Tofacitinib oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of tofacitinib.
Drugs List
Therapeutic Indications
Uses
Active polyarticular juvenile idiopathic arthritis unresponsive to DMARDs
Ankylosing spondylitis
Moderate to severe active rheumatoid arthritis-other regimens unsuitable
Moderate/severe ulcerative colitis: when other treatment is inappropriate
Psoriatic arthritis when inadequate response or intolerant to prior DMARDs
Dosage
Adults
Rheumatoid arthritis (in combination with methotrexate or as monotherapy if intolerant to methotrexate or if methotrexate is inappropriate)
5mg twice daily or 11mg prolonged release tablet once daily.
Psoriatic arthritis (in combination with methotrexate or as monotherapy if intolerant to methotrexate or if methotrexate is inappropriate)
5mg twice daily or 11mg prolonged release tablet once daily.
Ulcerative colitis
Initial
10mg twice daily for 8 weeks. If inadequate response to initial treatment occurs, 10mg twice daily may be extended for a further 8 weeks.
Maintenance
5mg twice daily if adequate response to initial treatment occurs. This can be increased to 10mg in patients not at risk for venous thromboembolism (VTE), however this is not recommended in those at risk of VTE unless no suitable alternative treatment.
10mg twice daily may be considered in patients who have failed prior tumour necrosis factor antagonist treatment.
Ankylosing spondylitis
5mg twice daily or 11mg prolonged release tablet once daily.
Children
Children 2 years of age and older (in combination with methotrexate or as monotherapy if intolerant to methotrexate or if methotrexate is inappropriate)
Active, polyarticular juvenile idiopathic arthritis
Juvenile psoriatic arthritis
Body weight 10kg to less than 20kg:
3.2mg (3.2ml of oral solution) twice daily.
Body weight 20kg to less than 40kg:
4mg (4ml of oral solution) twice daily.
Body weight 40kg and over:
5mg (5ml of oral solution or one 5mg tablet) twice daily.
Patients with Renal Impairment
Creatinine clearance 50 to 80ml/minute: No dose adjustment.
Creatinine clearance 30 to 49ml/minute: No dose adjustment.
Creatinine clearance less than 30ml/minute: If the indicated dose is 5mg twice daily in normal renal function, reduce dose to 5mg once daily. If the indicated dose is 10mg twice daily in normal renal function, reduce to 5mg twice daily.
Patients with severe renal impairment should remain on a reduced dose even after haemodialysis.
Patients with Hepatic Impairment
Mild hepatic impairment (Child Pugh A): No dose adjustment.
Moderate hepatic impairment (Child Pugh B): If the indicated dose is 5mg twice daily in normal hepatic function, reduce dose to 5mg once daily. If the indicated dose is 10mg twice daily in normal hepatic function, reduce to 5mg twice daily.
Severe hepatic impairment (Child Pugh C): Contraindicated.
Additional Dosage Information
Adults
Absolute Lymphocyte Count (ALC)
ALC equal to or greater than 750 cells per cubic millimetre: No dose adjustments.
ALC 500 to 750 cells per cubic millimetre: Patients receiving 5mg twice daily or 11mg once daily, interrupt treatment until ALC is greater than 750 cells per cubic millimetre, then resume treatment. Patients receiving 10mg twice daily, reduce dose to 5mg twice daily.
ALC less than 500 cells per cubic millimetre: Discontinue treatment if lab value confirmed by repeat testing within 7 days.
Absolute Neutrophil Count (ANC)
ANC greater than 1000 cells per cubic millimetre: No dose adjustments.
ANC 500 to 1000 cells per cubic millimetre: Patients receiving 5mg twice daily or 11mg once daily, interrupt treatment until ANC is greater than 1000 cells per cubic millimetre, then resume treatment. In patients receiving 10mg twice daily, reduce dose to 5mg twice daily.
ANC less than 500 cells per cubic millimetre: Discontinue treatment if lab value confirmed by repeat testing within 7 days.
Haemoglobin Value
Equal to or less than 2g/dL decrease and equal to or greater than 9g/dL: No dose adjustments.
Greater than 2g/dL decrease or less than 8g/dL (confirmed by repeat testing): Interrupt treatment until haemoglobin values have normalised, then resume treatment.
Children 2 years of age and older
Absolute Lymphocyte Count (ALC)
If less than 750 cells per cubic millimetre: Do not initiate treatment.
ALC greater than or equal to 750 cells per cubic millimetre:
No dose adjustment.
ALC 500 to 750 cells per cubic millimetre for 2 sequential tests:
Dose should be reduced or interrupted until ALC is greater than 750 cells per cubic millimetre.
In patient receiving 5mg twice daily, interrupt treatment until ALC is greater than 750 cells per cubic millimetre, then resume treatment if clinically appropriate.
