clinical insight

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Clinical Insight

August 2018

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Recent FDA Approvals New Medications

TRADE NAME (generic name)

MANUFACTURER DOSAGE FORM STRENGTH

INDICATION(S) APPROVAL DATE

Poteligeo (mogamulizumab-kpkc)

Kyowa Kirin, Inc. Injection, 20 mg/5 mL

For the treatment of adult patients with relapsed or refractory mycosis fungoides or Sézary syndrome after at least one prior systemic therapy.

August 8, 2018

Galafold (migalastat hydrochloride)

Amicus Therapeutics US, Inc.

Capsules, 150 mg

For the treatment of adults with a confirmed diagnosis of Fabry disease and an amenable galactosidase alpha gene (GLA) variant based on in vitro assay data.

August 10, 2018

Annovera (segesterone acetate; ethinyl estradiol)

Population Council Inc.

Vaginal Ring, 0.15 mg;0.013 mg/day

For use by females of reproductive potential to prevent pregnancy.

August 10, 2018

Onpattro (patisiran)

Alnylam Pharmaceuticals, Inc.

Injection, 2 mg/mL

For the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

August 10, 2018

Diacomit (stiripentol)

Biocodex SA Capsules: 250 mg and 500 mg Powder for Oral Suspension: 250 mg and 500 mg per packet

For the treatment of seizures associated with Dravet syndrome in patients 2 years of age and older taking clobazam.

August 20, 2018

Oxervate (cenegermin-bkbj)

Dompé farmaceutici S.p.A.

Ophthalmic Solution, 0.002% (20 mcg/mL)

For the treatment of neurotrophic keratitis.

August 22, 2018

Takhzyro (lanadelumab-flyo)

Dyax Corp Injection, 300 mg/2 mL (150 mg/mL)

For prophylaxis to prevent attacks of hereditary angioedema (HAE) in patients 12 years and older.

August 23, 2018

Xerava (eravacycline)

Tetraphase Pharmaceuticals, Inc.

Injection, 50 mg

For the treatment of complicated intra-abdominal infections in patients 18 years of age and older.

August 27, 2018

Pifeltro (doravirine)

Merck Sharp & Dohme Corp.

Tablet, 100 mg

For the treatment of HIV-1 infection in adult patients with no prior antiretroviral treatment history.

August 30, 2018



TRADE NAME (generic name)

MANUFACTURER DOSAGE FORM STRENGTH

INDICATION(S) APPROVAL DATE

Delstrigo (doravirine; lamivudine; tenofovir disoproxil fumarate)

Merck Sharp & Dohme Corp.

Tablet, 100 mg/ 300 mg/ 300 mg

For use as a complete regimen for the treatment of HIV-1 infection in adult patients with no antiretroviral treatment history.

August 30, 2018

New Combinations and Formulations

TRADE NAME (generic name) MANUFACTURER DOSAGE FORM

STRENGTH INDICATION(S) APPROVAL DATE

Tigecycline (tigecycline)

Amneal Biosciences LLC

Injection, 50 mg

For use in patients 18 years of age and older for: (1) complicated skin and skin structure infections; (2) complicated intra-abdominal infections; (3) community-acquired bacterial pneumonia.

August 2, 2018

Orkambi (lumacaftor/ ivacaftor)

Vertex Pharmaceuticals Incorporated

Oral Granules, 100 mg/125 mg and 150 mg/188 mg per packet

For the treatment of cystic fibrosis (CF) in patients age 2 years and older who are homozygous for the F508del mutation in the CFTR gene.

August 7, 2018

SoluPrep (chlorhexidine gluconate; isopropyl alcohol)

3M Topical Solution, 2%; 70%

For use as a patient preoperative skin preparation, for preparation of the skin prior to surgery, and to help reduce bacteria that can potentially cause skin infection.

August 8, 2018

Jornay PM (methylphenidate hydrochloride)

Ironshore Pharmaceuticals & Development, Inc.

Extended Release Tablets, 20 mg, 40 mg, 60 mg, 80 mg, and 100 mg

For the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years and older.

August 8, 2018

Arakoda (tafenoquine)

Sixty Degrees Pharmaceuticals, LLC

Tablet, 100 mg

For the prophylaxis of malaria in patients aged 18 years and older.

August 8, 2018

Lamivudine, Nevirapine, and Zidovudine

Micro Labs USA Inc. Tablets, 150 mg/200 mg/300 mg

For use alone as a complete regimen or in combination with other antiretroviral drugs for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35 kg.

August 13, 2018



TRADE NAME (generic name) MANUFACTURER DOSAGE FORM

STRENGTH INDICATION(S) APPROVAL DATE

Cequa (cyclosporine)

Sun Pharmaceutical Industries, Inc.

Ophthalmic Solution, 0.09%

To increase tear production in patients with keratoconjunctivitis sicca (dry eye).

August 14, 2018

Efavirenz, Lamivudine and Tenofovir Disoproxil Fumarate

Aurobindo Pharma USA, Inc.

Tablets, 600 mg/300 mg/300 mg

For the treatment of HIV-1 infection in adult and pediatric patients weighing at least 40 kg.

August 15, 2018

Lopinavir and Ritonavir

Mylan Pharmaceuticals Inc.

Oral Granules, 40 mg/10 mg

For the treatment of HIV-1 infection in combination with other antiretroviral agents in adults and pediatric patients 14 days and older.

August 16, 2018

Inveltys (loteprednol etabonate)

Kala Pharmaceuticals, Inc.

Ophthalmic Solution, 1%

For the treatment of post-operative inflammation and pain following ocular surgery.

August 22, 2018

Altreno (tretinoin)

Dow Pharmaceutical Sciences

Topical Lotion, 0.05%

For the topical treatment of acne vulgaris in patients 9 years of age and older.

