I. New Pharmaceuticals: New Molecular Entities and New Biologic License Applications Approved in 2014
Akynzeo (NME; new combination)
(Netupitant [NME] and palonosetron; Eisai)
Class/route: Antiemetic; oral
Indication: For the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of chemotherapy
Beleodaq (NME)
(Belinostat; Spectrum Pharmaceuticals)
Class/route: Histone deacetylase inhibitor; intravenous
Indication: For the treatment of patients with relapsed or refractory peripheral T-cell lymphoma, a type of NHL
Approval considerations: Accelerated approval, priority review, orphan drug
Belsomra (NME)
(Suvorexant; Merck, Sharpe & Dohme Corporation)
Class/route: Orexin receptor antagonist; oral
Indication: For the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance
Blincyto (BLA)
(Blinatumomab; Amgen)
Class/route: CD19-directed CD3 T-cell engager; intravenous
Indication: Treatment of Philadelphia chromosome–negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia
Approval considerations: Breakthrough therapy, priority review, orphan drug, REMS
Cerdelga (NME)
(Eliglustat; Genzyme)
Class/route: Glucosylceramide synthase inhibitor; oral
Indication: For long-term treatment of adults with Gaucher disease type 1 who are CYP2D6 extensive metabolizers, intermediate metabolizers, or poor metabolizers as detected by an FDA-cleared test
Approval considerations: Priority review, orphan drug
Cyramza (BLA)
(Ramucirumab; Eli Lilly)
Class/route: Human vascular endothelial growth factor receptor-2 antagonist; intravenous
Indications: As a single agent or in combination with paclitaxel, for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma, in patients with disease progression during or after previous fluoropyrimidine- or platinum-containing chemotherapy; in combination with docetaxel, for the treatment of metastatic non–small-cell lung cancer in patients with disease progression during or after platinum-based chemotherapy
Approval considerations: Priority review, orphan drug
Dalvance (NME)
(Dalbavancin; Durata Therapeutics)
Class/route: Glycopeptide antibiotic; intravenous
Indication: Treatment of adults with acute bacterial skin and skin structure infections caused by susceptible isolates of the gram-positive microorganisms Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus anginosus
Approval consideration: Priority review, QIDP
Entyvio (BLA)
(Vedolizumab; Takeda Pharmaceuticals)
Class/route: Integrin receptor antagonist; intravenous
Indications: Treatment of adults with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to a TNF blocker or an immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids; treatment of adults with moderately to severely active Crohn’s disease who have had an inadequate response with, lost response to, or were intolerant to a TNF blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids
Approval consideration: Priority review
Esbriet (NME)
(Pirfenidone; InterMune)
Class/route: Pyridone; oral
Indication: Treatment of idiopathic pulmonary fibrosis
Approval considerations: Breakthrough therapy, fast track, priority review, orphan drug
Farxiga (NME)
(Dapaglifozin; Bristol-Myers Squibb/AstraZeneca)
Class/route: SGLT2 inhibitor; oral
Indications: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
Harvoni (NME; new combination)
(Ledipasvir [NME] and sofosbuvir; Gilead Sciences)
Classes/route: Fixed-dose combination of an HCV NS5A inhibitor and an HCV nucleotide analog NS5B polymerase inhibitor; oral
Indication: Treatment of genotype 1 chronic hepatitis C infection in adults; first fixed-dose combination without interferon or ribavirin
Approval considerations: Priority review, breakthrough therapy
[2015 new dosages approved: 5 mg; 10 mg]
Hetlioz (NME)
(Tasimelteon; Vanda Pharmaceuticals)
Class/route: Melatonin receptor agonist; oral
Indication: Treatment of non–24-hour sleep-wake disorder
Approval considerations: Priority review, orphan drug
Impavido (NME)
(Miltefosine; Paladin Therapeutics)
Class/route: Anthelmintic antineoplastic; oral
Indications: For the treatment of individuals aged ≥12 years weighing ≥66 lb (30 kg) with visceral leishmaniasis resulting from Leishmania donovani; cutaneous leishmaniasis resulting from Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis; and mucosal leishmaniasis resulting from L braziliensis
Approval considerations: Fast track, priority review, orphan drug
Jardiance (NME)
(Empagliflozin; Boehringer Ingelheim)
Class/route: SGLT2 inhibitor; oral
Indication: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
Jublia (NME)
(Efinaconazole; Valeant Pharmaceuticals International)
Class/route: Triazole antifungal agent; topical
Indication: For the treatment of onychomycosis of the toenails resulting from Trichophyton rubrum and Trichophyton mentagrophytes
Kerydin (NME)
(Tavaborole; Anacor Pharmaceuticals)
Class/route: Oxaborole antifungal; topical
Indication: For the treatment of onychomycosis of the toenails resulting from Trichophyton rubrum or Trichophyton mentagrophytes
Keytruda (BLA)
(Pembrolizumab; Merck)
Class/route: PD-1–blocking antibody; intravenous
Indication: Treatment of patients with unresectable or metastatic melanoma and disease progression after ipilimumab therapy and, if BRAF V600 mutation–positive, a BRAF inhibitor
Approval considerations: Breakthrough therapy, accelerated approval, priority review, orphan drug
Lumason (NME)
(Sulfur hexafluoride lipid microsphere; Bracco Diagnostics)
Class/route: Ultrasound contrast agent; intravenous
Indication: For use in patients with suboptimal echocardiograms to opacify the left-ventricular chamber and to improve the delineation of the left-ventricular endocardial border
Lynparza (NME)
(Olaparib; AstraZeneca)
Class/route: Poly (ADP-ribose) polymerase inhibitor; oral
Indications: For advanced ovarian cancer in patients with deleterious or suspected deleterious germline BRCA mutation (as detected by an FDA-approved test) who have been treated with 3 or more previous lines of chemotherapy
Approval considerations: Accelerated approval, priority review, orphan drug
Movantik (NME)
(Naloxegol; AstraZeneca)
Class/route: Peripherally acting opioid receptor antagonists; oral
Indication: For opioid-induced constipation in adults with chronic noncancer pain
Approval consideration: Priority review
Myalept (BLA)
(Metreleptin; Amylin Pharmaceuticals)
Class/route: Leptin analog; subcutaneous
Indication: For the treatment of complications of leptin deficiency, as replacement therapy, in addition to diet, in patients with congenital generalized or acquired generalized lipodystrophy
Approval considerations: Priority review, orphan drug, REMS
Neuraceq (NME)
(Florbetaben F18 injection; Piramal Imaging)
Class/route: Radioactive diagnostic agent; intravenous
