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2011 Updates in Therapeutics:

The Pharmacotherapy Preparatory Course


Mens and Womens Health

Shareen Y. El-Ibiary, Pharm.D., BCPS


Associate Professor of Pharmacy Practice
Midwestern University- College of Pharmacy Glendale

Conflict of Interest Disclosures


Shareen Y. El-Ibiary, Pharm.D., BCPS
No conflicts of interest
Nothing to disclose for this presentation

Objectives
1. Recommend appropriate treatment options for
patients with menopausal symptoms, osteoporosis,
infertility and sexual dysfunction.

2. Identify drugs that are considered safe and unsafe in


pregnancy and lactation.

3 Modify contraceptive regimens based on estrogen-


3.
and progestin-related-adverse effects or drug
interactions.

4. Devise a pharmacotherapeutic plan for appropriate


contraceptive use, misused contraceptive methods,
and use of emergency contraception.

5. Identify the common sexually transmitted diseases


and recommend appropriate pharmacotherapy.

1
Agenda
Menopause
Osteoporosis
Contraception
Pregnancy and Lactation
Infertility
Sexually Transmitted Infections
Sexual Dysfunction in Men
Endometriosis*
Polycystic Ovary Syndrome*

Patient Case 1
N.I. is a 51-year-old woman complaining of hot
flashes and vaginal irritation. Has tried exercise, diet,
and antidepressants and is unsuccessful. Otherwise
healthy with no history of cancer and no surgeries.
States hot flashes are interfering with her daily
activities and wants to try hormone therapy.

Which one of the following was proved statistically


significant with conjugated estrogen and
medroxyprogesterone acetate and should be
mentioned to N.I.?

A. Decreased risk of strokes.


B. Decreased risk of MI.
C. Increased risk of fractures.
D. Increased risk of DVT.
Page 37

Signs & Symptoms


Vasomotor Psychosomatic
Hot flashes/flushes* Pressure/tightness in
Night sweats* head or body
Psychological HA
Anxiety Muscle/joint pain
Depression Numb/tingling feelings
Insomnia Loss of feeling in hands
Mood Swings or feet
Vaginal Dryness Dizzy or faint
Genitourinary atrophy* Difficulty breathing

*Directly related to estrogen deficiency

2
Hormone Regimens
Unopposed Estrogen
PEPI Trial, JAMA. 1995 Jan 8;273(3):199-208.
Estrogen plus cyclic progestogen
(progestin)
Estrogen plus daily progestogen
Heart and Estrogen/Progestin Replacement
Study, JAMA. 1998 Aug 19;280(7):605-13)
Womens Health Initiative WHI JAMA. 2002 Jul
17;288(3):321-33

Summary of findings (pg 36)


Risk or Benefit Relative Risk Absolute Risk each
year
Heart attacks 1.29 or 29% 7 more cases in 10,000
women
Breast Cancer 1.26 or 26% 8 more cases in 10,000
women
Strokes 1.41 or 41% 8 more cases in 10,000
women
Blood clots 2.11 or 111% 18 more cases in
10,000 women

Hip fractures 0.66 or 33% 5 fewer cases in


10,000 women
Colon Cancer 0.63 or 37% 6 fewer cases in
10,000 women
Dementia* 2.05 or 105% 23 more cases in
10,000 women over 65

Updates
Ovarian cancer, JAMA. 2009 Jul
15;302(3):298-305
Noted about 1 extra case per 8300
women taking HT, controversial, rare
Lung cancer , Lancet. 2009 Oct
10;374(9697):1243-51.
Incidence per year similar between groups
More deaths in HT group related to non-small-
cell lung cancer (62 vs 31 deaths; 009% vs
005%; HR 187, 122-288, p=0004)
Not designed to evaluate lung cancer, smokers,
past smokers, average age 60, more studies
needed

3
References
Estrogen and progestogen use in
postmenopausal women: 2010 position
statement of The North American
Menopause Society
Menopause Vol. 17; No. 2 pp 242-55.
Also found at
http://www.menopause.org/PSht10.pdf

Recommendations NAMS 2010


Moderate to severe vasomotor symptoms:
Primary indication for HT
Recommend lowest effective dose, (pg 37-39)
Moderate to severe vaginal symptoms:
Recommend local ET vs. systemic therapy
Sexual function:
HT not recommended for sole treatment of diminished
libido
Urinary Health:
Systemic HT may worsen stress incontinence, local ET
therapy may UTI, help with vaginal atrophy urge
incontinence
Osteoporosis:
HT indication for prevention, hip fractures, used only
when alternate therapies are not appropriate

Therapy duration lowest dose for least


amount of time, check after 3 months to
1yyear if asymptomatic;
y p ; if symptoms
y p
occur, treat for an additional 3 months,
best to keep less than 5 years of
treatment
Contraindications:
Breast cancer, CVD, stroke, history of
blood clots

4
Alternatives for Vasomotor
Symptoms (pg 40)
Fluoxetine (Prozac) 20 mg PO daily
Paroxetine (Paxil) 20 mg PO daily
Venlafaxine (Effexor) 75 mg PO daily
Decreased frequency and severity of
hot flashes vs. placebo
Others
Loprinzi C et al. The Lancet 2000;356:2059-2063.
Loprinzi C et al. Journ Clin Oncol 2002;20(6):1578-1583.
Stearns C et al. Annal Oncol 2000;11:17-22.

