Key points from the evidence
The content of this evidence summary was up-to-date in March 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.
Currently, 0.4% glyceryl trinitrate rectal ointment (Rectogesic 4 mg/g rectal ointment, ProStrakan) is the only licensed treatment for chronic anal fissure in the UK. It is indicated for the relief of pain associated with chronic anal fissure in adults, but is not licensed for children or young people under 18 years. Topical 0.2% glyceryl trinitrate ointment does not currently have a UK licence for treating chronic anal fissures, or for any other indication. Therefore, its use is unlicensed.
There is some suggestion that the strength of glyceryl trinitrate (0.2% or 0.4%) does not influence the efficacy but increases the incidence of side effects, particularly headache, hence the requests for use of the 0.2% strength. However, no studies were identified that directly compared 0.2% with 0.4% glyceryl trinitrate ointment for treating chronic anal fissure. Only small placebo controlled trials were available to assess the effect of these different strengths indirectly.
Very limited evidence from indirect comparisons in 2 small randomised controlled trials (RCTs; only 47 and 23 adults were analysed in the 0.2% ointment groups in each trial) suggested that 0.2% glyceryl trinitrate ointment might be as effective as 0.4% glyceryl trinitrate at healing anal fissure after an 8-week treatment period in adults. However, in 1 of these studies, neither glyceryl trinitrate strength showed a statistically significant difference from placebo in healing rate.
Limited evidence from 1 small RCT (181 people analysed) showed that lower glyceryl trinitrate ointment strengths were associated with fewer reported headaches in adults.
No evidence was identified to assess the effectiveness or side effects of 0.2% glyceryl trinitrate ointment to treat chronic anal fissure in children or young people under 18 years.
It is not known whether applying less ointment of the same strength, rather than reducing the strength of ointment applied, might have an effect on the incidence or headache.
The evidence for unlicensed 2% topical diltiazem hydrochloride is discussed in detail in the evidence summary Chronic anal fissure: 2% topical diltiazem hydrochloride.
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.