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Pharmaceutical Approval Update January 2015

Kunj Gohil PharmD, RPh

Meningococcal Group B Vaccine (Trumenba)

Manufacturer: Pfizer Inc., Philadelphia, Pennsylvania

Date of Approval: October 29, 2014

Indication: Trumenba is indicated for active immunization to prevent invasive disease caused by Neisseria meningitidis serogroup B. The vaccine is approved for use in individuals 10 through 25 years of age.

Trumenba’s approval was based on demonstration of immune response, as measured by serum bactericidal activity, against four serogroup B strains representative of prevalent strains in the United States. The effectiveness of the product against diverse serogroup B strains has not been confirmed. Trumenba is contraindicated in patients with a history of severe allergic reaction after a previous dose of the product.

Drug Class: Trumenba is a vaccine.

Uniqueness of Drug: Protection against invasive meningococcal disease is conferred mainly by complement-mediated, antibody-dependent killing of N. meningitidis.

Warnings and Precautions:

Management of allergic reactions. Epinephrine and other appropriate agents used to manage rapid-onset allergic reactions must be immediately available in case an acute anaphylactic reaction occurs following administration of Trumenba.

Altered immunocompetence. Individuals with altered immunocompetence may have reduced immune responses to Trumenba.

Dosage and Administration: Administer Trumenba intramuscularly as a three-dose series (0.5 mL each) at months 0, 2, and 6.

Commentary: Trumenba is the first and only vaccine approved to protect against disease caused by N. meningitidis serogroup B. This is the same strain that caused a small outbreak in New Jersey and California in 2013. Due to the severity of this disease, Trumenba was approved through the Food and Drug Administration (FDA) accelerated approval pathway. It was supported by results from studies targeting four strains of serogroup B.

Sources:, Trumenba prescribing information

Antihemophilic Factor (Recombinant), Porcine Sequence (Obizur)

Manufacturer: Baxter International Inc., Deerfield, Illinois

Date of Approval: October 23, 2014

Indication: Obizur, antihemophilic factor (recombinant), porcine sequence, is a recombinant DNA-derived anti-hemophilic factor indicated for the treatment of bleeding episodes in adults with acquired hemophilia A. Its safety and efficacy have not been established in patients with baseline anti-porcine factor VIII inhibitor titer greater than 20 BU (Bethesda units). Obizur is not indicated for the treatment of congenital hemophilia A or von Willebrand disease. It is contraindicated in patients who have had life-threatening hypersensitivity reactions to Obizur or its components (which include traces of hamster proteins).

Drug Class: Obizur is a factor VIII replacement (anti-hemophilic factor).

Uniqueness of Drug: Obizur temporarily replaces the inhibited endogenous factor VIII that is needed for effective hemostasis in patients with acquired hemophilia A.

Warnings and Precautions:

Hypersensitivity reactions. Such reactions can occur with Obizur, which contains trace amounts of hamster proteins. Early signs of allergic reactions, which can progress to anaphylaxis, include angioedema, chest tightness, dyspnea, hypotension, wheezing, urticaria, and pruritus. Immediately discontinue administration and initiate appropriate treatment if allergic or anaphylactic-type reactions occur.

Inhibitory antibodies. Use appropriate assays to monitor patients for the development of inhibitory antibodies, which have occurred with Obizur. If the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled after administration of the product, suspect the presence of an antiporcine factor VIII antibody. If such inhibitory antibodies to antiporcine factor VIII are suspected and there is a lack of clinical response, consider other therapeutic options.

Monitoring laboratory tests. Perform a one-stage clotting assay to confirm that adequate factor VIII levels have been achieved and maintained as follows:

  • Monitor factor VIII activity 30 minutes and three hours after the initial dose.
  • Monitor factor VIII activity 30 minutes after subsequent doses.

