Health Plan Insights
January 2020 Updates from December 2019
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Recent FDA Approvals New Medications TRADE NAME DOSAGE FORM APPROVAL MANUFACTURER INDICATION(S) (generic name) STRENGTH DATE Avsola Amgen Inc. Injection, Biosimilar to Remicade. For the treatment December 6, 2019 (infliximab-axxq) 100 mg/20 mL of/reducing the signs and symptoms of: Crohn’s disease, pediatric Crohn’s disease, ulcerative colitis, rheumatoid arthritis in combination with methotrexate, psoriatic arthritis, and plaque psoriasis. Vyondys 53 Sarepta Intravenous Solution, For the treatment of Duchenne muscular December 12, (golodirsen) Therapeutics, Inc. 50 mg/mL dystrophy (DMD) in patients who have a 2019 confirmed mutation of the DMD gene that is amenable to exon 53 skipping. Padcev Astellas Injection, For the treatment of adult patients with locally December 18, (enfortumab 20 mg/vial and 30 advanced or metastatic urothelial cancer who 2019 vedotin-ejfv) mg/vial have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting. Conjupri CSPC Ouyi Tablets, For use alone or in combination with other (levamlodipine) Pharmaceutical 1.25 mg, 2.5 mg, and antihypertensive agents for the treatment of December 19, Co., Ltd. 5 mg hypertension, to lower blood pressure. 2019 Caplyta Intra-Cellular Capsules, For the treatment of schizophrenia in adults. December 20, (lumateperone) Therapies, Inc. 42 mg 2019 Tissue Blue Dutch Ophthalmic Ophthalmic Solution, To selectively stain the internal limiting December 20, (brilliant blue g) Research 0.025% membrane (ILM). 2019 Dayvigo Eisai R&D Tablets, For the treatment of adult patients with December 20, (lemborexant) Management Co., 5 mg and 10 mg insomnia, characterized by difficulties with 2019 Ltd sleep onset and/or sleep maintenance. Enhertu Daiichi Sankyo Injection, For the treatment of adult patients with December 20, (fam- 100 mg unresectable or metastatic HER2-positive 2019 trastuzumab breast cancer who have received two or more deruxtecan-nxki) prior anti-HER2-based regimens in the metastatic setting. Ubrelvy Allergan Tablets, For the acute treatment of migraine with or December 23, (ubrogepant) 10 mg and 50 mg without aura in adults. 2019
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New Combinations and Formulations TRADE NAME DOSAGE FORM APPROVAL MANUFACTURER INDICATION(S) (generic name) STRENGTH DATE Nouress Avadel Legacy Injection, For use as an additive to amino acids December 13, 2019 (cysteine 50 mg/mL solutions to meet nutritional requirements of hydrochloride) neonates (preterm and term infants less than one month of age) requiring total parenteral nutrition. Arazlo Dow Topical Lotion, For the topical treatment of acne vulgaris in December 18, 2019 (tazarotene) Pharmaceuticals 0.045% patients 9 years of age and older. Genosyl Vero Biotech Gas Inhalation, To improve oxygenation and reduce the December 20, 2019 (nitric oxide) 20 ppm need for extracorporeal membrane oxygenation in term and near-term (>34 weeks gestation) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension in conjunction with ventilatory support and other appropriate agents.
New Generics APPROVAL GENERIC NAME TRADE NAME DOSAGE FORM MANUFACTURER(S) DATE Sucralfate Carafate Oral Suspension Amneal Pharmaceuticals LLC December 2, 2019 Fingolimod Gilenya Capsules Biocon Pharma Inc.; HEC Pharm USA Inc.; December 4, 2019 Hydrochloride Sun Pharmaceutical Industries, Inc. Everolimus Afinitor Tablets Teva Pharmaceuticals USA, Inc.; Par December 9, 2019 Pharmaceutical Inc. (excl. 10 mg) Sodium Teradecyl Sotradecol Injection Custopharm, Inc. December 9, 2019 Sulfate Etonogestrel and NuvaRing Vaginal Ring Amneal Pharmaceuticals LLC December 11, 2019 Ethinyl Estradiol Alvimopan Entereg Capsules Watson Laboratories Inc. December 19, 2019 Diazoxide Proglycem Oral Suspension E5 Pharma Inc. December 20, 2019 Apixaban Eliquis Tablets Mylan Pharmaceuticals Inc.; Micro Labs December 23, 2019 Limited Ziprasidone Geodon Injection Gland Pharma Limited December 26, 2019 Mesylate Mirabegron Myrbetriq Extended Release Sawai USA Inc. December 27, 2019 Tablets
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Pipeline New Medication Pipeline MECHANISM OF ANTICIPATED DRUG NAME GENERIC NAME ROUTE INDICATION(S) ACTION APPROVAL DATE Pedmark Sodium Intravenous Chelating agent Chemotherapy-induced 2H 2019 Thiosulfate ototoxicity Tazemetostat Tazemetostat Oral EZH2 inhibitor Soft tissue sarcoma 01/23/2020
Dificid (oral Fidaxomicin Oral Narrow-spectrum Clostridium difficile 01/24/2020 suspension) macrocyclic antibiotic associated diarrhea Palforzia TBD Oral Allergen Allergy to peanuts 01/2020 immunotherapy BLU-285 Avapritinib Oral Receptor tyrosine Gastrointestinal cancer 02/14/2020 kinase inhibitor ETC-1002 Bempedoic Acid Oral ATP citrate lyase Hypercholesterolemia 02/21/2020 inhibitor Barhemsys Amisulpride Intravenous Atypical antipsychotic Postoperative nausea 02/26/2020 and vomiting Bempedoic Acid / Bempedoic Acid; Oral Intestinal cholesterol Hypercholesterolemia 02/26/2020 Ezetimibe Ezetimibe absorption inhibitor, ATP citrate lyase inhibitor ALD403 Eptinezumab Intravenous Calcitonin gene- Migraine 02/2020 related peptide inhibitor Empa + Lina + Met Empagliflozin; Oral Biguanides, Sodium- Diabetes Mellitus 02/2020 XR Linagliptin; glucose linked Metformin transporter 2 inhibitor, Dipeptidyl peptidase-4 inhibitor Teprotumumab Teprotumumab Intravenous Insulin-like growth Thyroid eye disease 03/08/2020 factor-1 receptor antagonist ITCA 650 Exenatide Implant Glucagon-like Diabetes Mellitus 03/09/2020 peptide-1 agonist Fintepla Fenfluramine Oral Serotonin reuptake Dravet syndrome 03/25/2020 inhibitor Lennox-Gastaut syndrome
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MECHANISM OF ANTICIPATED DRUG NAME GENERIC NAME ROUTE INDICATION(S) ACTION APPROVAL DATE Ozanimod Ozanimod Oral Sphingosine 1- Relapsing multiple 03/25/2020 phosphate receptor sclerosis modulators HTX-011 Bupivacaine; Injectable Nonsteroidal anti- Post-operative pain 03/26/2020 Meloxicam inflammatory drugs, Amide anesthetic Triferic Ferric Intravenous Iron supplement Anemia in end stage 03/28/2020 Pyrophosphate renal disease Citrate BHV-3000 Rimegepant Oral Calcitonin gene- Migraine 1Q 2020 related peptide inhibitor Bronchitol Mannitol Inhaled Mucolytic Cystic fibrosis, 1Q 2020 Bronchiectasis LCI699 Osilodrostat Oral Aldosterone synthase Cushing's disease in 1Q 2020 inhibitor adult patients PRO 140 Leronlimab Subcutaneous Entry inhibitor HIV infection 1Q 2020
MenQuadfi Meningococcal Intramuscular Meningitis B vaccine Meningococcal disease 04/25/2020 Conjugate Vaccine Ongentys Opicapone Oral Catechol-O- Motor deficit 04/26/2020 methyltransferase inhibitor Sarclisa Isatuximab Intravenous Anti-CD38 antibody Multiple myeloma 04/30/2020 Prostate cancer Non- small cell lung cancer Remimazolam Remimazolam Intravenous Benzodiazepine Sedation 04/2020
Dasotraline Dasotraline Oral Serotonin, Binge eating disorder 05/14/2020 norepinephrine and dopamine reuptake inhibitor RG7916 Risdiplam Oral Splicing modulator Spinal muscular atrophy 05/24/2020
Amphora Citric Acid; L- Intravaginal pH buffer Pregnancy prevention 05/25/2020 Lactic Acid; Potassium Bitartrate 800.361.4542 | envisionrx.com 5
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MECHANISM OF ANTICIPATED DRUG NAME GENERIC NAME ROUTE INDICATION(S) ACTION APPROVAL DATE INCB054828 Pemigatinib Oral Fibroblast growth Biliary tract cancer 05/30/2020 factor receptor inhibitor IMMU-132 Sacituzumab Intravenous Cytotoxic agent, Anti- Hormone receptor 06/02/2020 Govitecan Trop2 antibody positive breast cancer Inebilizumab Inebilizumab Intravenous Anti-CD19 antibody Neuromyelitis optica 06/2020
Orilissa Elagolix Oral Luteinizing hormone Uterine fibroids 2Q 2020 releasing hormone antagonist Selumetinib Selumetinib Oral MEK inhibitor Neurofibromatosis 2Q 2020 Sulphate Bimatoprost SR Bimatoprost Ophthalmic Prostaglandin analog Glaucoma or Ocular 1H 2020 Implant Hypertension VP-102 Cantharidin Topical Blistering agent Molluscum contagiosum 07/13/2020 Verruca vulgaris (common warts) UX007 Triheptanoin Oral Lipid replacement Long-chain fatty acid 07/31/2020 therapy oxidation disorders, Glucose transporter-1 deficiency AGN-150998 Abicipar Pegol Ophthalmic Vascular endothelial Wet age-related macular 07/2020 growth factor inhibitor degeneration Viaskin Peanut TBD Topical Allergen Allergy to peanuts 08/05/2020 immunotherapy TRC101 Veverimer Oral Acid binder Metabolic acidosis 08/22/2020
Winlevi Cortexolone 17a- Topical Antiandrogens Acne vulgaris 08/27/2020 Propionate SA237 Satralizumab Subcutaneous Interleukin 6 receptor Neuromyelitis optica 08/2020 (IL-6R) antagonist
