Docstoc

Educational Objectives

Document Sample
Educational Objectives Powered By Docstoc
					Pharmacology Update for                                                                                                       March 20, 2009
                                                                                                                                   Webinar
Women’s Health Care Staff—Part I




                                          Women’
                  Pharmacology Update for Women’s                                        Disclosure
                      Health Care Staff: Part I
                           Glen E. Farr, Pharm.D.                     I have no real or perceived vested interests
                                                                       that relate to this presentation nor do I have
                           Professor of Clinical Pharmacy
                                                                       any relationships with pharmaceutical
                     University of Tennessee College of Pharmacy
                                                                       companies, biomedical device
                             Suite 213, 600 Henley Street
                                                                       manufacturers, and/or other corporations
                                 Knoxville, TN 37996                   whose products or services are related to
                                     865- 974-
                                     865-974-6605                      pertinent therapeutic areas.
                                    gfarr@utk.edu
                            Presented as a Webinar
                                March 20, 2009




                                                                            Pharmacology Update for
                 Educational Objectives                                     Women’s Health Care Staff:
                Differentiate between FDA                                        Disclosure
                 regulations and DSHEA
                 regulations of medications and                        I have no real or perceived vested interests that
                 supplements.
                                                                       relate to this presentation nor do I have any
                Compare and contrast various
                 pharmacological agents and                            relationships with pharmaceutical companies,
                 dosage forms used for                                 biomedical device manufactures, and/or other
                 contraception.                                        corporations whose products or services are
                List the four most common drug                        related to pertinent therapeutic areas.
                 interactions with hormonal
                 contraceptives.
                                                                       Glen E. Farr, Pharm.D.




                 Drug Development and Regulation                                  New Drug Approvals
                                                                      In 2006, the FDA approved 22 new molecular
                                                                       entities.
                                                                      For 2007, the number was 18 new molecular
                                                                       entities, the lowest number in several years.
                                                                           For comparison, in 1996 there were 62 new drugs
                                                                            approved— that’               drug-
                                                                            approved—that’s more than a drug-a-week!




Glen E. Farr, Pharm.D.
Professor of Clinical Pharmacy
University of Tennessee                                                                                                                   1
Pharmacology Update for                                                                                                                                                             March 20, 2009
                                                                                                                                                                                         Webinar
Women’s Health Care Staff—Part I




                                                                                                     FDA: Do You Want
                        2008 New Drug Approvals
                                                                                                    Markers Or Outcomes?
                For 2008, the FDA approved 24 "first-of-a-
                                                 "first- of-                                        Vytorin® Avandia®
                                                                                     Concern over Vytorin®, Avandia® and the ACCORD trial have
                                                                                     prompted FDA to question whether they should approve drugs
                 kind" drugs, which represents more products                         based on biological measures, like cholesterol and blood sugar,
                 than were approved in any of the previous three                     without evidence they improve more meaningful measures like
                                                                                     survival.
                 years.                                                             The FDA posture has been shifting to an outcome based
                    However, industry observers suggest that the year               evaluation. For example, Drug "X" reduces blood pressure but
                                                                                     will it prevent stroke and heart attack? (A shotgun blast to the
                     will be remembered for delays in the FDA approval               chest will also lower blood pressure; effective but no positive
                     process, with deadlines missed on 32 out of 159                 outcome).
                     applications through October 31.                               If FDA makes the shift to outcome based approval, drugs will
                                                                                     take longer to approve and the cost will increase.

                                                                                                                              Philly.com, March 4, 2008




                  FDA Requirement for Reporting
                                                                                                   Are U. S. Drugs Safe?
                      Adverse Drug Effects
                Originally effective January 1,                                    Only 27% of the public
                 2009, the FDA was to require a toll                                 feels "very confident"
                      (1-
                 free (1-800) telephone number for                                   that prescription drugs
                 reporting adverse events on the
                 labeling of new and refill
                                                                                     sold in the U.S. are safe.
                 prescription and OTC products                                                     FDA’
                                                                                     Is this due to FDA’s
                 dispensed in an outpatient setting.                                 taking steps to continue
                Note: In November 2008 this                                         alerting consumers about
                 requirement was delayed until                                       drug-
                                                                                     drug-safety issues?
                 July 1, 2009.
                                       pharmacist.com FocusXtra, 9/22/2008                                            Wall Street Journal, December 9, 2008




                       Generics ~65% of all Rxs                                            Definition of a Generic Drug
                Generic drugs accounted for approximately 65%                         •   A drug product that is the same as
                 of all prescriptions in 2007—up from 63% in
                                         2007—                                             brand drug in:
                 2006.                                                                       • Active ingredient
                    In contrast, generics accounted for 20% of all                          • Strength
                     prescriptions in 1984, the year the FDA                                 • Dosage form
                     implemented a law aimed at making it easier to get
                                                                                             • Route of administration
                     generic drugs on the market (ANDA).
                                                                                             • Quality
                However, brand name drugs made up about
                 80% of dollars spent on prescription drugs.                                 • Therapeutic effect
                                                                             Food and Drug Administration Web site. Productivity Documentation in the Division of Bioequivalence.
                                                                             Available at: http://www.fda.gov/cder/mapp/5210-3.pdf. Accessed February 16, 2006.
                                       IMS Health Inc., February 12, 2008
                                                                             Food and Drug Administration Web site. Glossary of Terms. Available at:
                                                                             http://www.fda.gov/cder/drugsatfda/glossary.htm. Accessed February 16, 2006.




