2015: The Year in Specialty Drugs

SPECIALTY PHARMACEUTICALS featured prominently in the FDA’s new drug approval and expanded indications list once again in 2015. Below is the first of a 2-part summary of specialty pharmacy—related FDA approvals and expanded indications that took place this year.

Part 2, which will be featured in the next issue of Specialty Pharmacy Times, will include oncology drugs and late-breaking FDA actions. Please consult product prescribing monographs for complete information including dosing regimens.

Bleeding Disorders

Ixinity (coagulation factor IX (recombinant), Emergent BioSolutions Inc) was approved by the FDA on April 30, 2015, for adults and children at least ≥ 12 years of age with hemophilia B for control and prevention of bleeding episodes, as well as perioperative management. Ixinity is not indicated for induction of immune tolerance in patients with hemophilia B, however. Ixinity is available as a lyophilized powder for reconstitution in color coded, single-use glass vials containing nominally 500, 1000, or 1500 IU of factor IX activity per vial. It comes packaged with a 10-mL syringe pre-filled with 5-mL of sterile water for injection with plunger rod attached, vial adapter with filter, and a sterile 20-mL LUER-LOK administration syringe. None of the kit components are made with natural rubber latex. The dosage and duration of Ixinity treatment depends on the severity of the factor IX deficiency, on the location and extent of the bleeding and the patient’s clinical condition, age, and pharmacokinetic parameters of factor IX, such as incremental recovery and half-life.^{1, 2}

Nuwiq (coagulation factor VIII (recombinant), Octapharma) was approved on September 15, 2015, for hemophilia A on-demand treatment and control of bleeding episodes in adults and children, perioperative management of bleeding, and routine prophylaxis to reduce the frequency of bleeding episodes. Nuwiq is not indicated for the treatment of von Willebrand Disease. The drug is the first B-domain deleted recombinant factor VIII (FVIII) derived from a human cell-line, not chemically modified or fused with another protein, designed for the treatment of patients with hemophilia A (congenital FVIII deficiency). Nuwiq is available as a lyophilized powder for reconstitution in single-use vials containing approximately 250, 500, 1000 or 2000 IU Factor VIII potency. The drug is administered via intravenous infusion only and comes in a kit that includes a single-use vial of Nuwiq concentrate, a pre-filled syringe containing 2.5-mL sterile water for injection, a vial adapter, butterfly needle and alcohol swabs. The frequency and duration of therapy depends on severity of the FVIII deficiency, the location and extent of bleeding, and the patient’s clinical condition.^3,4

Coagadex (coagulation factor X (human), Bio Products Laboratory Ltd) was approved on October 20, 2015, for the treatment of mild hereditary factor X deficiency in patients aged 12 and older for on-demand treatment, control of bleeding episodes, and perioperative management. Perioperative management of bleeding during major surgery in patients with moderate and severe hereditary factor X deficiency has yet to be studied. The FDA granted Coagadex orphan product designation for the above indications; it was also granted fast track designation and priority review. Coagadex is available as a lyophilized powder for reconstitution in single-use glass vials containing nominally 250 IU or 500 IU of factor X activity, packaged with 2.5-mL or 5-mL of sterile water for injection, respectively, and a Mix2Vial transfer device. The dosage and duration of Coagadex treatment depends on the severity of the factor X deficiency, on the location and extent of the bleeding and on the patient’s clinical condition.^5,6

Adynovate (antihemophilic factor [recombinant] pegylated, Baxalta Inc) was approved by the FDA on November 13, 2015 for adolescent and adult patients aged 12 and older with hemophilia A (congenital factor VIII deficiency) for on-demand treatment, control of bleeding episodes, and routine prophylaxis to reduce the frequency of bleeding episodes. Adynovate is not indicated for the treatment of von Willebrand disease. Adynovate’s pegylated form allows it to last longer in the blood, potentially requiring less frequent injections than the unmodified form. Adynovate is available as a lyophilized powder for reconstitution in single-use vials containing approximately 250, 500, 1000, or 2000 IU of factor VIII potency. It is packaged with a diluent vial containing 5 mL of sterile water for injection, and a BAXJECT II Hi-Flow Needleless Transfer Device. The dosage and duration of treatment with Adynovate depends on the severity of factor VIII deficiency, the location and extent of the bleed, and the patient’s clinical condition. Careful monitoring of replacement therapy is necessary in cases of serious or life-threatening bleeding episodes.^7,8

Inflammatory Conditions

Cosentyx (secukinumab, Novartis Pharmaceutical Corp.) was approved January 21, 2015, for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Cosentyx is a human interleukin-17A (IL-17A) antagonist that binds to IL-17A, which is a protein involved in inflammation. By doing so, Cosentyx inhibits IL-17A’s ability to trigger the inflammatory response involved in the development of plaque psoriasis. Cosentyx is available as a 150 mg/ml single-use Sensoready pen and a single-use prefilled syringe. It is also available as a lyophilized powder in a single-use vial for reconstitution, but this is only for use by health care professionals. Cosentyx is intended for use under the guidance and supervision of a physician. If deemed appropriate by caregivers, patients may self-inject after proper training in subcutaneous injection technique using the Sensoready pen or prefilled syringe. The recommended dose is 300-mg by subcutaneous injection at Weeks 0, 1, 2, 3, and 4, followed by 300-mg every 4 weeks. For some patients, a dose of 150 mg may be sufficient.^9,10

