Obstetrics, gynaecology, and urinary-tract disorders

7 Obstetrics, gynaecology, and urinary-tract disorders

7.1 Drugs used in obstetrics

7.1 7.1.1 Drugs used in obstetrics Prostaglandins and oxytocics 429

7.1.1.1 Ductus arteriosus

7.1.1 Prostaglandins and oxytocics

7.1.2 Mifepristone

7.1.2 Mifepristone

7.1.3 Myometrial relaxants

7.1.3 Myometrial relaxants

7.2 Treatment of vaginal and vulval conditions

Because of the complexity of dosage regimens in

7.2.1 Preparations for vaginal and obstetrics, in all cases detailed specialist literature vulval changes

should be consulted.

7.2.2 Vaginal and vulval infections

7.3 Contraceptives

7.3.1 Combined hormonal contra- ceptives

7.1.1 Prostaglandins and

7.3.2 Progestogen-only contraceptives 443

oxytocics

7.3.2.1 Oral progestogen-only contra- ceptives

Prostaglandins and oxytocics are used to induce abor-

7.3.2.2 Parenteral progestogen-only tion or induce or augment labour and to minimise blood

contraceptives loss from the placental site. They include oxytocin, 444 7

carbetocin, ergometrine, and the prostaglandins. All

7.3.2.3 Intra-uterine progestogen-only induce uterine contractions with varying degrees of

Obst

device

pain according to the strength of contractions induced.

7.3.3 Spermicidal contraceptives

etrics,

Induction of abortion Gemeprost, administered

7.3.4 Contraceptive devices

vaginally as pessaries is the preferred prostaglandin

7.3.5 Emergency contraception

for the medical induction of late therapeutic abortion.

gynaec

7.4 Gemeprost ripens the cervix before surgical abortion,

Drugs for genito-urinary disor-

particularly in primigravidas. The prostaglandin miso-

ders 449 prostol (section 7.1.2) is given by mouth or by vaginal ology

7.4.1 Drugs for urinary retention

administration to induce medical abortion [unlicensed

7.4.2 Drugs for urinary frequency, indication]; intravaginal use ripens the cervix before

enuresis, and incontinence surgical abortion [unlicensed indication]. Extra-amniotic and ,

dinoprostone is rarely used nowadays.

7.4.3 Drugs used in urological pain

Pre-treatment with mifepristone (section 7.1.2) can

urinary-tract

7.4.4 Bladder instillations and urolo- facilitate the process of medical abortion. It sensitises gical surgery

the uterus to subsequent administration of a prostaglan-

7.4.5 Drugs for erectile dysfunction

din and, therefore, abortion occurs in a shorter time and with a lower dose of prostaglandin.

This chapter also includes advice on the drug man-

Induction and augmentation of labour Dino- disor

agement of the following: prostone is available as vaginal tablets, pessaries and emergency contraception, p. 448

vaginal gels for the induction of labour. The intravenous

ders

induction of abortion, below solution is rarely used; it is associated with more side- induction and augmentation of labour, below

effects.

nocturnal enuresis, p. 454 Oxytocin (Syntocinon premature labour, p. 434 c ) is administered by slow intra- prevention and treatment of post-partum

venous infusion, using an infusion pump, to induce or haemorrhage, p. 430

augment labour, usually in conjunction with amniotomy. priapism, p. 456

Uterine activity must be monitored carefully and hyperstimulation avoided. Large doses of oxytocin

For hormonal therapy of gynaecological disorders see may result in excessive fluid retention. section 6.4.1 (including HRT), section 6.5.1 and sec-

Misoprostol is given orally or vaginally for the induc- tion 6.7.2.

tion of labour [unlicensed indication].

