Tofacitinib
Tofacitinib is a Disease Modifying Anti-Rheumatic Drug (DMARD) that suppresses the immune system to treat moderate to severe rheumatoid arthritis.
Tofacitinib is currently used to treat rheumatoid arthritis with and without the medication methotrexate. Tofacitinib is also used to treat psoriatic arthritis and ulcerative colitis.
Tofacitinib belongs to a class of medications known as Janus Kinase (JAK) inhibitors. It is the first medication of this class to be approved for clinical trials and was first approved for use as a prescription medicine in 2012.
Taking Tofacitinib
Tofacitinib is one of the few therapies for arthritis that is available as an oral tablet. The standard dose is either one 11 mg tablet taken once a day or a 5 mg tablet, taken twice every day.
Tofacitinib does not work right away. It can take about 2 to 8 weeks before patients start feeling better, and it can take 3 to 6 months to feel the maximum effect of this medication. If the dose is changed, it can take 2-8 weeks to feel the effects.
Important Tests and Risks
Tofacitinib can make it a bit harder for people to fight off infections.
Patients taking this medicine should call their doctor they have a fever, think they have an infection, or have been prescribed antibiotics to treat an infection.
Patients should coordinate with their doctor to stop treatment before any surgery. It can be re-started once things have healed and there’s no sign of infection. Most patients stop the medication a week before surgery. It can be restarted 10-14 days after the surgery as long as there is no sign of infection.
Patients should discuss all vaccinations with their doctor because some (live vaccines) are not advisable to get while taking Tofacitinib.
Regular blood tests are necessary when taking Tofacitinib.
Doctors will advise patients how frequently they want to run tests to make sure that the medicine isn’t affecting the kidneys, liver, blood counts, or cholesterol levels.
Testing is usually required once every 1 to 3 months.
Tofacitinib may increase your risk of developing shingles. Please talk to your doctor about the shingles vaccine.
Tofacitinib may increase your risk of blood clots in the legs (deep venous thrombosis or DVT) or in the lungs (pulmonary embolism or PE). Any new leg swelling or shortness of breath should be taken seriously and reviewed by a doctor.
All patients should have a TB (tuberculosis) skin test and a chest x-ray before starting treatment.
Science
One way that cells in the body communicate with each other is with special signalling proteins called cytokines. Cytokines are made and released by cells and drift around and until they encounter another cell and bind to a receptor on its surface.
When a cytokine binds to the surface of a cell, it passes its message to the cell’s nucleus (its “brain” or command centre) using a process called signal transduction. The nucleus responds to a signal by producing the appropriate protein or peptide that’s coded for in its DNA (this is called activation of transcription).
One of the important signal transduction pathways in the body uses an enzyme called Janus Kinase (JAK) and another molecule called Signal Transducer and Activation of Transcription (STAT) to send a signal to a cell’s nucleus.
The JAK-STAT pathway is important for sending signals related to bone marrow and immune system activation.
Tofacitinib is a small molecule that enters a cell and binds to the ATP binding site on the enzyme Janus Kinase (JAK). In doing this, it prevents JAK from activating STAT. This blocks the process of sending a signal to the cell’s nucleus.
In rheumatoid arthritis, psoriatic arthritis, ulcerative colitis and many other autoimmune disorders, the immune system is not functioning correctly. It attacks the body’s own tissues the same way it attacks disease-causing germs.
By disrupting a key signal sending process related to immune system activation, Tofacitinib interferes with the ability of immune system cells to talk with each other. When these cells can’t communicate as effectively, they have a hard time coordinating their attack on the body’s joints. The result is improvement in the symptoms of a patient’s arthritis.
Safety
The most common side effects of Tofacitinib include include upper respiratory tract infections (common cold, sinus infections) and related symptoms.
Tofacitinib might also cause headaches or diarrhea. Patients should tell their doctor if these effects are troublesome.
LESS SERIOUS side-effects include:
- Nausea, indigestion, and diarrhea
- Headaches
- Upper respiratory tract infection (nasopharyngitis)
- Cholesterol Levels – Tofacitinib may increase cholesterol levels. This will be monitored through blood tests
MORE SERIOUS side-effects include:
- Infection – There have been serious and rare infections associated with the use of Tofacitinib. Any infections or fevers should be taken very seriously and reviewed by a doctor
- Blood Counts – Tofacitinib can cause changes in the numbers of white blood cells (which are needed to fight infection) and red blood cells (which carry oxygen)
- Liver – Tofacitinib may irritate the liver. This does not usually cause symptoms but may be found on blood tests. It is uncommon and usually reversible when regularly monitored with your monthly blood tests
- Bowels – Tofacitinib may increase the risk of bowel perforation. This is very rare.
- Kidneys – Tofacitinib may cause a slight decrease in kidney function in some people (increased creatinine). This is monitored through regular blood tests.
- Blood Clots – Tofacitinib may increase the risk of blood clots in the legs (deep venous thrombosis or DVT) or in the lungs (pulmonary embolism or PE). Any new leg swelling or shortness of breath should be taken seriously and reviewed by a doctor.
- Shingles – Tofacitinib may increase your risk of developing shingles. Please talk to your doctor about the shingles vaccine.
- Cancer – Tofacitinib has very rarely been associated with developing cancer. Tell your doctor if you have had cancer in the past.
How to minimize the side-effects of Tofacitinib:
- Patients should take the medicine twice a day, as prescribed by their doctor
- Patients should get regular blood tests as requested by their doctor to monitor for side effects, and remember to attend their appointments
Patients should contact their doctor before intentionally missing a dose of Tofacitinib. However, in the following situations, it would be advisable to stop taking the medicine and call a doctor:
- Fever
- An infection or signs of an infection
- Pregnancy or Breast Feeding
Patients who are about to have surgery should discuss stopping Tofacitinib with their doctor.
Some medications may not be safe to take with Tofacitinib including ketoconazole, fluconazole, and rifampin. Patients should always discuss all of the medications that they are taking with their doctor.
Some medications may increase the risk of infection and should not be taken with Tofacitinib, including biologics and other potent immunosuppressive medications such as cyclosporine or azathioprine.
Patients taking Tofacitinib should call their doctor if they feel sick and want to stop, or if they are concerned about any side effects.
Other reasons to call a doctor while taking Tofacitinib include:
- Developing a fever or suspected infection
- Planning for surgery
- Becoming pregnant or planning on pregnancy
- Planning on getting any vaccinations
- New leg swelling or shortness of breath
- Severe abdominal pain
Anyone who becomes pregnant while taking Tofacitinib should notify their doctor.
Pregnancy and medicationsResources
DIN
- 02522896 (5 mg tablet)