16 weeks, patients with inadequate response may benefit from an increase in dosing frequency to 40mg every week

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The benefits and risks of continued weekly adalimumab therapy should be carefully reconsidered in a patient with an inadequate response 24 weeks after the increase in dosing frequency

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Axial spondyloarthritis including ankylosing spondylitis (AS)
- For the treatment of adults with severe axial spondyloarthritis, including ankylosing spondylitis, who have had an inadequate response to conventional therapy or are intolerant to nonsteroidal anti-inflammatory drugs (NSAIDs)
- For the treatment of adults with active ankylosing spondylitis who have had an inadequate response to conventional therapy

• SC: 40mg, admin. as a single dose, every other week

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Glucocorticoids, salicylates, nonsteroidal anti-inflammatory medicines, analgesics or disease modifying anti-rheumatic medicines can be continued during treatment with adalimumab

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Crohn’s disease
- For reducing signs and symptoms and inducing and maintaining clinical remission in 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 lost response to or are intolerant to infliximab

• SC: 160mg, at week 0 (dose can be admin. as 4 injections in one day or as 2 injections per day for 2 consecutive days); Then: 80mg, at week 2, followed 2 weeks later by a maintenance dose of 40mg every other week

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Aminosalicylates, corticosteroids, and/or immunomodulatory agents (e.g. 6- mercaptopurine and azathioprine) may be continued during treatment with adalimumab

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Some patients may derive additional benefit from increasing the dosing frequency of adalimumab to 40 mg every week. Some patients who have not responded by week 4 may benefit from continued maintenance therapy through week 12. Continued therapy should be carefully reconsidered in a patient not responding within this time period. During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice guidelines

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Ulcerative colitis
- For treatment of moderately to severely active ulcerative colitis in adult patients 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

• SC: 160mg, at week 0 (dose can be admin. as 4 injections in one day or as 2 injections per day for 2 consecutive days); Then: 80mg, at week 2; After induction treatment, the recommended dose is 40mg every other week

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Aminosalicylates, corticosteroids, and/or immunomodulatory agents (e.g., 6-mercaptopurine and azathioprine) may be continued during treatment with adalimumab. During maintenance treatment, corticosteroids may be tapered in accordance with clinical practice guidelines

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Some patients who experience decrease in their response may benefit from an increase in dosing frequency to 40mg adalimumab every week. Available data suggest that clinical response is usually achieved within 2-8 weeks of treatment. Adalimumab should only be continued in patients who have responded during the first 8 weeks of therapy

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Hidradenitis suppurativa
- For the treatment of active moderate to severe hidradenitis suppurativa (acne inversa) in adult patients, including treatment of inflammatory lesions and prevention of worsening of abscesses and draining fistulas 

• SC: Initial: 160mg, at day 1 (given as four 40mg injections in one day or as two 40mg injections per day for two consecutive days); Followed by: 80mg, two weeks later at day 15 (given as two 40mg injections in one day); Two weeks later (day 29): Continue with a dose of 40mg every week (antibiotics may be continued during treatment with adalimumab if necessary)

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Should treatment need to be interrupted, adalimumab may be re-introduced. In patients without any benefit after 12 weeks of treatment, continued therapy should be reconsidered

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Uveitis
- For the treatment of non-infectious intermediate, posterior and panuveitis in adult patients

• SC: Initial: 80mg, followed by 40mg given every other week starting one week after the initial dose

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Adalimumab can be used alone or in combination with corticosteroids, which may be tapered in accordance with clinical practice, or other non-biologic immunomodulatory agents

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All indications
Patients treated with adalimumab should be given the special alert card. After proper training in injection technique, patients may self-inject with adalimumab if their medical practitioner determines that it is appropriate and with medical follow-up as necessary. During treatment with adalimumab, other concomitant therapies (e.g., corticosteroids and/or immunomodulatory agents) should be optimised
See additional prescribing points for administration directions

Paed. forms avail. in SA and covered in this monograph: inj, pfp, pfs

South African registered indications and dosages

Treatment should be initiated and supervised by specialist medical practitioner experienced in the diagnosis and treatment of conditions for which adalimumab is indicated

Polyarticular juvenile idiopathic arthritis
- For reducing the signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis (JIA)

Younger than 2 years or < 10kg

• Not established for use

Older than 2 years

• SC: Based on body weight, see table below

Paediatric patients (2 years of age and older)	Dose
10kg - < 30kg	20mg every other week
≥ 30kg	40mg every other week

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Methotrexate, glucocorticoids, NSAIDs and/or analgesics may be continued during treatment with adalimumab

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Available data suggest that clinical response is usually achieved within 12 weeks of treatment. Continued therapy should be carefully reconsidered in a patient not responding within this time period