Indication: For positron emission tomography imaging of the brain to estimate beta-amyloid neuritic plaque density in adults with cognitive impairment who are being evaluated for Alzheimer’s disease and other causes of cognitive decline
Northera (NME)
(Droxidopa; Chelsea Therapeutics)
Class/route: Vasopressor; oral
Indication: Treatment of orthostatic dizziness, lightheadedness, or the “feeling that you are about to black out” in adults with symptomatic neurogenic orthostatic hypotension caused by primary autonomic failure (Parkinson’s disease, multiple system atrophy, and pure autonomic failure), dopamine beta-hydroxylase deficiency, and nondiabetic autonomic neuropathy
Approval considerations: Accelerated approval, priority review, orphan drug
Ofev (NME)
(Nintedanib; Boehringer Ingelheim)
Class/route: Tyrosine kinase inhibitor; oral
Indication: Treatment of idiopathic pulmonary fibrosis
Approval considerations: Breakthrough therapy, fast track, priority review, orphan drug
Opdivo (BLA)
(Nivolumab; Bristol-Myers Squibb)
Class/route: PD-1–blocking antibody; intravenous
Indication: Treatment of unresectable or metastatic melanoma and disease progression after ipilimumab and, if BRAF V600 mutation–positive, a BRAF inhibitor
Approval considerations: Breakthrough therapy, accelerated approval, priority review, orphan drug
[2015 new indication: lung cancer]
Orbactiv (NME)
(Oritavancin; The Medicines Company)
Class/route: Lipoglycopeptide antibacterial drug; intravenous
Indication: Treatment of adults with acute bacterial skin and skin structure infections caused or suspected to be caused by susceptible bacteria, including S aureus (including methicillin-susceptible and methicillin-resistant strains), various Streptococcus species, and Enterococcus faecalis
Approval considerations: Priority review, QIDP
Otezla (NME)
(Apremilast; Celgene)
Class/route: Phosphodiesterase 4 inhibitor; oral
Indications: Treatment of adults with active psoriatic arthritis, and patients with moderate-to-severe plaque psoriasis who are candidates for phototherapy or systemic therapy
Plegridy (BLA)
(Peginterferon beta-1a; Biogen Idec)
Class/route: Interferon beta; subcutaneous
Indication: Treatment of relapsing forms of multiple sclerosis
Rapivab (NME)
(Peramivir; BioCryst Pharmaceuticals)
Class/route: Neuraminidase inhibitor; intravenous
Indication: Treatment of acute uncomplicated influenza in patients aged ≥18 years who have been symptomatic for no more than 2 days
Sivextro (NME)
(Tedizolid phosphate; Cubist Pharmaceuticals)
Class/route: Oxazolidinone-class antibacterial; intravenous and oral
Indication: Treatment of adults with acute bacterial skin and skin structure infections caused by designated susceptible bacteria, including S aureus (including methicillinresistant strains and methicillin-susceptible strains), various Streptococcus species, and E faecalis
Approval considerations: Priority review, QIDP
Striverdi Respimat (NME)
(Olodaterol; Boehringer Ingelheim)
Class/route: Long-acting beta2-adrenergic agonist; oral inhalation
Indication: For long-term, once-daily maintenance bronchodilator treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema
Sylvant (BLA)
(Siltuximab; Janssen Biotech)
Class/route: Interleukin-6 antagonist; intravenous
Indication: Treatment of patients with multicentric Castleman’s disease who are HIV-negative and human herpesvirus-8–negative
Approval considerations: Priority review, orphan drug
Tanzeum (BLA)
(Albiglutide; GlaxoSmithKline)
Class/route: GLP-1 receptor agonist; subcutaneous
Indication: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
Approval consideration: REMS
Trulicity (BLA)
(Dulaglutide; Lilly)
Class/route: GLP-1 receptor agonist; subcutaneous
Indication: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
Approval consideration: REMS
Viekira Pak (NME; new combination)
(Ombitasvir [NME], paritaprevir [NME], and ritonavir, copackaged with dasabuvir [NME]; AbbVie)
Classes/route: HCV NS5A inhibitor, HCV NS3/4A protease inhibitor, and HCV nonnucleoside NS5B palm polymerase inhibitor; oral
Indication: For the treatment, with or without ribavirin, of patients with genotype 1 chronic HCV infection, including those with compensated cirrhosis; fixed-dose combination
Approval considerations: Breakthrough therapy, priority review
Vimizim (BLA)
(Elosulfase alfa; BioMarin Pharmaceutical)
Class/route: Hydrolytic lysosomal glycosaminoglycan–specific enzyme; intravenous
Indication: Treatment of mucopolysaccharidosis type IVA (Morquio A syndrome)
Approval considerations: Priority review, orphan drug
Xtoro (NME)
(Finafloxacin; Alcon Laboratories)
Class/route: Fluoroquinolone antimicrobial; topical otic suspension
Indication: Treatment of acute otitis externa caused by susceptible strains of Pseudomonas aeruginosa and S aureus
Approval consideration: Priority review
Zerbaxa (NME; new combination)
(Ceftolozane [NME] and tazobactam; Cubist Pharmaceuticals)
Class/route: A cephalosporin antibacterial drug and a beta-lactamase inhibitor; intravenous
Indications: For the treatment of complicated intra-abdominal infections, in combination with metronidazole, and for the treatment of complicated urinary tract infections, including pyelonephritis
Approval considerations: Priority review, QIDP
Zontivity (NME)
(Vorapaxar; Merck)
Class/route: Protease-activated receptor-1 antagonist; oral
Indication: For the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease
Zydelig (NME)
(Idelalisib; Gilead Sciences)
Class/route: Phosphoinositide-3 kinase-delta inhibitor; oral
Indications: Treatment of relapsed chronic lymphocytic leukemia, in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy because of other comorbidities; relapsed follicular B-cell NHL in patients who have received at least 2 previous systemic therapies; and relapsed small lymphocytic lymphoma in patients who have received at least 2 previous systemic therapies
Approval considerations: Accelerated approval, priority review, orphan drug, REMS
Zykadia (NME)
(Ceritinib; Novartis)
Class/route: ALK tyrosine kinase inhibitor; oral
Indication: Treatment of ALK-positive metastatic non–small-cell lung cancer in patients who have progressed on or are intolerant to crizotinib
Approval considerations: Breakthrough therapy, accelerated approval, priority review, orphan drug
ALK indicates anaplastic lymphoma kinase; BLA, biologic license application; COPD, chronic obstructive pulmonary disease; FDA, US Food and Drug Administration; GLP-1, glucagon-like peptide-1; HCV, hepatitis C virus; NHL, non-Hodgkin lymphoma; NME, new molecular entity; QIDP, Qualified Infectious Disease Product; PD-1, programmed-cell death 1; REMS, Risk Evaluation and Mitigation Strategy; SGLT2, sodium-glucose cotransporter 2; TNF, tumor necrosis factor.