Patient Case 1
Response Cards
N.I. is a 51-year-old woman complaining of hot
flashes and vaginal irritation. She has tried exercise,
diet, and antidepressants to help relieve her hot
flashes but has been unsuccessful. She is otherwise
healthy with no history of cancer and no surgeries.
She states her hot flashes are interfering with her
daily activities and wants to try hormone therapy.

Which one of the following was proved statistically


significant with conjugated estrogen and
medroxyprogesterone acetate and should be
mentioned to N.I.?

A. Decreased risk of strokes.


B. Decreased risk of MI.
C. Increased risk of fractures.
D. Increased risk of DVT. Page 37

Patient Case 1, Question 2


2. Which one of the following HT treatments
should be recommended to N.I.?

A Alora patch 0
A. 0.025
025 mg; change patch
twice weekly
B. Climara 0.025 mg; change patch once
weekly
C. Prempro 0.3 mg/1.5 mg; take 1 tablet PO
daily
D. Premarin 0.625 mg; take 1 tablet PO
daily
Page 37

5
Patient Case 1
N.I. is a 51-year-old woman complaining
of hot flashes and vaginal irritation. She
has tried exercise, diet, and
antidepressants to help relieve her hot
flashes but has been unsuccessful. She
is otherwise healthy with no history of
cancer and no surgeries. She states her
hot flashes are interfering with her daily
activities and wants to try hormone
therapy.
Page 37

Patient Case 1, Question 2


2. Which one of the following HT treatments
should be recommended to N.I.?

A Alora patch 0
A. 0.025
025 mg; change patch
twice weekly
B. Climara 0.025 mg; change patch once
weekly
C. Prempro 0.3 mg/1.5 mg; take 1 tablet PO
daily
D. Premarin 0.625 mg; take 1 tablet PO
daily
Page 37

Patient Case 2, Question 3


3. C.A. is a 71-year-old white woman who rarely drinks
alcohol, does not smoke, and exercises for 30
minutes 3 times/week. She takes calcium 500 mg
/vitamin D 400 IU 3 times/day. She is 53 and weighs
140 lbs. Her BMD T-score is 1.8 at the hipp and 2.6
at the spine. Which one of the following statements is
the correct diagnosis for C.A.?

A. Normal BMD of the spine.


B. Osteopenia of the spine.
C. Osteoporosis of the spine.
D. Osteoporosis is defined when a fracture has
occurred.
18 (50)
Page 45

6
Osteoporosis Definitions
World Health Organization Definitions

1. Normal = BMD within 1 standard deviation


(SD) of the young adult mean

2. Osteopenia = BMD between 1 SD and


2.5 SD below the young adult mean

3. Osteoporosis = BMD at least 2.5 SD

Risk Factors
Female Estrogen deficiency
White race Low body mass index (BMI) or
low weight
Poor nutrition, long-term low-
Family history of osteoporosis
calorie intake Low calcium and vitamin D
Early menopause (before age intake
45) or prolonged Sedentary lifestyle, decreased
premenopausal amenorrhea y
mobility
Drugs: Cigarette smoking
Alcoholism
Glucocorticoids
Dementia
Heparin Impaired eyesight despite
Anticonvulsants adequate correction
Excessive levothyroxine Previous fractures
History of falls
GnRH agonists
Lithium
Cancer drugs
Page 41

Risk Assessment Page 41


FRAX Score Platform created to
calculate 10-year risk of major
osteoporotic fracture (hip-best use,
spine, wrist, shoulder)
http://www.shef.ac.uk/FRAX/ or
www.nof.org
f
Includes 10 risk factors: Age, Sex, Wt, Ht,
low femoral neck BMD, parental hx of
fractures, tobacco use, glucocorticoids,
rheumatoid arthritis, >2 units of alcohol
daily, other secondary causes
Dual-energy x-ray absorptiometry (DXA)

7
Screening Recommendations
(Women) Page 41
BMD Measurements:
All women >65 years
Postmenopausal women with medical
causes of bone loss (hyperparathyroidism,
steroid
t id use))
Postmenopausal women age 50 with risk
factors: fracture after menopause, wt <127
lbs or BMI <21 kg/m2 , smoker, parent w/
hip fracture, rheumatoid arthritis, alcohol >
2 units/day
Postmenopausal women with fragility
fracture

Screening Recommendations
(Men)
BMD Measurements:
Older than 70 years old
Ages 50-70
50 70 with risk factors or previous
fractures

23 (45)

References
NAMS Position Paper Published 2010
Menopause Vol. 17; No.1 pp 24-25.
Also found at
http://www.menopause.org/PSosteo10.pdf
AACE Medical Guidelines for Diagnosis and
Treatment of Postmenopausal
Osteoporosis
Endocr Pract. 2010;16(Suppl 3)
Found at www.aace.org

8
Patient Case 2, Question 3
Answer
3. C.A. is a 71-year-old white woman who rarely drinks
alcohol, does not smoke, and exercises for 30
minutes 3 times/week. She takes calcium 500 mg
/vitamin D 400 IU 3 times/day. She is 53 and weighs
140 lb. Her BMD T-score is 1.8 at the hipp and
2.6 at the spine. Which one of the following
statements is the correct diagnosis for C.A.?