Humira (adalimumab, AbbVie) received an expanded indication on September 10, 2015, for the treatment of moderate-to-severe hidradenitis suppurativa (HS). Humira is the only FDA-approved therapy for adults with HS. The drug was initially approved by the FDA in 2002 for the treatment of rheumatoid arthritis. It has since received indications for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult and pediatric Crohn’s disease, adult ulcerative colitis, and plaque psoriasis. Humira is available as a subcutaneous injection in a prefilled glass syringe containing 10-mg/0.2-mL, 20-mg/0.4-mL, or 40-mg/0.8-mL. It is also available in a 40-mg/0.8-mL single-use prefilled syringe and in a 40-mg/0.8-mL single use glass vial for institutional use only. The recommended starting dose for HS is 160-mg on day 1, which is given as four 40-mg injections or as two 40-mg injections per day on days 1 and 2. The second dose of 80-mg (two 40-mg injections in one day) is given on day 15 followed by the third dose of 40-mg given on day 29 and subsequent doses of 40-mg given every week.

Cystic Fibrosis

Kalydeco (ivacaftor, Vertex Pharmaceuticals) received an expanded indication on March 18, 2015, for children 2 to 5 years with cystic fibrosis (CF) who have 1 of 10 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R or R117H). The CFTR potentiator was originally approved in 2012 for the treatment of CF in patients 6 years and older with any of the above mutations. Kalydeco is not effective in patients with CF who are homozygous for the F508del mutation in the CFTR gene. The drug is available in 150 mg tablets and unit dose packets of 50- and 75-mg oral granules. The recommended dosage in adults and pediatric patients 6 years and older is one 150-mg tablet taken orally every 12 hours with fat-containing food. The dosage for pediatric patients aged 2 years to less than 6 years weighing less than 14kg is one 50-mg packet given orally every 12 hours. For pediatric patients aged 2 to under 6 years weighing more than 14kg, the dosage is one 75-mg packet given orally every 12 hours. Each packet should be mixed with 5-mL of soft food or liquid. Kalydeco is not recommended in patients less than 2 years of age. The dose should be reduced in patients with moderate and severe hepatic impairment or when Kalydeco is co-administered with moderate or strong CYP3A inhibitors.^13,14

On July 2, 2015, the FDA approved Vertex Pharmaceuticals’ Orkambi (lumacaftor 200-mg/ivacaftor 125-mg). Orkambi is a combination of lumacaftor and ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, indicated for the treatment of CF in patients 12 years and older who are homozygous for the F508del mutation in the CFTR gene. If the patient’s genotype is unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene. Orkambi is available in a 112-tablet box containing a 4-week supply of 7 daily blister strips with 4 tablets per strip. The recommended dosage in adults and pediatric patients 12 years and older is 2 tablets taken orally every 12 hours with fat-containing foods. The dose should be adjusted for patients with hepatic impairment and taking CYP3A inhibitors.^15,16

HIV

Evotaz (atazanvir 300-mg and cobicistat 150-mg, Bristol-Myers Squibb Co) was approved on January 29, 2015, in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults. Evotaz is a fixed-dose combination drug containing atazanvir, a protease inhibitor marketed individually as Reyataz, and cobicistat, a CYP3A inhibitor, marketed individually as Tybost. Evotaz is not recommended for use in treatment-experienced patients with end-stage renal disease managed with hemodialysis and in patients with hepatic impairment. The recommended dosage of Evotaz in adults is 1 tablet taken orally once daily with food in combination with other antiretroviral agents.^17,18

Prezcobix (darunavir 800-mg and cobicistat 150-mg, Janssen Therapeutics) was approved on January 29, 2015, for use in combination with other antiretroviral agents in treatment-naive and treatment-experienced patients with HIV with no darunavir resistance-associated substitutions. Prezcobix is a fixed-dose combination drug containing darunavir, a protease inhibitor marketed individually as Prezista, and cobicistat, a CYP3A inhibitor marketed individually as Tybost. Since Prezcobix contains darunavir, a sulfonamide moiety, patients with a known sulfonamide allergy should be monitored after initiating treatment. Prezcobix is not recommended for patients with severe hepatic impairment. Co-administration with tenofovir disoproxil fumarate is not advised in patients with an estimated creatinine clearance less than 70-mL/min. The recommended dosage for Prezcobix in adults is 1 tablet taken orally once daily with food in combination with other antiretroviral agents.^{19, 20}

Genvoya (cobicistat, elvitegravir, emtricitabine and tenofovir alafenamide, Gilead Sciences, Inc) was approved on November 5, 2015, as a complete regimen for the treatment of HIV-1 infection. The drug was approved for use in adults and pediatric patients 12 years and older with no antiretroviral treatment history or to replace the current antiretroviral regimen in patients virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Genvoya. Genvoya is a 4-drug combination tablet consisting of 150-mg of elvitegravir, an HIV-1 integrase strand transfer inhibitor, 150-mg of cobicistat, and 200-mg of emtricitabine and 10-mg of tenofovir alafenamide, which are both HIV-1 nucleoside analog reverse transcriptase inhibitors. The recommended dosage of Genvoya is 1 tablet taken orally once daily with food.^{21, 22}