August 23, 2018

New Generics

GENERIC NAME TRADE NAME DOSAGE FORM MANUFACTURER(S) APPROVAL DATE

Tadalafil Adcirca Tablets Mylan Pharmaceuticals Inc. August 3, 2018 Epinephrine EpiPen and EpiPen Jr. Injection Teva Pharmaceuticals USA, Inc. August 16, 2018



Pipeline New Medication Pipeline

DRUG NAME GENERIC NAME

ROUTE MECHANISM OF ACTION

INDICATION(S) ANTICIPATED APPROVAL DATE

PF-06463922 Lorlatinib Oral Tyrosine kinase inhibitor

Non-small cell lung cancer (NSCLC)

8/1/2018

Dacomitinib Dacomitinib Oral Tyrosine kinase inhibitor

Non-small cell lung cancer (NSCLC)

9/1/2018

Dasotraline Dasotraline Oral Serotonin, norepinephrine and dopamine reuptake inhibitor (SNDRI)

Attention deficit hyperactivity disorder

9/1/2018

TEV-48125 Fremanezumab

Subcutaneous Calcitonin gene-related peptide (CGRP) inhibitor

Migraine 9/16/2018

Arikayce Liposomal amikacin

Inhaled Aminoglycoside antibiotic

Nontuberculous mycobacteria lung infections

9/28/2018

PTK 0796 Omadacycline Oral Intravenous

Aminomethylcycline antibiotic

Acute Bacterial Skin and Skin Structure Infections

10/1/2018

LY2951742 Galcanezumab Subcutaneous Calcitonin gene-related peptide (CGRP) inhibitor

Migraine 10/2/2018

Baremsis Amisulpride Intravenous Atypical antipsychotic Postoperative nausea and vomiting

10/5/2018

Duvelisib Duvelisib Oral Phosphoinositide 3-kinase (PI3K) inhibitor

Chronic lymphocytic leukemia

10/5/2018

Tegsedi Inotersen Subcutaneous Protein synthesis inhibitor

Familial amyloid polyneuropathy

10/6/2018

REGN2810 Cemiplimab Intravenous Programmed cell death 1 (PD-1) inhibitor

Cutaneous squamous cell carcinoma (CSCC)

10/28/2018

LR-769 Eptacog Beta Intravenous Coagulation factor VII (recombinant)

Hemophilia A or B 11/1/2018

Mavenclad Cladribine Oral Antimetabolites Relapsing-remitting multiple sclerosis

11/1/2018

Olinvo Oliceridine Intravenous Opioid agonist Acute pain 11/2/2018






Yutiq Fluocinolone Acetonide

Intravitreal Corticosteroid Non-infectious uveitis 11/5/2018

TD-4208 Revefenacin Inhaled Long-acting muscarinic antagonist (LAMA)

Chronic obstructive pulmonary disease

11/13/2018

Zemcolo Rifamycin-SV Oral Rifamycin antibacterial Diarrhea caused by certain organisms

11/16/2018

NI-0501 Emapalumab Intravenous Type II interferon inhibitor

Hemophagocytic lymphohistiocytosis

11/20/2018

Firdapse Amifampridine Phosphate

Oral Potassium Channel Inhibitor

Lambert-Eaton myasthenic syndrome

11/25/2018

LOXO-101 Larotrectinib Oral Tropomyosin receptor kinases (TRK) inhibitor

Solid tumors 11/26/2018

ASP2215 Gilteritinib Oral Receptor tyrosine kinase inhibitor

Acute myeloid leukemia

11/29/2018

PF-04449913 Glasdegib Oral Hedgehog signalling pathway inhibitor

Acute myeloid leukemia

12/1/2018

Talazoparib Talazoparib Oral Poly (ADP-ribose) polymerase (PARP) inhibitor

Breast cancer 12/1/2018

XaraColl Bupivacaine Implant Amide anesthetic Post-operative pain 12/2/2018

SAGE-547 Brexanolone Intravenous GABA Modulators Postpartum depression 12/19/2018

JZP-110 Solriamfetol Oral CNS stimulant Excessive sleepiness in narcolepsy

12/20/2018

Resolor Prucalopride Oral 5-HT4 serotonin receptor agonist

Chronic idiopathic constipation

12/21/2018

Calaspargase pegol

Calaspargase Pegol

Intravenous Antineoplastic enzymes

Acute lymphocytic leukemia

12/22/2018

Xofluza Baloxavir marboxil

Oral Endonuclease inhibitor Acute uncomplicated influenza

12/24/2018

Dextenza Dexamethasone

Ophthalmic Implant

Corticosteroid Post-operative pain, Allergic conjunctivitis

12/28/2018

VivaGel BV Astodrimer Sodium

Intravaginal Anti-infective Bacterial vaginosis caused by certain organisms

1/1/2019






IMMU-132 Sacituzumab Govitecan

Intravenous Cytotoxic agent Anti-Trop2 antibody

Breast cancer 1/18/2019

ALKS 5461 Buprenorphine; Samidorphan

Oral Opioid antagonist Opioid partial agonist

Major depressive disorder

1/31/2019

Duobrii Halobetasol Propionate; Tazarotene

Topical Corticosteroid Retinoids

Moderate to severe chronic plaque psoriasis

2/1/2019

Evosyal (Branded Competitor of Botox, Xeomin, Dysport, & Botox Cosmetic)

PrabotulinumtoxinA

Injectable Neurotoxins Glabellar frown lines 2/1/2019

Iclaprim Iclaprim Intravenous Diaminopyrimidine antibiotic

Acute Bacterial Skin and Skin Structure Infections

2/13/2019

ALXN1210 Ravulizumab Intravenous Complement Inhibitors Treatment of paroxysmal nocturnal hemoglobinuria

2/18/2019

Elzonris Tagraxofusp Injectable Antineoplastics Acute myeloid leukemia

2/21/2019

Zynquista Sotagliflozin Oral SGLT1 and SGLT2 inhibitor

Improve glycemic control in type 1 and/or type 2 diabetes

3/22/2019

Rekynda Bremelanotide Injectable Peptide melanocortin receptor agonist

Female sexual dysfunction

3/23/2019

Duaklir Aclidinium Bromide; Formoterol

Inhaled Long-acting beta-2 adrenoreceptor agonist (LABA) Long-acting muscarinic antagonist (LAMA)

Chronic obstructive pulmonary disease

3/31/2019

Herceptin SC Trastuzumab Subcutaneous Anti-HER2 antibody HER2-positive breast cancer

5/1/2019

NKTR-181 TBD Oral Opioid agonist Moderate to severe chronic low back pain

5/28/2019






Jatenzo Testosterone Undecanoate

Oral Androgens Deficiency or absence of endogenous testosterone

1H 2019

BAF312 Siponimod Oral Sphingosine 1-phosphate (S1P) receptor modulators

Secondary progressive multiple sclerosis

1H 2019

N8-GP Coagulation Factor VIII (Recombinant)

Intravenous Coagulation factor VIII (recombinant)

Hemophilia A 1Q 2019

Evenity Romosozumab Subcutaneous Sclerostin inhibitor Postmenopausal osteoporosis

1Q 2019

Seysara Sarecycline Oral Tetracycline antibiotic Acne vulgaris 2H 2018

KPT-330 (Oral) Selinexor Oral Nuclear export inhibitor

Multiple myeloma 2H 2019

Hydexor Acetaminophen; Hydrocodone; Promethazine

Oral COX inhibitor H1 histamine receptor antagonist Opioid agonist

Symptoms associated with acute opioid withdrawal

2Q 2018

Scenesse Afamelanotide Implant Alpha-melanocyte stimulating hormone (alpha-MSH) analog

