Capsules, ivory, metyrapone 250 mg, net price 100-cap pack = £363.66. Label: 21, counselling, driving
6.7.4 Somatomedins
Somatomedins are a group of polypeptide hormones structurally related to insulin and commonly known as insulin-like growth factors (IGFs). Mecasermin, a human insulin-like growth factor-I (rhIGF-I), is the principal mediator of the somatotropic effects of human growth hormone and is used to treat growth failure in children and adolescents with severe primary insulin-like growth factor-I deficiency.
MECASERMIN
(Recombinant human insulin-like growth factor-I; rhIGF-I)
Indications see notes above
Cautions correct hypothyroidism before initiating treatment; diabetes mellitus (adjustment of antidiabetic therapy may be necessary), monitor ECG before and on termination of treatment (and during treatment if ECG abnormal), papilloedema (see under Side-effects), monitor for disorders of the epiphysis of the hip (monitor for limping), monitor for signs of tonsillar hypertrophy (snoring, sleep apnoea, and chronic middle ear effusions)
Contra-indications evidence of tumour activity (discontinue treatment)
Pregnancy avoid unless essential; contraception advised in women of child-bearing potential
Breast-feeding avoid
Side-effects headache, funduscopy for papilloedema recommended if severe or recurrent headache, visual problems, nausea and vomiting occur — if papilloedema confirmed consider benign intracranial hypertension (rare cases reported); cardiomegaly, ventricular hypertrophy, tachycardia; convulsions, sleep apnoea, night terrors, dizziness, nervousness; tonsillar hypertrophy (see Cautions above); hypoglycaemia (especially in first month, and in younger children), hyperglycaemia, gynaecomastia; arthralgia, myalgia; visual disturbance, impaired hearing; antibody formation; injection-site reactions (rotate site)
Dose
By subcutaneous injection, ADOLESCENT and CHILD over 2 years, initially 40 micrograms/kg twice daily for 1 week, if tolerated increase dose in steps of 40 micrograms/kg to max. 120 micrograms/kg twice daily; discontinue if no response within 1 year
Counselling Dose should be administered just before or after food; do not increase dose if a dose is missed
Note Reduce dose if hypoglycaemia occurs despite adequate food intake; withhold injection if patient unable to eat
Increlex® (Ipsen) 
Injection, mecasermin 10 mg/mL, net price 4-mL vial = £605.00. Counselling, administration
Excipients include benzyl alcohol (avoid in neonates, see Excipients)
7 Obstetrics, gynaecology, and urinary-tract disorders
This chapter also includes advice on the drug management of the following:
For hormonal therapy of gynaecological disorders see section 6.4.1 (including HRT), section 6.5.1 and section 6.7.2.
7.1 Drugs used in obstetrics
Because of the complexity of dosage regimens in obstetrics, in all cases detailed specialist literature should be consulted.
7.1.1 Prostaglandins and oxytocics
Prostaglandins and oxytocics are used to induce abortion or induce or augment labour and to minimise blood loss from the placental site. They include oxytocin, carbetocin, ergometrine, and the prostaglandins. All induce uterine contractions with varying degrees of pain according to the strength of contractions induced.
Induction of abortion Gemeprost, a prostaglandin administered vaginally as pessaries, is suitable for the medical induction of late therapeutic abortion; gemeprost is also used to ripen the cervix before surgical abortion, particularly in primigravidas. The prostaglandin misoprostol (section 7.1.2) is given by mouth, buccally, sublingually, or vaginally, to induce medical abortion [unlicensed indication]; intravaginal use ripens the cervix before surgical abortion [unlicensed indication]. Extra-amniotic dinoprostone is rarely used nowadays.
Pre-treatment with mifepristone (section 7.1.2) can facilitate the process of medical abortion. It sensitises the uterus to subsequent administration of a prostaglandin and, therefore, abortion occurs in a shorter time and with a lower dose of prostaglandin.
Induction and augmentation of labour Dinoprostone is available as vaginal tablets, pessaries and vaginal gels for the induction of labour. The intravenous solution is rarely used; it is associated with more side-effects.
Oxytocin (Syntocinon®) is administered by slow intravenous infusion, using an infusion pump, to induce or augment labour, usually in conjunction with amniotomy. Uterine activity must be monitored carefully and hyperstimulation avoided. Large doses of oxytocin may result in excessive fluid retention.
Misoprostol is given orally or vaginally for the induction of labour [unlicensed indication].
Prevention and treatment of haemorrhage Bleeding due to incomplete miscarriage or abortion can be controlled with ergometrine and oxytocin (Syntometrine®) given intramuscularly, the dose is adjusted according to the patient’s condition and blood loss. This is commonly used before surgical evacuation of the uterus, particularly when surgery is delayed. Oxytocin and ergometrine combined are more effective in early pregnancy than either drug alone.
