Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://emc.medicines.org.uk), or the British National Formulary (BNF) (www.bnf.org).

• There is little difference in efficacy between different antispasmodics.
• Antimuscarinics more are likely to cause adverse effects than direct-acting smooth muscle relaxants or peppermint oil.
• Direct-acting smooth muscle relaxants, such as mebeverine and alverine, have some selectivity for smooth intestinal muscle and have relatively few adverse effects.
• Peppermint oil has antispasmodic properties and directly relaxes gastrointestinal smooth muscle.
• Antimuscarinics (anticholinergics) such as hyoscine butylbromide and dicycloverine are poorly selective and are likely to cause antimuscarinic adverse effects.
• There is good evidence that standard-release and modified-release mebeverine are equally effective.
• CKS recommends mebeverine, alverine citrate, and therapeutic peppermint oil.

• Antispasmodics may be used on an 'as required' basis [AGA, 2002]:
• Up to three times a day for acute attacks of pain, or
• Before meals if postprandial symptoms predominate.
• Direct-acting smooth muscle relaxants are generally well tolerated, occasional heartburn and perianal irritation may occur with therapeutic peppermint oil.
• There are no clinically significant drug interactions reported with mebeverine, alverine, or therapeutic doses of peppermint oil [BNF 55, 2008].
• Direct-acting smooth muscle relaxants are contraindicated in people with a paralytic ileus [BNF 55, 2008].
• Because there is a lack of published evidence in humans concerning the use of mebeverine hydrochloride, alverine citrate, or therapeutic doses of peppermint oil in pregnancy, the use of these drugs during pregnancy is not recommended [NTIS, 2008a].

• Loperamide is the antimotility drug of choice in diarrhoea-predominant irritable bowel syndrome (IBS) [NICE, 2008].
• Loperamide is not licensed for the treatment of IBS, but is licensed for the treatment of diarrhoea [ABPI Medicines Compendium, 2008].
• Loperamide is recommended for long-term use because it is available without prescription, does not have an antimuscarinic component, and does not induce euphoria at any dose.

• Loperamide should be given in a dose of 2 mg to 4 mg, up to four times daily, for diarrhoea-predominant irritable bowel syndrome.
• Advise people to adjust the dose of antimotility drug according to response. The aim is to produce a soft, well-formed stool.

[Mertz, 2003; NICE, 2008]

• Adverse effects include abdominal cramps, dizziness, drowsiness, skin reactions (including urticaria), paralytic ileus, and abdominal bloating [BNF 55, 2008].
• There are no significant drug interactions with loperamide [ABPI Medicines Compendium, 2008; BNF 55, 2008].
• Do not use loperamide in people with conditions where inhibition of peristalsis should be avoided (e.g. abdominal distension), or in people with active ulcerative colitis or antibiotic-associated colitis.
• Loperamide should be used with caution in people with liver disease because of reduced first-pass metabolism [Micromedex, 2009].
• There are very limited data available of the effects of loperamide during pregnancy. Although the data available do not indicate a specific teratogenic risk, there is insufficient information to recommend its use in pregnancy [NTIS, 2008b].

• Flatulence and bloating are the most common adverse effects. They can usually be avoided or reduced by increasing the dose gradually.
• Adequate fluid intake is important to prevent intestinal obstruction. This may be difficult for frail or elderly people, and for children.
• If intestinal obstruction is suspected, do not use bulk-forming laxatives.

[ABPI Medicines Compendium, 2006]

• Start at the lowest dose and, if necessary, increase it every few days until one or two soft, formed stools are produced every 1 or 2 days.
• An adequate fluid intake is important to prevent intestinal obstruction.
• Bulk-forming laxatives should not be taken immediately before going to bed.

[ABPI Medicines Compendium, 2006]

• Tricyclic antidepressants (TCAs) are the antidepressants of choice in the management of irritable bowel syndrome (IBS).
• Most studies of TCAs in IBS have used amitriptyline or trimipramine.
• CKS therefore recommends the use of either of these TCAs in the management of IBS.
• Neither amitriptyline or trimipramine are licensed for the management of IBS.
• Selective serotonin reuptake inhibitors (SSRIs) should be considered for people with IBS only if TCAs have been shown to be ineffective.
• Citalopram, fluoxetine, and paroxetine have been studied in the management of IBS.
• CKS therefore recommends the use of one of these three SSRIs in the management of IBS.
• These SSRIs are not licensed for the management of IBS.

[National Collaborating Centre for Nursing and Supportive Care, 2008]

• Treatment with a TCA should be started at a low dose (5 mg to 10 mg equivalent of amitriptyline), which should be taken once at night and reviewed regularly. The dose may be increased, but should not usually need to exceed 30 mg.
• The following doses of SSRIs have been studied and are therefore recommended:
• Citalopram 10 mg to 20 mg daily.
• Fluoxetine 20 mg daily.
• Paroxetine 10 mg to 20 mg daily.

• After prescribing either a TCA or SSRI for the first time in IBS, the person should be followed up after 4 weeks and then at 6–12 monthly intervals thereafter [NICE, 2008].