OCTOBER 2020

CLINICAL
ALERT
YOUR MONTHLY SOURCE FOR DRUG INFORMATION HIGHLIGHTS

EDITORIAL STAFF
EDITOR IN CHIEF BEHAVIORAL
TRENDING COVID-19
Maryam Tabatabai HEALTH
PharmD TOPICS UPDATE
CORNER
EXECUTIVE EDITOR
Anna Schreck Bird
PharmD

DEPUTY EDITORS
Jessica Czechowski
PharmD DRUG
RECENT
INFORMATION PIPELINE
Lara Frick FDA
PharmD, BCPS, BCPP HAPPENINGS & NEWS
APPROVALS
Carole Kerzic
HIGHLIGHTS
RPh

Leslie Pittman
PharmD
 TRENDING
TOPICS
NEW WEEKLY GROWTH HORMONE THERAPY
The United States (US) Food and Drug Administration (FDA)
has approved Novo Nordisk’s once-weekly human growth
hormone (HGH) analog, somapacitan-beco (Sogroya®).
Somapacitan-beco is indicated for the replacement of
endogenous growth hormone (GH) in adults with growth
hormone deficiency (GHD), which is a rare disorder
caused by insufficient GH production. Management
of adults with GHD includes GH replacement therapy.
Recombinant GH, somatropin, is available from multiple
manufacturers and is also indicated for adults with GHD.
However, these products are given as daily subcutaneous
(SC) injections. Somapacitan-beco provides an additional
once-weekly GH therapy for adults with GHD.
Somapacitan-beco is supplied as a 10 mg/1.5 mL solution
in a single-patient-use prefilled pen that allows for
individualizing the patient dose in 0.05 mg increments
ranging from 0.05 mg to 4 mg. The patient can self-
administer the product by SC injection into the abdomen
or thigh following training by a healthcare professional
(HCP). The initial dose for treatment-naïve patients and
those switching from daily GH therapy with somatropin is
1.5 mg once weekly. The weekly dose is titrated every 2
to 4 weeks by 0.5 mg to 1.5 mg until the desired response
is reached (based on serum insulin-like growth factor 1
[IGF-1] levels), up to the maximum recommended dose
of 8 mg once weekly. The dose should be decreased, as
needed, due to adverse reactions and/or serum IGF-1
levels greater than the normal range. Patients who are ≥ 65
years old, have moderate hepatic impairment, or are on
oral estrogen therapy require alternative starting doses.
The efficacy and safety of somapacitan-beco were assessed
in a randomized, double-blind, placebo-controlled, 35-
week study conducted in treatment-naïve adult patients
with GHD. Patients received somapacitan-beco weekly,
somatropin daily, or placebo. Efficacy was based on the
percentage change of truncal fat, which is regulated by
GH. At week 34, somapacitan-beco resulted in a -1.06%
2 | OCTOBER 2020
reduction in the change from baseline in truncal fat
compared to a 0.47% increase with placebo (treatment
difference, -1.53%; 95% confidence interval [CI],
-2.68 to -0.38). Patients on daily somatropin also
demonstrated a decrease in truncal fat (-2.23%) from
baseline.
Somapacitan-beco is contraindicated in patients with
active malignancy, acute critical illness, hypersensitivity
to the product, and active proliferative or severe non-
proliferative diabetic retinopathy. It also carries a number
of warnings and precautions, including an increased
risk of neoplasm, glucose intolerance and diabetes,
intracranial hypertension, pancreatitis, hypoadrenalism,
fluid retention, hypothyroidism, and lipohypertrophy
or lipoatrophy. Patients should receive a fundoscopic
exam prior to starting and periodically during therapy
to exclude papilledema (swelling of the optic nerve),
which can be a symptom of intracranial hypertension.
BOXED WARNING REMOVED FOR DM DRUG
The FDA has removed the boxed warning on the risk of
amputations from the product labeling of the diabetes
medications canagliflozin (Invokana®) and canagliflozin/
metformin hydrochloride (Invokamet®, Invokamet® XR).
The prior boxed warning was added in 2017, following a
determination that the risk for amputation was significant
compared to the potential benefit of therapy for use as an
adjunct to diet and exercise for decreasing blood glucose
levels in adults with type 2 diabetes mellitus (DM). Other
clinical benefits leading to additional indication approvals
have resulted in increased benefits of the drug, and the
risk of amputation is suggested to be lower than previously
reported, especially with appropriate monitoring. As a
result, the FDA has determined that the boxed warning
should be removed. As there remains an increased risk
with canagliflozin, the potential for amputation is still
included in the Warnings and Precautions section of the
product labeling.
TRENDING TOPICS continued
HCTZ AND THE RISK OF SKIN CANCER
The FDA has approved label changes for drugs
containing hydrochlorothiazide (HCTZ) to notify
HCPs and patients about the small but increased
risk of non-melanoma skin cancer (basal cell skin
cancer or squamous cell skin cancer) associated with
HCTZ. The FDA Sentinel Initiative study determined
that the increased risk of skin cancer was primarily
linked to squamous cell carcinoma (SCC). In patients
on HCTZ, the increased risk was about 1 additional
case per 16,000 patients per year.
BEHAVIORAL HEALTH CORNER:
APA SCHIZOPHRENIA GUIDELINES
The American Psychiatric Association (APA) updated
their guidelines on the treatment of schizophrenia.
Regarding drug therapy, patients with schizophrenia
are recommended to receive treatment with an
antipsychotic medication with monitoring for efficacy
and adverse effects. An antipsychotic should be
continued in patients with symptom improvement.
The use of clozapine is recommended specifically in
patients who are treatment-resistant or when the risk