Glen E. Farr, Pharm.D.
Professor of Clinical Pharmacy
University of Tennessee                                                                                                                                                                         2
Pharmacology Update for                                                                                                                                                                           March 20, 2009
                                                                                                                                                                                                       Webinar
Women’s Health Care Staff—Part I



                                                                                                                                      Comparison of PK Profiles
                                 Pharmacokinetic Profile                                                                             to Determine Bioequivalence
                                  of a Reference Drug
                                                                                                                                                                            Test Formulation (Generic)
                                                                             Reference Formulation                                                                          Reference Formulation
                 Concentration




                                                                                                                            Concentration
                                                                                                                                            The AUC and Cmax of the generic must
                                                                                                                                            meet 80% - 125% of the brand in order
                                         AUC                                                                                                         to be deemed BE


                                                                     Time
             Food and Drug Administration Web site. Approved Drug Products with Therapeutic Equivalence Evaluations.                                                    Time
             Accessed February 16, 2006.
                                                                                                                       Food and Drug Administration Web site.




                                  FDA Requirements for                                                                                      Misconceptions Concerning
                                    Bioequivalence                                                                                              Generic Variability
                                 Reference                                                                                                                      80%-
                                                                                                                             There are misconceptions about the “80%-125%
                                   Drug                                          • Despite their variance,
                                                                                   Products A and B are
                                                                                                                             rule.”
                                                                                                                             rule.”
                                 Product A                                         considered bioequivalent to                    Some take this to mean that the amount of drug in
                                                                                   the reference drug                              the PRODUCT can vary by 20%.
                                 Product B                                       • Product C is not                               Others think it refers to the amount of drug
                                                                                   bioequivalent to the
                                                                                   reference drug
                                                                                                                                   ABSORBED, or the average BLOOD levels.
                                 Product C
                                                                                                                            These assumptions are wrong.
                                               80%        100%            125%


                                 Food and Drug Administration Web site.                                                                                         Pharmacist’s Letter, July 2008




                                 Misconceptions Concerning                                                                                  Misconceptions Concerning
                                     Generic Variability                                                                                        Generic Variability
                 This originates from a lack of understanding of                                                           The important point is that these results can't
                  the statistical tests required to show                                                                     vary much for the confidence interval to fit
                  bioequivalence.                                                                                            within the accepted range.
                 A generic drug must show that the 90%                                                                     In the majority of cases, generic equivalents are
                  CONFIDENCE INTERVAL of the mean rate
                                                                                                                             within 4% of the brand name and produce the
                  and extent of absorption is within 80% to 125%
                  of the brand.                                                                                              same therapeutic results.
                 The confidence interval is a statistical test to
                  indicate how much results vary from the mean.
                                                        Pharmacist’s Letter, July 2008                                                                          Pharmacist’s Letter, July 2008




Glen E. Farr, Pharm.D.
Professor of Clinical Pharmacy
University of Tennessee                                                                                                                                                                                       3
Pharmacology Update for                                                                                                                          March 20, 2009
                                                                                                                                                      Webinar
Women’s Health Care Staff—Part I




                         Cardiovascular Generic                                              Cardiovascular Generic
                           Drugs Equivalent                                                    Drugs Equivalent
                Data from a study published in the December 3,                   Results from 47 studies showed that in
                 2008 issue of JAMA concluded that evidence                                            brand-
                                                                                   randomized trials, brand-name ß-blockers,
                 "does not support the notion that brand-name
                                                    brand-                         antiplatelet agents, statins, ACE inhibitors, alpha
                 drugs used in cardiovascular disease are superior                 blockers, antiarrhythmic agents and warfarin
                                                                                   showed 100% clinical equivalence to the generic
                 to generic drugs," despite numerous editorials
                                                                                   versions.
                 that "counsel against the interchangeability of
                                                                                  In addition, the clinical equivalence between
                 generic drugs."
                                                                                   brand-
                                                                                   brand-name and generic treatments was 91% for
                                                                                   diuretics and 71% for calcium channel blockers.
                                        JAMA. 2008;300(21):2514-2526                                        JAMA. 2008;300(21):2514-2526




                                                                                Dietary Supplement Health &
                    Recent Developments with                                   Education Act of 1994 (DSHEA)
                 Dietary Supplements and Herbals
                                                                                In              90’
                                                                                       the early 90’s, many consumers did
                                                                                   not want the FDA, or any government
                                                                                   agency, interfering with their ability to
                                                                                           natural”
                                                                                   use a “natural” substance.
                                                                                     The Dietary Supplement Health &
                                                                                      Education Act of 1994 (DSHEA)
                                                                                                             DSHEA)
                                                                                       amended the Food, Drug and Cosmetic
                                                                                       Act to address these agents.




                                                                                            Bio-
                                                                                   FDA Says Bio-identical Hormones
                     DSHEA Requirements
                                                                                        Claims Unsupported
              DSHEA       promulgated that botanical                             On January 9, 2008, the FDA warned 7 pharmacies
                 products cannot be removed from the                                       "bio-
                                                                                   selling "bio-identical" hormones over the Internet that
                 market if they:                                                   they were breaking the law with false and misleading
                  (1) make no health claims                                       claims about the benefits for menopausal women.
                                                                                      The FDA sent letters ordering the pharmacies to stop
                  (2) are not proven unsafe                                           claiming their hormones were better than approved
                  (3) prominently display the disclaimer:                             menopause therapies and could prevent and treat serious
                     “This statement has not been evaluated by the Food and           conditions such as Alzheimer's, strokes and cancer.
                      Drug Administration. This product is not intended to        FDA said there was no reliable scientific evidence to
                                                            disease.”
                      diagnose, treat, cure, or prevent any disease.”              support the assertions.
                                                                                                             Reuters, January 9, 2008