Hepatitis C

Technivie (ombitasvir, paritaprevir and ritonavir, AbbVie Inc) was approved on July 24, 2015, for use in combination with ribavirin for the treatment of hepatitis C virus (HCV) genotype 4 infections in patients without cirrhosis. Technivie is a fixed-dose combination of ombitasvir, an HCV NS5A inhibitor; paritaprevir, an HCV NS3/4A protease inhibitor; and ritonavir, a CYP3A inhibitor. Technivie is dispensed in a monthly carton for a total of 28 days of therapy. Each monthly carton contains 4 weekly cartons containing 7 daily dose packs. Each tablet of Technivie contains 12.5-mg ombitasvir, 75-mg paritaprevir, and 50-mg ritonavir. The recommended dosage is 2 tablets taken orally once daily in the morning with a meal regardless of fat or calorie content. Technivie is recommended for use in combination with ribavirin, but can also be used on its own for treatment-naïve patients who cannot take or tolerate ribavirin.^{23, 24}

Daklinza (daclatasvir, Bristol-Myers Squibb) was approved by the FDA on July 24, 2015, for use in adult patients in combination with Sovaldi (sofosbuvir) for HCV genotype 3 infections. Daklinza is the first drug to demonstrate safety and efficacy in genotype 3 HCV infections without the need for co-administration of interferon or ribavirin. Daklinza was reviewed under the FDA’s priority review program. Patients with cirrhosis taking Daklinza have shown reduced sustained virologic response rates. Daklinza is available in a 60-mg and 30-mg tablet. The recommended dosage of Daklinza is 60-mg, taken orally once daily in combination with sofosbuvir for 12 weeks. Daklinza may be taken with or without food. The optimal duration of Daklinza and sofosbuvir for patients with cirrhosis has not been established. If sofosbuvir is permanently discontinued in a patient administered Daklinza with sofosbuvir, then Daklinza should also be discontinued.^{25, 26}

Harvoni (ledipasvir and sofosbuvir, Gilead Sciences, Inc.) received an expanded approval on November 12, 2015, for treatment of patients with genotype 4, 5, and 6 chronic HCV infection and in patients co-infected with HIV. In addition, Harvoni plus ribavirin for 12 weeks was approved as an alternate therapy to 24 weeks of Harvoni in treatment-experienced, genotype 1 patients with cirrhosis. Harvoni was initially approved in October 2014 for the treatment of patients 18 years and older with HCV genotype 1 infection. A single table of Harvoni contains 90-mg of the HCV NS5A inhibitor ledipasvir and 400-mg of sofosbuvir, an HCV nucleotide analog NS5B polymerase inhibitor. The recommended dosage is 1 tablet taken orally once daily with or without food. Treatment duration depends on the genotype, if the patient is treatment naïve or treatment experienced, and if the patient is with or without cirrhosis.^{27, 28}

Multiple Sclerosis

Glatopa (glatiramer acetate injection, Sandoz, Inc.) was approved by the FDA on April 16, 2015, as the first generic version of Teva’s Copaxone (glatiramer acetate injection), a 20-mg/mL once-daily treatment for patients age 18 years and older with relapsing-forms of multiple sclerosis. Glatopa is available in a 20-mg/mL single-dose, prefilled glass syringes with an attached half-inch length and 29 gauge needles in individual blister packages of 30 counts with alcohol preps. The recommended dose of Glatopa is 20-mg/mL once daily via subcutaneous injection only. Glatopa 20-mg/mL and Teva’s Copaxone in the 40-mg per mL dosage are not interchangeable.^{29, 30}

Betaconnect, Bayer HealthCare’s electronic auto injector used exclusively with Betaseron (interferon beta-1b) for relapsing-remitting multiple sclerosis, was approved by the FDA on September 25, 2015. The new auto injector offers quiet, customizable injection speed and depth settings with an optional back-up reminder function that alerts the patient when it’s time for their next injection.^{31, 32}

Specialty Ophthalmics

Lucentis (ranibizumab, Genentech) was granted an expanded indication on February 6, 2015, for the treatment of diabetic retinopathy (DR) in patients with diabetic macular edema (DME). Lucentis is a vascular endothelial growth factor (VEGF) inhibitor. Lucentis was initially approved in 2010 for the treatment of macular edema following retinal vein occlusion and later in 2012 for the treatment of DME. Lucentis is available in 2 dosage strengths: 10-mg/mL (Lucentis 0.5mg) and 6-mg/mL (Lucentis 0.3mg) in single use glass vials designed to provide 0.05-mL. The recommended dosage of Lucentis for patients with DR with DME is 0.3-mg (0.05-mL of 6-mg/mL solution) administered by intravitreal injection once monthly (about 28 days).^{33, 34}

Eylea (aflibercept, Regeneron Pharm) received an expanded indication on March 25, 2015, for the treatment of DR with DME. Eylea is a VEGF inhibitor formulated as an injection for the eye. Eylea was originally approved in 2011 to treat patients with wet (neovascular) age-related macular degeneration, a leading cause of vision loss and blindness in Americans aged 60 and older. Later in 2014, Eylea received an additional approval for the treatment of patients with DME and macular edema following retinal vein occlusion. The recommended dosage of Eylea in patients with DR with DME is 2-mg (0.05-mL) every 4 weeks for the first 5 injections, followed by 2-mg (0.05-mL) via intravitreal injection once every 8 weeks.^35-38

