Tofacitinib (Oral)

Tofacitinib is a Janus kinase (JAK) inhibitor used to treat rheumatoid arthritis that works by suppressing the immune system.

Overview

Rheumatoid arthritis is an autoimmune disease which affects joints and internal organs. It is caused by a malfunctioning immune system creating cells that attack the joint lining tissue, causing inflammation and pain in the joints.

JAK enzymes play a critical role in the transfer of information across cells. JAK inhibitors, like Tofacitinib, prevent this communication from taking place, thereby reducing inflammation and relieving pain for the patient.

Tofacitinib is usually prescribed when other anti-rheumatic drugs have failed to provide sufficient relief and is often used in conjunction with other drugs such as methotrexate. However, tofacitinib can also be used as monotherapy in patients that have an allergic reaction to methotrexate.

Conditions treated

  • Rheumatoid Arthritis (RA)
  • Psoriatic Arthritis (PsA)

Type of medicine

  • Janus kinase (JAK) Inhibitor

Side effects

Patients taking tofacitinib may suffer from a number of minor side effects, including headaches and common cold symptoms, such as a sore throat and runny nose. These symptoms are quite common, so there is no need to consult your doctor unless they complicate an existing condition or persist for more than a couple of weeks.

In a small number of cases, patients may suffer more serious allergic reactions. If patients begin to show any of the following symptoms, they should contact a doctor for more advice:

  • Urticaria (hives)
  • Difficulty breathing
  • Swelling of the face, lips, tongue or throat
  • Vomiting
  • Changes in bowel habits

Tofacitinib also increases the risk of infection, so if patients begin to suffer from any of the following symptoms, they should stop using the medication immediately and consult their doctor:

  • Fever, chills, night sweats
  • Cough with mucus and blood
  • Chronic tiredness
  • Pain or burning when you urinate
  • Body aches, flu symptoms, (sores in your mouth)
  • Stabbing chest pain, wheezing, shortness of breath
  • Skin redness or swelling

In a small number of patients, tofacitinib may cause severe liver damage. Call your doctor immediately if you begin to suffer from:

  • Low fever
  • Itching
  • Upper stomach pain
  • Loss of appetite
  • Dark urine, clay colored stools
  • Jaundice (yellowing of the skin or eyes)

This is not a complete list of potential side effects, patients may react with the drug in different ways. Patients who suffer any other sort of medical reaction should call their doctor for advice. Reactions can also be reported to the Food & Drug Administration (FDA) at 1-800-FDA-1088.

Dosage

Tofacitinib is a prescription only medication which must be prescribed by a qualified health professional. Recommended dosage amounts will be supplied by a physician. Recommend general dosage instructions are printed on the packaging, but these may be amended by a doctor depending on any underlying medical conditions or adverse reactions to the medication by the patient. Always consult your doctor's advice before taking any prescribed medicine.

A standard tablet of tofacitinib is 5 mg, white in color and round in shape. An extended release (XR) tablet of 11 mg, is also available, this is pink in color and oval in shape. The recommended daily dosage of tofacitinib is two 5 mg tablets taken twice daily, or a single extended release XR tablet (11 mg), taken once each day.

Tofacitinib should be taken orally with or without food and can be administered as monotherapy or in combination with other nonbiologic disease-modifying antirheumatic drugs such as methotrexate. The tablets should be swallowed whole, with water if necessary, the tablet should remain intact and should not be chewed, crushed or split before ingestion.

If taking the extended release (XR) version of the tablet, it is not unusual for tablet remnants to pass into the stool.

A physician will typically start by prescribing two daily doses of 5 mg tablets but may move patients on to a single 11 mg XR tablet once any potentially adverse reactions have been discounted. If the patient suffers any adverse reaction, either infection or allergic, the dosage may be amended or in severe cases cancelled entirely.

Missed dose - if a dose is missed, it can be taken up to an hour after the scheduled time for the 5 mg tablet and up to four hours for the 11 mg, extended release tablet. However, if the time elapsed takes you close to your next scheduled dose, it is better to skip a dosage and return to your usual schedule. DO NOT double dose.