II. New Combinations and New Indications Approved in 2014
Afrezza (new indication)
(Insulin human; MannKind Corporation)
Class/route: Insulin human; inhaled powder
New indication: Rapid-acting insulin to be used at the beginning of each meal to improve glycemic control in adults with type 1 or type 2 diabetes mellitus
New formulation: Rapid-acting inhaled insulin
Approval consideration: REMS
Akynzeo (new combination) See NMEs/BLAs listing
Arzerra (new indication)
(Ofatumumab; GlaxoSmithKline)
Class/route: CD20 monoclonal antibody; intravenous
New indication: For first-line treatment, in combination with chlorambucil, of treatment-naïve patients with CLL for whom fludarabine-based therapy is inappropriate
Existing indication: For the treatment of patients with CLL that is refractory to fludarabine or to alemtuzumab
Avastin (new indications)
(Bevacizumab; Genentech)
Class/route: VEGF-specific angiogenesis inhibitor; intravenous
New indications: For the treatment of persistent, recurrent, or metastatic cervical cancer in combination with paclitaxel and cisplatin or paclitaxel and topotecan; and for the treatment of platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan
Existing indications: First-line or second-line treatment of metastatic colorectal cancer with intravenous 5-fluorouracil–based chemotherapy; for second-line treatment of metastatic colorectal cancer in patients who have progressed on a first-line bevacizumab-containing regimen with fluoropyrimidine- irinotecan- or, fluoropyrimidine-oxaliplatin–based chemotherapy; with carboplatin and paclitaxel for first-line treatment of unresectable, locally advanced, recurrent or metastatic nonsquamous non–small-cell lung cancer; and as a single agent for adults with progressive glioblastoma after previous therapy; metastatic renal-cell carcinoma with interferon alfa
Approval consideration: Priority review
Contrave (new combination)
(Naltrexone and bupropion; Takeda Pharmaceuticals)
Classes/route: Opioid antagonist and aminoketone antidepressant; oral
Indication: As an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index of ≥30 kg/m2 or ≥27 kg/m2 in the presence of at least ≥1 weight-related comorbidities
Eliquis (new indications)
(Apixaban; Bristol-Myers Squibb)
Class/route: Factor Xa inhibitor anticoagulant; oral
New indications: For prophylactic therapy of DVT that may lead to PE in patients who have undergone hip/knee replacement surgery; for the treatment of DVT and PE, and for risk reduction of recurrent DVT and PE after initial therapy
Existing indication: For risk reduction of stroke and systemic embolism in patients with nonvalvular atrial fibrillation
Approval consideration: REMS
Eylea (new indications)
(Aflibercept; Regeneron Pharmaceuticals)
Class/route: VEGF inhibitor; intravitreal
New indications: For the treatment of diabetic macular edema; first VEGF inhibitor approved for dosing on a less than monthly basis for the treatment of diabetic macular edema
Existing indications: For the treatment of neovascular (wet) age-related macular degeneration, and for the treatment of macular edema after retinal vein occlusion
Approval considerations: Breakthrough therapy, priority review
[2015 new indication: Diabetic retinopathy in patients with diabetic macular edema]
Harvoni (new combination) See NMEs/BLAs listing
Humira (new patient population)
(Adalimumab; AbbVie)
Class/route: Tumor necrosis factor blocker; subcutaneous
New patient population: Pediatric Crohn’s disease patients aged ≥6 years
Indications: For reducing the signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adults with moderately to severely active rheumatoid arthritis; reducing the signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients aged ≥2 years; reducing the signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adults with active psoriatic arthritis; reducing the signs and symptoms of active ankylosing spondylitis in adults; reducing the signs and symptoms and inducing and maintaining clinical remission in adults with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy; reducing the signs and symptoms and inducing and maintaining clinical remission in patients aged ≥6 years with moderately to severely active Crohn’s disease who have had an inadequate response to corticosteroids or immunomodulators, such as azathioprine, 6-mercaptopurine, or methotrexate; inducing and sustaining clinical remission in adults with moderately to severely active ulcerative colitis who have had an inadequate response to immunosuppressants, such as corticosteroids, azathioprine, or 6-mercaptopurine; treatment of adults with moderate-to-severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate
Imbruvica (new indication)
(Ibrutinib; Pharmacyclics)
Class/route: Bruton’s tyrosine kinase inhibitor; oral
New indications: Treatment of patients with relapsed CLL who have received at least 1 previous therapy and treatment of patients with CLL with 17p deletion
Existing indication: Treatment of patients with mantle-cell lymphoma who have received at least 1 previous therapy
Approval considerations: Breakthrough therapy, priority review, orphan drug
[2015 new indication: Waldenström’s macroglobulinemia]
Invega Sustenna (new indication)
(Paliperidone palmitate; Janssen Pharmaceuticals)
Class/route: Atypical antipsychotic; oral
New indication: For the once-monthly treatment of schizoaffective disorder, as monotherapy and as an adjunct to mood stabilizers and/or antidepressants (first FDA approval for this indication)
Indication: Treatment of schizophrenia
Invokamet (new combination)
(Canagliflozin and metformin hydrochloride; Janssen Pharmaceuticals)
Classes/route: SGLT2 inhibitor and biguanide; oral
Indication: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are not adequately controlled with a regimen containing metformin or canagliflozin or in patients already receiving canagliflozin and metformin