Active management of the third stage of labour reduces the risk of postpartum haemorrhage; oxytocin is given by intramuscular injection [unlicensed] on delivery of the anterior shoulder or, at the latest, immediately after the baby is delivered. Alternatively, ergometrine 500 micrograms with oxytocin 5 units (Syntometrine® 1 mL) can be given by intramuscular injection in the absence of hypertension; oxytocin alone causes less nausea, vomiting, and hypertension than when given with ergometrine.
In excessive uterine bleeding, any placental products remaining in the uterus should be removed. Oxytocic drugs are used to treat postpartum haemorrhage caused by uterine atony; treatment options are as follows:
oxytocin 5 units by slow intravenous injection (dose may be repeated), followed in severe cases by intravenous infusion of oxytocin 40 units in 500 mL infusion fluid (prolonged administration — see Appendix 4) at a rate that controls uterine atony or
ergometrine 250–500 micrograms by intramuscular injection or
ergometrine 250–500 micrograms by slow intravenous injection (use with caution — risk of hypertension) or
ergometrine 500 micrograms with oxytocin 5 units (Syntometrine® 1 mL) by intramuscular injection
Carboprost has an important role in severe postpartum haemorrhage unresponsive to ergometrine and oxytocin.
Misoprostol [unlicensed] can be used in postpartum haemorrhage when oxytocin, ergometrine, and carboprost are not available or are inappropriate.
CARBETOCIN
Indications prevention of uterine atony after caesarean section
Cautions hyponatraemia; cardiovascular disease (avoid if severe); migraine; asthma
Contra-indications pre-eclampsia and eclampsia; epilepsy
Hepatic impairment manufacturer advises avoid
Renal impairment manufacturer advises avoid
Side-effects nausea, vomiting, abdominal pain, metallic taste; flushing, hypotension, chest pain; dyspnoea; headache, tremor, dizziness; anaemia; back pain; pruritus; feeling of warmth, chills; tachycardia and sweating also reported
Dose
By slow intravenous injection over 1 minute, a single dose of 100 micrograms, as soon as possible after delivery, preferably before removal of placenta
CARBOPROST
Indications postpartum haemorrhage due to uterine atony in patients unresponsive to ergometrine and oxytocin
Cautions history of glaucoma or raised intra-ocular pressure, asthma, hypertension, hypotension, anaemia, jaundice, diabetes, epilepsy; uterine scars; excessive dosage may cause uterine rupture; interactions: Appendix 1 (prostaglandins)
Contra-indications untreated pelvic infection; cardiac or pulmonary disease
Hepatic impairment manufacturer advises avoid
Renal impairment manufacturer advises avoid
Side-effects nausea, vomiting and diarrhoea, hyperthermia and flushing, bronchospasm; less frequent effects include raised blood pressure, dyspnoea, and pulmonary oedema; chills, headache, diaphoresis, dizziness; cardiovascular collapse also reported; erythema and pain at injection site reported
Dose
By deep intramuscular injection, 250 micrograms repeated if necessary at intervals of not less than 15 minutes; total dose should not exceed 2 mg (8 doses)
DINOPROSTONE
Indications see notes above and under preparations below
Cautions history of asthma, glaucoma and raised intra-ocular pressure; hypertension; history of epilepsy; uterine scarring; monitor uterine activity and fetal status (particular care if history of uterine hypertony); uterine rupture; see also notes above; monitor for disseminated intravascular coagulation after parturition; risk factors for disseminated intravascular coagulation; effect of oxytocin enhanced (care needed in monitoring uterine activity when used in sequence); interactions: Appendix 1 (prostaglandins)
Contra-indications active cardiac, or pulmonary disease; placenta praevia or unexplained vaginal bleeding during pregnancy, ruptured membranes, major cephalopelvic disproportion or fetal malpresentation, history of caesarean section or major uterine surgery, untreated pelvic infection, fetal distress, grand multiparas and multiple pregnancy, history of difficult or traumatic delivery; avoid extra-amniotic route in cervicitis or vaginitis
Hepatic impairment manufacturers advise avoid
Renal impairment manufacturers advise avoid
Side-effects nausea, vomiting, diarrhoea; other side-effects include uterine hypertonus, severe uterine contractions, pulmonary or amniotic fluid embolism, abruptio placenta, fetal distress, maternal hypertension, bronchospasm, rapid cervical dilation, fever, backache; uterine hypercontractility with or without fetal bradycardia, low Apgar scores; cardiac arrest, uterine rupture, stillbirth or neonatal death also reported; vaginal symptoms (warmth, irritation, pain); after intravenous administration — flushing, shivering, headache, dizziness, temporary pyrexia and raised white blood cell count; disseminated intravascular coagulation reported; also local tissue reaction and erythema after intravenous administration and possibility of infection after extra-amniotic administration
Dose
See under preparations, below
Important Do not confuse dose of Prostin E2® vaginal gel with that of Prostin E2® vaginal tablets — not bioequivalent.
