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