Jakafi (new indication)
(Ruxolitinib; Incyte Corporation)
Class/route: Janus-associated kinase inhibitor; oral
New indication: For the treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea
Existing indication: For the treatment of intermediate-risk or high-risk myelofibrosis
Approval considerations: Priority review, orphan drug
Lemtrada (new indication)
(Alemtuzumab; Genzyme Corporation)
Class/route: CD52-directed cytolytic monoclonal antibody; intravenous
New indication: For the treatment of patients with relapsing forms of multiple sclerosis
Existing indication: For the treatment of B-cell CLL
Mekinist plus Tafinlar (new combination)
(Trametinib and dabrafenib; GlaxoSmithKline)
Classes/route: BRAF kinase inhibitor and MEK kinase inhibitor; oral
Indication: For the treatment of advanced melanoma that is unresectable or metastatic in patients with the BRAF V600E or BRAF V600K mutation
Approval considerations: Accelerated approval, priority review
Minivelle (new indication)
(Estradiol; Noven Pharmaceuticals)
Class/route: Estrogen; transdermal
New indication: For the prevention of postmenopausal osteoporosis
Existing indication: Treatment of moderate-to-severe vasomotor symptoms resulting from menopause
Namzaric (new combination)
(Memantine hydrochloride extended release and donepezil hydrochloride; Forest Laboratories)
Classes/route: NMDA receptor antagonist and acetylcholinesterase inhibitor; oral
Indication: For the treatment of moderate-to-severe dementia of the Alzheimer’s type in patients stabilized on memantine hydrochloride and donepezil hydrochloride
Obredon (new combination)
(Hydrocodone bitartrate and guaifenesin; Novotec Pharma)
Classes/route: Opioid antitussive and expectorant; oral
Indications: For the symptomatic relief of cough and to loosen mucus associated with the common cold
Olysio (new combination)
(Simeprevir; Janssen; for use with sofosbuvir [Sovaldi; Gilead])
Class/route: HCV NS3/4A protease inhibitor; oral
New combination: For use in combination with sofosbuvir as an all-oral, interferon-free, ribavirin-free treatment for adults with genotype 1 chronic HCV infection
Existing combination: For the treatment of genotype 1 chronic HCV infection in combination with pegylated interferon and ribavirin regimen
Omidria (new combination)
(Phenylephrine and ketorolac; Omeros Corporation)
Classes/route: Alpha 1-adrenergic receptor agonist and nonselective cyclooxygenase inhibitor; intraocular
Indications: For the maintenance of pupil size by preventing intraoperative miosis and for reducing postoperative pain
Onexton (new combination)
(Clindamycin/benzoyl peroxide; Valeant Pharmaceuticals International)
Class/route: Lincosamide antibacterial; topical gel
Indication: For the topical treatment of acne vulgaris in patients aged ≥12 years
Ozurdex (new indication)
(Dexamethasone; Allergan)
Class/route: Corticosteroid; intravitreal injection
New indication: For the treatment of diabetic macular edema
Existing indications: Treatment of macular edema after branch retinal vein occlusion or central retinal vein occlusion, and for the treatment of noninfectious uveitis affecting the posterior segment of the eye
Priftin (new indication)
(Rifapentine; sanofi-aventis)
Class/route: Rifamycin antimycobacterial; oral
New indication: In combination with isoniazid, for the treatment of latent tuberculosis infection in patients aged ≥2 years who are at high risk for progression to
tuberculosis disease
Existing indication: For the treatment of active pulmonary tuberculosis in adults and children aged ≥12 years caused by Mycobacterium tuberculosis
Promacta (new indication)
(Eltrombopag; GlaxoSmithKline)
Class/route: Thrombopoietin receptor agonist; oral
New indication: For the treatment of patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy
Existing indications: For the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy; thrombocytopenia in patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy
Approval considerations: Breakthrough therapy, priority review
Saxenda (new version of Victoza; new indication)
(Liraglutide [rDNA origin] injection; Novo Nordisk)
Class/route: GLP-1 receptor agonist; subcutaneous
New indication: For chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity in adults with an initial body mass index
≥30 kg/m2 or ≥27 kg/m2 and at least 1 weight-related comorbid condition; this is a new version of Victoza (liraglutide [rDNA origin]), which is indicated for adults with type 2 diabetes
Approval consideration: REMS
Somatuline Depot (new indication)
(Lanreotide; Ipsen Pharmaceuticals)
Class/route: Somatostatin analog; injection
New indication: For the treatment of patients with unresectable, moderately or well-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors to improve progression-free survival
Existing indication: For the long-term treatment of acromegalic patients who have had an inadequate response to or cannot be treated with surgery and/or radiotherapy
Soolantra (new indication; new formulation)
(Ivermectin 1%; Galderma)
Class/route: Antibiotic-free anti-inflammatory cream; topical
New indication: For once-daily treatment of patients with inflammatory lesions, bumps, and pimples, of rosacea; this is the first time ever ivermectin cream is approved for use in humans; it was previously only available for use (in different form) in livestock
New formulation: 1% cream for humans
Trezix (new combination)
(Acetaminophen, caffeine, and dihydrocodeine bitartrate; WraSer Pharmaceuticals)
Classes/route: Nonopiate, nonsalicylate analgesic and antipyretic; central nervous system and cardiovascular stimulant; and semisynthetic narcotic analgesic; oral
Indication: Relief of moderate-to-moderately severe pain
Triumeq (new combination)
