7: Obstetrics, Gynaecology and Urinary Tract Disorders

Please select a topic:

7.1 Drugs used in obstetrics / 7.2 Treatment of vaginal and vulval conditions
7.3 Contraceptives / 7.4 Drugs for genitourinary disorders

Changes to the Formulary since previous version

(22.8.2013)

Section / Change / Reason for change
7.3 / REMOVED: Etynodiol diacetate 500 micrograms (Femulen) / Product discontinued

7.1 Drugs used in obstetrics

Prostaglandins and oxytocics

  • Carboprost 250 micrograms injection
  • Dinoprostone 3mg vaginal tablets
  • Dinoprostone 10mg/ml extra-amniotic solution
  • Dinoprostone 750 microgram intravenous solution
  • Ergometrine 500 microgram injection
  • Gemeprost 1mg pessaries
  • Oxytocin 10 units/ml injection
  • Syntometrine 1ml injection (containing ergometrine maleate 500micrograms with oxytocin 5units/mL)

Mifepristone

  • Mifepristone 200mg tablets

Prescribing notes

  • Mifepristone should be ordered in the controlled drug book

Myometrial relaxants

  • Atosiban 6.75mg/0.9ml and 37.5mg/5ml injection

7.2 Treatment of vaginal and vulval conditions

Preparations for vaginal atrophy

  • Estriol 0.1% cream (Ovestin)
  • Estriol 0.01% cream (Gynest)
  • Estriol 500 microgram pessaries (Ortho-Gynest)
  • Estradiol 10 microgram MR vaginal tabs (Vagifem)

Composition

- Ovestin® intravaginal cream (15g pack with applicator): estriol 0.1% intravaginal cream.

- Gynest® intravaginal cream (80g pack with applicator): estriol 0.1% intravaginal cream.

- Ortho-Gynest® pessaries (500micrograms): estriol 500 micrograms

- Vagifem® vaginal tablets m/r (15-applicator pack): estradiol 10microgram vaginal tablets.

Prescribing notes
  • Local oestrogens can improve local vaginal and bladder symptoms caused by oestrogen deficiency; systemic therapy is necessary for vasomotor symptoms.
  • Most women with significant vulvo-vaginal problems will require long-term treatment particularly if sexually active.
  • Vagifem® may be useful in women who do not find creams difficult or messy to use. It is more expensive Ovestin®.
  • Women using long-term vaginal oestrogen treatments do not need cyclical progestogen therapy.
  • Symptoms recur when local vaginal oestrogens are discontinued; there is no fixed duration of use and each woman should be assessed individually.
  • The lowest effective dose should be used for the shortest duration possible.

Anti-infective drugs

  • Clotrimazole 1% cream
  • Clotrimazole 200mg and 500mg pessaries

Other infections

  • Clindamycin 2% vaginal cream

Prescribing notes

Management of sexually transmitted disease (general notes)

  • With any genital symptoms always consider the possibility of sexually transmitted infection (STI). If an STI is found, there is a strong possibility of others also being present so it is expedient to check. If facilities and skills are available, this can be done by the GP. Otherwise, refer to GUM especially for tests of cure and contact tracing. Of the conditions considered here, only thrush and bacterial vaginosis are considered non-STIs although they can occur concurrently with STIs.

Thrush

  • Clotrimazole is available over-the-counter.
  • There is no evidence that treating the partner of women suffering from candidiasis is helpful.
  • Patients who are inserting intravaginal cream or pessaries into the vagina, may also apply topical clotrimazole cream to the vulva.

7.3 Contraceptives

General notes

  • Most contraceptive failures are due to poor compliance which is strongly influenced by

acceptability. It is important therefore to accept that women may prefer one particular method ofcontraception and even one particular brand to another despite similar or identical composition.

  • Discontinuation rates of all methods of contraception are high and many women change to a lesseffective method. Good counselling about risks, side effects and benefits should improve

continuation. Long acting reversible methods (LARC), particularly implants and intra-uterine

methods, have higher continuation rates and are independent of compliance for their effectiveness.

