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US POM dosing guide 2016 .pdf



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POMALYST® (pomalidomide) is a thalidomide analogue indicated, in combination with
dexamethasone, for patients with multiple myeloma who have received at least two prior
therapies including lenalidomide and a proteasome inhibitor and have demonstrated
disease progression on or within 60 days of completion of the last therapy.
POMALYST is only available through a restricted distribution program, POMALYST REMS®.

patients with
mpairment.
to learn more

POMALYST offers the convenience of
once-daily oral dosing for patients with
relapsed/refractory multiple myeloma

ing)

Comprehensive Cancer
ded Option When Used

NEW DATA: POMALYST can be used in
patients with all levels of renal impairment
(see inside for dosing)

at least two prior therapies, including
ave demonstrated disease progression

elines in Oncology (NCCN Guidelines®)
e Cancer Network, Inc 2016. All rights
omplete version of the guideline, go
K®, NCCN®, NCCN GUIDELINES®, and all
rehensive Cancer Network, Inc.

RNINGS

RTERIAL THROMBOEMBOLISM

SELECTED SAFETY INFORMATION: BOXED WARNINGS
WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISM
Embryo-Fetal Toxicity

is a thalidomide analogue.
severe birth defects or embryo-fetal
negative pregnancy tests before

• POMALYST is contraindicated in pregnancy. POMALYST is a thalidomide analogue.
Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal
death. In females of reproductive potential, obtain 2 negative pregnancy tests before
starting POMALYST treatment.

f contraception or continuously abstain
opping POMALYST treatment.

• Females of reproductive potential must use 2 forms of contraception or continuously abstain
from heterosexual sex during and for 4 weeks after stopping POMALYST treatment.

ution program called POMALYST REMS®.

POMALYST is only available through a restricted distribution program called POMALYST REMS®.
Venous and Arterial Thromboembolism

(PE), myocardial infarction, and
d with POMALYST. Prophylactic
ials. Thromboprophylaxis is
ased on assessment of the patient’s

on pages 6-7 and accompanying
NGS.

arfilzomib and pomalidomide in
h baseline risk factors. Ann Oncol.
A, et al. Pomalidomide plus lowple myeloma and moderate renal
homa. 2016;7:1-6.

VLIMID® are registered

16

US-POM160030

• Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and
stroke occur in patients with multiple myeloma treated with POMALYST. Prophylactic
antithrombotic measures were employed in clinical trials. Thromboprophylaxis is
recommended, and the choice of regimen should be based on assessment of the patient’s
underlying risk factors.
CONTRAINDICATIONS
• Pregnancy: POMALYST can cause fetal harm and is contraindicated in females who are
pregnant. If POMALYST 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.
Please see additional Important Safety Information on pages 6-7 and accompanying
full Prescribing Information, including Boxed WARNINGS.

POMALYST is an oral therapy that
can be taken at home or wherever
is convenient for your patients

POMALYST can be used in
patients with all levels
of renal impairment

The recommended starting dose is 4 mg/day on Days 1-21 of a
28-day cycle

Renal impairment is common in patients with relapsed/refractory
multiple myeloma1

• POMALYST should be given in combination with dexamethasone

• Up to 50% of patients develop renal complications during the course of their disease2

• Females of reproductive potential must have negative pregnancy testing and use
contraception methods before initiating POMALYST

POMALYST can be used in patients with severe renal impairment,
including those on dialysis

In the Phase 3 trial, low-dose dex was given on Days 1, 8, 15, and 22
of a 28-day cyclea:

• For patients with severe renal impairment requiring dialysis, the recommended dose
is 3 mg daily (25% dose reduction)

• Dex 40 mg for patients ≤75 years

• On hemodialysis days, take POMALYST following hemodialysis

• Dex 20 mg for patients >75 years
a

In general, POMALYST pharmacokinetics were not significantly
affected by renal impairment

Dex dose and schedule are based on the Phase 3 trial .