In addition, monitor the development of inhibitory anti bodies to Obizur. Perform a Nijmegen Bethesda inhibitor assay if expected plasma factor VIII activity levels are not attained or if bleeding is not controlled with the expected dose of the product. Use Bethesda units (BU) to report inhibitor levels.

Dosage and Administration: Dose, dosing frequency, and duration of treatment with Obizur depend on the location and severity of the bleeding episode, target factor VIII levels, and the patient’s clinical condition. Monitor replacement therapy in cases of major surgery or life-threatening bleeding episodes. The dose should be administered intravenously and titrated based on factor VIII recovery levels and individual clinical response. Use aseptic technique when reconstituting Obizur (which is supplied as a lyophilized powder for solution).

Commentary: Acquired hemophilia A is a rare bleeding disorder caused by antibodies directed against the patient’s own blood-clotting factor, factor VIII. This life-threatening disorder affects both males and females equally and is not a genetic disorder. Typically, this disorder is related to other conditions, but, more than half the time, a direct cause cannot be identified. Trials with Obizur included 28 patients and demonstrated effectiveness in the treatment of severe bleeding episodes. Obizur received an orphan drug designation, as it is intended for a rare condition.

Sources: Obizur prescribing information,

Pirfenidone (Esbriet)

Manufacturer: InterMune, Inc., Brisbane, California

Date of Approval: October 15, 2014

Indication: Pirfenidone is indicated for the treatment of idiopathic pulmonary fibrosis (IPF).

Drug Class: Pirfenidone is a transforming growth factor-beta inhibitor and tumor necrosis factor-alpha inhibitor.

Uniqueness of Drug: The mechanism of action of pirfenidone in the treatment of IPF has not been established.

Warnings and Precautions:

Elevated liver enzymes. Conduct liver function tests (alanine transaminase [ALT], aspartate aminotransferase [AST], and bilirubin) prior to the initiation of therapy with pirfenidone in all patients, then monthly for the first six months and every three months thereafter. Dosage modifications or interruption may be necessary for liver enzyme elevations.

Photosensitivity reaction or rash. Instruct patients to avoid or minimize exposure to sunlight (including sunlamps), to use a sunblock (SPF 50 or higher), and to wear clothing that protects against sun exposure. Additionally, instruct patients to avoid concomitant medications known to cause photosensitivity. Dosage reduction or discontinuation may be necessary in some cases of photosensitivity reaction or rash.

Gastrointestinal disorders. The most common (more than 2%) gastrointestinal (GI) events that led to dosage reduction or interruption were nausea, diarrhea, vomiting, and dyspepsia. The incidence of GI events was highest early in the course of treatment (with highest incidence occurring during the initial three months) and decreased over time. Dosage modifications may be necessary in some cases of GI adverse reactions.

Dosage and Administration: The recommended daily maintenance dosage of Esbriet is 801 mg (three 267-mg capsules) three times a day with food for a total of 2,403 mg a day. Doses should be taken at the same time each day. Upon initiation, titrate to the full dosage over a 14-day period.

Commentary: Idiopathic pulmonary fibrosis is a severe, debilitating disease in which a patient’s deep lung tissue becomes thick, stiff, and/or scarred over time. This prevents the lungs from transferring oxygen into the patient’s bloodstream and can cause severe complications. Until October 15, 2014, no medications were FDA-approved for the treatment of IPF, but on that day, both Esbriet and nintedanib (Ofev, Boehringer Ingelheim Pharmaceuticals) were approved. With similar launch dates and markets, it will be interesting to see if one medication takes leadership within this market.

Sources:, Esbriet prescribing information,,

Nintedanib (Ofev)

Manufacturer: Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut

Date of Approval: October 15, 2014

Indication: Nintedanib is indicated for the treatment of idiopathic pulmonary fibrosis (IPF).

Drug Class: Ofev is a fibroblast growth factor receptor (FGFR) antagonist, platelet-derived growth factor receptor (PDGFR) antagonist, and vascular endothelial growth factor receptor (VEGFR) antagonist.