  • NICE concluded that all LARC, but particularly implants and the IUD/IUS, are more cost effectivethan either the condom or oral contraception even if discontinued after only one year of use.
  • When a contraceptive is used for management of gynaecological conditions, such as menorrhagiaor dysmenorrhoea, the risk/benefit ratio changes and it may be prescribed for women who wouldhave relative contra–indications if they were using it solely for contraception.
  • Young people often have difficulties with consistent and correct use of condoms and oral

contraceptives. If the progestogen-only pill is chosen the newer pill (Cerazette®) should be the POPof choice as it has a twelve hour window when pills are missed.

  • Some drugs, including enzyme–inducers and antibiotics, may impair the efficacy of oralcontraceptives.

Combined oral contraceptives

  • Ethinyloestradiol 20 micrograms plus desogestrel 150 micrograms (Mercilon®)
  • Ethinyloestradiol 20 micrograms plus norethisterone 1mg (Loestrin 20®)
  • Ethinyloestradiol 30 micrograms plus norethisterone 1.5mg (Loestrin 30®)
  • Ethinyloestradiol 20 micrograms plus gestodene 75 micrograms (Femodette®, Millinette 20/75®)
  • Ethinyloestradiol 30 micrograms plus desogestrel 150 micrograms (Marvelon®, Gedarel 30/150®)
  • Ethinyloestradiol 30 micrograms plus gestodene 75 micrograms (Femodene®, Millinette 30/75®)
  • Ethinyloestradiol 30 micrograms plus gestodene 75 micrograms and placebo (Femodene ED®)
  • Ethinyloestradiol 30 micrograms plus levonorgestrel 150 micrograms (Microgynon 30®, Rigevidon®, Ovranette®, Levest®)
  • Ethinyloestradiol 30 micrograms plus levonorgestrel 150 micrograms and placebo (Microgynon 30 ED®)
  • Ethinyloestradiol 35 micrograms plus norgestimate 250 micrograms (Cilest®, Ovysmen®)
  • Ethinyloestradiol with norethisterone, triphasic (Trinovum®)
  • Ethinyloestradiol with levonorgestrel and placebo, triphasic (Logynon ED®)
  • Drospirenone 3mg with ethinylestradiol 30micrograms (Yasmin®)

Prescribing notes

  • The following products are considered interchangeable:
  • Rigevidon®, Ovranette® and Microgynon 30®
  • Femodene® and Millnette 30/75®
  • Marvelon® and Gederal 30/150®
  • Different doses of oestrogen may be associated with different side–effect profiles in individualwomen. For most, a pill containing 30micrograms oestrogen is recommended.
  • The risk of breast cancer appears to be unrelated to the dose of oestrogen.
  • There is no good evidence for any difference in breast cancer, cardiovascular risk or cycle controlwith different progestogens.
  • The risk of cardiovascular disease (including venous thromboembolism) is higher with pills

containing 50 micrograms oestrogen but there is no evidence for a difference in cardiovascular riskbetween 20 and 30 micrograms.

  • The MHRA has agreed that while evidence suggests that combined oral contraceptives (COCs) havea higher risk of venous thromboembolism, the absolute risk of venous thromboembolism is small.

The relative risk of venous thromboembolism in healthy non-pregnant women taking COCs ofsecond generation progestogens is about 3 times that of non-users of COCs or 5 times for COCs ofthird generation progestogens. However the absolute risk is considerably smaller than thatassociated with pregnancy. Provided that this is made clear to the user, there is no restriction onprescription of these pills.

  • Women with acne often benefit from the oestrogen component of combined hormonal

contraception. If acne is a particular problem, choose a pill containing a less androgenic

progestogen (e.g. desogestrel, Marvelon®) or consider co-cyprindiol 2000/35.