POMALYST does not require dose adjustments for patients
with renal impairment, excluding patients with severe renal
impairment on dialysis
Important Dosing Information
• POMALYST may be taken with water, and with or without food

• Mean exposure (AUC) to pomalidomide increased by 38% in patients with severe
renal impairment requiring dialysis

Patients with renal impairment,
excluding those on dialysis, can take POMALYST
at the recommended 4 mg starting dose

• Inform patients not to break, chew, or open the capsules
• Monitor CBCs every week for the first 8 weeks and monthly thereafter. Patients may require dose
interruption and/or modification
• 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
• Avoid concomitant use of POMALYST with strong inhibitors of CYP1A2. Consider alternative
treatments. If a strong CYP1A2 inhibitor must be used, reduce POMALYST dose by 50%

If immediate prior therapy was REVLIMID® (lenalidomide),
patients can receive POMALYST

Mild

4 mg

Severe

Moderate

(not on dialysis)

4 mg

4 mg

Severe

(on dialysis)

3 mg

SELECTED SAFETY INFORMATION: USE IN SPECIFIC POPULATIONS
• Renal Impairment: Reduce POMALYST dose by 25% in patients with severe renal impairment
requiring dialysis. Take dose of POMALYST following hemodialysis on hemodialysis days.
• Hepatic Impairment: Reduce POMALYST dose by 25% in patients with mild to moderate
hepatic impairment and 50% in patients with severe hepatic impairment.

REVLIMID®
(lenalidomide)

progression
+ low-dose dex

POMALYST, in combination with dex, is indicated for patients with multiple myeloma who have
received at least 2 prior therapies, including REVLIMID and a proteasome inhibitor, and have
demonstrated disease progression on or within 60 days of completion of the last therapy.

Please see additional Important Safety Information on pages 6-7 and accompanying
full Prescribing Information, including Boxed WARNINGS.
2

3

With dose interruptions and
reductions, the majority of patients
did not need to discontinue treatment

Dose modifications
may help your patients
stay on therapy

8% of patients discontinued POMALYST + low-dose dex due to adverse
reaction(s) in the Phase 3 trial (POMALYST + low-dose dex arm, n=300)

Hematologic toxicities in the Phase 3 trial:
• Neutropenia was the most frequently reported Grade 3/4 adverse reaction, followed by anemia
and thrombocytopenia
° Neutropenia of any grade was reported in 51.3% of patients in the trial

Dose modifications of POMALYST due to adverse reaction(s)

° Grade 3/4 neutropenia was 48.3%, and febrile neutropenia was 9.3%
• Monitor patients for hematologic toxicities, especially neutropenia. Monitor complete blood
counts weekly for the first 8 weeks and monthly thereafter

67

%

Dose interruption

27

8

Dose reduction

Discontinuation

%

%

Dose modification instructions for hematologic toxicities
Neutropenia

Dose Modification

Start at 4 mg
ANC <500 per mcL or
febrile neutropenia
(fever ≥38.5°C and
ANC <1,000 per mcL)
ANC returns to ≥500 per mcL

• The median time to the first dose interruption and first dose reduction of POMALYST
was 4.1 weeks and 4.5 weeks, respectively

POMALYST is available in the following dosage strengths:

For each subsequent
drop <500 per mcL
Return to >500 per mcL

Interrupt POMALYST treatment,
follow CBC weekly
Resume POMALYST treatment
at 3 mg daily
Interrupt POMALYST treatment
Resume POMALYST treatment at
1 mg less than the previous dose

Dose Modification

Thrombocytopenia
Start at 4 mg

4 mg

2 mg

3 mg

1 mg

(Capsules shown are not actual size)

SELECTED SAFETY INFORMATION: WARNINGS AND PRECAUTIONS
• Venous and Arterial Thromboembolism: See Boxed WARNINGS on page 6. 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.
• Dizziness and Confusional State: In patients taking POMALYST in clinical trials, 14% experienced
dizziness (1% Grade 3 or 4) and 7% a confusional state (3% Grade 3 or 4). 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.

Platelets <25,000 per mcL

Interrupt POMALYST treatment,
follow CBC weekly

Platelets return to >50,000
per mcL

Resume POMALYST treatment
at 3 mg daily

For each subsequent
drop <25,000 per mcL

Interrupt POMALYST treatment

Return to ≥50,000 per mcL

Resume POMALYST treatment at
1 mg less than the previous dose

For other Grade 3 or 4 toxicities:
• Hold treatment and restart treatment at 1 mg less than the previous dose when toxicity
has resolved to ≤Grade 2 at the physician’s discretion
• To initiate a new cycle of POMALYST, the neutrophil count must be at least 500 per mcL
and the platelet count must be at least 50,000 per mcL
Permanently discontinue POMALYST for angioedema,
skin exfoliation, bullae, or any other severe
dermatologic reaction.