7.1.1 Prostaglandins and oxytocics BNF 57 NICE guidance

CARBOPROST

Induction of labour (updated July 2008) Indications postpartum haemorrhage due to uterine Available at www.nice.org.uk

atony in patients unresponsive to ergometrine and oxytocin

Cautions history of glaucoma or raised intra-ocular Prevention and treatment of haemorrhage Bleed-

pressure, asthma, hypertension, hypotension, anae- ing due to incomplete abortion can be controlled with ergometrine and oxytocin (Syntometrine c

mia, jaundice, diabetes, epilepsy; uterine scars;

excessive dosage may cause uterine rupture; inter- muscularly, the dose is adjusted according to the

) given intra-

actions: Appendix 1 (prostaglandins) patient’s condition and blood loss. This is commonly

Contra-indications untreated pelvic infection; car- used before surgical evacuation of the uterus, particu-

diac, renal, pulmonary, or hepatic disease larly when surgery is delayed. Oxytocin and ergo-

Side-effects ders nausea, vomiting and diarrhoea, hyper-

metrine combined are more effective in early pregnancy thermia and flushing, bronchospasm; less frequent than either drug alone.

disor effects include raised blood pressure, dyspnoea, and

Active management of the third stage of labour reduces pulmonary oedema; chills, headache, diaphoresis, the risk of postpartum haemorrhage; ergometrine

dizziness; cardiovascular collapse also reported; 500 micrograms with oxytocin 5 units (Syntometrine c erythema and pain at injection site reported

1 mL) is given by intramuscular injection on delivery of

Dose

the anterior shoulder or, at the latest, immediately after

By deep intramuscular injection , 250 micrograms given alone by intramuscular injection [unlicensed],

urinary-tract the baby is delivered. Alternatively, oxytocin may be

repeated if necessary at intervals of 1½ hours (in particularly if ergometrine is inappropriate (e.g. in pre-

severe cases the interval may be reduced but should , and eclampsia); oxytocin alone causes less nausea, vomi-

not be less than 15 minutes); total dose should not ting, and hypertension than when given with ergo-

exceed 2 mg (8 doses) Hemabate c ology (Pharmacia) metrine. A

Injection , carboprost as trometamol salt (trometha- aec In excessive uterine bleeding, any placental products remaining in the uterus should be removed. Oxytocic mine salt) 250 micrograms/mL, net price 1-mL amp =

gyn £18.20 (hosp. only)

drugs are used to treat postpartum haemorrhage caused

by uterine atony; treatment options are as follows: .

DINOPROSTONE etrics,

oxytocin 5–10 units by slow intravenous injection,

followed in severe cases by intravenous infusion of oxytocin 5–30 units in 500 mL infusion fluid at a Indications see notes above and under preparations

Obst

rate that controls uterine atony or

below Cautions history of asthma, glaucoma and raised

7 . ergometrine by intramuscular injection or

intra-ocular pressure; hypertension; history of epi- .

ergometrine 250–500 micrograms by intravenous lepsy; uterine scarring; monitor uterine activity and injection (use with caution—risk of hypertension) or

fetal status (particular care if history of uterine .

ergometrine 500 micrograms with oxytocin 5 units hypertony); uterine rupture; see also notes above; (Syntometrine c 1 mL) by intramuscular injection

monitor for disseminated intravascular coagulation Carboprost has an important role in severe postpartum

after parturition; risk factors for disseminated intra- haemorrhage unresponsive to ergometrine and oxy-

vascular coagulation; effect of oxytocin enhanced tocin.

(care needed in monitoring uterine activity when used in sequence); interactions: Appendix 1 (prosta-

Misoprostol [unlicensed] may be an alternative in post-

glandins)

partum haemorrhage unresponsive to ergometrine, oxy- Contra-indications active cardiac, pulmonary, renal tocin, and carboprost.

or hepatic disease; placenta praevia or unexplained vaginal bleeding during pregnancy, ruptured mem-