Erythropoietic protoporphyria (EPP)

2Q 2019

BI 655066 Risankizumab Subcutaneous Interleukin 23 (IL-23) antagonist

Moderate to severe plaque psoriasis

2Q 2019

BAY 94-9027 Coagulation Factor VIII

Intravenous Coagulation factor VIII (recombinant)

Hemophilia A 3Q 2018

CAT-8015 Moxetumomab Pasudotox

Intravenous Cytotoxic agent Anti-CD22 antibody

Chronic lymphocytic leukemia

3Q 2018

Alicaforsen Alicaforsen Rectal Antisense oligonucleotide

Pouchitis Pending

RVT-802 TBD Soft Tissue Tissue-based regenerative therapy

Primary immunodeficiency

Pending

V419 Viral vaccine; Bacterial vaccine

Intramuscular Viral vaccine Bacterial vaccine

Diphtheria Tetanus Whooping cough Poliomyelitis Haemophilus

Pending






influenzae type B (Hib) Hepatitis B

Xeglyze Abametapir Topical Antiparasitic agent Head lice infection Pending

IVIG-SN Human Immunoglobulin

Intravenous Immunoglobulins (IgG) Primary immunodeficiency

Pending

2018 New Generic Pipeline

ANTICIPATED LAUNCH DATE

BRAND NAME GENERIC NAME BRAND MANUFACTURER

INDICATION(S) 2017 US SALES

09/24/2018 MOVIPREP Ascorbic Acid; Polyethylene Glycol 3350; Potassium Chloride; Sodium Ascorbate; Sodium Chloride; Sodium Sulfate

Salix; Valeant Bowel cleansing $38M

09/27/2018 CIALIS Tadalafil Eli Lilly Benign Prostatic Hyperplasia

$1,933M

3Q 2018 ABSTRAL Fentanyl Citrate Sentynl; Orexo Breakthrough cancer pain

$7M

3Q 2018 LETAIRIS Ambrisentan Gilead Pulmonary Arterial Hypertension

$215M

3Q 2018 LEVITRA (2.5 mg)

Vardenafil Hydrochloride

Bayer Erectile Dysfunction <$10M

3Q 2018 LEVITRA (20 mg) Vardenafil Hydrochloride

Bayer Erectile Dysfunction $103M

3Q 2018 LEVITRA (5, 10 mg)

Vardenafil Hydrochloride

Bayer Erectile Dysfunction $24M

3Q 2018 PRECEDEX (50 mL, 100 mL bottles)

Dexmedetomidine Hydrochloride

Hospira; Pfizer Sedation $155M

3Q 2018 REMODULIN Treprostinil United Therapeutics Pulmonary Arterial Hypertension

$671MNNet sales






3Q 2018 SENSIPAR Cinacalcet Hydrochloride

Amgen Secondary hyperparathyroidism associated with chronic kidney disease

$1,722M

10/21/2018 ONFI (oral suspension)

Clobazam H. Lundbeck A/S Lennox-Gastaut syndrome

$215M

10/21/2018 ONFI (tablets) Clobazam H. Lundbeck A/S Lennox-Gastaut syndrome

$538M

10/22/2018 VIVLODEX Meloxicam Iroko; iCeutica Osteoarthritis pain $24M

11/18/2018 FINACEA GEL Azelaic Acid Bayer Rosacea $66M

11/26/2018 NEXIUM 24HR (tablet)

Esomeprazole Magnesium

AstraZeneca; Pfizer Gastroesophageal Reflux Disease

TBD

12/15/2018 CANASA Mesalamine Forest; Allergan Inflammatory Bowel Disease

$244M

4Q 2018 PYLERA Bismuth Subcitrate Potassium; Metronidazole; Tetracycline

Aptalis; Allergan Gastrointestinal Ulcers $30M

4Q 2018 RAPAFLO Silodosin Allergan Benign Prostatic Hyperplasia

$206M

2H 2018 ANDROGEL (1.62%) (packets)

Testosterone AbbVie Deficiency or absence of endogenous testosterone

TBD

2H 2018 ANDROGEL (1.62%) (pump)

Testosterone AbbVie Deficiency or absence of endogenous testosterone

$952M

2H 2018 FLECTOR Diclofenac Epolamine

IBSA Institut Biochemique; Pfizer

Acute Pain $127M

2H 2018 RESTASIS Cyclosporine Allergan Dry eye $1,769M

2018 ASTAGRAF XL Tacrolimus Astellas Prophylaxis of organ rejection

$12M

2018 BYETTA Exenatide Synthetic

AstraZeneca Improve glycemic control in type 1 and/or type 2 diabetes

$244M






2018 CUPRIMINE (250 mg)

Penicillamine Aton; Valeant Rheumatoid arthritis, Wilson's disease

$120M

2018 KALETRA (tablets)

Lopinavir; Ritonavir

AbbVie HIV-1 infection $87M

2018 LOTEMAX (gel) Loteprednol Etabonate

Bausch + Lomb; Valeant

Post-operative inflammation and pain following ocular surgery

$114M

2018 LOTEMAX (suspension)

Loteprednol Etabonate

Bausch + Lomb; Valeant

Ocular Pain $85M

2018 NEXIUM (20 mg and 40 mg packets for oral suspension)

Esomeprazole Magnesium

AstraZeneca Gastroesophageal Reflux Disease

$50M

2018 NORVIR (capsules)

Ritonavir AbbVie HIV-1 infection <$10M

2018 NUVARING Ethinyl Estradiol; Etonogestrel

Organon; Merck & Co Contraception $822M

2018 PROVENTIL-HFA Albuterol Sulfate 3M; Merck & Co Asthma $207M

2018 SPRIX Ketorolac Tromethamine

Egalet Moderate to severe pain

<$10M

2018 SUPRENZA Phentermine Hydrochloride

Citius Pharma; Alpex Pharma; Akrimax Pharmaceuticals

Obesity <$10M

2018 TRACLEER (film-coated tablet)

Bosentan Actelion; Janssen Pulmonary arterial hypertension

$83M

2018 TRISENOX Arsenic Trioxide Cephalon; Teva Leukemia $67M

2018-2019 ADVAIR DISKUS Fluticasone Propionate; Salmeterol Xinafoate

GSK Asthma $4,313M

2018-2019 AZASITE Azithromycin Akorn Bacterial conjunctivitis $18M

2018-2019 FENTORA Fentanyl Citrate Cephalon; Teva Breakthrough cancer pain

$109M

2018-2019 MINIVELLE Estradiol Noven Menopause $111M






2018-2019 MOXEZA Moxifloxacin Hydrochloride

Alcon; Novartis Bacterial conjunctivitis $12M

2018-2019 OMEPRAZOLE (tablet) (Dexcel)

