Published: 4 June 2020


Medicines associated with fistulas

Prescriber Update 41(2): 38–39
June 2020

Key Messages

  • Medicines such as axitinib, bevacizumab, nicorandil, pazopanib and tocilizumab are associated with the development of fistulas.


The Centre for Adverse Reactions Monitoring (CARM) received a report concerning a 68-year-old female patient on long-term tocilizumab (CARM ID: 124763). The patient developed a colovaginal fistula, secondary to tocilizumab-induced diverticulitis. Both undesirable effects are described in the Actemra (tocilizumab) data sheet1.


A fistula is an abnormal connection between two hollow spaces or organs and can occur in many different parts of the body2–4. Fistulas are often named according to the spaces or organs that are connected together, for example, rectovaginal (rectum and vagina), tracheoesophageal (trachea and oesophagus) or enterocutaneous (small bowel and skin).

Causes of fistula include surgery, trauma, infection or inflammation2–4. Diverticulitis is inflammation and/or infection of a diverticulum (a sac-like protrusion of the colonic wall).4 Fistula formation is one of the complications of diverticulitis, with most diverticular fistulas occurring between the colon and the bladder (colovesical) and the colon and the vagina (colovaginal)4.

Some medicines are also associated with the development of fistulas. Table 1 provides a few examples (not a comprehensive list), including the information in the data sheet.

Table 1: Examples* of medicines that have been associated with the development of fistulas

Trade name (active ingredient) New Zealand data sheet information regarding fistulas
(data sheet URL)
Inlyta (axitinib) In clinical trials, fistulas were reported in 0.6% of patients, and gastrointestinal perforation and fistula reported in 2% of patients. (
Avastin (bevacizumab) Depending on the study population being treated, gastrointestinal fistula formation was reported in 2.0–8.2% of patients and non-gastrointestinal fistula reported in 0.1–1.8% of patients. Fistulas have also been reported in the post-marketing setting (frequency unknown). (
Ikorel (nicorandil) Patients with diverticular disease may be at particular risk of fistula formation or bowel perforation during nicorandil treatment. Gastrointestinal ulcers are reported as a rare (≥0.01 and <0.1%) adverse reaction. If advanced, these ulcers may develop into fistulating disease. (
Votrient (pazopanib) In clinical studies, gastrointestinal fistula was reported as an uncommon (≥0.1 and <1%) adverse reaction. (
Actemra (tocilizumab) In clinical trials, gastrointestinal perforation was reported at a rate of 0.26–0.28 events per 100 patient years. Gastrointestinal perforation was primarily reported as a complication of diverticulitis, including generalised purulent peritonitis, lower gastrointestinal perforation, fistula and abscess. Diverticulitis is reported as an uncommon (≥0.1% and <1%) adverse reaction. (

* This table contains examples only and is not a comprehensive list.


  1. Roche Products (New Zealand) Limited. 2019. Actemra New Zealand Data Sheet April 2019. URL: (accessed 26 March 2020).
  2. Stein SL. 2019. Enterocutaneous and enteroatmospheric fistulas. In: UpToDate 15 January 2019. URL: (accessed 26 March 2020).
  3. Toglia, MR. 2019. Rectovaginal and anovaginal fistulas. In: UpToDate 16 September 2019. URL: (accessed 24 April 2020).
  4. Pemberton JH. 2019. Diverticular fistulas. In: UpToDate 26 March 2019. URL: (accessed 24 April 2020).
Hide menus
Show menus
0 1 2 4 5 6 7 9 [ /