Please see additional Important Safety Information on pages 6-7 and accompanying
full Prescribing Information, including Boxed WARNINGS.
4

5

WARNINGS AND PRECAUTIONS (continued)

Important Safety Information
WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISM
Embryo-Fetal Toxicity
• POMALYST is contraindicated in pregnancy. POMALYST is a thalidomide analogue.
Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal
death. In females of reproductive potential, obtain 2 negative pregnancy tests before
starting POMALYST treatment.
• Females of reproductive potential must use 2 forms of contraception or continuously abstain
from heterosexual sex during and for 4 weeks after stopping POMALYST treatment.
POMALYST is only available through a restricted distribution program called POMALYST REMS®.
Venous and Arterial Thromboembolism
• Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and
stroke occur in patients with multiple myeloma treated with POMALYST. Prophylactic
antithrombotic measures were employed in clinical trials. Thromboprophylaxis is
recommended, and the choice of regimen should be based on assessment of the patient’s
underlying risk factors.
CONTRAINDICATIONS
• Pregnancy: POMALYST can cause fetal harm and is contraindicated in females who are
pregnant. If POMALYST 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.

• Neuropathy: In patients taking POMALYST in clinical trials, 18% experienced neuropathy
(2% Grade 3 in one trial) and 12% peripheral neuropathy.
• Second Primary Malignancies: Cases of acute myelogenous leukemia have been reported
in patients receiving POMALYST as an investigational therapy outside of multiple myeloma.
• Tumor Lysis Syndrome (TLS): TLS may occur in patients treated with POMALYST. Patients
at risk are those with high tumor burden prior to treatment. These patients should be
monitored closely and appropriate precautions taken.
ADVERSE REACTIONS
Nearly all patients treated with POMALYST + low-dose dex experienced at least one adverse
reaction (99%). The most common adverse reactions included neutropenia (51.3%), fatigue
and asthenia (46.7%), upper respiratory tract infection (31%), thrombocytopenia (29.7%),
pyrexia (26.7%), dyspnea (25.3%), diarrhea (22%), constipation (21.7%), back pain
(19.7%), cough (20%), pneumonia (19.3%), bone pain (18%), edema peripheral (17.3%),
peripheral neuropathy (17.3%), muscle spasms (15.3%), and nausea (15%). Grade 3 or 4
adverse reactions included neutropenia (48.3%), thrombocytopenia (22%), and
pneumonia (15.7%).
DRUG INTERACTIONS
Avoid concomitant use of POMALYST with strong inhibitors of CYP1A2. Consider alternative
treatments. If a strong CYP1A2 inhibitor must be used, reduce POMALYST dose by 50%.

WARNINGS AND PRECAUTIONS

USE IN SPECIFIC POPULATIONS

• Embryo-Fetal Toxicity & Females of Reproductive Potential: See Boxed WARNINGS

• Pregnancy: See Boxed WARNINGS. If pregnancy does occur during treatment,
immediately discontinue the drug and refer patient to an obstetrician/gynecologist
experienced in reproductive toxicity for further evaluation and counseling. There is a
POMALYST 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.

– Males: Pomalidomide is present in the semen of patients receiving the drug. 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. Males must not donate sperm.
– Blood Donation: Patients must not donate blood during treatment with POMALYST and for
1 month following discontinuation of POMALYST therapy because the blood might be given
to a pregnant female patient whose fetus must not be exposed to POMALYST.
• POMALYST REMS® Program: See Boxed WARNINGS
– Prescribers and pharmacies must be certified with the POMALYST REMS program by
enrolling and complying with the REMS requirements; pharmacies must only dispense to
patients who are authorized to receive POMALYST. Patients must sign a Patient-Physician
Agreement Form and comply with REMS requirements; female patients of reproductive
potential who are not pregnant must comply with the pregnancy testing and
contraception requirements and males must comply with contraception requirements.
– Further information about the POMALYST REMS program is available at
www.CelgeneRiskManagement.com or by telephone at 1-888-423-5436.
• Venous and Arterial Thromboembolism: See Boxed WARNINGS. 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.
• Hematologic Toxicity: Neutropenia (46%) was the most frequently reported Grade 3/4
adverse reaction in patients taking POMALYST in clinical trials, followed by anemia and
thrombocytopenia. Monitor complete blood counts weekly for the first 8 weeks and
monthly thereafter. Patients may require dose interruption and/or modification.
• 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. After return to baseline values, treatment at a
lower dose may be considered.