Uniqueness of Drug: Nintedanib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs) and nonreceptor tyrosine kinases (nRTKs). Nintedanib inhibits the following RTKs: PDGFR-α and -β; FGFR-1, -2, and -3; VEGF-1, -2, and -3; and Fms-like tyrosine kinase-3. Among them, FGFR, PDGFR, and VEGFR have been implicated in IPF pathogenesis. Nintedanib binds competitively to the adenosine triphosphate binding pocket of these receptors and blocks the intracellular signaling that is crucial for the proliferation, migration, and transformation of fibroblasts representing essential mechanisms of the IPF pathology. In addition, nintedanib inhibits the following nRTKs: Lck, Lyn, and Src kinases.

Warnings and Precautions:

Elevated liver enzymes. Conduct liver function tests (ALT, AST, and bilirubin) prior to treatment with nintedanib, monthly for three months, every three months thereafter, and as clinically indicated. Dosage modifications or interruption may be necessary for liver enzyme elevations.

Gastrointestinal disorders. Dosage modifications or treatment interruptions may be necessary in patients with adverse reactions of diarrhea.

Treat diarrhea at first signs with adequate hydration and antidiarrheal medication (e.g., loperamide), and consider treatment interruption if diarrhea continues. Nintedanib treatment may be resumed at the full dosage (150 mg twice daily) or at a reduced dosage (100 mg twice daily), which subsequently may be increased to the full dosage. If severe diarrhea persists despite symptomatic treatment, discontinue treatment with nintedanib.

For nausea or vomiting that persists despite appropriate supportive care, including antiemetic therapy, dose reduction or treatment interruption may be required. Nintedanib treatment may be resumed at the full dosage (150 mg twice daily) or at a reduced dosage (100 mg twice daily), which subsequently may be increased to the full dosage. If severe nausea or vomiting does not resolve, discontinue treatment with nintedanib.

Embryofetal toxicity. Nintedanib can cause fetal harm when administered to a pregnant woman. If nintedanib is used during pregnancy, or if the patient becomes pregnant while taking nintedanib, the patient should be advised of the potential hazard to a fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with nintedanib and to use adequate contraception during treatment and at least three months after the last dose of the medication.

Arterial thromboembolic events. Use caution when treating patients at a higher cardiovascular risk, including those with known coronary artery disease. Consider treatment interruption in patients who develop signs or symptoms of acute myocardial ischemia.

Risk of bleeding. Use nintedanib in patients with a known risk of bleeding only if the anticipated benefit outweighs the potential risk.

Gastrointestinal perforation. Based on the mechanism of action, nintedanib may increase the risk of GI perforation. Use caution when treating patients who have had recent abdominal surgery. Discontinue therapy with nintedanib in patients who develop GI perforation. Only use nintedanib in patients with a known risk of GI perforation if the anticipated benefit outweighs the potential risk.

Dosage and Administration: The recommended dosage of Ofev is 150 mg twice daily administered approximately 12 hours apart. Capsules should be taken with food and swallowed whole with liquid. The capsules should not be chewed or crushed because of a bitter taste. The effect of chewing or crushing of the capsule on the pharmacokinetics of nintedanib is not known. If a dose is missed, the next dose should be taken at the next scheduled time. Advise the patient not to make up for a missed dose. Do not exceed the recommended maximum daily dosage of 300 mg.

Commentary: Idiopathic pulmonary fibrosis is a serious, debilitating disease that gradually thickens, stiffens, and/or scars a patient’s deep lung tissue. As a result, the lungs cannot transfer oxygen into the patient’s bloodstream, potentially causing severe complications. Ofev and Esbriet were approved on the same day in October 2014—making them the first FDA-indicated medications for the treatment of IPF. It remains to be seen whether one medication will become more successful than the other.

Sources: Ofev prescribing information,,

Author bio: 
Dr. Gohil is Central Services Manager with Medical Services at MediMedia Managed Markets in Yardley, Pennsylvania.