CARBETOCIN branes, major cephalopelvic disproportion or fetal

malpresentation, history of caesarean section or Indications prevention of uterine atony after caesar-

major uterine surgery, untreated pelvic infection, fetal ean section

distress, grand multiparas and multiple pregnancy, Cautions hyponatraemia; cardiovascular disease

history of difficult or traumatic delivery; avoid extra- (avoid if severe); migraine; asthma

amniotic route in cervicitis or vaginitis Contra-indications pre-eclampsia and eclampsia;

Side-effects nausea, vomiting, diarrhoea; other side- epilepsy; hepatic impairment; renal impairment

effects include uterine hypertonus, severe uterine Side-effects nausea, vomiting, abdominal pain,

contractions, pulmonary or amniotic fluid embolism, metallic taste; flushing, hypotension, chest pain; dys-

abruptio placenta, fetal distress, maternal hyper- pnoea; headache, tremor, dizziness; anaemia; back

tension, bronchospasm, rapid cervical dilation, fever, pain; pruritus; feeling of warmth, chills; tachycardia

backache; uterine hypercontractility with or without and sweating also reported

fetal bradycardia, low Apgar scores; cardiac arrest, Dose

uterine rupture, stillbirth or neonatal death also . By intravenous injection , a single dose of

reported; vaginal symptoms (warmth, irritation, pain); 100 micrograms, as soon as possible after delivery,

after intravenous administration—flushing, shivering, preferably before removal of placenta

headache, dizziness, temporary pyrexia and raised white blood cell count; disseminated intravascular

Pabal c (Ferring) TA coagulation reported; also local tissue reaction and Injection , carbetocin 100 micrograms/mL, net price

erythema after intravenous administration and pos- 1-mL amp = £18.00

sibility of infection after extra-amniotic administration

BNF 57

7.1.1 Prostaglandins and oxytocics 431

Dose . See under preparations, below

GEMEPROST

Important Do not confuse dose of Prostin E2 vaginal gel Indications see under Dose with that of Prostin E2 vaginal tablets—not bioequivalent.

Cautions obstructive airways disease, cardiovascular insufficiency, raised intra-ocular pressure, cervicitis or Propess c (Ferring) A vaginitis; interactions: Appendix 1 (prostaglandins)

Pessaries (within retrieval device), releasing dino- Important For warnings relating to use of gemeprost in a prostone approx. 10 mg over 24 hours; net price 1-

patient undergoing induction of abortion with mifepristone, pessary pack = £30.00

see under Mifepristone and Note below Dose by vagina , cervical ripening and induction of labour at

Contra-indications unexplained vaginal bleeding, term, 1 pessary (in retrieval device) inserted high into posterior

uterine scarring, placenta praevia fornix and removed when cervical ripening adequate; if oxytocin necessary, remove 30 minutes before oxytocin infusion; remove if

Side-effects vaginal bleeding and uterine pain; cervical ripening inadequate after 24 hours (dose not to be

nausea, vomiting, or diarrhoea; headache, muscle repeated)

weakness, dizziness, flushing, chills, backache, dys-

c Prostin E2 pnoea, chest pain, palpitation and mild pyrexia; (Pharmacia) A uterine rupture reported (most commonly in multi- Intravenous solution U, for dilution and use as an

paras or if history of uterine surgery or if given with infusion, dinoprostone 1 mg/mL, net price 0.75-mL

intravenous oxytocics); also reported severe hypo- amp = £8.52; 10 mg/mL, 0.5-mL amp = £18.40 (both

tension, coronary artery spasm and myocardial hosp. only; rarely used, consult product literature for

infarction

dose and indications)

Dose

Extra-amniotic solution U, dinoprostone 10 mg/ . By vagina , cervical ripening prior to first trimester mL. Net price 0.5-mL amp (with diluent) = £18.40

surgical abortion, 1 mg inserted into posterior fornix (hosp. only; less commonly used nowadays, consult

3 hours before surgery product literature for dose and indications)

