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Updates In Women’s Health

Presented by

Emma Merrells Rph., BCACP, BCGP

Clinical Pharmacist, Overton Brooks VAMC

July 15, 2017

Louisiana Pharmacists Association

ReviewofCommonWomen’sHealthConcerns

Contraception, Menopause,

Health Screenings & Vaccines

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Objectives

• To provide an overview of contraception methods including

emergency contraception.

• To provide updated information related to menopause and

hormone replacement therapy.

• To provide a review of the new pregnancy & lactation rule.

• To provide drug updates specific for women.

• To review current women’s health screening guidelines and vaccine recommendations

Unintended Pregnancy

A pregnancy that is reported to have been either unwanted or mistimed

Risks

• Delayed prenatal care• Possible pregnancy related morbidities; anemia, VTE, and

pregnancy induced hypertension• Risk to the infant due to risky behavior of the mother such as

tobacco & Alcohol use

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Barriers to Hormonal Contraception

• Provider knowledge, training and counseling

• Obtaining a prescription (pap test , pelvic exam & breast exams are not medically necessary for the provision of hormonal contraception.)

• Obtaining the contraceptive (employer or insurance refusal, cost, & legal restrictions)

Effectiveness of Family Planning Methods

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Emergency Contraception

• The 3 methods of emergency contraception:

1. emergency contraception pills (ECPs)

levonorgestrel

ulipristal

2. Combined oral contraceptive pills or the Yuzpe Method

3. Copper-bearing intrauterine devices (IUDs)

Emergency Contraception Counseling

• When to take

• Adverse effects

• When to start or restart regular contraception

• When to expect next cycle

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Emergency Contraception

• Some factors to consider when choosing emergency contraception:

1. time since unprotected intercourse

2. patient weight

3. eligibility for and access to each method

4. acceptability of a copper IUD for long term

contraception

Patient Case

• EM is a 16 year old woman seeking emergency contraception. Wt. 74kg. She reports that unprotected intercourse occurred 2 days ago and that she was afraid to seek counseling. She is a high school student and does not desire to become pregnant at this time. She is not currently using any method of contraception.

• which of the following would be the best emergency contraceptive for this patient.

A. Copper IUD

B. Ulipristal acetate 30 mg

C. COC pill ( yuzpe regimen)

D. Levonorgestrel 0.75mg or Levonortesterol 1.5mg)

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Menopause

Stages of Menopause

• Pre-menopause

• Peri-menopause

• Menopause:

a. Natural

b. Drug induced

c. Surgery induced

• Post menopause

Menopause

• Menopause is the final menstrual period which can be confirmed after going 12 consecutive months without a period or when both ovaries are surgically removed or damaged.

• Symptoms include hot flashes, irritability, vaginal dryness, sleep disturbances & depression

• Increased risk for osteoporosis

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Genitourinary Syndrome of Menopause (GSM)

Vulvovaginal atrophy (VVA)

Lower urinary tract symptoms

a. Vaginal dryness, irritation, itching, burning

b. Dyspareunia

c. Urinary frequency, urgency, dysuria

d. Increased risk of UTI

e. Decreased sexual libido

Non-hormonal Options for Treatment of GSM

Vaginal Lubricants

1.  Water based

2.  Oil based

3.  Silicone based    

Vaginal moisturizers:

1.  Polycarbophil-based

2. silicone based ovule

3. Water based

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Hormonal Options for Treatment of GSM

Vaginal estrogen products:

1. Creams

2. Vaginal tablets  & inserts

3. Vaginal ring

Estrogen Receptor Agonist/Antagonist

Prasterone (Intrarosa®)

• Vaginal inserts for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause, Approved November 2016

• Dosage and administration: one vaginal insert once daily at bedtime

• Vaginal Insert: 6.5 mg of prasterone.

• Contraindications: Undiagnosed abnormal genital bleeding.

• Warnings and precautions: Current or past history of breast cancer.

• Adverse reactions: vaginal discharge & abnormal pap smear readings

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Estrogen Receptor Agonist/Antagonist

• Ospemifene is an estrogen agonist/antagonist indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause

• Dose: 1 tablet (60mg) once daily with food.