  • Co–cyprindiol 2000/35 (composed of cyproterone acetate 2mg, ethinylestradiol 35micrograms) is a treatment for severe acne that has not responded to oral antibiotics or for moderately severe hirsutism and only in those patients may it also be used as an oral contraceptive (see section 13.6(a)). Most acne improves with any COC; co-cyprindiol is more expensive and recent evidence suggests an increased risk of venous thromboembolism. Some women with acne or hirsutism requiring contraception may benefit. This is a good example of the need to consider a risk–benefit ratio in women with relative contra−indications.
  • In accordance with MHRA guidance, co–cyprindiol 2000/35 should be withdrawn 3–4 cycles after the treated condition has completely resolved. For acne, substitution with another COC is likely to maintain the improvement but hirsutism is likely to recur. A COC containing a less androgenic progestogen e.g. Gedarel® 30/150, could be substituted but co-cyprindiol 2000/35 may need to be continued.
  • In women with severe hyperandogenism, symptoms usually recur when treatment with cocyprindiolis stopped. In these women treatment may be continued until the symptoms are judgedunlikely to recur. The decision of when to stop, should be judged on a case by case basis.
  • Cycle control is no better with triphasic or biphasic COCs and they are more complicated to use.
  • Mercilon® and Gedarel 20/150® (ethinylestradiol 20 micrograms, desogestrel 150 micrograms) contain a lower dose ofoestrogen and may be associated with a better side–effect profile in women complaining ofoestrogenic symptoms such as breast enlargement/mastalgia.
  • Women aged over 40 years can be advised that no contraceptive method is contraindicated by agealone and that that combined hormonal contraception can be used unless there are co-existing diseases or risk factors.

Transermal Combined Hormonal Contraceptives

  • Evra® patch

Prescribing notes

  • Evra® patches should be restricted for use in women who are unlikely to comply well with combined oral contraceptives.
  • Side-effects, risks and benefits of Evra® patches are likely to be the same as those for the combined oral contraceptive pill. Evidence suggests no benefit of the transdermal route for COC in terms of reducing the risk of VTE.

Progesterone only contraceptives

  • Norethisterone 350 micrograms (Micronor)
  • Desogestrol 75 micrograms (Cerazette)

Prescribing notes

  • Progestogen-only pills (POPs) are associated with irregular bleeding in up to 40% of users. Bleeding patterns do not tend to improve with time and are not likely to be any different with a different progestogen.
  • There is no evidence for any clinical advantage of any one brand of POP; Micronor® is currently less expensive than alternatives.
  • Norgeston® contains levonorgestrel, a slightly less androgenic progestogen; it may be the preferred brand for women with oily skin.
  • Cerazette® is more expensive but has been shown to inhibit ovulation to a substantially greater extent than other POPs. It should be reserved for women who cannot tolerate oestrogen containing contraceptives or in whom those preparations are contraindicated. It may also be recommended for women with a history of ectopic pregnancy who take a POP.
  • Cerazette® is also recommended for less compliant women as they are still protected up to 12 hours after missing a pill, whereas only 3 hours with other POPs.
  • It is no longer recommended that women who weigh over 70kg are prescribed two progestogen-only pills (POPs) a day.

Parenteral Progesterone only contraceptives

  • Medroxyprogesterone acetate 150mg/ml injection (Depo-provera)
  • Etonogestrel 68mg implant (Nexplanon)

Dose

- Depo-Provera® injection (medroxyprogesterone acetate 150mg/mL aqueous suspension): by deep intramuscular injection, 150mg within first 5 days of cycle or within first 5 days after parturition (delay until 6 weeks after parturition if breast-feeding); for long-term contraception, repeated every 12 weeks (if interval greater than 12 weeks and 5 days, exclude pregnancy before next injection and advise patient to use additional contraceptive measures (e.g. barrier) for 14 days after the injection).

- Nexplanon® implant (etonogestrel 68mg in one flexible rod): by subdermal implantation, Consult product literature for insertion instructions.

Prescribing notes

  • Nexplanon® insertion and removal requires specialist training.
  • Nexplanon® is a low dose long–acting progestogen which suppresses ovulation in all women.

Contraceptive effect lasts for 3 years and there have been no pregnancies reported.

