l HEPATIC IMPAIRMENT Manufacturer advises use with
caution in mild to moderate insufficiency—half-life may be
prolonged; avoid in severe insufficiency.
l PATIENT AND CARER ADVICE Warn patient or carers to tell
doctor immediately if sore throat, mouth ulcers, bruising,
fever, malaise, or non-specific illness develops.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: capsule, oral
▶ Carbimazole (Non-proprietary)
Carbimazole 5 mg Carbimazole 5mg tablets | 100 tablet P £84.80 DT = £21.36
Carbimazole 10 mg Carbimazole 10mg tablets | 100 tablet P £81.32 DT = £81.32
Carbimazole 15 mg Carbimazole 15mg tablets | 100 tablet P £115.98–£127.50 DT = £122.75
Carbimazole 20 mg Carbimazole 20mg tablets | 100 tablet P £208.17 DT = £92.01
ANTITHYROID DRUGS › THIOURACILS
▶ Adult: Initially 200–400 mg daily in divided doses until
the patient becomes euthyroid, then reduced to
50–150 mg daily in divided doses, initial dose should
be gradually reduced to the maintenance dose
DOSE EQUIVALENCE AND CONVERSION
▶ When substituting, carbimazole 1 mg is considered
equivalent to propylthiouracil 10 mg but the dose may
need adjusting according to response.
l INTERACTIONS → Appendix 1: propylthiouracil
SIDE-EFFECTS, FURTHER INFORMATION Severe hepatic
reactions have been reported, including fatal cases and
cases requiring liver transplant—discontinue if significant
liver-enzyme abnormalities develop.
l PREGNANCY Propylthiouracil can be given but the
blocking-replacement regimen is not suitable.
Propylthiouracil crosses the placenta and in high doses
may cause fetal goitre and hypothyroidism—the lowest
dose that will control the hyperthyroid state should be
used (requirements in Graves’ disease tend to fall during
l BREAST FEEDING Present in breast milk but this does not
preclude breast-feeding as long as neonatal development
is closely monitored and the lowest effective dose is used.
Amount in milk probably too small to affect infant; high
doses may affect neonatal thyroid function.
Monitoring Monitor infant’s thyroid status.
l HEPATIC IMPAIRMENT Manufacturer advises caution (risk
Dose adjustments Manufacturer advises consider dose
Dose adjustments Use three-quarters normal dose if eGFR
Use half normal dose if eGFR less than
l MONITORING REQUIREMENTS Monitor for hepatotoxicity.
l PATIENT AND CARER ADVICE Patients should be told how
to recognise signs of liver disorder and advised to seek
prompt medical attention if symptoms such as anorexia,
nausea, vomiting, fatigue, abdominal pain, jaundice, dark
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension, oral
▶ Propylthiouracil (Non-proprietary)
(Lugol’s Solution; Aqueous Iodine Oral Solution)
Thyrotoxicosis (pre-operative)
▶ BY MOUTH USING ORAL SOLUTION
▶ Adult: 0.1–0.3 mL 3 times a day
DOSE EQUIVALENCE AND CONVERSION
▶ Doses based on the use of an aqueous oral solution
containing iodine 50 mg/mL and potassium iodide
l CAUTIONS Not for long-term treatment
l PREGNANCY Neonatal goitre and hypothyroidism.
l BREAST FEEDING Stop breast-feeding. Danger of neonatal
hypothyroidism or goitre. Appears to be concentrated in
l DIRECTIONS FOR ADMINISTRATION For oral solution, dilute
l MEDICINAL FORMS Forms available from special-order
manufacturers include: oral solution
Thyroid hormones are used in hypothyroidism
(myxoedema), and also in diffuse non-toxic goitre,
Hashimoto’s thyroiditis (lymphadenoid goitre), and thyroid
carcinoma. Neonatal hypothyroidism requires prompt
treatment for normal development. Levothyroxine sodium
below (thyroxine sodium) is the treatment of choice for
In infants and children with congenital hypothyroidism
and juvenile myxoedema, the dose of levothyroxine sodium
should be titrated according to clinical response, growth
assessment, and measurements of plasma thyroxine and
Liothyronine sodium p. 774 has a similar action to
levothyroxine sodium but is more rapidly metabolised and
has a more rapid effect. Its effects develop after a few hours
and disappear within 24 to 48 hours of discontinuing
treatment. It may be used in severe hypothyroid states when a
Liothyronine sodium by intravenous injection is the
treatment of choice in hypothyroid coma. Adjunctive therapy
includes intravenous fluids, hydrocortisone p. 676, and
treatment of infection; assisted ventilation is often required.
