Xeljanz – Emerging Litigation

XELJANZ – Case Review – Focus Blocks

XELJANZ is the citrate salt of Tofacitinib, a JAK inhibitor. XELJANZ is supplied for oral administration as 5 mg Tofacitinib (equivalent to 8 mg Tofacitinib citrate) white round, immediate-release film-coated tablet.

XELJANZ (Tofacitinib) is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to methotrexate. It may be used as monotherapy or in combination with methotrexate or other non-biologic disease-modifying antirheumatic drugs (DMARDs).

Nov. 6, 2012 — FDA has approved Pfizer’s Xeljanz (Tofacitinib), a first-of-its-kind treatment for rheumatoid arthritis.

Mechanism Of Action:

Tofacitinib is a Janus kinase (JAK) inhibitor. JAKs are intracellular enzymes which transmit signals arising from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoiesis and immune cell function.

Manufacturer: Pfizer Laboratories Div Pfizer Inc and U.S. Pharmaceuticals

Dosage forms and strengths:

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Contraindications:

  1. Liver problems
  2. Kidney problems
  3. Any stomach area (abdominal) pain or been diagnosed with diverticulitis or ulcers in stomach or intestines
  4. Have had a reaction to Tofacitinib or any of the ingredients in Xeljanz
  5. Have recently received or are scheduled to receive a vaccine.
  6. Have any other medical conditions (Plan to become pregnant or are pregnant)
  7. Fever, sweating, or chills
  8. Warm, red, or painful skin or sores on your body
  9. Muscle aches
  10. Shortness of breath
  11. Burning when you urinate o blood in phlegm or urinating more often than normal
  12. Weight loss
  13. Have diabetes, HIV, or a weak immune system
  14. Have TB, or have been in close contact with someone with TB
  15. Live or have lived, or have traveled to certain parts of the country (such as the Ohio and Mississippi River valleys and the Southwest) where there is an increased chance for getting certain kinds of fungal infections (histoplasmosis, coccidioidomycosis, or blastomycosis).
  16. Have or have had hepatitis B or C

FDA Drug Safety Communication

March 2014 – Non-melanoma skin cancers (NMSCs) have been reported in patients treated with Xeljanz. Periodic skin examination is recommended for patients who are at increased risk for skin cancer.

June 2015Viral Reactivation: The risk of herpes zoster is increased in patients treated with XELJANZ and appears to be higher in patients treated with XELJANZ in Japan

FDA Public Warning

Limitations of Use: Use of Xeljanz in combination with biologic DMARDs or with potent immunosuppressants such as Azathioprine and Cyclosporine is not recommended.

Serious Side Effects:

  1. Serious infections: Xeljanz is a medicine that affects immune system. Patients treated with Xeljanz are at increased risk for developing serious infections leading to hospitalization or death, including active tuberculosis (TB), invasive fungal infections, bacterial, viral and other infections due to opportunistic pathogens.

Xeljanz intake causes Hepatitis B or C activation infection in people who carry the virus in their blood.

  1. Cancer and immune system problems: Xeljanz may increase risk of certain cancers by changing the way your immune system works.
  • Lymphoma and other cancers including skin cancers can happen in patients taking Xeljanz.
  • Some people who have taken Xeljanz with certain other medicines to prevent kidney transplant rejection have had a problem with certain white blood cells growing out of control (Epstein Barr Virus-associated post transplant lymphoproliferative disorder).
  1. Tears (perforation) in the stomach or intestines: Some people taking Xeljanz get tears in their stomach or intestine. This happens most often in people who also take nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or methotrexate.
  1. Changes in certain laboratory test results: Healthcare provider should do blood tests before starting Xeljanz and while taking Xeljanz to check for the following side effects:
  • Changes in lymphocyte counts
  • Low neutrophil counts
  • Low red blood cell count

Health care provider should routinely check certain liver tests. Patient should not receive Xeljanz if lymphocyte count, neutrophil count, or red blood cell count is too low or liver tests are too high.

They may also have changes in other laboratory tests, such as blood cholesterol levels. Healthcare provider should do blood tests to check cholesterol levels 4 to 8 weeks after receiving Xeljanz, and as needed after that.

Common side effects

  • Upper respiratory tract infections (common cold, sinus infections)
  • Headache
  • Diarrhea
  • Nasal congestion
  • Sore throat, and runny nose (nasopharyngitis)

CASE REVIEW FOCUS AREAS:

1. Whether the patient was prescribed Xeljanz?

2. Reason for Xeljanz Prescription?

Dosage and Intake details

  • Critical Review of
  • Physician Drug Prescription Details
  • Pharmacy Dispensing Details
  • Pharmacy Refill Details

Details of Pharmacy Dispensing Details are taken as Confirmatory

  • Did the patient have any pre-existing conditions, allergies or contraindications for Xeljanz?
  • What was the injury due to Xeljanz?

When and where was the injury diagnosed? Whether hospitalized? Dates of hospitalization?

  • Treatment/management. Any complications
  • Follow-up visits for treatment/management of injury.
  • Outcome/prognosis. Resolution of injury?

Specific Focus:

Identify and report cases with the following scenarios:-

  1. No Injuries: Patient took Xeljanz but did not develop any injuries
  2. No Xeljanz intake: Patient was given a different drug and not Xeljanz. Hold case and communicate to client
  3. Xeljanz contraindicated in patient but still prescribed
  4. Any medical/surgical/Family history, social history that could have had an effect on the injury

Missing record communication:

Identify and report on missing medical records

Apart from identifying critical missing records that are important for the case, provide a detailed outline on what records are needed, why we need them, how did we get a clue that these records are missing and whether the records missing are confirmatory/probable. This will also help in following up and retrieving the records.

Missing Records are presented in the following format

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