If the patient is suspected to have taken an overdose or is showing any of the following symptoms, contact the Poison Control Center immediately on 1-800-22201-222:

  • Extremely fast heartbeat
  • Shallow breathing
  • Unconsciousness
  • Seizures
  • Loss of coordination
  • Flush complexion

Major drug interactions

Using Tofacitinib with other drugs can cause a number of adverse reactions in the patient, including inflammation of the liver, increased risk of infection and increased risk of cancer in some patients. Therefore, it is important for the physician to determine what other medications - both prescribed and over the counter - the patient is taking before prescribing Tofacitinib.

The following is a list of medicines that are known to cause severe adverse reactions when prescribed with Tofacitinib:

  • Carbamazepine
  • Enzalutamide
  • Fosphenytoin
  • Mitotane
  • Phenytoin
  • Primidone
  • Rifabutin
  • Rifampin
  • Rifapentine
  • St John's Wort

The above list is not all-inclusive - Tofacitinib is known to have 268 major drug interactions with 797 brands - so it is important that physicians check for all possible interactions before prescribing Tofacitinib.

Some medicines are also known to interact with Tofacitinib but can be combined by lowering the dosage of either to reduce the risk of an adverse reaction. In this case, the physician should closely monitor the patient and adjust the dosage if necessary.

The following is a list of medicines which may negatively interact with Tofacitinib:

Leflunomide - Using Tofacitinib with leflunomide increases the risk of serious infection. Because leflunomide stays in the bloodstream for a prolonged period after the last dose, care must be taken to ensure no traces of leflunomide are left in the bloodstream before prescribing Tofacitinib.

Methotrexate - Using Tofacitinib with methotrexate can cause serious and potentially fatal infections. Combining medications that affect bone marrow and the immune system also increases the risk of various forms of cancer developing over time.

PredniSONE - Using Tofacitinib with PredniSONE greatly increases the risk of a potentially fatal infection in the patient. PredniSONE also affects liver function, so using the two drugs together may cause long-term liver damage.

Moderate drug interactions:

Tofacitinib is known to have 124 moderate drug interactions with 486 brands, with the two most common interactions listed below:

Nexium (esomeprazole) - combining Tofacitinib with nexium can increase the amount of it in the bloodstream. While this is not a concern on its own, it is something physicians need to be aware of if the patient is using Tofacitinib in combination with other drugs. In such cases the patient may experience low blood cell counts, anemia and elevated blood lipid levels.

Omeprazole - combining Tofacitinib with omeprazole increases the amount of Tofacitinib in the bloodstream. This increases the risk of infection if the drug is prescribed in conjunction with other drugs. Potential side effects also include: low blood cell counts, anemia and elevated blood lipid levels.

Warnings

Infections - Taking Tofacitinib reduces the number of white blood cells in the bloodstream, significantly increasing the risk of infection from bacterial, mycobacterial, invasive fungal, viral and other opportunistic pathogens. The following infections have been reported in patients taking Tofacitinib to ease rheumatoid arthritis and psoriatic arthritis:

  • Pneumonia
  • Cellulitis
  • Herpes zoster
  • Urinary tract infections
  • Diverticulitis
  • Appendicitis

Prescribing tofacitinib should be avoided if the patient has an existing chronic or current infection, including localized infection.

The risk of infection may also be higher if the patient is suffering from lymphopenia, so individual lymphocyte counts should be assessed before recommending dosage. Continual monitoring for lymphopenia should also be carried out while the drug is being taken.

Patients can also play a part in reducing the risk of infection by taking the following precautions:

Avoid people with known viruses or infections, call your doctor if you start to get a fever or chills, begin coughing or get a hoarse voice or suffer any lower back or side pain.

If you notice any unusual bleeding or bruising on your body, your stool becomes black and tarry, blood appears in urine or small red spots appear on your skin, call your doctor immediately.

Don't share a toothbrush and make sure your brush head is clean. Also notify your doctor if you intend to get any dental work done.

Try not to touch your nose, mouth or eyes unless you have washed your hands recently.

Be careful when using sharp objects, a cut greatly increases the risk of infection.

Avoid playing contact sports where your body may be subject to bruising or other injuries may occur.

Tuberculosis - if a patient has a past history of latent or active tuberculosis or if the patient has been exposed to tuberculosis, or has travelled in an area where tuberculosis is endemic. Antituberculosis therapy should be carried out before prescribing tofacitinib. Consultation with a physician who has experience treating tuberculosis is also recommended.

Patients should also be closely monitored for symptoms of tuberculosis throughout the course of therapy, including those that tested negative for the disease prior to the start of therapy.

