The medical letter on drugs and therapeutics september 14 2015

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IN THIS ISSUE

Influenza Vaccine for 2015-2016 .......................................................................................p 125
Choice of Contraceptives.....................................................................................................p 127

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The Medical Letter

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on Drugs and Therapeutics
Objective Drug Reviews Since 1959

Volume 57

ISSUE

ISSUE No.

1433
1477

September 14, 2015
Take CME Exams

ALSO IN THIS ISSUE

Choice of Contraceptives.....................................................................................................p 127

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Influenza Vaccine for 2015-2016
Related article(s) since publication

Annual vaccination against influenza A and B viruses
is recommended for everyone ≥6 months old without a
specific contraindication.1
EFFECTIVENESS — The effectiveness of the seasonal
vaccine in preventing influenza in healthy adults
depends on the match between the vaccine and
circulating strains. Vaccine effectiveness is highest
(50-80% in young adults; lower in the elderly) when
the match is close, but even when the match is poor,
vaccination has been shown to reduce the risk of
laboratory-confirmed influenza, hospitalization for
influenza, and death.2,3
Quadrivalent vs Trivalent – All of the trivalent and
quadrivalent seasonal influenza vaccines available in
the US contain the same two influenza A virus antigens. Trivalent vaccines contain only one influenza B
virus antigen. Quadrivalent vaccines contain virus
antigens from the two genetic lineages of influenza B
that have been circulating globally since the 1980s,
increasing the likelihood that the vaccine will provide

protection against currently circulating strains.4
Live vs Inactivated – Comparative studies in adults
18-49 years old have generally found the inactivated
and live-attenuated vaccines to be similarly effective
or the inactivated vaccine to be more effective.5-7
Early randomized trials in children found the liveattenuated vaccine to be more effective than the
inactivated vaccine. In 2014, the CDC Advisory
Committee on Immunization Practices (ACIP)
recommended use of the live-attenuated vaccine
over the inactivated vaccine in healthy children 2-8
years old. Observational data from recent seasons,
however, have not found the live-attenuated vaccine
to be consistently more effective in children.8,9 For the

Table 1. 2015-2016 Vaccine Composition and
Recommendations
COMPOSITION
Trivalent Vaccine (Inactivated)
A/California/7/2009 H1N1-like
A/Switzerland/9715293/2013 H3N2-like
B/Phuket/3073/2013-like (Yamagata lineage)
Quadrivalent Vaccine (Live-Attenuated or Inactivated)
A/California/7/2009 H1N1-like
A/Switzerland/9715293/2013 H3N2-like
B/Phuket/3073/2013-like (Yamagata lineage)
B/Brisbane/60/2008-like (Victoria lineage)
WHO SHOULD BE VACCINATED
Everyone ≥6 months old without a specific contraindication,
including pregnant women
TIMING

Now through the end of the influenza season (about May 2016)1
CHOICE OF VACCINE2
Healthy Children 2-17 years old3
Live-attenuated vaccine (FluMist Quadrivalent) or
standard-dose inactivated vaccine4
Healthy Adults <65 years old
Standard-dose inactivated vaccine5 or
live-attenuated vaccine (18-49 years)
Adults ≥65 years old
Fluzone High-Dose or standard-dose inactivated vaccine5
Pregnant Women
Standard-dose inactivated vaccine5
Patients with Egg Allergy
FluBlok (≥18 years)6
Patients with Needle Aversion
Afluria with needle-free injector or Fluzone Intradermal
DOSAGE
Standard-Dose Inactivated Vaccine
Children 6-35 months old: 0.25 mL IM7
Adults and children ≥3 years old: 0.5 mL IM7
Intradermal Vaccine
Adults ≤64 years old: 0.1 mL
Live-Attenuated Vaccine
Children and adults 2-49 years old: 0.1 mL in each nostril7
1. Serum antibodies reach maximum levels in most adults about 2 weeks
after vaccination and generally persist for at least 6-8 months.
2. See Table 2 for available vaccines and specific age recommendations.
3. For 2015-2016, the ACIP no longer recommends a preference for the liveattenuated vaccine over the inactivated vaccine in children 2-8 years old.
4. The ACIP recommends that Afluria not be administered to children <9
years old due to a possible increased risk of fever and febrile seizures.

5. Quadrivalent vaccine is preferred when available.
6. Other inactivated vaccines may be used with caution.
7. Children 6 months to 8 years old who are being vaccinated for the first
time or who have not received at least 2 lifetime doses of the trivalent or
quadrivalent vaccine before July 1, 2015 should receive 2 doses at least 4
weeks apart. Children in this age group who received ≥2 doses of trivalent
or quadrivalent vaccine at any time before July 1, 2015 require only 1 dose.

125

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September 14, 2015

Table 2. Seasonal Influenza Vaccines for 2015-2016
Vaccine

Formulations

Mercury Content

Recommended Age

Cost1

0.5 mL syringe2
5 mL multidose vial
0.5 mL vial2
0.5 mL syringe2
0.5 mL syringe2
5 mL multidose vial
5 mL multidose vial
0.5 mL syringe2

none
24.5 mcg/0.5 mL dose
none
none
<1 mcg/0.5 mL dose
25 mcg/0.5 mL dose
25 mcg/0.5 mL dose
none

≥9 years3
≥9 years3,4
≥18 years
≥18 years
≥4 years
≥4 years
≥6 months7
≥65 years

$12.30

11.55
32.75
19.67
15.23
14.01
10.69
31.209

0.5 mL syringe2
5 mL multidose vial
0.25 mL syringe
0.5 mL syringe2
0.5 mL vial2
5 mL multidose vial
0.1 mL microinjection syringe2

none
<25 mcg/0.5 mL dose
none
none
none
25 mcg/0.5 mL dose
none

≥3 years
≥3 years
6-35 months
≥3 years
≥3 years
≥6 months7

18-64 years

16.05
15.05
21.70
17.15
17.97
16.15
20.009

none

2-49 years12

23.70

Inactivated Influenza Vaccine (IIV)
Trivalent (IIV3)
Afluria (bioCSL)
FluBlok (Protein Sciences)
Flucelvax (Novartis)6
Fluvirin (Novartis)

5

Fluzone (Sanofi Pasteur)
Fluzone High-Dose 8
Quadrivalent (IIV4)
Fluarix Quadrivalent (GSK)
FluLaval Quadrivalent (GSK)

Fluzone Quadrivalent
(Sanofi Pasteur)

Fluzone Intradermal  Quadrivalent10

Live-Attenuated Influenza Vaccine (LAIV)
FluMist Quadrivalent
(Medimmune)

0.2 mL sprayer11

1.