Glen E. Farr, Pharm.D.
Professor of Clinical Pharmacy
University of Tennessee                                                                                                                                      4
Pharmacology Update for                                                                                                                             March 20, 2009
                                                                                                                                                         Webinar
Women’s Health Care Staff—Part I




                      Mortality With Antioxidants                                                    Folic Acid Does Not
                                                                                                      Reduce CVD Risk
                The February 28, 2007 JAMA examined 68
                 randomized trials involving 232,606 adults in                          Folic acid supplementation has not
                 385 publications comparing beta carotene,                               been shown to reduce risk of
                 vitamin A, vitamin C, and vitamin E showed                                                          all-
                                                                                         cardiovascular diseases or all-cause
                 mortality increases as follows:                                         mortality among participants with
                  Vitamin A: 16%                                                        prior history of vascular disease,
                  Beta carotene: 7%                                                                     meta-
                                                                                         according to a meta-analysis in the
                  Vitamin E: 4%
                                                                                                                        JAMA.
                                                                                         December 13, 2006 issue of JAMA.
                                           JAMA. 2007;297:842-857                                                  JAMA. 2006;296:2720-2726




                          Folic Acid, Calcium and                                              Alternatives to Rxs for PMS:
                          Vitamin D in Pregnancy                                                     Calcium is Best
                                                                                      Calcium   has the best evidence, for both
                  NIH  supports the use of
                                                                                         treatment and possibly prevention of PMS.
                  folic acid in pregnant
                                                                                          Recommend    1000 to 1200 mg/day of
                  women to prevent fetal
                                                                                           elemental calcium to improve mood, bloating,
                  neural tube defects and                                                  food cravings, and pain.
                  calcium and vitamin D to                                                Tell women it takes a few months to see an
                  prevent osteoporosis.                                                    improvement.
                      Annals of Internal Medicine 2006;145:372-85                                            Prescriber’s Letter, August 2005




                  American Heart Association (AHA)                                                     Role of Vitamin D
                                   Omega-
                      Recommends Omega-3’s
                                                                                        Vitamin D is necessary for optimal absorption of
                                                       omega-
                     The AHA has endorsed the use of omega-3 fatty                       calcium. In addition, recent research suggests that it
                     acids for secondary prevention of cardiovascular                    may play a role in diabetes, MS, TB, colon cancer and
                                                                                         even the flu.
                     (CV) events in people with documented coronary
                                                                                        We only have 3 ways of boosting our blood levels of
                     artery disease (CAD).                                               vitamin D:
                                                               the AHA has
                       This recommendation is the first time that                          increasing sun exposure
                       recommended a nutritional supplement for CAD                                   vitamin-
                                                                                             intake of vitamin-D rich foods
                       prevention.                                                          taking vitamin D supplements
                    The recommendation calls for approximately 1 g/d                                African-
                                                                                         Elderly and African-Americans (the darker the skin, the
                     of a mixture DHA and EPA.                                           less production of vitamin D from sunlight) are
                                                                                         especially vulnerable.
                                             Mayo Clin Proc. March 2008;83:324-332                                Prescriber’s Letter, March 2008




Glen E. Farr, Pharm.D.
Professor of Clinical Pharmacy
University of Tennessee                                                                                                                                         5
Pharmacology Update for                                                                                                                   March 20, 2009
                                                                                                                                               Webinar
Women’s Health Care Staff—Part I




                              Dose of Vitamin D                                          American Academy of Pediatrics
                                                                                        Updated Guidelines for Vitamin D
                Recommend 400 to 800 IU/day of vitamin D
                                                                                       AAP has issued updated guidelines for vitamin
                 for adults under age 50, and 800 to 1000 IU for
                                                                                        D intake in infants, children, and teens to
                 age 50 and up, to prevent deficiency.                                  prevent rickets and vitamin D deficiency.
                Explain that 400 IU/day of vitamin D is not                           The updated guidelines replace the 2003
                 enough to decrease fractures in older adults, and                      recommended 200 IU per day.
                 doses up to 2000 IU/day are safe.                                     The new recommendations call for a daily intake
                    Recommend at least 800 IU per day for the elderly                  of 400 IU per day of vitamin D for all infants,
                                                                                        children, and adolescents beginning in the first
                                                                                        few days of life.
                                            Prescriber’s Letter, March 2008                             Pediatrics, November 5, 2008




                      Glucosamine/Chondroitin                                       Minimal Health Benefits from Garlic
                      Arthritis Intervention Trial:
                     Does Not Slow Cartilage Loss                                    Garlic,   highly touted as a
                  2-
                 A 2-year study of how well glucosamine and                             natural way to reduce
                 chondroitin slow cartilage loss in osteoarthritis                      cholesterol levels, does
                 did not slow disease progression over placebo.                         not do so, Stanford
                    The study was conducted at 9 sites.                                University researchers
                                                                                        reported in February 26,
                                                                                        2007 Archives of Internal
                                                                                        Medicine.
                                                                                        Medicine.
                              Arthritis & Rheumatism, Vol. 58, October 2008
                                                                                                      Arch Intern Med. 2007;167:346-353
                              The Journal of the American College of Rheumatology




             Probiotic Align® for Digestive Upset
                       Align®                                                           Recent Developments in
                Align®
                 Align®, which contains                                                   the Pharmacological
                 Bifantis (bifidobacterium
                 infantis) is being marketed
                                                                                        Aspects of Contraception
                 OTC to “help manage a
                 full range of episodic
                            upsets.”
                 digestive upsets.”