  • No more than 20% of women will experience amenorrhoea; the rest will have unpredictable andsometimes prolonged bleeding. This point should be covered carefully during counselling.
  • Nexplanon® is more cost effective than either the combined pill or condoms even if used for onlyone year.
  • Depo-Provera® can cause menstrual dysfunction and weight gain. By the end of the first year of use, 80% of women will have become amenorrhoeic or have scanty infrequent periods.
  • When Depo-Provera® is stopped ovarian activity can take up to a year to recover.
  • Depo-Provera® is associated with hypoestrogenism and amenorrhoea; recent data have suggested that this is unlikely to have long-term detrimental effects on bone mineral density.
  • The effectiveness of Depo-Provera® is unaffected by enzyme-inducing drugs and the inter-injection interval need not be altered.
  • The CSM advises that Depo–Provera® can be used by adolescents who have yet to achieve theirpeak bone mass if other methods are unacceptable or unsuitable. Young women often findcompliance with condoms or oral contraceptives difficult.

Emergency contraception

  • Levonorgestrel 1500 microgram tablets (Levonelle One-Step)
  • Ulipristal acetate tablets 30mg (EllaOne®) - Restricted

Dose

-Levonelle® One-Steptablets containing levonorgestrel 1500 micrograms: 2 tablets to be taken together, as soon as possible, preferably within 12 hours, and no later than 72 hours after unprotected intercourse.

-Ulipristal acetate tablets 30mg: 1 tablet to be taken as soon as possible following UPSI, but nolater than 120 hours

Prescribing notes

  • There is no evidence that hormonal EC is teratogenic. It does not work if a woman is already pregnant. Pregnancy can usually be excluded on the basis of the menstrual history; pelvic examination and/or pregnancy testing is only indicated if pregnancy is suspected on clinical grounds.
  • Levonelle®-1500 is available over-the-counter as Levonelle® One-Step.
  • Women who require emergency contraception while using liver-enzyme-inducing drugs should beadvised that an intrauterine device is the preferred option. Those that prefer to take a hormonalemergency contraceptive may be advised to double the dose of levonorgsetrel i.e 2 tablets ofLevonelle®–1500. Ulipristal acetate, is metabolised by cytochrome P450 and its efficacy may bereduced by enzyme-inducing drugs. Increasing the dose of ulipristal is not currently recommendedas there is no evidence that this is effective.
  • If vomiting occurs within 2 hours of taking Levonelle®–1500 or 3 hours of taking ulipristal, a

replacement dose can be given. If an antiemetic is required domperidone is preferred.

  • A copper IUD is an alternative form of emergency contraception. It can be inserted up to 5 daysafter UPSI. An IUD (or advice on how to obtain one) should be offered to all women attending forEC even if presenting within 72 hours of UPSI.
  • If the timing of the ovulation can be estimated, insertion of an IUD can be beyond 5 days of UPSIas long as it is not beyond 5 days of ovulation.

Contraceptive devices

  • Femidom, Multiload 375, and Nova-T
  • Levonorgestrel 20 micrograms/24 hours intra-uterine device (Mirena)
  • Flat spring diaphragm, practice diaphragm

Dose

- Mirena® intra-uterine device releasing levonorgestrel 20micrograms/24hours: insert into uterine cavity within 7 days of onset of menstruation (anytime if replacement); effective for 5 years.

Prescribing notes

  • Mirena® is a highly effective method of contraception. Many women experience quite frequent and prolonged spotting for the first 3-6 months; thereafter amenorrhoea is common. Patients should be counselled accordingly. Systemic absorption may cause side-effects e.g. acne or greasy skin.
  • IUD insertions should be performed by someone who has been properly trained, regularly updated and performs regular insertions.
  • Copper IUDs provide long-acting highly effective contraception for at least 5 years and do not rely on compliance for their efficacy. Devices which contain less than 300mm of copper should no longer be used as they are less effective.
  • Condoms are available free of charge from Family Planning Services, and certain GPs.
  • Condoms are the only method which protect against sexually transmitted diseases including HIV; condom users should be informed about emergency contraception.