(Abacavir, dolutegravir, and lamivudine; ViiV Healthcare)
Classes/route: Integrase strand transfer inhibitor (dolutegravir) and nucleoside analogue reverse transcriptase inhibitors (abacavir and lamivudine); oral
Indication: For the treatment of patients with HIV-1 infection
Velcade (new indications)
(Bortezomib; Millennium Pharmaceuticals)
Class/routes: Proteasome inhibitor; intravenous, subcutaneous
New indications: Retreatment of adults with multiple myeloma that had previously responded to bortezomib and relapsed at least 6 months after completion of previous treatment with bortezomib; first-line treatment of newly diagnosed patients with mantle-cell lymphoma
Existing indications: For the treatment of patients with multiple myeloma or with mantle-cell lymphoma
Viekira Pak (new combination) See NMEs/BLAs listing
Vitekta (new combination)
(Elvitegravir; Gilead Sciences)
Class/route: HIV-1 integrase strand transfer inhibitor; oral
Indication: Used in combination with an HIV protease inhibitor coadministered with ritonavir and with other antiretroviral drug(s) for the treatment of HIV-1 infection in antiretroviral treatment–experienced adults
Xgeva (new indication)
(Denosumab; Amgen)
Class/route: RANK ligand inhibitor; subcutaneous
New indication: Treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy
Existing indications: Prevention of skeletal-related events in patients with bone metastases from solid tumors, and for the treatment of adults and skeletally mature adolescents with giant-cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity
Approval consideration: Orphan drug
Xigduo XR (new combination)
(Dapagliflozin and metformin hydrochloride extended release; AstraZeneca)
Classes/route: SGLT2 inhibitor and biguanide; oral
Indication: To improve glycemic control in adults with type 2 diabetes when treatment with dapagliflozin and with metformin is appropriate
Xolair (new indication)
(Omalizumab; Genentech)
Class/route: Anti-immunoglobulin E antibody; subcutaneous
New indication: First biologic and first medicine approved by the FDA for the treatment of chronic idiopathic urticaria in adults and adolescents aged ≥12 years who remain symptomatic despite H1 antihistamine treatment
Existing indication: Treatment of moderate-to-severe persistent asthma in patients aged ≥12 years with a positive skin test or in vitro reactivity to a perennial aeroallergen and symptoms that are inadequately controlled with inhaled corticosteroids
Zerbaxa (new combination) See NMEs/BLAs listing
Zorvolex (new indication)
(Diclofenac; Iroko Pharmaceuticals)
Class/route: NSAID; oral
New indication: For the management of osteoarthritis pain
Existing indication: For the management of mild-to-moderate acute pain
BLA indicates biologic license application; CLL, chronic lymphocytic leukemia; DVT, deep-vein thrombosis; GLP-1, glucagon-like peptide-1; HCV, hepatitis C virus; NMDA, N-methyl-D-aspartate; NME, new molecular entity; NSAID, nonsteroidal anti-inflammatory drug; PE, pulmonary embolism; REMS, Risk Evaluation and Mitigation Strategy; SGLT2, sodium-glucose cotransporter 2; VEGF, vascular endothelial growth factor.
III. New Formulations/Dosage Forms/Dosages/Patient Population Approved in 2014
Abilify Maintena (new dosage form)
(Aripiprazole; Otsuka Pharmaceutical)
Class/route: Atypical antipsychotic; intramuscular
New dosage form: Extended-release injectable suspension in a prefilled dual-chamber syringe
Indication: For the treatment of schizophrenia
Acticlate (new dosages)
(Doxycycline hyclate USP; Aqua Pharmaceuticals)
Class/route: Tetracycline-class antimicrobial; oral
New dosages: 75-mg and 150-mg tablets
Indications: For the treatment of Rickettsial infections, sexually transmitted infections, respiratory tract infections, specific bacterial infections, ophthalmic infections, and anthrax, including inhalational anthrax (postexposure); alternative treatment for selected infections when penicillin is contraindicated; adjunctive therapy in acute intestinal amebiasis and severe acne; prophylaxis of malaria
Arnuity Ellipta (new formulation)
(Fluticasone furoate; GlaxoSmithKline)
Class/route: Corticosteroid; oral inhalation
New formulation: Once-daily oral inhalation of 100 mcg or 200 mcg using Ellipta inhaler
Indication: For the once-daily maintenance treatment of asthma as prophylactic therapy in patients aged ≥12 years
Auryxia (new formulation)
(Ferric citrate: Keryx Biopharmaceuticals)
Class/route: Phosphate binder; oral
New formulation: The first and only absorbable iron-based phosphate binder proven to manage hyperphosphatemia
Indication: For the control of serum phosphorus levels in patients with chronic kidney disease on dialysis
Aveed (new formulation)
(Testosterone undecanoate; Endo Pharmaceuticals)
Class/route: Androgen; intramuscular injection
New formulation: Intramuscular; already available in oral, subcutaneous, buccal, and transdermal formulations
Indication: For testosterone replacement therapy in adult men for conditions associated with a deficiency or absence of endogenous testosterone, such as congenital or acquired primary hypogonadism, or congenital or acquired hypogonadotropic hypogonadism
Approval consideration: REMS
Bunavail (new formulation)
(Buprenorphine and naloxone; BioDelivery Sciences)
Class/route: Partial opioid agonist; oral
New formulation: Buccal film
Indication: For the maintenance treatment of opioid dependence
Bydureon (new dosage form)
(Exenatide; AstraZeneca)
Class/route: GLP-1 receptor agonist; subcutaneous
New dosage form: Extended-release formula in a 2-mg pen; already available as a single-dose tray containing a 2-mg vial
Indication: As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
Copaxone (new dosage)
(Glatiramer acetate; Teva Pharmaceutical Industries)
Class/route: Immunomodulator; subcutaneous injection