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2020 New Generic Pipeline ANTICIPATED BRAND US BRAND NAME GENERIC NAME INDICATION(S) LAUNCH DATE MANUFACTURER SALES Past expected VIMOVO Esomeprazole Horizon Pharma; Multiple arthritis indications $578M launch date Magnesium; Naproxen Aralez; Nuvo Pharm Past expected OSMOPREP Sodium Phosphate, Salix; Valeant; Bausch Bowel cleansing $8M launch date Dibasic, Anhydrous; Health Sodium Phosphate, Monobasic, Monohydrate Past expected SAMSCA Tolvaptan Otsuka Hypervolemic and $113M launch date euvolemic hyponatremia Past expected APTENSIO XR Methylphenidate Rhodes Attention deficit hyperactivity $36M launch date Hydrochloride disorder Past expected AZASITE Azithromycin Akorn Bacterial conjunctivitis $7M launch date Past expected NEXIUM 24HR Esomeprazole AstraZeneca; Pfizer Heartburn TBD launch date (tablet) Magnesium Past expected NOXAFIL Posaconazole Merck & Co Prophylaxis of $25M launch date (suspension) invasive Aspergillus and Candida infections Past expected ZYTIGA (500 Abiraterone Acetate Janssen Prostate cancer $532M launch date mg) Past expected DESONATE Desonide Bayer; LEO Pharma; Atopic dermatitis $11M launch date Dow Pharmaceutical Sciences Past expected EVZIO Naloxone Hydrochloride Kaléo Pharma Opioid overdose $57M launch date Past expected LOTEMAX (gel) Loteprednol Etabonate Bausch + Lomb; Post-operative inflammation $118M launch date Valeant; Bausch and pain following ocular Health surgery Past expected MOVIPREP Ascorbic Acid; Salix; Valeant; Bausch Bowel cleansing $34M launch date Polyethylene Glycol Health 3350; Potassium Chloride; Sodium Ascorbate; Sodium Chloride; Sodium Sulfate Past expected MOXEZA Moxifloxacin Alcon; Novartis Bacterial conjunctivitis $8M launch date Hydrochloride Past expected NORVIR Ritonavir AbbVie HIV-1 infection TBD launch date (capsules)
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ANTICIPATED BRAND US BRAND NAME GENERIC NAME INDICATION(S) LAUNCH DATE MANUFACTURER SALES Past expected PREPOPIK Citric Acid; Magnesium Ferring Bowel cleansing launch date Oxide; Sodium $12M Picosulfate Past expected PRESTALIA Amlodipine Besylate; Symplmed; Marina Hypertension TBD launch date Perindopril Arginine Biotech; Adhera Past expected RESTASIS Cyclosporine Allergan Dry eye $1,611M launch date Past expected SPRIX Ketorolac Tromethamine Egalet; Ascend Moderate to severe pain launch date Therapeutics; Zyla; TBD Besins Healthcare Past expected SUPRENZA Phentermine Citius Pharma; Alpex Obesity launch date Hydrochloride Pharma; Akrimax TBD Pharmaceuticals Past expected VIVLODEX Meloxicam Egalet; iCeutica; Zyla Osteoarthritis pain $16M launch date 2019-2020 AFINITOR (10 Everolimus Novartis Multiple cancer indication $394M mg) 2019-2020 CUVPOSA Glycopyrrolate Merz Sialorrhea $22M
2019-2020 EMEND (for Aprepitant Merck & Co Chemotherapy-induced oral nausea and vomiting $1M suspension) 2019-2020 FERRIPROX Deferiprone ApoPharma; Apotex Treatment of chronic iron TBD (tablet) overload 2019-2020 KALETRA Lopinavir; Ritonavir AbbVie HIV-1 infection $64M (tablets) 2019-2020 NEXIUM (2.5 Esomeprazole AstraZeneca Gastroesophageal reflux mg, 5 mg, 10 Magnesium disease mg packets for $35M oral suspension) 2019-2020 NEXIUM (20 mg Esomeprazole AstraZeneca Gastroesophageal reflux and 40 mg Magnesium disease $43M packets for oral suspension) 2019-2020 OMNARIS Ciclesonide Sunovion; Covis Allergic rhinitis $10M Pharma; AstraZeneca
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ANTICIPATED BRAND US BRAND NAME GENERIC NAME INDICATION(S) LAUNCH DATE MANUFACTURER SALES 2019-2020 SYNDROS Dronabinol Insys Therapeutics Chemotherapy-induced nausea and vomiting, cachexia or an unexplained $3M significant weight loss in AIDS 2019-2021 RESCULA Unoprostone Isopropyl Sucampo; R-Tech Open-angle glaucoma or n/a Ueno ocular hypertension 2019-2021 ULESFIA Benzyl Alcohol Concordia; Shionogi Head lice infection $2M
Launched SILENOR Doxepin Hydrochloride Somaxon Insomnia Pharmaceuticals; $47M Pernix Therapeutics; Currax Launched ACZONE 7.5% Dapsone Allergan; Almirall Acne vulgaris $263M
Launched NOVOLOG (10 Insulin Aspart Novo Nordisk Diabetes mellitus $2330M mL vial) Recombinant Launched NOVOLOG Insulin Aspart Novo Nordisk Diabetes mellitus $3,462M FLEXPEN Recombinant Launched NOVOLOG MIX Insulin Aspart Protamine Novo Nordisk Diabetes mellitus 70/30 (10 mL Recombinant; Insulin $229M vial) Aspart Recombinant Launched NOVOLOG MIX Insulin Aspart Protamine Novo Nordisk Diabetes mellitus 70/30 Recombinant; Insulin $782M FLEXPEN Aspart Recombinant Launched NOVOLOG Insulin Aspart Novo Nordisk Diabetes mellitus $85M PENFILL Recombinant 01/22/2020 ONSOLIS Fentanyl Citrate BioDelivery Sciences Breakthrough cancer pain n/a International, Inc. 03/07/2020 RENOVA Tretinoin Valeant Cosmetic skin treatment $4M (0.02%) 03/08/2020 SOMATULINE Lanreotide Acetate Ipsen Long-term treatment of DEPOT acromegalic patients, carcinoid syndrome, $507M Neuroendocrine tumors (NETs)
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ANTICIPATED BRAND US BRAND NAME GENERIC NAME INDICATION(S) LAUNCH DATE MANUFACTURER SALES 03/10/2020 ZORTRESS Everolimus Novartis Prophylaxis of organ rejection $146M
03/29/2020 TAYTULLA Ethinyl Estradiol; Allergan Contraception $149M Norethindrone Acetate 04/26/2020 OXYTROL FOR Oxybutynin Bayer; Allergan Overactive bladder $1M WOMEN symptoms 04/30/2020 APTIVUS Tipranavir Boehringer Ingelheim HIV-1 infection $4M (capsule) 04/30/2020 APTIVUS (oral Tipranavir Boehringer Ingelheim HIV-1 infection TBD solution) 05/03/2020 SKLICE Ivermectin Arbor Pharmaceuticals Head lice infection $90M
05/10/2020 NYMALIZE Nimodipine Arbor Pharmaceuticals Subarachnoid hemorrhage from ruptured intracranial $28M berry aneurysms 05/15/2020 DEPO-SUBQ Medroxyprogesterone Pfizer Contraception, $4M PROVERA 104 Acetate endometriosis 05/18/2020 GEODON (oral Ziprasidone Pfizer Schizophrenia, bipolar n/a suspension) Hydrochloride disorder
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Medication with Significant Label Changes TRADE NAME SUMMARY OF LABEL CHANGES (generic name) Acticlate 5 Warnings and Precautions Tooth Development (doxycycline hyclate) (Newly added information) Advise the patient of the potential risk to the fetus if ACTICLATE or ACTICLATE CAP is used during pregnancy [see Use in Specific Populations (8.1, 8.4)]. Inhibition of Bone Growth (Newly added subsection; see label for complete information)
Bethkis 5 Warnings and Precautions 5.1 Ototoxicity (tobramycin) Newly added information underlined: … Ototoxicity, manifested as both auditory and vestibular toxicity, has been reported with parenteral aminoglycosides. Vestibular toxicity may be manifested by vertigo, ataxia or dizziness. Patients with known or suspected auditory or vestibular dysfunction should be closely monitored when taking BETHKIS. Monitoring may include obtaining audiometric evaluations and serum tobramycin levels. If ototoxicity is noted, the patient should be managed as medically appropriate, including potentially discontinuing BETHKIS. 5.2 Nephrotoxicity Newly added information underlined: Nephrotoxicity was not seen during BETHKIS clinical studies but has been associated with aminoglycosides as a class. Patients with known or suspected renal dysfunction or taking concomitant nephrotoxic drugs along with BETHKIS should have serum concentrations of tobramycin and laboratory measurements of renal function obtained at the discretion of the treating physician. If nephrotoxicity develops, the patient should be managed as medically appropriate, including potentially discontinuing BETHKIS until serum concentrations fall below 2 mcg/mL. 5.3 Neuromuscular Disorders Newly added information underlined: BETHKIS should be used cautiously in patients with muscular disorders. Aminoglycosides, including tobramycin, may aggravate muscle weakness because of a potential curare-like effect on neuromuscular function. Neuromuscular blockade, respiratory failure, and prolonged respiratory paralysis may occur more commonly in patients with underlying neuromuscular disorders, such as myasthenia gravis or Parkinson’s disease. Prolonged respiratory paralysis may also occur in patients receiving concomitant neuromuscular blocking agents. If neuromuscular blockade occurs, it may be reversed by the administration of calcium salts but mechanical assistance may be necessary. 5.6 Embryo-Fetal Toxicity Newly added information underlined: Aminoglycosides can cause fetal harm when administered to a pregnant woman. Aminoglycosides cross the placenta, and streptomycin has been associated with several reports of total, irreversible, bilateral congenital deafness in pediatric patients exposed in utero. However, systemic absorption of tobramycin following inhaled administration is expected to be minimal [see Clinical Pharmacology (12.3)]. Patients who use BETHKIS during pregnancy, or become pregnant while taking BETHKIS should be apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)]. Newly added subsection follows: 5.7 Concomitant Use of Systematic Aminoglycosides Patients receiving concomitant BETHKIS and parenteral aminoglycoside therapy should be monitored as clinically appropriate for toxicities associated with aminoglycosides as a class. Serum tobramycin levels should be monitored.