Malignancy and Lymphoproliferative disorders - During clinical trials 11 patients developed solid cancers, with one developing a lymphoma in the first 12 months of exposure. If a patient is suffering from a known malignancy, other than a non-melanoma skin cancer which has been successfully treated. Care should be taken to asses the risks to the patient before starting therapy with tofacitinib.

Non-melanoma skin cancer - some patients have reported developing non-melanoma skin cancer during a course of tofacitinib. It is recommended that patients who are at risk of developing skin cancer receive periodic skin examinations during treatment.

Gastrointestinal perforations - A small number of cases of gastrointestinal perforations have been reported in patients using tofacitinib to treat rheumatoid arthritis. Although it is not know what role tofacitinib may have played in this small sample, physicians should proceed with caution when prescribing tofacitinib to patients at risk of gastrointestinal perforations. Patients who complain about the onset of intestinal pain should also be closely examined.

Pregnancy - Patients who are pregnant are advised not to take tofacitinib. Patients who become pregnant while taking tofacitinib should notify their doctor immediately. It is not fully understood how tofacitinib affects the fetus in humans, but animal studies have shown that tofacitinib does have the potential to affect a developing fetus and may increase the risk of miscarriage.

If a patient becomes pregnant while taking tofacitinib, they should be encouraged to enroll in the tofacitinib pregnancy registry. Patients can call 1-877-311-8972 toll free for more information.

There is also insufficient data on the risk of breast feeding while taking tofacitinib. It is not known if the drug is passed on to breast milk, so nursing is not advised when taking tofacitinib. Physicians should advise patients to stop breast feeding or suspend the use of tofacitinib in such cases.

Vaccinations - Live vaccines should not be administered while the patient is under the treatment of tofacitinib. Physicians should consult current immunization and vaccination guidelines regarding immunosuppressive agents for recommended intervals between vaccination and the start of any tofacitinib therapy. Care should also be taken to ensure the patient is not living with someone who has recently had a live vaccine, including measles, mumps, and rubella.

General - Since tofacitinib is administered orally caution should be taken when prescribing to patients with pre-existing gastrointestinal narrowing (pathologic or iatrogenic). There have been instances of obstruction in the gastrointestinal tract by ingestion of drugs using a non-deformable extended release formulation such as that used by tofacitinib.

Storage

Tofacitinib should be stored at room temperature, 20°C to 25°C (68°F to 77°F). Temperatures below 15°C should be avoided at all costs. The storage location should ideally be in a secure cupboard or medicine cabinet where the pills are protected from exposure to direct sunlight and moisture.

The individual pills should remain sealed until ingestion. If any pills are left after the course of treatment, the patient should discuss the most appropriate method of destruction with their pharmacist or healthcare professional. It is important that out of date medication is NOT left in the medicine cabinet where it is at risk of being ingested by mistake.

Summary

Tofacitinib is a very effective, orally administered drug, that has proved successful at relieving the symptoms of moderate and severe rheumatoid arthritis (RA) and Psoriatic Arthritis (PsA). It is usually prescribed to patients that have not responded to treatment using traditional anti-rheumatic such as methotrexate. While usually combined with other drugs, such as methotrexate, to provide pain relief and reduce inflammation. Tofacitinib can also be taken as monotherapy.

Tofacitinib is a new class of nonbiological disease-modifying antirheumatic drug (DMARD) which uses Janus kinase (JAK) inhibitors to bind type I cytokine receptors to paired JAK1/JAK3 receptors. This has the result of decreasing synovial inflammation thereby preventing structural joint damage in sufferers of RA.

However, because this is a new class of drug it is important that it is administered correctly to avoid any complications or side effects. Physicians will have to weigh up the patient's medical history before prescribing tofacitinib, with careful monitoring required throughout the course of treatment in order to prevent potentially deadly infections or side effects from occurring.

While the long list of potential side effects may be daunting for patients, the risk of suffering such effects or developing an infection is rare, so long as the correct dosage levels are set and the patient's medical history has been taken into account. It is therefore imperative that patients follow dosage instructions carefully and report any changes in their health to their doctor immediately.

So long as dosage levels are carefully monitored, tofacitinib is safe for the vast majority of patients and provides welcome pain relief for sufferers of rheumatoid and psoriatic arthritis. Especially those who have not responded to conventional anti-rheumatic drugs such as methotrexate.

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Last Reviewed:
December 23, 2017
Last Updated:
April 05, 2018
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