for suicide attempt or suicidality remains significant
despite other treatment. In patients with aggressive
behavior that continues to be significant despite
other treatments, clozapine is suggested. Long-acting
injectable (LAI) antipsychotics are suggested to be
used when the patient prefers these agents or in
those with a history of poor or uncertain adherence.
Notable drug therapy statements on treatment
of antipsychotic-related adverse effects are also
provided and include the use of an anticholinergic
for patients with acute dystonia. For patients with
parkinsonism associated with antipsychotic therapy,
APA suggests lowering the dose, switching therapy to
another antipsychotic, or use of an anticholinergic.
For patients with akathisia, lowering the dose,
switching therapy to another antipsychotic, or use
of a benzodiazepine or a beta-blocker are suggested.
For moderate, severe, or disabling tardive dyskinesia,
use of a reversible vesicular monoamine transporter 2
(VMAT2) inhibitor is recommended. In addition to drug
therapy recommendations, the guidelines also provide
recommendations regarding patient assessment,
treatment planning, and psychosocial interventions.
Word count: 742
COVID-19: NOTABLE DEVELOPMENTS
The FDA has approved an Emergency Use Authorization
(EUA) for investigational convalescent plasma for the
treatment of novel coronavirus infection (COVID-19)
in hospitalized patients. Based on current evidence,
the potential benefit of convalescent plasma has
been determined to be greater than the potential
risks. There are currently no approved alternative
therapies, and COVID-19 convalescent plasma may
improve disease severity or shorten the course of
illness in hospitalized patients.
The EUA allows for distribution of COVID-19
convalescent plasma and administration by HCPs for
treating suspected or laboratory-confirmed COVID-19
in hospitalized patients. The FDA notes that potential
adverse effects include allergic reactions, transfusion-
associated circulatory overload or lung injury, and
transfusion-transmitted infections. The agency also
states that the EUA does not replace randomized clinical
trials, which are crucial for definitively determining
the safety and efficacy of COVID-19 convalescent
plasma for COVID-19 illness.
The National Institutes of Health (NIH)’s COVID-19
Treatment Guideline Panel has released a statement
on the EUA advising that the data are currently
inadequate to recommend for or against use of
convalescent plasma for COVID-19. Although data
suggest that serious adverse reactions are rare,
the long-term effects have not been evaluated.
Furthermore, it should not be considered standard
of care for COVID-19 patients, and prospective,
sufficiently powered, controlled, randomized studies
are required to assess its efficacy and safety.
The FDA has announced a public meeting of the
Vaccines and Related Biological Products Advisory
Committee will be held on October 22, 2020. The
meeting will focus on the development and approval
of vaccines for the prevention of COVID-19.
For more resources on COVID-19, visit the Magellan
Rx Coronavirus Update webpage. For the most current
information, visit the FDA, the Centers for Disease
Control and Prevention (CDC), the NIH, and the World
Health Organization (WHO) websites. State and local
health departments also provide valuable information
regarding management in local communities.
 DRUG INFORMATION
HAPPENINGS &
HIGHLIGHTS
• Following reports of nitrosamine impurities, the FDA
issued a communication regarding their work to mitigate
shortages of rifampin (Rifadin®) and rifapentine (Priftin®).
The agency will temporarily allow distribution of rifampin
containing 1-methyl-4-nitrosopiperazine (MNP) or
rifapentine containing 1-cyclopentyl-4-nitrosopiperazine
(CPNP) greater than the acceptable intake limits in
an effort to maintain access until impurities can be
reduced or eliminated. For additional details, view the
FDA’s Communication. Furthermore, the FDA has issued
guidance to industry on the detection and prevention
of these impurities.
• Emergent, the manufacturer of the naloxone nasal
spray (Narcan®), has announced the FDA approval of
an extension to the shelf life of the product. Previously
24 months, the shelf life has been extended to
36 months. Naloxone nasal spray is an opioid antagonist
FDA-approved for the emergency treatment of opioid
overdose, as characterized by respiratory and/or central
nervous system (CNS) depression.
• Bayshore has announced a voluntary recall of 1 lot of
metformin hydrochloride (HCl) extended-release (ER)
tablets USP, 500 mg, supplied in 1,000-count bottles
and 1 lot of metformin HCl ER tablets USP, 750 mg,
supplied in 100-count bottles that are within expiry.
The recall is to the consumer level and is due to the
detection of N-Nitrosodimethylamine (NDMA) levels
above the acceptable daily intake limit. For details,
view the recall announcement. For more information
and for updates on NDMA in metformin-containing
products, visit the FDA’s website.
• Mylan has received FDA approval for the first generic
version of Biogen’s dimethyl fumarate (Tecfidera®).
Dimethyl fumarate is indicated for the treatment of
relapsing forms of multiple sclerosis (MS) in adults, to
include clinically isolated syndrome, relapsing-remitting
disease, and active secondary progressive disease.
It is available as an oral delayed-release capsule in
the strengths of 120 mg and 240 mg. For additional
details on the new generic, view the manufacturer’s
press release.