Propess® (Ferring) 
Pessaries (within retrieval device), releasing dinoprostone approx. 10 mg over 24 hours;net price 1-pessary pack = £30.00
Dose by vagina, cervical ripening and induction of labour at term, 1 pessary (in retrieval device) inserted high into posterior fornix and removed when cervical ripening adequate; if oxytocin necessary, remove 30 minutes before oxytocin infusion; remove if cervical ripening inadequate after 24 hours (dose not to be repeated)
Prostin E2® (Pharmacia) 
Intravenous solution 
, for dilution and use as an infusion, dinoprostone 1 mg/mL, net price 0.75-mL amp = £8.52; 10 mg/mL, 0.5-mL amp = £18.40 (both hosp. only; rarely used, consult product literature for dose and indications)
Extra-amniotic solution 
, dinoprostone 10 mg/mL, net price 0.5-mL amp (with diluent) = £18.40 (hosp. only; less commonly used nowadays, consult product literature for dose and indications)
Vaginal gel, dinoprostone 400 micrograms/mL, net price 2.5 mL (1 mg) = £13.28; 800 micrograms/mL, 2.5 mL (2 mg) = £13.28
Dose by vagina, induction of labour, inserted high into posterior fornix (avoid administration into cervical canal), 1 mg (unfavourable primigravida 2 mg), followed after 6 hours by 1–2 mg if required; max. [gel] 3 mg (unfavourable primigravida 4 mg)
Vaginal tablets, dinoprostone 3 mg, net price 8-vaginal tab pack = £106.23
Dose by vagina, induction of labour, inserted high into posterior fornix, 3 mg, followed after 6–8 hours by 3 mg if labour is not established; max. 6 mg [vaginal tablets]
Note Prostin E2 Vaginal Gel and Vaginal Tablets are not bioequivalent
ERGOMETRINE MALEATE
Indications see notes above
Cautions cardiac disease; hypertension; multiple pregnancy; acute porphyria (section 9.8.2); interactions: Appendix 1 (ergot alkaloids)
Contra-indications induction of labour, first and second stages of labour, vascular disease, severe cardiac disease, sepsis, severe hypertension, eclampsia
Hepatic impairment manufacturer advises caution in mild or moderate impairment and avoid in severe impairment
Renal impairment manufacturer advises caution in mild or moderate impairment and avoid in severe impairment
Side-effects nausea, vomiting, abdominal pain; chest pain, arrhythmias (including bradycardia), palpitation, hypertension, vasoconstriction; dyspnoea, pulmonary oedema; headache, dizziness; tinnitus; rash; very rarely myocardial infarction
Dose
See notes above
Ergometrine (Non-proprietary) 
Injection, ergometrine maleate 500 micrograms/mL, net price 1-mL amp = 93p
GEMEPROST
Indications see under Dose
Cautions obstructive airways disease, cardiovascular insufficiency, raised intra-ocular pressure, cervicitis or vaginitis; interactions: Appendix 1 (prostaglandins)
Important For warnings relating to use of gemeprost in a patient undergoing induction of abortion with mifepristone, see under Mifepristone and Note below
Contra-indications unexplained vaginal bleeding, uterine scarring, placenta praevia
Renal impairment manufacturer advises avoid
Side-effects vaginal bleeding and uterine pain; nausea, vomiting, or diarrhoea; headache, muscle weakness, dizziness, flushing, chills, backache, dyspnoea, chest pain, palpitation and mild pyrexia; uterine rupture reported (most commonly in multiparas or if history of uterine surgery or if given with intravenous oxytocics); also reported severe hypotension, coronary artery spasm and myocardial infarction
Dose
By vagina, cervical ripening prior to first trimester surgical abortion, 1 mg inserted into posterior fornix 3 hours before surgery
Second trimester abortion, 1 mg inserted into posterior fornix every 3 hours for max. of 5 administrations; second course may begin 24 hours after start of treatment (if treatment fails pregnancy should be terminated by another method)
Second trimester intra-uterine death, 1 mg inserted into posterior fornix every 3 hours for max. of 5 administrations only; monitor for coagulopathy
Note If used in combination with mifepristone, carefully monitor blood pressure and pulse for 3 hours
OXYTOCIN
Indications see under Dose and notes above
Cautions induction or enhancement of labour — presence of borderline cephalopelvic disproportion (avoid if significant), secondary uterine inertia, mild or moderate pregnancy-induced hypertension or cardiac disease, women over 35 years or with history of lower-uterine segment caesarean section (see also under Contra-indications below); risk factors for disseminated intravascular coagulation; monitor for disseminated intravascular coagulation after parturition; avoid large infusion volumes and restrict fluid intake by mouth (risk of hyponatraemia and water-intoxication — see also Appendix 4); effects enhanced by concomitant prostaglandins (very careful monitoring of uterine activity); caudal block anaesthesia (may enhance hypertensive effects of sympathomimetic vasopressors); see also interactions: Appendix 1 (oxytocin)
Contra-indications hypertonic uterine contractions, fetal distress; any condition where spontaneous labour or vaginal delivery inadvisable; avoid prolonged administration in oxytocin-resistant uterine inertia, severe pre-eclamptic toxaemia, or severe cardiovascular disease