• Lactation: There is no information regarding the presence of pomalidomide in human
milk, the effects of POMALYST on the breastfed infant, or the effects of POMALYST on milk
production. Pomalidomide was excreted in the milk of lactating rats. Because many drugs
are excreted in human milk and because of the potential for adverse reactions in breastfed
infants from POMALYST, advise a nursing woman to discontinue breastfeeding during
treatment with POMALYST.
• Pediatric Use: Safety and effectiveness have not been established in pediatric patients.
• Geriatric Use: No dosage adjustment is required for POMALYST based on age. Patients
>65 years of age were more likely than patients ≤65 years of age to experience pneumonia.
• Renal Impairment: Reduce POMALYST dose by 25% in patients with severe renal
impairment requiring dialysis. Take dose of POMALYST following hemodialysis on
hemodialysis days.
• Hepatic Impairment: Reduce POMALYST dose by 25% in patients with mild to moderate
hepatic impairment and 50% in patients with severe hepatic impairment.
• Smoking Tobacco: Advise patients that smoking may reduce the efficacy of POMALYST.
Cigarette smoking reduces the AUC of pomalidomide by 32% by CYP1A2 induction.

6

POMALYST can be use
mild to severe ren
Visit POMALYST.com

(see inside f

Pomalidomide (POMALYST) is a Nat
Network® (NCCN®) Category 1 Reco
in Combination With Dexamethaso

Indicated for patients with multiple myeloma who have
an immunomodulatory agent and a proteasome inhibit
on or within 60 days of completion of the last therapy.

Referenced with permission from the NCCN Clinical Prac
for Multiple Myeloma, Version 3.2016. © National Com
reserved. Accessed June 14, 2016. To view the most rec
online to NCCN.org. NATIONAL COMPREHENSIVE CANCER
other NCCN Content are trademarks owned by the Natio

SELECTED SAFETY INFORMATION: BOX

WARNING: EMBRYO-FETAL TOXICITY and VENOUS
Embryo-Fetal Toxicity

• POMALYST is contraindicated in pregnancy. PO
Thalidomide is a known human teratogen tha
death. In females of reproductive potential, o
starting POMALYST treatment.

• Females of reproductive potential must use 2
from heterosexual sex during and for 4 weeks

POMALYST is only available through a restricted
Venous and Arterial Thromboembolism

• Deep venous thrombosis (DVT), pulmonary em
stroke occur in patients with multiple myelom
antithrombotic measures were employed in cl
recommended, and the choice of regimen sho
underlying risk factors.

Please see accompanying full Prescribing Information, including Boxed WARNINGS.

Please see additional Important Safety Infor
full Prescribing Information, including Boxed

Learn more about POMALYST at:
POMALYST.com/hcp

• Hypersensitivity Reactions: Angioedema and severe dermatologic reactions have been
reported. Discontinue POMALYST for angioedema, skin exfoliation, bullae, or any other
severe dermatologic reactions, and do not resume therapy.
• Dizziness and Confusional State: In patients taking POMALYST in clinical trials, 14%
experienced dizziness (1% Grade 3 or 4) and 7% a confusional state (3% Grade 3 or 4).
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.

NEW DATA

POMALYST is only available through a restricted
distribution program, POMALYST REMS®.
7

REFERENCES: 1. Dimopoulos MA, Sonneveld P, Siegel D
patients with relapsed and/or refractory multiple mye
2015;26(11):2247-2256. 2. Siegel DS, Weisel KC, Dimo
dose dexamethasone in patients with relapsed/refrac
impairment: a pooled analysis of three clinical trials.

POMALYST®, POMALYST REMS
trademarks of Celgene Corpo

© 2016 Celgene Corporation

POMALYST® (pomalidomide) is a tha
dexamethasone, for patients with m
therapies including lenalidomide an
disease progression on or within 60

ical trials, 18% experienced neuropathy
uropathy.

yelogenous leukemia have been reported
nal therapy outside of multiple myeloma.

atients treated with POMALYST. Patients
treatment. These patients should be
aken.

se dex experienced at least one adverse
ns included neutropenia (51.3%), fatigue
ction (31%), thrombocytopenia (29.7%),
), constipation (21.7%), back pain
pain (18%), edema peripheral (17.3%),
.3%), and nausea (15%). Grade 3 or 4
hrombocytopenia (22%), and

hibitors of CYP1A2. Consider alternative
sed, reduce POMALYST dose by 50%.

