HormonalContraceptives:wheredowebegin?

StephanieSchauner,PharmDClinicalAssociateProfessorUMKCSchoolofPharmacyschauners@umkc.edu

ClinicalPharmacistGoppert-TrinityFamilyCareClinic

KansasCity,MO 1

LearningObjectives

Describethemechanismofaction,formulations,doses,andusesofhormonalcontraceptives.Comparethebenefitsvs.risksoforalcontraceptives.Developappropriatecounselingpointstosharewithpatientsregardingoralcontraceptives.Identifyusefulresourcesavailableforhormonaluseofcontraceptives.

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Disclosure:

• StephanieSchauner doesnothaveanypotentialconflictsofinterestinrelationtothispresentation.

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UnintendedPregnancyintheUS

Finer,Zolna.Contraception.2011.

Unintended49%

Unintendedbirths

Electiveabortions

Fetallosses

Intended:51%

51% 23%

21%5%

1YEAR:6.7MILLION PREGNANCIES

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5

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7Source:Guttmacher Institute

HealthyPeople2020FamilyPlanningFP-1-16

• IncreasethenumberofintendedpregnanciesFP-1– 51%56%

• Increasethepercentageofwomenaged15to44yearsthatadoptorcontinueuseofthemosteffectiveormoderatelyeffectivemethodsofcontraceptionFP-16

– 63.1%69.3%

healthypeople.gov/2020/topics-objectives/topic/family-planning/objectives 8

PharmacistsasPrescribers

• Severalstateswithlegislationpending–Missouri

HowdoIstayuptodatewithmy

knowledgeonthistopic?

Whataretheprocessesand

procedurerequiredforimplementingtheseservices?

DoIknowenoughabout

contraceptivestosafelyprescribe?

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Self-Assessment

• Understandingofthemenstrualcycle

• Knowledgeofavailablecontraceptiveproducts

• Comfortwithabilitytosafelyandeffectivelyprescribeoralcontraceptives

1 2 3 4 5

1 2 3 4 5

1 2 3 4 5

1=Least5=Most10

MenstrualCycle

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ClassificationsofContraception• Intercourse-relatedmethods

– Physicalbarriers:condoms,diaphragm,cervicalcap,periodicabstinence• Hormonalmethods

– Combinedcontraceptives(estrogen+progestin)• Oral• Patch• Ring

– Progestinonly• Oral• Injection• Intrauterinedevice

• Non-hormonal• Copperintrauterinedevice

• Permanentmethods– Femaletuballigation– Malevasectomy

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13Source:USDepartmentofHealthand

HumanServicesCentersforDiseaseControlandPrevention

14Source:GuttmacherInstitute

COMBINEDHORMONALCONTRACEPTIVES(CHC)Oral

Describethemechanismofaction,formulations,doses,andusesof hormonalcontraceptives

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MechanismofAction

• PreventthedevelopmentofthedominantfolliclebysuppressingFSHsecretion

• PreventovulationbysuppressingLHsecretion

• Thickencervicalmucus• Causealterationsintheendometriallining

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EstrogenComponent

• Ethinyl estradiol(EE)–Mostcommonform

• Mestranol– BiologicallyinactiveprodrugofEE– Bioequivalentto35µgofethinylestradiol

• Estradiolvalerate– Convertedtothenaturallyoccurringestrogen,estradiol

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ProgestinComponent

Generation NameFirst(Estrane Family) Norethindrone

Norethindrone acetateEthynodiol diacetate

Second(Gonane Family) LevonorgestrelNorgestrel

Third(Gonane Family) DesogestrelNorgestimate

Fourth (Other) DrospirenoneDienogest

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Progestin GenerationActivityProfile