Omeprazole Dexcel; Perrigo Gastroesophageal Reflux Disease

<$10M

2018-2019 PRESTALIA Amlodipine Besylate; Perindopril Arginine

Symplmed; Marina Biotech

Hypertension <$10M

2018-2019 QUILLIVANT XR Methylphenidate Hydrochloride

NextWave Pharmaceuticals; Pfizer

Attention Deficit Hyperactivity Disorder

$193M

2018-2019 SAMSCA Tolvaptan Otsuka Hypervolemic and euvolemic hyponatremia

$107M

2018-2019 TRAVATAN Z Travoprost Alcon; Novartis Glaucoma $544M

2018-2020 AMRIX Cyclobenzaprine Hydrochloride

Ivax; Teva; Cephalon Muscle spasms $104M

2018-2020 BREVIBLOC DOUBLE STRENGTH PREMIXED (100 mL bag)

Esmolol Hydrochloride

Baxter Control of perioperative tachycardia and hypertension

$36M

2018-2020 BREVIBLOC PREMIXED (250 mL bag)

Esmolol Hydrochloride

Baxter Supraventricular tachycardia including atrial fibrillation

$66M

2018-2020 OMNARIS Ciclesonide Sunovion; Covis Pharma; AstraZeneca

Allergic Rhinitis $10M

2018-2020 ZORTRESS Everolimus Novartis Prophylaxis of organ rejection

$130M

2018-2021 RESCULA Unoprostone Isopropyl

Sucampo; R-Tech Ueno

Glaucoma N/A



Medication with Significant Label Changes TRADE NAME (GENERIC NAME) SUMMARY OF LABEL CHANGES

Abraxane (Paclitaxel)

5 Warnings and Precautions 5.5 Hypersensitivity (additions underlined) Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have been reported. Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with this drug. Cross-hypersensitivity between ABRAXANE and other taxane products has been reported and may include severe reactions such as anaphylaxis. Patients with a previous history of hypersensitivity to other taxanes should be closely monitored during initiation of ABRAXANE therapy. 5.8 Embryo-Fetal Toxicity Based on mechanism of action and findings in animals, ABRAXANE can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of paclitaxel formulated as albumin-bound particles to rats during pregnancy at doses lower than the maximum recommended human dose, based on body surface area, caused embryo-fetal toxicities, including intrauterine mortality, increased resorptions, reduced numbers of live fetuses, and malformations. Advise females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception and avoid becoming pregnant during treatment with ABRAXANE and for at least six months after the last dose of ABRAXANE. Based on findings from genetic toxicity and animal reproduction studies, advise male patients with female partners of reproductive potential to use effective contraception and avoid fathering a child during treatment with ABRAXANE and for at least three months after the last dose of ABRAXANE.

Cellcept (mycophenalate mofetil)

Boxed Warning (Additions and/or revisions are underlined)

Use during pregnancy is associated with increased risks of first trimester pregnancy loss and congenital malformations. Avoid if safer treatment options are available. Females of reproductive potential must be counseled regarding pregnancy prevention and planning.

Increased risk of development of lymphoma and other malignancies, particularly of the skin. Increased susceptibility to bacterial, viral, fungal and protozoal infections, including opportunistic

infections and viral reactivation of hepatitis B and C, which may lead to hospitalizations and fatal outcomes.

5 Warnings and Precautions (Physicians Labeling Rule (PLR) Conversion; Newly Added Subsections; please refer to labeling) 5.1 Embryofetal Toxicity 5.2 Lymphoma and Other Malignancies 5.3 Serious Infections 5.4 Blood Dyscrasias: Neutropenia and Pure Red Cell Aplasia (PRCA) 5.5 Gastrointestinal Complications 5.6 Patients with Hypoxanthine-Guanine Phosphoribosyl-Transferase Deficiency (HGPRT) 5.7 Immunizations 5.8 Local Reactions with Rapid Intravenous Administration 5.9 Risks in Patients with Phenylketonuria 5.10 Semen Donation

Cosmegen (dactinomycin)

5 Warnings and Precautions (PLR conversion: subsections created as below, please see label for complete information) 5.1 Secondary Malignancy or Leukemia 5.2 Veno-occlusive Disease



TRADE NAME (GENERIC NAME) SUMMARY OF LABEL CHANGES

5.3 Extravasation 5.4 Myelosuppression 5.5 Immunizations 5.6 Severe Mucocutaneous Reactions 5.7 Renal Toxicity 5.8 Hepatotoxicity 5.9 Potentiation of Radiation Toxicity and Radiation Recall 5.10 Embryo-Fetal Toxicity

Cytovene (ganciclovir sodium)

Boxed Warning (Additions and/or revisions are underlined) WARNING: HEMATOLOGIC TOXICITY, IMPAIRMENT OF FERTILITY, FETAL TOXICITY, MUTAGENESIS AND CARCINOGENESIS • Hematologic Toxicity: Granulocytopenia, anemia, thrombocytopenia, and pancytopenia have

been reported in patients treated with CYTOVENE-IV. • Impairment of Fertility: Based on animal data and limited human data, CYTOVENE-IV may cause

temporary or permanent inhibition of spermatogenesis in males and suppression of fertility in females.

• Fetal Toxicity: Based on animal data, CYTOVENE-IV has the potential to cause birth defects in humans.

• Mutagenesis and Carcinogenesis: Based on animal data, CYTOVENE-IV has the potential to cause cancers in humans.

5 Warnings and Precautions 5.3 Impairment of Fertility (Additions and/or revisions are underlined) Based on animal data and limited human data, CYTOVENE-IV at the recommended human dose (RHD) may cause temporary or permanent inhibition of spermatogenesis in males, and may cause suppression of fertility in females. Advise patients that fertility may be impaired with the use of CYTOVENE-IV.

Eylea (aflibercept)

5 Warnings and Precautions 5.3 Thromboembolic Events (additions underlined) There is a potential risk of arterial thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors, including EYLEA. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The incidence of reported thromboembolic events in wet AMD studies during the first year was 1.8% (32 out of 1824) in the combined group of patients treated with EYLEA compared with 1.5% (9 out of 595) in patients treated with ranibizumab; through 96 weeks, the incidence was 3.3% (60 out of 1824) in the EYLEA group compared with 3.2% (19 out of 595) in the ranibizumab group.