Private sector cost (including excise tax) per dose as of August 3, 2015 according to the CDC Vaccine Price List. Available at />programs/vfc/awardees/vaccine-management/price-list/. Accessed September 3, 2015.
2. Sold in boxes of 10.
3. FDA-approved for use in persons ≥5 years old. The ACIP recommends that Afluria not be administered to children <9 years old due to a possible increased
risk of fever and febrile seizures.
4. Adults 18-64 years old can receive the vaccine via a needle and syringe or a needle-free jet injector.
5. Recombinant hemagglutinin vaccine. Considered to be egg-free.
6. Cell culture-based vaccine. Contains trace amounts of egg protein.
7. Dose for children 6-35 months old is 0.25 mL and for those ≥3 years old is 0.5 mL.
8. Fluzone High-Dose is an alternative to standard-dose inactivated vaccines for persons ≥65 years old; it contains 60 mcg of hemagglutinin antigen from each
strain compared to 15 mcg in the conventional vaccine.
9. Approximate WAC per dose. WAC = wholesaler acquisition cost or manufacturer’s published price to wholesalers; WAC represents a published catalogue or
list price and may not represent an actual transactional price. Source: AnalySource® Monthly. August 5, 2015. Reprinted with permission by First Databank,
Inc. All rights reserved. ©2015. www.fdbhealth.com/policies/drug-pricing-policy.
10. Contains 9 mcg of hemagglutinin antigen from each strain.
11. Each syringe-like sprayer contains a single 0.2-mL dose given intranasally (0.1 mL in each nostril); sold in boxes of 10.
12. Not recommended for pregnant women, persons who are immunosuppressed or have an egg allergy, or children 2-4 years old who have asthma or have had a
wheezing episode in the previous 12 months.

2015-2016 season, the ACIP has not recommended
either vaccine over the other for use in children.1
High-Dose vs Standard-Dose – Older adults may have
a lower antibody response to influenza vaccination
than younger adults and their antibody levels may
decline more rapidly.10-12 In a randomized study in
31,989 adults ≥65 years old, the high-dose vaccine
(Fluzone High-Dose) induced significantly higher
antibody responses and was superior to the standarddose vaccine in preventing laboratory-confirmed
influenza illness (1.4% incidence with the high-dose
vaccine vs 1.9% with the standard-dose vaccine),
with a lower risk of serious adverse events.13-15
Large retrospective cohort studies have found the
high-dose vaccine and the standard-dose vaccine
to be similarly effective or the high-dose vaccine
to be more effective in reducing hospitalization for
influenza-related illness in older patients.16,17
CARDIOVASCULAR BENEFITS — A meta-analysis of
6 randomized trials found that influenza vaccination
126

was associated with a reduced risk of major adverse
cardiovascular events in patients at high risk for
cardiovascular disease; the reduction in risk was
greatest in those with a recent history of acute coronary
syndrome.18
PREGNANCY — Vaccination of pregnant women not
only protects them against influenza-associated
illness, which can be especially severe during

pregnancy, but also protects their infants for up to the
first 6 months of life.19,20
ADVERSE EFFECTS — Influenza vaccination has been
associated with Guillain-Barré syndrome, but the
absolute risk is very low, and influenza infection itself
has also been associated with the syndrome.21,22
Inactivated – Except for soreness at the injection
site, adverse reactions to inactivated vaccines are
uncommon. In clinical trials, Fluzone High-Dose and
Fluzone Intradermal Quadrivalent have caused more
injection-site reactions than standard-dose vaccines.
Delivery of Afluria by needle-free jet injector has caused


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more mild to moderate local reactions than delivery by
needle and syringe.
Live – The intranasal live-attenuated vaccine is
generally well tolerated, but it can cause runny nose,
nasal congestion, and sore throat. Rapid influenza
diagnostic tests may be falsely positive if used within
a week after vaccination with FluMist Quadrivalent.
Patients vaccinated with the live attenuated vaccine
may shed the vaccine-strain virus for a few days
after vaccination, but person-to-person transmission
has been rare, and serious illness resulting from
transmission has not been reported. Nevertheless,

persons who care for severely immunocompromised
patients in protected environments should not receive
the live vaccine or should avoid contact with the
patients for 7 days after receiving it.
CONCLUSION — Seasonal influenza vaccine is
recommended for everyone ≥6 months old without a
specific contraindication, including pregnant women.
Quadrivalent vaccine is generally preferred when it
is available. The high-dose vaccine may be more
effective than the standard-dose vaccine in preventing
influenza illness in adults ≥65 years old, and it appears
to be safe. ■
1. LA Grohskopf et al. Prevention and control of influenza with
vaccines: recommendations of the Advisory Committee on Immunization Practices, United States, 2015-16 influenza season.
MMWR Morb Mortal Wkly Rep 2015; 64:818.
2. KL Nichol et al. Effectiveness of influenza vaccine in the community-dwelling elderly. N Engl J Med 2007; 357:1373.
3. M Darvishian et al. Effectiveness of seasonal influenza vaccine in
community-dwelling elderly people: a meta-analysis of test-negative design case-control studies. Lancet Infect Dis 2014; 14:1228.
4. T Heikkinen et al. Impact of influenza B lineage-level mismatch
between trivalent seasonal influenza vaccines and circulating
viruses, 1999-2012. Clin Infect Dis 2014; 59:1519.
5. AS Monto et al. Comparative efficacy of inactivated and live attenuated influenza vaccines. N Engl J Med 2009; 361:1260.
6. CS Ambrose et al. The relative efficacy of trivalent live attenuated and inactivated influenza vaccines in children and adults.
Influenza Other Respir Viruses 2011; 5:67.
7. CJ Phillips et al. Comparison of the effectiveness of trivalent
inactivated influenza vaccine and live, attenuated influenza
vaccine in preventing influenza-like illness among US military
service members, 2006-2009. Clin Infect Dis 2013; 56:11.
8. Advisory Committee on Immunization Practices (ACIP). Summary Report: October 29–30, 2014 (meeting minutes). Atlanta,
Georgia: US Department of Health and Human Services, CDC;

2014. Available at www.cdc.gov/vaccines/acip/meetings/
downloads/min-archive/min-2014-10.pdf. Accessed September 3, 2015.
9. Advisory Committee on Immunization Practices (ACIP). Summary Report: February 26, 2015 (meeting minutes). Atlanta, Georgia: US Department of Health and Human Services, CDC; 2015.
Available at www.cdc.gov/vaccines/acip/meetings/downloads/
min-archive/min-2015-02.pdf. Accessed September 3, 2015.
10. K Goodwin et al. Antibody response to influenza vaccination in
the elderly: a quantitative review. Vaccine 2006; 24:1159.