ProgestinClass EstrogenActivity

ProgestinActivity

AndrogenActivity

Comments

FirstGeneration ++++++

++++++++

+++++

Associatedwithmorebreakthroughbleeding

SecondGeneration -

-+++++++

+++++++

Morepotentthan1stgeneration– associatedwithmoreandrogenicsideeffects

ThirdGeneration -

+/-++

++++++++

Fewerandrogenicandmetaboliceffectsversus2ndgeneration– higherriskofVTE

Fourth/OtherGeneration

--

+/-+/-

--

Antiandrogeneffects,higher riskofVTE 19

Formulations• Monophasic– ratioofestrogen:progestin isfixedthroughoutthecycle

• Multiphasic– Biphasic– Triphasic– Four-phasic

• Extendedcycle– Delaysmenstruation

• Continuouscycle– Eliminatesmenstruation

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DosingofCHCs

• Estrogen– 20mcgisagoodstartingdose– 30mcgiftakingCYP450inducers

• Progestins withlowandrogenicactivity*<1mgnorethindrone (1st generation)≤0.1mgoflevonorgestrel (2nd generation)≤0.25mgofnorgestimate (3rd generation)

21*generalruleofthumb

CHCAdverseEffects

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PROGESTIN-ONLYCONTRACEPTIVESOral

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ProgestinONLY

• Advantages– Maybeusedinlactatingwomen– Maybeusedinwomenwithestrogencontraindications

• Disadvantages– Increasedamenorrheaorfrequentspotting– Mustbetakenatsametimeeveryday

• PatientEducation– Misseddose(see“MissedDoses”slides)– Irregularmenses

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Howdothedifferentestrogencomponentsavailableincombinedhormonal

contraceptivescompare?

A. Estradiolvalerate isthemostcommonformoccurringincommerciallyavailableoralcontraceptives

B. Estradiolvalerate isthemosteffectiveformC. Ethinyl estrodial isconvertedtoanaturally

occurringestrogenD. Mestranolisthebiologicallyinactive

prodrugofethinyl estradiol

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Whichofthefollowingistruewhencomparingmonophasichormonalcontraceptivestomultiphasichormonalcontraceptives?

A. MonophasicarehardertouseB. Monophasicareafixedratioofestrogento

progestinthroughoutthecycleC. Multiphasichavemorestudiestosupport

theiruseD. Multiphasicareassociatedwithlessside

effects

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COMBINEDHORMONALCONTRACEPTIVES(CHC)Oral

Objective2Comparethebenefitsvs.risksoforalcontraceptives.

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Choosingthe“Right”Contraceptive

• Mustconsiderthepatient’s:– Medicalhistory

• Doesthepatienthaveacontraindicationtoestrogen?– Medicationuse

• Whatothermedicationsdoesthepatienttake?• Arethereanysignificantdruginteractionsmayimpactthecontraceptiveofchoice?

– Preferences• Doesthepatient“know”whattheyprefertouse?Why?• Isthepatientpreference:safe,realistic,affordable,etc

– Adherence• Canthepatientmaintaintheregimen?

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CDCMedicalEligibilityCriteria(MEC)

Categoriesof medicaleligibilitycriteriaforcontraceptiveuse

1 =Aconditionforwhichthereisnorestrictionfortheuseofthecontraceptivemethod

2=Acondition forwhichtheadvantagesofusingthemethodgenerallyoutweighthetheoreticalorprovenrisks

3 =Aconditionforwhichthetheoreticalorprovenrisksusuallyoutweightheadvantagesofusingthemethod

4 =Aconditionthatrepresentsanunacceptablehealthriskifthecontraceptivemethodisused

29CentersforDiseaseControlandPrevention2016

UnacceptablehealthriskMECcat4

• BreastfeedingorNon-breastfeeding<21dayspostpartum

• History/riskoforcurrentdeepveinthrombosis/pulmonaryembolism(notonanticoagulanttherapy);thrombogenic mutations