Genvoya (cobicistat; elvitegravir; emtricitabine; tenofovir

4 Contraindications Section has been reformatted by removing the table and moving the associated clinical comments to Sectionm 7 in Table 5; please refer to label. 5 Warnings and Precautions 5.4 New Onset or Worsening Renal Impairment Additions and/or revisions underlined:




alafenamide fumarate)

Prior to or when initiating GENVOYA, and during treatment with GENVOYA on a clinically appropriate schedule, assess serum creatinine … In patients with chronic kidney disease, also assess serum phosphorus …

Imbruvica (ibrutinib)

5 Warnings and Precautions 5.1 Hemorrhage (Additions and/or revisions are underlined) Fatal bleeding events have occurred in patients treated with IMBRUVICA. Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post procedural hemorrhage) have occurred in 3% of patients, with fatalities occurring in 0.3% of 1,011 patients exposed to IMBRUVICA in clinical trials. Bleeding events of any grade, including bruising and petechiae, occurred in 44% of patients treated with IMBRUVICA… 5.2 Infections (Additions and/or revisions are underlined) Fatal and non-fatal infections (including bacterial, viral, or fungal) have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 24% of 1,011 patients exposed to IMBRUVICA in clinical trials… 5.3 Cytopenias (Additions and/or revisions are underlined) Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (23%), thrombocytopenia (8%), and anemia (3%) based on laboratory measurements occurred in patients with B-cell malignancies treated with single agent IMBRUVICA… 5.4 Cardiac Arrhythmias (Additions and/or revisions are underlined) Fatal and serious cardiac arrhythmias have occurred with IMBRUVICA therapy. Grade 3 or greater ventricular tachyarrhythmias occurred in 0.2% of patients, and Grade 3 or greater atrial fibrillation and atrial flutter occurred in 4% of 1,011 patients exposed to IMBRUVICA in clinical trials. These events have occurred particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of cardiac arrhythmias… 5.5 Hypertension (Additions and/or revisions are underlined) Hypertension has occurred in 12% of 1,011 patients treated with IMBRUVICA in clinical trials with a median time to onset of 5 months (range, 0.03 to 22 months)… 5.6 Second Primary Malignancies (Additions and/or revisions are underlined) Other malignancies (9%) including non-skin carcinomas (2%) have occurred in 1,011 patients treated with IMBRUVICA in clinical trials. The most frequent second primary malignancy was non-melanoma skin cancer (6%)…

Ingrezza (valbenazine tosylate)

4 Contraindications 4 CONTRAINDICATIONS (Additions and/or revisions are underlined) INGREZZA is contraindicated in patients with a history of hypersensitivity to valbenazine or any components of INGREZZA. Rash, urticaria, and reactions consistent with angioedema (e.g., swelling of the face, lips, and mouth) have been reported.

Inlyta (axitinib)

5 Warnings and Precautions 5.13 Pregnancy (Additions and/or revisions are underlined) Based on its mechanism of action and findings from animal studies, INLYTA can cause fetal harm when administered to a pregnant woman. There are no available human data to inform the drug-associated risk. In




developmental toxicity studies in mice, axitinib was teratogenic, embryotoxic and fetotoxic at maternal exposures that were lower than human exposures at the recommended clinical dose. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception during treatment with INLYTA and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with INLYTA and for 1 week after the last dose.

Jadenu, Jadenu Sprinkle (deferasirox)

5 Warnings and Precautions Additions and/or revisions underlined: 5.5 Age-Related Risk of Toxicity Pediatric Patients … These events were frequently associated with volume depletion or with continued Exjade doses in the 20-40 mg/kg/day range equivalent to 14-28 mg/kg/day JADENU when body iron burden was approaching or in the normal range. Interrupt JADENU … 5.6 Overchelation … An analysis of pediatric patients treated with Exjade in pooled clinical trials (n = 158), found a higher rate of renal adverse events among patients receiving doses greater than 25 mg/kg/day equivalent to 17.5 mg/kg/day JADENU, while their serum ferritin values … 5.10 Auditory and Ocular Abnormalities … The frequency of auditory adverse events irrespective of causality was increased among pediatric patients, who received Exjade doses greater than 25 mg/kg/day equivalent to 17.5 mg/kg/day JADENU when serum ferritin was less …

Keytruda (pembrolizumab)

5 Warnings and Precautions 5.5 Immune-Mediated Nephritis and Renal Dysfunction (Additions and/or revisions are underlined) …Nephritis occurred in 1.7% of 405 patients receiving KEYTRUDA in combination with pemetrexed and platinum in the KEYNOTE-189 study, including Grade 3 (1%) and Grade 4 (0.5%) nephritis. The median time to onset was 3.2 months (range: 16 days to 11.1 months) and the duration ranged from 1.6 to 16.8+ months. Six (86%) of the 7 patients received systemic corticosteroids, with all 6 receiving high-dose corticosteroids for a median duration of 3 days (range: 1 to 17 days) followed by a corticosteroid taper. Nephritis led to discontinuation of KEYTRUDA in 5 (1.2%) patients. Nephritis resolved in 2 (29%) of the 7 patients.

Lenvima (lenvatinib mesylate)

5 Warnings and Precautions 5.1 Hypertension (subsection revised, additions underlined) Hypertension occurred in 73% of patients in SELECT (DTC) receiving LENVIMA 24 mg orally once daily and in 45% of patients in REFLECT (HCC) receiving LENVIMA 8 mg or 12 mg orally once daily. The median time to onset of new or worsening hypertension was 16 days in SELECT and 26 days in REFLECT. Grade 3 hypertension occurred in 44% of patients in SELECT and in 24% in REFLECT. Grade 4 hypertension occurred <1% in SELECT and Grade 4 hypertension was not reported in REFLECT. In patients receiving LENVIMA 18 mg orally once daily with everolimus in InStudy 205 (RCC), hypertension was reported in 42% of patients LENVIMAand the median time to onset of new or worsening hypertension was 35 days. Grade 3 hypertension occurred in 13% of patients. Systolic blood pressure greater than or equal to160 mmHg occurred in 29% of patients and diastolic blood pressure grfeater than or equal to100 mmHg occurred in 21%. Serious complications of poorly controlled hypertension have been reported.