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) Caduet 5 Warnings and Precautions 5.1Myopathy and Rhabdomyolysis (amlodipine … besylate; Table 2. Atorvastatin Drug Interactions Associated with Increased Risk of Myopathy/Rhabdomyolysis atorvastatin calcium) (addition of the following to Table 2, please refer to label for complete information) letermovir when co-administered with cyclosporine letemovir
Carnexiv 5 Warnings and Precautions 5.5Hypersensitivity (carbamazepine)
(additions underlined) Cases of anaphylaxis and angioedema involving the larynx, glottis, lips, and eyelids have been reported in patients after taking the first or subsequent doses of oral carbamazepine. Angioedema associated with laryngeal edema can be fatal. If a patient develops any of these reactions after treatment with CARNEXIV, the drug should be discontinued and an alternative treatment started. These patients should not be rechallenged with the drug.
Cellcept 5 Warnings and Precautions 5.2 Lymphoma and Other Malignancies (mycophenolate (additions underlined) mofetil and … For patients with increased risk for skin cancer, exposure to sunlight and UV light should be limited by mycophenolate wearing protective clothing and using a broad-spectrum sunscreen with a high protection factor. mofetil … 5.7 Immunizations hydrochlroride) (additions underlined) During treatment with CELLCEPT, the use of live attenuated vaccines should be avoided (e.g., intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines) and patients should be advised that vaccinations may be less effective. Advise patients to discuss with the physician before seeking any immunizations.
Cleocin T 5 Warnings and Precautions (Additions and/or revisions underlined) (clindamycin Precautions phosphate) Nursing Mothers It is not known whether clindamycin is excreted in breast milk following use of CLEOCIN T. However, orally and parenterally administered clindamycin has been reported to appear in breast milk. Clindamycin has the potential to cause adverse effects on the breast-fed infant's gastrointestinal flora. Monitor the breast- fed infant for possible adverse effects on the gastrointestinal flora, such as diarrhea, candidiasis (thrush, diaper rash) or rarely, blood in the stool indicating possible antibiotic-associated colitis. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for clindamycin and any potential adverse effects on the breast-fed child from clindamycin or from the underlying maternal condition. Clinical Considerations If used during lactation and CLEOCIN T is applied to the chest, care should be taken to avoid accidental ingestion by the infant.
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) Clolar 5 Warnings and Precautions 5.11 Embryo-Fetal Toxicity (clofarabine) (Additions and/or revisions underlined) Based on findings from animal reproductive studies and the drug’s mechanism of action, Clolar can cause fetal harm when administered to a pregnant woman. Intravenous doses of clofarabine in rats and rabbits administered during organogenesis at doses that were below the maximum recommended human dose of 52 mg/m2 based on body surface area (mg/m2) caused an increase in resorptions, malformations, and variations. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment with Clolar and for at least 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with Clolar and for at least 3 months after the last dose.
Cresemba 5 Warnings and Precautions 5.4 Embryo-Fetal Toxicity (isavuconazonium Additions and/or revisions underlined: sulfate) Based on findings from animal reproduction studies, CRESEMBA may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus … … Isavuconazonium chloride administration was associated with dose-related increases in the incidences of rudimentary cervical ribs in rats and rabbits at 30 and 45 mg/kg, respectively, doses equivalent to about one fifth and one tenth of the human maintenance dose based on AUC comparisons. In rats, dose-related increases in the incidences of zygomatic arch fusion and supernumerary ribs/rudimentary supernumerary ribs were also noted at 30 mg/kg and above, equivalent to one fifth the maintenance human dose based on AUC comparisons [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use an effective method of contraception during treatment with CRESEMBA and for 28 days after the final dose [see Use in Specific Populations (8.3)].
Depo-SubQ Boxed Warning (PLR conversion; please refer to label) Provera 104 4 Contraindications (medroxy- (PLR conversion; please refer to label) progesterone 5 Warnings and Precautions acetate) (PLR conversion; please refer to label)
Descovy 5 Warnings and Precautions 5.4 New Onset or Worsening Renal Impairment (emtricitabine; (additions underlined) tenofovir … alafenamide DESCOVY is not recommended in individuals with estimated creatinine clearance of 15 to below 30 mL per fumarate) minute, or in individuals with estimated creatinine clearance below 15 mL per minute who are not receiving chronic hemodialysis.
Desvenlafaxine 5 Warnings and Precautions 5.2Serotonin Syndrome (desvenlafaxine (additions and/or revisions underlined) fumarate) Serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective-serotonin reuptake inhibitors (SSRIs), including desvenlafaxine extended-release tablets, can precipitate serotonin syndrome, a potentially life- threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John's Wort), and with drugs that impair metabolism of serotonin, i.e., MAOIs. … The concomitant use of desvenlafaxine extended-release tablets with MAOIs is contraindicated. In addition, do not initiate desvenlafaxine extended-release tablets in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking desvenlafaxine extended-release tablets, discontinue desvenlafaxine extended-release tablets before initiating treatment with the MAOI. Monitor all patients taking desvenlafaxine extended-release tablets for the emergence of serotonin syndrome. Discontinue treatment Treatmentwith desvenlafaxine extended-release tablets and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of desvenlafaxine extended-release tablets with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. 5.4 Increased Risk of Bleeding (additions and/or revisions underlined) Drugs that interfere with serotonin reuptake inhibition, including desvenlafaxine extended-release tablets, may increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case- control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to SSRIs and SNRIs have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages. Inform patients about the risk of bleeding associated with the concomitant use of desvenlafaxine extended- release tablets and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor coagulation indices when initiating, titrating, or discontinuing desvenlafaxine extended-release tablets. 5.5 Angle Closure Glaucoma (additions underlined) …Avoid use of antidepressants, including desvenlafaxine extended-release tablets, in patients with untreated anatomically narrow angles.
Divigel Boxed Warning (additions underlined) (estradiol) … Only daily oral 0.625 mg CE was studied in the estrogen-alone substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events and dementia to lower CE doses, other routes of administration, or other estrogen-alone products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen-alone therapy, taking into account her individual risk profile. ... Only daily oral 0.625 mg CE and 2.5 mg MPA were studied in the estrogen plus progestin substudy of the WHI. Therefore, the relevance of the WHI findings regarding adverse cardiovascular events, dementia and breast cancer to lower CE plus other MPA doses, other routes of administration, or other estrogen plus progestin products is not known. Without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products. Discuss with your patient the benefits and risks of estrogen plus progestin therapy, taking into account her individual risk profile. … 800.361.4542 | envisionrx.com 14
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) 4 Contraindications (addition underlined) … Known anaphylactic reaction, angioedema, or hypersensitivity to Divigel
Dostinex 5 Warnings and Precautions PRECAUTIONS (cabergoline) (additions underlined) … Psychiatric: Impulse control/compulsive behaviors, including pathological gambling, increased libido, and hypersexuality have been reported in patients treated with dopamine agonists including cabergoline. This has been generally reversible upon reduction of the dose or treatment discontinuation (See Postmarketing Surveillance data). Prescribers should consider dose reduction or stopping the medication if a patient develops such urges while taking cabergoline.
Doxorubicin Boxed Warning (Additions and/or revisions underlined) Hydrochloride Cardiomyopathy: Myocardial damage, including acute left ventricular failure, can occur with (doxorubicin hcl) doxorubicin hydrochloride. The risk of cardiomyopathy is proportional to the cumulative exposure with incidence rates from 1% - 20% for cumulative doses ranging from 300 mg/m2 to 500 mg/m2 when doxorubicin hydrochloride is administered every 3 weeks. The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Assess left ventricular ejection fraction (LVEF) before and regularly during and after treatment with doxorubicin hydrochloride. Secondary Malignancies: Secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) occur at a higher incidence in patients treated with anthracyclines, including doxorubicin hydrochloride. Extravasation and Tissue Necrosis: Extravasation of doxorubicin hydrochloride can result in severe local tissue injury and necrosis requiring wide excision of the affected area and skin grafting. Immediately terminate the drug and apply ice to the affected area. 4 Contraindications (Additions and/or revisions underlined) Doxorubicin Hydrochloride Injection/for Injection are contraindicated in patients with: Severe myocardial insufficiency Recent (occurring within the past 4-6 weeks) myocardial infarction Severe persistent drug-induced myelosuppression Severe hepatic impairment (defined as Child Pugh Class C or serum bilirubin level greater than 5 mg/dL) Severe hypersensitivity reaction to doxorubicin hydrochloride, including anaphylaxis 5 Warnings and Precautions 5.1 Cardiomyopathy and Arrhythmias (Additions and/or revisions underlined) Cardiomyopathy Doxorubicin hydrochloride can result in myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy is generally proportional to the cumulative exposure. Include prior doses of other anthracyclines or anthracenediones in calculations of total cumulative dosage for doxorubicin hydrochloride. Cardiomyopathy may develop during treatment or up to several years after completion of treatment and can include decrease in LVEF and signs and symptoms of congestive heart
