Mercadante, S., Arcuri, E., Fusco, F., Tirelli, W., Villari, P., Bussolino, C. ... Ripamonti, C. (2005). Randomized double-blind, double-dummy crossover clinical trial of oral tramadol versus rectal tramadol administration in opioid-naive cancer patients with pain. Supportive Care in Cancer, 13, 702–707.

To compare the analgesic activity and tolerability of orally administered and rectally administered tramadol

In this crossover trial, 30 patients started with orally administered tramadol and switched to rectally administered tramadol and 30 patients started with rectally administered tramadol and switched to orally administered tramadol.

• The sample was composed of 60 patients, with moderate to severe cancer pain (a score of 4 or greater on a 0–10 scale) of nonneurpoathic origin, who were no longer responsive to nonopioid drugs.
• Of all participants, 36 were female and 24 were male. Forty-four patients completed both periods.
• Mean patient age was 66.1 years.
• The sample contained multiple types of primary tumors.

The study was conducted in Italy.

Multicenter, randomized double-blind, double-dummy crossover trial

• Numeric scale, 0–10, Likert verbal (0 = none, 1 = slight, 2 = moderate, 3 = severe), to measure pain intensity 
• Numeric scale, 0–10, to measure pain relief
• Likert verbal scale (none, slight, moderate, severe), to measure pain relief
• Likert scale, 0–3 (none, slight, moderate, severe), to measure symptoms
• Scale, 0–4 (0 = disturbed, 1 = frequent waking, 2 = not restorative, 3 = good, 4 = very good), to measure sleep
• Whether rectal passage occured within one hour of rectal administration
• Physican's and patient's judgment of efficacy of treatment (0 = absent, 1 = poor, 2 = slight, 3 = good, 4 = excellent), assessed at the end of each crossover phase
• Patients' rating of global satisfaction (0 = absent, 1 = poor, 2 = slight, 3 = good, 4 = excellent) with treatment

• Fifteen patients dropped out because of adverse effects; one patient refused treatment.
• Most physicians and patients favored oral administration.Three patients eliminated suppository within one hour of rectal administration.
• Authors found no differences in the adverse effect profiles of orally and rectally administered tramadol.

Rectal administration of tramadol appears to be a reliable, noninvasive alternative method of pain control for patients who are no longer responsive to nonopioid analgesics and who are unable to take oral tramadol. Rectal administration of tramadol appears to be as safe and effective as oral administration.

The study had a high dropout rate, with 25% of patients dropping out.

Rectal irritation has occurred with rectal administration of tramadol. If the patient is neutropenic or thrombocytopenic, rectal administration may be contraindicated. Patients with diarrhea will have difficulty maintaining and absorbing tramadol. Patients with lack of rectal tone will not be able to keep the suppository in the rectal vault.