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Adalimumab has not been studied in patients with polyarticular juvenile idiopathic arthritis less than two years of age or in patients with a weight below 10kg

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Crohn's disease
- For reducing signs and symptoms and inducing and maintaining clinical remission in paediatric patients, with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy

Younger than 6 years: 

• Not established for use

Between 6-17 years

• SC: Based on body weight, see table below

Patient weight	Induction dose	Maintenance dose Starting at Week 4
< 40kg	Week 0: 80mg Week 2: 40mg	20mg every other week
≥ 40kg	Week 0: 160mg Week 2: 80mg	40mg every other week

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Some patients may benefit from increasing the frequency to weekly if a disease flare or an inadequate response is experienced during maintenance dosing

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Adalimumab has not been studied in children with Crohn’s disease age less than 6 years

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Paediatric plaque psoriasis
- For the treatment of severe chronic plaque psoriasis who have had an inadequate response to or are inappropriate candidates for topical therapy and phototherapy

Younger than 4 years

• Not established for use

Between 4-17 years 

• SC: Based on body weight, see table below

Patients weight	Dose
15kg to < 30kg	Initial: 20mg; Followed by: 20mg given every other week starting one week after the initial dose
≥ 30kg	Initial: 40mg; Followed by: 40mg given every other week starting one week after the initial dose

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Continued therapy beyond 16 weeks should be carefully considered in a patient not responding within this time period. If retreatment with adalimumab is indicated, the above guidance on dose and treatment duration should be followed

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There is no relevant use of adalimumab in children aged less than 4 years in this indication

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Paediatric uveitis
- For the treatment of chronic non-infectious uveitis

Younger than 2 years

• Not established for use

Older than 2 years

• SC: Based on body weight, see table below

Paediatric patients (2 years of age and older)	Initial dose (admin. 1 week prior to maintenance therapy)	Dose
< 30kg	Loading dose: 40mg	20mg every other week
≥ 30kg	Loading dose: 80mg	40mg every other week

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Adalimumab may be used in combination with methotrexate or other non-biologic immunomodulatory agents based on clinical judgment

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Adalimumab has not been studied in patients with chronic non-infections uveitis less than 2 years of age

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All indications
Adalimumab may be available in other strengths and/or presentations depending on the individual treatment needs
Patients treated with adalimumab should be given the special alert card. After proper training in injection technique, patients may self-inject with adalimumab if their medical practitioner determines that it is appropriate and with medical follow-up as necessary. During treatment with adalimumab, other concomitant therapies (e.g., corticosteroids and/or immunomodulatory agents) should be optimised
See additional prescribing points for administration directions

Pregnancy 

• Caution
• 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
• In a prospective cohort registry, 257 women with rheumatoid arthritis (RA) or Crohn's disease (CD) treated with adalimumab at least during the first trimester and 120 women with RA or CD not treated with adalimumab were enrolled. The primary endpoint was the birth prevalence of major birth defects. The rate of pregnancies ending with at least one live born infant with a major birth defect was 6/69 (8.7%) in the adalimumab-treated women with RA and 5/74 (6.8%) in the untreated women with RA (unadjusted OR 1.31, 95% CI 0.38-4.52) and 16/152 (10.5%) in the adalimumab-treated women with CD and 3/32 (9.4%) in the untreated women with CD (unadjusted OR 1.14, 95% CI 0.31-4.16). The adjusted OR (accounting for baseline differences) was 1.10 (95% CI 0.45-2.73) with RA and CD combined. There were no distinct differences between adalimumab-treated and untreated women for the secondary endpoints spontaneous abortions, minor birth defects, preterm delivery, birth size and serious or opportunistic infections and no stillbirths or malignancies were reported. The interpretation of data may be impacted due to methodological limitations of the study, including small sample size and non-randomized design
• In a developmental toxicity study conducted in monkeys, there was no indication of maternal toxicity, embryotoxicity or teratogenicity. Preclinical data on postnatal toxicity of adalimumab are not available 
• Due to its inhibition of TNF-alpha, 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

Breastfeeding

• Compatible
• 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, adalimumab can be used during breastfeeding

Renal Impairment 

• Caution; no information available

Hepatic Impairment 

• Caution; no information available

Elderly 

• Caution; no dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warning

Central Nervous System Disorders

• Depression
• Anxiety
• Insomnia
• Headache
• Paraesthesia
• Migraine
• Nerve root compression
• Cerebrovascular accident
• Tremor
• Neuropathy
• Multiple sclerosis
• Demyelinating disorders
• Meningitis 