Control blood pressure prior to initiating LENVIMA. Monitor blood pressure after 1 week, then every 2 weeks for the first 2 months, and then at least monthly thereafter during treatment. Withhold and resume at a reduced dose when hypertension is controlled or permanently discontinue LENVIMA based on severity. 5.10 Hypocalcemia (subsection revised, additions underlined) In SELECT (DTC), Grade 3 to 4 hypocalcemia occurred in 9% of patients receiving LENVIMA. In 65% of cases, hypocalcemia improved or resolved following calcium supplementation, with or without dose interruption or dose reduction. In Study 205 (RCC), Grade 3 to 4 hypocalcemia occurred in 6% of patients treated with LENVIMA with everolimus. In REFLECT (HCC), Grade 3 hypocalcemia occurred in 0.8% of LENVIMA-treated patients Monitor blood calcium levels at least monthly and replace calcium as necessary during treatment. Withhold and resume at reduced dose upon recovery or permanently discontinue LENVIMA depending on severity. 5.11 Reversible Posterior Leukoencephalopathy Syndrome (subsection revised; additions underlined) Across clinical studies of 1823 patients who received LENVIMA as a single agent, reversible posterior leukoencephalopathy syndrome (RPLS) occurred in 0.3%. Confirm the diagnosis of RPLS with magnetic resonance imaging. Withhold and resume at a reduced dose upon recovery or permanently discontinue LENVIMA depending on severity and persistence of neurologic symptoms. 5.12 Hemorrhagic Events (subsection revised, additions underlined) Serious including fatal hemorrhagic events can occur with LENVIMA. Across SELECT (DTC), Study 205 (RCC) and REFLECT (HCC), hemorrhagic events of any grade occurred in 29% of the 799 patients treated with LENVIMA as a single agent or in combination with everolimus. The most frequently reported hemorrhagic events (all grades and occurring in at least 5% of patients) were epistaxis and hematuria. In SELECT, Grade 3 to 5 hemorrhage occurred in 2% of patients receiving LENVIMA, including 1 fatal intracranial hemorrhage among 16 patients who received LENVIMA and had CNS metastases at baseline. In Study 205, Grade 3 to 5 hemorrhage occurred in 8% of patients receiving LENVIMA with everolimus, including 1 fatal cerebral hemorrhage. In REFLECT, Grade 3 to 5 hemorrhage occurred in 5% of patients receiving LENVIMA, including 7 fatal hemorrhagic events. Serious tumor related bleeds, including fatal hemorrhagic events, occurred in patients treated with LENVIMA in clinical trials and in the post-marketing setting. In post-marketing surveillance, serious and fatal carotid artery hemorrhages were seen more frequently in patients with anaplastic thyroid carcinoma (ATC) than in other tumor types. The safety and effectiveness of LENVIMA in patients with ATC have not been demonstrated in clinical trials. Consider the risk of severe or fatal hemorrhage associated with tumor invasion or infiltration of major blood vessels (e.g. carotid artery). Withhold and resume at reduced dose upon recovery or permanently discontinue LENVIMA based on the severity. 5.13 Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction (subsection revised, additions underlined) LENVIMA impairs exogenous thyroid suppression. In SELECT (DTC), 88% of all patients had a baseline thyroid stimulating hormone (TSH) level less than or equal to 0.5 mU/L. In those patients with a normal TSH at baseline, elevation of TSH level >0.5 mU/L was observed post baseline in 57% of LENVIMA-treated patients. Grade 1 or 2 hypothyroidism occurred in 24% of patients receiving LENVIMA with everolimus in Study 205 (RCC) and in 21% of patients receiving LENVIMA in REFLECT (HCC). In those patients with a normal or low TSH at baseline, an elevation of TSH was observed post baseline in 70% of patients receiving LENVIMA in REFLECT and 60% of patients receiving LENVIMA with everolimus in Study 205.




Monitor thyroid function prior to initiating LENVIMA and at least monthly during treatment. Treat hypothyroidism according to standard medical practice. 5.15 Embryo-Fetal Toxicity (additions underlined) … Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with LENVIMA and for at least 30 days after the last dose. 5.2 Cardiac Dysfunction (Subsection revised, additions underlined) Serious and fatal cardiac dysfunction can occur with LENVIMA. Across clinical trials in 799 patients with DTC, RCC or HCC, Grade 3 or higher cardiac dysfunction (including cardiomyopathy, left or right ventricular dysfunction, congestive heart failure, ventricular hypokinesia, or in left or right ventricular ejection fraction more than 20% from baseline) occurred in 3% of LENVIMA -treated patients. Monitor patients for clinical symptoms or signs of cardiac dysfunction. Withhold and resume at a reduced dose upon recovery or permanently discontinue LENVIMA based on severity. 5.3 Arterial Thromboembolic Events (subsection revised, additions underlined) Among patients receiving LENVIMA or LENVIMA with everolimus, arterial thromboembolic events of any severity occurred in 2% ofpatients in Study 205 (RCC), 2% of patients in REFLECT (HCC) and 5% of patients in SELECT (DTC). Grade 3 to 5 arterial thromboembolic events ranged from 2% to 3% across all clinical trials. Permanently discontinue LENVIMA following an arterial thrombotic event. The safety of resuming LENVIMA after an arterial thromboembolic event has not been established and LENVIMA has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months. 5.4 Hepatotoxicity (subsection revised, additions underlined) Across clinical studiesenrolling 1327 LENVIMA-treated patients with malignancies other than HCC, serious hepatic adverse reactions occurred in 1.4% of patients. Fatal events including hepatic failure, acute hepatitis and hepatorenal syndrome, occurred in 0.5% of patients. In REFLECT (HCC), hepatic encephalopathy (including hepatic encephalopathy, encephalopathy, metabolic encephalopathy, and hepatic coma) occurred in 8% of LENVIMA-treated patients and 3% of sorafenib-treated patients Grade 3 to 5 hepatic encephalopathy occurred in 5% of LENVIMA-treated patientsand 2% of sorafenib-treated patients. Grade 3 to 5 hepatic failure occurred in 3% of LENVIMA-treated patients and 3% of sorafenib-treated patients. Two percent of patients discontinued LENVIMA and 0.2% discontinued sorafenib due to hepatic encephalopathy and 1% of patients discontinued lenvatinib or sorafenib due to hepatic failure.Monitor liver function prior to initiating LENVIMA, then every 2 weeks for the first 2 months, and at least monthly thereafter during treatment. Monitor patients with HCC closely for signs of hepatic failure, including hepatic encephalopathy. Withhold and resume at a reduced dose upon recovery or permanently discontinue LENVIMA based on severity. 5.5 Renal Failure or Impairment (subsection revised, additions underlined) Serious including fatal renal failure or impairment can occur with LENVIMA. Renal impairment occurred in 14% of patients receiving LENVIMA in SELECT (DTC) and in 7% of patients receiving LENVIMA in REFLECT (HCC). Grade 3 to 5 renal failure or impairment occurred in 3% (DTC) and 2% (HCC) of patients, including 1 fatality in each study. In Study 205 (RCC), renal impairment or renal failure occurred in 18% of patients receiving LENVIMA with everolimus, including Grade 3 in 10% of patients. Initiate prompt management of diarrhea or dehydration/hypovolemia. Withhold and resume at a reduced dose upon recovery or permanently discontinue LENVIMA for renal failure or impairment based on severity.




