FEATURE
SIDEBAR 2
What Makes a Good Violence-Prevention Program?
The U.S. Department of Labor’s Occupational Safety and
Health Administration offers the following recommenda-
tions for hospitals, long-term care facilities, community care
settings, and field workers in crafting their violence-preven-
tion programs.
Management commitment and employee participation:
Acknowledge the value of and allocate appropriate authority
and resources to establish a safe and healthful, violence-free
workplace.
Worksite analysis: Perform a step-by-step assessment of
the workplace (with workers and employers) to find existing
or potential hazards that may lead to incidents of workplace
violence.
Hazard prevention and control: Identify and evaluate control
options for workplace hazards, then select feasible controls
to eliminate or reduce hazards, with continued follow-up to
evaluate their effectiveness.
Safety and health training: Educate all staff members about
potential hazards and how to protect themselves and their
coworkers through established policies and procedures.
Record keeping and program evaluation: Maintain accurate
records of injuries, illnesses, incidents, assaults, hazards,
corrective actions, patient histories, and training to deter-
mine the prevention plan’s overall effectiveness.
Source: OSHA. Guidelines for preventing workplace violence for healthcare and social service work-
ers. Accessed September 27, 2018, from https://www.osha.gov/Publications/osha3148.pdf.
S:7”
Venous thromboembolic events (VTE) occurred in
4.7% of patients treated with POMALYST and
Low-dose Dex, and 1.3% of patients treated with
high-dose dexamethasone. Arterial thromboembolic
events include terms for arterial thromboembolic
events, ischemic cerebrovascular conditions, and
ischemic heart disease. Arterial thromboembolic
events occurred in 3.0% of patients treated with
POMALYST and Low-dose Dex, and 1.3% of
patients treated with high-dose dexamethasone.
Patients with known risk factors, including prior
thrombosis, may be at greater risk, and actions
should be taken to try to minimize all modifiable
factors (e.g., hyperlipidemia, hypertension, smoking).
Thromboprophylaxis is recommended, and the
choice of regimen should be based on assessment
of the patient’s underlying risk factors.
5.4 Increased Mortality in Patients with Multiple
Myeloma When Pembrolizumab Is Added to a
Thalidomide Analogue and Dexamethasone
In two randomized clinical trials in patients with
multiple myeloma, the addition of pembrolizumab
to a thalidomide analogue plus dexamethasone, a
use for which no PD-1 or PD-L1 blocking antibody
is indicated, resulted in increased mortality. Treatment
of patients with multiple myeloma with a PD-1 or
PD-L1 blocking antibody in combination with a
thalidomide analogue plus dexamethasone is not
recommended outside of controlled clinical trials.
5.6 Hepatotoxicity
Hepatic failure, including fatal cases, has occurred
in patients treated with POMALYST. Elevated levels
of alanine aminotransferase and bilirubin have also
been observed in patients treated with POMALYST.
Monitor liver function tests monthly. Stop POMALYST
upon elevation of liver enzymes and evaluate. After
return to baseline values, treatment at a lower dose
may be considered.
5.7 Severe Cutaneous Reactions Including
Hypersensitivity Reactions
Angioedema and severe cutaneous reactions
including Stevens-Johnson syndrome (SJS), toxic
epidermal necrolysis (TEN) and drug reaction with
eosinophilia and systemic symptoms (DRESS) have
been reported. DRESS may present with a
cutaneous reaction (such as rash or exfoliative
dermatitis), eosinophilia, fever, and/or
lymphadenopathy with systemic complications
such as hepatitis, nephritis, pneumonitis,
myocarditis, and/or pericarditis. Discontinue
POMALYST for angioedema, skin exfoliation, bullae,
or any other severe cutaneous reactions such as
SJS, TEN or DRESS, and do not resume therapy
[see Dosage and Administration (2.2)].
5.8 Dizziness and Confusional State
In trials 1 and 2 in patients who received POMALYST
+ Low-dose Dex, 14% of patients experienced
dizziness and 7% of patients experienced a
confusional state; 1% of patients experienced
Grade 3 or 4 dizziness, and 3% of patients experienced
Grade 3 or 4 confusional state. Instruct patients to
avoid situations where dizziness or confusional
state may be a problem and not to take other
medications that may cause dizziness or confusional
state without adequate medical advice.
5.9 Neuropathy
In trials 1 and 2 in patients who received POMALYST
+ Low-dose Dex, 18% of patients experienced
neuropathy, with approximately 12% of the patients
experiencing peripheral neuropathy. Two percent of
5.10 Risk of Second Primary Malignancies
Cases of acute myelogenous leukemia have been
reported in patients receiving POMALYST as an
investigational therapy outside of multiple myeloma.