Glen E. Farr, Pharm.D.
Professor of Clinical Pharmacy
University of Tennessee                                                                                                                               6
Pharmacology Update for                                                                                                                                   March 20, 2009
                                                                                                                                                               Webinar
Women’s Health Care Staff—Part I




                                                                                   Approximate Dosage Equivalents of
                                     Estrogens
                                                                                   Estradiol and Conjugated Estrogens
                Estrogen refers both to natural estrogen hormones in                                        (Premarin®
                                                                                       Conjugated Estrogens (Premarin®): 0.625 mg
                 the body and estrogen products used in medications.
                                                                                      17-
                                                                                       17-β estradiol: 1.0 mg
                 The main forms of endogenous estrogen are:
                    Estrone, a weaker estrogen produced both in the ovaries and
                     Estrone,                                                         Ethinyl estradiol: 0.005 mg or 5 µg
                     in fat tissue from other hormones, and the main estrogen
                     after menopause (E1)
                    Estradiol,
                     Estradiol, the main estrogen made by the ovaries before
                                                    17-
                     menopause (also described as 17-beta estradiol and E2)
                    Estriol,
                     Estriol, the weakest of the three main forms of estrogen,
                     made in the body from other estrogens (E3)




                 Newer Dosage Forms of Estrogen:                                                  Estradiol Vaginal Ring
                             Estradiol Vaginal Ring                                               (Estring® Femring®
                                                                                                  (Estring®, Femring®)
                             (Estring® Femring®
                             (Estring®, Femring®)                                      Femring® provides more estradiol.
                                                                                      Femring®
                Estring® was approved in 1997.
                 Estring®                                                                 Estring®
                                                                                           Estring® releases only 7.5 µg/day of estradiol and it's only
                                                                                           for treating vaginal symptoms such as atrophic vaginitis.
                Femring®
                 Femring® was approved in 2003.                                           Femring®
                                                                                           Femring® provides either 50 or 100 µg/day of estradiol.
                                                                     3-
                     These are estradiol vaginal rings that provide a 3-                   This higher dose makes it useful for hot flashes.
                     month supply of estradiol.                                       Femring®
                                                                                       Femring® will need a progestin to prevent endometrial
                How are they different?                                               hyperplasia.
                    Both are vaginal rings and both release estradiol for                                           Estring®
                                                                                       A progestin is not needed with Estring® because very
                     90 days.                                                          little estrogen is absorbed.




                                     Progestins                                                             Progestins
                Progesterone is naturally produced by the                            Endogenous progesterone is responsible for
                 ovaries, and it softens the uterus lining into a                      inducing secretory activity in the endometrium
                 spongy bed that holds a fertilized egg.                                       estrogen-
                                                                                       of the estrogen-primed uterus in preparation
                Progesterone is primarily used to treat                               for the implantation of a fertilized egg and for
                 amenorrhea, abnormal uterine bleeding, or as a                        the maintenance of pregnancy.
                 contraceptive.                                                       It is secreted from the corpus luteum in
                                                                                       response to LH.




Glen E. Farr, Pharm.D.
Professor of Clinical Pharmacy
University of Tennessee                                                                                                                                               7
Pharmacology Update for                                                                                                                                          March 20, 2009
                                                                                                                                                                      Webinar
Women’s Health Care Staff—Part I




                                                                                                                     Developing a Family
                                     Progestins
                                                                                                                     Planning Formulary
                Progesterone is derived from testosterone, so
                 these have androgenic effects.
                Progestins and estrogens have similar chemical
                 structure.    Are There Differences In Hormones?
                                  Sometimes, Small Differences Can Have Profound Effects

                                Testosterone           OH    Progesterone         COCH3
                                                 3HC                        3HC

                                          CH3                       CH3



                                 O                          O                      OH
                                                                             3HC




                                                       Estradiol

                                                             HO




                      Family Planning Medication                                                                 Monophasic vs. Biphasic
                     Formulary: Oral Contraceptives                                                                  vs. Triphasic
              Two    oral contraceptive products                                                                                    bi- tri-           OC’
                                                                                                            There is no evidence that bi- or tri-phasic OC’s
                                                                                                                                        OC’        vice-
                                                                                                            are superior to monophasic OC’s, or vice-versa.
                 should be on formulary:
                                                                                                             Triphasic oral contraceptives, in which the progestin
                  one  containing at least 30 mcg of ethinyl                                                 dose gradually increases throughout the cycle, were
                   estradiol.                                                                                 introduced to improve cycle control and to decrease
                                                                                                              adverse events.
                  an agent with a lower estrogen exposure
                                                                                                             Biphasic oral contraceptives are available but are
                   to contain 25 mcg of ethinyl estradiol.                                                    rarely prescribed in the United States.

                              State of Georgia FP Formulary 8-8-07                                      Treatment Guidelines from The Medical Letter, December 2007




                      Family Planning Medication                                                                Family Planning Medication
                        Formulary: Progestins                                                                     Formulary: Progestins
             Generation      Progestin            Estrogenic         Progestational        Androgenic
                                                                                                         2ndand 3rd generation progestins
             First        Norethindrone                 ++                   ++              ++           appear to be superior to 1st generation
                          Norgestrel                     -                   ++              ++
             Second       Levonorgestrel                 -                  ++++            ++++
                                                                                                          agents in the areas of discontinuation
             Third        Norgestimate                   -                   ++               ++          and cycle control
                          Desogestrel                   +/-
                                                        +/-                 ++++              ++
                                                                                                         Breakthrough bleeding is less with 3rd
             Fourth       Drospirenone                   -                   +/-
                                                                             +/-               -
                                                                                                          compared to 2nd generation pills.
                              State of Georgia FP Formulary 8-8-07                                                     State of Georgia FP Formulary 8-8-07