Side-effects nausea, vomiting; arrhythmia; headache; rarely disseminated intravascular coagulation, rash, and anaphylactoid reactions (with dyspnoea, hypotension, or shock); uterine spasm (may occur at low doses), uterine hyperstimulation (usually with excessive doses — may cause fetal distress, asphyxia, and death, or may lead to hypertonicity, tetanic contractions, soft-tissue damage or uterine rupture); water intoxication and hyponatraemia associated with high doses with large infusion volumes of electrolyte-free fluid (see also under Dose below); placental abruption and amniotic fluid embolism also reported on overdose
Dose
Induction of labour for medical reasons or stimulation of labour in hypotonic uterine inertia, by intravenous infusion (not to be started for at least 6 hours after administration of vaginal prostaglandin), initially 0.001–0.004 units/minute, increased at intervals of at least 30 minutes until a maximum of 3–4 contractions occur every 10 minutes (0.01 units/minute is often adequate) up to max. 0.02 units/minute; if regular contractions not established after total of 5 units stop induction attempt (may be repeated next day starting again at 0.001–0.004 units/minute)
Important Careful monitoring of fetal heart rate and uterine motility essential for dose titration (avoid intravenous injection during labour); discontinue immediately in uterine hyperactivity or fetal distress
Caesarean section, by slow intravenous injection immediately after delivery, 5 units
Prevention of postpartum haemorrhage, after delivery of placenta, by slow intravenous injection, 5 units (if infusion used for induction or enhancement of labour, increase rate during third stage and for next few hours).
Important Avoid rapid intravenous injection (may transiently reduce blood pressure)
Note Can be given in a dose of 10 units by intramuscular injection [unlicensed route] instead of oxytocin with ergometrine (Syntometrine®), see notes above
Treatment of postpartum haemorrhage, by slow intravenous injection, 5 units (dose may be repeated), followed in severe cases by intravenous infusion of 40 units in 500 mL infusion fluid at a rate sufficient to control uterine atony
Important Avoid rapid intravenous injection (may transiently reduce blood pressure); prolonged administration, see warning below
Incomplete, inevitable, or missed miscarriage, by slow intravenous injection, 5 units followed if necessary by intravenous infusion, 0.02–0.04 units/minute or faster
Important Prolonged intravenous administration at high doses with large volume of fluid (which is possible in inevitable or missed miscarriage or postpartum haemorrhage) may cause water intoxication with hyponatraemia. To avoid: use electrolyte-containing diluent (i.e. not glucose), increase oxytocin concentration to reduce fluid, restrict fluid intake by mouth; monitor fluid and electrolytes.
Note Oxytocin doses in the BNF may differ from those in the product literature
Syntocinon® (Novartis) 
Injection, oxytocin, net price 5 units/mL, 1-mL amp = 80p; 10 units/mL, 1-mL amp = 91p
7.1.1.1 Drugs affecting the ductus arteriosus
This section is not included in the BNF. For the management of ductus arteriosus, see BNF for Children section 2.14.
7.1.2 Mifepristone
Mifepristone, an antiprogestogenic steroid, sensitises the myometrium to prostaglandin-induced contractions and ripens the cervix. For termination of pregnancy, a single dose of mifepristone is followed by administration of a prostaglandin (gemeprost or misoprostol [unlicensed]). Guidelines of the Royal College of Obstetricians and Gynaecologists (November 2011) include the following [unlicensed] regimens for inducing medical abortion:
For gestation up to 49 days, mifepristone 200 mg by mouth followed 24–48 hours later by misoprostol 400 micrograms by mouth
For gestation at 50–63 days, mifepristone 200 mg by mouth followed 24–48 hours later by misoprostol 800 micrograms vaginally, buccally, or sublingually; if abortion has not occurred 4 hours after misoprostol dose, a further dose of misoprostol 400 micrograms may be given vaginally or by mouth
For gestation between 9 and 13 weeks, mifepristone 200 mg by mouth followed 36–48 hours later by misoprostol 800 micrograms vaginally, followed if necessary by a maximum of 4 further doses at 3-hourly intervals of misoprostol 400 micrograms vaginally or by mouth
For gestation between 13 and 24 weeks, mifepristone 200 mg by mouth followed 36–48 hours later by misoprostol 800 micrograms vaginally, followed if necessary by a maximum of 4 further doses at 3-hourly intervals of misoprostol 400 micrograms vaginally or by mouth; if abortion has not occurred 3 hours after the last dose of misoprostol, a further dose of mifepristone may be given, and misoprostol may be recommenced 12 hours later
MIFEPRISTONE
Indications see under dose
