Workplace Violence
Continued from page 140
– meaning there are many opportunities for conflicts to
arise. Mr. Nerette said his team is called on regularly to
manage potentially hazardous situations.
“Many of our patients are managing diseases that require
prolonged hospital stays or may require multiple visits to
the hospital each week,” he noted. “As patients and caregivers
navigate the continuum of care, they bring external issues
with them. And sometimes family members feel the need to
advocate on the patient’s behalf, but they’re doing so from a
position of emotion rather than facts or data.”
As the saying goes, an ounce of prevention is worth a
pound of cure, so Mr. Nerette and his security team try
to address aggressive or agitated behavior early – before it
escalates to violence.
“My primary concern is the safety of everybody in the
environment, specifically our workforce,” he said. “When
someone shows the inability to behave appropriately in the
environment, it compromises our ability to deliver great
care.”
If inappropriate behavior persists, Mr. Nerette’s next
step is drawing up a behavioral contract with patients
and families, mandating that, for the patient to continue
to receive care, he or she will act appropriately.
In recalcitrant or extreme cases, the patient can be
asked to seek care elsewhere.
“When people don’t feel safe, they don’t perform at
their best,” he continued. “If the patient creates a situation
where our providers aren’t delivering the best possible care,
we could be doing a disservice to the patient by continu-
ing care. Perhaps these situations create an opportunity for
the patient to reevaluate his or her circumstances and seek
elsewhere care that fits his or her needs.”
It is a tough conversation, but not an uncommon one,
S:7”
a Percentage did not meet the criteria to be
considered as an adverse reaction for POMALYST
for that category of event (i.e., all adverse events or
Grade 3 or 4 adverse events).
b Serious adverse reactions were reported in at least
3 patients in the POM + Low-dose Dex arm, AND at
least 1% higher than the High-dose-Dex arm
percentage.
Data cutoff: 01 March 2013
Other Adverse Reactions
Other adverse reactions of POMALYST in patients
with multiple myeloma, not described above, and
considered important:
Cardiac disorders: Myocardial infarction, Atrial
fibrillation, Angina pectoris, Cardiac failure
congestive
Ear and labyrinth disorders: Vertigo
Gastrointestinal disorders: Abdominal pain
General disorders and administration site
conditions: General physical health deterioration,
Non-cardiac chest pain, Multi-organ failure
Hepatobiliary disorders: Hyperbilirubinemia
Infections and infestations: Pneumocystis jiroveci
pneumonia, Respiratory syncytial virus infection,
Neutropenic sepsis, Bacteremia, Pneumonia
respiratory syncytial viral, Cellulitis, Urosepsis,
Septic shock, Clostridium difficile colitis, Pneumonia
streptococcal, Lobar pneumonia, Viral infection,
Lung infection
Investigations: Alanine aminotransferase increased,
Hemoglobin decreased
Injury, poisoning and procedural complications:
Fall, Compression fracture, Spinal compression
fracture
Metabolism and nutritional disorders:
Hyperkalemia, Failure to thrive
Nervous System disorders: Depressed level of
consciousness, Syncope
Psychiatric disorders: Mental status change
Renal and urinary disorders: Urinary retention,
Hyponatremia
Reproductive system and breast disorders: Pelvic
pain
Respiratory, thoracic, and mediastinal disorders:
Interstitial lung disease, Pulmonary embolism,
Respiratory failure, Bronchospasm
Vascular disorders: Hypotension
6.2 Postmarketing Experience
The following adverse reactions have been identified
during post approval use of POMALYST. 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.
Blood and lymphatic system disorders: Pancytopenia
Gastrointestinal disorders: Gastrointestinal
hemorrhage
Hepatobiliary disorders: Hepatic failure (including
fatal cases), elevated liver enzymes
Immune system disorders: Allergic reactions (e.g.,
angioedema, urticaria)
Infections and infestations: Hepatitis B virus
reactivation, Herpes zoster
Neoplasms benign, malignant and unspecified
(incl cysts and polyps): Tumor lysis syndrome,
basal cell carcinoma, and squamous cell carcinoma
of the skin
Skin and Subcutaneous Tissue Disorders:
Stevens-Johnson Syndrome, toxic epidermal
necrolysis, drug reaction with eosinophilia and
systemic symptoms (DRESS)
7 DRUG INTERACTIONS
7.1 Drugs That Affect Pomalidomide Plasma
Concentrations
Pomalidomide is primarily metabolized by CYP1A2
and CYP3A4. Pomalidomide is also a substrate for
P-glycoprotein (P-gp).