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September 14, 2015

11. JY Song et al. Long-term immunogenicity of influenza vaccine
among the elderly: risk factors for poor immune response and
persistence. Vaccine 2010; 28:3929.
12. J Castilla et al. Decline in influenza vaccine effectiveness with
time after vaccination, Navarre, Spain, season 2011/12. Euro
Surveill 2013; 18:pii:20388.
13. CA DiazGranados et al. Efficacy of high-dose versus standarddose influenza vaccine in older adults. N Engl J Med 2014;
371:635.
14. CA DiazGranados et al. Prevention of serious events in adults 65
years of age or older: a comparison between high-dose and standard-dose inactivated influenza vaccines. Vaccine 2015 July 26
(epub).
15. CA DiazGranados et al. Efficacy and immunogenicity of high-dose
influenza vaccine in older adults by age, comorbidities, and frailty.
Vaccine 2015; 33:4565.
16. DM Richardson et al. Comparative effectiveness of high-dose versus standard-dose influenza vaccination in community-dwelling
veterans. Clin Infect Dis 2015; 61:171.
17. HS Izurieta et al. Comparative effectiveness of high-dose versus
standard-dose influenza vaccines in US residents aged 65 years

and older from 2012 to 2013 using Medicare data: a retrospective
cohort analysis. Lancet Infect Dis 2015; 15:293.
18. JA Udell et al. Association between influenza vaccination and
cardiovascular outcomes in high-risk patients: a meta-analysis. JAMA 2013; 310:1711.
19. MG Thompson et al. Effectiveness of seasonal trivalent influenza
vaccine for preventing influenza virus illness among pregnant
women: a population-based case-control study during the 20102011 and 2011-2012 influenza seasons. Clin Infect Dis 2014;
58:449.
20. SA Madhi et al. Influenza vaccination of pregnant women and
protection of their infants. N Engl J Med 2014; 371:918.
21. JC Kwong et al. Risk of Guillain-Barré syndrome after seasonal
influenza vaccination and influenza health-care encounters: a
self-controlled study. Lancet Infect Dis 2013; 13:769.
22. LL Polakowski et al. Chart-confirmed Guillain-Barré syndrome
after 2009 H1N1 influenza vaccination among the Medicare
population, 2009-2010. Am J Epidemiol 2013; 178:962.

▶

Choice of Contraceptives
Related article(s) since publication

Implants, intrauterine devices (IUDs), and sterilization
are the most effective contraceptive methods available. Pills, patches, rings, and injectables, when used
correctly, are also highly effective in preventing pregnancy. Barrier and fertility-based methods have the
highest rates of failure.1,2
AN IMPLANT — Nexplanon, a single-rod implant
containing the progestin etonogestrel, is placed under
the skin on the inside of the non-dominant upper
arm and is effective for up to 3 years. As with other

progestin-based methods, bleeding irregularities are
common. Implants, once placed, require no adherence
and provide long-term protection against pregnancy.
Fertility returns rapidly after removal.3
INTRAUTERINE DEVICES — The 4 IUDs currently
available in the US are all highly effective in preventing
127


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September 14, 2015

Table 1. Efficacy of Contraceptives

Method

Failure Rate1
Typical Perfect
Use
Use
Some Advantages

Implant
Nexplanon

0.05%

0.05%

Intrauterine devices (IUDs)
ParaGard T 380A
Mirena

0.8%
0.2%

–
–

Liletta

0.15%2

–

Skyla

0.4%

–

0.5%

0.5%

0.15%

0.10%

6%

0.2%

Combination
oral contraceptives

9%

0.3%

Progestin-only
oral contraceptives

9%

0.3%

Transdermal
Xulane

9%

0.3%

Vaginal

NuvaRing

9%

0.3%

Diaphragm
with spermicide

12%

6%

Cervical cap

16-32%

9-26%

Sterilization
Female

Male
Injectable
Depo-Provera

Condom without spermicide
Female
21%
Male

5%

Convenience; long-term contraception;
no patient compliance required; rapid
return of fertility after removal
Convenience; long-term contraception;
no patient compliance required; rapid
return of fertility after removal
Effective for 10 years; nonhormonal
Decreased menstrual bleeding and
dysmenorrhea
Decreased menstrual bleeding and
dysmenorrhea
Smaller T-frame and narrower insertion tube

Irregular bleeding; removal complications

Rare uterine perforation; risk of infection with
insertion; anemia
Irregular/heavy bleeding and dysmenorrhea
Irregular bleeding in first 3-6 months, followed
by amenorrhea; ovarian cysts
Irregular bleeding in first 3-6 months; ovarian
cysts
Irregular bleeding in first 3-6 months; ovarian
cysts; amenorrhea in only 6% of users after 1 year

Long-term contraception; no patient
compliance required

Potential for surgical complications; regret among
young women; reversal often not possible and
expensive
Long-term contraception; no patient
Pain at surgical site; regret among young men;
compliance required
reversal often not possible and expensive
Convenience; same as progestin-only
Delayed return to fertility; irregular bleeding and
oral contraceptives
amenorrhea; weight gain; may decrease bone
mineral density
Protection against ovarian and endoIncreased rate of thromboembolism, stroke, and
metrial cancer, PID, and dysmenorrhea myocardial infarction in older smokers; nausea;
headache; contraindicated with breastfeeding
Protection against PID, iron-deficiency Irregular, unpredictable bleeding; must take at
anemia, and dysmenorrhea; safe in
same time every day
breastfeeding women and those with
cardiovascular risk
Convenience of once-weekly applicaDysmenorrhea and breast discomfort may be
tion; same benefits as combination
more frequent than with oral contraceptives;
oral contraceptives
application site reactions; detachment; increased
estrogen exposure compared to oral contraceptives
Excellent cycle control; rapid return to
Discomfort; vaginal discharge
fertility after removal; convenience of

once-monthly insertion
Low cost; may reduce risk of cervical
High failure rate; cervical irritation; increased risk
cancer
of urinary tract infection and toxic shock syndrome;
some require fitting by healthcare professional;
may be difficult to obtain; available only by
prescription
Low cost; effective for 48 hours; reap- High failure rate; cervical irritation; pap smear
plication of spermicide not required
abnormalities; limited sizes available; increased
risk of toxic shock syndrome; may be difficult to
obtain; available only by prescription
Protection against STIs; covers external genitalia; OTC
Protection against STIs; OTC

18%

2%

Withdrawal
Sponge

22%
12-24%

4%
9-20%

Fertility awareness-based

methods
Standard Days method
TwoDay method
Ovulation method
Symptothermal method
Spermicide
alone

24%

–

No drugs or devices
OTC; low cost; no fitting required; provides 24 hours of protection
Low cost; no drugs or devices

–
–
–
–
28%

5%
4%
3%
0.4%
18%

OTC

85%

85%

No method

Some Adverse Effects/Disadvantages

—

High failure rate; difficult to insert; poor acceptability
High failure rate; allergic reactions; poor acceptability; breakage possible
High failure rate
High failure rate; contraindicated during menses;
increased risk of toxic shock syndrome
High failure rate; may be difficult to learn; requires
relatively long periods of abstinence

High failure rate; local irritation; must be reapplied
with repeat intercourse; increased risk of HIV
transmission
—

STIs = sexually transmitted infections; PID = pelvic inflammatory disease; OTC = over the counter
1. Risk of unintended pregnancy during first year of use; adapted from J Trussel and KA Guthrie in RA Hatcher et al, Contraceptive Technology, 20th revised ed.,
New York: Ardent Media, 2011.
2. DL Eisenberg et al. Contraception 2015; 92:10.

