Drugs List

Administration

For oral administration.

Tablets should be taken with liquid and may be taken with or without food. The tablets must be swallowed whole and not chewed, divided or crushed.

Contraindications

Children under 18 years - see 'Dosage - Children'

Severe hepatic impairment (Child Pugh C)

Urinary retention

Gastric retention
Severe ulcerative colitis
Toxic megacolon

Uncontrolled narrow-angle glaucoma

Myasthenia gravis

Pregnancy - see Pregnancy section

Precautions and Warnings

Before darifenacin therapy is started, other causes of frequent urination (such as renal failure or cardiac failure) should be considered.

Appropriate antibiotic therapy should be started if the patient presents with a urinary tract infection.

Use with caution in patients with the following:
Renal impairment - see 'Dosage - Renal Impairment'.
Mild to moderate hepatic impairment (Child Pugh A/B)- see 'Dosage - Hepatic Impairment'
Autonomic neuropathy
Hiatus hernia
Clinically significant bladder outflow obstruction
Risk factors for urinary retention
Severe constipation
Risk factors for gastrointestinal obstructive disorders (e.g. pyloric stenosis)
Gastro-intestinal obstruction
Reduced gastrointestinal motility
Gastroesophageal reflux
Narrow-angle glaucoma (treated)

Breastfeeding - see Lactation section

Use with caution in elderly patients, especially if they are frail, as darifenacin clearance is decreased with age.

Darifenacin is a selective muscarinic M3 receptor antagonist. Nevertheless, prescribers should be aware that the following conditions may be aggravated by antimuscarinics:
Hyperthyroidism
Congestive cardiac failure
Coronary artery disease
Cardiac arrhythmia
Tachycardia
Hypertension
Prostatic hyperplasia

The safety and efficacy of darifenacin has not been established in patients with a neurogenic cause for detrusor overactivity.

No studies on the effects of darifenacin on the ability to drive or operate machinery have been performed. As with other antimuscarinic drugs, caution should be exercised as abnormal vision, dizziness, insomnia and somnolence may occur.

Treatment with darifenacin could potentially mask the symptoms of gallbladder disease.

Grapefruit products may increase the plasma levels of darifenacin - advise patients not to consume grapefruit products.

St John's Wort may reduce the plasma level of darifenacin - advise patients not to self-medicate with St John's Wort.

Caution should be used when prescribing antimuscarinics to patients with pre-existing cardiac diseases.

As with other antimuscarinics, patients should be instructed to discontinue darifenacin and seek immediate medical attention if they experience oedema of the tongue or laropharynx, or difficulty breathing.

Pregnancy and Lactation

Pregnancy

Not recommended for use during pregnancy.

There are no studies with darifenacin in human pregnancy. Animal studies have shown toxicity to parturition, peri- and post-natal development at high doses. However, Briggs (2011) states that inadvertent exposure appears to represent a low risk of embryo/foetal harm.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

It is not known if darifenacin is excreted into human breast milk, however Hale (2010) states that its chemistry would probably limit its transfer into human milk. Animal studies have demonstrated that darifenacin is excreted in breast milk.

Use with caution during lactation as darifenacin is a strong anticholinergic muscarinic agents and could cause urinary retention, dry mouth, mydriasis, constipation and other GI symptoms in the breastfed infant.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Dry mouth
Constipation
Headache
Abdominal pain
Asthenia
Facial oedema
Hypertension
Dyspepsia
Nausea
Diarrhoea
Flatulence
Ulcerative stomatitis
Increase in serum ALT/AST
Peripheral oedema
Oedema
Dizziness
Insomnia
Somnolence
Abnormal thinking
Rhinitis
Cough increased
Dyspnoea
Dry skin
Rash
Pruritus
Sweating
Dry eyes
Abnormal vision
Urinary tract disorders
Erectile dysfunction
Urinary tract infections
Vaginitis
Bladder pain
Blurred vision
Urinary retention
Dysgeusia
Angioedema
Weakness
Mouth ulcers
Mood changes
Hallucinations
Nasal dryness

Presentation

Modified release tablet containing 7.5mg darifenacin (as hydrobromide)

Modified release tablet containing 15mg darifenacin (as hydrobromide)

Drugs List

Dosage

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Administration

For oral administration.

Tablets should be taken with liquid and may be taken with or without food. The tablets must be swallowed whole and not chewed, divided or crushed.