5.11 Tumor Lysis Syndrome
Tumor lysis syndrome (TLS) may occur in patients
treated with pomalidomide. Patients at risk for TLS
are those with high tumor burden prior to treatment.
These patients should be monitored closely and
appropriate precautions taken.
6 ADVERSE REACTIONS
The following adverse reactions are described in
detail in other labeling sections:
• Fetal Risk [see Boxed Warning, Warnings and
Precautions (5.1, 5.2)]
• Venous and Arterial Thromboembolism [see
Boxed Warning, Warnings and Precautions (5.3)]
• Increased Mortality in Patients with Multiple
Myeloma When Pembrolizumab Is Added to a
Thalidomide Analogue and Dexamethasone [see
Warnings and Precautions (5.4)]
• Hematologic Toxicity [see Warnings and
Precautions (5.5)]
• Hepatotoxicity [see Warnings and Precautions
(5.6)]
• Severe Cutaneous Reactions Including
Hypersensitivity Reactions [see Warnings and
Precautions (5.7)]
• Dizziness and Confusional State [see Warnings
and Precautions (5.8)]
• Neuropathy [see Warnings and Precautions (5.9)]
• Risk of Second Primary Malignancies [see
Warnings and Precautions (5.10)]
• Tumor Lysis Syndrome [see Warnings and
Precautions (5.11)]
6.1 Clinical Trials Experience
Multiple Myeloma
Because clinical trials are conducted under widely
varying conditions, adverse reaction rates observed
in the clinical trials of a drug cannot be directly
compared to rates in the clinical trials of another drug
and may not reflect the rates observed in practice.
In Trial 1, data were evaluated from 219 patients
(safety population) who received treatment with
POMALYST + Low-dose Dex (112 patients) or
POMALYST alone (107 patients). Median number
of treatment cycles was 5. Sixty-seven percent of
patients in the study had a dose interruption of
either drug due to adverse reactions. Forty-two
percent of patients in the study had a dose reduction
of either drug due to adverse reactions. The
discontinuation rate due to adverse reactions was 11%.
In Trial 2, data were evaluated from 450 patients
(safety population) who received treatment with
POMALYST + Low-dose Dex (300 patients) or High-
dose Dexamethasone (High-dose Dex) (150 patients).
The median number of treatment cycles for the
POMALYST + Low-dose Dex arm was 5. In the
POMALYST + Low-dose Dex arm, 67% of patients
had a dose interruption of POMALYST, the median
time to the first dose interruption of POMALYST
was 4.1 weeks. Twenty-seven percent of patients
had a dose reduction of POMALYST, the median
time to the first dose reduction of POMALYST was
4.5 weeks. Eight percent of patients discontinued
POMALYST due to adverse reactions.
Tables 2 and 3 summarize the adverse reactions
reported in Trials 1 and 2, respectively.
In Trial 1 of 219 patients who received POMALYST
alone a (N=107) or POMALYST + Low-dose Dex
(N=112), all patients had at least one adverse
reaction.*
Adverse reactions ≥10% in either arm, respectively,
included: Blood and lymphatic system disorders:
Neutropenia b (53%, 49%), Anemia b (38%, 42%),
Thrombocytopenia b (26%, 23%), Leukopenia (13%,
20%), Febrile neutropenia b (<10%, <10%),
Lymphopenia (4%, 15%); General disorders and
administration site conditions: Fatigue and
asthenia b (58%, 63%), Edema peripheral (25%,
17%), Pyrexia b (23%, 32%), Chills (10%, 13%);
Gastrointestinal disorders: Nausea b (36%, 24%),
Constipation b (36%, 37%), Diarrhea (35%, 36%),
Vomiting b (14%, 14%); Musculoskeletal and
connective tissue disorders: Back pain b (35%,
32%), Musculoskeletal chest pain (23%, 20%),
Muscle spasms (22%, 20%), Arthralgia (17%,
15%), Muscular weakness (14%, 13%), Bone pain
(12%, 7%), Musculoskeletal pain (12%, 17%),
Pain in extremity (8%, 14%); Infections and
infestations: Upper respiratory tract infection
(37%, 29%), Pneumonia b (28%, 34%), Urinary
tract infection b (10%, 17%), Sepsis b (<10%, <10%);
Metabolism and nutrition disorders: Decreased
appetite (23%, 19%), Hypercalcemia b (22%, 12%),
Hypokalemia (12%, 12%), Hyperglycemia (11%,
15%), Hyponatremia (11%, 13%), Dehydration b
(<10%, <10%), Hypocalcemia (6%, 12%);
Respiratory, thoracic and mediastinal disorders:
Dyspnea b (36%, 45%), Cough (17%, 22%),
Epistaxis (17%, 11%), Productive cough (9%,
13%), Oropharyngeal pain (6%, 11%); Nervous
system disorders: Dizziness (22%, 18%),
Peripheral neuropathy (22%, 18%), Headache
(15%, 13%), Tremor (10%, 13%); Skin and
subcutaneous tissue disorders: Rash (21%, 16%),
Pruritus (15%, 9%), Dry skin (9%, 11%),
Hyperhidrosis (8%, 16%), Night sweats (5%, 13%);
Investigations: Blood creatinine increased b (19%,
10%), Weight decreased (15%, 9%), Weight
increased (1%, 11%); Psychiatric disorders:
Anxiety (13%, 7%), Confusional state b (12%, 13%),
Insomnia (7%, 16%); Renal and urinary disorders:
Renal failure b (15%, 10%).