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) failure (CHF). The probability of developing cardiomyopathy is estimated to be 1 to 2% at a total cumulative dose of 300 mg/m2 of doxorubicin hydrochloride, 3 to 5% at a dose of 400 mg/m2, 5 to 8% at a dose of 450 mg/m2, and 6 to 20% at a dose of 500 mg/m2, when doxorubicin hydrochloride is administered every 3 weeks. There is an additive or potentially synergistic increase in the risk of cardiomyopathy in patients who have received radiotherapy to the mediastinum or concomitant therapy with other known cardiotoxic agents, such as cyclophosphamide and trastuzumab. Pericarditis and myocarditis have also been reported during or following doxorubicin hydrochloride treatment. Assess left ventricular cardiac function (e.g., MUGA or echocardiogram) prior to initiation of Doxorubicin Hydrochloride Injection/for Injection, during treatment to detect acute changes, and after treatment to detect delayed cardiotoxicity. Increase the frequency of assessments as the cumulative dose exceeds 300 mg/m2. Use the same method of assessment of LVEF at all time points. Discontinue Doxorubicin Hydrochloride Injection/for Injection in patients who develop signs or symptoms of cardiomyopathy. Consider the use of dexrazoxane to reduce the incidence and severity of cardiomyopathy due to doxorubicin hydrochloride administration in patients who have received a cumulative doxorubicin hydrochloride dose of 300 mg/m2 and who will continue to receive doxorubicin hydrochloride. Arrhythmias Doxorubicin hydrochloride can result in arrhythmias, including life-threatening arrhythmias, during or within a few hours after doxorubicin hydrochloride administration and at any time point during treatment. Tachyarrhythmias, including sinus tachycardia, premature ventricular contractions, and ventricular tachycardia, as well as bradycardia, can occur. Electrocardiographic changes, including non-specific ST-T wave changes, atrioventricular and bundle-branch block can also occur. These electrocardiographic changes may be transient and self-limited and may not require a dosage modification of doxorubicin hydrochloride. 5.2 Secondary Malignancies (Additions and/or revisions underlined) The risk of developing secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) is increased following treatment with doxorubicin hydrochloride. Cumulative incidences ranged from 0.2% at five years to 1.5% at 10 years in two separate trials involving the adjuvant treatment of women with breast cancer. These leukemias generally occur within 1 to 3 years of treatment. 5.3 Extravasation and Tissue Necrosis (Additions and/or revisions underlined) Extravasation of doxorubicin hydrochloride can cause severe local tissue injury manifesting as blistering, ulceration, and necrosis requiring wide excision of the affected area and skin grafting. Extravasation should be considered if a patient experiences a burning or stinging sensation or shows other evidence indicating peri-venous infiltration or extravasation; however, extravasation may be present in patients who do not experience a stinging or burning sensation or when blood return is present on aspiration of the infusion needle. When given via a peripheral venous line, infuse Doxorubicin Hydrochloride Injection/for Injection over 10 minutes or less to minimize the risk of thrombosis or perivenous extravasation. If extravasation is suspected, immediately discontinue the intravenous injection or continuous intravenous infusion. Apply ice to the site intermittently for 15 minutes, 4 times a day for 3 days. In adults, if appropriate, administer dexrazoxane at the site of extravasation as soon as possible and within the first 6 hours after extravasation. 5.4 Severe Myelosuppression (Additions and/or revisions underlined) Doxorubicin hydrochloride can cause myelosuppression. In Study 1, the incidence of severe myelosuppression was: grade 4 leukopenia (0.3%), grade 3 leukopenia (3%), and grade 4 thrombocytopenia 800.361.4542 | envisionrx.com 16
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) (0.1%). A dose-dependent, reversible neutropenia is the predominant manifestation of myelosuppression from doxorubicin hydrochloride. (Additions and/or revisions underlined) Doxorubicin hydrochloride can cause myelosuppression. In Study 1, the incidence of severe myelosuppression was: grade 4 leukopenia (0.3%), grade 3 leukopenia (3%), and grade 4 thrombocytopenia (0.1%). A dose-dependent, reversible neutropenia is the predominant manifestation of myelosuppression from doxorubicin hydrochloride. When doxorubicin hydrochloride is administered every 21 days, the neutrophil count reaches its nadir 10 to 14 days after administration with recovery usually occurring by day 21. Obtain complete blood counts prior to each treatment and carefully monitor patients during treatment for possible clinical complications due to myelosuppression. Delay next dose of Doxorubicin Hydrochloride Injection/for Injection if severe myelosuppression has not improved. Consider dose reduction for patients with prolonged myelosuppression based on severity of reaction. 5.5 Use in Patients with Hepatic Impairment (Additions and/or revisions underlined) The clearance of doxorubicin is decreased in patients with elevated serum bilirubin with an increased risk of toxicity. Doxorubicin Hydrochloride Injection/for Injection is contraindicated in patients with severe hepatic impairment (defined as Child Pugh Class C or serum bilirubin level greater than 5 mg/dL). Reduce the dose of Doxorubicin Hydrochloride Injection/for Injection in patients with serum bilirubin levels of 1.2 to 5 mg/dL. Obtain liver tests including ALT, AST, alkaline phosphatase, and bilirubin prior to and during therapy. 5.6 Tumor Lysis Syndrome (Additions and/or revisions underlined) Doxorubicin hydrochloride can induce tumor lysis syndrome in patients with rapidly growing tumors. Evaluate blood uric acid levels, potassium, calcium, phosphate, and creatinine after initial treatment. Hydration, urine alkalinization, and prophylaxis with allopurinol to prevent hyperuricemia may minimize potential complications of tumor lysis syndrome. 5.7 Potentiation of Radiation Toxicity and Radiation Recall (Additions and/or revisions underlined) Doxorubicin hydrochloride can increase radiation-induced toxicity to the myocardium, mucosa, skin, and liver. Radiation recall, including but not limited to cutaneous and pulmonary toxicity, can occur in patients who receive doxorubicin hydrochloride after prior radiation therapy. 5.8 Embryo-Fetal Toxicity (Additions and/or revisions underlined) Based on findings in animals and its mechanism of action, Doxorubicin Hydrochloride Injection/for Injection can cause fetal harm when administered to a pregnant woman; avoid the use of Doxorubicin Hydrochloride Injection/for Injection during the 1st trimester. Available human data do not establish the presence or absence of major birth defects and miscarriage related to the use of doxorubicin hydrochloride during the 2nd and 3rd trimesters. Doxorubicin hydrochloride was teratogenic and embryotoxic in rats and rabbits at doses lower than the recommended human dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Doxorubicin Hydrochloride Injection/for Injection and for 6 months after treatment. Advise males with female partners of reproductive potential to use effective contraception during treatment with Doxorubicin Hydrochloride Injection/for Injection and for 3 months after treatment. Advise males with pregnant partners to use condoms during treatment with Doxorubicin Hydrochloride Injection/for Injection and for at least 10 days after the final dose.
Duavee 5 Warnings and Precautions Premenopausal Women 800.361.4542 | envisionrx.com 17
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) (bazedoxifene (Newly added information) Additionally, there is concern regarding inadvertent drug exposure in pregnancy in women of reproductive acetate; estrogens, potential who become pregnant, due to risk of fetal harm [see Use in Specific Populations (8.1)]. conjugated)
Emgality 5 Warnings and Precautions 5.1Hypersensitivity Reactions (galcanezumab- (additions underlined) gnlm) Hypersensitivity reactions, including dyspnea, urticaria, and rash, have occurred with EMGALITY in clinical studies and the postmarketing setting. Cases of anaphylaxis and angioedema have also been reported in the postmarketing setting. If a serious or severe hypersensitivity reaction occurs, discontinue administration of EMGALITY and initiate appropriate therapy. Hypersensivity reactions can occur days after administration and may be prolonged.
Extraneal 5 Warnings and Precautions 5.1 Unrecognized Hypoglycemia Resulting From Drug-Device Interaction (icodextrin) (additions and/or revisions underlined) When measuring blood glucose levels in patients using EXTRANEAL (icodextrin) Peritoneal Dialysis Solution, do not use blood glucose monitoring devices using glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ)-, glucose-dye-oxidoreductase (GDO)-, and some glucose dehydrogenase flavin-adenine dinucleotide (GDH-FAD)-based methods because these systems may result in falsely elevated glucose readings (due to the presence of maltose). Falsely elevated glucose readings have led patients or health care providers to withhold treatment of hypoglycemia or to administer insulin inappropriately leading to unrecognized hypoglycemia. Falsely elevated glucose levels may be measured up to two weeks following cessation of EXTRANEAL (icodextrin) therapy when GDH-PQQ, GDO, and GDH-FAD-based blood glucose monitors and test strips are used.
Additionally, other glucose-measuring technologies, such as continuous glucose monitoring systems, may or may not be compatible with EXTRANEAL. Always contact the device manufacturer for current information regarding compatibility and intended use of the device in the dialysis patient population. For additional information, please contact the Baxter Renal Clinical Help Line 1-888-RENAL-HELP or visit www.glucosesafety.com.
Forfivo XL 5 Warnings and Precautions 5.2 Neuropsychiatric Adverse Events and Suicide Risk in Smoking Cessation Treatment (bupropion (additions underlined) hydrochloride) …The healthcare provider should evaluate the severity of the adverse events and the extent to which the patient is benefiting from treatment, and consider options including continued treatment under closer monitoring, or discontinuing treatment. In many postmarketing cases, resolution of symptoms after discontinuation of bupropion was reported. However, the symptoms persisted in some cases; therefore, ongoing monitoring and supportive care should be provided until symptoms resolve. Gilenya 5 Warnings and Precautions Human Papilloma Virus (HPV) Infection (fingolimod) (Newly added subsection) Human papilloma virus (HPV) infections, including papilloma, dysplasia, warts, and HPV-related cancer, have been reported in patients treated with GILENYA in the postmarketing setting. Vaccination against HPV should be considered prior to treatment initiation with GILENYA, taking into account vaccination
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) recommendations. Cancer screening, including Papanicolaou (Pap) test, is recommended as per standard of care for patients using an immunosuppressive therapy. Fetal Risk (Additions and/or revisions underlined) Based on findings from animal studies, GILENYA may cause fetal harm when administered to a pregnant woman. In animal reproduction studies conducted in rats and rabbits, developmental toxicity was observed with administration of fingolimod at doses less than the recommended human dose. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Because it takes approximately 2 months to eliminate GILENYA from the body, advise females of reproductive potential to use effective contraception to avoid pregnancy during and for 2 months after stopping GILENYA treatment [see Use in Specific Populations (8.1, 8.3)]. Tumefactive Multiple Sclerosis (Newly added subsection) MS relapses with tumefactive demyelinating lesions on imaging have been observed during GILENYA therapy and after GILENYA discontinuation in the postmarketing setting. Most reported cases of tumefactive MS in patients receiving Gilenya have occured within the first 9 months after GILENYA initiation, but tumefactive MS may occur at any point during treatment. Cases of tumefactive MS have also been reported within the first 4 months after Gilenya discontinuation. Tumefactive MS should be considered when a severe MS relapse occurs during GILENYA treatment, especially during initiation, or after discontinuation of GILENYA, prompting imaging evaluation and initiation of appropriate treatment. Malignancies (Additions and/or revisions underlined) Cutaneous Malignancies Melanoma, squamous cell carcinoma and Merkel cell carcinoma have been reported with GILENYA in the postmarketing setting.
