Hepatosplenic T-Cell Lymphoma

ISSUE: FDA continues to receive reports of a rare cancer of white blood cells (known as Hepatosplenic T-Cell Lymphoma or HSTCL, primarily in adolescents and young adults being treated for Crohn’s disease and ulcerative colitis with medicines known as tumor necrosis factors (TNF) blockers, as well as with azathioprine, and/or mercaptopurine.  TNF blockers include Remicade (infliximab), Enbrel (etanercept), Humira (adalimumab), Cimzia (certolizumab pegol) and Simponi (golimumab).

BACKGROUND: HSTCL is an aggressive (fast-growing) cancer and is usually fatal. The majority of cases reported were in patients being treated for Crohn’s disease or ulcerative colitis, but also included a patient being treated for psoriasis and two patients being treated for rheumatoid arthritis. FDA is now updating the number of reported cases of HSTCL.Although most reported cases of HSTCL occurred in patients treated with a combination of medicines known to suppress the immune system, including the TNF blockers, azathioprine, and/or mercaptopurine, there have been cases reported in patients receiving azathioprine or mercaptopurine alone.

RECOMMENDATIONS:

·      Educate patients and caregivers about the signs and symptoms of malignancies such as HSTCL so that they are aware of and can seek evaluation and treatment of any signs or symptoms. These may include splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, and weight loss.

·      Monitor for the emergence of malignancies when a patient has been treated with TNF blockers, azathioprine, and/or mercaptopurine.

·      Know that people with rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis and plaque psoriasis may be more likely to develop lymphoma than the general U.S. population. Therefore, it may be difficult to measure the added risk of TNF blockers, azathioprine, and/or meracaptopurine.

 Exparel

Generic Name: bupivacaine liposome injectable suspension
Date of Approval: October 28, 2011
Company: Pacira Pharmaceuticals, Inc.

Treatment for: Postsurgical Pain

The U.S. Food and Drug Administration (FDA) has approved Exparel (bupivacaine liposome injectable suspension) 1.3% for administration into the surgical site to produce postsurgical analgesia.Exparel combines bupivacaine with DepoFoam®, a delivery technology that delivers medication over a desired time period. By utilizing the DepoFoam platform, a single dose of Exparel delivers bupivacaine for an extended period of time, providing analgesia with reduced opioid requirements for up to 72 hours. Exparel represents the first and only multivesicular liposome local anesthetic that can be utilized in the peri- or postsurgical setting in the same fashion as current local anesthetics, which provide a relatively short duration of efficacy.

The safety of Exparel has been evaluated in 21 clinical trials, which include over 1300 subjects in the safety database. Exparel administered locally into the surgical site was evaluated in 10 randomized, double-blind, clinical studies involving 823 patients undergoing various surgical procedures. Patients were administered a dose ranging from 66 mg to 532 mg of Exparel. Exparel is contraindicated in obstetrical paracervical block anesthesia. Other formulations of bupivacaine should not be administered within 96 hours following administration of Exparel. In these studies, the most common adverse reactions (incidence >10%) following Exparel administration were nausea, constipation, and vomiting.

Highlights of Prescribing Information

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Indications and Usage

Exparel is a liposome injection of bupivacaine, an amide local anesthetic, indicated for single-dose infiltration into the surgical site to produce postsurgical analgesia.

Dosage and Administration

Exparel is intended for single-dose administration only. The recommended dose of Exparel is based on the surgical site and the volume required to cover the area.

Inject Exparel slowly into soft tissue via infiltration.

Dosage Forms and Strengths

Exparel (bupivacaine liposome injectable suspension)

·      10 mL single use vial, 1.3% (13.3 mg/mL)

·      20 mL single use vial, 1.3% (13.3 mg/mL)

Contraindications

Exparel is contraindicated in obstetrical paracervical block anesthesia.

Warnings and Precautions

·      Monitoring of cardiovascular and neurological status, as well as vital signs should be performed during and after injection of Exparel as with other local anesthetic products.

·      Because amide-type local anesthetics, such as bupivacaine, are metabolized by the liver, Exparel should be used cautiously in patients with hepatic disease. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations.

·      Other formulations of bupivacaine should not be administered within 96 hours following administration of Exparel. 

Shamna 

Sr lecturer

Alshifa college of pharamcy