Patients with thyroid disorders may be eligible for the
Medicines Use Review service provided by a community
pharmacist. For further information, see Advanced Pharmacy
Services in Guidance on prescribing p. 1.
▶ Adult 18–49 years: Initially 50–100 micrograms once
daily; adjusted in steps of 25–50 micrograms every
3–4 weeks, adjusted according to response;
maintenance 100–200 micrograms once daily, dose to
be taken preferably at least 30 minutes before
breakfast, caffeine-containing liquids (e.g. coffee, tea),
▶ Adult 50 years and over: Initially 25 micrograms once
daily; adjusted in steps of 25 micrograms every
4 weeks, adjusted according to response; maintenance
50–200 micrograms once daily, dose to be taken
preferably at least 30 minutes before breakfast,
caffeine-containing liquids (e.g. coffee, tea), or other
Hypothyroidism in patients with cardiac disease | Severe
▶ Adult: Initially 25 micrograms once daily; adjusted in
steps of 25 micrograms every 4 weeks, adjusted
according to response; maintenance
50–200 micrograms once daily, dose to be taken
preferably at least 30 minutes before breakfast,
caffeine-containing liquids (e.g. coffee, tea), or other
Hyperthyroidism (blocking-replacement regimen) in
▶ Adult: 50–150 micrograms daily therapy usually given
l CONTRA-INDICATIONS Thyrotoxicosis
corticosteroid therapy before starting levothyroxine)
▶ Cardiovascular disorders Baseline ECG is valuable because
changes induced by hypothyroidism can be confused with
l INTERACTIONS → Appendix 1: thyroid hormones
SIDE-EFFECTS, FURTHER INFORMATION Initial dosage in
patients with cardiovascular disorders If metabolism
increases too rapidly (causing diarrhoea, nervousness,
rapid pulse, insomnia, tremors and sometimes anginal
pain where there is latent myocardial ischaemia), reduce
dose or withhold for 1–2 days and start again at a lower
l PREGNANCY Levothyroxine may cross the placenta.
Excessive or insufficient maternal thyroid hormones can
Dose adjustments Levothyroxine requirement may
Monitoring Assess maternal thyroid function before
conception (if possible), at diagnosis of pregnancy, at
antenatal booking, during both the second and third
trimesters, and after delivery (more frequent monitoring
required on initiation or adjustment of levothyroxine).
l BREAST FEEDING Amount too small to affect tests for
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: capsule, oral
▶ Levothyroxine sodium (Non-proprietary)
Levothyroxine sodium anhydrous 12.5 microgram Levothyroxine
sodium 12.5microgram tablets | 28 tablet P £1.20–£2.80 DT =
Levothyroxine sodium anhydrous 25 microgram Levothyroxine
sodium 25microgram tablets | 28 tablet P £3.05 DT = £1.63 | 500 tablet P £41.61–£56.25
Levothyroxine sodium 25microgram tablets lactose free |
Levothyroxine sodium anhydrous 50 microgram Levothyroxine
sodium 50microgram tablets lactose free | 100 tablet P s
Levothyroxine sodium 50microgram tablets | 28 tablet P £1.50
DT = £1.03 | 1000 tablet P £36.79–£55.71
Levothyroxine sodium anhydrous 75 microgram Levothyroxine
sodium 75microgram tablets | 28 tablet P £2.10–£4.00 DT = £2.73
Levothyroxine sodium anhydrous 100 microgram Levothyroxine
sodium 100microgram tablets lactose free | 100 tablet P s