Cautions asthma (avoid if severe and uncontrolled); haemorrhagic disorders and anticoagulant therapy; prosthetic heart valve or history of endocarditis (see section 5.1 table 2); risk factors for or existing cardiovascular disease; adrenal suppression (may require corticosteroid); interactions: Appendix 1 (mifepristone)
Important For warnings relating to use of gemeprost in a patient undergoing induction of abortion with mifepristone, see under Gemeprost
Contra-indications uncontrolled severe asthma; suspected ectopic pregnancy (use other specific means of termination); chronic adrenal failure; acute porphyria (section 9.8.2)
Hepatic impairment manufacturer advises avoid
Renal impairment manufacturer advises avoid
Side-effects gastro-intestinal cramps; uterine contractions, vaginal bleeding (sometimes severe) may occur between administration of mifepristone and surgery (and rarely abortion may occur before surgery); less commonly hypersensitivity reactions including rash and urticaria; rarely hypotension, malaise, headache, fever, hot flushes, dizziness, and chills; infections (including toxic shock syndrome) also reported
Dose
Medical termination of intra-uterine pregnancy of up to 49 days gestation, by mouth, mifepristone 600 mg as a single dose under medical supervision followed 36–48 hours later (unless abortion already complete) by gemeprost 1 mg by vagina or misoprostol 400 micrograms by mouth [unlicensed]; alternative regimen, mifepristone 200 mg by mouth as a single dose followed 36–48 hours later (unless abortion already complete) by gemeprost 1 mg by vagina; observe for at least 3 hours (or until bleeding or pain at acceptable level); follow-up visit within 2 weeks to verify complete expulsion and to assess vaginal bleeding
Medical termination of intra-uterine pregnancy of 50–63 days gestation, by mouth, mifepristone 600 mg (200 mg also effective) as a single dose under medical supervision, followed 36–48 hours later (unless abortion already complete) by gemeprost 1 mg by vagina; observe for at least 3 hours (or until bleeding or pain at acceptable level); follow-up visit within 2 weeks to verify complete expulsion and to assess vaginal bleeding
Cervical ripening before mechanical cervical dilatation for termination of pregnancy of up to 84 days gestation, by mouth, mifepristone 200 mg as a single dose under medical supervision 36–48 hours before procedure
Termination of pregnancy of 13–24 weeks gestation (in combination with a prostaglandin), by mouth, mifepristone 600 mg (200 mg may be effective) as a single dose under medical supervision followed 36–48 hours later by gemeprost 1 mg by vagina every 3 hours up to max. 5 mg or misoprostol (see above [unlicensed]); if abortion does not occur, 24 hours after start of treatment repeat course of gemeprost 1 mg by vagina up to max. 5 mg; follow-up visit after appropriate interval to assess vaginal bleeding recommended
Note Careful monitoring of blood pressure and pulse essential for 3 hours after administration of gemeprost pessary (risk of profound hypotension)
Labour induction in fetal death in utero where prostaglandin or oxytocin inappropriate, by mouth, mifepristone 600 mg daily as a single dose for 2 days under medical supervision; if labour not started within 72 hours of first dose, another method should be used
7.1.3 Myometrial relaxants
Tocolytic drugs postpone premature labour and they are used with the aim of reducing harm to the child. However, there is no satisfactory evidence that the use of these drugs reduces mortality. The greatest benefit is gained by using the delay to administer corticosteroid therapy or to implement other measures which improve perinatal health (including transfer to a unit with neonatal intensive care facility).
The oxytocin receptor antagonist, atosiban, is licensed for the inhibition of uncomplicated premature labour between 24 and 33 weeks of gestation. Atosiban may be preferable to a beta2 agonist because it has fewer side-effects.
The dihydropyridine calcium-channel blocker nifedipine (section 2.6.2) also has fewer side-effects than a beta2 agonist. Nifedipine [unlicensed indication] can be given initially in a dose of 20 mg followed by 10–20 mg 3–4 times daily adjusted according to uterine activity.
The beta2 agonists salbutamol and terbutaline are licensed for inhibiting uncomplicated premature labour between 22 and 37 weeks of gestation to permit a delay in delivery of up to 48 hours. Use of high-dose short-acting beta2 agonists in obstetric indications has been associated with serious, sometimes fatal cardiovascular events in the mother and fetus, particularly when used for a prolonged period of time. Oral therapy is no longer recommended and parenteral therapy should be restricted to a maximum duration of 48 hours, given under the supervision of a specialist, and with close monitoring (see under Beta2 agonists).
Indometacin (section 10.1.1), a cyclo-oxygenase inhibitor, also inhibits labour [unlicensed indication] and it can be useful in situations where a beta2 agonist is not appropriate; however, there are concerns about neonatal complications such as transient impairment of renal function and premature closure of ductus arteriosus.