ALC less than 500 cells per cubic millimetre:
Discontinue treatment if lab value confirmed by repeat testing within 7 days.
Absolute Neutrophil Count (ANC)
If less than 1200 cells per cubic millimetre: Do not initiate treatment.
ANC greater than 1000 per cubic millimetre: No dose adjustment.
ANC 500 to 1000 cells per cubic millimetre for 2 sequential tests:
Dose should be reduced or interrupted until ANC is greater than 1000 cells per cubic millimetre.
Patients receiving 5mg twice daily, interrupt treatment until ALC is greater than 1000 cells per cubic millimetre, then resume treatment if clinically appropriate.
ANC less than 500 cells per cubic millimetre:
Discontinue treatment if lab value confirmed by repeat testing within 7 days.
Haemoglobin Value
If less than 10g/dL: Do not initiate treatment.
Equal to or less than 2g/dL decrease and equal to or greater than 9g/dL: No dose adjustment.
Greater than 2g/dL decrease or less than 8g/dL (confirmed by repeat testing): Interrupt treatment until haemoglobin values have normalised, then resume treatment.
Switching to different dosage form
Patients treated with 5mg tablets twice daily may be switched to 11mg prolonged release tablets once daily on the day following last 5mg dose.
Patients treated with 11mg prolonged release tablets once daily may be switched to 5mg tablets twice daily on the day following last 11 mg dose.
Patients with the body weight 40kg and over who are treated with tofacitinib 5ml oral solution twice daily may be switched to tofacitinib 5mg tablets twice daily. Patients with the body weight less than 40kg cannot be switched from tofacitinib oral solution.
Contraindications
Absolute lymphocyte count below 0.75 x 10 to the power of 9/L
Children under 2 years
Haemoglobin concentration below 10g/dL at baseline in children
Haemoglobin concentration below 9g/dl
Neutrophil count below 1.0 x 10 to the power of 9 / L at baseline
Neutrophil count below 1.2 x 10 to the pwer of 9/L at baseline in children
Predisposition to pulmonary embolism - if used for ulcerative colitis
Severe infection
Breastfeeding
Pregnancy
Severe hepatic impairment
Tuberculosis
Precautions and Warnings
Asian ancestry
Females of childbearing potential
History of herpes zoster infection
History of recurrent infection
Immobilisation
Infection
Lymphocyte count between 0.5 and 0.75 x 10 to the power 9/L
Major surgery
Obese patients with a BMI greater than 30kg/m2
Patients over 65 years
Percutaneous coronary intervention
Predisposition to gastrointestinal perforation
Predisposition to infection
Predisposition to pulmonary embolism
Predisposition to venous thromboembolism
Risk factors for cardiovascular disorder
Tobacco smoking
Angina
Cardiac failure
Coronary arteriosclerosis
Diabetes mellitus
Diverticulitis
Elevated serum transaminases
Galactosaemia
Glucose-galactose malabsorption syndrome
Hepatitis
Hereditary fructose intolerance
History of cancer
History of respiratory disease
History of tuberculosis
History of venous thromboembolism
Hypertension
Lactose intolerance
Malignant neoplasm
Moderate hepatic impairment
Myocardial infarction
Renal impairment - creatinine clearance below or equal to 30ml/minute
Administration of live vaccines is not recommended
Before initiating screen all patients for viral hepatitis
Administration of live vaccines should occur 4 weeks before initiation
Before starting therapy ensure immunisations are up to date
Consider prophylactic anti-tuberculosis therapy if appropriate
Monitor patients for non-melanoma skin cancer prior to and during treatment
Not all available brands/formulations are licensed for use in children
Not all available products are licensed for all uses
Not all available strengths are licensed for all indications
Prior to starting therapy screen for latent tuberculosis
Treat and control infections prior to commencing therapy
Treatment to be initiated and supervised by a specialist
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain lactose
Some formulations contain propylene glycol
Staff: Not to be handled by pregnant staff
Advise patient to report signs of gastrointestinal perforation immediately
Monitor lymphocytes prior to and every 3 months during treatment
Investigate signs and symptoms suggesting an infection
Monitor blood counts before initiation,at 1-2 months,then every 3 months
Monitor hepatic function regularly
Monitor serum lipids 1-2 months after initiation
Monitor skin changes
Advise patient of thromboembolic symptoms and to report them if they occur
Advise patient to report symptoms of infection immediately
Advise patient to seek med advice if signs/symptoms of tuberculosis develop
Immunosuppressive drugs may increase risk of malignancy
Increased risk of hypoglycaemia
Increased risk of venous thromboembolism
Risk of developing opportunistic infections
Discontinue if allergic reaction occurs
Discontinue if lymphocyte count less than 0.5 x 10 to the power of 9/L
Discontinue if neutrophil count less than 0.5 x 10 to the power of 9/L
Discontinue if venous thromboembolism develops
Interrupt therapy if neutrophil count <1.0x10 to the power 9/L
Interrupt treatment if severe infection develops
Suspend if drug induced liver injury is suspected
Suspend if haemoglobin decreases by >2g/dL or falls below 8g/dL
Advise patient not to take St John's wort concurrently
Grapefruit juice should not be taken simultaneously
Female: Contraception required during and for 1 month after treatment
Advise patients to report any new or worsening cardiovascular symptoms
Patients with ulcerative colitis at high risk of pulmonary embolism should not be started on tofacitinib as higher doses (10mg twice a day) have been associated with an increased risk.