Levothyroxine sodium 100microgram tablets | 28 tablet P £1.50
DT = £1.03 | 1000 tablet P £36.79–£56.07
Levothyroxine sodium anhydrous 25 microgram Eltroxin
25microgram tablets | 28 tablet P £2.54 DT = £1.63
Levothyroxine sodium anhydrous 50 microgram Eltroxin
50microgram tablets | 28 tablet P £1.77 DT = £1.03
Levothyroxine sodium anhydrous 100 microgram Eltroxin
100microgram tablets | 28 tablet P £1.78 DT = £1.03
▶ Levothyroxine sodium (Non-proprietary)
Levothyroxine sodium anhydrous 5 microgram per
1 ml Levothyroxine sodium 25micrograms/5ml oral solution sugar
free sugar-free | 100 ml P £118.63 DT = £94.98
Levothyroxine sodium anhydrous 10 microgram per
1 ml Levothyroxine sodium 50micrograms/5ml oral solution sugar
free sugar-free | 100 ml P £91.22 DT = £89.12
Levothyroxine sodium anhydrous 20 microgram per
1 ml Levothyroxine sodium 100micrograms/5ml oral solution sugar
free sugar-free | 100 ml P £165.00 DT = £164.98
Levothyroxine sodium anhydrous 25 microgram per
1 ml Levothyroxine sodium 125micrograms/5ml oral solution sugar
free sugar-free | 100 ml P £185.00
▶ Adult: Initially 10–20 micrograms daily; increased to
60 micrograms daily in 2–3 divided doses, dose should
be increased gradually, smaller initial doses given for
▶ BY SLOW INTRAVENOUS INJECTION
▶ Adult: 5–20 micrograms every 12 hours, increased to
5–20 micrograms every 4 hours if required,
alternatively initially 50 micrograms for 1 dose, then
25 micrograms every 8 hours, reduced to
DOSE EQUIVALENCE AND CONVERSION
▶ 20–25 micrograms of liothyronine sodium is equivalent
to approximately 100 micrograms of levothyroxine
▶ Brands without a UK licence may not be bioequivalent
and dose adjustment may be necessary.
l CONTRA-INDICATIONS Thyrotoxicosis
corticosteroid therapy before starting liothyronine)
▶ Cardiovascular disorders Baseline ECG is valuable because
changes induced by hypothyroidism can be confused with
l INTERACTIONS → Appendix 1: thyroid hormones
▶ Rare or very rare Alopecia . angina pectoris (more common
at excessive dosage). arrhythmia (more common at
excessive dosage). diarrhoea (more common at excessive
dosage). heat intolerance . muscle cramps . muscle
weakness . palpitations (more common at excessive
dosage).tachycardia (more common at excessive dosage). vomiting (more common at excessive dosage)
dosage). oedema .restlessness (more common at excessive
dosage). skin reactions .tremor (more common at
excessive dosage). weight decreased
▶ With intravenous use Menstruation irregular
SIDE-EFFECTS, FURTHER INFORMATION Initial dosage in
patients with cardiovascular disorders
If metabolism increases too rapidly (causing diarrhoea,
nervousness, rapid pulse, insomnia, tremors and
sometimes anginal pain where there is latent myocardial
ischaemia), reduce dose or withhold for 1–2 days and start
l PREGNANCY Does not cross the placenta in significant
amounts. Excessive or insufficient maternal thyroid
hormones can be detrimental to fetus.
Dose adjustments Liothyronine requirement may increase
Monitoring Assess maternal thyroid function before
conception (if possible), at diagnosis of pregnancy, at
antenatal booking, during both the second and third
trimesters, and after delivery (more frequent monitoring
required on initiation or adjustment of liothyronine).