Increlex 4 Contraindications … (mecasermin Malignant Neoplasia recombinant) INCRELEX is contraindicated in pediatric patients with malignant neoplasia or a history of malignancy. 5 Warnings and Precautions 5.1 Hypoglycemia (addition underlined) … Patients should avoid engaging in any high-risk activities (e.g., driving, exercise, etc.) within 2 to 3 hours after dosing, particularly during the initiation of INCRELEX treatment until tolerability and a stable dose have been established. … 5.7 Malignant Neoplasia (newly added subsection) There have been postmarketing reports of malignant neoplasms in pediatric patients who have received treatment with INCRELEX. The cases of malignant neoplasms represented a variety of different malignancies. It is unknown whether there is any relationship between INCRELEX therapy and new occurrence of neoplasia. The occurrence of neoplasia was mostly reported in patients with rare genetic conditions of short stature associated with an increased risk of cancer, or in patients with other cancer predisposing conditions. The tumors were observed also more frequently in patients who received INCRELEX at higher than recommended doses, or at doses that produced serum IGF-1 levels above the normal reference ranges for age and sex.
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) Monitor all patients receiving INCRELEX carefully for development of neoplasms. Advise patients/caregivers to report development of new neoplasms. If malignant neoplasia develops, discontinue INCRELEX treatment. 5.8 Risk of Serious Adverse Reactions in Infants due to Benzyl Alcohol Preserved Solution (additions and/or revisions underlined) Serious and fatal adverse reactions including "gasping syndrome" can occur in neonates and infants treated with benzyl alcohol-preserved drugs, including INCRELEX. The "gasping syndrome" is characterized by central nervous system depression, metabolic acidosis, and gasping respirations. Use of INCRELEX in infants is not recommended.
Juxtapid 5 Warnings and Precautions Embryo-Fetal Toxicity (lomitapide (New subsection added) mesylate) Based on findings from animal studies, JUXTAPID use is contraindicated in pregnancy since it may cause fetal harm [see Contraindications (4), Use in Specific Populations (8.1, 8.3)]. In animal reproduction studies in rats and ferrets, embryonic death and fetal malformations were observed at clinically relevant exposures. Females of reproductive potential should have a negative pregnancy test before starting JUXTAPID. Advise females of reproductive potential to use effective contraception during therapy with JUXTAPID and for two weeks after the final dose. If pregnancy is detected, discontinue JUXTAPID.
Kaletra 4 Contraindications (Additions underlined) (lopinavir; ritonavir) • KALETRA is contraindicated with drugs that are potent CYP3A inducers where significantly reduced lopinavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance and cross-resistance [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)]. - Anticancer Agents: apalutamide
Kitabis Pak 5 Warnings and Precautions 5.5 Embryo-Fetal Toxicity (tobramycin) (additions underlined) Aminoglycosides can cause fetal harm when administered to a pregnant woman. Aminoglycosides cross the placenta, and streptomycin has been associated with several reports of total, irreversible, bilateral congenital deafness in pediatric patients exposed in utero. However, systemic absorption of tobramycin following inhaled administration is expected to be minimal .Patients who use KITABIS PAK during pregnancy, or become pregnant while taking tobramycin inhalation solution should be apprised of the potential hazard to the fetus.
Kuvan 5 Warnings and Precautions 5.2 Upper Gastrointestinal Mucosal Inflammation (sapropterin (new subsection added) dihydrochloride) Gastrointestinal (GI) adverse reactions suggestive of upper GI mucosal inflammation have been reported with Kuvan. Serious adverse reactions included esophagitis and gastritis .If left untreated, these could lead to severe sequelae including esophageal stricture, esophageal ulcer, gastric ulcer, and bleeding and such complications have been reported in patients receiving Kuvan. Monitor patients for signs and symptoms of upper GI mucosal inflammation. 5.3 Hypophenylalaninemia (additions underlined)
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) In clinical trials of Kuvan, some PKU patients experienced hypophenylalaninemia (low blood Phe) during treatment with Kuvan. In a clinical study of pediatric patients younger than 7 years old treated with Kuvan 20 mg/kg per day, the incidence of hypophenylalaninemia was higher than in clinical trials of older patients. 5.4 Monitoring Blood Phe Levels During Treatment (additions underlined) Prolonged elevations of blood Phe levels in patients with PKU can result in severe neurologic damage, including severe intellectual disability, developmental delay, microcephaly, delayed speech, seizures, and behavioral abnormalities. Conversely, prolonged levels of blood Phe that are too low have been associated with catabolism and endogenous protein breakdown, which has been associated with adverse developmental outcomes. Active management of dietary Phe intake while taking Kuvan is required to ensure adequate Phe control and nutritional balance. Monitor blood Phe levels during treatment to ensure adequate blood Phe level control. Frequent blood monitoring is recommended in the pediatric population. 5.5 Lack of Biochemical Response to Kuvan (additions underlined) Some patients with PKU do not show biochemical response (reduction in blood Phe) with treatment with Kuvan. In two clinical trials at a Kuvan dose of 20 mg/kg per day, 56% to 75% of pediatric PKU patients showed a biochemical response to Kuvan, and in one clinical trial at a dose of 10 mg/kg per day, 20% of adult and pediatric PKU patients showed a biochemical response to Kuvan.
Latuda 5 Warnings and Precautions 5.6 Metabolic Changes (lurasidone (additions underlined) hydrochloride) … Pediatric Patients (6 to 17 years) In a 104-week, open-label study in pediatric patients with schizophrenia, bipolar depression, or autistic disorder, 7 % of patients with a normal baseline fasting glucose experienced a shift to high at endpoint while taking lurasidone. … Pediatric Patients (6 to 17 years) In a 104-week, open-label study of pediatric patients with schizophrenia, bipolar depression, or autistic disorder, shifts in baseline fasting cholesterol from normal to high at 27% (HDL cholesterol) of patients taking lurasidone. Of patients with normal baseline fasting triglycerides, 12% experienced shifts to high. … Pediatric Patients (6 to 17 years) In a long-term, open-label study that enrolled pediatric patients with schizophrenia, bipolar depression, or autistic disorder from three short-term, placebo-controlled trials, 54% (378/701) received lurasidone for 104 weeks. The mean increase in weight from open-label baseline to Week 104 was 5.85 kg. To adjust for normal growth, z-scores were derived (measured in standard deviations [SD]), which normalize for the natural growth of children and adolescents by comparisons to age- and sex-matched population standards. A z-score change <0.5 SD is considered not clinically significant. In this trial, the mean change in z-score from open-label baseline to Week 104 was -0.06 SD for body weight and -0.13 SD for body mass index (BMI), indicating minimal deviation from the normal curve for weight gain. 5.7 Hyperprolactinemia (additions underlined) … Pediatric Patients (6 to 17 years) In a 104-week, open-label study of pediatric patients with schizophrenia, bipolar depression, or autistic disorder, the median changes from baseline to endpoint in serum prolactin levels were
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) -0.20 ng/mL (all patients), -0.30 ng/mL (females), and -0.05 ng/mL (males). The proportions of patients with a markedly high prolactin level (greater than or equal to 5 times the upper limit of normal) at any time during open-label treatment were 2% (all patients), 3% (females), and 1% (males). Adverse events among females in this trial that are potentially prolactin-related include galactorrhea (0.6%). Among male patients in this study, decreased libido was reported in one patient (0.2%) and there were no reports of impotence, gynecomastia, or galactorrhea.
Levemir, Levemir 4 Contraindications (Additions and/or revisions underlined) FlexPen, Levemir LEVEMIR is contraindicated: FlexTouch, · During episodes of hypoglycemia [see Warnings and Precautions (5.3)] Levemir Innolet, 5 Warnings and Precautions and Levemir Never Share a LEVEMIR FlexTouch Pen, Needle, or Syringe Between Patients (Section title revised) PenFill (Additions and/or revisions underlined) (insulin detemir LEVEMIR FlexTouch prefilled pens must never be shared between patients, even if the needle is recombinant) changed. Patients using LEVEMIR vials should never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens. Hypoglycemia (Extensive changes; please refer to label) Hypoglycemia Due to Medication Errors (Newly added subsection) Hypersensitivity and Allergic Reactions (Additions and/or revisions underlined) Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including LEVEMIR. If hypersensitivity reactions occur, discontinue LEVEMIR; treat per standard of care and monitor until symptoms and signs resolve. LEVEMIR is contraindicated in patients who have had hypersensitivity reactions to insulin detemir or any of the excipients [see Contraindications (4)]. Hypokalemia (Newly added subsection)
Lynparza 5 Warnings and Precautions 5.3 Embryo-Fetal Toxicity (olaparib) (Additions and/or revisions underlined) Lynparza can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. In an animal reproduction study, administration of olaparib to pregnant rats during the period of organogenesis caused teratogenicity and embryo-fetal toxicity at exposures below those in patients receiving the recommended human dose of 300 mg twice daily. Apprise pregnant women of the potential hazard to a fetus and the potential risk for loss of the pregnancy. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of Lynparza. Based on findings from genetic toxicity and animal reproduction studies, advise male patients with female partners of reproductive potential or who are pregnant to use effective contraception during treatment and for 3 months following the last dose of Lynparza.
Norvir 4 Contraindications (Additions and/or revisions underlined) (ritonavir)
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) NORVIR is contraindicated with drugs that are potent CYP3A inducers where significantly reduced ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance and cross-resistance [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)]. Anticancer Agents: apalutamide
Odefsey 5 Warnings and Precautions 5.5 New Onset or Worsening Renal Impairment (emtricitabine; (additions underlined) rilpivirine hcl; tenofovir … ODEFSEY is not recommended in patients with estimated creatinine clearance of 15 to below 30 mL per alafenamide minute, or in patients with estimated creatinine clearance below 15 mL per minute who are not receiving chronic hemodialysis. fumarate) … 5.8 Immune Reconstitution Syndrome (addition underlined) … Autoimmune disorders (such as Graves’ disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution, however, the time to onset is more variable, and can occur many months after initiation of treatment.