• Warnings: Endometrial cancer and cardiovascular disorders.

• Contraindications: Women with undiagnosed abnormal genital bleeding, known or suspected estrogen-dependent neoplasia, active DVT, pulmonary embolism (PE), or a history of these conditions, active arterial thromboembolic disease [for example, stroke and myocardial infarctions, or a history of these conditions

Vasomotor Symptoms (hot flashes)

Some risk factors • Smoking

• Reduced physical activity

• Obesity

• Socioeconomic factors

• Hormonal concentrations

• Ethnic factors

Duration

• Penn Ovarian Study – 4.9 to 10 years

• SWAN (Study of women across the nation (ranges from 4.5 to 11.8 years)

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Summary of Menopause VMSTreatment Guidelines

The North American Menopause Society Remedies such as soy, isoflavone supplements, black cohosh, vitamin E, and

omega-3 fatty acids are usually low risk but with efficacy similar to placebo. HRT is the most effective treatment for VMS. Compounded bioidentical hormones are

not recommended. SSRI’s, SNRI’s (paroxetine, escitalopram, venlafaxine, desvenlafaxine) are effective, gabapentin and clonidine reduce hot ashes but lack

FDA approval.

American College of Obstetricians and GynecologistsSystemic HRT is the most effective therapy. SSRIs, SNRIs, clonidine, and

gabapentin are alternatives Phytoestrogens, herbal supplements, and lifestyle modifications are not efficacious modalities .

Alternative Therapies

• Soy Isoflavones

• Black Cohosh

• Evening Primrose Oil

• Paced respirations

• Mind-body therapies

• Weight loss

• Exercise

• Acupuncture

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Non-hormonal Agents for VMS

Medication Notes

Clonidine risk of postural hypotension and

anticholinergic effects

Gabapentin & Pregablin several daily doses, CNS adverse

effects may be treatment limiting

SNRI’s: Venlafaxine

Desvenlafaxine

nausea & vomiting, risk of sexual

dysfunction, drug interactions

SSRI’s Citalopram, Escitalopram

Paroxetine

risk of sexual dysfunction, avoid

paroxetine with tamoxifen

Tissue Selective Estrogen Complex

• Duvaee®

bazedoxifene-conjugated equine estrogen 20mg/0.45mg

treatment of moderate to severe VMS and prevention of osteoporosis

• contraindicated in hepatic impairment

has not been studied in renal impairment

• contraindicated with tranexamic acid

caution with INH, PZA, rifampin & warfarin

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Hormonal ReplacementTherapies

Estrogen

• Oral tablets

• Transdermal

• Vaginal tablets, creams, and rings

Progestin

• Medroxyprogesterone acetate

Provera®, generics available – 5mg to 10mg(administer cyclically 12-14 days/month)

• Micronized progesterone*

Prometrium® -200mg (administer cyclically 12days/month)

Estrogen/Progestin

• Oral continuous

• Oral continuous-combined

• Oral intermittent-combined

• Transdermal continuous-combined

PREGNANCY AND LACTATION LABELING RULE (PLLR)

Understanding The FDA Update

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CURRENT LABELINGVS

NEW LABELING

Pregnancy Subsection

• Includes information for a pregnancy exposure registry for the medication if one is available.

• Pregnancy exposure registries collect and maintain data on the effects of the drug used by pregnant women.

• This section will include a risk summary, clinical considerations and data.

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Lactation(formerly nursing mother)

• Provides information about using the drug while breastfeeding.

• Amount of drug in the breast milk

• Potential effects on breast fed infant.

Reproductive Risk(female and male)

• Includes the information about the need for pregnancy testing.

• Contraception recommendations

• Information about infertility as it relates to the drug.

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New Drugs and Drug Updates

Women Specific

Fluconazole

• Association Between Use of Oral Fluconazole During Pregnancy and Risk of Spontaneous Abortion and Stillbirth, January 2016

• Safety Announcement April 26, 2016

• [8‐03‐2011] The U.S. Food and Drug Administration (FDA) is informing the public that chronic, high doses (400‐800 mg/day) of the antifungal drug Diflucan (fluconazole) may be associated with a rare and distinct set of birth defects in infants whose mothers were treated with the drug during the first trimester of pregnancy. This risk does not appear to be associated with a single, low dose of fluconazole 150 mg to treat vaginal yeast infection (candidiasis).

