Evidence review: safety
Two of the RCTs (n=140) included in the Cochrane review found that glyceryl trinitrate had significantly more adverse effects than topical diltiazem (details not given, pooled odds ratio [OR] 3.57, 95% confidence interval [CI] 1.28 to 9.97). In a third study (Shrivastava et al. 2007), none of the 30 participants randomised to topical diltiazem ointment reported side effects, whereas 20 (67%) participants randomised to the glyceryl trinitrate reported headache.
In 1 of the additional RCTs (Sanei et al. 2009), headache occurred in 58.8% of participants randomised to glyceryl trinitrate and none in those randomised to diltiazem (p=0.001). Of the 51 participants randomised to glyceryl trinitrate, 14 (27.5%) discontinued treatment because of headache and elected to receive surgery. Two participants (3.9%) randomised to diltiazem reported pruritus but none of those randomised to glyceryl trinitrate reported this.
In 1 RCT (Samim et al. 2012), perianal itching after application of the cream was reported in 1 (1.7%) participant randomised to botulinum toxin and 11 (14.9%) participants randomised to diltiazem (p=0.012). No other adverse effects were reported.
In the single RCT in children (Cevik et al. 2009), 1 participant randomised to glyceryl trinitrate ointment and 1 randomised to topical diltiazem ointment experienced perianal dermatitis. The authors stated that no other children experienced significant side effects, but that headache could not be assessed because of the age of the children.
 Shrivastava UK, Jain BK, Kumar P et al. (2007) A comparison of the effects of diltiazem and glyceryl trinitrate ointment in the treatment of chronic anal fissure: a randomized clinical trial. Surgery Today 37: 482–5
 Sanei B, Mahmoodieh M, Masoudpour H (2009) Comparison of topical glyceryl trinitrate with diltiazem ointment for the treatment of chronic anal fissure: a randomized clinical trial. Acta Chirurgica Belgica 109: 727–30
 Abd Elhady HM, Othman IH, Hablus MA et al. (2009) Long-term prospective randomised clinical and manometric comparison between surgical and chemical sphincterotomy for treatment of chronic anal fissure. South African Journal of Surgery 47: 112–4
 Samim M, Twigt B, Stoker L et al. (2012) Topical diltiazem cream versus botulinum toxin a for the treatment of chronic anal fissure: a double-blind randomized clinical trial. Annals of Surgery 255: 18–22
 Suvarna R, Panchami, Guruprasad RD (2012) Chemical sphicterotomy versus surgical sphicterotomy in the management of chronic fissure in ANO: A prospective, randomized trial. Journal of Clinical and Diagnostic Research 6: 1018–21
 Cevik M, Boleken ME, Koruk I et al. (2012) A prospective, randomized, double-blind study comparing the efficacy of diltiazem, glyceryl trinitrate, and lidocaine for the treatment of anal fissure in children. Pediatric Surgery International 28: 411–6