New dosage: Three-times weekly of 40 mg/mL, a less frequent dose than the 20 mg/mL daily that is still available for use
Indication: For the treatment of patients with relapsing form of multiple sclerosis
Dyloject (new dosage form)
(Diclofenac; Hospira)
Class/route: NSAID; intravenous
New dosage form: Intravenous bolus injection over 15 seconds
Indications: For use in adults for the management of mild-to-moderate pain and for the management of moderate-to-severe pain alone or in combination with opioid analgesics
Embeda (new formulation)
(Morphine sulfate and naltrexone hydrochloride; Pfizer)
Classes/route: Opioid agonist and opioid antagonist; oral
New formulation: Has properties that are expected to reduce oral abuse when the drug is crushed; capsules should be swallowed whole to avoid exposure to a potentially fatal dose of morphine
Indication: For the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate
Epanova (new formulation)
(Omega-3-carboxylic acids; AstraZeneca)
Class/route: Omega-3 fatty acid; oral
New formulation: Omega-3 in free fatty acid form
Indications: As an adjunct to diet to reduce triglyceride levels in adults with severe (≥500 mg/dL) hypertriglyceridemia
Erwinaze (new dosage form)
(Asparaginase Erwinia chrysanthemi; Jazz Pharmaceuticals)
Class/routes: Antineoplastic; intramuscular, intravenous
New dosage form: Intravenous
Indication: As a component of a multiagent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia who have developed hypersensitivity to Escherichia coli–derived asparaginase
Evzio (new formulation)
(Naloxone hydrochloride; Kaleo)
Class/routes: Opioid antagonist; intramuscular, subcutaneous
New formulation: Handheld autoinjector
Indication: For the treatment of proliferating infantile hemangioma requiring systemic therapy
Approval consideration: Priority review
Granix (new dosage form)
(Tbo-filgrastim; Teva Pharmaceutical Industries)
Class/route: Leukocyte growth factor; subcutaneous
New dosage form: Injection for self-administration by patients and caregivers; previously only for administration by a healthcare professional
Indication: For reduction in the duration of severe neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia
Hemangeol (new formulation)
(Propranolol hydrochloride; Pierre Fabre Dermatologie)
Class/route: Beta-adrenergic blocker; oral
New formulation: Oral solution for pediatric use
Indication: For the treatment of proliferating infantile hemangioma requiring systemic therapy
Approval consideration: Orphan drug
Hysingla ER (new formulation)
(Hydrocodone bitartrate; Purdue Pharma)
Class/route: Opioid agonist; oral
New formulation: Extended-release opioid tablet with abuse-deterrent properties that make it difficult to crush, break, or dissolve, which is intended to reduce, but not entirely prevent, abuse of the drug when taken orally/chewed
Indication: For the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate
Approval considerations: Priority review, REMS
Iluvien (new dosage form)
(Fluocinolone acetonide intravitreal implant; Alimera Sciences)
Class/route: Corticosteroid; intravitreal injection
New dosage form: Single injection of the microinsert provides sustained treatment for 36 months
Indication: Treatment of diabetic macular edema in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure
Incruse Ellipta (new formulation)
(Umeclidinium; GlaxoSmithKline)
Class/route: Anticholinergic; oral inhalation
New formulation: Once-daily bronchodilator
Indication: For long-term, once-daily maintenance treatment of airflow obstruction in patients with COPD
Izba (new dosage)
(Travoprost; Alcon Laboratories)
Class/route: Prostaglandin analog; ophthalmic solution
New dosage: 0.003% ophthalmic solution; already available as a 0.004% solution
Indication: For reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension
Kalbitor (new patient population)
(Ecallantide; Dyax Corporation)
Class/route: Plasma kallikrein inhibitor; subcutaneous
New patient population: For the treatment of patients aged ≥12 years; previously indicated only for adults
Indication: Treatment of acute attacks of hereditary angioedema in patients aged ≥12 years
Kalydeco (new patient population)
(Ivacaftor; Vertex Pharmaceuticals Incorporated)
Class/route: CFTR; oral
New patient population: Treatment of cystic fibrosis in patients aged ≥6 years who have the R117H mutation in the CFTR gene
Indication: For the treatment of cystic fibrosis in patients aged ≥6 years who have 1 of the following mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R
[2015 new patient population: All indications were expanded to include patients aged 2-5 years]
Kerydin (new dosage form)
(Tavaborole; Anacor Pharmaceuticals)
Class/route: Oxaborole antifungal; topical
New dosage form: First oxaborole antifungal available as a topical solution
Indication: Topical treatment of onychomycosis of the toenails from Trichophyton rubrum or Trichophyton mentagrophytes
Lumizyme (new patient population)
(Alglucosidase alfa; Genzyme Corporation)
Class/route: Hydrolytic lysosomal glycogen-specific enzyme; intravenous
New patient population: Treatment of patients with infantile-onset Pompe disease, including patients aged <8 years
Existing indication: For patients aged ≥8 years with Pompe disease
Minivelle (new dosage) See New Combinations/Indications listing
Monovisc (new dosage form)
(Sodium hyaluronate; Anika Therapeutics)
Class/route: High-molecular-weight hyaluronic acid; intra-articular
New dosage form: First FDA-approved single injection with hyaluronic acid from a nonanimal source
Indication: For the treatment of pain in osteoarthritis of the knee in patients who have failed to respond adequately to conservative nonpharmacologic therapy or simple analgesics (eg, acetaminophen)
Natesto (new formulation)
(Testosterone; Endo Pharmaceuticals)