Hypercholesterolemia

Praluent (alirocumab, Sanofi-Aventis) was approved by the FDA on July 24, 2015, as an adjunct to diet and maximally tolerated statin therapy for adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease requiring additional lowering of low-density lipoprotein cholesterol (LDL-C). The effect of Praluent on cardiovascular morbidity and mortality has not been determined. Praluent is a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor antibody. Praluent is available at 75-mg/mL or 150-mg/mL strengths in either a single-dose prefilled pen or a single dose pre-filled syringe for subcutaneous use that patients can self-administer. The recommended starting dose of Praluent is 75-mg administered subcutaneously once every 2 weeks. If LDL-C response is inadequate, the dosage may be increased to the maximum dosage of 150-mg every 2 weeks.^{39, 40}

Repatha (evolocumab, Amgen Inc) was approved by the FDA on August 27, 2015, as an adjunct to diet and maximally tolerated statin therapy for adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (CVD), in patients who require additional lowering of LDL-C. Repatha is also indicated as an adjunct to diet and other LDL-lowering therapies (eg, statins, ezetimibe, LDL apheresis) for the treatment of patients with homozygous familial hypercholesterolemia (HoFH) requiring additional lowering of LDL-C. The effect of Repatha on cardiovascular morbidity and mortality has not been determined. Repatha is a monoclonal antibody targeting PCSK9 inhibitor available as a single-use 140-mg prefilled SureClick autoinjector or prefilled syringe for SC use that patients can self-administer. For adults with HoFH, the recommended dose is 420-mg once a month. In patients with HeFH or patients with primary hyperlipidemia with established clinical atherosclerotic CVD, the recommended dose is either 140-mg every 2 weeks or 420-mg once monthly.^{41, 42}

Miscellaneous Specialty Approvals

Natpara (parathyroid hormone, NPS Pharmaceuticals, Inc) was approved on January 23, 2015, as the first parathyroid hormone (PTH) for adults for hypoparathyroidism. Natpara is a bioengineered replica of human PTH for use with calcium and vitamin D to control low blood calcium (hypocalcemia) in people with low PTH blood levels. Due to the potential risk of osteosarcoma (bone cancer) associated with Natpara, it is only available through the Natpara Risk Evaluation and Mitigation Strategy program. As a result, the drug is reserved for patients who do not respond well to treatment with calcium and active forms of vitamin D alone. Natpara is supplied as a multiple-dose, dual-chamber glass cartridge containing a sterile lyophilized powder and a sterile diluent for reconstitution in 4 dosage strengths of 25-, 50-, 75-, or 100-mcg. Each cartridge is designed for use with a reusable mixing device for product reconstitution and a reusable Q-Cliq pen injector for drug delivery. Each medication cartridge delivers 14 doses. Dosing is based on each patient’s individualized needs, with a goal serum calcium level in the lower half of the normal range.^{43, 44}

Cresemba (isavuconazonium sulfate, Astellas Pharma US, Inc) was approved on March 6, 2015, for the treatment of adults with invasive aspergillosis and invasive mucormycosis, both rare but serious infections. The azole antifungal is the sixth approved drug product designated as a Qualified Infectious Disease Product. Cresemba is available in both oral and IV dosage formulations. Cresemba capsules contain 186-mg of isavuconazonium sulfate (equivalent to 100-mg of isavuconazole). Cresemba for injection is supplied in a single-dose vial as a sterile lyophilized powder containing 372-mg of isavuconazonium sulfate (equivalent to 200-mg of isavuconazole). The recommended loading dose for Cresemba is 372-mg (equivalent to 200-mg of isavuconazole) every 8 hours for 6 doses (48 hours) via oral (2 capsules) or IV administration. The maintenance dose of Cresemba is 372-mg (equivalent to 200-mg of isavuconazole) once daily via oral (2 capsules) or IV administration starting 12 to 24 hours after the last loading dose. The capsules can be taken with or without food, and the injection must be administered via an in-line filter over a minimum of 1 hour.^{45, 46}

Cholbam (cholic acid, Asklepion Pharmaceuticals LLC) was approved on March 17, 2015, as a bile acid for the treatment of pediatric patients (3 weeks and older) and adult patients with bile acid synthesis disorders due to single enzyme defects. The drug was also approved for patients with peroxisomal disorders, including Zellweger spectrum disorders, who exhibit manifestations of liver disease, steatorrhea (presence of fat in the stool), or complications from decreased fat-soluble vitamin absorption. Patients with this disorder lack the enzymes needed to synthesize cholic acid, a primary bile acid normally produced in the liver from cholesterol. Cholbam is available in 50-mg and 250-mg capsules. The recommended dose is 10- to 15-mg/kg once daily or in 2 divided doses. In patients with familial hypertriglyceridemia, the dosage is 11- to 17-mg/kg once daily or in 2 divided doses. Dosage can be adjusted based on the clinical response. Cholbam should be taken with food at least 1 hour before, or 4 to 6 hours (or at as great an interval as possible) after, a bile acid binding resin or aluminum-based antacid.^{47, 48}

