Interview George R. Buchanan, MD
Continued from page 39
levels of evidence — high- or
low-quality. Obviously, the
strongest evidence came from
randomized controlled clinical
trials (RCTs), while the lowest
grade of evidence resulted
generally from observational
studies or studies that had flaws
of one kind or another.
However, given the paucity of
high-quality research in SCD, if
we relied solely on high-grade
evidence from RCTs, the report
would have been very short. So,
we incorporated a third level
of “moderate” evidence to be
able to make recommendations
in most areas. With the graded
evidence in hand, we began the
actual process of developing
recommendations in those five
areas, and this process took a
couple of years.
The guidelines really stress
the underuse of the two
approved treatments for
SCD. Why do you think this
is a problem, and how do
the guidelines tackle those
issues?
After about two years of
planning, we made the
decision to initially release
recommendations for
hydroxyurea use. Since 1998,
hydroxyurea has been the only
FDA-approved treatment for
SCD; its approval was based
on very carefully conducted,
definitive RCTs by the National
Institutes of Health (NIH).
Patients receiving hydroxyurea
had fewer crises, fewer episodes
of chest syndrome, fewer
hospitalizations, and longer
lifespans than those who took
placebo.
T:7”
This brief summary does not include all the
information needed to use POMALYST®
(pomalidomide) safely and effectively. See full
Prescribing Information for POMALYST.
WARNING: EMBRYO-FETAL TOXICITY and
VENOUS 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
[see Contraindications (4), Warnings and
Precautions (5.1), and Use in Specific
Populations (8.1, 8.6)].
POMALYST is only available through a restricted
distribution program called POMALYST REMS™
[see Warnings and Precautions (5.2)].
Venous Thromboembolism
• Deep venous thrombosis (DVT) and pulmonary
embolism (PE) occur in patients with multiple
myeloma treated with POMALYST. Prophylactic
anti-thrombotic measures were employed in
the clinical trial. Consider prophylactic
measures after assessing an individual
patient’s underlying risk factors [see Warnings
and Precautions (5.3)].
2 DOSAGE AND ADMINISTRATION
2.1 Multiple Myeloma
Females of reproductive potential must have
negative pregnancy testing and use contraception
methods before initiating POMALYST [see
Warnings and Precautions (5.1) and Use in Specific
Populations (8.6)].
The recommended starting dose of POMALYST is
4 mg once daily orally on Days 1-21 of repeated
28-day cycles until disease progression.
POMALYST may be given in combination with
dexamethasone [see Clinical Studies (14.1)].
POMALYST may be taken with water. Inform
patients not to break, chew, or open the capsules.
POMALYST should be taken without food (at least
2 hours before or 2 hours after a meal).
Table 1: Dose Modification Instructions for
POMALYST for Hematologic Toxicities
Toxicity
Neutropenia
• ANC <500 per mcL or
febrile neutropenia
(fever more than or
equal to 38.5°C and
ANC <1,000 per mcL)
• ANC return to more
than or equal to
500 per mcL
Dose Modification
• For each subsequent
drop <500 per mcL
• Return to more than or
equal to 500 per mcL
Interrupt POMALYST
treatment
Resume POMALYST
treatment at 1 mg less
than the previous dose
Thrombocytopenia
• Platelets <25,000 per
mcL
Interrupt POMALYST
treatment, follow CBC
weekly
Resume POMALYST
treatment at 3 mg daily
• Platelets return to
>50,000 per mcL
Interrupt POMALYST
treatment, follow CBC
weekly
Resume POMALYST
treatment at 3 mg daily
• For each subsequent
drop <25,000 per mcL
• Return to more than
or equal to 50,000 per
mcL
Interrupt POMALYST
treatment
Resume POMALYST
treatment at 1 mg less
than previous dose
ANC, absolute neutrophil count.
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 less than or
equal 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. If toxicities
occur after dose reductions to 1 mg, then
discontinue POMALYST.
2.3 Dose Adjustment for Strong CYP1A2 Inhibitors
in the Presence of Strong CYP3A4 and P-gp
Inhibitors
Avoid co-administration of strong inhibitors of
CYP1A2. If necessary to co-administer strong
inhibitors of CYP1A2 in the presence of strong
inhibitors of CYP3A4 and P-gp, reduce POMALYST
dose by 50%. No clinical efficacy or safety data
exist [see Drug Interactions (7.1) and Clinical
Pharmacology (12.3)].
4 CONTRAINDICATIONS
Pregnancy
POMALYST can cause fetal harm when administered
to a pregnant female [see Warnings and Precautions
(5.1) and Use in Specific Populations (8.1)].
POMALYST is contraindicated in females who are
pregnant. Pomalidomide is a thalidomide analogue
and is teratogenic in both rats and rabbits when
administered during F