Atosiban
ATOSIBAN
Indications uncomplicated premature labour (see notes above)
Cautions monitor blood loss after delivery; intra-uterine growth restriction; abnormal placental site
Contra-indications eclampsia and severe pre-eclampsia, intra-uterine infection, intra-uterine fetal death, antepartum haemorrhage (requiring immediate delivery), placenta praevia, abruptio placenta, intra-uterine growth restriction with abnormal fetal heart rate, premature rupture of membranes after 30 weeks’ gestation
Hepatic impairment no information available
Renal impairment no information available
Side-effects nausea, vomiting, tachycardia, hypotension, headache, dizziness, hot flushes, hyperglycaemia, injection-site reaction; less commonly pruritus, rash, fever, insomnia
Dose
By intravenous injection, initially 6.75 mg over 1 minute, then by intravenous infusion 18 mg/hour for 3 hours, then 6 mg/hour for up to 45 hours; max. duration of treatment 48 hours
Beta2 agonists
Cautions Beta agonists should be used with caution in patients with hypertension, mild to moderate pre-eclampsia, hyperthyroidism, and hypokalaemia (particular risk with potassium-depleting diuretics — see also Hypokalaemia). Patients with suspected cardiovascular disease should be assessed by a cardiologist before initiating therapy — see also Contra-indications, below). It is important to monitor blood pressure, pulse rate (should not exceed 120 beats per minute), ECG (discontinue treatment if signs of myocardial ischaemia develop), blood glucose and lactate concentrations, and the patient’s fluid and electrolyte status (avoid over-hydration — discontinue drug immediately and initiate diuretic therapy if pulmonary oedema occurs). Beta2 agonists should also be used with caution in diabetes — monitor blood glucose (risk of hyperglycaemia and ketoacidosis, especially with intravenous beta2 agonists).
Contra-indications Beta2 agonists are contra-indicated in patients with a history of cardiac disease and in patients with significant risk factors for myocardial ischaemia; they should also be avoided in pulmonary hypertension, antepartum haemorrhage, intra-uterine infection, intra-uterine fetal death, placenta praevia, abruptio placenta, threatened miscarriage, cord compression, and eclampsia or severe pre-eclampsia.
Side-effects Side-effects of the beta2 agonists include nausea, vomiting, pulmonary oedema (see Cautions above), palpitation, tachycardia, arrhythmias, myocardial ischaemia, hypotension, peripheral vasodilation, headache, tremor, hyperglycaemia, hypokalaemia (see Cautions), muscle cramps and tension, and hypersensitivity reactions (including angioedema, urticaria, rash, bronchospasm, hypotension, and collapse).
SALBUTAMOL
(Albuterol)
Indications uncomplicated premature labour under specialist supervision (see notes above); asthma (section 3.1.1)
Cautions see notes above; interactions: Appendix 1 (sympathomimetics, beta2)
Contra-indications see notes above
Side-effects see notes above
Dose
By intravenous infusion, initially 10 micrograms/minute, rate increased gradually according to response at 10-minute intervals until contractions diminish then increase rate slowly until contractions cease (max. rate 45 micrograms/minute); maintain rate for 1 hour after contractions have stopped, then gradually reduce by 50% every 6 hours; max. duration 48 hours
TERBUTALINE SULFATE
Indications uncomplicated premature labour under specialist supervision (see notes above); asthma (section 3.1.1)
Cautions see notes above; interactions: Appendix 1 (sympathomimetics, beta2)
Contra-indications see notes above
Side-effects see notes above; also reported sleep disturbances and behavioural disturbances
Dose
By intravenous infusion, 5 micrograms/minute for 20 minutes, increased every 20 minutes in steps of 2.5 micrograms/minute until contractions have ceased (more than 10 micrograms/minute should seldom be given — 20 micrograms/minute should not be exceeded), continue for 1 hour then decrease every 20 minutes in steps of 2.5 micrograms/minute to lowest dose that maintains suppression; max. total duration 48 hours
7.2 Treatment of vaginal and vulval conditions
Symptoms are often restricted to the vulva, but infections almost invariably involve the vagina which should also be treated. Applications to the vulva alone are likely to give only symptomatic relief without cure.
Aqueous medicated douches may disturb normal vaginal acidity and bacterial flora.
Topical anaesthetic agents give only symptomatic relief and may cause sensitivity reactions. They are indicated only in cases of pruritus where specific local causes have been excluded.
Systemic drugs are required in the treatment of infections such as gonorrhoea and syphilis (section 5.1).
7.2.1 Preparations for vaginal and vulval changes
Topical HRT for vaginal atrophy
A cream containing an oestrogen may be applied on a short-term basis to improve the vaginal epithelium in menopausal atrophic vaginitis. It is important to bear in mind that topical oestrogens should be used in the smallest effective amount to minimise systemic effects. Modified-release vaginal tablets and an impregnated vaginal ring are now also available.
The risk of endometrial hyperplasia and carcinoma is increased when systemic oestrogens are administered alone for prolonged periods (section 6.4.1.1). The endometrial safety of long-term or repeated use of topical vaginal oestrogens is uncertain; treatment should be reviewed at least annually, with special consideration given to any symptoms of endometrial hyperplasia or carcinoma.
