Evidence Hierarchy
1. Systematic Review & Network Meta-Analysis — Wang et al., 2025
Wang C, Ni J, Xiong Y, Chen J, Li B, Xu L. The efficacy of diltiazem, glyceryl trinitrate, nifedipine, minoxidil, and lidocaine for the medical management of anal fissure: a systematic review and network meta-analysis of randomized controlled trials. Int J Surg. 2025;111(4):3020–3029. doi:10.1097/JS9.0000000000002263. PMID:39878173.
22 RCTs; 1,770 participants. Nifedipine demonstrated the highest healing rate among the pharmacological treatments evaluated.
2. Clinical Practice Guideline — SIUCP, 2023
Brillantino A, Renzi A, Talento P, Iacobellis F, Brusciano L, Monaco L, et al. The Italian Unitary Society of Colon-Proctology (SIUCP: Società Italiana Unitaria di Colonproctologia) guidelines for the management of anal fissure. BMC Surg. 2023;23(1):311. doi:10.1186/s12893-023-02223-z. PMID:37833715.
GRADE-based guideline supporting topical calcium-channel blockers as a non-surgical treatment option for chronic anal fissure.
3. Randomised Controlled Trial — Perrotti et al., 2002
Perrotti P, Bove A, Antropoli C, Molino D, Antropoli M, Balzano A, De Stefano G, Attena F. Topical nifedipine with lidocaine ointment vs. active control for treatment of chronic anal fissure: results of a prospective, randomized, double-blind study. Dis Colon Rectum. 2002;45(11):1468–1475. doi:10.1007/s10350-004-6452-1. PMID:12432293.
110 patients with chronic anal fissure. Direct evidence for the 0.3% nifedipine + 1.5% lidocaine combination, including the reported 94.5% healing rate.
4. Supporting Randomised Controlled Trials
Acute thrombosed external haemorrhoids
Perrotti P, Antropoli C, Molino D, et al. Conservative treatment of acute thrombosed external hemorrhoids with topical nifedipine. Dis Colon Rectum. 2001;44(3):405–409. doi:10.1007/BF02259975. PMID:11289288.
Post-haemorrhoidectomy pain
Perrotti P, Dominici P, Grossi E, Cerutti R, Antropoli C. Topical nifedipine with lidocaine ointment versus active control for pain after hemorrhoidectomy: results of a multicentre, prospective, randomized, double-blind study. Can J Surg. 2010;53(1):17–24. PMID:20100408. PMCID.
5. Haemorrhoidal Disease Guideline — SIUCP, 2024
Brillantino A, Renzi A, Talento P, et al. The Italian Unitary Society of Colon-Proctology (Società Italiana Unitaria di Colonproctologia) guidelines for the management of acute and chronic hemorrhoidal disease. Ann Coloproctol. 2024;40(4):287–320. doi:10.3393/ac.2023.00871.0124.
Evidence statement
The current evidence base supports topical nifedipine as an established non-surgical pharmacological approach to anal fissure, with the 2025 network meta-analysis providing contemporary comparative evidence for fissure healing and the Perrotti trial providing direct evidence for the 0.3% nifedipine + 1.5% lidocaine combination.
For HCP communications, the strongest and most defensible positioning is therefore chronic primary anal fissure, with the additional haemorrhoidectomy and thrombosed-haemorrhoid studies presented as supporting evidence rather than as primary product indications.
All efficacy and indication statements should be aligned with the applicable Marketing Authorisation, SmPC and UK promotional requirements before use in promotional materials.