Contraindications

Children under 18 years - see 'Dosage - Children'

Severe hepatic impairment (Child Pugh C)

Urinary retention

Gastric retention
Severe ulcerative colitis
Toxic megacolon

Uncontrolled narrow-angle glaucoma

Myasthenia gravis

Pregnancy - see Pregnancy section

Precautions and Warnings

Before darifenacin therapy is started, other causes of frequent urination (such as renal failure or cardiac failure) should be considered.

Appropriate antibiotic therapy should be started if the patient presents with a urinary tract infection.

Use with caution in patients with the following:
Renal impairment - see 'Dosage - Renal Impairment'.
Mild to moderate hepatic impairment (Child Pugh A/B)- see 'Dosage - Hepatic Impairment'
Autonomic neuropathy
Hiatus hernia
Clinically significant bladder outflow obstruction
Risk factors for urinary retention
Severe constipation
Risk factors for gastrointestinal obstructive disorders (e.g. pyloric stenosis)
Gastro-intestinal obstruction
Reduced gastrointestinal motility
Gastroesophageal reflux
Narrow-angle glaucoma (treated)

Breastfeeding - see Lactation section

Use with caution in elderly patients, especially if they are frail, as darifenacin clearance is decreased with age.

Darifenacin is a selective muscarinic M3 receptor antagonist. Nevertheless, prescribers should be aware that the following conditions may be aggravated by antimuscarinics:
Hyperthyroidism
Congestive cardiac failure
Coronary artery disease
Cardiac arrhythmia
Tachycardia
Hypertension
Prostatic hyperplasia

The safety and efficacy of darifenacin has not been established in patients with a neurogenic cause for detrusor overactivity.

No studies on the effects of darifenacin on the ability to drive or operate machinery have been performed. As with other antimuscarinic drugs, caution should be exercised as abnormal vision, dizziness, insomnia and somnolence may occur.

Treatment with darifenacin could potentially mask the symptoms of gallbladder disease.

Grapefruit products may increase the plasma levels of darifenacin - advise patients not to consume grapefruit products.

St John's Wort may reduce the plasma level of darifenacin - advise patients not to self-medicate with St John's Wort.

Caution should be used when prescribing antimuscarinics to patients with pre-existing cardiac diseases.

As with other antimuscarinics, patients should be instructed to discontinue darifenacin and seek immediate medical attention if they experience oedema of the tongue or laropharynx, or difficulty breathing.

Pregnancy and Lactation

Pregnancy

Not recommended for use during pregnancy.

There are no studies with darifenacin in human pregnancy. Animal studies have shown toxicity to parturition, peri- and post-natal development at high doses. However, Briggs (2011) states that inadvertent exposure appears to represent a low risk of embryo/foetal harm.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

It is not known if darifenacin is excreted into human breast milk, however Hale (2010) states that its chemistry would probably limit its transfer into human milk. Animal studies have demonstrated that darifenacin is excreted in breast milk.

Use with caution during lactation as darifenacin is a strong anticholinergic muscarinic agents and could cause urinary retention, dry mouth, mydriasis, constipation and other GI symptoms in the breastfed infant.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Effects on Ability to Drive and Operate Machinery

No studies on the effects of darifenacin on the ability to drive or operate machinery have been performed.

As with other antimuscarinic drugs, side effects such as abnormal vision, dizziness, insomnia and somnolence may occur. Although reports of these effects with darifenacin are rare, advise patients that they should not drive or operate machinery if affected.

Counselling

Advise patients that the tablets must be swallowed whole and not chewed, divided or crushed.

Advise patients that they should not consume grapefruit products while taking darifenacin.

Advise patients that they should not self-medicate with St John's Wort while taking darifenacin.

Advise patients that if they do experience adverse effects such as blurred vision or dizziness, they should not drive or operate machinery.

Side Effects

Dry mouth
Constipation
Headache
Abdominal pain
Asthenia
Facial oedema
Hypertension
Dyspepsia
Nausea
Diarrhoea
Flatulence
Ulcerative stomatitis
Increase in serum ALT/AST
Peripheral oedema
Oedema
Dizziness
Insomnia
Somnolence
Abnormal thinking
Rhinitis
Cough increased
Dyspnoea
Dry skin
Rash
Pruritus
Sweating
Dry eyes
Abnormal vision
Urinary tract disorders
Erectile dysfunction
Urinary tract infections
Vaginitis
Bladder pain
Blurred vision
Urinary retention
Dysgeusia
Angioedema
Weakness
Mouth ulcers
Mood changes
Hallucinations
Nasal dryness

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Reference Sources

British National Formulary, 63rd Edition (2012) Pharmaceutical Press, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Emselex 7.5mg and 15mg prolonged-release tablets. Novartis Pharmaceuticals UK Ltd. Revised December 2011.