A. Normal BMD of the spine.


B. Osteopenia of the spine.
C. Osteoporosis of the spine.
D. Osteoporosis is defined when a fracture has
occurred.
Page 45

Lifestyle Modifications
Recommendations
Advise patient to avoid smoking and to
consume only moderate amounts of alcohol.
Encourage regular weight-bearing and
muscle-strengthening exercise.
Encourage adequate intake of calcium (at
least 1200 mg/day) and vitamin D (600800
IU/day). For older than 70 years 800 IU/day
Assess fall risks
Page 43, 45

Patient Case 2, Question 4


4. Which one of the following is the best
treatment for C.A.?
A. Teriparatide 20 mcg g SQ daily
y
B. Alendronate 70 mg PO Qweek
C. Miacalcin nasal spray 1 spray (200
IU) in one nostril daily
D. No additional therapy required,
continue on calcium and vitamin D
Page 45

9
Start Drug Therapy
Based on NOF, AACE, and NAMS
recommendations:
Hip or spine fracture
T-score <-2.5 or below at hip, spine, or
f
femoral l neck
k
T-score between -1.0 and -2.5 with a 10-
year probability of a hip fracture 3% OR a
10-year probability of a major
osteoporosis-related fracture 20% based
on the FRAX tool (US-adapted WHO
algorithm)
Pages 41, 42

Current Treatments
Bisphosphonates (1st line)
SERMs
Teriparatide (rPTH 134)
Estrogen Therapy
Calcitonin
Denosumab
Others
Pages 42-45

Bisphosphonates
Inhibit osteoclasts, reduce bone resorption
Adverse effects: Oral agents most common is
esophageal/gastric irritation
Must be taken on an empty stomach and remain
upright for at least 30 min. (60 min for ibandronate)
Reduce risk of vertebral fractures by 40-70%
Reduce risk of non-vertebral fractures (hip) by 20-
35%
Only use in patients with GFR of > 30mls /min
Osteonecrosis of jaw,
spontaneous fractures (?) Pages 42 - 43

10
Bisphosphonates
Alendronate (Fosamax) PO daily or weekly
Risedronate (Actonel) PO daily, weekly,
monthly
**Risedronate (Atelvia) PO weekly (delayed
release, take 30 min. after breakfast, avoid
PPI use))
Ibandronate (Boniva) PO daily, monthly or IV
Q 3 months
Zolendronic acid (Reclast) IV yearly or Q 2
years for prevention
Etidronate (approved in Canada for
osteoporosis) Pages 42 - 43

Drug Indications Dosing and Routes


Alendronate Prevention/Treatment of 10 mg PO daily
(Fosamax, Osteoporosis in Postmenopausal 70 mg PO weekly
Fosamax D) Women, Increase BMD in Men, 5 mg PO daily for prevention
Glucocorticoid induced osteoporosis 35 mg PO daily for prevention
Pagets Disease
Risedronate Prevention/Treatment of 5 mg PO daily
(Actonel, Osteoporosis in Postmenopausal 35 mg PO weekly
Actonel with Women, Increase BMD in Men, 75 mg on 2 cons. days monthly
Calcium
Calcium, Glucocorticoid-induced osteoporosis 150 mg PO monthly
Atelvia) Pagets Disease
Ibandronate Prevention and Treatment of 2.5 mg PO daily
(Boniva) Osteoporosis in Men and Women 150 mg PO monthly
3 mg IV Q 3 months
Zolendronic Prevention/Treatment of 5 mg IV yearly
Acid Osteoporosis in Postmenopausal 5 mg IV Q 2 years (prevention
(Reclast) Women, Increase BMD in Men, in women)
Glucocorticoid-induced osteoporosis
Pagets Disease
Etidronate Approved for use in Canada

Current Treatments
SERMs (Selective Estrogen Receptor
Modulators)
Raloxifene 60 mg PO daily, only SERM approved
for prevention and treatment of osteoporosis
risk of vertebral fracture by 55% (MORE data)
in women with T-score < -2.5 and by 30% in
women with low T-scores
No effect observed for non-vertebral (hip) fracture
Adverse Effects: VTE events, may cause hot
flashes or leg cramps
Pages 43 - 44

11
Teriparatide (rPTH 134)
Subcutaneous inj 20 mcg/day for up to 18-24
months, bone formation
Approved for treatment for those at high risk of
fracture
Rare risk of bone tumors (seen in rats)
Estrogen Therapy
Approved for prevention
Calcitonin
Approved for treatment, inhibits resorption, usually
alternative if other agents cannot be used
Nasal spray 200 IU daily, best for vertebral
fractures- reported 33%
May help with bone pain
Page 44

Denosumab (Prolia) approved 2010


Inhibits osteoclast-mediated bone resorption,
monoclonal antibody binds to RANKL (receptor
activator of nuclear factor ligand), cytokine
essential for formation,
formation function
function, survival of
osteoclasts
Dose 60 mg subcutaneously every 6 months
Increased BMD hip (6%) and spine (9%)
Reduced spinal fracture risk by 68%, hip fracture
risk by 40%
Safety issues
Possible infections
Hypocalcemia
Page 44

Patient Case 2, Question 4


Response Cards
4.Which one of the following is the best
treatment for C.A.?
A. Teriparatide 20 mcg g SQ daily
y
B. Alendronate 70 mg PO Qweek
C. Miacalcin nasal spray 1 spray (200
IU) in one nostril daily
D. No additional therapy required,
continue on calcium and vitamin D
Page 45

12
Patient Case 4, Question 5
5. S.E. is a 28-year-old woman who would like to get
pregnant soon. Her medical history includes
hypertension and seasonal allergies. Her drugs
include lisinopril, nasal saline spray, and folic acid.
Whi h one off th
Which the ffollowing
ll i iis bbestt tto ttreatt h
her
hypertension while pregnant or trying to conceive?

