Key points from the evidence

Key points from the evidence

The content of this evidence summary was up-to-date in January 2013. See summaries of product characteristics (SPCs), British national formulary (BNF), BNF for children (BNFc) or the MHRA or NICE websites for up-to-date information.

Diltiazem hydrochloride is a calcium channel blocker and vasodilator. It increases blood flow to smooth muscles and relaxes muscle tone. Oral preparations of diltiazem hydrochloride are licensed in the UK to treat angina and hypertension.

Topical diltiazem hydrochloride is not licensed in the UK for treating chronic anal fissure or any other indication. Therefore, its use for treating chronic anal fissure is unlicensed.

An alternative topical treatment, 0.4% glyceryl trinitrate (Rectogesic 4 mg/g rectal ointment, ProStrakan), is licensed in the UK for the relief of pain associated with chronic anal fissure in adults. However, it is associated with a high frequency of headaches which can be severe and cause people to stop treatment.

One Cochrane systematic review (4 RCTs; assessed as up-to-date November 2011) and 5 additional RCTs (neither considered by nor excluded from the Cochrane review) provide the evidence for this summary. The Cochrane review and 2 additional RCTs found that the efficacy of 2% topical diltiazem hydrochloride was not statistically significantly different from topical glyceryl trinitrate in adults, but limited evidence indicates a reduced frequency of headaches. An additional RCT found that the efficacy of 2% topical diltiazem hydrochloride was not statistically significantly different from botulinum toxin injection. Two additional RCTs suggest that topical diltiazem was less effective than surgical sphincterotomy, but statistical analysis was not performed. An additional small RCT in children aged 0–12 years found that 2% topical diltiazem hydrochloride was more effective than 0.2% topical glyceryl trinitrate. Fissure healing and recurrence rate estimates from the studies varied widely because of variation in the study methodologies, populations, and follow-up.

Mild headache, perianal itching and perianal dermatitis have been reported with the use of 2% topical diltiazem hydrochloride.

The NHS price for 2% diltiazem cream is £73.83 per 30 g tube and the NHS price for 2% diltiazem ointment is £163.07 per 30 g tube. The licensed topical glyceryl trinitrate product, Rectogesic 4 mg/g rectal ointment, costs £34.80 per 30 g tube (costs exclude VAT and are taken from the Drug Tariff, February 2013).

An application for a marketing authorisation (product licence) for 4% diltiazem hydrochloride cream for use in chronic anal fissure is in the process of submission by S.L.A. Pharma (UK) Ltd but this product is not expected to come to market until the last quarter of 2013/14 at the earliest.

About this evidence summary

'Evidence summaries: unlicensed or off-label medicines' summarise the published evidence for selected unlicensed or off-label medicines that are considered to be of significance to the NHS, where there are no clinically appropriate licensed alternatives. The summaries provide information for clinicians and patients to inform their decision-making and support the construction and updating of local formularies.

The summaries support decision-making on the use of an unlicensed or off-label medicine for an individual patient, where there are good clinical reasons for its use, usually when there is no licensed medicine for the condition requiring treatment, or the licensed medicine is not appropriate for that individual.

The strengths and weaknesses of the relevant evidence are critically reviewed within this summary, but this summary is not NICE guidance.