CLINICAL NEWS
Why should doctors care about the
narrative of clinical encounters?
Dr. Ofri: The patient’s story is the primary
clinical data in the medical encounter.
From the stories, we get the most impor-
tant information for clinical diagnoses.
But, beyond that, the narrative places the
patient’s illness in context. So, a 30-year-
old soccer player’s pneumonia isn’t the
same as a 77-year-old artist’s pneumonia.
To be effective clinicians, we need to
understand our patients’ narratives. Then,
even beyond that, it is the narrative that
makes the medical experience interesting,
for both patient and doctors. Without the
narrative, we could just have a computer
making the diagnosis from a checklist
provided by the patient.
Dr. Sekeres: All of medicine is based on
storytelling. A patient comes to us and tells
us a story of illness; we listen to that story
and compare it with others we’ve heard
to determine a diagnosis. We may call on
consultants to help, so we tell them stories
about what is occurring with our patient
and why we need their help. They then tell
us a story about what they feel is transpir-
ing. We write those stories in the medical
record. So, medicine is narrative. We’re
proficient storytellers, but often, we don’t
take the time to reflect on those stories and
how important storytelling is to us.
REVLIMID [lenalidomide] capsules, for oral use
the full spectrum of potential human embryo-fetal developmental effects
for lenalidomide. Since elderly patients are more likely to have decreased renal function,
care should be taken in dose selection. Monitor renal function.
Following daily oral administration of lenalidomide from Gestation Day 7
through Gestation Day 20 in pregnant rabbits, fetal plasma lenalidomide
concentrations were approximately 20-40% of the maternal C max .
Following a single oral dose to pregnant rats, lenalidomide was detected
in fetal plasma and tissues; concentrations of radioactivity in fetal tissues
were generally lower than those in maternal tissues. These data indicated
that lenalidomide crossed the placenta. 8.6 Renal Impairment
Adjust the starting dose of REVLIMID based on the creatinine clearance
value and for patients on dialysis [see Dosage and Administration (2.4)].
8.2 Lactation
Risk Summary
There is no information regarding the presence of lenalidomide in human
milk, the effects of REVLIMID on the breastfed infant, or the effects of
REVLIMID on milk production. Because many drugs are excreted in
human milk and because of the potential for adverse reactions in
breastfed infants from REVLIMID, advise women not to breastfeed during
treatment with REVLIMID.
8.3 Females and Males of Reproductive Potential
Pregnancy Testing
REVLIMID 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 REVLIMID therapy
and during therapy. Advise females of reproductive potential that they
must avoid pregnancy 4 weeks before therapy, while taking REVLIMID,
during dose interruptions and for at least 4 weeks after completing
therapy.
Females of reproductive potential must have 2 negative pregnancy tests
before initiating REVLIMID. The first test should be performed within
10-14 days, and the second test within 24 hours prior to prescribing
REVLIMID. 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. REVLIMID 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 REVLIMID, during
therapy, during dose interruptions, and continuing for 4 weeks following
discontinuation of REVLIMID 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
Lenalidomide is present in the semen of males who take REVLIMID.
Therefore, males must always use a latex or synthetic condom during
any sexual contact with females of reproductive potential while taking
REVLIMID and for up to 4 weeks after discontinuing REVLIMID, even if
they have undergone a successful vasectomy. Male patients taking
REVLIMID must not donate sperm.
8.4 Pediatric Use
Safety and effectiveness have not been established in pediatric patients.
8.5 Geriatric Use
MM Maintenance Therapy: Overall, 10% (106/1018) of patients were
65 years of age or older, while no patients were over 75 years of age.
Grade 3 or 4 AEs were higher in the REVLIMID arm (more than 5%
higher) in the patients 65 years of age or older versus younger patients.
The frequency of Grade 3 or 4 AEs in the Blood and Lymphatic System
Disorders were higher in the REVLIMID arm (more than 5% higher) in
the patients 65 years of age or older versus younger patients. There were
not a sufficient number of patients 65 years of age or older in REVLIMID
maintenance studies who experienced either a serious AE, or discontinued
therapy due to an AE to determine whether elderly patients respond
relative to safety differently from younger patients.
10 OVERDOSAGE
There is no specific experience in the management of lenalidomide
overdose in patients with MM, MDS, or MCL. In dose-ranging studies in
healthy subjects, some were exposed to up to 200 mg (administered
100 mg BID) and in single-dose studies, some subjects were exposed to
up to 400 mg. Pruritus, urticaria, rash, and elevated liver transaminases
were the primary reported AEs. In clinical trials, the dose-limiting toxicity
was neutropenia and thrombocytopenia.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies with lenalidomide have not been conducted.
Lenalidomide was not mutagenic in the bacterial reverse mutation assay
(Ames test) and did not induce chromosome aberrations in cultured
human peripheral blood lymphocytes, or mutations at the thymidine
kinase (tk) locus of mouse lymphoma L5178Y cells. Lenalidomide did
not increase morphological transformation in Syrian Hamster Embryo
assay or induce micronuclei in the polychromatic erythrocytes of the
bone marrow of male rats.
A fertility and early embryonic development study in rats, with
administration of lenalidomide up to 500 mg/kg (approximately 200 times
the human dose of 25 mg, based on body surface area) produced no
parental toxicity and no adverse effects on fertility.
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved Patient labeling (Medication
Guide)
Embryo-Fetal Toxicity
Advise patients that REVLIMID is contraindicated in pregnancy [see
Boxed Warning and Contraindications (4.1)]. REVLIMID is a thalidomide
analogue and can 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 REVLIMID and for at least 4 weeks after
completing therapy.
• Initiate REVLIMID 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
REVLIMID therapy, during dose interruption and for 4 weeks after she
has completely finished taking REVLIMID. 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 REVLIMID 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
REVLIMID and for up to 4 weeks after discontinuing REVLIMID, even if
they have undergone a successful vasectomy.
• Advise male patients taking REVLIMID 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
REVLIMID, during dose interruptions and for 4 weeks following
discontinuation of REVLIMID [see Warnings and Precautions (5.1)].
REVLIMID REMS program
Because of the risk of embryo-fetal toxicity, REVLIMID is only available
through a restricted program called the REVLIMID REMS program [see
Warnings and Precautions (5.2)].
What do you think are the challenges
that make it difficult for clinicians to
engage in narrative medicine?
Dr. Ofri: The biggest challenges are the
time constraints and the overwhelming
tide of documentation brought on by the
electronic health record (EHR) system.
What was once a human interaction has
become a data-entry exercise. To restore
the doctor-patient relationship, we need to
allow the human connection to occur.