Topical oestrogens are also used in postmenopausal women before vaginal surgery for prolapse when there is epithelial atrophy.
For a general comment on hormone replacement therapy, including the role of topical oestrogens, see section 6.4.1.1.
OESTROGENS, TOPICAL
Indications see notes above
Cautions see notes above; see also Oestrogens for HRT (section 6.4.1.1); interrupt treatment periodically to assess need for continued treatment
Contra-indications see notes above; see also Oestrogens for HRT (section 6.4.1.1)
Hepatic impairment see Combined Hormonal Contraceptives, section 7.3.1
Pregnancy see Combined Hormonal Contraceptives, section 7.3.1
Breast-feeding avoid; adverse effects on lactation; see also Combined Hormonal Contraceptives, section 7.3.1
Side-effects see notes above; see also Oestrogens for HRT (section 6.4.1.1); local irritation
Gynest® (Marlborough) 
Intravaginal cream, estriol 0.01%, net price 80 g with applicator = £4.67
Excipients include arachis (peanut) oil
Condoms may damage latex condoms and diaphragms
Dose insert 1 applicatorful daily, preferably in the evening until improvement occurs, reduced to 1 applicatorful twice a week; attempts to discontinue should be made at 3–6 month intervals with re-examination
Ortho-Gynest® (Janssen) 
Pessaries, estriol 500 micrograms, net price 15 pessaries = £4.73
Excipients include butylated hydroxytoluene
Condoms damages latex condoms and diaphragms
Dose insert 1 pessary daily, preferably in the evening, until improvement occurs; maintenance 1 pessary twice a week; attempts to reduce or discontinue should be made at 3–6 month intervals with re-examination
Ovestin® (Aspen) 
Intravaginal cream, estriol 0.1%, net price 15 g with applicator = £4.45
Excipients include cetyl alcohol, polysorbates, stearyl alcohol
Condoms effect on latex condoms and diaphragms not yet known
Dose insert 1 applicator-dose daily for 2–3 weeks, then reduce to twice a week (discontinue every 2–3 months for 4 weeks to assess need for further treatment); vaginal surgery, 1 applicator-dose daily for 2 weeks before surgery, resuming 2 weeks after surgery
Vagifem® (Novo Nordisk) 
Vaginal tablets, f /c, estradiol 10 micrograms in disposable applicators, net price 24-applicator pack = £16.72
Excipients none as listed in section 13.1.3.
Condoms no evidence of damage to latex condoms and diaphragms
Dose insert 1 vaginal tablet daily for 2 weeks then reduce to 1 tablet twice weekly
Vaginal ring
Estring® (Pharmacia) 
Vaginal ring, releasing estradiol approx. 7.5 micrograms/24 hours, net price 1-ring pack = £31.42. Label: 10, patient information leaflet
Dose for postmenopausal urogenital conditions (not suitable for vasomotor symptoms or osteoporosis prophylaxis), to be inserted into upper third of vagina and worn continuously; replace after 3 months; max. duration of continuous treatment 2 years
Non-hormonal preparations for vaginal atrophy
Replens MD® and Sylk® are acidic, non-hormonal vaginal moisturisers; Replens MD® provides a high moisture content for up to 3 days.
7.2.2 Vaginal and vulval infections
Effective specific treatments are available for the common vaginal infections.
Fungal infections
Candidal vulvitis can be treated locally with cream, but is almost invariably associated with vaginal infection which should also be treated. Vaginal candidiasis is treated primarily with antifungal pessaries or cream inserted high into the vagina (including during menstruation). Single-dose preparations offer an advantage when compliance is a problem. Local irritation may occur on application of vaginal antifungal products.
Imidazole drugs (clotrimazole, econazole, fenticonazole, and miconazole) are effective against candida in short courses of 1 to 14 days according to the preparation used; treatment can be repeated if initial course fails to control symptoms or if symptoms recur. Vaginal applications may be supplemented with antifungal cream for vulvitis and to treat other superficial sites of infection.
Oral treatment of vaginal infection with fluconazole or itraconazole (section 5.2.1) is also effective.
Vulvovaginal candidiasis in pregnancy Vulvovaginal candidiasis is common during pregnancy and can be treated with vaginal application of an imidazole (such as clotrimazole), and a topical imidazole cream for vulvitis. Pregnant women need a longer duration of treatment, usually about 7 days, to clear the infection. Oral antifungal treatment should be avoided during pregnancy.
Recurrent vulvovaginal candidiasis Recurrence of vulvovaginal candidiasis is particularly likely if there are predisposing factors, such as antibacterial therapy, pregnancy, diabetes mellitus, or possibly oral contraceptive use. Reservoirs of infection may also lead to recontamination and should be treated; these include other skin sites such as the digits, nail beds, and umbilicus as well as the gastro-intestinal tract and the bladder. The partner may also be the source of re-infection and, if symptomatic, should be treated with a topical imidazole cream at the same time.