Class/route: Androgen; intranasal
New formulation: Nasal gel; already available as a topical gel, subcutaneous pellet, transdermal patch, oral tablet, intramuscular injection, buccal patch
Indication: For replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone
Noxafil (new formulation)
(Posaconazole; Merck Sharp & Dohme Corporation)
Class/routes: Azole antifungal; intravenous, oral
New formulation: Intravenous injection; already available as delayed-release tablets and oral suspension
Indications: As an intravenous injection, delayed-release tablets, and oral suspension, for prophylaxis of invasive Aspergillus and Candida infections in patients at high risk of developing these infections as a result of being severely immunocompromised, such as recipients of hematopoietic stem-cell transplant with graft versus host disease or those with hematologic malignancies with prolonged neutropenia from chemotherapy; as an oral suspension, for the treatment of oropharyngeal candidiasis, including oropharyngeal candidiasis refractory to itraconazole and/or fluconazole
Approval consideration: Priority review
Pennsaid 2% (new dosage)
(Diclofenac sodium; Horizon Pharma)
Class/route: NSAID; topical
Indication: For the treatment of osteoarthritis pain of the knee
New dosage: First twice-daily topical NSAID available in the United States for the treatment of pain of osteoarthritis of the knee
Priftin (new patient population) See New Combinations/Indications listing
Purixan (new formulation)
(Mercaptopurine; Nova Laboratories)
Class/route: Nucleoside metabolic inhibitor; oral
New formulation: Oral suspension
Indication: For the treatment of patients with acute lymphoblastic leukemia as a component of a combination maintenance therapy regimen
Approval consideration: Orphan drug
QNASL (new formulation, new patient population)
(Beclomethasone dipropionate; Teva Pharmaceutical Industries)
Class/route: Corticosteroid; intranasal
New formulation: 40-mcg nasal aerosol for children aged 4-11 years; already available in 80-mcg nasal aerosol for patients aged ≥12 years
Indication: For the treatment of nasal symptoms associated with allergic rhinitis
Qudexy XR (new formulation)
(Topiramate; Upsher-Smith Laboratories)
Class/route: Antiepileptic; oral
New formulation: Extended-release capsules
Indications: As initial monotherapy in patients aged ≥10 years with partial-onset or primary generalized tonic-clonic seizures; as an adjunctive therapy in patients ≥2 years with partial-onset or primary generalized tonic-clonic seizures; and as an adjunctive therapy in patients ≥2 years with seizures associated with Lennox-Gastaut syndrome
Rapivab (new formulation)
(Peramivir; BioCryst Pharmaceuticals)
Class/route: Neuraminidase inhibitor; intravenous
New formulation: Single intravenous dose
Indication: Treatment of acute uncomplicated influenza in patients aged ≥18 years who have been symptomatic for no more than 2 days
Rasuvo (new formulation)
(Methotrexate; Medac Pharma)
Class/route: Folate analog metabolic inhibitor; subcutaneous
New formulation: Subcutaneous; already available in oral, intramuscular, intravenous, intra-arterial, and intrathecal formulations
Indications: For the management of patients with severe, active rheumatoid arthritis or with polyarticular juvenile idiopathic arthritis who are intolerant of or had an inadequate response to first-line therapy, and for the symptomatic control of severe, recalcitrant, disabling psoriasis in adults who are not adequately responsive to other forms of therapy
Retin-A Micro (new dosage form)
(Tretinoin gel; Valeant Pharmaceuticals)
Class/route: Retinoid; topical
New dosage form: Tretinoin gel microsphere, 0.08%
Indication: Treatment of acne vulgaris
Reyataz (new formulation)
(Atazanavir; Bristol-Myers Squibb)
Class/route: Protease inhibitor; oral
New formulation: Oral powder; already available as a capsule
Indication: For use in combination with other antiretroviral agents for the treatment of HIV-1 infection for patients aged ≥3 months weighing ≥10 kg
Approval consideration: Priority review
Ryanodex (new dosage)
(Dantrolene sodium; Eagle Pharmaceuticals)
Class/route: Skeletal muscle relaxant; intravenous
New dosage: 250-mg single-vial dose
Indications: Treatment of malignant hyperthermia in conjunction with appropriate supportive measures, and for the prevention of malignant hyperthermia in patients at high risk
Approval considerations: Priority review, orphan drug
Signafor Lar (new formulation)
(Pasireotide; Novartis)
Class/route: Somatostatin analog; intramuscular
New formulation: Injectable suspension
Indication: For the treatment of patients with acromegaly who have had an inadequate response to surgery and/or for whom surgery is not an option
Approval consideration: Orphan drug
Soolantra (new formulation) See New Combinations/Indications listing
Sotylize (new formulation)
(Sotalol hydrochloride; Arbor Pharmaceuticals)
Class/route: Antiarrhythmic; oral
New formulation: Oral solution; already available as an oral tablet
Indications: For the treatment of life-threatening ventricular arrhythmias, and for the maintenance of normal sinus rhythm in patients with highly symptomatic atrial fibrillation/flutter
Spiriva Respimat (new dosage form)
(Tiotropium bromide; Boehringer Ingelheim)
Class/route: Anticholinergic; oral inhalation
New dosage form: Slow-moving mist in an inhaled spray
Indications: For the long-term, once-daily maintenance treatment of bronchospasm associated with COPD and for reducing COPD exacerbations
Targiniq ER (new formulation)
(Oxycodone hydrochloride extended-release and naloxone hydrochloride extended-release tablets; Purdue Pharma)
Classes/route: Opioid agonist and opioid antagonist; oral
New formulation: Extended-release/long-acting oral tablets with abuse-deterrent properties that are expected to deter, but not entirely prevent, opioid abuse via snorting or injection