5.6 Proteinuria (subsection revised, additions underlined) Proteinuria occurred in 34% of LENVIMA-treated patients in SELECT (DTC) and in 26% of LENVIMA-treated patients in REFLECT (HCC). Grade 3 proteinuria occurred in 11% and 6% in SELECT and REFLECT, respectively. In Study 205 (RCC), proteinuria occurred in 31% of patients receiving LENVIMA with everolimus and 14% of patients receiving everolimus. Grade 3 proteinuria occurred in 8% of patients receiving LENVIMA with everolimus compared to 2% of patients receiving everolimus. Monitor for proteinuria prior to initiating LENVIMA and periodically during treatment. If urine dipstick proteinuria greater than or equal to 2+ is detected, obtain a 24-hour urine protein. Withhold and resume at a reduced dose upon recovery or permanently discontinue LENVIMA on severity. 5.7 Diarrhea (subsection revised, additions underlined) Of the 737 patients treated with LENVIMA in SELECT (DTC) and REFLECT (HCC), diarrhea occurred in 49% of patients, including Grade 3 in 6%. In Study 205 (RCC), diarrhea occurred in 81% of patients receiving LENVIMA with everolimus, including Grade 3 in 19%. Diarrhea was the most frequent cause of dose interruption/reduction and diarrhea recurred despite dose reduction. Promptly initiate management of diarrhea. Withhold and resume at a reduced dose upon recovery or permanently discontinue LENVIMA. 5.8 Fistula Formation and Gastrointestinal Perforation (subsection revised, additions underlined) Of 799 patients treated with LENVIMA or LENVIMA with everolimus in SELECT (DTC), Study 205 (RCC) and REFLECT (HCC), fistula or gastrointestinal perforation occurred in 2%. Permanently discontinue LENVIMA in patients who develop gastrointestinal perforation of any severity or Grade 3 or 4 fistula. 5.9 QT Interval Prolongation (subsection revised, additions underlined) In SELECT (DTC), QT/QTc interval prolongation occurred in 9% of LENVIMA-treated patients and QT interval prolongation of >500 ms occurred in 2%.In Study 205 (RCC), QTc interval increases of >60 ms occurred in 11% of patients receiving LENVIMA with everolimus and QTc interval> 500 ms occurred in 6%. In REFLECT (HCC), QTc interval increases of> 60 ms occurred in 8% of LENVIMA-treated patients and QTc interval> 500 ms occurred in 2%. Monitor and correct electrolyte abnormalities at baseline and periodically during treatment. Monitor electrocardiograms in patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics. Withhold and resume at reduced dose of LENVIMA upon recovery based on severity.

Nexium IV (esomeprazole sodium)

5 Warnings and Precautions 5.11 Fundic Gland Polyps (Newly added subsection) PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated.

Nuvessa (metronidazole)

5 Warnings and Precautions 5.1 Central and Peripheral Nervous System Effects Additions and/or revisions underlined: Convulsive seizures, encephalopathy, aseptic meningitis, optic and peripheral neuropathy, the latter …




… patients with central nervous system diseases. Discontinue promptly if abnormal neurologic signs develop.

Prepopik (citric acid; magnesium oxide; sodium picosulfate)

5 Warnings and Precautions 5.1 Serious Fluid and Electrolyte Abnormalities (additions underlined) …In adult clinical trials orthostatic changes were documented up to seven days post colonoscopy. In a single study of patients 9 to 16 years of age, approximately 20% of patients in Prepopik arms had orthostatic changes (changes in blood pressure and/or heart rate) compared with approximately 7% of those who received the comparator (PEG.These changes occurred up to five days post colonoscopy. … 5.4 Use in Patients with Renal Impairment (additions underlined) Prepopik is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 mL/min), accumulation of magnesium in plasma may occur.As with other magnesium containing bowel preparations, use caution when prescribing Prepopik for patients with mild to moderate renal impairment or patients taking concomitant medications that may affect renal function (such as diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or non-steroidal anti- inflammatory drugs. These patients may be at increased risk for renal injury. Advise these patients of the importance of adequate hydration before, during and after the use of Prepopik. Consider performing baseline and post- colonoscopy laboratory tests (electrolytes, creatinine, and BUN) in these patients.

Progesterone (progesterone)

Contraindications (Additions and/or revisions are underlined)

Known sensitivity to sesame oil/seeds. 5 Warnings and Precautions WARNINGS (Additions and/or revisions are underlined) Acute eosinophilic pneumonia has been reported in patients receiving progesterone in sesame oil. In reported cases associated with progesterone in sesame oil, patients developed fever, dyspnea with hypoxic respiratory insufficiency, and diffuse pulmonary infiltrates. In general, patients developed eosinophilic pneumonia 2 to 4 weeks after starting progesterone in sesame oil and improved when progesterone in sesame oil was discontinued and a different formulation of progesterone and/or steroid therapy was initiated. Patients who develop these signs and symptoms while receiving progesterone in sesame oil should undergo prompt medical evaluation, and progesterone in sesame oil should be discontinued immediately.

Sabril (vigabatrin)

Boxed Warning 6.2 Post Marketing Experience (Additions and/or revisions are underlined) Skin and Subcutaneous Tissue Disorders: Angioedema, maculo-papular rash, pruritus, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)), alopecia

Stribild (cobicistat; elvitegravir; emtricitabine;

4 Contraindications Contraindications (Newly added subsection)

Alpha 1-adrenoreceptor antagonist: alfuzosin Anticonvulsants: carbamazepine, phenobarbital, phenytoin Antimycobacterial: rifampin




tenofovir disoproxil fumarate)

Antipsychotics: lurasidone, pimozide Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine GI Motility Agent: cisapride Herbal Products: St. John’s wort (Hypericum perforatum) HMG-CoA Reductase Inhibitors: lovastatin, simvastatin Phosphodiesterase-5 (PDE-5) Inhibitor: sildenafil when administered as Revatio® for the treatment of

pulmonary arterial hypertension Sedative/hypnotics: triazolam, orally administered midazolam

5 Warnings and Precautions 5.2 New Onset or Worsening Renal Impairment (Additions are underlined) … Prior to initiation and during use of STRIBILD, on a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. Discontinue STRIBILD in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Initiation of STRIBILD in patients with estimated creatinine clearance below 70 mL per minute is not recommended.