• Cerebrovascular orcoronaryarterydisease

• Migraineswithaura,anyage• Majorsurgerywithprolonged

immobilization• Currentandhistoryofischemic

heartdisease• Historyofcerebrovascularaccident• Complicatedvalvular heartdisease

• Moderatelyorsignificantlyimpairedcardiacfunction;normalormildlyimpairedcardiacfunction<6months

• Systolicbloodpressure≥160mmHgordiastolic≥100mmHg

• Complicatedsolidorgantransplantation

• Currentbreastcancer• Severe(decompensated)cirrohsis• Benignhepatocellularadenomaor

malignantlivertumor• Smoking≥15cigarettes/day&≥ 35

yearsofage• SLE;positiveorunknown

antiphospholipidantibodies

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ExamplefromCDCMEC

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ThrombosisRisk

32FDADrugSafetyInformation

VTERiskandContraceptive

Patch3rd &4th generationCHCsVaginalring

Progestin-only(IUD,oral,implant)

FirstgenerationCHCsSecondgenerationCHCs

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GreaterRisk

LowerRisk

DrugInteractions

• Interferenceofabsorption• Liverenzymeinduction– anti-epilepticdrugs(AEDs)

• Usealternativecontraception• Reportedantibioticcases:– Tetracycline– Minocycline– Erthromycin– Penicillins– Cephalosporins

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DrugInteractionsDrugsinterferingwithOCEfficacy OCinterferingwithEfficacy ofOtherDrugs

↑ ↓ ↑ ↓

AscorbicacidAPAP-scheduledAtorvastatinRosuvastatin

NNRTIsPIs

AnticonvulsantsAntibioticsRifampin

TheophyllineSt. John’sWort

NNRTI-nevirapinePIs

SulfonamidesGriseofulvinBosentanTacrolimusModafinil

AlprazolamChlordiazepoxide

DiazepamTheophyllineCaffeine

CyclosporineCorticosteroids

AlcoholB-Blockers

TCAsRopiniroleZolmitriptan

TemazepamWarfarin

Thyroid agentsHypoglycemicsMethyldopaMetforminAmprenavir

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AdditionalBenefitsofCHCs

• Regulatemenstrualcycle• Decreaseriskofanemia• Decreaseincidenceofovariancysts• Decreaseriskofovariananduterinecancers• Decreaseacne• Decreasepelvicinflammatoryrisk

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PatientEducationforOralCHCUse

• Compliance• Misseddoses(see“MissedDosesslides)• NoprotectionagainstSTIs/HIV– Condomuse

• Signs/symptomsofVTE– ACHES• Abdominalpain,chestpain,headache,eyeproblems,severelegpain

• Druginteractions37

COMBINEDHORMONALCONTRACEPTIVES(CHC)Oral

Objective3 Developappropriatecounselingpoints toshare

withpatientsregardingoral contraceptives.38

InitiatingOralContraceptives

• QuickStart– Contraceptivemethodstartedimmediately– Backupmethodx7days

• Day1Start– Contraceptivemethodstartedonthefirstdayofmenses

• SundayStart– FirstSundayafternextmensesbegins– Backupmethodx7days

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MissedDoses– CHC(Oral)

40PharmacistsLetter.June2014

MissedDoses– ProgestinOnly(Oral)Late/Missedpill>3hourssinceitshouldhave beentaken

• Takeonepillassoonaspossible.• Takethe remainingpillsattheusual

time,evenifitmeanstakingtwopillsinthesameday.

• Useback-upcontraception(condoms)oravoidintercourseuntilpillshavebeentakenontimefortwoconsecutivedays.

• Consideremergencycontraceptionifunprotectedintercoursehasoccurred.

41PharmacistsLetter.June2014

Monitoring

• 3-6monthsafterinitiation• Followupwithaprimarycareprovider• Wellwomanexam• Papanicolaou andpelvicexam• Breastexams– selfandclinical• Appropriatelabwork

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AccordingtotheCDCMECdocument,aconditionthatrepresentsanunacceptable

healthriskifthecontraceptivemethodisused,wouldbenotedwithanumber4.