CYP1A2 inhibitors:
In healthy volunteers, co-administration of
fluvoxamine, a strong CYP1A2 inhibitor, increased
C max and AUC of pomalidomide by 24% and 125%
respectively. Increased pomalidomide exposure
increases the risk of exposure related toxicities.
Avoid co-administration of strong CYP1A2
inhibitors (e.g. ciprofloxacin and fluvoxamine)
[see Dosage and Administration (2.3)]. If
co-administration is unavoidable, reduce the
POMALYST dose [see Dosage and Administration
(2.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors
pregnancy outcomes in females exposed to
POMALYST during pregnancy as well as female
partners of male patients who are exposed to
POMALYST. This registry is also used to understand
the root cause for the pregnancy. Report any
suspected fetal exposure to POMALYST to the FDA
via the MedWatch program at 1-800-FDA-1088 and
also to Celgene Corporation at 1-888-423-5436.
Risk Summary
Based on the mechanism of action and findings
from animal studies, POMALYST can cause embryo-
fetal harm when administered to a pregnant female
and is contraindicated during pregnancy [see
Boxed Warning, Contraindications (4), and
Warnings and Precautions (5.1)].
POMALYST is a thalidomide analogue. Thalidomide
is a human teratogen, inducing a high frequency of
severe and life-threatening birth defects such as
amelia (absence of limbs), phocomelia (short
limbs), hypoplasticity of the bones, absence of
bones, external ear abnormalities (including anotia,
micropinna, small or absent external auditory canals),
facial palsy, eye abnormalities (anophthalmos,
microphthalmos), and congenital heart defects.
Alimentary tract, urinary tract, and genital
malformations have also been documented, and
mortality at or shortly after birth has been reported
in about 40% of infants.
Pomalidomide was teratogenic in both rats and
rabbits when administered during the period of
organogenesis. Pomalidomide crossed the placenta
after administration to pregnant rabbits [see Data].
If this drug is used during pregnancy or if the patient
becomes pregnant while taking this drug, the patient
should be apprised of the potential risk to a fetus.
If pregnancy does occur during treatment,
immediately discontinue the drug. Under these
conditions, refer patient to an obstetrician/
gynecologist experienced in reproductive toxicity
for further evaluation and counseling. Report any
suspected fetal exposure to POMALYST to the FDA
via the MedWatch program at 1-800-FDA-1088 and
also to Celgene Corporation at 1-888-423-5436.
The estimated background risk of major birth
defects and miscarriage for the indicated population
is unknown. The estimated background risk in the
U.S. general population of major birth defects is
2%-4% and of miscarriage is 15%-20% of clinically
recognized pregnancies.
Data
Animal Data
Pomalidomide was teratogenic in both rats and
rabbits in the embryo-fetal developmental studies
when administered during the period of organogenesis.
In rats, pomalidomide was administered orally to
pregnant animals at doses of 25 to 1000 mg/kg/day.
Malformations or absence of urinary bladder, absence of
thyroid gland, and fusion and misalignment of lumbar
and thoracic vertebral elements (vertebral, central,
and/or neural arches) were observed at all dose levels.
There was no maternal toxicity observed in this study.
The lowest dose in rats resulted in an exposure (AUC)
approximately 85-fold of the human exposure at the
recommended dose of 4 mg/day. Other embryo-fetal
toxicities included increased resorptions leading to
decreased number of viable fetuses.
In rabbits, pomalidomide was administered orally to
pregnant animals at doses of 10 to 250 mg/kg/day.
Increased cardiac malformations such as
interventricular septal defect were seen at all doses
with significant increases at 250 mg/kg/day. Additional
malformations observed at 250 mg/kg/day included
anomalies in limbs (flexed and/or rotated fore-
and/or hindlimbs, unattached or absent digit) and
In Trial 2 of 450 patients who received POMALYST
+ Low-dose Dex (N=300) or High-dose Dex (N=150),
at least one adverse reaction was reported in 99%
of patients.