. Second trimester abortion, 1 mg inserted into poster- Vaginal gel , dinoprostone 400 micrograms/mL, net

ior fornix every 3 hours for max. of 5 administrations; price 2.5 mL (1 mg) = £13.28; 800 micrograms/mL,

second course may begin 24 hours after start of

2.5 mL (2 mg) = £13.28 treatment (if treatment fails pregnancy should be Dose by vagina , induction of labour, inserted high into posterior

terminated by another method) fornix (avoid administration into cervical canal), 1 mg (unfavour- able primigravida 2 mg), followed after 6 hours by 1–2 mg if

. Second trimester intra-uterine death, 1 mg inserted required; max. [gel] 3 mg (unfavourable primigravida 4 mg)

into posterior fornix every 3 hours for max. of 5 Vaginal tablets , dinoprostone 3 mg. Net price 8-

administrations only; monitor for coagulopathy vaginal tab pack = £106.23

Note If used in combination with mifepristone, carefully moni- Dose by vagina , induction of labour, inserted high into posterior

tor blood pressure and pulse for 3 hours fornix, 3 mg, followed after 6–8 hours by 3 mg if labour is not

A Note Prostin E2 Vaginal Gel and Vaginal Tablets are not bioequivalent

Gemeprost (Sanofi-Aventis) established; max. 6 mg [vaginal tablets]

Pessaries , gemeprost 1 mg. Net price 5-pessary pack

Obst

etrics, ERGOMETRINE MALEATE

OXYTOCIN

Indications see under Dose and notes above Indications see notes above

Cautions induction or enhancement of labour—pre- Cautions cardiac disease; hypertension; multiple

sence of borderline cephalopelvic disproportion

gynaec

pregnancy; acute porphyria (section 9.8.2); hepatic (avoid if significant), secondary uterine inertia, mild or impairment (avoid if severe; Appendix 2); renal

moderate pregnancy-induced hypertension or cardiac impairment (avoid if severe; Appendix 3); interac-

disease, women over 35 years or with history of

ology

tions: Appendix 1 (ergot alkaloids) lower-uterine segment caesarean section (see also Contra-indications

under Contra-indications below); risk factors for dis- induction of labour, first and sec- ond stages of labour, vascular disease, severe cardiac

and ,

seminated intravascular coagulation; monitor for dis-

disease, sepsis, severe hypertension, eclampsia seminated intravascular coagulation after parturition; avoid large infusion volumes and restrict fluid intake

urinary-tract

Side-effects nausea, vomiting, headache, dizziness, by mouth (risk of hyponatraemia and water-intoxica- tinnitus, abdominal pain, chest pain, palpitation, dys-

tion—see also Appendix 6); effects enhanced by pnoea, bradycardia, transient hypertension, vasocon-

concomitant prostaglandins (very careful monitoring striction; stroke, myocardial infarction and pulmonary

of uterine activity); caudal block anaesthesia (may oedema also reported

enhance hypertensive effects of sympathomimetic Dose

disor

vasopressors); see also interactions: Appendix 1

. See notes above

(oxytocin) Contra-indications hypertonic uterine contractions,

ders

Ergometrine (Non-proprietary) A fetal distress; any condition where spontaneous Injection , ergometrine maleate 500 micrograms/mL.

labour or vaginal delivery inadvisable; avoid pro- Net price 1-mL amp = 60p

longed administration in oxytocin-resistant uterine inertia, severe pre-eclamptic toxaemia, or severe

With oxytocin cardiovascular disease Syntometrine c (Alliance) A Side-effects nausea, vomiting; arrhythmia; headache;

Injection , ergometrine maleate 500 micrograms, rarely disseminated intravascular coagulation, rash, oxytocin 5 units/mL. Net price 1-mL amp = £1.31

and anaphylactoid reactions (with dyspnoea, hypo- Dose by intramuscular injection , 1 mL; by intravenous injection ,

tension, or shock); uterine spasm (may occur at low no longer recommended

doses), uterine hyperstimulation (usually with exces-

7.1.1 Prostaglandins and oxytocics BNF 57 sive doses—may cause fetal distress, asphyxia, and

genital heart defects, prior to corrective surgery in death, or may lead to hypertonicity, tetanic contrac-

centres where intensive care is immediately available. tions, soft-tissue damage or uterine rupture); water