A. TrueB. False

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LYisa22y.o.femalewhorecentlystartedanoralCHCcontaining30mcgofEEand0.15mglevonorgestrel.Sheisonherthirdpackof

pillsandstatesshefeelsreallytired,iscrankyallthetime,andshehasgained3lbs.Shewantstokeeptakingapill,butisgoingtostopthisoneduetotheproblemssheishaving.Whatcourseofactionwould

yourecommend?

A. Stayonthesamepill.Theseadverseeffectswillgoaway.

B. SwitchtoaCHCwith3mgofdrospirenone.C. SwitchtoaCHCwith20mcgofEE.D. SwitchtoaCHCwith0.35mgofnorgestimate.

COMBINEDHORMONALCONTRACEPTIVES(CHC)Oral

Objective4 Identifyusefulresourcesavailablefor

hormonalcontraceptives. 45

UsefulResources• CDCMedicalEligibilityCriteriaforContraceptiveUse

• http://www.cdc.gov/mmwr/volumes/65/rr/pdfs/rr6503.pdf• WorldHealthOrganization– http://www.who.int/topics/family_planning/en/– MedicalEligibilityCriteriaforContraceptiveUse

• http://www.who.int/reproductivehealth/publications/family_planning/9789241563888/en

• PharmacistsLetter• PlannedParenthood– http://www.plannedparenthood.com

• AssociationofReproductiveHealthProfessionals(ARHP)– http://www.arhp.org

• http://www.womenshealth.gov46

References1. DiPiro,JT.Pharmacotherapy,APathophysiologic Approach.McGrawHill.2014.2. Guitierrez,K.(2008)inPrimaryPharmacotherapeutics:Clinical ReasoningCare(2nd ed)Saunders.St.Louis,MO.

Chapter58:HormonalContraceptivesandRelatedDrugs.3. AssociationofReproductiveHealthProfessionals.Web.4Feb2013.http://www.arhp.org4. Women’sHealth.Web.4Feb2013.http://www.womenshealth.gov5. Lexi-CompOnline.http://www.lexi.com6. ManagingContraceptivePillPatientsbyRichardP.Dickey13th edition7. WorldHealthOrganization.Web.4Feb2013.http://www.who.int/topics/contraception/en/8. CentersforDiseaseControlandPrevention.MedicalEligibilityCriteriaforContraceptiveUse.

http://www.cdc.gov/mmwr/volumes/65/rr/pdfs/rr6503.pdf9. Koda-Kimble,M,etal.AppliedTherapeutics:TheClinicalUseofDrugs.EighthEdition.LippincottWilliams&Wilkins.

2005.Chapter45:Contraception.10. PlannedParenthood.Web.4Feb2013.http://www.plannedparenthood.org/health-topics/morning-after-

pill/emergency-contraception-pill-chart-19304.htm11. UnintendedPregnancyintheUnitedStates.Guttmacher Institute.March201612. ContraceptiveUseintheUnitedStates.Guttmacher Institute.October2015.13. TheNationalCampaigntoPreventTeenandUnplannedPregnancy.Briefly:UnplannedPregnancyAmong20-

Somethings:TheFullStory.May2008.Availableathttp://www.thenationalcampaign.org/resources/pdf/briefly-unplanned-pregnancy-among-20somethings-the-full-story.pdf.AccessedMarch10,2011.

14. Lesnewski,Retal.“PreventingGapsWhenSwitchingContraceptives.”AmericanFamilyPhysician83(2011):567-570.http:www.reproductiveaccess.org

15. MissedDosesofHormonalContraception.PharmacistLetter.June2014.16. HormonalContraception.PharmacistLetter.March2013.17. FamilyPlanning.HealthyPeople2020.OfficeofDiseasePreventionandHealthPromotion.Web.14July2016.

https://www.healthypeople.gov/2020/topics-objectives/topic/family-planning/objectives

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