All Adverse Reactions ≥5% in POMALYST + Low-
dose Dex arm, and at least 2% points higher than
the High-dose-Dex arm included: Blood and
lymphatic system disorders: Neutropenia b (51%,
21%), Thrombocytopenia (30%, 29%) a , Leukopenia
(13%, 5%), Febrile neutropenia b (9%, 0%);
General disorders and administration site
conditions: Fatigue and asthenia (47%, 43%),
Pyrexia b (27%, 23%), Edema peripheral (17%,
11%), Pain (4%, 2%) a ; Infections and infestations:
Upper respiratory tract infection b (31%, 13%),
Pneumonia b (19%, 13%), Neutropenic sepsis b (1%,
0%) a ; Gastrointestinal disorders: Diarrhea (22%,
19%), Constipation (22%, 15%), Nausea (15%,
11%), Vomiting (8%, 4%); Musculoskeletal and
connective tissue disorders: Back pain b (20%,
16%), Bone Pain b (18%, 14%), Muscle spasms
(15%, 7%), Arthralgia (9%, 5%), Pain in extremity
(7%, 6%) a ; Respiratory, thoracic and mediastinal
disorders: Dyspnea b (25%, 17%), Cough (20%,
10%), Chronic obstructive pulmonary disease b
(2%, 0%) a ; Nervous system disorders: Peripheral
neuropathy (17%, 12%), Dizziness (12%, 9%),
Headache (8%, 5%), Tremor (6%, 1%), Depressed
level of consciousness (2%, 0%) a ; Metabolism and
nutrition disorders: Decreased appetite (13%, 8%),
Hypokalemia (9%, 8%) a , Hypocalcemia (4%, 6%) a ;
Skin and subcutaneous tissue disorders: Rash
(8%, 1%), Pruritus (7%, 3%), Hyperhidrosis (5%,
1%); Investigations: Neutrophil count decreased
(5%, 1%), Platelet count decreased (3%, 2%) a ,
White blood cell count decreased (3%, 1%) a ,
Alanine aminotransferase increased (2%, 1%) a ,
Aspartate aminotransferase increased (1%, 1%) a ,
Lymphocyte count decreased (1%, 1%) a ; Renal and
urinary disorders: Renal failure (10%, 12%) a ;
Injury, poisoning and procedural complications:
Femur fracture b (2%, 1%) a ; Reproductive system
and breast disorders: Pelvic pain (2%, 2%) a .
In Trial 2, Grade 3/4 at least one adverse reaction
was reported in 86% of patients treated with
POMALYST + Low-dose Dex (N=300) and 85% with
High-dose Dex (N=150).
Grade 3/4 Adverse Reactions ≥1% in POMALYST +
Low-dose Dex arm, and at least 1% point higher
than the High-dose-Dex arm, respectively, included:
Blood and lymphatic system disorders:
Neutropenia b (48%, 16%), Thrombocytopenia
(22%, 26%) a , Leukopenia (9%, 3%), Febrile
neutropenia b (9%, 0%); General disorders and
administration site conditions: Fatigue and
asthenia (9%, 12%) a , Pyrexia b (3%, 5%) a , Edema
peripheral (1%, 2%) a , Pain (2%, 1%); Infections and
infestations: Upper respiratory tract infection b (3%,
1%), Pneumonia b (16%, 10%), Neutropenic sepsis b
(1%, 0%); Gastrointestinal disorders: Diarrhea
(1%, 1%) a , Constipation (2%, 0%), Nausea (1%,
1%) a , Vomiting (1%, 0%); Musculoskeletal and
connective tissue disorders: Back pain b (5%, 4%),
Bone pain b (7%, 5%), Muscle spasms (0%, 1%) a ,
Arthralgia (1%, 1%) a , Pain in extremity (2%, 0%);
Respiratory, thoracic and mediastinal disorders:
Dyspnea b (6%, 5%), Cough (1%, 1%) a , Chronic
obstructive pulmonary disease b (1%, 0%); Nervous
system disorders: Peripheral neuropathy (2%, 1%) a ,
Dizziness (1%, 1%) a , Headache (0%, 0%) a , Tremor
(1%, 0%) a , Depressed level of consciousness (1%,
0%); Metabolism and nutrition disorders:
Decreased appetite (1%, 1%) a , Hypokalemia (4%, 3%),
Hypocalcemia (2%, 1%); Skin and subcutaneous
tissue disorders: Rash (1%, 0%), Pruritus (0%, 0%) a ,
Hyperhidrosis (0%, 0%) a ; Investigations: Neutrophil
count decreased (5%, 1%), Platelet count decreased
(3%, 1%), White blood cell count decreased (3%,
0%), Alanine aminotransferase increased (2%, 0%),
Aspartate aminotransferase increased (1%, 0%),
Lymphocyte count decreased (1%, 0%); Renal and
urinary disorders: Renal failure (6%, 5%); Injury,
poisoning and procedural complications: Femur
fracture b (2%, 1%); Reproductive system and
breast disorders: Pelvic pain (1%, 0%).