See BNF for Children (section 2.14) for further advice on intoxication and hyponatraemia associated with high

maintaining the patency of the ductus arteriosus. doses with large infusion volumes of electrolyte-free fluid (see also under Dose below); placental abruption and amniotic fluid embolism also reported on over-

ALPROSTADIL

dose Indications congenital heart defects in neonates prior Dose

to corrective surgery; erectile dysfunction (section . Induction of labour for medical reasons or stimulation

of labour in hypotonic uterine inertia, by intravenous Cautions see notes above; history of haemorrhage, infusion (not to be started for at least 6 hours after

avoid in hyaline membrane disease, monitor arterial

ders

administration of vaginal prostaglandin), initially pressure; interactions: Appendix 1 (prostaglandins) 0.001–0.004 units/minute, increased at intervals of

Side-effects apnoea (particularly in neonates under

disor

at least 30 minutes until a maximum of 3–4 con-

2 kg), flushing, bradycardia, hypotension, tachycardia, tractions occur every 10 minutes (0.01 units/minute

cardiac arrest, oedema, diarrhoea, fever, convulsions, is often adequate) up to max. 0.02 units/minute;

disseminated intravascular coagulation, hypokal- max. 5 units in 1 day (may be repeated next day

aemia; cortical proliferation of long bones and weak- starting again at 0.001–0.004 units/minute) Important

ening of the wall of the ductus arteriosus and of Careful monitoring of fetal heart rate and uterine motility essential for dose titration (avoid intravenous

pulmonary artery may follow prolonged use; gastric-

urinary-tract

injection during labour); discontinue immediately in uterine outlet obstruction reported hyperactivity or fetal distress

Dose

and , . Caesarean section, by slow intravenous injection . By intravenous infusion , initially 10 nanograms/kg/ immediately after delivery, 5 units

minute, adjusted according to response in steps of . Prevention of postpartum haemorrhage, after delivery

5–10 nanograms/kg/minute; max. 100 nanograms/

ology

of placenta, by slow intravenous injection , 5 units (if kg/minute (but associated with increased side-

aec

infusion used for induction or enhancement of

effects)

labour, increase rate during third stage and for next Note Alprostadil doses in BNF may differ from those in

gyn

few hours).

product literature

Important Avoid rapid intravenous injection (may transi- ently reduce blood pressure) c Prostin VR (Pharmacia) A

etrics,

Note Can be given in a dose of 10 units by intramuscular Intravenous solution , alprostadil 500 micrograms/ injection [unlicensed route] instead of oxytocin with ergo-

mL in alcohol. For dilution and use as an infusion. Net metrine (Syntometrine ), see notes above

Obst price 1-mL amp = £75.19 (hosp. only)

. Treatment of postpartum haemorrhage, by slow

7 intravenous injection , 5–10 units, followed in severe cases by intravenous infusion of 5–30 units in

Closure of ductus arteriosus

500 mL infusion fluid at a rate sufficient to control uterine atony

Indometacin (indomethacin) is used to close a patent Important Avoid rapid intravenous injection (may transi-

ductus arteriosus in premature babies, probably by ently reduce blood pressure); prolonged administration, see

inhibiting prostaglandin synthesis. See BNF for Children warning below

(section 2.14) for further advice on closure of the ductus . Incomplete, inevitable, or missed abortion, by slow

arteriosus.

intravenous injection , 5 units followed if necessary by intravenous infusion , 0.02–0.04 units/minute or faster

INDOMETACIN

Important Prolonged intravenous administration at high doses (Indomethacin) with large volume of fluid (as possible in inevitable or missed abortion or postpartum haemorrhage) may cause water

Indications patent ductus arteriosus in premature intoxication with hyponatraemia. To avoid: use electrolyte-

babies (under specialist supervision in neonatal containing diluent (i.e. not glucose), increase oxytocin con- centration to reduce fluid, restrict fluid intake by mouth;

intensive care unit); uncomplicated premature labour monitor fluid and electrolytes.