does occur during treatment,
nt to an obstetrician/gynecologist
valuation and counseling. There is a
itors pregnancy outcomes in females
s female partners of male patients who
ed to understand the root cause for the
to POMALYST to the FDA via the MedWatch
Corporation at 1-888-423-5436.

presence of pomalidomide in human
fant, or the effects of POMALYST on milk
ilk of lactating rats. Because many drugs
otential for adverse reactions in breastfed
to discontinue breastfeeding during

been established in pediatric patients.

for POMALYST based on age. Patients
65 years of age to experience pneumonia.

% in patients with severe renal
LYST following hemodialysis on

25% in patients with mild to moderate
ere hepatic impairment.

may reduce the efficacy of POMALYST.
ide by 32% by CYP1A2 induction.

POMALYST is only available through

NEW DATA
POMALYST can be used in patients with
mild to severe renal impairment.
Visit POMALYST.com/hcp to learn more
(see inside for dosing)

Pomalidomide (POMALYST) is a National Comprehensive Cancer
Network® (NCCN®) Category 1 Recommended Option When Used
in Combination With Dexamethasone

NEW DATA: P
patients with all

(see

Indicated for patients with multiple myeloma who have received at least two prior therapies, including
an immunomodulatory agent and a proteasome inhibitor, and have demonstrated disease progression
on or within 60 days of completion of the last therapy.
Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®)
for Multiple Myeloma, Version 3.2016. © National Comprehensive Cancer Network, Inc 2016. All rights
reserved. Accessed June 14, 2016. To view the most recent and complete version of the guideline, go
online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all
other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc.

SELECTED SAFETY INFORMATION: BOXED WARNINGS

SELECTED SAFETY INFORMATIO

WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISM

WARNING: EMBRYO-FETAL TOXICITY an

Embryo-Fetal Toxicity

Embryo-Fetal Toxicity

• POMALYST is contraindicated in pregnancy. POMALYST is a thalidomide analogue.
Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal
death. In females of reproductive potential, obtain 2 negative pregnancy tests before
starting POMALYST treatment.

• POMALYST is contraindicated in preg
Thalidomide is a known human terat
death. In females of reproductive po
starting POMALYST treatment.

• Females of reproductive potential must use 2 forms of contraception or continuously abstain
from heterosexual sex during and for 4 weeks after stopping POMALYST treatment.

• Females of reproductive potential m
from heterosexual sex during and fo

POMALYST is only available through a restricted distribution program called POMALYST REMS®.

POMALYST is only available through a r

Venous and Arterial Thromboembolism

Venous and Arterial Thromboembolism

• Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and
stroke occur in patients with multiple myeloma treated with POMALYST. Prophylactic
antithrombotic measures were employed in clinical trials. Thromboprophylaxis is
recommended, and the choice of regimen should be based on assessment of the patient’s
underlying risk factors.

• Deep venous thrombosis (DVT), pulm
stroke occur in patients with multipl
antithrombotic measures were empl
recommended, and the choice of reg
underlying risk factors.

ation, including Boxed WARNINGS.

POMALYST at:
m/hcp

POMALYST offers th
once-daily oral dos
relapsed/refractor

Please see additional Important Safety Information on pages 6-7 and accompanying
full Prescribing Information, including Boxed WARNINGS.
REFERENCES: 1. Dimopoulos MA, Sonneveld P, Siegel D, et al. Carfilzomib and pomalidomide in
patients with relapsed and/or refractory multiple myeloma with baseline risk factors. Ann Oncol.
2015;26(11):2247-2256. 2. Siegel DS, Weisel KC, Dimopoulos MA, et al. Pomalidomide plus lowdose dexamethasone in patients with relapsed/refractory multiple myeloma and moderate renal
impairment: a pooled analysis of three clinical trials. Leuk Lymphoma. 2016;7:1-6.

POMALYST®, POMALYST REMS®, and REVLIMID® are registered
trademarks of Celgene Corporation.
© 2016 Celgene Corporation

08/16

US-POM160030

CONTRAINDICATIONS

• Pregnancy: POMALYST can cause feta
pregnant. If POMALYST is used durin
taking this drug, the patient should

Please see additional Important Saf
full Prescribing Information, includi


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