All patients should be monitored for signs of venous thromboembolism including pulmonary embolism and deep vein thrombosis. Tofacitinib should be used with caution in patients with known risk factors for venous thromboembolism.
Retinal venous thrombosis have been reported in patients treated with tofacitinib, advise patient to report symptoms of retinal venous thrombosis.
Patients with a history of latent or active Tuberculosis (TB) but tested negative for TB should also be considered for antituberculosis therapy prior to initiation of treatment. Monitor patients closely, including those who tested negative for latent TB, for the development of signs and symptoms of TB.
It is recommended patients with a history of chronic lung disease should be treated with caution as they may be more susceptible to infections.
Routine monitoring of liver tests should be performed throughout treatment and caution is recommended in patients with elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST), particularly when using combination therapy with potentially hepatotoxic medicinal products such as methotrexate.
Patients with a known history of chickenpox or those who are seropositive for varicella zoster virus (VZV) should only have the zoster vaccination if the vaccination is considered necessary. Vaccinations with live vaccines should occur at least two weeks, but preferably four weeks before the initiation of treatment.
In patients with cardiovascular and malignancy risk factors the use of tofacitinib may be considered only if no suitable alternative treatment is available.
Pregnancy and Lactation
Pregnancy
Tofacitinib is contraindicated during pregnancy.
Use of tofacitinib is contraindicated during pregnancy by the manufacturer. Animal studies have shown teratogenic effects. Human data is limited and as such a potential risk cannot be ruled out.
Lactation
Tofacitinib is contraindicated during breastfeeding.
Use of tofacitinib during breastfeeding is contraindicated by the manufacturer. Animal data reports significant levels of tofacitinib in the breast milk, however presence in human breast milk is unknown. Effects on exposed infants are unknown.
Side Effects
Abdominal pain
Abnormal liver function tests
Anaemia
Angioedema
Appendicitis
Arthralgia
Atypical mycobacterial infection
Bacteraemia
Bacterial pneumonia
BK virus infection
Bronchitis
Cellulitis
Cough
Creatine phosphokinase increased
Cryptococcosis infection
Cytomegalovirus infection
Dehydration
Diarrhoea
Diverticulitis
Dyslipidaemia
Dyspepsia
Dyspnoea
Elevated serum LDL cholesterol
Encephalitis
Erythema
Fatigue
Gamma glutamyl transferase (GGT) increased
Gastritis
Gastro-enteritis
Headache
Hepatic steatosis
Herpes simplex
Herpes zoster
Hyperlipidaemia
Hypersensitivity reactions
Hypertension
Increase in creatinine
Increase in serum transaminases
Increased susceptibility and severity of infections
Increases in hepatic enzymes
Infections
Influenza
Insomnia
Joint swelling
Ligament injury
Listeriosis
Lymphoma
Lymphopenia
Lymphoproliferative disorders
Malignancies
Meningitis
Muscle strain
Musculoskeletal pain
Mycobacterial infection
Naso-sinus congestion
Nasopharyngitis
Nausea
Necrotising fasciitis
Neutropenia
Non melanoma skin cancer
Oesophageal candidiasis
Opportunistic infections
Paraesthesia
Peripheral oedema
Pharyngitis
Pneumocystis jiroveci pneumonia
Pneumonia
Pruritus
Pulmonary embolism
Pyelonephritis
Pyrexia
Rash
Retinal vein thrombosis
Sepsis
Septic arthritis
Serum creatinine increased
Sinusitis
Staphylococcal infection
Tendon inflammation
Tuberculosis
Upper respiratory tract infection
Urinary tract infections
Urosepsis
Urticaria
Venous thrombosis
Viral infection
Vomiting
Weight gain
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: February 2022
Reference Sources
Summary of Product Characteristics: Xeljanz 5mg film-coated tablets. Pfizer Limited. Revised October 2022.
Summary of Product Characteristics: Xeljanz 10mg film-coated tablets. Pfizer Limited. Revised October 2022.
Summary of Product Characteristics: Xeljanz 11mg prolonged release tablets. Pfizer Limited. Revised October 2022.
Summary of Product Characteristics: Xeljanz 1 mg/mL oral solution. Pfizer Limited. Revised September 2022.
Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.