[unlicensed indication] (section 7.1.3); rheumatoid Note Oxytocin doses in the BNF may differ from those in the

disease (section 10.1.1) product literature

Cautions may mask symptoms of infection; may Syntocinon c (Alliance) A reduce urine output by 50% or more (monitor care-

Injection , oxytocin, net price 5 units/mL, 1-mL amp fully—see also under Anuria or Oliguria, below) and = 89p; 10 units/mL, 1-mL amp = £1.01

precipitate renal impairment especially if extracellular volume depleted, heart failure, sepsis, or hepatic

With ergometrine impairment, or if receiving nephrotoxic drugs; may See Syntometrine c , p. 431

induce hyponatraemia; monitor renal function and electrolytes; inhibition of platelet aggregation (moni- tor for bleeding); interactions: Appendix 1 (NSAIDs) Anuria or oliguria If anuria or marked oliguria (urinary

7.1.1.1 Ductus arteriosus

output less than 0.6 mL/kg/hour) at time of scheduled second or third dose, delay until renal function returns to normal

Contra-indications untreated infection, bleeding

Maintenance of patency

(especially with active intracranial haemorrhage or gastro-intestinal bleeding); thrombocytopenia, coa-

Alprostadil (prostaglandin E ) is used to maintain gulation defects, necrotising enterocolitis, renal patency of the ductus arteriosus in neonates with con-

impairment

BNF 57

7.1.2 Mifepristone 433

Side-effects haemorrhagic, renal, gastro-intestinal (section 9.8.2); hepatic impairment; renal impairment; (including necrotising enterocolitis), metabolic, and

breast-feeding (Appendix 5) coagulation disorders; pulmonary hypertension,

Side-effects gastro-intestinal cramps; uterine con- intracranial bleeding, fluid retention, and exacerba-

tractions, vaginal bleeding (sometimes severe) may tion of infection

occur between administration of mifepristone and Dose

surgery (and rarely abortion may occur before sur- . By intravenous injection , over 20–30 minutes (using

gery); less commonly hypersensitivity reactions

a suitable syringe driver), 3 doses at intervals of 12– including rash and urticaria; rarely hypotension,

24 hours (provided urine output remains adequate), malaise, headache, fever, hot flushes, dizziness, and NEONATE under 48 hours, 200 micrograms/kg then

chills; infections (including toxic shock syndrome) 100 micrograms/kg then 100 micrograms/kg; NEO-

also reported

NATE 2–7 days, 200 micrograms/kg then 200 micr-

Dose

ograms/kg then 200 micrograms/kg; NEONATE over . Medical termination of intra-uterine pregnancy of up

7 days, 200 micrograms/kg then 250 micrograms/ to 49 days gestation, by mouth , mifepristone 600 mg kg then 250 micrograms/kg; solution prepared with

as a single dose under medical supervision followed 1–2 mL sodium chloride 0.9% or water for injections

36–48 hours later (unless abortion already com- (not glucose and no preservatives) If ductus arteriosus reopens a second course of 3 injections

plete) by gemeprost 1 mg by vagina or misoprostol may be given 48 hours after first course

400 micrograms by mouth [unlicensed]; alternative

c regimen, mifepristone 200 mg by mouth Indocid PDA as a single (IDIS) A dose followed 36–48 hours later (unless abortion Injection , powder for reconstitution, indometacin (as

already complete) by gemeprost 1 mg by vagina ; observe for at least 3 hours (or until bleeding or pain

(hosp. only) at acceptable level); follow-up visit within 2 weeks to verify complete expulsion (if treatment fails essential that pregnancy be terminated by another method) and to assess vaginal bleeding