Orbactiv 5 Warnings and Precautions 5.2 Hypersensitivity (oritavancin (addition underlined) diphosphate) Serious hypersensitivity reactions, including anaphylaxis, have been reported with the use of ORBACTIV. … 5.3 Infusion Related Reactions (additions underlined) …Infusion reactions characterized by chest pain, back pain, chills and tremor have been observed with the use of ORBACTIV, including after the administration of more than one dose of ORBACTIV during a single course of therapy. Stopping or slowing the infusion may result in cessation of these reactions. The safety and effectiveness of more than one dose of ORBACTIV during a single course of therapy have not been established. 5.7 Development of Drug Resistant Bacteria (addition underlined)
Prescribing ORBACTIV in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug- resistant bacteria.
Otrexup and 4 Contraindications (Additions and/or revisions underlined) Otrexup PFS Otrexup is contraindicated in the following: (methotrexate) • Pregnancy Otrexup can cause embryo-fetal toxicity and fetal death when administered during pregnancy [see Warnings and Precautions (5.2) and Use in Specific Populations (8.1)]. 5 Warnings and Precautions Organ System Toxicity Hepatic:
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) (Newly added subsection; see label for complete information) Embryo-Fetal Toxicity (Extensive changes; please refer to label) Effects on Reproduction (Extensive changes; please refer to label)
Paricalcitol 4 Contraindications (Additions and/or revisions underlined) (paricalcitol) Paricalcitol Injection is contraindicated in patients with: Known hypersensitivity to paricalcitol or any inactive ingredient in Paricalcitol Injection. Hypersensitivity adverse reactions have been reported [e.g., angioedema (including laryngeal edema) and urticaria].
Parlodel 5 Warnings and Precautions WARNINGS (bromocriptine (additions underlined) mesylate) … While hypotension during the start of therapy with Parlodel occurs in some patients, in rare cases serious adverse events, including hypertension, myocardial infarction, seizures, stroke, have been reported in postpartum women treated with Parlodel for the inhibition of lactation. … Although a causal relationship between Parlodel administration and hypertension, seizures, strokes, and myocardial infarction in postpartum women has not been established, use of the drug for prevention of physiological lactation, or in patients with uncontrolled hypertension is not recommended.
Persantine 5 Warnings and Precautions PRECAUTIONS (dipyridamole) (additions underlined) ... Stress Testing with Intravenous Dipyridamole and Other Adenosinergic Agents: Clinical experience suggests that patients being treated with PERSANTINE tablets who also require pharmacological stress testing with intravenous dipyridamole or other adenosinergic agents (e.g. adenosine, regadenoson) should interrupt PERSANTINE tablets for 48 hours prior to stress testing. Intake of PERSANTINE tablets within 48 hours prior to stress testing with intravenous dipyridamole or other adenosinergic agents may increase the risk for cardiovascular side effects of these agents and may impair the sensitivity of the test.
Rayos Warnings and Precautions (prednisone) Embryo-Fetal Toxicity (Section title revised) (Additions and/or revisions underlined) Prednisone can cause fetal harm when administered to a pregnant woman. Human studies suggest a small but inconsistent increased risk of orofacial clefts with use of corticosteroids during the first trimester of pregnancy. Published animal studies show prednisolone to be teratogenic in rats, rabbits, hamsters, and mice with increased incidence of cleft palate in offspring. Intrauterine growth restriction and decreased birth weight have also been reported with corticosteroid use during pregnancy, however, the underlying maternal condition may also contribute to these risks. If this drug is used during pregnancy, or if the patient becomes
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) pregnant while using this drug, advise the patient about the potential harm to the fetus [see Use in Specific Populations (8.1)].
Sirturo 5 Warnings and Precautions 5.3 Risk of Development of Resistance to Bedaquiline (bedaquiline (newly added subsection) fumarate) A potential for development of resistance to bedaquiline in M. tuberculosis exists.. Bedaquiline must only be used in an appropriate combination regimen for the treatment of pulmonary MDR-TB to reduce the risk of development of resistance to bedaquiline.
Solage 5 Warnings and Precautions 5.1 Risk of Embryofetal Toxicity (mequinol; tretinoin) (newly added subsection) Based on findings in animal studies, Solagé may cause fetal harm. Avoid use in pregnant women. 5.2 Phototoxicity and Risk of Sunburn (subsection title revised, additions underlined) …Patients must be advised to use protective clothing and comply with a comprehensive sun avoidance program (including using sunscreen) when using Solagé. … 5.3 Local Adverse Reactions (additions underlined) … Tretinoin has been reported to cause severe irritation of eczematous skin, including the development of skin fissures. Solagé should be used with caution in patients with this condition. … Avoid concomitant use of other potentially irritating topical products (such as products with high concentration of alcohol, astringents, spices or lime, medicated soaps or shampoos, permanent wave solutions, electrolysis, hair depilatories or waxes, or products with a strong skin drying effect). Weather extremes, such as wind or cold may be more irritating to patients using Solagé. 5.4 Hypopigmentation (newly added subsection) Hypopigmentation has occurred with Solagé use. Solagé should be used with caution by patients with a history, or family history, of vitiligo, as they might be more susceptible to hypopigmentation, which can also be more severe in these patients.
Stavzor 4 Contraindications (Additions and/or revisions underlined) (valproic acid) For use in prophylaxis of migraine headaches: STAVZOR is contraindicated in women who are pregnant and in women of childbearing potential who are not using effective contraception [see Warnings and Precautions (5.2, 5.3, 5.4) and Use in Specific Populations (8.1)]. 5 Warnings and Precautions Hepatotoxicity Patients with Known or Suspected Mitochondrial Disease (Newly added information) Valproate-induced acute liver failure and liver-related deaths have been reported in patients with hereditary neurometabolic syndromes caused by mutations in the gene for mitochondrial DNA polymerase gamma (POLG) (e.g., Alpers-Huttenlocher Syndrome) at a higher rate than those without these syndromes. Most of
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) the reported cases of liver failure in patients with these syndromes have been identified in children and adolescents. Structural Birth Defects (Section title revised) (Additions and/or revisions underlined) Pregnancy registry data show that maternal valproate use can cause neural tube defects and other structural abnormalities (e.g., craniofacial defects, cardiovascular malformations, hypospadias, limb malformations). Decreased IQ Following in utero Exposure (Newly added information) It is not known when during pregnancy cognitive effects in valproate-exposed children occur. Use in Women of Childbearing Potential (Additions and/or revisions underlined) Because of the risk to the fetus of decreased IQ, neurodevelopmental disorders, and major congenital malformations (including neural tube defects), which may occur very early in pregnancy, valproate should not be administered to a woman of childbearing potential unless other medications have failed to provide adequate symptom control or are otherwise unacceptable. This is especially important when valproate use is considered for a condition not usually associated with permanent injury or death such as prophylaxis of migraine headaches [see Contraindications (4)]. Women should use effective contraception while using valproate. Women of childbearing potential should be counseled regularly regarding the relative risks and benefits of valproate use during pregnancy. This is especially important for women planning a pregnancy and for girls at the onset of puberty; alternative therapeutic options should be considered for these patients [see Boxed Warning and Use in Specific Populations (8.1)]. Bleeding and Other Hematopoietic Disorders (Section title revised) (Additions and/or revisions underlined) Valproate is associated with dose-related thrombocytopenia. In a clinical trial of valproate as monotherapy in patients with epilepsy, 34/126 patients (27%) receiving approximately 50 mg/kg/day on average, had at least one value of platelets = 75 x 109/L. Approximately half of these patients had treatment discontinued, with return of platelet counts to normal. In the remaining patients, platelet counts normalized with continued treatment. In this study, the probability of thrombocytopenia appeared to increase significantly at total valproate concentrations of = 110 mcg/mL (females) or = 135 mcg/mL (males). The therapeutic benefit which may accompany the higher doses should therefore be weighed against the possibility of a greater incidence of adverse effects. Valproate use has also been associated with decreases in other cell lines and myelodysplasia. Because of reports of cytopenias, inhibition of the secondary phase of platelet aggregation, and abnormal coagulation parameters (e.g., low fibrinogen, coagulation factor deficiencies, acquired von Willebrand’s disease), measurements of complete blood counts and coagulation tests are recommended before initiating therapy and at periodic intervals. It is recommended that patients receiving STAVZOR be monitored for blood counts and coagulation parameters prior to planned surgery and during pregnancy [see Use in Specific Populations (8.1)]. Evidence of hemorrhage, bruising, or a disorder of hemostasis/coagulation is an indication for reduction of the dosage or withdrawal of therapy. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity Reactions (Section title revised) (Additions and/or revisions underlined) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as Multiorgan Hypersensitivity, has been reported in patients taking valproate. DRESS may be fatal or life-threatening. 800.361.4542 | envisionrx.com 26
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) DRESS typically, although not exclusively, presents with fever, rash, lymphadenopathy, and/or facial swelling, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its expression, other organ systems not noted here may be involved. It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Valproate should be discontinued and not be resumed if an alternative etiology for the signs or symptoms cannot be established.
Sumavel DosePro 5 Warnings and Precautions Hypersensitivity Reactions (sumatriptan (Section title revised) succinate) (Additions and/or revisions underlined) Hypersensitivity reactions, including anaphylaxis and angioedema, have occurred in patients receiving Sumavel DosePro.
Sylvant 5 Warnings and Precautions 5.2 Vaccinations (siltuximab) (additions underlined) Do not administer live vaccines to patients or infants born to patients receiving SYLVANT because IL-6 inhibition may interfere with the normal immune response to new antigens.
Tagrisso 5 Warnings and Precautions Erythema Multiforme and Stevens-Johnson Syndrome (osimertinib (Newly added subsection) mesylate) Postmarketing cases consistent with Stevens-Johnson syndrome (SJS) and erythema multiforme major (EMM) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if SJS or EMM is suspected and permanently discontinue if confirmed. Postmarketing Experience (Newly added subsection) The following adverse reactions have been identified during post-approval use of TAGRISSO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cutaneous: Stevens-Johnson syndrome, erythema multiforme.