Indication: For the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate
Approval consideration: REMS
Tivorbex (new dosages)
(Indomethacin; Iroko Pharmaceuticals)
Class/route: NSAID; oral
New dosages: 20 mg orally 3 times daily or 40 mg orally 2 or 3 times daily; already available as 25-mg and 50-mg doses
Indication: For the treatment of mild-to-moderate acute pain in adults
Tybost (new formulation)
(Cobicistat; Gilead Sciences)
Class/route: CYP3A inhibitor; oral
New formulation: Administered once daily in combination with the protease inhibitors atazanavir or darunavir
Indication: To increase systemic exposure of atazanavir or darunavir (once-daily dosing regimen) in combination with other antiretroviral agents in the treatment of HIV-1 infection
Uceris (new formulation)
(Budesonide; Salix Pharmaceuticals)
Class/route: Glucocorticosteroid; rectal foam
New formulation: Rectal foam; already available in extended-release tablet
Indication: For the induction of remission in patients with active mild-to-moderate distal ulcerative colitis extending up to 40 cm from the anal verge
Vazculep (new dosages/formulation)
(Phenylephrine hydrochloride; Éclat Pharmaceuticals)
Class/route: Alpha-1 adrenergic receptor agonist; intravenous
New dosages/formulation: 5-mL and 10-mL pharmacy bulk package vials; already available as a 1-mL single-use vial
Indication: For the treatment of clinically important hypotension resulting primarily from vasodilation in the setting of anesthesia
Vogelxo (new formulation)
(Testosterone; Upsher-Smith Laboratories)
Class/route: Androgen; topical
New formulation: Gel formulation
Indication: For testosterone replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone, such as primary hypogonadism (congenital or acquired) and hypogonadotropic hypogonadism (congenital or acquired)
Xartemis XR (new formulation)
(Oxycodone hydrochloride and acetaminophen; Mallinckrodt Brand Pharmaceuticals)
Class/route: Opioid agonist; oral
New formulation: Extended-release tablet
Indication: For the management of acute pain severe enough to require opioid treatment and for which alternative treatment options are inadequate
Approval consideration: Priority review
Zubsolv (new dosage)
(Buprenorphine and naloxone; Orexo US)
Class/route: Partial opioid agonist; sublingual
New dosages: 8.6-mg/2.1-mg and 11.4-mg/2.9-mg buprenorphine/naloxone CIII sublingual tablets; already available as 5.7-mg/1.4-mg and 1.4-mg/0.36-mg tablets
Indication: For the maintenance treatment of opioid dependence
CFTR indicates cystic fibrosis transmembrane conductance regulator; COPD, chronic obstructive pulmonary disease; GLP-1, glucagon-like peptide-1; NSAID, nonsteroidal anti-inflammatory drug; REMS, Risk Evaluation and Mitigation Strategy.
IV. New Vaccines and New Blood Products Approved in 2014
Alprolix (new blood product)
(Coagulation factor IX [recombinant], Fc fusion protein; Biogen Idec)
Route: Intravenous
Indications: In adults and children with hemophilia B to control and prevent bleeding episodes, for perioperative management, and for routine prophylaxis to prevent or reduce the frequency of bleeding episodes
Elocate (new blood product)
(Antihemophilic factor [recombinant], Fc fusion protein; Biogen Idec)
Route: Intravenous
Indications: In adults and children with hemophilia A (congenital factor VIII deficiency) for the control and prevention of bleeding episodes, for perioperative management, and for routine prophylaxis to prevent or reduce the frequency of bleeding episodes
Fluzone Quadrivalent (new vaccine)
(Influenza vaccine; Sanofi Pasteur)
Route: Intradermal
Indication: For active immunization for the prevention of influenza disease caused by influenza A subtype viruses and influenza type B viruses contained in the vaccine
Gardasil 9 (new vaccine)
(Human papillomavirus 9-valent vaccine, recombinant; Merck Sharp & Dohme Corporation)
Route: Intramuscular
Indications: For girls and women aged 9-26 years for the prevention of cervical, vulvar, vaginal, and anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58; genital warts caused by HPV types 6 and 11; and precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58, including CIN grade 2/3 and cervical adenocarcinoma in situ, cervical intraepithelial neoplasia grade 1, vulvar intraepithelial neoplasia grades 2 and 3, vaginal intraepithelial neoplasia grades 2 and 3, and anal intraepithelial neoplasia grades 1, 2, and 3. Also for boys aged 9-15 years for the prevention of anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58; genital warts caused by HPV types 6 and 11; and precancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and anal intraepithelial neoplasia grades 1, 2, and 3
Obizur (new blood product)
(Antihemophilic factor [recombinant], porcine sequence; Baxter International)
Route: Intravenous
Indication: Treatment of bleeding episodes in adults with acquired hemophilia A
Ruconest (new blood product)
(C1 esterase inhibitor [recombinant]; Salix Pharmaceuticals)
Route: Intravenous
Indication: For the treatment of acute attacks in adult and adolescent patients with hereditary angioedema
Trumenba (new vaccine)
(Meningococcal group B vaccine; Wyeth Pharmaceuticals)
Route: Intramuscular
Indication: For active immunization to prevent invasive disease caused by Neisseria meningitidis serogroup B in individuals aged 10-25 years
CIN indicates cervical intraepithelial neoplasia; HPV, human papillomavirus.
V. Drugs Already Marketed Without an FDA-Approved New Drug Application
Vasostrict
(Vasopressin; Par Pharmaceutical)
Class/route: Peripheral vasoconstrictor; intravenous
Indication: To increase blood pressure in adults with vasodilatory shock (eg, postcardiotomy or sepsis) who remain hypotensive despite fluids and catecholamines