A. Continue on lisinopril
B. Discontinue lisinopril and all other medications
C. Discontinue lisinopril and start methyldopa
D. Continue lisinopril and add metoprolol
Page 48

Drug Use in Pregnancy


Folic Acid 400 1000 mcg daily before
conception and first 12 -15 days
Assess drug use if trying to conceive
Teratogen drug or environmental
agent that has potential to cause
abnormal fetal growth
Consider trimester and timing of
medication administration
Assess drug vs. benefit
Page 46

FDA Classifications
Simpler Form:
A: Controlled studies show no risk
B: No evidence of risk in humans
C: Risk cannot be ruled out
D: Positive evidence of risk
X: Contraindicated in pregnancy

Page 46

13
Known Teratogens
Isotretinoin ACE inhibitors
Methotrexate DES
Alcohol Streptomycin
Mercuryy Warfarin
Lead
Thalidomide
Carbamazepine
Androgens
Lithium
Cocaine Tetracycline
Phenytoin Vitamin A
Valproate Statins
Topiramate
See page 47 for more complete lists

Conditions in Pregnancy
GI
Nausea and vomiting, constipation,
heartburn
Hypertension
yp
Anticoagulation
Diabetes ADA Guidelines
Depression APA and ACOG
guidelines

Page 49 - 51

Drug Use in Lactation


Consider risk vs. benefit
Pump and Dump/Save
Choose drugs with shorter half-lives
Drugs enter human milk if they are:
Highly lipid soluble
In high concentration in the mothers plasma
Low in molecular weight (<500)
Low in protein binding
Easily cross into the brain

Page 48-49 Hale, Thomas. Medications and Mothers Milk. 11th Edition 2004

#43

14
Patient Case 4, Question 5
5. S.E. is a 28-year-old woman who would like to get
pregnant soon. Her medical history includes
hypertension and allergies. Her drugs include
lisinopril, nasal saline spray, and folic acid. Which
one of the following is best to treat her
hypertension
yp while ppregnant
g or trying
y g to conceive?

A. Continue on lisinopril
B. Discontinue lisinopril and all other medications
C. Discontinue lisinopril and start methyldopa
D. Continue lisinopril and add metoprolol

Page 48

Patient Case 5, Question 6


6. Y.G. is a 33-year-old woman who was initiated on
Mircette 4 months ago for contraception. She has
break-through bleeding at the start of her active
pills that lasts a few days before resolving. The
physician
p y wants to change
g the OC. Which one of
the following OCs on her formulary should the
physician prescribe?

A. Continue on Mircette for another 3 months


B. Change to Ortho-Cept
C. Change to Loestrin 21
D. Change to Lessina

Page 58

Patient Case 5, Question 6 Page 58


Name of OC Estrogen Progestin Androgen
Property property property

Mircette (Desogestrel Low High Low


0.15mg /EE 20mcg)

Ortho Cept
Ortho-Cept Intermediate High Low
(Desogestrel 0.15mg
/EE 30 mcg)
Lessina Low Low Low
(Levonorgestrel
0.1mg/EE 20mcg)
Loestrin 21 Low Low High
(Norethindrone acetate
1.5 mg/ 30 mcg)

15
Contraceptive Methods
Combined Hormonal Contraceptives
Oral tablet, chewable tablet
Patch
Vaginal
g Ring g
Progestin Only
Oral tablet
Injection
Implant
Intrauterine system
Non-hormonal

46

Starting Methods
(Combined Hormonal Contraception)
Sunday Start-
Start- 1st Sunday after
menses begins
First
Fi t DDay St
Startt- Start
Start- St t method
th d first
fi t
day of menses
Quick Start-
Start- Start method at clinic
regardless of time in cycle

Page 59-60

Contraindications for Combined


Contraceptives (Category 4)
Breastfeeding <6 wks
Major surgery with prolonged
postpartum
mobilization
Smoker 35 yrs Known thrombogenic
Multiple risk factors for CVD mutations
BP >160/100 Current
C t and
d hi
history
t off
Vascular disease ischemic heart disease
Current or history of Stroke (history of CVA)
DVT/PE Complicated valvular heart
Complicated diabetes disease
Presence of liver tumors, Migraine headache with aura
severe cirrhosis, or active Current breast cancer
viral hepatitis
Page 56-57
http://www.who.int/reproductive-health/publications/MEC_3/summary_tables.html

16
Page 57
Side Effects of Combined
Contraceptives
ESTROGENIC PROGESTATIONAL &
Nausea, vomiting ANDROGENIC**
Bloating, edema Headaches
Irritability Increased
I d appetite
tit
Cyclic weight gain Increased weight
Cyclic headache gain
Hypertension Depression, fatigue
Breast fullness, Changes in libido
tenderness Hair loss,
hirsutism**
Acne, oily skin**

Managing Side Effects


Nausea
Related to estrogen content
Take at bedtime or with food
Acne
Choose less androgenic formulation or
increased estrogen
Break Through Bleeding

Page 57

Management of Side Effects:


Breakthrough Bleeding and Spotting
If unexpected bleeding occurs, use additional
contraception until bleeding completely ceases
Rule out potential causes (e.g., PID)
Encourage
E continuation
ti ti if fifirstt ffew cycles
l
When switch is indicated:
Increase estrogen dose:
If bleeding begins during first 14 days
If absence of withdrawal menses
If menses continues into active pill cycle

Page 57

17
Management of Side Effects:
Breakthrough Bleeding and Spotting
When switch is indicated:
Change progestin:
If bleeding begins after 14 days (of active med)
Progestin should have higher progestational
and/or androgenic activity
Increase both estrogen and progestin:
If bleeding occurs midcycle

Page 57

Patient Case 5, Question 6


6. Y.G. is a 33-year-old woman who was initiated on
Mircette 4 months ago for contraception. She has
break-through bleeding during at the start of her
active pills that lasts a few days before resolving.
The pphysician
y wants to change
g the OC. Which one
of the following OCs on her formulary should the
physician prescribe?

A. Continue on Mircette for another 3 months


B. Change to Ortho-Cept
C. Change to Loestrin 21
D. Change to Lessina

Page 58

Patient Case 5, Question 6 Page 58


Name of OC Estrogen Progestin Androgen
Property property property

Mircette (Desogestrel Low High Low


0.15mg /EE 20mcg)

Ortho Cept
Ortho-Cept Intermediate High Low
(Desogestrel 0.15mg
/EE 30 mcg)
Lessina Low Low Low
(Levonorgestrel
0.1mg/EE 20mcg)
Loestrin 21 Low Low High
(Norethindrone acetate
1.5 mg/ 30 mcg)

18
Patient Case 5, Question 6
6. Y.G. is a 33-year-old woman who was initiated on
Mircette 4 months ago for contraception. She has
break-through bleeding at the start of her active
pills that lasts a few days before resolving. The
physician
p y wants to change
g the OC. Which one of
the following OCs on her formulary should the
physician prescribe?

A. Continue on Mircette for another 3 months


B. Change to Ortho-Cept
C. Change to Loestrin 21
D. Change to Lessina

Page 58

Patient Case 6, Question 7


7. L.M. is a 37-year-old woman, going to get married,
needs birth control pills for now, wants children in a
year. PMH: hypertension x 2 years, GERD, admits to
2 glasses of wine/week and smokes pack per day.
Meds: HCTZ 25 mg PO daily, Lotrel 5/20
(amlodipine/benazepril) PO daily, Prilosec 20 mg
((omeprazole)
p ) PO daily,
y, and occasional ibuprofen.
p
She is 57, Weight: 210 lbs. (95kg) Which one of the
following contraceptive products should the physician
prescribe?

A. Ortho-Evra
B. YAZ
C. Micronor
D. Mirena

Page 67

Combined Contraceptives:
Drug Interactions
Hepatic enzyme inducers
Agents most likely to cause breakdown of estrogen or
progestin: phenobarbital, phenytoin, topiramate,
p ,p
carbamazepine, primidone
Sodium valproate, ethosuximide, lamotrigine* and
vigabatrin do not effect contraceptive hormone levels
Management
Use another method
Use different anticonvulsant
Increase dose of contraceptive

Page 58,59

19
Combined Contraceptives:
Drug Interactions
Recommendations by Council of Scientific Affairs to AMA
Rifampin - significant risk of failure; counsel about the use of
additional nonhormonal contraceptive methods during the
course of rifampin therapy
Other antibiotics - small risk of interactions; not possible to
identify women who may be at risk of OC failure. Recent
WHO/CDC eligibility criteria classified as category 1.
Counsel about the additional use of nonhormonal
contraception or alternate methods for:
Those not comfortable with small risk of interaction
Those with previous failures or who develop
breakthrough bleeding during use of antibiotics
WHO Medical Eligibility for Contraception 2009
Obstet Gynecol 2001;98:53-60

Combined Contraceptives: Drug


Interactions (Page 58,59)
Protease inhibitors
Can cause changes in mean AUC of estrogen
Consider different contraceptive options
St. Johns wort
Induces cytochrome P450 and could decrease
effectiveness of oral contraceptives
Concurrent condom use is excellent safety measure
Specific product interactions: Drospirenone
(Found in YAZ, Yasmin, Safyral and Beyaz)
Interacts with NSAIDs, ACE Inhibitors, potassium
Increased ethinyl estradiol levels
Reported with atorvastatin, ascorbic acid,
acetaminophen, ketoconazole and itraconazole

Controversies
Transdermal Patch
Increased exposure to estrogen, 60% more
estrogen than in women taking 35 mcg of EE
? Increased risk of VTE, cardiovascular and
cerebrovascular events
Less effective in women > 198 lbs. , (90kg)
Extended Use of Hormonal Contraception
3 month formulations
1 year formulations
Breakthrough bleeding common
Page 61

20
New Products
Natazia (estradiol valerate/dienogest)
Quadriphasic
Safyral (ethinyl estradiol 30 mcg /drospirenone 3 mg)
Beyaz }
Contains 0 0.451
451 mg levomefolate calcium (folic acid)
(ethinyl estradiol 20 mcg /drospirenone 3 mg)

Lo Loestrin Fe (ethinyl estradiol 10 mcg/


norethindrone acetate 1 mg)
Lowest ethinyl estradiol oral formulation
Iron tablets instead of placebo (2 tabs of 75 mg
ferrous fumarate)
Page 60