Cardiovascular Disorders

• Tachycardia
• Myocardial infarction
• Arrhythmia
• Congestive heart failure
• Cardiac arrest
• Hypertension
• Flushing
• Haematoma
• Aortic aneurysm
• Vascular arterial occlusion
• Thrombophlebitis
• Chest pain 

Respiratory Disorders

• Asthma
• Dyspnoea
• Cough
• Pulmonary embolism
• Interstitial lung disease
• Chronic obstructive pulmonary disease
• Pneumonitis
• Pleural effusion
• Pulmonary fibrosis
• Lower and upper respiratory tract infection
• Pneumonia
• Sinusitis
• Pharyngitis
• Nasopharyngitis
• Tuberculosis 

Gastrointestinal Disorders

• Abdominal pain
• Nausea and vomiting
• Gastrointestinal haemorrhage
• Dyspepsia
• Gastro-esophageal reflux disease
• Sicca syndrome
• Dysphagia
• Intestinal perforation
• Viral gastroenteritis
• Oral infections 
• Diverticulitis 

Hepatobiliary Disorders

• Increased hepatic enzymes
• Cholecystitis
• Cholelithiasis
• Hepatic steatosis
• Increased bilirubin
• Hepatitis
• Pancreatitis
• Reactivation of hepatitis
• Autoimmune hepatitis
• Hepatic failure
• Increased lactate dehydrogenase 

Genitourinary Disorders

• Renal impairment
• Haematuria
• Nocturia
• Erectile dysfunction
• Vulvovaginal mycotic infection
• Pyelonephritis 

Endocrine and Metabolic Disorders

• Increased lipids
• Hypokalaemia
• Increased uric acid
• Abnormal sodium levels
• Hypocalcaemia
• Hyperglycaemic
• Hypophosphatemia
• Dehydration

Musculoskeletal Disorders

• Musculoskeletal pain
• Muscle spasms
• Increased creatine phosphokinase
• Rhabdomyolysis
• Systemic lupus erythematosus
• Lupus-like syndrome
• Joint infections 

Skin and Subcutaneous Tissue Disorders

• Facial oedema
• Rash
• Worsening or new onset of psoriasis
• Urticaria
• Bruising
• Purpura
• Dermatitis
• Onychoclasis
• Hyperhidrosis
• Alopecia
• Pruritus
• Night sweats
• Scarring
• Erythema multiforme
• Stevens-Johnson syndrome
• Cutaneous vasculitis
• Worsening of symptoms of dermatomyositis
• Injection site reactions
• Skin and soft tissue infections
• Skin cancer excluding melanoma

Immune, Blood and Lymphatic System Disorders

• Angioedema
• Impaired healing
• Fever 
• Inflammation
• Coagulation and bleeding disorders
• Positive autoantibody test
• Viral herpes
• Sepsis
• Candidiasis
• Influenza
• Fungal infections
• Opportunistic infections
• Bacterial infections 
• Neoplasms
• Leukopenia
• Anaemia
• Leucocytosis
• Thrombocytopenia
• Idiopathic thrombocytopenic purpura
• Pancytopenia
• Hypersensitivity
• Allergies
• Sarcoidosis
• Vasculitis
• Anaphylaxis 

Sensory Disorders

• Visual impairment
• Conjunctivitis
• Blepharitis
• Eye swelling
• Diplopia
• Vertigo
• Deafness
• Tinnitus
• Ear infections 
• Eye infections 

• Methotrexate 
• Anakinra
• Abatacept
• Live vaccines

• Tuberculosis screening
• Full blood count 
• Differential white cell count 
• Dermatological examination
• Hepatitis B screening

Specific cases may require 

• Cardiovascular examination
• Neurological examination

Method of administration

• Patients may self-inject adalimumab if their medical practitioner determines that it is appropriate and with medical follow-up, as necessary, after proper training in injection technique
• Sites for self-injection include the thigh or abdomen. Injection sites should be rotated
• New injections should never be given into areas where the skin is tender, bruised, red or hard
• Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration, whenever solution and container permit
• Adalimumab should not be mixed in the same syringe with other medicine
• Any unused product or waste material should be disposed of in accordance with local requirements
• Refer to full instructions for use provided in the product specific patient information leaflet

Adalimumab is a recombinant monoclonal antibody that binds to human tumour necrosis factor alpha (TNF-alpha), thereby interfering with binding to TNFα receptor sites and subsequent cytokine-driven inflammatory processes. Adalimumab also lyses surface TNF expressing cells in vitro in the presence of complement.

Injection (per 0.8ml) 40mg

• Amgevita PFP (Amgen)
• Amgevita PFS (Amgen)
• Humira pen (AbbVie) originator
• Humira pre-filled syringe (AbbVie) originator