Oral contraceptive prescribing
description
Transcript of Oral contraceptive prescribing
Oral contraceptive prescribing
• clinical pharmacology– mechanism of action– ADME
• interactions
• adverse reactions
• benefits and harms
what are they
• around since late 1950’s
• social revolution
• progestogen /oestrogen
• variety of components and doses
• changes over time in both
components
• oestrogen– ethinyoestradiol
– mestranol
• progestogen– norethisterone
– norgestrel
– Levonorgestrel
– medroxyprogesterone
– ethynodiol diacetate
– gestodene
– desogestrel
doses• monophasic
• oestrogen - up to 50g/day• progestogen - up to 1mg/day
• biphasic• oestrogen: constant• progestogen: eg 11 days @50, 10 @125 g
• triphasic• oestrogen 30/40/30• progestogen 50/75/125
clinical pharmacology
• mechanism of action– inhibit secretion of FSH, LH - inhibit ovulation– additional actions on endometrium tubal
motility, cervical mucosa
• absorption – well absorbed orally
• distribution– bound to plasma proteins– albumin, SBG, others
clinical pharmacology
metabolism
• Oestrogens– first pass clearance
• metabolised in liver, conjugated
• excreted in the bile - (estradiol vs EE)
• enterohepatic circulation
• Progestogens– depends on which one - “natural” progestogen
extensive first pass metabolism
excretion
• urinary
• remember the bile duct
CBD
PV
HV STO
About 40-60 % of estrogen removedin the first pass through the liver
HMW conjugates are excreted in bile
interactions (1)
• antibiotics– impaired absorption (effect on gut enzymes)
reduced bacterial sulfatase leading to reduced entero-hepatic recycling
– enzyme induction -> increased clearance, lower plasma estrogen concentrations (eg rifampicin, griseofulvin, anticonvulsants, St John’s Wort)
interactions (2)
• anticonvulsants– Older drugs are enzyme inducers -> increased clearance
and reduced concentration and failure (phenytoin, phenobarbitone, primidone, carbamazepine). No effect of sodium valproate
– Newer drug have variable effects (no change with gabapentin, lamotrigine, tiagabine, levetiracetam) (induction with topiramate and oxcarbazepine)
– try higher dose estrogen pills, double product dosing– valproate less of a problem
adverse reactions
• estrogen excess– late cycle breakthrough bleeding– menorrhagia/dysmenorrhoea– nausea/vomiting– fluid retention– breast tenderness
adverse reactions
• progestogen excess– amenorrhoea– acne/oily skin– weight gain– mood changes– depressed libido– breast tenderness
other risks
• thromboembolic disorder– high dose oestrogen - Inman, dose response
relationship– worse with other risk factors (age, smoking)– ?third generation progestogens– differentiating effects on VTE and other
cardiovascular disease
big picture risks
• endometrial cancer– progestogen is protective
• ovarian cancer– protective
• breast cancer– jury out /data unconvincing
• cervical cancer– confounded
other benefits
• reduction in menstrual flow - may lower incidence of anemia
• reduction in dysmenorrhoea
• possible reduction in auto-immune thyroid disease, rheumatoid arthritis
• some protection against PID
risk of nonfatal VTE
Pregnancy 3rd gen Ist gen Non-users
AR(per100000womenyears)
60 30 15 5
RR 12 6 3 1
% ofwomenfree of VTE
99.94 99.97 99.985 99.995
other issues
• compliance
• gastro.
• missing pills
• alternative forms of hormonal contraception
balance sheet
• benefits– effective contraception
– other health benefits
– long-term health and social impact
• harms– immediate adverse
effects
– risk of failure
– long-term health effects
other uses
• morning after pill– EE 100mcg + norgestrel 1mg within 72 hours,
2 doses– Failure rate of about 1%