FEATURE
Mr. Nerette said. “Honestly, we have that conversation at
least once or twice a month.”
From a legal perspective, added Mr. Glasser, other than
in emergency situations, “a physician would be allowed
to refrain from treating under circumstances in which a
patient becomes violent and the physician does not believe
it is safe or appropriate to treat.”
“Organizations that understand, prepare for, and are
resourced to manage the threat of violence against their
employees do better, because even people who are poten-
tially violent require health care,” said Mr. Nerette. “It’s just
a matter of asking ourselves, ‘How do we deliver that care
in a way that’s safe for all involved?’”
Playing Defense
In 2017, Dr. Arnetz and her group published findings from
one of the few randomized, large-scale studies to assess the
impact of preventive strategies for violence in the hospi-
tal workplace. 10 “Our goal was to develop what I called
‘standardized methods’ for the development of violence-
prevention plans,” she explained. “Any hospital can do this
– it doesn’t take a lot of money or time.”
The study included 41 units across seven U.S. hospitals,
21 of which were randomized into an intervention group.
These units were provided with unit-level violence data,
along with data from other units for comparison, and a
checklist of possible environmental, administrative, and
behavioral interventions derived from OSHA guidelines.
Control units received no data.
“We then gave them the task of putting together an action
plan based on the data they had received,” she continued.
The solutions proposed by unit staff were practical, var-
ied, and, for the most part, relatively inexpensive and simple
S:7”
associated skeletal malformations (not ossified
metacarpal, misaligned phalanx and metacarpal,
absent digit, not ossified phalanx, and short not
ossified or bent tibia), moderate dilation of the
lateral ventricle in the brain, abnormal placement
of the right subclavian artery, absent intermediate
lobe in the lungs, low-set kidney, altered liver
morphology, incompletely or not ossified pelvis,
an increased average for supernumerary thoracic
ribs, and a reduced average for ossified tarsals.
No maternal toxicity was observed at the low dose
(10 mg/kg/day) that resulted in cardiac anomalies
in fetuses; this dose resulted in an exposure (AUC)
approximately equal to that reported in humans at
the recommended dose of 4 mg/day. Additional
embryo-fetal toxicity included increased resorption.
Following daily oral administration of pomalidomide
from Gestation Day 7 through Gestation Day 20 in
pregnant rabbits, fetal plasma pomalidomide
concentrations were approximately 50% of the
maternal C max at all dosages (5 to 250 mg/kg/day),
indicating that pomalidomide crossed the placenta.
8.2 Lactation
Risk Summary
There is no information regarding the presence of
pomalidomide in human milk, the effects of
POMALYST on the breastfed child, or the effects of
POMALYST on milk production. Pomalidomide was
excreted in the milk of lactating rats [see Data ].
Because many drugs are excreted in human milk
and because of the potential for adverse reactions
in a breastfed child from POMALYST, advise women
not to breastfeed during treatment with POMALYST.
Data
Animal Data
Following a single oral administration of pomalidomide
to lactating rats approximately 14 days postpartum,
pomalidomide was transferred into milk, with milk
to plasma ratios of 0.63 to 1.46.
8.4 Pediatric Use
Safety and effectiveness have not been established
in pediatric patients.
8.5 Geriatric Use
No dosage adjustment is required for POMALYST
based on age.
Of the total number of patients in clinical studies of
POMALYST, 44% were aged older than 65 years,
while 10% were aged older than 75 years. No
overall differences in effectiveness were observed
between these patients and younger patients. In
these studies, patients older than 65 years were
more likely than patients less than or equal to
65 years of age to experience pneumonia.
8.6 Renal Impairment
In patients with severe renal impairment requiring
dialysis, the AUC of pomalidomide increased by
38% and the rate of SAE increased by 64% relative
to patients with normal renal function; therefore,
starting dose adjustment is recommended. For
patients with severe renal impairment requiring
dialysis, POMALYST should be administered after
the completion of hemodialysis on dialysis days
because exposure of pomalidomide could be
significantly decreased during dialysis [see Dosage
and Administration (2.4)].
8.7 Hepatic Impairment
Pomalidomide is metabolized primarily by the liver.
Following single dose administration, the AUC of
pomalidomide increased 51%, 58%, and 72% in
subjects with mild (Child-Pugh class A), moderate
(Child-Pugh class B), and severe (Child-Pugh class C)
hepatic impairment compared to subjects with
normal liver function. Dose adjustment is
recommended in patients with hepatic impairment
[see Dosage and Administration (2.5)].
8.8 Smoking Tobacco
Cigarette smoking reduces pomalidomide AUC by
32% due to CYP1A2 induction. Advise patients that
smoking may reduce the efficacy of pomalidomide.
10 OVERDOSAGE
No specific information is available on the treatment
of overdose with pomalidomide. Hemodialysis can
remove pomalidomide from circulation.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of
Fertility
Studies examining the carcinogenic potential of
pomalidomide have not been conducted. One of
12 monkeys dosed with 1 mg/kg of pomalidomide
(an exposure approximately 15-fold of the exposure
in patients at the recommended dose of 4 mg/day)
developed acute myeloid leukemia in a 9-month
repeat-dose toxicology study.
Pomalidomide was not mutagenic or clastogenic
in a battery of tests, including the bacteria reverse
mutation assay (Ames test), the in vitro assay using
human peripheral blood lymphocytes, and the
micronucleus test in orally treated rats administered
doses up to 2000 mg/kg/day.
