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Pharmaceutical Approval Update May 2015
Manufacturer: Sandoz, Princeton, New Jersey
Date of Approval: March 6, 2015
Indication: Zarxio is indicated:
- To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever.
- For reducing the time to neutrophil recovery and the duration of fever following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML).
- To reduce the duration of neutropenia and neutropenia-related clinical sequelae in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone-marrow transplantation.
- For the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis.
- For chronic administration to reduce the incidence and duration of sequelae of neutropenia in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.
The medication is contraindicated in patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors (G-CSFs) such as filgrastim or pegfilgrastim products.
Drug Class: Zarxio (filgrastim-sndz) is a 175 amino acid human G-CSF manufactured by recombinant DNA technology.
Uniqueness of Drug: G-CSF found in the body regulates the production of neutrophils in the bone marrow and affects neutrophil progenitor proliferation, differentiation, and selected end-cell functions. These functions include enhanced phagocytic ability, priming of the cellular metabolism associated with respiratory burst, antibody-dependent killing, and the increased expression of some cell-surface antigens.
Warnings and Precautions:
Splenic rupture. Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture.
Acute respiratory distress syndrome (ARDS). Evaluate patients who develop fever and lung infiltrates or respiratory distress for ARDS. Discontinue filgrastim-sndz in patients with ARDS.
Serious allergic reactions. Provide symptomatic treatment for allergic reactions. Allergic reactions, including anaphylaxis, can reoccur within days after the discontinuation of initial anti-allergic treatment in patients receiving filgrastim products. Permanently discontinue filgrastim-sndz in patients with serious allergic reactions.
Sickle cell disorders. Sickle cell crisis, in some cases fatal, has been reported with the use of filgrastim products in patients with sickle cell trait or sickle cell disease.
Alveolar hemorrhage and hemoptysis. Alveolar hemorrhage manifesting as pulmonary infiltrates and hemoptysis requiring hospitalization have been reported in healthy donors treated with filgrastim products undergoing peripheral blood progenitor cell (PBPC) collection mobilization. Hemoptysis resolved with discontinuation of filgrastim.
Capillary leak syndrome (CLS). Patients who develop symptoms of CLS should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care.
Severe chronic neutropenia (SCN). Confirm the diagnosis of SCN before initiating filgrastim-sndz therapy. If a patient with SCN develops abnormal cytogenetics or myelodysplasia, the risks and benefits of continuing filgrastim-sndz should be considered carefully.
Thrombocytopenia. Monitor platelet counts for patients receiving therapy.
Leukocytosis in cancer patients receiving myelosuppressive chemotherapy. It is recommended that filgrastimsndz therapy be discontinued if the absolute neutrophil count (ANC) surpasses 10,000/mm3 after the chemotherapy-induced ANC nadir has occurred. Monitor complete blood counts (CBCs) at least twice weekly during therapy.
Leukocytosis in PBPC collection and therapy. During the period that filgrastim-sndz is being administered for PBPC mobilization in cancer patients, discontinue filgrastim-sndz if the leukocyte count rises to more than 100,000/mm3.
Cutaneous vasculitis. Hold filgrastim-sndz therapy in patients with cutaneous vasculitis. Filgrastim-sndz may be started at a reduced dose when the symptoms resolve and the ANC has decreased.
Potential effect on malignant cells. The safety of filgrastim products in chronic myeloid leukemia (CML) and myelodysplasia has not been established.
Simultaneous use with chemotherapy and radiation therapy is not recommended. Do not use filgrastim-sndz in the period from 24 hours before through 24 hours after the administration of cytotoxic chemotherapy. Avoid the simultaneous use of filgrastim-sndz with chemotherapy and radiation therapy.
Nuclear imaging. Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone-imaging changes. This should be considered when interpreting bone-imaging results.
Dosage and Administration: In cancer patients receiving myelosuppressive chemotherapy or induction and/or consolidation chemotherapy for AML, the recommended starting dosage of filgrastim-sndz is 5 mcg/kg per day, administered as a single daily subcutaneous injection, by short intravenous (IV) infusion (15 to 30 minutes), or by continuous IV infusion.
In cancer patients undergoing bone-marrow transplantation (BMT), the recommended dosage of filgrastim-sndz following BMT is 10 mcg/kg per day given as an IV infusion for no longer than 24 hours.
In patients undergoing autologous PBPC collection and therapy, the recommended dosage of filgrastim-sndz for the mobilization of autologous PBPC is 10 mcg/kg per day given by subcutaneous injection.
In patients with SCN, the recommended starting dosage is 6 mcg/kg as a twice-daily subcutaneous injection.
In patients with idiopathic or cyclic neutropenia, the recommended starting dosage is 5 mcg/kg as a single daily subcutaneous injection.
Commentary: Zarxio represents a major milestone in drug development as the first biosimilar approved by the Food and Drug Administration (FDA) for use in the U.S. Two types of biological products are designed to provide an alternative to currently marketed biologic medications: “interchangeable” and “biosimilar” products. These products can be approved only if they have the same mechanism of action, route of administration, dosage form, and strength as a reference product. Unlike a biosimilar, an interchangeable product—which must duplicate the effects of the original even more closely—can be substituted by a pharmacist without consulting the prescriber. Although both categories of drugs are evaluated to ensure that they are as efficacious and safe as their reference products, it remains to be seen how physicians and insurers will approach these new medications.
Manufacturer: United Therapeutics, Silver Spring, Maryland
Date of Approval: March 10, 2015
Indication: Dinutuximab is indicated for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2, and 13-cisretinoic acid.