128

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pregnancy. IUDs have high satisfaction and continuation rates and may be the most cost-effective of all
reversible methods of contraception.
ParaGard T 380A, a copper-containing IUD, is FDAapproved for up to 10 years of use. It has been shown
to be effective for up to 20 years in some women.4
Mirena is FDA-approved for up to 5 years of use, but
it has been shown to be effective for up to 7 years. It
releases 20 mcg/day of levonorgestrel initially, which
decreases gradually to 10 mcg/day over 5 years.
Mirena has an approved secondary indication for
heavy menstrual bleeding.
Skyla is FDA-approved for up to 3 years of use. It
releases 14 mcg/day of levonorgestrel initially, which
decreases gradually to 5 mcg/day over 3 years.
Skyla is slightly smaller than Mirena, which might
be advantageous in nulliparous women. One study
comparing Mirena with 2 smaller devices, including
one similar to Skyla, found that women receiving the
smaller devices were more likely to report little or no
pain than those undergoing Mirena placement.5
Liletta, which is the same size as Mirena, releases
18.6 mcg/day of levonorgestrel initially, which
decreases gradually to 12.6 mcg over 3 years. It is
FDA-approved for up to 3 years of use.6
Benefits – IUDs, once inserted, require no
adherence and provide long-term protection against

pregnancy; fertility is restored upon removal. All
of the levonorgestrel-releasing IUDs can reduce
dysmenorrhea.
Adverse Effects – Uterine perforation can occur during
IUD placement. The copper IUD may cause heavy
bleeding and cramping. All of the IUDs can cause
irregular or heavy bleeding in the first 3-6 months after
placement. IUD-associated infection is mainly related
to insertion; women who have a low risk of acquiring
a sexually transmitted infection are unlikely to develop
an IUD-associated infection. Ovarian cysts have been
reported with all levonorgestrel-releasing IUDs.
STERILIZATION — Tubal sterilization procedures can
be done abdominally or hysteroscopically. Abdominal
procedures are performed using various techniques to
cut, cauterize, or clip the fallopian tubes via laparoscopy
or minilaparotomy. Hysteroscopic methods involve
placing devices into the fallopian tubes that cause (after
several months) tubal occlusion. Essure is the only
such device currently approved in the US.7 Its labeling
states that tubal occlusion should be confirmed three

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September 14, 2015

months post-operatively; an alternate form of birth
control should be used until the confirmatory test.
ORAL CONTRACEPTIVES — Most oral contraceptives
available in the US are a combination of the estrogen

ethinyl estradiol and a progestin. The estrogen and
progestin content of these pills has been reduced over
the years to decrease the incidence of adverse effects.
The lower-dose formulations (≤20 mcg of ethinyl
estradiol) are effective, but they may have a higher risk
of failure and can cause changes in bleeding patterns
(irregular, frequent, or prolonged). A table listing some
common oral hormonal contraceptives can be found
online at medicalletter.org/downloads/TML1477b-2.pdf.
Monophasic vs Multiphasic – Monophasic oral
contraceptives contain fixed doses of estrogen
and progestin in each active pill. Multiphasic oral
contraceptives vary the dose of one or both hormones
during the pill cycle. Many multiphasic pills have
a lower total hormone dose per cycle; there is no
convincing evidence that they cause fewer adverse
effects or improve bleeding patterns compared to
monophasic pills.
Shorter or Fewer Hormone-Free Intervals – Most
traditional oral contraceptives are packaged as a 21/7
cycle (21 days of active tablets and 7 days of placebo),
resulting in 13 scheduled bleeding episodes each year.
Newer regimens include fewer hormone-free days per
28-day cycle (2-4 placebo tablets) or extended cycles
with fewer withdrawal bleeds per year. Most studies
found that use of extended-cycle contraceptives results
in fewer menstrual symptoms such as headache,
bloating, and menstrual pain.8 Several products are
designed and packaged for extended cycles, but
any traditional 21/7 oral contraceptive can be used

continuously by skipping some or all of the placebo pills.
Non-Contraceptive Benefits – Women who take
combination oral contraceptives have a reduced risk
of both epithelial ovarian and endometrial cancer. This
benefit is detectable within one year of use and appears
to persist for years after discontinuation. Other benefits
include a reduction in dysfunctional uterine bleeding and
dysmenorrhea, a lower incidence of ectopic pregnancy
and benign breast disease, and an increase in hemoglobin concentrations. Many women also benefit from the
convenience of menstrual regularity. All combination
oral contraceptives increase sex hormone binding
globulin and decrease free testosterone concentrations,
which can lead to improvements in hirsutism and acne.
Combination oral contraceptives are also often used offlabel to treat polycystic ovary syndrome.
129


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Choice of a Progestin – Progestins such as desogestrel
and norgestimate have less androgenic activity and are
claimed to improve acne more than older progestins,
but these claims have not been substantiated by
controlled trials. Combination oral contraceptives
containing drospirenone, a synthetic progestin with
antiandrogenic and antimineralocorticoid activity,
have been shown to improve symptoms associated
with premenstrual dysphoric disorder (PMDD),

hirsutism, and acne, but whether they are more
effective than other combination oral contraceptives
for these indications is not known.9
Adverse Effects – Estrogens can cause nausea
and breast tenderness and enlargement. Oral
contraceptives with lower doses of ethinyl estradiol
have a higher incidence of bleeding disturbances.
Unexpected bleeding or spotting is common with all
extended-cycle or continuous regimens, particularly
during the initial cycles.
Other Risks – Older formulations of combination oral
contraceptives containing ≥50 mcg of ethinyl estradiol
were associated with an increased risk of myocardial infarction and ischemic stroke, particularly in
women who smoked or had uncontrolled hypertension;
these risks are decreased with formulations that have
lower doses of ethinyl estradiol. Users of contraceptives
with lower estrogen doses have a risk of venous
thromboembolism (VTE) that is 2-3 times higher than
that of non-users; this risk is lower, however, than the
risk of VTE associated with pregnancy.
A case-control study in over 10,000 women with
VTE found that current exposure to any combination
contraceptive was associated with an increased risk
of VTE (adjusted odds ratio 2.97) compared to no
exposure in the previous year. Exposure to certain
progestins (desogestrel, gestodene, drospirenone, and
cyproterone) was associated with a higher risk of VTE
(odds ratios ranged from 1.52 to 1.80) compared to
levonorgestrel.10
Estrogen-containing contraceptives are not recommended for smokers (≥15 cigarettes/day) who are ≥35

years old or for women who have hypertension, coronary
artery disease, heart failure, cerebrovascular disease,
diabetes with end-organ damage, or migraine headaches
with focal neurological symptoms, or for those who
are at risk for VTE. Their use is also contraindicated in
women with a history of breast cancer, a thromboembolic
disorder, or liver disease. Progestin-only or nonhormonal
methods are preferred in women at increased risk of
cardiovascular or thromboembolic events.
130