In Trial 1, Grade 3/4 at least one adverse reaction
reported in 92% of patients treated with
POMALYST a alone (N=107) and 91% with
POMALYST + Low-dose Dex (N=112).*
Grade 3/4 Adverse Reactions ≥ 5% in either arm,
respectively, included: Blood and lymphatic system
disorders: Neutropenia b (48%, 41%), Anemia b
(23%, 21%), Thrombocytopenia b (22%, 19%),
Leukopenia (7%, 10%), Febrile neutropenia b (6%,
3%), Lymphopenia (2%, 7%); General disorders
and administration site conditions: Fatigue and
asthenia b (12%, 17%), Edema peripheral (0%, 0%),
Pyrexia b (<5%, <5%), Chills (0%, 0%);
Gastrointestinal disorders: Nausea b (<5%, <5%),
Constipation b (<5%, <5%), Diarrhea (<5%, <5%),
Vomiting b (<5%, 0%); Musculoskeletal and
connective tissue disorders: Back pain b (14%,
10%), Musculoskeletal chest pain (<5%, 0%),
Muscle spasms (<5%, <5%), Arthralgia (<5%,
<5%), Muscular weakness (6%, 4%), Bone pain
(<5%, <5%), Musculoskeletal pain (<5%, <5%),
Pain in extremity (0%, <5%); Infections and
infestations: Upper respiratory tract infection
(<5%, <5%), Pneumonia b (20%, 29%), Urinary
tract infection b (2%, 9%), Sepsis b (6%, 5%);
Metabolism and nutrition disorders: Decreased
appetite (<5%, 0%), Hypercalcemia b (10%, 1%),
Hypokalemia (<5%, <5%), Hyperglycemia (<5%,
<5%), Hyponatremia (<5%, <5%) Dehydration b
(5%, 5%), Hypocalcemia (0%, <5%); Respiratory,
thoracic and mediastinal disorders: Dyspnea b
(8%, 13%), Cough (0%, 0%), Epistaxis (<5%, 0%),
Productive cough (0%, 0%), Oropharyngeal pain
(0%, 0%); Nervous system disorders: Dizziness
(<5%, <5%), Peripheral neuropathy (0%, 0%),
Headache (0%, <5%), Tremor (0%, 0%); Skin and
subcutaneous tissue disorders: Rash (0%, <5%),
Pruritus (0%, 0%), Dry skin (0%, 0%),
Hyperhidrosis (0%, 0%), Night sweats (0%, 0%);
Investigations: Blood creatinine increased b (6%,
3%), Weight decreased (0%, 0%), Weight
increased (0%, 0%); Psychiatric disorders: Anxiety
(0%, 0%), Confusional state b (6%, 3%), Insomnia
(0%, 0%); Renal and urinary disorders: Renal
failure b (8%, 7%).
* Regardless of attribution of relatedness to
POMALYST.
a POMALYST alone arm includes all patients
randomized to the POMALYST alone arm who
took study drug; 61 of the 107 patients had
dexamethasone added during the treatment period.
b Serious adverse reactions were reported in at least
2 patients in any POMALYST treatment arm.
Data cutoff: 01 March 2013
5.5 Hematologic Toxicity
In trials 1 and 2 in patients who received
POMALYST + Low-dose Dex, neutropenia was the
most frequently reported Grade 3/4 adverse reaction,
followed by anemia and thrombocytopenia.
Neutropenia of any grade was reported in 51% of
patients in both trials. The rate of Grade 3/4
neutropenia was 46%. The rate of febrile neutropenia
was 8%.
Monitor patients for hematologic toxicities, especially
neutropenia. Monitor complete blood counts weekly
for the first 8 weeks and monthly thereafter. Patients
may require dose interruption and/or modification
[see Dosage and Administration (2.2)].
patients experienced Grade 3 neuropathy in trial 2.
There were no cases of Grade 4 neuropathy adverse
reactions reported in either trial.