Chronic anal fissure: 2% topical diltiazem hydrochloride

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)^[19]. 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^[20].

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)^[21]. 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 (Abd Elhady et al. 2009), headache was reported by 2 (5%) participants randomised to diltiazem and 6 (15%) participants randomised to glyceryl trinitrate (p value not stated)^[22].

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^[23].

In 1 RCT (Suvarna et al. 2012), mild headache was reported in 5 (5.5%) participants randomised to diltiazem and none of those randomised to surgery (p<0.0001)^[24].

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^[25]. 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.