7: Obstetrics, Gynaecology and Urinary Tract Disorders

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

(17.3.2014)

Section / Change / Reason for change
7.3 / ADDED: Generic Combined hormonal contraceptives. / Gateshead Medicines Management Committee Approval
7.4 / REMOVED: Distigmine / 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

·  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 of contraception 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 less effective 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 effective than 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 menorrhagia or dysmenorrhoea, the risk/benefit ratio changes and it may be prescribed for women who would have 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 POP of choice as it has a twelve hour window when pills are missed.

·  Some drugs, including enzyme–inducers and antibiotics, may impair the efficacy of oral contraceptives.

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:

o  Rigevidon®, Ovranette® and Microgynon 30®

o  Femodene® and Millnette 30/75®

o  Cimizt®, Marvelon® and Gederal 30/150®

o  Mercilon® and Gederal 20/150®

o  TriRegol® and Logynon®

o  Lizinna® and Cilest®

o  Lucette® and Yasmin®

·  Different doses of oestrogen may be associated with different side–effect profiles in individual women. For most, a pill containing 30micrograms oestrogen is recommended.

·  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 risk between 20 and 30 micrograms.

·  The MHRA has agreed that while evidence suggests that combined oral contraceptives (COCs) have a 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 of second generation progestogens is about 3 times that of non-users of COCs or 5 times for COCs of third generation progestogens. However the absolute risk is considerably smaller than that associated with pregnancy. Provided that this is made clear to the user, there is no restriction on prescription 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 cocyprindiol is stopped. In these women treatment may be continued until the symptoms are judged unlikely 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 of oestrogen and may be associated with a better side–effect profile in women complaining of oestrogenic symptoms such as breast enlargement/mastalgia.

·  Women aged over 40 years can be advised that no contraceptive method is contraindicated by age alone and that that combined hormonal contraception can be used unless there are co-existing diseases or risk factors.

MHRA Drug Safety Update

Combined hormonal contraceptives: risk of venous thromboembolism—clarification of advice

Article date: March 2014

Summary

The February 2014 edition of Drug Safety Update included an article about combined hormonal contraceptives (CHCs) and risk of venous thromboembolism. This article refers to a letter that was sent to healthcare professionals through the Central Alerting System on Jan 22, 2014. Annexes 2–4 of the letter advise what contraception a woman should use instead of CHCs in the event of: major surgery; a period of prolonged immobilisation; or if she smokes and is older than 35 years.

The annexes recommend that a non-hormonal form of contraception should be used in these situations; however, they ought to have stated that a different form of contraception should be used. This clarified advice allows for use of progestogen-only contraception or non-hormonal contraception. Correct information is provided on the MHRA website.

Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON392873

MHRA Drug Safety Update

Combined hormonal contraceptives and venous thromboembolism: review confirms risk is small – consider risk factors and remain vigilant for signs and symptoms

Article date: February 2014

Summary

A review of the latest evidence on the risk of thromboembolism in association with combined hormonal contraceptives (CHCs) has concluded that:

• the risk of blood clots with all low-dose CHCs is small

• there is good evidence that the risk of venous thromboembolism (VTE) may vary between products, depending on the progestogen

• CHCs that contain levonorgestrel, norethisterone, or norgestimate have the lowest risk of VTE • the benefits of any CHC far outweigh the risk of serious side effects

• prescribers and women should be aware of the major risk factors for thromboembolism, and of the key signs and symptoms.

Link: http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON377649

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

·  The following products are considered interchangeable:

o  Cerelle®, Zelleta® and Cerazette®

·  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.

·  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.

·  The efficacy of the POP will be affected by enzyme-inducing drugs and an alternative contraceptive method should be sought.

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 and sometimes 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 only one year.

·  Nexplanon® is affected by concomitant use of enzyme-inducing drugs. An alternative contraceptive method should be sought.

·  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 their peak bone mass if other methods are unacceptable or unsuitable. Young women often find compliance with condoms or oral contraceptives difficult.

MHRA Drug Safety Update

St John’s wort: interaction with hormonal contraceptives, including implants—reduced contraceptive effect