Glen E. Farr, Pharm.D.
Professor of Clinical Pharmacy
University of Tennessee                                                                                                                                                      8
Pharmacology Update for                                                                                                                   March 20, 2009
                                                                                                                                               Webinar
Women’s Health Care Staff—Part I




                      Family Planning Medication                                         Family Planning Medication
                        Formulary: Progestins                                              Formulary: Progestins
                Desogestrel, a 3rd generation
                 progestin has a higher risk                                     The 4th    generation agent drospirenone
                 of VTE than 2nd generation                                         has minimal side effects and positive
                 progestins such as                                                 effects regarding fluid retention.
                 levonorgestrel.
                                                                                     However,      the need to monitor for
                                                                                        hyperkalemia and the cost of the pill
                                                                                        itself, may outweigh the benefits.
                               State of Georgia FP Formulary 8-8-07                              State of Georiga FP Formulary 8-8-07




                  Choosing the Most Appropriate                                      Choosing the Most Appropriate
                       Oral Contraceptive                                                 Oral Contraceptive
                                       bleeding,
                 For breakthrough bleeding, encourage women to try                        Tri- Cyclen® Estrostep®      Yaz®
                                                                                    Ortho Tri-Cyclen®, Estrostep®, and Yaz® are
                 a pill for at least 3 months before deciding if
                 breakthrough bleeding is a problem. Explain that                                 acne.
                                                                                    approved for acne.
                 missed pills also lead to spotting.                               But most OCs are helpful because estrogen
                If the problem persists, suggest a pill with more
                 estrogen for EARLY breakthrough bleeding, around                   decreases testosterone levels.
                 the first week after menses.
                Recommend one with more estrogen AND progestin
                     MID-
                 for MID-cycle bleeding, around days 14 to 21.
                Suggest one with more progestin for LATE
                 breakthrough bleeding.

                                Prescriber’s Letter, December 2007                                Prescriber’s Letter, December 2007




                  Choosing the Most Appropriate                                      Choosing the Most Appropriate
                       Oral Contraceptive                                                 Oral Contraceptive
                Estrogen may initially cause weight gain due to                   Dysmenorrhea or PMS symptoms may
                 water and sodium retention, but long-term
                                                   long-                                                       continuous-
                                                                                    improve with extended or continuous-cycle pills:
                 weight gain isn't likely.                                          Seasonale® Seasonique® Lybrel®
                                                                                    Seasonale®, Seasonique®, Lybrel® since the
                                                                                    hormone-
                                                                                    hormone-free interval is shorter or absent.
                Pills with androgenic activity sometimes
                                                                                                Yasmin® Yaz®
                                                                                    Recommend Yasmin® or Yaz® for patients
                 stimulate appetite.
                                                                                    who complain of bloating.
                    If this is suspected, suggest trying a pill that is less          These contain drospirenone, a progestin that blocks
                     androgenic.                                                                                                    Yaz®
                                                                                        aldosterone and has a mild diuretic effect. Yaz® is
                                                                                        the first oral contraceptive approved for
                                                                                        premenstrual dysphoric disorder (PMDD).
                                Prescriber’s Letter, December 2007                                  Prescriber’s Letter, December 2007




Glen E. Farr, Pharm.D.
Professor of Clinical Pharmacy
University of Tennessee                                                                                                                               9
Pharmacology Update for                                                                                                       March 20, 2009
                                                                                                                                   Webinar
Women’s Health Care Staff—Part I




                  Risks & Benefits of Oral                                   Risks and Benefits of
                      Contraceptives                                       Combination Contraceptives
                                                                                  Evidenced-Based Review
                                                                      Risks:
                                                                       Risks:
                                                                           3-
                                                                         A 3-6 fold increase in the incidence of venous
                                                                         thromboembolism (VTE) apparent by the 4th
                                                                         month of use and highest between 6 and 12 months
                                                                            2-
                                                                        A 2-6 fold increase in the risk of ischemic stroke
                                                                         among women with a history of migraine
                                                                        Increase in cervical cancer risk after 5 or more years
                                                                         of use.
                                                                               AFP, December 1, 2006, Volume 74, #11




                     Risks and Benefits of                                   Risks and Benefits of
                   Combination Contraceptives                              Combination Contraceptives
              No   associated increase in risk of:
                                                                    Little  evidence of improvement of
                 weight  gain                                         dysfunctional uterine bleeding or that they
                 breast cancer
                                                                       decrease heavy menstrual bleeding more
              No   change in                                          than other proposed treatments of low
                 breast   milk production                                          (Danocrine®
                                                                       dose danazol (Danocrine®), or naproxen
                 infant   growth or weight                            (Naprosyn®
                                                                       (Naprosyn®).
                           AFP, December 1, 2006, Volume 74, #11           AFP, December 1, 2006, Volume 74, #11




                     Risks and Benefits of                             Oral Contraceptives Protects Long
                   Combination Contraceptives                            Term Against Ovarian Cancer
              Benefits:                                                 meta-
                                                                       A meta-analysis of 45 studies concluded that the
                 Lower   incidence of ovarian, endometrial and        longer women stay on the pill, the lower their
                  colorectal cancer without regard to duration         risk of developing ovarian cancer, which is more
                  of use                                               common after age 50.
                 A reduction in primary dysmenorrheal pain
                                                                      For example, women who take the pill for 15
                  after 1-3 months
                        1-                                             years cut their risk in half.
                 Improvement in acne in trials of 6 months of
                  use
                     AFP, December 1, 2006, Volume 74, #11                 The Lancet, Volume 371, Number 9609, January 26, 2008