l BREAST FEEDING Amount too small to affect tests for
l PRESCRIBING AND DISPENSING INFORMATION
Switching to a different brand Patients switched to a different
brand should be monitored (particularly if pregnant or if
heart disease present) as brands without a UK licence may
not be bioequivalent. Pregnant women or those with heart
disease should undergo an early review of thyroid status,
and other patients should have thyroid function assessed if
experiencing a significant change in symptoms. If
liothyronine is continued long-term, thyroid function tests
should be repeated 1–2 months after any change in brand.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: tablet, capsule, oral
suspension, oral solution, solution for injection
▶ Liothyronine sodium (Non-proprietary)
Liothyronine sodium 20 microgram Liothyronine 20microgram
tablets | 28 tablet P £245.29 DT = £206.71
▶ Cytomel (Imported (United States))
Liothyronine sodium 5 microgram Cytomel 5microgram tablets | 100 tablet P s
Liothyronine sodium 25 microgram Cytomel 25microgram tablets
Powder for solution for injection
▶ Liothyronine sodium (Non-proprietary)
Liothyronine sodium 20 microgram Liothyronine 20microgram
powder for solution for injection vials | 5 vial P £1,567.50
1 Bladder and urinary disorders page 776
1.1 Urinary frequency, enuresis, and incontinence 776
2 Bladder instillations and urological surgery 790
3.1 Contraception, combined 795
3.2 Contraception, devices 802
3.3 Contraception, emergency 803
3.4 Contraception, oral progestogen-only 805
3.5 Contraception, parenteral progestogen-only 809
3.6 Contraception, spermicidal 811
4 Erectile and ejaculatory conditions page 812
5.2 Postpartum haemorrhage 824
5.4 Termination of pregnancy 825
6 Vaginal and vulval conditions 827
6.1 Vaginal and vulval infections 828
6.1a Vaginal and vulval bacterial infections 828
6.1b Vaginal and vulval fungal infections 829
1.1 Urinary frequency, enuresis,
Urinary frequency, enuresis and
Urinary frequency and incontinence
Incontinence in adults which arises from detrusor instability
is managed by combining drug therapy with conservative
methods for managing urge incontinence such as pelvic floor
exercises and bladder training; stress incontinence is
generally managed by non-drug methods. Duloxetine p. 367
can be added and is licensed for the treatment of moderate
to severe stress incontinence in women; it may be more
effective when used as an adjunct to pelvic floor exercises.
Antimuscarinic drugs reduce symptoms of urgency and
urge incontinence and increase bladder capacity.
Oxybutynin hydrochloride p. 778 also has a direct relaxant
effect on urinary smooth muscle. Side-effects limit the use of
oxybutynin hydrochloride, but they may be reduced by
starting at a lower dose. A modified-release preparation of
and side-effects of tolterodine tartrate p. 780 are comparable
to those of modified-release oxybutynin hydrochloride.
Flavoxate hydrochloride p. 778 has less marked side-effects
but it is also less effective. Darifenacin p. 777, fesoterodine
fumarate p. 777, propiverine hydrochloride p. 779,
solifenacin succinate p. 779, and trospium chloride p. 781 are
newer antimuscarinic drugs licensed for urinary frequency,
urgency, and incontinence. The need for continuing
antimuscarinic drug therapy should be reviewed every
4–6 weeks until symptoms stabilise, and then every
Propantheline bromide p. 86 and tricyclic antidepressants
were used for urge incontinence but they are little used now
because of their side-effects. The use of imipramine
hydrochloride p. 376 is limited by its potential to cause
Mirabegron p. 781, a selective beta3 agonist, is licensed for
the treatment of urinary frequency, urgency, and urge
incontinence associated with overactive bladder syndrome.
Purified bovine collagen implant (Contigen ®, Bard) is
indicated for urinary incontinence caused by intrinsic
sphincter deficiency (poor or non-functioning bladder outlet
mechanism). The implant should be inserted only by
surgeons or physicians trained in the technique for injection
See also Nocturnal enuresis in children below.
Nocturnal enuresis in children
Nocturnal enuresis is the involuntary discharge of urine
during sleep, which is common in young children. Children
are generally expected to be dry by a developmental age of
5 years, and historically it has been common practice to
consider children for treatment only when they reach
7 years; however, symptoms may still persist in a small
proportion by the age of 10 years.
g For children under 5 years, treatment is usually
unnecessary as the condition is likely to resolve
spontaneously. Reassurance and advice can be useful for
g Initially, advice should be given on fluid intake, diet,
toileting behaviour, and use of reward systems. For children
who do not respond to this advice (more than 1–2 wet beds
per week), an enuresis alarm should be the recommended
treatment for motivated, well-supported children. Alarms in
children under 7 years should be considered depending on
the child’s maturity, motivation and understanding of the
alarm. Alarms have a lower relapse rate than drug treatment
776 Genito-urinary system BNF 78
g Treatment using an alarm should be reviewed after
4 weeks and continued until a minimum of 2 weeks’
uninterrupted dry nights have been achieved. If complete
dryness is not achieved after 3 months but the condition is
still improving and the child remains motivated to use the
alarm, it is recommended to continue the treatment.
Combined treatment with desmopressin p. 667, or the use of
desmopressin alone, is recommended if the initial alarm
treatment is unsuccessful or it is no longer appropriate or
g Treatment with oral or sublingual desmopressin is
recommended for children over 5 years of age when alarm
away from home). Desmopressin alone can also be used if
there has been a partial response to a combination of
desmopressin and an alarm following initial treatment with
an alarm alone. Treatment should be assessed after 4 weeks
and continued for 3 months if there are signs of response.