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September 14, 2015

Progestin-Only – “Minipills,” which are taken daily
without a hormone-free interval, are predominantly
used by breastfeeding women and those in whom
estrogen is poorly tolerated or contraindicated, such
as women ≥35 years old who smoke. Irregular bleeding
is common with progestin-only pills; taking the pill
at the same time each day is crucial in preventing
breakthrough bleeding and pregnancy.
Drug Interactions – Some drugs taken concurrently,
including rifampin (Rifadin, and others), several antiHIV drugs, anticonvulsants, and St. John’s wort, can
induce the metabolism of oral contraceptives and
decrease their effectiveness. Contraceptive failure
has also been reported with concurrent use of
some antibiotics, including penicillins and tetracyclines; a cause-and-effect relationship has not been
established.

OTHER HORMONAL CONTRACEPTIVES — Injectable
Contraceptives – Injectable contraceptives containing
medroxyprogesterone are effective and eliminate
the need for daily adherence. Medroxyprogesterone
acetate is injected intramuscularly (Depo-Provera,
and generics) or subcutaneously (Depo-SubQ Provera
104) once every 3 months. Amenorrhea is common
and irregular bleeding can occur. Weight gain,
headache, and decreases in bone mineral density
have been reported. Because of the risk of loss of bone
mineral density, labeling for both injectable products
recommends discontinuing their use after 2 years
unless no acceptable alternative is available, but the
American College of Obstetricians and Gynecologists
has urged practitioners to continue the injections
after 2 years when their clinical judgement is that
such use is appropriate.11 The return of fertility can
be delayed for 6-12 months (median 10 months) after
the last injection.
Transdermal Patch – Xulane, a generic version of the (no
longer marketed) Ortho Evra patch, delivers an average
daily dose of 20 mcg of ethinyl estradiol and 0.15 mg of
norelgestromin. A new patch is applied to the buttock,
lower abdomen, back, or upper outer arm each week for
3 weeks, followed by one patch-free week. Its efficacy
is similar to that of combination oral contraceptives,
although it may be less effective in women who weigh
≥90 kg. The adverse effects and risks of the patch are
similar to those of combination oral contraceptives,
but patch users are exposed to higher average levels of

estrogen than users of combination oral contraceptives
containing 30-35 mcg of ethinyl estradiol. Compliance
may be improved compared to oral contraceptives, but
breakthrough bleeding is more common in the first 2


The Medical Letter

®

cycles. Skin irritation at the application site can occur and
may lead to discontinuation.
Vaginal Contraceptive Ring – NuvaRing is inserted
intravaginally by the patient (no fitting is necessary)
and left in place for 3 weeks, followed by one ringfree week. It can be left in place for up to 4 weeks
and the number of ring-free days can be reduced. It
delivers a daily dose of 15 mcg of ethinyl estradiol
and 0.12 mg of etonogestrel, the active metabolite
of desogestrel. If the ring is removed for more than
3 hours, backup contraception should be used until
the ring has been in place for 7 consecutive days. The
ring offers excellent cycle control and a rapid return
to fertility after removal. Reasons for discontinuation
have included device-related discomfort, headaches,
and vaginal discharge. Its efficacy is similar to that of
combination oral contraceptives, but users report less
nausea, acne, irritability, and depression.
EMERGENCY CONTRACEPTION — Hormonal methods
of emergency contraception, which apparently
prevent or delay ovulation, can prevent 50-80% of

pregnancies.12
Progestin-Only ECPs – Progestin-only emergency
contraception pills (ECPs) available in the US include
Plan B One-Step, Next Choice One Dose, and several
generic formulations of these. Since 2013, progestinonly ECPs have been available over the counter with
no age restrictions. All progestin-only ECPs use
levonorgestrel, either as a single dose of 1.5 mg or as
two doses of 0.75 mg taken 12 hours apart. Progestinonly ECPs should be started as soon as possible within
72 hours after unprotected intercourse, although
some studies indicate that they may be effective if
taken within 5 days.13 Side effects include headache,
abdominal pain, and breast tenderness. Nausea and
vomiting occur less frequently with levonorgestrel
alone than with estrogen-progestin combinations.
Progestin-only ECPs decrease in efficacy with
increasing body mass index (BMI).14
Antiprogestin ECPs – Ulipristal acetate (Ella), an
antiprogestin, is FDA-approved for emergency
contraception.15 It is only available by prescription
and is approved for use up to 5 days after unprotected
intercourse. Ulipristal acetate is the most effective
hormonal option for emergency contraception. A
meta-analysis found that women who took ulipristal
acetate for emergency contraception within 120
hours after unprotected intercourse were less likely
to become pregnant than those who took progestinonly ECPs.16 Its adverse effects are similar to those of

Vol. 57 (1477)

September 14, 2015

levonorgestrel. Ulipristal acetate should be considered a
first-line hormonal option for emergency contraception,
especially for overweight or obese women.17
Copper IUD – A copper IUD inserted within 5 days
after intercourse is the most effective method of
emergency contraception.14 Pregnancy rates as low
as 0.1% have been reported with use of the copper
IUD.18 It may cause heavy bleeding and cramping.
IUD-associated infection is mainly related to
insertion; women who are at low risk of acquiring a
sexually transmitted infection have a minimal risk of
an IUD-associated infection.
Combined ECPs – Many oral contraceptives can also
be used in doses suitable for emergency contraception;
26 combined estrogen and progestin (usually ethinyl
estradiol and levonorgestrel) oral contraceptives
are available in the US for this indication. All are
recommended for use in 2 doses 12 hours apart. They
are somewhat less effective than other hormonal
methods. Doses should be taken as soon as possible
within 72 hours after unprotected intercourse. Patients
who vomit within 1 hour of administration should
repeat the dose.
Adverse Effects – Nausea and vomiting occur
less frequently with levonorgestrel alone than
with estrogen-progestin combinations. Headache,
abdominal pain, and breast tenderness have been
reported with both progestin-only and combination
oral contraceptives. No fetal malformations caused

by unsuccessful use of hormones for emergency
contraception have been reported.
BARRIER CONTRACEPTIVES — The effectiveness
of barrier contraceptives is highly user-dependent.
These methods have much higher failure rates than
hormonal contraceptives, IUDs, or sterilization.
Diaphragms and Cervical Caps – Diaphragms and
cervical caps are used with spermicide and placed
over the cervix. Diaphragms can be inserted up
to 6 hours before intercourse and should not be
removed for 6 hours afterward; they should not be
left in place for more than 24 hours because of the
danger of toxic shock syndrome. Spermicide must
be reapplied for each act of intercourse. Cervical
caps can be left in place for up to 48 hours, and
do not require additional spermicide with repeated
intercourse. Whether these devices have protective
effects against HIV or other sexually transmitted
infections is unclear. Diaphragms and cervical caps
are not routinely stocked in pharmacies and may be
difficult to obtain.
131