Contraceptive Methods
Combined Hormonal Contraceptives
Oral tablet
Patch
g
Vaginal Ringg
} Pages 59 - 63 for use,
missed doses
Progestin Only
Oral tablet
Injection
Implant
Intrauterine system
Non-hormonal

POPs: Patient Counseling


Take one pill at the SAME TIME daily
until end of pack. Start next pack the
next day. y
More than a 3 hour delay is considered
to be a missed dose
If a pill is missed, take missed pill(s) and
use backup for 48 hours. Consider
using EC if sex in past 3-5 days.
Page 64

21
Depot Medroxyprogesterone
Acetate (DMPA) Injection
Injection administered Q 11-13 weeks
Side effects
Weight gain
Mood issues, other progestin related
effects
Long return to fertility
Possible decrease in BMD, especially in
younger women with use > 5 years
Page 64, 65

Levonorgestrel
IUS

T-shaped intrauterine contraceptive


Releases 20 mcg/day of levonorgestrel
Effective for 5 years with less than failure rate
Quick return to fertility
US product: Mirena

Page 66,67

Page 67
Implantable Rod
Implanon (etonogestrel)
Releases 25-45 mcg/day over 3 years
Very effective, suppresses ovulation in 97% of cycles

g and effectiveness
Concern with weight
Limited information in women > 130% of their
body weight

Common side effects:


Swelling, bruising, irritation
Irregular menses ~18%
Amenorrhea occurs in ~22%
Other side effects similar to progestin only
Does not appear to affect BMD

22
Patient Case 6, Question 7
Response Cards
6. L.M. is a 37-year-old woman, states she is going to
get married soon and would like to begin birth control
pills for now but would like to have children in a year
or so. Past medical history includes hypertension x 2
years, GERD, admits to 2 glasses of wine/week and
smokes pack per day. Her medications include
HCTZ 25 mg PO daily, Lotrel 5/20
( l di i /b
(amlodipine/benazepril)il) PO d
daily,
il PPrilosec
il 20 mg
(omeprazole) PO daily, and occasional ibuprofen.
She is 57, Weight: 210 lbs. (95kg) Which one of the
following contraceptive products should the physician
prescribe?

A. Ortho-Evra
B. YAZ
C. Micronor
D. Mirena Page 67

EC Methods
Yuzpe Regimen estrogen + progestin
Levonorgestrel progestin only
Plan B (Next Choice) (0.75 mg, 2 tablets in package), tablets
may be taken 12 hours apart or together at one time.
Plan B One Step (1.5 mg, 1 tablet taken as soon as possible
after unprotected intercourse).
OTC for 17 years and older
Ulipristal acetate Selective Progesterone
Receptor Modulator (SPRM)
Ella 30 mg, 1 tablet taken as soon as possible after
unprotected intercourse, labeled for 120 hours, prescription-
only
Copper IUD (up to 5 days after ovulation)
Mifepristone (off label use, up to 5 days after
sexual intercourse)
Pages 68,69

Indications
Unprotected intercourse in the past 72 hours
(120 hours)
Contraceptive failure
Condom breaks
Missed oral contraceptive pills
Expulsion of IUD or vaginal ring
Patch fell off for long period of time
Displacement of barrier method (diaphragm)
Sexual assault
Exposure to teratogen

Page 68
ACOG Practice Bulletin, Int J of Gynecol Obstet, 2002;78:191-198

23
EC Mechanism of Action
Not clear: depends on time of administration, best
prior to ovulation time
1. Prevents or delays
ovulation
2. Traps sperm in
thickened cervical
mucus
3. May interfere with
fertilization
4. May interfere with
implantation
(controversial)
May causes
endometrial changes Does not cause an abortion
Probably acts prior ACOG Practice Bulletin No. 112, May 2010
#71 to implantation

Effectiveness
(use after one act of unprotected intercourse)
If 100 women have unprotected
sex in the 2nd or 3rd week of
their cycle

88 will become
pregnant without
EC
2 will become pregnant
using combined EC (75%
reduction)
1 will become pregnant
using progestin EC (88%
reduction) Trussell J et al. FPP. 1996;28:58
1996;28:58--64,87 and WHO, 1998

Patient Case Question


(From Self-Assessment Questions, #9, pg. 33)

9. K.G. is a 33-year-old woman who has been trying to


conceive for the last year. Her husbands medical
exam is normal and it is found that K.G. is not
ovulating every month. She has not tried any
medications
di ti previously
i l to
t induce
i d ovulation.
l ti Whi
Which h
of the following medications is best to start K.G. to
induce ovulation?

A. Ovidrel (hCG)
B. Synarel (GnRH agonist)
C. Pergonal (hMG)
D. Clomid (clomiphene citrate)

24
Infertility
Potential Causes
85% of couples conceive in 1 year, 15% infertile

Men (male factor) Women (female factor)


Endocrine Ovulatory
Anatomic Cervical
S
Sexual
lddysfunction
f ti Pelvic
Medical conditions
Polycystic ovary
syndrome
Endometriosis
Pelvic inflammatory
disease
Uterine fibroids
Idiopathic
73 (15)
Page 70 - 71

Fertility Agents
1. Clomiphene citrate 1st line agent
2. Human menopausal gonadotropin
(hMG)
3. Follicle-stimulating hormone (FSH)
4. Human chorionic gonadotropin (hCG)
5. Gonadotropin-releasing hormone
analogs (GnRH)
Page 70 - 71

Patient Case Question


(From Self-Assessment Questions, #9 pg. 33)

9. K.G. is a 33-year-old woman who has been trying to


conceive for the last year. Her husbands medical
exam is normal and it is found that K.G. is not
ovulating every month. She has not tried any
medications
di ti previously
i l to
t induce
i d ovulation.
l ti Whi
Which h
of the following medications is best to start K.G. to
induce ovulation?