Treatment against candida may need to be extended for 6 months in recurrent vulvovaginal candidiasis. Some recommended regimens [all unlicensed] include:
initially, fluconazole (section 5.2.1) by mouth 150 mg every 72 hours for 3 doses, then 150 mg once every week for 6 months;
initially, intravaginal application of a topical imidazole for 10–14 days, then clotrimazole vaginally 500-mg pessary once every week for 6 months;
initially, intravaginal application of a topical imidazole for 10–14 days, then itraconazole (section 5.2.1) by mouth 50–100 mg daily for 6 months.
PREPARATIONS FOR VAGINAL AND VULVAL CANDIDIASIS
Indications see notes above
Cautions interactions: Appendix 1 (miconazole)
Pregnancy see notes above
Side-effects occasional local irritation
Dose
See under preparations below
Clotrimazole (Non-proprietary)
Cream (topical), clotrimazole 1%, net price 20 g = £1.70; 50 g = £4.25
Condoms check with manufacturer of cream for effect on latex condoms and diaphragms
Dose apply to anogenital area 2–3 times daily
Pessary, clotrimazole 500 mg, net price 1 pessary with applicator = £3.45
Dose insert 1 pessary at night as a single dose; can be repeated once if necessary
Canesten® (Bayer Consumer Care)
Cream (topical), clotrimazole 1%, net price 20 g = £2.14; 50 g = £3.50
Excipients include benzyl alcohol, cetostearyl alcohol, polysorbates
Condoms damages latex condoms and diaphragms
Dose apply to anogenital area 2–3 times daily
Thrush Cream (topical), clotrimazole 2%, net price 20 g = £4.46
Excipients include benzyl alcohol, cetostearyl alcohol, polysorbates
Condoms damages latex condoms and diaphragms
Dose apply to anogenital area 2–3 times daily
Intravaginal cream (10% VC®) 
, clotrimazole 10%, net price 5-g applicator pack = £4.50
Excipients include benzyl alcohol, cetostearyl alcohol, polysorbates
Condoms damages latex condoms and diaphragms
Dose insert 5 g at night as a single dose; can be repeated once if necessary
Note Brands for sale to the public include Canesten® Internal Cream
Cream Combi, clotrimazole 10% vaginal cream and 2% topical cream, net price 5-g vaginal cream (with applicator) and 10-g topical cream = £8.21
Excipients include benzyl alcohol, cetostearyl alcohol, polysorbates
Condoms damages latex condoms and diaphragms
Dose see under individual components
Pessaries, clotrimazole 100 mg, net price 6 pessaries with applicator = £3.50; 200 mg, 3 pessaries with applicator = £3.10
Condoms damages latex condoms and diaphragms
Dose insert 200 mg for 3 nights or 100 mg for 6 nights; course can be repeated once if necessary
Pessary, clotrimazole 500 mg, net price 1 pessary with applicator = £2.00
Condoms damages latex condoms and diaphragms
Dose insert 1 pessary at night as a single dose; can be repeated once if necessary
Pessary Combi, clotrimazole 500-mg pessary and cream (topical) 2%, net price 1 pessary and 10-g cream = £8.21
Condoms damages latex condoms and diaphragms
Excipients include benzyl alcohol, cetostearyl alcohol, polysorbates
Dose see under individual components
Soft Gel Pessary, clotrimazole 500 mg, net price 1 pessary with applicator = £6.41
Condoms damages latex condoms and diaphragms
Dose insert 1 pessary at night as a single dose; can be repeated once if necessary
Soft Gel Pessary Combi, clotrimazole 500-mg soft gel pessary and cream (topical) 2%, net price 1 pessary and 10-g cream = £5.73
Excipients include benzyl alcohol, cetostearyl alcohol, polysorbates
Condoms damages latex condoms and diaphragms
Dose see under individual components
Gyno-Daktarin® (Janssen) 
Intravaginal cream, miconazole nitrate 2%, net price 78 g with applicators = £4.33
Excipients include butylated hydroxyanisole
Condoms damages latex condoms and diaphragms
Dose insert 5-g applicatorful once daily for 10–14 days or twice daily for 7 days; course can be repeated once if necessary; topical, apply to anogenital area twice daily
Ovule (= vaginal capsule) (Gyno-Daktarin 1®), miconazole nitrate 1.2 g in a fatty basis, net price 1 ovule = £2.94
Excipients include hydroxybenzoates (parabens)
Condoms damages latex condoms and diaphragms
Dose insert 1 ovule at night as a single dose; can be repeated once if necessary
Gyno-Pevaryl® (Janssen) 
Cream, econazole nitrate 1%, net price 15 g = £2.11; 30 g = £3.78
Excipients none as listed in section 13.1.3.
Condoms damages latex condoms and diaphragms
Dose insert 5-g applicatorful intravaginally and apply to vulva at night for at least 14 nights; course can be repeated once if necessary
Note Applicator available separately from Marlborough
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