Jadenu (deferasirox, Novartis Pharmaceuticals) tablets were approved on March 20, 2015, as a new formulation of Exjade (deferasirox tablets for oral suspension) for the treatment of chronic iron overload from blood transfusions in patients 2 years and older, and chronic iron overload in non-transfusion-dependent thalassemia syndromes in patients 10 years and older. Jadenu is a once-daily oral iron chelator that can be swallowed whole, unlike Exjade (deferasirox) tablets that need to be mixed into a suspension prior to administration. Jadenu is a film-coated tablet available in 90-, 180-, and 360-mg tablets. Jadenu should be taken orally once daily on an empty stomach or with a light meal at the same time each day. The drug should not be taken with aluminum-containing antacid products. The recommended starting dose of Jadenu is 14-mg/kg per day, but the dose can be titrated in increments of 3.5- to 7-mg/kg up to a maximum dose of 28-mg/kg per day.^{49, 50}

Anthrasil (anthrax immune globulin intravenous [Human], Cangene Corp) was approved on March 24, 2015, for the treatment of patients with inhalational anthrax in combination with appropriate antibacterial drugs. Inhalational anthrax is a rare disease that can occur after exposure to infected animals or contaminated animal products, or as a result of an intentional release of anthrax spores. It is caused by breathing in the spores of the bacterium Bacillus anthracis. The effectiveness of Anthrasil is based solely on efficacy studies conducted in animal models of inhalational anthrax. Anthrasil is available in single-use vials containing a minimum potency of ≥60 units by Toxin 60 Neutralization Assay. Some limitations associated with Anthrasil include that it does not have direct antibacterial activity, does not cross the blood-brain barrier, and does not prevent or treat meningitis; there have also been no studies of Anthrasil in pediatric, geriatric, or obese populations. Anthrasil should be administered by slow IV infusion using an infusion pump.^{51, 52}

Rapamune (sirolimus, Wyeth Pharmaceuticals) received an expanded indication on May 28, 2015, for the treatment of lymphangioleiomyomatosis (LAM), a rare, progressive lung disease that primarily affects women of childbearing age. Rapamune, the first drug approved to treat LAM, received orphan product designation for this indication. Rapamune, which is available as both a tablet and oral solution, was originally approved in 1999 as an immunosuppressive agent to help prevent organ rejection in patients 13 years and older receiving kidney transplants. The recommended initial dosage of Rapamune for the treatment of LAM is 2 mg/day. The dosage can be adjusted to achieve sirolimus trough concentrations between 5- and15-ng/mL. Rapamune is available in a 1-mg/mL oral solution, with tablets available in 0.5-, 1-, and 2-mg strengths.^{53, 54}

Promacta (eltrombopag, GlaxoSmithKline and Novartis Pharmaceuticals) received an expanded indication on June 12, 2015, for the treatment of children 6 years and older with chronic immune thrombocytopenia (cITP). Furthermore, on August 24, 2015, the FDA expanded Promacta’s indication to treat low blood platelet count in pediatric patients aged 1 and older with cITP. Promacta can be used in these children when they have not achieved a sufficient response to corticosteroids, immunoglobulins or a splenectomy. Promacta is an oral thrombopoietin receptor agonist that works by helping induce proliferation and differentiation of bone marrow stem cells to increase production of blood cells. It was first approved in November 2008 for the treatment of thrombocytopenia in patients with cITP who had an insufficient response to corticosteroids, immunoglobulins or splenectomy. Promacta also treats thrombocytopenia in patients with chronic HCV to allow the initiation and maintenance of interferon-based therapy. In August 2014, Promacta was also approved for patients with severe aplastic anemia who had an insufficient response to immunosuppressive therapy. Promacta is available in 12.5-, 25-, 50-, 75-, and 100-mg tablets. It is to be taken on an empty stomach 1 hour before or 2 hours after a meal, and at least 2 hours before or 4 hours after any medications or products containing polyvalent cations such as antacids, calcium-rich foods, and mineral supplements. For patients treated for cITP, the recommended dose is 50-mg once daily for adults and pediatric patients 6 years and older and 25-mg once daily for pediatric patients aged 1 to 5 years. A reduction in dose may be needed for patients with hepatic impairment and some patients of East Asian ancestry. Additionally, the dose may need to be adjusted in order to maintain a platelet count >50 x 10 9/L. The dose should not exceed 75 mg per day.^55-57

Envarsus XR (tacrolimus extended-release tablets, Veloxis Pharmaceuticals A/S) was approved on July 10, 2015, for prophylaxis from kidney transplant rejection in patients converted from tacrolimus immediate-release formulations in combination with other immunosuppressants. Envarsus XR extended-release tablets are not interchangeable or substitutable with other tacrolimus extended-release or immediate-release products. The drug is available in extended-release tablets at doses of 0.75-, 1-, and 4-mg. Envarsus XR is to be taken once daily on an empty stomach, preferably in the morning. Patients should avoid eating grapefruit or drinking grapefruit juice or alcohol while on the medication. Due to the increased risk of developing lymphomas and other malignancies (especially of the skin) from immunosuppression, patients are advised to limit exposure to sunlight and ultraviolet light by wearing protective clothing and using sunscreen. The recommended starting dose is 80% of the pre-conversion daily dose of tacrolimus immediate-release. Patients with severe hepatic impairment may require a lower starting dose.^{58, 59}