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• NNRTI (non-nucleoside reverse transcriptase inhibitor)

• Drug Interaction Update• Progestin-releasing implants

• Decrease contraceptive efficacy

• Includes levonorgestral & etonogestral

Efavirenz (Sustiva®)

Darunavir (Prezista®)

• The updated label now recommends that pregnant women receive darunavir 600 mg with ritonavir 100 mg, taken with food twice daily. 

• Darunavir 800 mg plus ritonavir 100 mg once daily should be considered only in certain pregnant patients already on a stable regimen of darunavir 800 mg with ritonavir 100 mg once daily before becoming pregnant who are virologically suppressed (HIV‐1 RNA < 50 copies per mL) and in whom a change to twice‐daily darunavir 600 mg/ritonavir 100 mg may compromise tolerability or compliance.

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• Indication: HSDD in premenopausal women

• MOA:  Serotonin 5HT1A agonist, Serotonin 5HT2A antagonist

• Adverse Effects: dizziness, difficulty falling asleep, nausea

• Drug Interactions: alcohol, strong CYP3A4 inhibitors

• Contraindications:  hepatic impairment

• REMS program: prescribers and pharmacist must be certified

flibanserin (Addyi®)

Tymlos®

• FDA Approves Tymlos (abaloparatide) for the Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture

• Dosage:  80mcg subq daily. (not more than 2 yeas in a lifetime)

• Warnings:  risk of osteosarcoma, 

• Adverse effects: , orthostatic hypotension, hypercalcemia, hypercalciuria and urolithiasis.

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New Contraceptive Devices

Kyleena®

• A levonorgestrel‐releasing intrauterine system, is a low‐dose progestin‐containing intrauterine system (IUS) indicated for the prevention of pregnancy for up to five years. Date of approval: September 16, 2016.

Caya®

• Diaphragm: became available in 2015

• Requires a prescription, but does not require fitting by a healthcare professional.

Newly Approved Chemo-Therapy Drugs

• Zejula® (niraparib) Capsules, approved March 27, 2017. (PARP) inhibitor for the maintenance treatment of patients with recurrent platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer.

• Kisqali ( ribociclib) tablets, approved March 13, 2017, ( a selective cyclin-kinase inhibitor) indicated for the combination treatment of postmenopausal women with HR+/HER2-metastatic breast cancer.

• Rubraca® (rucaparib) tablets, approved December 19, 2016. (PARP) inhibitor for treatment of advanced mutant BRCA ovarian cancer.

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Health Screenings & Vaccines

Women Specific

Routine Health Screenings for Women

• Pap smear

• Mammograms (BRCA 1 & BRCA 2 genetic testing)

• Colon Cancer Screening (colonoscopy)

• Chlamydial infection

• Diabetes

• Hepatitis C

• HIV

• Osteoporosis

• Heart disease

• Alcohol misuse screening and behavioral counseling

• depression

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Pregnancy Specific Health Screening

• Bacteriuria

• Hepatitis B & Hepatitis C

• HIV Infection

• Syphilis Infection

• Tobacco Use

• Gestational diabetes

• Chlamydial Infection

• Gonorrhea Infection

• Rh(D) incompatibility

• Iron Deficiency Anemia

Vaccines

• HPV – Gardisil® 9, Cevarix®

• Influenza

• Pneumococcal

• Varicella Zoster – women age 60yrs or >

• Td

• Tdap

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Gardasil 9®

GARDASIL®9 (Human Papillomavirus 9-valent Vaccine, Recombinant) helps

protect girls and women ages 9 to 26 against cervical, vaginal, vulvar, and anal

cancers and genital warts caused by 9 types of HPV. GARDASIL 9 helps protect

boys and men ages 9 to 26 against anal cancer and genital warts caused by

those same HPV types.

Updated Dosing Recommendations

Adolescents younger than age 15 need only two doses of the HPV vaccine,

given at least 6 months apart.