Glen E. Farr, Pharm.D.
Professor of Clinical Pharmacy
University of Tennessee                                                                                                                  10
Pharmacology Update for                                                                                                     March 20, 2009
                                                                                                                                 Webinar
Women’s Health Care Staff—Part I




                 Combination Oral Contraceptives                       Combination Oral Contraceptives
              WHO Recommendations Avoiding in Women With:              ACOG Recommendations Avoiding in Women With:
              Cardiovascular disease  Migraine with aura            Migraine H/A                  Hypertension or diabetes
              Uncontrolled            History of breast cancer      Smokers >35 years              with vascular disease or
               hypertension            Smokers >35 years of          Hx of thromboembolism          age >35
              Ischemic heart disease   age who smoke >15             CAD                           Hypertriglyceridemia
              History of stroke        cigarettes/day                CHF                           Hx of breast cancer
              Venous thromboembolic   Discourage during the 6                                      SLE with vascular
                                                                      Cerebrovascular disease
               disease                  weeks postpartum for                                          disease or nephritis
                                        women desiring to             <2 weeks postpartum
                                        breastfeed
                                                                             AFP, December 1, 2006, Volume 74, #11
                      AFP, December 1, 2006, Volume 74, #11




                   Oral Contraceptives Prescribed                              Oral Contraceptives
                         Online in the UK                                     Without a Rx in the UK
                An online service launched in June 2008              Under a pilot plan beginning 2009, UK
                 provides oral contraceptives to women in the          pharmacists are allowed to give women and girls
                 UK without requiring patients to meet a               aged 16 years and older the contraceptive pill
                            face- to-
                 physician face-to-face.                               without a prescription.
                Women interested in the service are required to
                                                                      Two areas in London will pilot the scheme,
                 register with the medical website Dr Thom and
                 answer an online questionnaire, after which           which will be extended countrywide if it is
                 doctors will decide whether to prescribe a 3-
                                                            3-         successful.
                 month course of oral contraceptives.

                                   BBC, June 23, 2008                                       BBC, December 10, 2008




                        FDA Approves Lybrel®
                                      Lybrel®                                               Lybrel®
                                                                              FDA Approves Lybrel®
                         for Continuous Use                                    for Continuous Use
                                                                    May                              Lybrel®
                                                                            2007, the FDA approved Lybrel® (90
                                                                       µg levonorgestrel + 20 µg ethinyl estradiol)
                                                                       as the first continuous use drug product
                                                                       for contraception.
                                                                                           day-
                                                                         It comes in a 28 day-pill pack without the placebo or
                                                                         pill-
                                                                         pill-free time interval.
                                                                        Cost is about $700 per year. This is comparable to
                                                                         Yaz® Seasonale®
                                                                         Yaz®, Seasonale®, etc.
                                                                                                  FDA News, May 22, 2007




Glen E. Farr, Pharm.D.
Professor of Clinical Pharmacy
University of Tennessee                                                                                                                11
Pharmacology Update for                                                                                                        March 20, 2009
                                                                                                                                    Webinar
Women’s Health Care Staff—Part I




                             The Medical Letter                                       Implantable Contraceptive:
                                        Lybrel®
                              Review of Lybrel®                                                    (Implanon®
                                                                                      Etonogestrel (Implanon®)
                While most women eventually achieve
                 amenorrhea, breakthrough bleeding or spotting                 In 2006, the FDA approved
                 is common, particularly in the first several                     matchstick-
                                                                                a matchstick-sized
                 months of use.                                                 contraceptive containing
                When the continuous regimen was discontinued                   etonogestrel that is inserted
                 after one year of use, menses generally resumed                in a woman's upper arm for
                 promptly.                                                      as long as 3 years.
                               long-
                 The potential long-term effects of continuous                     It delivers the equivalent to
                 hormone exposure are unknown.                                      ~15 µg of po ethinyl estradiol
                                   The Medical Letter, July 30, 2007




                       Implantable Contraceptive:                                                NuvaRing®
                                    (Implanon®
                       Etonogestrel (Implanon®)
                Fewer problems should
                 be reported with
                 Implanon®
                 Implanon® over
                 Norplant®
                 Norplant® because it
                 involves implanting only
                 one rod rather than 6
                       Norplant®
                 with Norplant®, and it
                 is inserted less deep in
                 the skin.




                                  NuvaRing®                                             Recent Developments
                                                                                                (Depo- Provera®
                                                                                    with DMPA (Depo-Provera®)
                Contains 0.120 mg of etonogestrel (the active
                                                                             The                     sustained-
                                                                                    IM injection is a sustained-release (i.e.,
                 metabolite of desogestrel) and 0.015 mg of
                 ethinyl estradiol.                                             'depo') product available in 2 strengths:
                Equivalent to ~15 µg of oral ethinyl estradiol                  150                                  (Depo-
                                                                                      mg/ml for use as a contraceptive (Depo-
                The ring stays in place for 3 weeks and is                       Provera®
                                                                                  Provera®)
                 replaced each month following menstruation.                     A 1/3 lower dose for the treatment of pain
                    If the ring is expelled, it can be washed off and                               (Depo-
                                                                                  from endometriosis (Depo-subQ Provera
                     reinserted. If the ring has been out for more than 3
                     hours, use back-up contraception.
                                                                                  104®
                                                                                  104®).
                                 back-
                                                                                                 http://www.goldstandard.com




Glen E. Farr, Pharm.D.
Professor of Clinical Pharmacy
University of Tennessee                                                                                                                   12
Pharmacology Update for                                                                                                                    March 20, 2009
                                                                                                                                                Webinar
Women’s Health Care Staff—Part I