Dysport (abobotulinumtoxinA, Medicis and Ipsen) received an expanded indication on July 16, 2015, for the treatment of upper limb spasticity in adult patients to decrease the severity of increased muscle tone in elbow, wrist, and finger flexors. Dysport is an acetylcholine release inhibitor and a neuromuscular blocking agent. It was originally approved in April 2009 for the treatment of cervical dystonia in adults to reduce the severity of abnormal head position and neck pain and for the temporary improvement in the appearance of moderate-to-severe glabellar lines in adults younger than 65 years. Dysport contains human albumin, therefore, there is a risk for transmission of Creutzfeldt-Jakob disease (CJD). However, no cases of transmission of viral diseases or CJD have ever been identified for albumin. Dysport is supplied as a 300- or 500-unit lyophilized powder in a sterile, single-use glass vial for reconstitution with preservative-free 0.9% sodium chloride injection USP. Dysport is injected intra-muscularly and the dose is dependent upon the therapeutic condition.^{60, 61}

Keveyis (dichlorphenamide, Taro Pharmaceutical Industries Ltd) was approved on August 10, 2015 for patients with primary hyperkalemic periodic paralysis or primary hypokalemic periodic paralysis, a group of rare hereditary disorders that cause episodes of muscle weakness or paralysis. Keveyis is the first therapy approved by the FDA for the treatment of primary periodic paralysis. Keveyis is an oral carbonic anhydrase inhibitor available in a 50-mg tablet, with a recommended starting dose of 50-mg twice daily up to a maximum recommended dosage of 200-mg daily. It should not be taken by patients who are allergic to sulfonamide-based medications.^{62, 63}

Procysbi (cysteamine bitartrate, Raptor Pharmaceutical) received an expanded indication on on August 17, 2015, for the treatment of children 2 to 6 years of age with nephropathic cystinosis. Procysbi is a cysteine-depleting agent initially approved in 2013 for nephropathic cystinosis in adults and children 6 years and older. Procysbi is available as a delayed-release capsule in 25-mg and 75-mg strengths. Capsules should be taken with fruit juice (except grapefruit juice) and separated by 1 hour before or after medications containing bicarbonate or carbonate. Patients should not eat for at least 2 hours before and for at least 30 minutes after taking Procysbi to maximize absorption. The recommended starting dosage of Procysbi for cysteamine-naïve patients is 0.2 to 0.3 g/m2 per day divided into 2 doses given every 12 hours. To help reduce the risk of adverse reactions, the dose may be increased gradually over 4 to 6 weeks until the maintenance dosage is achieved.^64-65

Xuriden (uridine triacetate, Wellstat Therapeutics Corporation), a pyrimidine analog uridine replacement therapy for patients with hereditary orotic aciduria, was approved on September 15, 2015. The FDA previously granted Xuriden orphan drug designation. Xuriden is available in 2-mg oral granule packets. The recommended starting dose of Xuriden is 60-mg/kg once daily, and the dose may be increased to 120-mg/kg (not to exceed 8 g) once daily for insufficient efficacy. Xuriden is to be administered with food (applesauce, pudding, or yogurt) or in milk or infant formula. Refer to prescribing information for preparation, administration, and complete weight-based dosing tables.^66-67 SPT