DRUG INFORMATION HAPPENINGS

• The American Board of Internal Medicine (ABIM) Foundation initiative, Choosing Wisely, released an American
Academy of Pediatrics (AAP) section providing evidence-based recommendations on therapies and practices
used for the management of asthma, respiratory disorders, and sleep conditions in pediatric patients.
• The American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP) have
published a new clinical practice guideline on the management of acute pain associated with non-low back
musculoskeletal injuries in outpatient adults.
• The American Society of Hematology (ASH) published 2020 guidelines for treating newly-diagnosed acute
myeloid leukemia (AML) in older adults.
• The US Preventive Services Task Force (USPSTF) has issued a final recommendation on behavioral counseling for
sexually transmitted infections (STIs). Behavioral counseling is recommended for all sexually active adolescents
and for adults who are at increased risk for STIs (Grade B).

4 | OCTOBER 2020
 PIPELINE
NEWS
UPCOMING PRESCRIPTION DRUG/BIOSIMILAR USER FEE ACT (PDUFA/BsUFA) DATES
DRUG NAME FORMULATION ANTICIPATED FDA
PROPOSED CLINICAL USE
MANUFACTURER THERAPEUTIC CLASS APPROVAL

tramadol • IV Postsurgical pain 10/09/2020

Fortress • Opioid agonist

zolmitriptan microneedle • Transdermal Acute migraine treatment 10/20/2020

patch • Triptan
Zosano

eflapegrastim • SC Chemotherapy-induced 10/23/2020

Spectrum • Colony stimulating factor neutropenia

REGN-EB3 • IV Ebola virus infection 10/23/2020

Regeneron • Antiviral antibody

loteprednol etabonate • Ophthalmic Dry eye syndrome 10/30/2020

0.25% • Glucocorticosteroid
Kala

mannitol dry powder • Inhalation Cystic fibrosis 10/30/2020

Pharmaxis • Mucolytic
viloxazine • Oral Attention deficit 11/06/2020
Supernus • Serotonin norepinephrine hyperactivity disorder
modulating agent (ADHD)
amphetamine • Oral ADHD 11/13/2020
(immediate-release, • CNS stimulant
tamper-resistant)
Arbor

naloxone prefilled syringe • IM Opioid overdose 11/13/2020

US WorldMeds • Opioid antagonist
samidorphan/olanzapine • Oral Bipolar disorder; 11/13/2020
Alkermes • Opioid antagonist/atypical Schizophrenia
antipsychotic

sutimlimab • IV Cold agglutinin disease 11/13/2020

Sanofi • Complement inhibitor
IM = intramuscular; IV = intravenous; SC = subcutaneous
 RECENT FDA
APPROVALS
DRUG NAME
DESCRIPTION
MANUFACTURER