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®

Condoms – Only condoms prevent both pregnancy
and sexually transmitted infections, including

HIV infection. Both male and female condoms are
available. Most male condoms in the US are latex; they
are effective when used correctly, but can break when
stored improperly or used with oil-based lubricants.
Alternatives for patients with latex sensitivity include
lamb intestine and synthetic polyurethane condoms.
Lamb condoms do not protect against viral infections.
Synthetic polyurethane male condoms are more likely
to break than latex condoms, and may be less effective
in preventing pregnancy. Female condoms have
the advantage of improved coverage of the external
genitalia, possibly offering better protection against
STIs. They can be used with either an oil- or waterbased lubricant.
Sponge – The Today sponge is an over-the-counter
barrier contraceptive containing the spermicide
nonoxynol-9. It is moistened in water and placed over
the cervix. The sponge is effective immediately after
insertion and, if left in place, intercourse may be repeated
for up to 24 hours. The sponge should remain in place
for 6 hours after the last act of intercourse. It should
be removed after 24-30 hours because of the risk of
toxic shock syndrome. Sponges have been inferior to
diaphragms in both effectiveness and continuation
rates. The availability of the sponge is inconsistent.
Spermicides – Nonoxynol-9 is available as a foam, film,
gel, cream, suppository, and tablet. It must be placed
in the vagina no more than 1 hour before intercourse
and reapplied before each act of intercourse. The
spermicide should be in contact with the cervix;
suppositories, films, and tablets need to dissolve in

order to be effective.
FERTILITY AWARENESS-BASED METHODS — Fertility
awareness-based methods of contraception involve
avoidance of intercourse or use of barrier methods
during the presumed fertile days of the menstrual
cycle. The approaches now recommended rely on
observation of changes in cervical mucus (ovulation),
changes in body temperature (symptothermal), and
estimation of the range of fertile days in the woman’s
usual menstrual cycle (Calendar Rhythm, TwoDay, and
Standard Days methods). Relatively long periods of
abstinence are necessary with all of these methods,
and failure rates are high.
CONCLUSION — Intrauterine devices (IUDs) and
hormonal implants require no compliance on the
part of the woman and are probably the most costeffective of all reversible contraceptives. Oral
132

Vol. 57 (1477)

September 14, 2015

contraceptives containing a low dose of estrogen
(≤35 mcg) and a progestin are highly effective and have
non-contraceptive benefits. Barrier contraceptives
have fewer systemic adverse effects than hormonal
contraceptives, but have much higher failure rates.
For emergency contraception, ulipristal acetate (Ella)
is the most effective hormonal option, but the copper
IUD (ParaGard T 380A) is the most effective method

overall. ■
1. AR Aiken and J Trussell. Recent advances in contraception.
F1000Prime Rep 2014; 6:113.
2. J Trussell and KA Guthrie. Choosing a contraceptive: efficacy,
safety, and personal consideration. In: RA Hatcher et al. Contraceptive Technology: 20th revised edition. New York: Ardent
Media 2011.
3. In brief: etonogestrel (Nexplanon) contraceptive implant. Med
Lett Drugs Ther 2012; 54:12.
4. I Sivin. Utility and drawbacks of continuous use of a copper T
IUD for 20 years. Contraception 2007; 75(6Suppl):S70.
5. K Gemzell-Danielsson et al. A randomized, phase II study describing the efficacy, bleeding profile, and safety of two lowdose levonorgestrel-releasing intrauterine contraceptive systems and Mirena. Fertil Steril 2012; 97:616.
6. Liletta - A third levonorgestrel-releasing IUD. Med Lett Drugs
Ther 2015; 57:99.
7. SG Chudnoff et al. Hysteroscopic essure inserts for permanent
contraception: extended follow-up results of a phase III multicenter international study. J Minim Invasive Gynecol 2015 April
24 (epub).
8. A Edelman et al. Continuous or extended cycle vs. cyclic use
of combined hormonal contraceptives for contraception. Cochrane Database Syst Rev 2014; (7):CD004695.
9. Three new oral contraceptives. Med Lett Drugs Ther 2006;
48:77.
10. Y Vinogradova et al. Use of combined oral contraceptives and
risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ 2015;
350:h2135.
11. American College of Obstetrics and Gynecologists. ACOG Committee Opinion No. 602: depot medroxyprogesterone acetate
and bone effects. Obstet Gynecol 2014; 123:1398.
12. DT Baird. Emergency contraception: how does it work? Reprod
Biomed Online 2009; 18 suppl 1:32.
13. G Piaggio et al. Effect on pregnancy rates of the delay in the
administration of levonorgestrel for emergency contraception:
a combined analysis of four WHO trials. Contraception 2011;

84:35.
14. American College of Obstetrics and Gynecologists. Practice
bulletin summary No. 152: emergency contraception. Obstet
Gynecol 2015; 126:685.
15. Ella: a new emergency contraceptive. Med Lett Drugs Ther
2011; 53:3.
16. AF Glasier. Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and
meta-analysis. Lancet 2010; 375:555.
17. A Glasier et al. The rationale for use of ulipristal acetate as first
line in emergency contraception: biological and clinical evidence. Gynecol Endocrinol 2014; 30:688.
18. K Cleland et al. The efficacy of intrauterine devices for emergency contraception: a systematic review of 35 years of experience. Hum Reprod 2012; 27:1994.

