TABLE 1.

Three-Day Induction Protocol for Injectable Hydromorphone and Diacetylmorphine in 3 Canadian Injectable Opioid Agonist Treatment (iOAT) Studies

Induction Doses for HDM and [DAM]* in Milligrams (mg)
Day 1
Dose 1: Give 10 mg [15 mg], wait 15 minutes. If no intoxication, add 15 mg [30 mg] more. Observe for 30 minutes†. If patient is fit to, she can leave and return at next dosing window period, in 3 hours.Dose 2: If earlier doses were well tolerated, give 25 mg [45 mg]. Wait 30 minutes. If no intoxication and patient so wishes, give 15 mg [30 mg] more. Observe for 30 minutes. Have patient leave and return at next dosing window period.Dose 3: If earlier doses were well tolerated, give 40 mg [75 mg]. Wait 30 minutes. If no intoxication and patient so wishes, give 15 mg [30 mg] more. Observe for 30 minutes. Patient then leaves is fit, and returns next day.
Day 2
Dose 1: Administer 40% of the total daily dose at Day 1 (up to a total of 45 mg [90 mg] if tolerated all possible doses on first day) Wait 30 minutes. If no intoxication and patient so wishes, give 15 mg [30 mg] more. Observe for 30 minutes. If patient is fit to leave can do so and return at next dosing window period.Dose 2: Administer the maximum tolerated amount of Dose 1 (ie, up to 60 mg [120 mg]). Wait 30 minutes. If no intoxication and patient so wishes, give 15 mg [30 mg] more. Observe for 30 minutes. If patient is fit to leave can do so and return at next dosing window period.Dose 3: Administer the maximum tolerated amount of Dose 2 (ie, up to 75 mg [150 mg]). Wait 30 minutes. If no intoxication and patient so wishes, give 15 mg [30 mg] more. Observe for 30 minutes. If patient is fit to leave can do so and return at next dosing window period.
Day 3
Administer the maximum tolerated amount at Day 2 (ie, up to 90 mg [180mg]) for the 3 doses on Day 3c.
Stabilization phase
On day 4 (after induction), patients continue to receive the maximum tolerated amount at Day 3 for the 3 doses. After consulting with the physician, adjust the dosage once a week until the patient feels comfortable and does not show any excessive intoxication or respiratory depression or until the maximum dose is reached (200 mg [400 mg]/dose or 500 mg [1000 mg]/day).
Maintenance phase
Doses can be adjusted upon discussing options between patient and physicians. Nurses can lower a patient's dose in any given session if there is a safety concern.

DAM, diacetylmorphine; HDM, hydromorphone. Induction doses are presented for HDM and for DAM in brackets.

^*During the NAOMI and SALOME clinical trials, medications were provided in DAM equivalents. HDM to DAM ration is 1:2. For open-label HDM an approximate ratio is used, with adjustments made where suited (eg, For day 1 dose 1 give 10 mg, rather than 7.5 mg of HDM as it is easier to dose).

^†This observation time can be reduced to 20 min, as it is currently in the Crosstown Clinic protocols, since peak plasma levels are reached immediately after injection (See Appendix for induction protocols currently being used).

^cIt is possible that some patients might need higher doses. In the first session, and after waiting 20–30 minutes, patients may be given 15 mg [30 mg] more if the patient wishes and there is no intoxication. This dose would then be given for the remaining doses.

An accelerated protocol for HDM is in place at Crosstown Clinic in Vancouver, adding +20 mg per session to cope with patients’ high opioid tolerance due to the use of potent street opioids like fentanyl. On the third day of the 3-day induction period on the accelerated protocol patients can reach a dose of up 130 mg 3 times daily, as compared to 90 mg on the regular protocol. The maximum daily dose for each day is calculated by summing each of the 3 daily doses.

Successful induction requires 6 separate injections on day 1 and on day 2. Injections could be either intravenous or intramuscular. Injection sites were often rotated for those injecting intramuscularly, given repeated injection at the same site could be painful. Those injecting intravenously may or may not rotate injection sites. Both injection site and rotation of sites was determined by patient preference.