A. Ovidrel (hCG)
B. Synarel (GnRH agonist)
C. Pergonal (hMG)
D. Clomid (clomiphene citrate)

25
Sexually Transmitted Infections/Diseases

Pages 73-80

Recently Updated 2010


Centers for Disease Control and
Prevention. Sexually transmitted
diseases treatment g
guidelines 2010.
MMWR 2010; 59: 1-110.
Available at www.cdc.gov/std/treatment/

Sexually Transmitted Infections


Herpes Simplex Virus (HSV)
Syphillis- Chancre, resolves in 26 weeks,
Benzathine penicillin G 50,000 units/kg up to 2.4
million units IM (adults), Doxy 100 mg PO BID x14 ds
Chlamydia Azithromycin 1 g in a single dose or
doxycycline 100 mg 2 times/day for 7 days
Gonorrhea Ceftriaxone 250 mg IM or cefixime 400
mg orallyall as a single dose PLUS treatment of
chlamydia if not ruled out
Fluoroquinolones no longer recommended because
of resistance
Abstain from sexual intercourse for at least 7 days
and until sexual partners are adequately treated.
Pages 74 - 77

26
HSV

Therapy can help control symptoms but


does not affect risk, frequency or
severity of recurrences (50-80% recur)
Virus
Vi remains
i llatent
t t iin sacrall d
dorsall roott
ganglia
Initial HSV infection
Acyclovir 400 mg orally 3 times/day for 710 days
Acyclovir 200 mg orally 5 times/day for 710 days
Famciclovir 250 mg orally 3 times/day for 710 days
Valacyclovir 1 g orally 2 times/day for 710 days
Page 74

HSV
Recurrent HSV infection
If treatment is initiated within 1 day of lesion onset,
patients with recurrent infections may benefit.
Acyclovir (see page 74 for various regimens)
Famciclovir
Valacyclovir
Suppressive therapy
Recommended in patients with six or more episodes
yearly (reassess annually the need for suppressive
therapy)
Acyclovir 400 mg orally 2 times/day
Famciclovir 250 mg orally 2 times/day
Valacyclovir 500 mg/day orally
Valacyclovir 1000 mg/day orally
Page 74

Patient Cases Question 10


Response Cards Page 74
10. D.H. returns to the clinic 10 months after her initial
herpes infection. She is troubled by all of the
recurrences she is having (seven to date). Which
one of the following therapies do you recommend?

A Valacyclovir 500 mg orally 2 times/day to be used for 5 days


A.
whenever she notices a recurrence beginning.

B. Acyclovir 400 mg orally 3 times/day to be used for 10 days


whenever she notices a recurrence beginning.

C. Suppressive therapy with famciclovir 250 mg orally 3


times/day.

D. Suppressive therapy with valacyclovir 500 mg/day orally.

27
Patient Cases Question 11
11. M.A. is a 24-year-old woman severe abdominal
pain, fever, dysuria, and a vaginal discharge. She is
sexually active with multiple partners. PMH
unremarkable except for recurrent genital herpes
(one or two episodes per year). Medications: Ortho
Tri-Cyclen, fluticasone (Flonase) as needed. Temp.
101.2F (38C), HR 92, RR 15, BP 117/75 mm Hg.
M.A. has adnexal tenderness, cervical motion
tenderness, and a vaginal discharge. Which one of
the following is the best empiric therapy?

A. Ampicillin/sulbactam 2 g every 6 hours for 14 days


B. Metronidazole 500 mg 3 times/day for 7 days
C. Cefotetan 2 g intravenously every 12 hours with
doxycycline 100 mg orally every 12 hours for 14 days
D. Ceftriaxone 125 mg intramuscularly 1 with
doxycycline 100 mg intravenously 2 times/day for 7
days
Page 76

Complications

Urethritis
Pelvic Inflammatory Disease
Syphilis (secondary,
(secondary latent,
latent tertiary,
tertiary
neuro)
Prostatitis

Please see page 75 - 78 for more info

Pelvic Inflammatory Disease


Treatment:
Parenteral treatment - discontinued 24 hours after clinical
improvement and switched to oral therapy for 14 days.
Regimen A: [cefotetan 2 g intravenously every 12 hours or
cefoxitin 2 g intravenously every 6 hours] PLUS doxycycline
100 mg intravenously or orally every 12 hours
Regimen B: clindamycin 900 mg intravenously every 8 hours
PLUS gentamicin intravenously/intramuscularly 2-mg/kg
g dose;; then 1.5 mg/kg
loading g g everyy 8 hours ((or once-dailyy
therapy)
Alternative regimens:
Ampicillin-sulbactam 3 g intravenously every 6 hours plus
doxycycline 100 mg intravenously or orally every 12 hours
Oral treatment
Ceftriaxone 250 mg intramuscularly once (other third-
generation cephalosporins also acceptable) or cefoxitin 2 g
intramuscularly plus probenecid 1 g orally once] PLUS
doxycycline 100 mg 2 times/day for 14 days with or without
metronidazole 500 mg orally 2 times/day for 14 days
Sexual partners of patients with PID within the past 60 days
should be tested and treated.