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Vol. 57 (1477)

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September 14, 2015

Table 2. Some Oral Hormonal Contraceptives
Drug

Progestin (mg)1

Estrogen (mcg)2

Cost3

Monophasic Combinations
Zovia 1/50E 28 (Actavis)
Ogestrel 0.5/50 28 (Actavis)

ethynodiol diacetate (1)
norgestrel4 (0.5)

ethinyl estradiol (50)
ethinyl estradiol (50)

$24.70
33.70

ethynodiol diacetate (1)

ethinyl estradiol (35)

norethindrone (1)

ethinyl estradiol (35)

norethindrone (0.5)

ethinyl estradiol (35)

22.20

22.20
22.10
62.20
19.90
64.60
62.20
58.30
21.70

norethindrone (0.4)

ethinyl estradiol (35)

norgestimate (0.25)

ethinyl estradiol (35)

desogestrel (0.15)

ethinyl estradiol (30)

drospirenone (3)

ethinyl estradiol (30)

levonorgestrel (0.15)

ethinyl estradiol (30)

norethindrone acetate (1.5)

ethinyl estradiol (30)

norgestrel4 (0.3)

ethinyl estradiol (30)

drospirenone (3)

ethinyl estradiol (20)

levonorgestrel (0.1)

ethinyl estradiol (20)

norethindrone acetate (1)

ethinyl estradiol (20)

norethindrone (1)

mestranol (50)

Kelnor 1/35 28 (Teva Women's)
Zovia 1/35E 28 (Actavis)
Necon 1/35 28 (Actavis)
Norinyl 1+35 28 (Actavis)
Nortrel 1/35 28 (Teva Women's)5
Ortho-Novum 1/35 28 (Janssen)
Brevicon 28 (Actavis)

Modicon 28 (Janssen)
Nortrel 0.5/35 28 (Teva Women's)
Balziva 28 (Teva Women's)
Femcon Fe 28 (Actavis)
Ovcon-35 28 (Actavis)
MonoNessa 28 (Actavis)
Ortho-Cyclen 28 (Janssen)
Sprintec 28 (Teva Women's)
Desogen 28 (Merck)
Reclipsen 28 (Actavis)
Yasmin 28 (Bayer)
Ocella 28 (Teva Women's)
Levora 28 (Actavis)
Portia 28 (Teva Women's)
Loestrin Fe 1.5/30 28 (Teva Women's)6
Microgestin Fe 1.5/30 28 (Actavis)6
Junel Fe 1.5/30 28 (Teva Women's)6
Cryselle 28 (Teva Women's)
Low-Ogestrel 28 (Actavis)
Yaz (Bayer)7,8
Beyaz (Bayer)7,9
Aviane 28 (Teva Women's)
Lessina 28 (Teva Women's)
Lutera 28 (Actavis)
Sronyx 28 (Actavis)
Loestrin Fe 1/20 28 (Teva Women's)6
Microgestin Fe 1/20 28 (Actavis)6
Junel Fe 1/20 28 (Teva Women's)6
Necon 1/50 28 (Actavis)
Norinyl 1+50 28 (Actavis)

32.30
118.50
125.90
21.70
38.30
21.70
47.70
20.40
93.90
55.20
23.20
23.20
97.20
21.50
21.50
22.90
22.90
93.90
124.70
23.70
23.60
23.70
23.70
97.10
21.50
53.70
22.10
67.80

Fe = contains iron
1. Different progestins are not equivalent on a milligram basis.
2. Ethinyl estradiol and mestranol are not equivalent on a milligram basis; the results of some studies indicate that 30-35 mcg of ethinyl estradiol is equivalent to
50 mcg of mestranol.
3. Approximate WAC for a one month's supply. WAC = wholesaler acquisition cost or manufacturer’s published price to wholesalers; WAC represents a published
catalogue or list price and may not represent an actual transactional price. Source: AnalySource® Monthly. August 5, 2015. Reprinted with permission by First
Databank, Inc. All rights reserved. ©2015. www.fdbhealth.com/policies/drug-pricing-policy.
4. The progestin norgestrel contains two isomers; only levonorgestrel is bioactive. The amount of norgestrel in each tablet is twice the amount of levonorgestrel.
5. Also available in a 21-day regimen.
6. Also available in a 21-day regimen that does not contain iron.
7. Also FDA-approved for moderate acne.
8. Yaz is taken as active pills for 24 days and placebo for 4 days.
9. Also contains 451 mcg of levomefolate calcium per tablet. Addition of levomefolate increases folate levels in order to reduce the risk of neural tube defect in a
pregnancy conceived during or shortly after oral contraceptive use. Beyaz is taken for 24 days followed by 4 days of levomefolate calcium alone.

e133


The Medical Letter

Vol. 57 (1477)

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September 14, 2015

Table 2. Some Oral Hormonal Contraceptives (continued)
Drug

Progestin (mg)1

Estrogen (mcg)2

Cost3

Necon 7/7/7 28 (Actavis)
Nortrel 7/7/7 28 (Teva Women's)
Ortho-Novum 7/7/7 28 (Janssen)

norethindrone (0.5, 0.75, 1)

ethinyl estradiol (35, 35, 35)

$25.80
21.70
34.70

Aranelle 28 (Teva Women's)
Leena 28 (Actavis)

norethindrone (0.5, 1, 0.5)

ethinyl estradiol (35, 35, 35)

28.30
28.30

Ortho Tri-Cyclen 28 (Janssen)7
TriNessa 28 (Actavis)7
Tri-Sprintec 28 (Teva Women's)7

norgestimate (0.18, 0.215, 0.25)

ethinyl estradiol (35, 35, 35)

38.30
24.60
24.60

Cyclessa 28 (Merck)
Velivet 28 (Teva Women's)

desogestrel (0.1, 0.125, 0.15)

ethinyl estradiol (25, 25, 25)

57.70
24.20

Multiphasic Combinations

Tri-Norinyl 28 (Actavis)

67.80

Ortho Tri-Cyclen Lo 28 (Janssen)

norgestimate (0.18, 0.215, 0.25)

ethinyl estradiol (25, 25, 25)

135.80

Estrostep Fe 28 (Actavis)7
Tilia Fe 28 (Actavis)7
Tri-Legest Fe 28 (Teva Women's)7

norethindrone acetate (1, 1, 1)

ethinyl estradiol (20, 30, 35)

135.90
45.70
41.20

Kariva 28 (Teva Women's)
Mircette 28 (Teva Women's)

desogestrel (0.15, 0, 0)

ethinyl estradiol (20, 0, 10)

43.20
101.40

Trivora 28 (Actavis)

levonorgestrel (0.05, 0.075, 0.125)

ethinyl estradiol (30, 40, 30)

20.60

Lo Loestrin Fe (Actavis)10

norethindrone acetate (1, 0)

ethinyl estradiol (10, 10)

98.00

Natazia (Bayer)11

dienogest (0, 2, 3, 0)

estradiol valerate (3, 2, 2, 1)

124.70

Progestin-Only
Camila 28 (Teva Women's)
Errin 28 (Teva Women's)
Heather 28 (Glenmark)
Jolivette 28 (Actavis)
Nora-BE 28 (Actavis)

norethindrone (0.35)

24.90
24.90

25.20
24.90
24.90

Extended-Cycle Contraceptives12
Introvale (Sandoz)
Quasense (Actavis)

levonorgestrel (0.15)

ethinyl estradiol (30)

55.0013
115.7013

Seasonique (Teva Women's)

levonorgestrel (0.15, 0)

ethinyl estradiol (30, 10)