In a fertility and early embryonic development
study in rats, drug-treated males were mated with
untreated or treated females. Pomalidomide was
administered to males and females at doses of
25 to 1000 mg/kg/day. When treated males were
mated with treated females, there was an increase
in post-implantation loss and a decrease in mean
number of viable embryos at all dose levels. There
were no other effects on reproductive functions or
the number of pregnancies. The lowest dose
tested in animals resulted in an exposure (AUC)
approximately 100-fold of the exposure in patients
at the recommended dose of 4 mg/day. When
treated males in this study were mated with untreated
females, all uterine parameters were comparable to
the controls. Based on these results, the observed
effects were attributed to the treatment of females.
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient
labeling (Medication Guide).
Embryo-Fetal Toxicity
Advise patients that POMALYST is contraindicated
in pregnancy [see Boxed Warning and
Contraindications (4)]. POMALYST is a thalidomide
analogue and may cause serious birth defects or
death to a developing baby [see Warnings and
Precautions (5.1) and Use in Specific Populations
(8.1)].
• Advise females of reproductive potential that they
must avoid pregnancy while taking POMALYST
and for at least 4 weeks after completing therapy.
• Initiate POMALYST treatment in females of
reproductive potential only following a negative
pregnancy test.
• Advise females of reproductive potential of the
importance of monthly pregnancy tests and the
need to use 2 different forms of contraception,
including at least 1 highly effective form,
simultaneously during POMALYST therapy, during
dose interruptions, and for 4 weeks after she has
completely finished taking POMALYST. Highly
effective forms of contraception other than tubal
ligation include IUD and hormonal (birth control
pills, injections, patch, or implants) and a partner’s
vasectomy. Additional effective contraceptive
methods include latex or synthetic condom,
diaphragm, and cervical cap.
• Instruct patient to immediately stop taking
POMALYST and contact her healthcare provider if
she becomes pregnant while taking this drug, if
she misses her menstrual period or experiences
unusual menstrual bleeding, if she stops taking
birth control, or if she thinks FOR ANY REASON
that she may be pregnant.
• Advise patient that if her healthcare provider is not
available, she should call Celgene Customer Care
Center at 1-888-423-5436 [see Warnings and
Precautions (5.1) and Use in Specific Populations
(8.3)].
• Advise males to always use a latex or synthetic
condom during any sexual contact with females
of reproductive potential while taking POMALYST
and for up to 4 weeks after discontinuing
POMALYST, even if they have undergone a
successful vasectomy.
• Advise male patients taking POMALYST that
they must not donate sperm [see Warnings and
Precautions (5.1) and Use in Specific Populations
(8.3)].
• All patients must be instructed to not donate
blood while taking POMALYST and for 4 weeks
following discontinuation of POMALYST [see
Warnings and Precautions (5.1)].
POMALYST REMS Program
Because of the risk of embryo-fetal toxicity,
POMALYST is only available through a restricted
program called POMALYST REMS [see Warnings
and Precautions (5.2)].
• Patients must sign a Patient-Physician Agreement
Form and comply with the requirements to receive
POMALYST. In particular, females of reproductive
potential must comply with the pregnancy testing,
contraception requirements, and participate in
monthly telephone surveys. Males must comply
with the contraception requirements [see Use in
Specific Populations (8.3)].
• POMALYST is available only from pharmacies
that are certified in POMALYST REMS program.
Provide patients with the telephone number and
website for information on how to obtain the
product.
8.3 Females and Males of Reproductive Potential
Pregnancy Testing
POMALYST can cause fetal harm when administered
during pregnancy [see Use in Specific Populations
(8.1)]. Verify the pregnancy status of females of
reproductive potential prior to initiating POMALYST
therapy and during therapy. Advise females of
reproductive potential that they must avoid
pregnancy 4 weeks before therapy, while taking
POMALYST, during dose interruptions and for at
least 4 weeks after completing therapy.
Females of reproductive potential must have 2
negative pregnancy tests before initiating POMALYST.
The first test should be performed within 10-14 days,
and the second test within 24 hours prior to
prescribing POMALYST. Once treatment has started
and during dose interruptions, pregnancy testing for
females of reproductive potential should occur weekly
during the first 4 weeks of use, then pregnancy
testing should be repeated every 4 weeks in females
with regular menstrual cycles. If menstrual cycles
are irregular, the pregnancy testing should occur
every 2 weeks. Pregnancy testing and counseling
should be performed if a patient misses her period
or if there is any abnormality in her menstrual
bleeding. POMALYST treatment must be discontinued
during this evaluation.
Contraception
Females
Females of reproductive potential must commit
either to abstain continuously from heterosexual
sexual intercourse or to use 2 methods of reliable
birth control simultaneously: one highly effective
form of contraception – tubal ligation, IUD, hormonal
(birth control pills, injections, hormonal patches,
vaginal rings, or implants), or partner’s vasectomy,
and 1 additional effective contraceptive method –
male latex or synthetic condom, diaphragm, or
cervical cap. Contraception must begin 4 weeks
prior to initiating treatment with POMALYST, during
therapy, during dose interruptions, and continuing
for 4 weeks following discontinuation of POMALYST
therapy. Reliable contraception is indicated even
where there has been a history of infertility, unless
due to hysterectomy. Females of reproductive
potential should be referred to a qualified provider
of contraceptive methods, if needed.
Males
Pomalidomide is present in the semen of males
who take POMALYST. Therefore, males must always
use a latex or synthetic condom during any sexual
contact with females of reproductive potential
while taking POMALYST and for up to 4 weeks
after discontinuing POMALYST, even if they have
undergone a successful vasectomy. Male patients
taking POMALYST must not donate sperm.
Infertility
Based on findings in animals, female fertility may
be compromised by treatment with POMALYST
[see Nonclinical Toxicology (13.1)].