References

Centers for Disease Control and Prevention (CDC). Update to CDC’s U.S. medical eligibility criteria for contraceptive use, 2010: revised recommendations for the use of contraceptive methods during the postpartum period. MMWR 2011;60(RR‐26):878‐83. 

Sally Rathe, PharmD BCPS, Updates In Contraception In: Dong BJ, Ellio DP, eds. Ambulatory Care Self‐Assessment Program, 2015 Book 2. Women’s and Men’s Care. Lenexa, KS: American College of Clinical Pharmacy, 2015:pages 5– 21. 

By Erin C. Raney, Pharm.D., BCPS, BC‐ADM, Menopausal Symptoms. In: Murphy JE, Lee MW, eds. Pharmacotherapy Self‐Assessment Program, 2016 Book 3. Women’s and Men’s Health. Lenexa, KS: American College of Clinical Pharmacy, 2016:pages 55 ‐69. 

Stuenkel CA, Davis SR, Gompel A, Lumsden MA, Murad MH, Pinkerton JV, Santen RJ. Treatment of symptoms of the menopause: an Endocrine Society clinical practice guideline. J ClinEndocrinol Metab. 2015 Nov;100(11):3975‐4011. [368 references] pubmed

Festin MPR, Peregoudov A, Seuc A, Kiarie J, Temmerman M. Effect of BMI and body weight on pregnancy rates with LNG as emergency contraception: analysis of four WHO HRP studies. Contraception. 2017;95(1):50-54. doi:10.1016/j.contraception.2016.08.001.

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REFERENCES

DANA G. CARROLL, PHARM.D., B.C.P.S., University of Oklahoma–Tulsa College of Medicine,

Tulsa, Oklahoma: Nonhormonal Therapies for Hot Flahes in Menopause; Am Fam

Physician. 2006 Feb 1;73(3):457-464.

PL Detail-Doucment, Improved Pregnancy and Lactation Drug Information. Pharmacist’s Letter/

Prescriber’s Letter. August 2015.

Raul Raz, Urinary Tract Infection in Postmenopausal Women. Korean Journal of Urology 2011;

52(12): 801-808.

Centers for Disease Control and Prevention. U.S. selected pratice recommendations for

Contraceptive use, 2013. MMWR 2013;62 (RR-5):1-59.

Centers for Disease Control and Prevention (CDC). U.S. medical eligibility criteria for contraceptive use, 2010. 

MMWR 2010;59(R R‐4):1‐81. 

U.S.Preventative Services Task Force; www.USPreventiveServicesTaskForce.org.

Cynthia A. Stuenkel, Susan R. Davis, Anne Gompel, Mary Ann Lumsden, M. Hassan Murad, JoAnn V. Pinkerton, Richard J. Santen; Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015; 100 (11): 3975-4011. doi: 10.1210/jc.2015-2236

Mølgaard-Nielsen D, Svanström H, Melbye M, Hviid A, Pasternak B. Association Between Use of Oral Fluconazole During Pregnancy and Risk of Spontaneous Abortion and Stillbirth. JAMA. 2016;315(1):58-67. doi:10.1001/jama.2015.17844

Avis NE, Crawford SL, Greendale G, Bromberger JT, Everson-Rose SA, Gold EB, Hess R, Joffe H, Kravitz HM, Tepper PG, Thurston RC, for the Study of Women’s Health Across the Nation (SWAN). Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition. JAMA Intern Med. 2015;175(4):531-539. doi:10.1001/jamainternmed.2014.8063

Whiteman MK1, Staropoli, CA, Langenberg PW, McCarter RJ, Kjerulff KH, Flaws Smoking, body mass and hotflashes in midlife women. Obstet Gynecol. 2003 Feb;101(2):264-72.

Gallicchio L1, Visvanathan K, Miller SR, Babus J, Lewis LM, Zacur H, Flaws JA. Body mass, estrogen levels and

hot flashes in midlife women. Am J Obstet Gynecol. 2005 Oct;193(4):1353-60.

Sun Z, Hao, Y, Zhang,M Efficary and safety of desvenlafaxine treatment for hot falashes associated with menopause;

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Epub 2013 Mar 20.

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