                                      Depo- Provera®
                 Black Box Warning on Depo-Provera®                                                      Depo- Provera®
                                                                                    Black Box Warning on Depo-Provera®
                   Related to Bone Mineral Density                                    Related to Bone Mineral Density
                Women who use Depo-Provera contraceptive injection
                                                                                   Depo-Provera contraceptive injection should be
                 may lose significant bone mineral density.
                                                                                    used as a long-term birth control method (e.g.,
                Bone loss is greater with increasing duration of use and
                 may not be completely reversible.
                                                                                    longer than 2 years) only if other birth control
                                                                                    methods are inadequate (see WARNINGS).
                It is unknown if use of Depo-Provera contraceptive
                 injection during adolescence or early adulthood, a
                 critical period of bone accretion, will reduce peak bone
                 mass and increase the risk of osteoporotic fracture in
                 later life.                                                                                    Depo-Provera® PI
                                              Depo-Provera® PI




                 Prescriber’
                 Prescriber’s Letter Take on Depo-
                                             Depo-                                                             Evra®
                                                                                    Updated Labeling for Ortho Evra®
             Provera®
             Provera® and Bone Mineral Density
                Women under 21 seem to be the most                                The FDA approved additional
                 vulnerable since they're still building bone.                                              Evra®
                                                                                    changes to the Ortho Evra® label to
                                            Depo- Provera®
                 Advise women not to use Depo-Provera® for                          include the results of a new
                 more than two years, unless other contraceptives                   epidemiology study that found that
                 aren't appropriate.                                                users of the birth control patch were
                                                                                    at higher risk of developing serious
                Recommend monitoring bone mineral density in                       blood clots, also known as venous
                 long-
                 long-term users.                                                   thromboembolism (VTE), than
                Encourage them to get enough calcium and                           women using birth control pills.
                 vitamin D.
                                  Prescriber’s Letter, January 2005                                  FDA Press Release, January 18, 2008




              J & J Settles Ortho Evra® Law Suits
                                  Evra®                                                    Drug Interactions with
                                                                                            Oral Contraceptives
              In   October 2008, J & J
                 paid $68 million to
                 settle hundreds of
                 cases brought by
                 women who used the
                         Evra®
                 Ortho Evra® patch.

                                 http://www.coreynahman.com, October 14, 2008




Glen E. Farr, Pharm.D.
Professor of Clinical Pharmacy
University of Tennessee                                                                                                                               13
Pharmacology Update for                                                                                                       March 20, 2009
                                                                                                                                   Webinar
Women’s Health Care Staff—Part I




                         Drug Interactions with                           Metabolism (Biotransformation)
                          Oral Contraceptives                                      Interactions
              The    four most common types of drugs that                  The enzymes most responsible for
                 interact with oral contraceptives to                        drug metabolism are commonly
                 decrease their efficacy are:                                referred to as “cytochrome P450
                                                                             enzymes.
                                                                             enzymes.”
                  Some   antibiotics
                                                                            These enzymes are most commonly
                  Some   anti-
                          anti-epileptic drugs (Anticonvulsants)
                                                                             found in the liver, but can also be
                          anti-
                  Some anti-HIV drugs (Protease Inhibitors)                 found in the intestines, lungs and
                       John’
                  St. John’s Wort                                           other organs.
                               Prescriber’s Letter, September 2005                         The Medical Letter, June 9, 2003




                Important Characteristics of Drug                         Metabolism (Biotransformation)
             Metabolism by Cytochrome P450 Enzymes
                                                                                   Interactions
             Substrate:                  CYP-
                                         CYP- 450      Hydrophilic
                Agent                      3A4         Metabolites        Some drugs   inhibit CYP isozymes thus
              requiring                    2C9
             metabolism                    2C8
                                                         Readily             decrease metabolism of substrate drugs
                                                       Excreted by
             “lipophilic”                  2D6
                                                         Kidney
                                                                             and increase their concentration.
                                           1A2
                Inhibitor:
                                         Metabolism                           The  azole antifungals such as
                Agent that                                                                   (Sporanox®
                                                                               Itraconazole (Sporanox®) are the most
               impairs the                              Increased
              ability of the             Plasma        Potential for
                                                                               potent inhibitors.
                 enzyme
                                          levels      Adverse Drug
             to metabolize
             the substrate                                Effects                          The Medical Letter, June 9, 2003




                                                                          Metabolism (Biotransformation)
                   Some CYP-450 Inhibitors
                                                                                   Interactions
                Amiodarone                               (Sporanox®
                                              Itraconazole (Sporanox®)    Some drugs induce or stimulate
                 (Cordarone®
                 (Cordarone®)                               (Nizoral®
                                              Ketoconazole (Nizoral®)     biosynthesis of CYP isozymes,
                            (Tagamet®
                 Cimetidine (Tagamet®)                     (Levaquin®
                                              Levofloxacin (Levaquin®)
                 Ciprofloxacin (Cipro®) 
                                                                          increasing metabolism of substrate
                               (Cipro®                       (Flagyl®
                                              Metronidazole (Flagyl®)
                                (Biaxin®
                 Clarithromycin (Biaxin®)    Norfloxacin (Noroxin®)
                                                           (Noroxin®
                                                                          drugs and lowering their concentration.
                Erythromycin                Ofloxacin (Floxin®)
                                                        (Floxin®              Rifampin   is the most well known.
                              (Luvox®
                 Fluvoxamine (Luvox®)                   (Paxil®
                                              Paroxetine (Paxil®)
                Grapefruit juice                           (Ketek®
                                              Telithromycin (Ketek®)
                Isoniazid (INH)                         (Ticlid®
                                              Ticlopidine (Ticlid®)                        The Medical Letter, June 9, 2003