Taxotere Boxed Warning (Additions and/or revisions underlined) (docetaxel) Treatment-related mortality associated with TAXOTERE is increased in patients with abnormal liver function, in patients receiving higher doses, and in patients with non- small cell lung carcinoma and a history of prior treatment with platinum-based chemotherapy who receive TAXOTERE as a single agent at a dose of 100 mg/m2. Avoid the use of TAXOTERE in patients with bilirubin > upper limit of normal (ULN), or to patients with AST and/or ALT >1.5 × ULN concomitant with alkaline phosphatase >2.5 × ULN. Patients with elevations of bilirubin or abnormalities of transaminase concurrent with alkaline phosphatase are at increased risk for the development of severe neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death. Patients with isolated elevations of transaminase >1.5 × ULN also had a higher rate of febrile neutropenia. Measure bilirubin, AST or ALT, and alkaline phosphatase prior to each cycle of TAXOTERE. 800.361.4542 | envisionrx.com 27
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) Do not administer TAXOTERE to patients with neutrophil counts of <1500 cells/mm3. Monitor blood counts frequently as neutropenia may be severe and result in infection. Do not administer TAXOTERE to patients who have a history of severe hypersensitivity reactions to TAXOTERE or to other drugs formulated with polysorbate 80. Severe hypersensitivity reactions have been reported in patients despite dexamethasone premedication. Hypersensitivity reactions require immediate discontinuation of the TAXOTERE infusion and administration of appropriate therapy. Severe fluid retention occurred in 6.5% (6/92) of patients despite use of dexamethasone premedication. It was characterized by one or more of the following events: poorly tolerated peripheral edema, generalized edema, pleural effusion requiring urgent drainage, dyspnea at rest, cardiac tamponade, or pronounced abdominal distention (due to ascites). 5 Warnings and Precautions 5.2 Hepatic Impairment (Additions and/or revisions underlined) Patients with elevations of bilirubin or abnormalities of transaminase concurrent with alkaline phosphatase are at increased risk for the development of severe neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death. Avoid TAXOTERE in patients with bilirubin > upper limit of normal (ULN), or to patients with AST and/or ALT >1.5 × ULN concomitant with alkaline phosphatase >2.5 × ULN. For patients with isolated elevations of transaminase >1.5 × ULN, consider TAXOTERE dose modifications. Measure bilirubin, AST or ALT, and alkaline phosphatase prior to each cycle of TAXOTERE therapy. 5.3 Hematologic Effects (Additions and/or revisions underlined) Perform frequent peripheral blood cell counts on all patients receiving TAXOTERE. Do not retreat patients with subsequent cycles of TAXOTERE until neutrophils recover to a level >1500 cells/mm3. Avoid retreating patients until platelets recover to a level >100,000 cells/mm3. 5.5 Hypersensitivity Reactions (Additions and/or revisions underlined) Monitor patients closely for hypersensitivity reactions, especially during the first and second infusions. Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or bronchospasm, or fatal anaphylaxis, have been reported in patients premedicated with 3 days of corticosteroids. Severe hypersensitivity reactions require immediate discontinuation of the TAXOTERE infusion and aggressive therapy. Do not rechallenge patients with a history of severe hypersensitivity reactions with TAXOTERE. 5.8 Cutaneous Reactions (Additions and/or revisions underlined) Localized erythema of the extremities with edema followed by desquamation has been observed. In case of severe skin toxicity, an adjustment in dosage is recommended. The discontinuation rate due to skin toxicity was 1.6% (15/965) for metastatic breast cancer patients. Among 92 breast cancer patients premedicated with 3-day corticosteroids, there were no cases of severe skin toxicity reported and no patient discontinued TAXOTERE due to skin toxicity. Severe cutaneous adverse reactions (SCARs) such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with docetaxel treatment. Patients should be informed about the signs and symptoms of serious skin manifestations and monitored closely. Permanent treatment discontinuation should be considered in patients who experience SCARs.
Tecfidera 5 Warnings and Precautions 5.2 Progressive Multifocal Leukoencephalopathy 800.361.4542 | envisionrx.com 28
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) (dimethyl fumarate) (additions and/or revisions underlined) … PML has also occurred in the postmarketing setting in the presence of lymphopenia (<0.9x109/L). While the role of lymphopenia in these cases is uncertain, the PML cases have occurred predominantly in patients with lymphocyte counts <0.8x109/L persisting for more than 6 months ... 5.3 Herpes Zoster and Other Serious Opportunistic Infections (new subsection added) Serious cases of herpes zoster have occurred with TECFIDERA, including disseminated herpes zoster, herpes zoster ophthalmicus, herpes zoster meningoencephalitis, and herpes zoster meningomyelitis. These events may occur at any time during treatment. Monitor patients on TECFIDERA for signs and symptoms of herpes zoster. If herpes zoster occurs, appropriate treatment for herpes zoster should be administered. Other serious opportunistic infections have occurred with TECFIDERA, including cases of serious viral (herpes simplex virus, West Nile virus, cytomegalovirus), fungal (Candida and Aspergillus), and bacterial (Nocardia, Listeria monocytogenes, Mycobacterium tuberculosis) infections. These infections have been reported in patients with reduced absolute lymphocyte counts (ALC) as well as in patients with normal ALC. These infections have affected the brain, meninges, spinal cord, gastrointestinal tract, lungs, skin, eye, and ear. Patients with symptoms and signs consistent with any of these infections should undergo prompt diagnostic evaluation and receive appropriate treatment. Consider withholding TECFIDERA treatment in patients with herpes zoster or other serious infections until the infection has resolved.
Technivie 4 Contraindications (additions underlined) (ombitasvir; … paritaprevir; . With drugs that are highly dependent on CYP3A for clearance and for which elevated plasma ritonavir) concentrations are associated with serious and/or life-threatening events : … . Microsomal triglyceride transfer protein inhibitor: lomitapide . With drugs that are moderate or strong inducers of CYP3A and strong inducers of CYP2C8 and may lead to reduced efficacy of VIEKIRA XR: . Androgen receptor inhibitor: apalutamide
Toptecan 4 Contraindications (Additions and/or revisions underlined) Hydrochloride Topotecan Injection is contraindicated in patients who have a history of severe hypersensitivity reactions to (topotecan hcl) topotecan. Reactions have included anaphylactoid reactions. 5 Warnings and Precautions 5.1 Myelosuppression (Additions and/or revisions underlined) Topotecan can cause severe myelosuppression. Grade 4 neutropenia occurred in 78% of 879 patients, with a median duration of 7 days and was most common during Cycle 1 (58% of patients). Grade 4 neutropenia associated with infection occurred in 13% and febrile neutropenia occurred in 5%. Sepsis occurred in 4% and was fatal in 1%. Grade 4 thrombocytopenia occurred in 27%, with a median duration of 5 days. Grade 3 or 4 anemia occurred in 37% of patients. Topotecan can cause fatal typhlitis (neutropenic enterocolitis). Consider the possibility of typhlitis in patients presenting with fever, neutropenia, and abdominal pain.
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) Administer the first cycle of Topotecan Injection only to patients with a baseline neutrophil count of greater than or equal to 1,500/mm3 and a platelet count greater than or equal to 100,000/mm3. Monitor blood counts frequently during treatment. Withhold and reduce dose of Topotecan Injection based on neutrophil counts, platelet counts and hemoglobin levels. 5.4 Embryo-Fetal Toxicity (Additions and/or revisions underlined) Based on animal data, topotecan can cause fetal harm when administered to a pregnant woman. Topotecan caused embryolethality, fetotoxicity, and teratogenicity in rats and rabbits when administered during organogenesis. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months after the last dose of Topotecan Injection. Advise males with a female partner of reproductive potential to use effective contraception during treatment with Topotecan Injection and for 3 months after the last dose.
Truxima 5 Warnings and Precautions Concomitant Use with Other Biologic Agents and DMARDS other than Methotrexate in RA, GPA and (rituximab-abbs) MPA (Newly added subsection) Limited data are available on the safety of the use of biologic agents or disease modifying antirheumatic drugs (DMARDs) other than methotrexate in RA patients exhibiting peripheral B-cell depletion following treatment with rituximab. Observe patients closely for signs of infection if biologic agents and/or DMARDs are used concomitantly. Use of concomitant immunosuppressants other than corticosteroids has not been studied in GPA or MPA patients exhibiting peripheral B-cell depletion following treatment with rituximab products. Immunization (Newly added information) For patients treated with TRUXIMA, physicians should review the patient’s vaccination status and patients should, if possible, be brought up-to-date with all immunizations in agreement with current immunization guidelines prior to initiating TRUXIMA and administer non live vaccines at least 4 weeks prior to a course of TRUXIMA. The effect of rituximab on immune responses was assessed in a randomized, controlled study in patients with RA treated with rituximab and methotrexate (MTX) compared to patients treated with MTX alone. A response to pneumococcal vaccination (a T-cell independent antigen) as measured by an increase in antibody titers to at least 6 of 12 serotypes was lower in patients treated with rituximab plus MTX as compared to patients treated with MTX alone (19% vs. 61%). A lower proportion of patients in the rituximab plus MTX group developed detectable levels of anti-keyhole limpet hemocyanin antibodies (a novel protein antigen) after vaccination compared to patients on MTX alone (47% vs. 93%). A positive response to tetanus toxoid vaccine (a T-cell dependent antigen with existing immunity) was similar in patients treated with rituximab plus MTX compared to patients on MTX alone (39% vs. 42%). The proportion of patients maintaining a positive Candida skin test (to evaluate delayed type hypersensitivity) was also similar (77% of patients on rituximab plus MTX vs. 70% of patients on MTX alone). Most patients in the rituximab-treated group had B-cell counts below the lower limit of normal at the time of immunization. The clinical implications of these findings are not known. Infusion-Related Reaction (Newly added information) For RA, GPA and MPA patients, methylprednisolone 100 mg intravenously or its equivalent is recommended 30 minutes prior to each infusion. Progressive Multifocal Leukoencephalopathy (PML) (Additions underlined)
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) JC virus infection resulting in PML and death can occur in rituximab product-treated patients with hematologic malignancies or with autoimmune diseases. The majority of patients with hematologic malignancies diagnosed with PML received rituximab in combination with chemotherapy or as part of a hematopoietic stem cell transplant. The patients with autoimmune diseases had prior or concurrent immunosuppressive therapy. Most cases of PML were diagnosed within 12 months of their last infusion of rituximab. Use in RA Patients Who Have Not Had Prior Inadequate Response to Tumor Necrosis Factor (TNF) Antagonists (Newly added subsection) While the efficacy of rituximab was supported in four controlled trials in patients with RA with prior inadequate responses to non-biologic DMARDs, and in a controlled trial in MTX- naïve patients, a favorable risk-benefit relationship has not been established in these populations. The use of TRUXIMA in patients with RA who have not had prior inadequate response to one or more TNF antagonists is not recommended [see Clinical Studies (14.6)].