Spermicidal contraceptives

  • Gygel®

Composition

- Gygel® gel: nonoxinol '9' 2% in a water-miscible base.

Prescribing notes

  • Spermicides are not recommended for use as the sole method of contraception but have been traditionally advised for use with the diaphragm and/or for lubrication for male condoms. All currently available spermicides contain nonoxinol '9' (N9) as the active compound. While N9 has been shown to be toxic to HIV in vitro, concerns have been raised regarding its detrimental effect on vaginal integrity and thereby on a possible increase in the risk of HIV/AIDS transmission. Research is ongoing. In the meantime there is no reason to alter the advice that contraceptive diaphragms should be used together with a spermicidal preparation.

7.4 Drugs for genito-urinary disorders

Drugs for urinary retention

  • Alfuzosin 10mg m/r tablets
  • Alfuzosin 2.5mg tablets
  • Doxazosin 1mg, 2mg and 4mg tablets
  • Prazosin 1mg tablets
  • Terazosin 2mg and 5mg tablets
  • Tamsulosin 400 microgram tablets

Dose

- Alfuzosintablets 2.5mg: elderly, initially 2.5mg twice daily. Max 10mg daily.
- Alfuzosintablets m/r 10mg: 10mg once daily.
- Tamsulosintablets m/r 400micrograms: 400micrograms daily.
- Doxazosintablets 1mg, 2mg, 4mg: initially 1mg daily; dose may be doubled at intervals of 1-2 weeks according to response, up to max 8mg daily; usual maintenance 2-4mg daily.
- Prazosintablets 1mg: 500micrograms twice daily, increased to max 2mg twice if necessary.

- Terazosin tablets2mg, 5mg: initially 1mg at bedtime, if necessary dose may be doubled at intervals of 1-2weeks up to a max 10mg once daily.

Prescribing notes
  • Tamsulosin should be prescribed generically as tamulosin MR.
  • Watchful waiting may be preferable to treatment in men with mild to moderate symptoms.
  • Alpha-blockers are the treatment of choice for benign prostatic obstruction, and are likely to provide symptom relief in men with prostates of any size. The effect should be noticed within several days, with full response after 4-6 weeks, and the benefit may be maintained for up to 3 years in those who continue to take the drug. There is a lack of published data on effect beyond 3 years.
  • All alpha-blockers are equally effective but there are differences in tolerability. Alfuzosin and tamsulosin are the same in terms of effectiveness and cost. Doxazosin is also a once daily preparation which may be prescribed if side-effects are encountered.
  • Alpha-blockers reduce blood pressure, and first doses may cause drowsiness and dizziness. Patients also receiving antihypertensives may need lower doses and supervision.

Parasympathomimetics

  • Distigmine 5mg tablets

Dose

- Distigminetablets 5mg: 5mg daily

Prescribing notes

  • Bethanechol is considered less suitable for prescribing and use been superseded by catheterisation.
  • Distigimine may be useful in patients with an upper motor neurone neurogenic bladder.

Drugs for urinary frequency, enuresis and incontinence

  • Duloxetine (Yentreve®) 20mg & 40mg capsules (Restricted)
  • Oxybutinin 2.5mg, 3mg and 5mg tablets
  • Oxybutinin 2.5mg/5ml elixir
  • Oxybutinin MR 5mg and 10mg tablets
  • Propantheline 15mg tablets
  • Solifenacin 5mg and 10mg tablets
  • Tolterodine 1mg tablets
  • Tolterodine 4mg MR capsules
  • Fesoterodine fumerate 4mg & 8mg MR tablets
  • Mirabegron 25mg and 50mg tablets

Dose

- Oxybutynin hydrochloridetablets 2.5mg, 3mg, 5mg: initially 2.5-5mg 2-3 times daily increased if necessary to max 5mg 4 times daily.
- Oxybutynin hydrochloridem/r tablets 5mg, 10mg: over 18 years, initially 5mg daily, adjusted according to response in 5mg steps at weekly intervals; max 30mg daily taken as a single dose.