Glen E. Farr, Pharm.D.
Professor of Clinical Pharmacy
University of Tennessee                                                                                                                  14
Pharmacology Update for                                                                                                            March 20, 2009
                                                                                                                                        Webinar
Women’s Health Care Staff—Part I




                                                                             Drug Interactions with
                    Some CYP-450 Inducers
                                                                       Oral Contraceptives and Antibiotics
                                 (Tegretol®
                 Carbamazepine (Tegretol®)                             {including Metronidazole (Flagyl) and Rifampin}
                Cigarette smoke                                       Women  have been warned for decades to
                Phenobarbital                                         use backup contraception when taking oral
                            (Dilantin®
                 Phenytoin (Dilantin®)                                 contraceptives and antibiotics together.
                Rifampin                                                   Thisstarted back in the '70s when a few
                Griseofulvin                                               women on OCs took rifampin and then got
                           (Norvir® Kaletra®
                 Ritonavir (Norvir®, Kaletra®)                              pregnant.
                    John’
                 St. John’s Wort




                    Drug Interactions with                                  Drug Interactions with
              Oral Contraceptives and Antibiotics                     Oral Contraceptives and Antibiotics
              We    now know that antibiotics other than                 There can be up to a 3% failure rate,
                 rifampin do not decrease efficacy of OCs.
                                                      OCs.                 regardless of antibiotic use.
                   Infact, some antibiotics like erythromycin,                A small number of women might be predisposed
                                                                                to a higher failure rate due to genetic metabolic
                                   (Biaxin®         trimethoprim-
                   clarithromycin (Biaxin®), and trimethoprim-                  variations, but it's difficult to determine who these
                                      (Bactrim® Septra®
                   sulfamethoxazole (Bactrim®), Septra®) may                    women are.
                   actually increase OC levels.
                                                                          To be on the safe side, tell women to continue
             Archer, JS, “Oral Contraceptives Efficacy and                 using backup contraception during the entire
             Antibiotic Interaction: A Myth Debunked,” J Am                course of antibiotics and for 7 days after.
             Acad Dermotol, 2002, 46:917-23




                     Drug Interactions with                             Anticonvulsant Agents that Do
             Oral Contraceptives and Anticonvulsants
                                                                        Not Compromise OC Efficacy
              Some    anticonvulsants
                 decrease the effectiveness of                                     (Neurontin®
                                                                       Gabapentin (Neurontin®)

                 OCs by inducing cytochrome                                           (Keppra®
                                                                       Levetiracetam (Keppra®)
                 P-450 enzymes.                                                   (Gabitril®
                                                                       Tiagabine (Gabitril®)

                                                                                  (Depakote®
                                                                       Valproate (Depakote®)

                                                                       Zonisamide           (Zonegran®
                                                                                             (Zonegran®)
                         “Epilepsy in Women” American Family
                         Physician, Vol. 66, No 8, October 15, 2002




Glen E. Farr, Pharm.D.
Professor of Clinical Pharmacy
University of Tennessee                                                                                                                       15
Pharmacology Update for                                                                                                           March 20, 2009
                                                                                                                                       Webinar
Women’s Health Care Staff—Part I




              Anticonvulsant Agents that Induce                                      Drug Interactions with
                   Liver Enzymes and May                                   Oral Contraceptives and Protease Inhibitors
                  Compromise OC Efficacy                                          anti-
                                                                               The anti-HIV antiretroviral protease inhibitors
                                    (Tegretol®
                     Carbamazepine (Tegretol®)                                  the level of estrogen in patients receiving
                              (Dilantin®
                     Phenytoin (Dilantin®)                                     hormonal replacement therapy or oral
                                                                               contraceptive agents.
                    Phenobarbital
                                                                              Thus women on PIs should be cautioned that
                                   (Trileptal®
                     Oxcarbazepine (Trileptal®)
                                                                               OCs may be ineffective.
                               (Topamax®
                     Topiramate (Topamax®)                                        Agents include:
                        Approved 2004 for migraine headache prophylaxis
                                (Lamictal®
                     Lamotrigine (Lamictal®)




                         Protease Inhibitor Agents                                     Drug Interactions with
                                                                                       Oral Contraceptives and
                                (Fortovase® Invirase®
                     Saquinavir (Fortovase®, Invirase®)                                        John’
                                                                                           St. John’s Wort
                              (Norvir®
                     Ritonavir (Norvir®)
                     Indinavir (Crixivan®)                                                                        John’
                                                                               One of the 10 constituents of St. John’s
                              (Crixivan®
                                                                                          naphtodiantrons,
                                                                               Wort, the naphtodiantrons, induces the
                               (Viracept®
                     Nelfinavir (Viracept®)
                                                                                             P-
                                                                               cytochrome P-450 hepatic microsomal
                                  (Agenerase®
                     Amprenavir (Agenerase®)                                   system, specifically the CYP3A4 isoenzyme.
                                         (Keletra
                     Lopinavir/ritonavir (Keletra)
                                                                              This results in a decrease in the effectiveness
                                (Reyataz®
                     Atazanavir (Reyataz®)                                     of oral contraceptives.
                                    (Lexiva®
                     Fosamprenavir (Lexiva®)
                                (Aptivus®
                     Tipranavir (Aptivus®)                                                           The Lancet, 2000;355:547-9




                                  Questions?




Glen E. Farr, Pharm.D.
Professor of Clinical Pharmacy
University of Tennessee                                                                                                                      16

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:8
posted:12/7/2011
language:English
pages:16