References

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• Ixinity [prescribing information]. Winnipeg, Manitoba, Canada: Emergent BioSolutions Inc; 2015.
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• Nuwiq [prescribing information]. Sweden: Octapharma; 2015.
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• Coagadex [prescribing information]. United Kingdom; Bio Products Laboratory Ltd; 2015.
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• Adynovate [prescribing information]. Westlake Village, CA: Baxalta, Inc: 2015.
• FDA approves new psoriasis drug Cosentyx [news release]. Silver Spring, MD: FDA; January 21, 2015. fda.gov/newsevents/newsroom/pressannouncements/ucm430969.htm. Accessed March 11, 2015
• Cosentyx [prescribing information]. East Hanover, NJ: Novartis Pharmaceutical Corp; 2015.
• Abbvie’s Humira (Adalimumab) receives first and only U.S. Food and Drug Administration Approval for moderate to severe hidradenitis suppurativa [press release]. North Chicago, IL: Abbvie; September 10, 2015. Available at: http://abbvie.mediaroom.com/2015-09-10-AbbVies-HUMIRA-Adalimumab-Receives-First-and-Only-U-S-Food-and-Drug-Administration-Approval-for-Moderate-to-Severe-Hidradenitis-Suppurativa. Accessed October 29, 2015.
• Humira [prescribing monograph]. North Chicago, IL: Abbvie; 2015.
• Vertex receives U.S. Food and Drug Administration approval of Kalydeco (ivacaftor) for children with cystic fibrosis ages 2 to 5 who have specific mutations in the CFTR gene [news release]. Boston, MA: Vertex Pharmaceuticals Inc; March 18, 2015. http://investors.vrtx.com/releasedetail.cfm?ReleaseID=902211. Accessed March 23, 2015.
• Kalydeco [prescribing information]. Boston, MA: Vertex Pharmaceuticals Inc; 2015.
• FDA approves new treatment for cystic fibrosis [news release]. Silver Spring, MD: FDA; July 2, 2015. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm453565.htm. Accessed October 1, 2015.
• Orkambi [prescribing information]. Boston, MA: Vertex Pharmaceuticals Inc; 2015.
• U.S. Food and Drug Administration approves Bristol-Myers Squibb’s Evotaz (atazanavir and cobicistat) for the treatment of HIV-1 infection in adults [press release]. Princeton, NJ: Bristol-Myers Squibb; January 29, 2015. http://news.bms.com/press-release/financial-news/us-food-and-drug-administration-approves-bristol-myers-squibbs-evotaz-a. Accessed March 12, 2015.
• Evotaz [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; 2015.
• Prezcobix (darunavir/cobicistat) approved in the U.S. for the treatment of adults living with HIV-1 [news release]. Titusville, NJ: PR Newswire; January 29, 2015. prnewswire.com/news-releases/prezcobix-darunavircobicistat-approved-in-the-us-for-the-treatment-of-adults-living-with-hiv-1-300028193.html. Accessed March 12, 2015.
• Prezcobix [prescribing information]. Titusville, NJ: Janssen Therapeutics; 2015.
• Genvoya [prescribing information]. Foster City, CA: Gilead Sciences; 2015.
• FDA approves new treatment for HIV [news release]. Silver Spring, MD: FDA; November 5, 2015. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm471300.htm. Accessed November 7, 2015.
• Technivie [prescribing information]. North Chicago, IL: AbbVie Inc; 2015.
• FDA approves Technivie for treatment of chronic hepatitis C genotype 4 [news release]. Silver Spring, MD: FDA; July 24, 2015. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455857.htm. Accessed October 26, 2015.
• FDA approves new treatment for chronic hepatitis C genotype 3 infections [news release]. Silver Spring, MD: FDA; July 24, 2015. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455888.htm. Accessed October 26, 2015.
• Daklinza [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; 2015.
• U.S. FDA approves new indications for Harvoni, Gilead’s once-daily single tablet regimen for chronic hepatitis C [news release]. Foster City, CA: Gilead Sciences, Inc; November 12, 2015. http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=2112200. Accessed November 17, 2015.
• Harvoni [prescribing information]. Foster City, CA: Gilead Sciences; 2014.
• Glaptopa [prescribing information]. Princeton, NJ: Sandoz, Inc; 2015.
• FDA approves first generic Copaxone to treat multiple sclerosis [news release]. Silver Spring, MD: FDA; April 16, 2015. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm443143.htm. Accessed April 20, 2015.
• Bayer receives FDA approval for Betaconnect - first and only electronic auto injector in relapsing-remitting multiple sclerosis (RRMS) treatment [news release]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; September 25, 2015. prnewswire.com/news-releases/bayer-receives-fda-approval-for-Betaconnect---first-and-only-electronic-autoinjector-in-relapsing-remitting-multiple-sclerosis-rrms-treatment-300149438.html. Accessed November 3, 2015.
• Betaseron [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; 1993.
• FDA approves Lucentis to treat diabetic retinopathy in patients with diabetic macular edema [news release]. Silver Spring, MD: FDA; February 6, 2015. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm433392.htm. Accessed March 20, 2015.
• Lucentis [prescribing information]. South San Francisco, CA: Genentech, Inc; 2015.
• Eylea (aflibercept) injection receives FDA approval for the treatment of diabetic retinopathy in patients with diabetic macular edema (DME) [news release]. Tarrytown, NY: PR Newswire; March 25, 2015. prnewswire.com/news-releases/eylea-aflibercept-injection-receives-fda-approval-for-the-treatment-of-diabetic-retinopathy-in-patients-with-diabetic-macular-edema-dme-300055839.html. Accessed March 26, 2015.
• Eylea (aflibercept) injection receives FDA approval for the treatment of diabetic macular edema (DME) [news release]. Tarrytown, NY: Regeneron Pharmaceuticals; July 29, 2014. http://files.shareholder.com/downloads/REGN/3851137698x0x772028/698A12F7-A8DC-4F89-B9E2-F8134AE6F3DE/REGN_News_2014_7_29_General_Releases.pdf. Accessed January 16, 2015.
• Eylea (aflibercept) injection receives FDA approval for macular edema following retinal vein occlusion (RVO) [news release]. Tarrytown, NY: Regeneron Pharmaceuticals; October 6, 2014. http://files.shareholder.com/downloads/REGN/3851137698x0x785011/289C9A9E-A261-4750-BBEB-6417A3510B5E/REGN_News_2014_10_6_General_Releases.pdf. Accessed January 16, 2015
• Eylea [prescribing information]. Tarrytown, NY: Regeneron Pharmaceuticals; 2011.
• Praluent [prescribing information]. Bridgewater, NJ: Sanofi-Aventis; 2015.
• FDA approves Praluent to treat certain patients with high cholesterol [news release]. Silver Spring, MD: FDA; July 24, 2015. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455883.htm. Accessed October 26, 2015
• Repatha [prescribing information]. Thousand Oaks, CA: Amgen Inc; 2015.
• FDA approves Repatha to treat certain patients with high cholesterol [news release]. Silver Spring, MD: FDA; August 27, 2015. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm460082.htm. Accessed October 28, 2015
• FDA approves Natpara to control low blood calcium levels in patients with hypoparathyroidism [news release]. Silver Spring, MD: FDA; January 23, 2015. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm431358.htm. Accessed March 12, 2015
• Natpara [prescribing information]. Bedminster, NJ: NPS Pharmaceuticals, Inc; 2015.
• Cresemba [prescribing information]. Northbrook, IL: Astellas Pharma US, Inc; 2015.
• FDA approves new antifungal drug Cresemba [news release]. Silver Spring, MD: FDA; March 6, 2015. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm437106.htm. Accessed March 23, 2015.
• Cholbam [prescribing information]. Baltimore, MD: Asklepion Pharmaceuticals LLC; 2015.
• FDA approves Cholbam to treat rare bile acid synthesis disorders [news release]. Silver Spring, MD: FDA; March 17, 2015. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm438572.htm. Accessed March 23, 2015.
• Novartis announces FDA approval for Jadenu to simplify treatment administration for patients with chronic iron overload, Novartis Pharmaceuticals, March 30, 2015 Available at: novartis.com/newsroom/media-releases/en/2015/1907710.shtml Accessed: April 23, 2015.
• Jadenu [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals; 2015.
• FDA approves treatment for inhalation anthrax [news release]. Silver Spring, MD: FDA; March 25, 2015. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm439752.htm. Accessed March 26, 2015.
• Anthrasil [prescribing information]. Winnipeg, Manitoba, Canada: Cangene Corp; 2015.
• Rapamune [prescribing information]. Philadelphia, PA: Wyeth Pharmaceuticals; 2015.
• FDA approves Rapamune to treat LAM, a very rare lung disease [news release]. Silver Spring, MD: FDA; May 28, 2015. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm448523.htm. Accessed July 9, 2015.
• FDA extends use of Promacta in young children with rare blood disorder [news release]. Silver Spring, MD: FDA; August 24, 2015. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm459430.htm. Accessed September 24, 2015.
• Promacta [prescribing information]. Research Triangle Park, NC: Novartis Pharmaceuticals; 2015.
• Novartis gains FDA approval for Promacta providing new option for children, ages 6 and older, with chronic ITP, a rare blood disorder [news release]. Basel, Switzerland: Novartis Pharmaceuticals; June 12, 2015. novartis.com/news/media-releases/novartis-gains-fda-approval-promacta%C2%AE-providing-new-option-children-ages-6-and. Accessed September 24, 2015.
• Veloxis Announces U.S. FDA Approval of Envarsus XR for Treatment of Kidney Transplant Patients, Veloxis Pharmaceuticals A/S, July 10, 2015 Available at: http://www.prnewswire.com/news-releases/veloxis-announces-us-fda-approval-of-envarsus-xr-for-treatment-of-kidney-transplant-patients- 300111754.html Accessed: October 6, 2015
• Envarsus XR [prescribing information]. Veloxis Pharmaceuticals A/S, July 2015Available at: http://www.envarsusxr.com/files/9214/3870/3957/Final_PI_8.4.15.pdf Accessed: October 6, 2015
• Dysport [prescribing information]. Basking Ridge, NJ: Ipsen Biopharmaceuticals; 2015.
• Ipsen Biopharmaceuticals, Inc announces FDA approval of Dysport (abobotulinumtoxinA) for injection in the treatment of upper limb spasticity in adults in the United States [news release]. Basking Ridge, NJ: Business Wire; July 16, 2015. businesswire.com/news/home/20150716006423/en/Ipsen-Biopharmaceuticals-Announces-FDA-Approval-Dysport%C2%AE-abobotulinumtoxinA Accessed October 26, 2015.
• Keveyis [prescribing information]. Hawthorne, NY: Taro Pharmaceutical Industries Ltd; 2015.
• FDA approves Taro’s Keveyis (dichlorphenamide) 50 mg tablets for primary hyperkalemic and hypokalemic periodic paralysis [news release]. Hawthorne, NY: Taro Pharmaceuticals Ltd; August 10, 2015. businesswire.com/news/home/20150810005655/en/FDA-Approves-Taro%E2%80%99s-Keveyis%E2%84%A2-dichlorphenamide-50-mg. Accessed October 27, 2015.
• Procysbi [prescribing information]. Novato, CA: Raptor Pharmaceutical; 2013.
• Raptor Pharmaceutical receives FDA approval of expanded label for Procysbi to treat children aged 2-6 years with nephropathic cystinosis [news release]. Novato, CA: Raptor Pharmaceutical; August 17, 2015. http://ir.raptorpharma.com/releasedetail.cfm?ReleaseID=927832. Accessed October 27, 2015.
• FDA approves new orphan drug to treat rare autosomal recessive disorder [news release]. Silver Spring, MD: FDA; September 4, 2015. fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm457867.htm. Accessed October 29, 2015.
• Xuridan [prescribing information]. Gaithersburg, MD: Wellstat Therapeutics Corp; 2015.