28
Patient Case 11 - Response Cards
11. M.A. is a 24-year-old woman who presents to the emergency
department with severe abdominal pain, fever, dysuria, and a
vaginal discharge. She is sexually active with multiple partners.
Her medical history is unremarkable except for recurrent genital
herpes (one or two episodes per year). Her medications on
admission include birth control pills (Ortho Tri-Cyclen) and
fluticasone (Flonase) as needed. On physical examination,
M.A.s vital signs include temperature 101.2F (38C), heart rate
92 beats/minute, respiration rate 15 breaths/minute, and BP
117/75 mm Hg. M.A. has adnexal tenderness, cervical motion
tenderness and a vaginal discharge.
tenderness, discharge Which one of the following
is the best empiric therapy?

A. Ampicillin/sulbactam 2 g every 6 hours for 14 days


B. Metronidazole 500 mg 3 times/day for 7 days
C. Cefotetan 2 g intravenously every 12 hours with doxycycline 100
mg orally every 12 hours for 14 days
D. Ceftriaxone 125 mg intramuscularly 1 with doxycycline 100 mg
intravenously 2 times/day for 7 days

Page 76

Patient Cases Question 11 answer


11. M.A. is a 24-year-old woman who presents to the emergency
department with severe abdominal pain, fever, dysuria, and a
vaginal discharge. She is sexually active with multiple partners.
Her medical history is unremarkable except for recurrent genital
herpes (one or two episodes per year). Her medications on
admission include birth control pills (Ortho Tri-Cyclen) and
fluticasone (Flonase) as needed. On physical examination,
M.A.s vital signs include temperature 101.2F (38C), heart rate
92 beats/minute, respiration rate 15 breaths/minute, and BP
117/75 mm Hg. M.A. has adnexal tenderness, cervical motion
tenderness and a vaginal discharge.
tenderness, discharge Which one of the following
is the best empiric therapy?

A. Ampicillin/sulbactam 2 g every 6 hours for 14 days 3 g


B. Metronidazole 500 mg 3 times/day for 7 days No
C. Cefotetan 2 g intravenously every 12 hours with doxycycline 100
mg orally every 12 hours for 14 days Yes
D. Ceftriaxone 125 mg intramuscularly 1 with doxycycline 100 mg
intravenously 2 times/day for 7 days
No

Page 76

Vaginal Infections
Bacterial Vaginosis
Metronidazole or clindamycin
Fishy odor
Women only treated
Trichomoniasis
Metronidazole
Yellow-green vaginal discharge
** All sexual partners should be treated
Vulvovaginal Candidiasis
OTC antifungals
Intense itchiness and beige, milky discharge
Pages 78-79

29
Patient Cases Question 13
13. A 65-year-old man presents to his physician
complaining of symptoms determined to be erectile
dysfunction (ED). He has a history of
hyperlipidemia, GERD, and glucose intolerance.
His current medications include atorvastatin 20 mgg
PO daily, omeprazole 20 mg PO daily, and aspirin
81 mg as tolerated. He states that he heard of
medications to help with his symptoms but does not
want to have to plan out his intimate moments.
What medication might work best for this patient?

A. Tadalafil
B. Vardenafil
C. Yohimbine
D. Bupropion Page 83 89

Sexual Dysfunction Men


Reduced libido from Ejaculation
organic or Premature
psychological Retarded
causes Absent
Low serum Retrograde
R t d
testosterone
concentrations
Erectile dysfunction
Increased
Psychological
concentrations of
serum prolactin Organic
Mixed
Others such as
Page 80 drugs

SD Treatment in Men
Treat organic cause
Non-pharm: vacuum pump devices, venous
constriction rings
Testosterone replacements: inj., dermal
patch, gel
Phosphodiesterase Type 5 inhibitors:
Sildenafil (Viagra) 50 mg PO 1 hr. prior
Tadalafil (Cialis) 10 mg PO 36 hrs. prior
Vardenafil (Levitra) 10 mg PO 1 hr prior
Yohimbine
Alprostadil: inj. or pellets
SSRIs premature ejaculation

Page 81,82

30
Patient Cases Question 13
response cards
13. A 65-year-old man presents to his physician
complaining of symptoms determined to be erectile
dysfunction (ED). He has a history of
hyperlipidemia, GERD, and glucose intolerance.
His current medications include atorvastatin 20 mgg
PO daily, omeprazole 20 mg PO daily, and aspirin
81 mg as tolerated. He states that he heard of
medications to help with his symptoms but does not
want to have to plan out his intimate moments.
What medication might work best for this patient?

A. Tadalafil
B. Vardenafil
C. Yohimbine Page 83
D. Bupropion

Patient Cases Question 13


answer
13. A 65-year-old man presents to his physician
complaining of symptoms determined to be erectile
dysfunction (ED). He has a history of
hyperlipidemia, GERD, and glucose intolerance.
His current medications include atorvastatin 20 mgg
PO daily, omeprazole 20 mg PO daily, and aspirin
81 mg as tolerated. He states that he heard of
medications to help with his symptoms but does not
want to have to plan out his intimate moments.
What medication might work best for this patient?

A. Tadalafil
B. Vardenafil
C. Yohimbine
D. Bupropion
Page 83

Questions

31