Repeated courses of desmopressin can be used in responsive
children who experience repeated recurrences of bedwetting,
but should be withdrawn gradually at regular intervals (for
1 week every 3 months) for full reassessment.
Under specialist supervision, nocturnal enuresis
associated with daytime symptoms (overactive bladder) can
be managed with desmopressin alone or in combination with
an antimuscarinic drug (such as oxybutynin hydrochloride
p. 778 or tolterodine tartrate p. 780 [unlicensed indication]).
Treatment should be continued for 3 months; the course can
The tricyclic antidepressant imipramine hydrochloride
p. 376 can be considered for children who have not
responded to all other treatments and have undergone
specialist assessment, however relapse is common after
withdrawal and children and their carers should be aware of
the dangers of overdose. Initial treatment should continue
for 3 months; further courses can be considered following a
medical review every 3 months. Tricyclic antidepressants
should be withdrawn gradually. h
Bedwetting in under 19s. National Institute for Health and
Care Excellence. Clinical guideline CG111. October 2010.
www.nice.org.uk/guidance/cg111
l CONTRA-INDICATIONS Gastro-intestinal obstruction . intestinal atony . myasthenia gravis (but some
enlargement (in adults). pyloric stenosis . severe
ulcerative colitis . significant bladder outflow obstruction . toxic megacolon . urinary retention
characterised by tachycardia . congestive heart failure
(may be worsened). coronary artery disease (may be
oesophagitis . hypertension . hyperthyroidism (due to
association with tachycardia). individuals susceptible to
angle-closure glaucoma . prostatic hyperplasia (in adults). pyrexia . ulcerative colitis
disorders . vision disorders . vomiting
▶ Rare or very rare Angioedema . confusion (more common
Driving and skilled tasks Antimuscarinics can affect the
performance of skilled tasks (e.g. driving).
Urinary frequency | Urinary urgency | Incontinence
▶ Adult: Initially 7.5 mg once daily, increased if necessary
l INTERACTIONS → Appendix 1: darifenacin
▶ Common or very common Abdominal pain . dry eye . nasal
l PREGNANCY Manufacturer advises avoid—toxicity in
l BREAST FEEDING Present in milk in animal studies—
l HEPATIC IMPAIRMENT Manufacturer advises caution in
moderate impairment; avoid in severe impairment (risk of
Dose adjustments Manufacturer advises maximum 7.5 mg
l PRESCRIBING AND DISPENSING INFORMATION The need for
continuing therapy for urinary incontinence should be
reviewed every 4–6 weeks until symptoms stabilise, and
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
CAUTIONARY AND ADVISORY LABELS 3, 25
▶ Emselex (Merus Labs Luxco S.a R.L.)
Darifenacin (as Darifenacin hydrobromide) 7.5 mg Emselex 7.5mg
modified-release tablets | 28 tablet P £25.48 DT = £25.48
Darifenacin (as Darifenacin hydrobromide) 15 mg Emselex 15mg
modified-release tablets | 28 tablet P £25.48 DT = £25.48
Fesoterodine fumarate 08-Feb-2019
Urinary frequency | Urinary urgency | Urge incontinence
▶ Adult: 4 mg once daily, increased if necessary up to
DOSE ADJUSTMENTS DUE TO INTERACTIONS
▶ Manufacturer advises max. 4 mg daily with concurrent
use of potent inhibitors of CYP3A4; avoid concurrent
use in patients who also have hepatic or renal
▶ For dose adjustments with concurrent use of moderate
inhibitors of CYP3A4 in patients with hepatic or renal
impairment, consult product literature.
l INTERACTIONS → Appendix 1: fesoterodine
BNF 78 Urinary frequency, enuresis, and incontinence 777
l PREGNANCY Manufacturer advises avoid—toxicity in
l BREAST FEEDING Manufacturer advises avoid—no
l HEPATIC IMPAIRMENT Manufacturer advises caution in
mild to moderate impairment; avoid in severe impairment
Dose adjustments Manufacturer advises increase dose
cautiously in mild impairment; maximum 4 mg daily in
Dose adjustments Increase dose cautiously if eGFR
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