New Drugs

clascoterone • NDA approval 08/26/2020

(Winlevi®) • Indicated for the topical treatment of acne vulgaris in patients ≥ 12 years of age
Cassiopea • Androgen receptor inhibitor
• Topical cream: 1% in a 60 g tube
• Recommended dosage is a thin layer (approximately 1 g) applied topically to affected
area twice daily
• Product availability is expected in early 2021

bupivacaine • 505(b)(2) NDA approval 08/28/2020

(Xaracoll®) • Indicated for use in adults for placement into the surgical site to produce postsurgical
Innocoll analgesia for up to 24 hours following open inguinal hernia repair; safety and efficacy
have not been established in other surgical procedures (e.g., orthopedic and boney
procedures)
• Amide local anesthetic
• Resorbable and biodegradable collagen implant: 100 mg bupivacaine per implant
(3 implants per package)
• Recommended dosage is 300 mg (3 implants); cut each implant in half using aseptic
technique prior to placing the dry implants into the surgical site; place 3 halves
below the site of mesh placement and 3 halves below the skin closure
• Product availability is expected in late 2020

somapacitan-beco • BLA approval 08/28/2020

(Sogroya®) • Indicated for the replacement of endogenous GH in adults with GHD
Novo Nordisk • Human GH analog
• Injection: 10 mg/1.5 mL (6.7 mg/mL) prefilled pen
• Recommended initial dosages are:
» 1.5 mg SC once weekly for treatment-naïve patients and those switching from
daily GH therapy
» 1 mg SC once weekly in patients ≥ 65 years of age and for those with moderate
hepatic impairment
» 2 mg SC once weekly in women taking oral estrogen
• Titrate dose based on serum IGF-1 level and clinical response; may increase dose
every 2 to 4 weeks by 0.5 mg to 1.5 mg; maximum dose is 8 mg once weekly
ANDA = Abbreviated New Drug Application; BLA = Biologics License Application; H = Half; NDA = New Drug Application; Q = Quarter; sBLA = Supplemental
Biologics License Application; sNDA = Supplemental New Drug Application; 505(b)(2) = FDA approval pathway that allows for submission of data from
studies not conducted by or for the applicant.

6 | OCTOBER 2020
RECENT FDA APPROVALS continued
DRUG NAME
DESCRIPTION
MANUFACTURER

New Drugs continued

azacitidine • NDA approval 09/01/2020; Orphan Drug, Priority Review

(Onureg®) • Indicated for continued treatment of adults with acute myeloid leukemia (AML)
Celgene who achieved 1st complete remission (CR) or complete remission with incomplete
blood count recovery (CRi) following intensive induction chemotherapy and who
are not able to complete intensive curative therapy
• Nucleoside metabolic inhibitor
• Tablets: 200 mg and 300 mg
• Recommended dosage is 300 mg orally once daily on days 1 to 14 of each 28-day
cycle; continue until disease progression or unacceptable toxicity; administer
an antiemetic before each dose for at least the first 2 cycles; follow appropriate
handling and disposal procedures for hazardous drugs
• Not a substitute for IV or SC azacitidine (Vidaza®)

tramadol HCl • 505(b)(2) NDA approval 09/01/2020

(Qdolo™) • Indicated for use in adults for the management of pain severe enough to require an
Athena Biosciences opioid analgesic and for which alternative treatments are inadequate; due to the
risks of addiction, abuse, and misuse with opioids, reserve for use in patients for
whom alternative treatments have not been tolerated or have provided inadequate
analgesia
• Opioid agonist
• Oral solution: 5 mg/mL
• Recommended initial dosage is 25 mg per day; may titrate the dose as described in
the product labeling as 25 mg (initial) to 50 mg increments every 3 days; maximum
400 mg per day, divided in doses given every 4 to 6 hours
• Boxed warnings for addiction, abuse, misuse; medication errors; life-threatening
respiratory depression; accidental ingestion; ultra-rapid metabolism in children;
neonatal opioid withdrawal syndrome; potential drug interaction with CYP450
isoenzymes; concomitant use with benzodiazepines or other CNS depressants;
requirement for Risk Evaluation and Mitigation Strategy (REMS) program
• Scheduled IV controlled substance

pralsetinib • NDA approval 09/04/2020; Accelerated Approval, Assessment Aid, Breakthrough

(Gavreto™) Therapy, Orphan Drug, Priority Review, Real-Time Oncology Review
Blueprint/Genentech • Indicated for the treatment of adults with metastatic rearranged during transfection (RET)
fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA-approved
test; continued approval may require demonstration of benefit in confirmatory
clinical trials
• Kinase inhibitor of wild-type RET and oncogenic RET fusions and mutations
• Capsule: 100 mg
• Recommended dosage is 400 mg orally once daily on an empty stomach (no food for
≥ 2 hours before and ≥ 1 hour after) with therapy continued until disease progression
or until unacceptable toxicity
ANDA = Abbreviated New Drug Application; BLA = Biologics License Application; H = Half; NDA = New Drug Application; Q = Quarter; sBLA = Supplemental
Biologics License Application; sNDA = Supplemental New Drug Application; 505(b)(2) = FDA approval pathway that allows for submission of data from studies
not conducted by or for the applicant.

References: fda.gov nih.gov psychiatryonline.org rarediseases.org

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