282.4013

LoSeasonique (Teva Women's)

levonorgestrel (0.1, 0)

ethinyl estradiol (20, 10)

282.4013

Quartette (Teva)

levonorgestrel (0.15, 0.15, 0.15, 0)

ethinyl estradiol (20, 25, 30, 10)

322.6013

Emergency Contraceptives
Ella (Afaxys)14
Next Choice One Dose (Actavis)16,17
Plan B One-Step (Teva Women's)16,17
Take Action (Teva)16,17

ulipristal acetate (30)
levonorgestrel (1.5)
levonorgestrel (1.5)
levonorgestrel (1.5)

35.8015
29.3015
32.5015
32.5015

10. Lo Loestrin Fe is taken as active pills for 26 days (24 days of the combination and 2 days of ethinyl estradiol only) followed by 2 days of iron tablets alone.
11. Natazia is taken as active pills for 26 days and placebo for 2 days.
12. Introvale and Quasense are taken on a 91-day cycle: 84 days of active pills and 7 days of placebo. Seasonique, LoSeasonique, and Quartette are also taken on
a 91-day cycle, but instead of placebo, the patient takes 10 mcg of ethinyl estradiol for 7 days.
13. Cost for a three-month supply.

14. One tablet orally within 120 hours after unprotected intercourse.
15. Cost of one tablet.
16. Available over the counter with no age restriction.
17. One tablet orally within 72 hours after unprotected intercourse.

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Issue 1477 Questions
(Correspond to questions #51-60 in Comprehensive Exam #73, available January 2016)

Influenza Vaccine for 2015-2016
1. Which of the following patients should not receive FluMist
Quadrivalent vaccine?
a. a 30-year-old pregnant woman
b. a 62-year-old man with diabetes
c. a 17-year-old girl with a history of egg allergy
d. none of the above patients should receive FluMist Quadrivalent
2. Compared to the standard-dose inactivated vaccine in patients
≥65 years old, the high-dose inactivated vaccine (Fluzone HighDose):
a. induces higher antibody responses
b. was superior in preventing laboratory-confirmed influenza
illness in a randomized study
c. may cause more injection-site reactions
d. all of the above
3. A 58-year-old woman with a history of asthma and
hypertension asks which flu shot she should get this year. You
tell her that you would recommend:
a. the live-attenuated intranasal vaccine
b. the high-dose inactivated vaccine
c. a standard-dose inactivated quadrivalent vaccine
d. she not be vaccinated this year
Choice of Contraceptives
4. Implants and intrauterine devices both:
a. require no patient compliance
b. provide long-term protection against pregnancy
c. permit rapid return of fertility after removal
d. all of the above
5. A 20-year-old nulliparous woman asks your advice about the
choice of an IUD as a contraceptive. You could tell her that:
a. the Paragard T 380A has been associated with an

increased risk of Wilson’s disease
b. Mirena has been approved for use for up to 10 years
c. Skyla is slightly smaller than Mirena and Liletta and might
be less painful on insertion
d. all of the above

6. Lower-dose oral contraceptives (≤20 mcg of ethinyl estradiol):
a. have a lower incidence of adverse effects
b. have a higher risk of failure
c. have a higher risk of bleeding problems
d. all of the above
7. Women who take combination oral contraceptives:
a. have a higher risk of ovarian cancer
b. have a higher risk of endometrial cancer
c. have a reduced risk of both ovarian and endometrial
cancer
d. have a higher incidence of benign breast disease
8. Injectable contraceptives containing medroxyprogesterone:
a. permit rapid return of fertility after stopping the injections
b. are not recommended for women who want to become
pregnant soon after stopping the injections
c. are injected weekly
d. increase bone mineral density
9. A 26-year-old woman who weighs 90 kg asks whether the
Xulane transdermal patch would be a suitable contraceptive for
her. You could tell her that the patch:
a. can cause irritation at the application site
b. must be reapplied daily
c. is more effective in heavy women
d. would not expose her to high levels of estrogen

10. The most effective method of emergency contraception is:
a. a progestin-only emergency contraception pill
b. ulipristal acetate (Ella)
c. a copper intrauterine device
d. two doses 12 hours apart of a combination oral
contraceptive

ACPE UPN: Per Issue Exam: 0379-0000-15-477-H01-P; Release: September 14, 2015, Expire: September 14, 2016
Comprehensive Exam 73: 0379-0000-16-073-H01-P; Release: January 2016, Expire: January 2017

EDITOR IN CHIEF: Mark Abramowicz, M.D.; EXECUTIVE EDITOR: Gianna Zuccotti, M.D., M.P.H., F.A.C.P., Harvard Medical School; EDITOR: Jean-Marie Pflomm, Pharm.D.;
ASSISTANT EDITORS, DRUG INFORMATION: Susan M. Daron, Pharm.D., Corinne Z. Morrison, Pharm.D., Michael P. Viscusi, Pharm.D.; CONSULTING EDITORS: Brinda M. Shah, Pharm.D.,
F. Peter Swanson, M.D; SENIOR ASSOCIATE EDITOR: Amy Faucard
CONTRIBUTING EDITORS: Carl W. Bazil, M.D., Ph.D., Columbia University College of Physicians and Surgeons; Vanessa K. Dalton, M.D., M.P.H., University of Michigan Medical School;
Eric J. Epstein, M.D., Albert Einstein College of Medicine; Jane P. Gagliardi, M.D., M.H.S., F.A.C.P., Duke University School of Medicine; David N. Juurlink, BPhm, M.D., Ph.D.,
Sunnybrook Health Sciences Centre; Richard B. Kim, M.D., University of Western Ontario; Franco M. Muggia, M.D., New York University Medical Center; Sandip K. Mukherjee,
M.D., F.A.C.C., Yale School of Medicine; Dan M. Roden, M.D., Vanderbilt University School of Medicine; Esperance A.K. Schaefer, M.D., M.P.H., Harvard Medical School; F. Estelle
R. Simons, M.D., University of Manitoba; Neal H. Steigbigel, M.D., New York University School of Medicine; Arthur M. F. Yee, M.D., Ph.D., F.A.C.R., Weill Medical College of Cornell
University
MANAGING EDITOR: Susie Wong; ASSISTANT MANAGING EDITOR: Liz Donohue; EDITORIAL ASSISTANT: Cheryl Brown
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VICE PRESIDENT AND PUBLISHER: Yosef Wissner-Levy
Founded in 1959 by
Arthur Kallet and Harold Aaron, M.D.
Copyright and Disclaimer: The Medical Letter, Inc. is an independent nonprofit organization that provides healthcare professionals with unbiased drug prescribing recommendations. The editorial
process used for its publications relies on a review of published and unpublished literature, with an emphasis on controlled clinical trials, and on the opinions of its consultants. The Medical Letter,
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