Drug Class: Unituxin is a chimeric monoclonal antibody.
Uniqueness of Drug: Dinutuximab binds to the glycolipid GD2, which is expressed on neuroblastoma cells and on normal cells of neuroectodermal origin, including the central nervous system and peripheral nerves. Dinutuximab binds to cell-surface GD2 and induces cell lysis of GD2-expressing cells through antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity.
Warnings and Precautions:
Serious infusion reactions. For mild-to-moderate infusion reactions such as transient rash, fever, rigors, and localized urticaria that respond promptly to antihistamines or antipyretics, decrease the dinutuximab infusion rate and monitor closely. Immediately interrupt or permanently discontinue dinutuximab and institute supportive management for severe or prolonged infusion reactions. Permanently discontinue dinutuximab and institute supportive management for life-threatening infusion reactions.
Pain and peripheral neuropathy. Discontinue dinutuximab if pain is not adequately controlled despite infusion-rate reduction and institution of maximum supportive measures. Permanently discontinue dinutuximab in patients with grade 2 peripheral motor neuropathy, grade 3 sensory neuropathy that interferes with daily activities for more than two weeks, or grade 4 sensory neuropathy.
Capillary leak syndrome. Immediately interrupt or discontinue dinutuximab and institute supportive management in patients with symptomatic or severe CLS.
Hypotension. Monitor patients closely for signs and symptoms of systemic infections and temporarily discontinue dinutuximab in patients who develop systemic infections until resolution of the infection.
Neurological disorders of the eye. Interrupt dinutuximab in patients experiencing dilated pupils with sluggish light reflex or other visual disturbances that do not cause visual loss. Upon resolution and if continued treatment with dinutuximab is warranted, decrease the dinutuximab dose by 50%. Permanently discontinue dinutuximab in patients with recurrent signs or symptoms of an eye disorder following dose reduction and in patients who experience loss of vision.
Bone marrow suppression. Monitor peripheral blood counts closely during therapy with dinutuximab.
Electrolyte abnormalities. Monitor serum electrolytes daily during therapy with dinutuximab.
Atypical hemolytic uremic syndrome. Permanently discontinue dinutuximab and institute supportive management for signs of hemolytic uremic syndrome.
Embryo-fetal toxicity. Advise females of reproductive potential to use effective contraception during dinutuximab treatment and for two months after the last dose.
Dosage and Administration: The recommended dose of dinutuximab is 17.5 mg/m2 per day administered as an IV infusion over 10 to 20 hours for four consecutive days for a maximum of five cycles.
Commentary: Neuroblastoma is a rare form of cancer that primarily occurs in children younger than 5 years of age. Unituxin is the only approved therapy specifically intended for patients with high-risk neuroblastoma. This therapy was approved with priority review and orphan drug designations; it was also given a rare pediatric disease priority review voucher, a designation designed to encourage the development of new therapies for rare pediatric conditions.
Manufacturer: Novartis Pharmaceuticals, East Hanover, New Jersey
Date of Approval: February 23, 2015
Indication: Panobinostat, in combination with bortezomib and dexamethasone, is indicated for the treatment of patients with multiple myeloma who have received at least two prior regimens, including bortezomib and an immunomodulatory agent.
Drug Class: Panobinostat is a histone deacetylase (HDAC) inhibitor.
Uniqueness of Drug: Inhibition of HDAC activity results in increased acetylation of histone proteins, an epigenetic alteration that results in a relaxing of chromatin, leading to transcriptional activation. This phenomenon may induce cell-cycle arrest and/or apoptosis of some transformed cells.
Warnings and Precautions:
Diarrhea. Interrupt panobinostat at the onset of moderate diarrhea (four to six stools per day). Ensure that patients initiating panobinostat therapy have antidiarrheal medications on hand.
Cardiac toxicities. Obtain electrocardiograms at baseline and periodically during treatment as clinically indicated. Monitor electrolytes during treatment and correct abnormalities as clinically indicated. If QT prolongation does not resolve, permanently discontinue panobinostat treatment.
Hemorrhage. Fatal and serious hemorrhage may occur during treatment with panobinostat.
Myelosuppression. Dose modifications are recommended for myelosuppression. Monitor CBCs more frequently in patients older than 65 years of age due to the increased frequency of myelosuppression in this population.
Infections. Monitor patients for signs and symptoms of infections during treatment; if an infection is diagnosed, institute appropriate anti-infective treatment promptly and consider interruption or discontinuation of panobinostat.
Hepatotoxicity. If abnormal liver function tests are observed, dose adjustments may be considered and the patient should be followed until values return to normal or pretreatment levels.
Embryo-fetal toxicity. Advise females of reproductive potential to avoid becoming pregnant while taking panobinostat. Advise sexually active females of reproductive potential to use effective contraception while taking panobinostat and for at least one month after the last dose of the medication. Advise sexually active males to use condoms while receiving treatment and for three months after their last dose of panobinostat.
Dosage and Administration: The recommended starting dose of panobinostat is 20 mg, taken orally once every other day for three doses per week in weeks 1 and 2 of each 21-day cycle for up to eight cycles.
Commentary: Multiple myeloma is a type of blood cancer that affects approximately 21,700 U.S. patients annually. Approval of Farydak for multiple myeloma for patients previously treated with two prior standard therapies follows a decision by the FDA’s Oncologic Drugs Advisory Committee to recommend against the original indication of relapsed multiple myeloma. Farydak received priority review and an orphan drug designation and was approved through the accelerated approval program.