Vascepa 5 Warnings and Precautions 5.1 Atrial Fibrillation/Flutter (icosapent ethyl) (new subsection added) VASCEPA is associated with an increased risk of atrial fibrillation or atrial flutter requiring hospitalization. In a double-blind, placebo-controlled trial of 8,179 statin-treated subjects with established cardiovascular disease (CVD) or diabetes plus an additional risk factor for CVD, adjudicated atrial fibrillation or atrial flutter requiring hospitalization for 24 or more hours occurred in 127 (3%) patients treated with VASCEPA compared to 84 (2%) patients receiving placebo [HR= 1.5 (95% CI 1.14, 1.98)]. The incidence of atrial fibrillation was greater in patients with a previous history of atrial fibrillation or atrial flutter. 5.2 Potential for Allergic Reactions in Patients with Fish Allergy (additions underlined) VASCEPA contains ethyl esters of the omega-3 fatty acid, eicosapentaenoic acid (EPA), obtained from the oil of fish. It is not known whether patients with allergies to fish and/or shellfish are at increased risk of an allergic reaction to VASCEPA. Inform patients with known hypersensitivity to fish and/or shellfish about the potential for allergic reactions to VASCEPA and advise them to discontinue VASCEPA and seek medical attention if any reactions occur. 5.3 Bleeding (new subsection added) VASCEPA is associated with an increased risk of bleeding. In a double-blind, placebo- controlled cardiovascular outcomes trial of 8,179 patients, 482 (12%) patients receiving VASCEPA experienced a bleeding event compared to 404 (10%) patients receiving placebo. Serious bleeding events occurred in 111 (3%) of patients on VASCEPA vs. 85 (2%) of patients receiving placebo. The incidence of bleeding was greater in patients receiving concomitant antithrombotic medications, such as aspirin, clopidogrel, or warfarin.
Ventavis 5 Warnings and Precautions 5.4 Avoid Contact with Skin and Eyes and Ingestion (iloprost) (Newly added subsection) Ventavis solution should not be allowed to come into contact with the skin or eyes ingestion of Ventavis solution should be avoided.
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) Viekira Pak and 4 Contraindications (additions underlined) Viekira XR … (dasabuvir sodium; . With drugs that are highly dependent on CYP3A for clearance and for which elevated plasma ombitasvir; concentrations are associated with serious and/or life-threatening events : paritaprevir; … . Microsomal triglyceride transfer protein inhibitor: lomitapide ritonavir) . With drugs that are moderate or strong inducers of CYP3A and strong inducers of CYP2C8 and may lead to reduced efficacy of VIEKIRA XR: . Androgen receptor inhibitor: apalutamide
Xeljanz and Xeljanz 5 Warnings and Precautions 5.4Thrombosis XR (additions underlined) (tofacitinib citrate) Thrombosis, including pulmonary embolism, deep venous thrombosis, and arterial thrombosis, have occurred in patients treated with XELJANZ and other Janus kinase (JAK) inhibitors used to treat inflammatory conditions. Patients with rheumatoid arthritis 50 years of age and older with at least one CV risk factor treated with XELJANZ 10 mg twice daily compared to XELJANZ 5 mg twice daily or TNF blockers in a large, ongoing postmarketing study had an observed increase in incidence of these events. Many of these events were serious and some resulted in death.
Xofigo Contraindications Additions and/or revisions underlined: (radium RA-223 None. dichloride) 5 Warnings and Precautions Newly added subsection: 5.3 Embryo-Fetal Toxicity The safety and efficacy of Xofigo have not been established in females. Based on its mechanism of action, Xofigo can cause fetal harm when administered to a pregnant female. Advise pregnant females and females of reproductive potential of the potential risk to a fetus. Advise male patients to use condoms and their female partners of reproductive potential to use effective contraception during and for 6 months after completing treatment with Xofigo [see Use in Specific Populations (8.1, 8.3) and Clinical Pharmacology (12.1)].
Xtandi 5 Warnings and Precautions 5.1 Seizure (enzalutamide) (Additions and/or revisions underlined) Seizure occurred in 0.5% of patients receiving XTANDI in seven randomized clinical trials. In these trials, patients with predisposing factors for seizure were generally excluded. Seizure occurred from 13 to 1776 days after initiation of XTANDI. Patients experiencing seizure were permanently discontinued from therapy, and all seizure events resolved. 5.3 Hypersensitivity (Additions and/or revisions underlined) Hypersensitivity reactions, including edema of the face (0.5%), tongue (0.1%), or lip (0.1%) have been observed with enzalutamide in seven randomized clinical trials. Pharyngeal edema has been reported in post-marketing cases. Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue XTANDI and promptly seek medical care. Permanently discontinue XTANDI for serious hypersensitivity reactions.
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) 5.4 Ischemic Heart Disease (Additions and/or revisions underlined) In the combined data of four randomized, placebo-controlled clinical studies, ischemic heart disease occurred more commonly in patients on the XTANDI arm compared to patients on the placebo arm (2.9% vs 1.3%). Grade 3-4 ischemic events occurred in 1.4% of patients on the XTANDI arm compared to 0.7% on the placebo arm. Ischemic events led to death in 0.4% of patients on the XTANDI arm compared to 0.1% on the placebo arm. 5.5 Falls and Fractures (Additions and/or revisions underlined) Falls and fractures occurred in patients receiving XTANDI. Evaluate patients for fracture and fall risk. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents. In the combined data of four randomized, placebo-controlled clinical studies, falls occurred in 11% of patients treated with XTANDI compared to 4% of patients treated with placebo. Falls were not associated with loss of consciousness or seizure. Fractures occurred in 10% of patients treated with XTANDI and in 4% of patients treated with placebo. Grade 3-4 fractures occurred in 3% of patients treated with XTANDI and in 2% of patients treated with placebo. The median time to onset of fracture was 336 days (range: 2 to 1914 days) for patients treated with XTANDI. Routine bone density assessment and treatment of osteoporosis with bone-targeted agents were not performed in the studies.
Zepatier 4 Contraindications (additions and/or revisions underlined) (elbasvir; … grazoprevir) ZEPATIER is contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh B or C) or those with any history of hepatic decompensation due to the risk of hepatic decompensation. … 5 Warnings and Precautions 5.3 Risk of Hepatic Decompensation/Failure in Patients with Evidence of Advanced Liver Disease (new subsection added) Postmarketing cases of hepatic decompensation/failure, including those with fatal outcomes, have been reported in patients treated with HCV NS3/4A protease inhibitor-containing regimens, including ZEPATIER.
Reported cases occurred in patients treated with HCV NS3/4A protease inhibitor-containing regimens with baseline cirrhosis with and without moderate or severe liver impairment (Child-Pugh B or C) as well as some patients without cirrhosis. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Hepatic laboratory testing should be performed in all patients. In patients with compensated cirrhosis (Child- Pugh A) or evidence of advanced liver disease, such as portal hypertension, more frequent hepatic laboratory testing may be warranted; and patients should be monitored for signs and symptoms of hepatic decompensation such as the presence of jaundice, ascites, hepatic encephalopathy, and variceal hemorrhage. Discontinue ZEPATIER in patients who develop evidence of hepatic decompensation/failure. ZEPATIER is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B or C) or those with any history of prior hepatic decompensation.
Zidovudine 5 Warnings and Precautions
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TRADE NAME SUMMARY OF LABEL CHANGES (generic name) (zidovudine) Lactic Acidosis and Severe Hepatomegaly with Steatosis (Additions and/or revisions underlined) Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues, including Zidovudine Tablets. A majority of these cases have been in women. Female sex and obesity may be risk factors for the development of lactic acidosis and severe hepatomegaly with steatosis in patients treated with antiretroviral nucleoside analogues. Immune Reconstitution Syndrome (Newly added information) Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment. Lipoatrophy (Newly added subsection) Treatment with Zidovudine Tablets has been associated with loss of subcutaneous fat. The incidence and severity of lipoatrophy are related to cumulative exposure. This fat loss, which is most evident in the face, limbs, and buttocks, may be only partially reversible and improvement may take months to years after switching to a non-zidovudine-containing regimen. Patients should be regularly assessed for signs of lipoatrophy during therapy with Zidovudine Tablets and other zidovudine-containing products, and if feasible, therapy should be switched to an alternative regimen if there is suspicion of lipoatrophy.
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Treatment Guideline Updates TITLE CITATION / LINK
Pilonidal Disease Clinical Practice Guidelines Johnson EK, Vogel JD, Cowan ML, et al. The American Society of Colon (2019) and Rectal Surgeons' Clinical Practice Guidelines for the Management of Pilonidal Disease. Dis Colon Rectum. 2019 Feb;62(2):146-157. Full text available at: https://www.fascrs.org/sites/default/files/downloads/publication/the- american-society-of-colon-practical-guideline-sinus-pilonidalis.pdf Out-of-Hospital Hypothermia Clinical Practice Wilderness Medical Society Clinical Practice Guidelines for the Out-of- Guidelines (2019) Hospital Evaluation and Treatment of Accidental Hypothermia: 2019 Update. Dow J, Giesbrecht GG, Danzl DF, et al. Wilderness Environ Med. 2019 Nov 15. pii: S1080-6032(19)30173-5. Available at: https://www.wemjournal.org/article/S1080-6032(19)30173-5/fulltext#sec2.6. Testosterone Treatment in Adult Men With Age- Testosterone Treatment in Adult Men With Age-Related Low Testosterone: Related Low Testosterone: A Clinical Guideline A Clinical Guideline from the American College of Physicians. Qaseem A, from the American College of Physicians (2020) Horwitch CA, Vvijan S, et al. American College of Physicians. Ann Intern Med. 2020 Jan 7. doi: 10.7326/M19-088. Available at: https://annals.org/aim/fullarticle/2758507/testosterone-treatment-adult-men- age-related-low-testosterone-clinical-guideline Standards of Medical Care in Diabetes, American Standards of Medical Care in Diabetes: 2020. American Diabetes Diabetes Association (2020) Association. January 01 2020; volume 43 issue Supplement 1. Available at: https://care.diabetesjournals.org/content/43/Supplement_1
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