About the Author

STACEY NESS, PHARM D, RPH, CSP, MSCS, AAHIVP, has worked in both national specialty pharmacy and payer organizations and has experience in clinical management, adherence, and persistency programs, as well as chronic disease cost optimization strategies. Dr. Ness is active in the Consortium of Multiple Sclerosis Centers, Academy of Managed Care Pharmacy, National Home Infusion Association, National Association of Specialty Pharmacy, Specialty Pharmacy Certification Board, and Hematology and Oncology Pharmacy Association, and has served on the Minnesota Medicaid Drug Formulary Committee since 2008. She is a certified multiple sclerosis specialist, a credentialed HIV pharmacist, a Certified Specialty Pharmacist, and currently serves as the director of specialty clinical services at Managed Health Care Associates, Inc, a health care services organization based in Florham Park, New Jersey.

RUBY MHAJAN, RPH, currently serves as a clinical pharmacist at Managed Health Care Associates, Inc, a health care services organization based in Florham Park, New Jersey. Ruby has over 13 years of exceptional experience as a clinical pharmacist, having worked in both the United States and Canada in various settings including retail, long-term care, home infusion/specialty, and a national outsourcing admixture pharmacy. Most recently, she served as a Director of Pharmacy for a Home Infusion/Specialty Pharmacy in New York.