Tagrisso (osimertinib mesylate)

7 Drug Interactions 7.2 Effect of Osimertinib on Other Drugs Additions and/or revisions underlined: Co-administering TAGRISSO with a breast cancer resistant protein (BCRP) or P-glycoprotein (P-gp) substrate increased the exposure of the substrate compared to administering it alone. Increased BCRP or P-gp substrate exposure may increase the risk of exposure- related toxicity. Monitor for adverse reactions of the BCRP or P-gp substrate, unless otherwise instructed in its approved labeling, when co-administered with TAGRISSO.

Valcyte (valganciclovir hydrochloride)

Boxed Warning WARNING: HEMATOLOGIC TOXICITY, IMPAIRMENT OF FERTILITY, FETAL TOXICITY, MUTAGENESIS AND CARCINOGENESIS Additions and/or revisions underlined:

Impairment of Fertility: Based on animal data and limited human data, VALCYTE may cause temporary or permanent inhibition of spermatogenesis in males and suppression of fertility in females. 5 Warnings and Precautions Additions and/or revisions underlined: 5.1 Hematologic Toxicity … complete blood counts with differential and platelet counts should be performed frequently, especially in infants, in patients with renal impairment … or in whom neutrophil counts are less than 1000 cells/?L at the beginning … 5.3 Impairment of Fertility Based on animal data and limited human data, VALCYTE at the recommended human…

Verzenio (abemaciclib)

5 Warnings and Precautions 5.1 Diarrhea (additions underlined) Diarrhea occurred in 81% of patients receiving VERZENIO plus an aromatase inhibitor in MONARCH 3, 86% of patients receiving VERZENIO plus fulvestrant in MONARCH 2, and 90% of patients receiving VERZENIO alone in MONARCH 1. Grade 3 diarrhea occurred in 9% of patients receiving VERZENIO plus an aromatase




inhibitor in MONARCH 3, 13% of patients receiving VERZENIO plus fulvestrant in MONARCH 2, and in 20% of patients receiving VERZENIO alone in MONARCH 1. Episodes of diarrhea have been associated with dehydration and infection. Diarrhea incidence was greatest during the first month of VERZENIO dosing. In MONARCH 3, the median time to onset of the first diarrhea event was 8 days, and the median duration of diarrhea for Grades 2 and 3 were 11 and 8 days, respectively. In MONARCH 2, the median time to onset of the first diarrhea event was 6 days, and the median duration of diarrhea for Grades 2 and 3 were 9 days and 6 days, respectively. In MONARCH 3, 19% of patients with diarrhea required a dose omission and 13% required a dose reduction. In MONARCH 2, 22% of patients with diarrhea required a dose omission and 22% required a dose reduction. The time to onset and resolution for diarrhea were similar across MONARCH 3, MONARCH 2, and MONARCH 1. … 5.2 Neutropenia (additions underlined) Neutropenia occurred in 41% of patients receiving VERZENIO plus an aromatase inhibitor in MONARCH 3, 46% of patients receiving VERZENIO plus fulvestrant in MONARCH 2, and 37% of patients receiving VERZENIO alone in MONARCH 1. A Grade greater than or equal to3 decrease in neutrophil count (based on laboratory findings) occurred in 22% of patients receiving VERZENIO plus an aromatase inhibitor in MONARCH 3, 32% of patients receiving VERZENIO plus fulvestrant in MONARCH 2, and in 27% of patients receiving VERZENIO in MONARCH 1. In MONARCH 3, the median time to first episode of Grade greater than or equal to 3 neutropenia was 33 days, and in MONARCH 2 and MONARCH 1 was 29 days. In MONARCH 3, median duration of Grade greater than or equal to 3 neutropenia was 11 days, and for MONARCH 2 and MONARCH 1 was 15 days. … 5.3 Hepatotoxicity (additions underlined) In MONARCH 3, Grade greater than or equal to 3 increases in ALT (6% versus 2%) and AST (3% versus 1%) were reported in the VERZENIO and placebo arms, respectively. In MONARCH 2, Grade greater than or equal to 3 increases in ALT (4% versus 2%) and AST (2% versus 3%) were reported in the VERZENIO and placebo arms, respectively. In MONARCH 3, for patients receiving VERZENIO plus an aromatase inhibitor with Grade greater than or equal to 3 ALT increased, median time to onset was 61 days, and median time to resolution to Grade <3 was 14 days. In MONARCH 2, for patients receiving VERZENIO plus fulvestrant with Grade greater than or equal to 3 ALT increased, median time to onset was 57 days, and median time to resolution to Grade <3 was 14 days. In MONARCH 3, for patients receiving VERZENIO plus an aromatase inhibitor with Grade greater than or equal to 3 AST increased, median time to onset was 71 days, and median time to resolution was 15 days. In MONARCH 2, for patients receiving VERZENIO plus fulvestrant with Grade greater than or equal to 3 AST increased, median time to onset was 185 days, and median time to resolution was 13 days. … 5.4 Venous Thromboembolism (additions underlined) In MONARCH 3, venous thromboembolic events were reported in 5% of patients treated with VERZENIO plus an aromatase inhibitor as compared to 0.6% of patients treated with an aromatase inhibitor plus placebo. In MONARCH 2, venous thromboembolic events were reported in 5% of patients treated with VERZENIO plus fulvestrant as compared to 0.9% of patients treated with fulvestrant plus placebo. Venous thromboembolic events included deep vein thrombosis, pulmonary embolism, pelvic venous thrombosis, cerebral venous sinus thrombosis, subclavian and axillary vein thrombosis, and inferior vena cava thrombosis. Across the clinical development program, deaths due to venous thromboembolism have been reported.




Vusion (miconazole nitrate; petrolatum, white, zinc oxide)

5 Warnings and Precautions Addition of the following subsection title: 5.1 Skin Irritation If irritation occurs …

Treatment Guideline Updates

TITLE CITATION/LINK

AAP Issues Updated Influenza Vaccine Recommendations

http://pediatrics.aappublications.org/content/early/2018/08/30/peds.2018-2367

Guidelines for the evaluation and treatment of perimenopausal depression: summary and recommendations

https://journals.lww.com/menopausejournal/Abstract/publishahead/Guidelines_for_the_evaluation_and_treatment_of.97498.aspx

CDC: Updated Influenza Vaccination Recommendations for 2018-2019

https://www.cdc.gov/mmwr/volumes/67/rr/rr6703a1.htm?s_cid=rr6703a1_e

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