Download Dose titration protocol for Intranasal fentanyl

Dose titration phase for intranasal opiates in hospice patients.
Goal – Find the appropriate, safe dose of medication that satisfactorily controls the patients pain, yet dose not over
sedate them or lead to respiratory compromise. Once the appropriate dose is found – this should be used for all future
episodes of breakthrough pain.
Medications most appropriate for adult breakthrough pain:
Sufentanil 50 mcg/ml generic formulation (8 to 10 times as potent as fentanyl).1
Fentanyl 500 mcg/ml compounded formulation.
 (In the extremely opiate tolerant patient with very difficult to control pain fentanyl can be compounded
to even higher concentrations of 1000 or 2000 mcg/ml based on data from Kress et al and Mercadante
et al).2, 3 If the initial titration phase fails with 500 mcg/ml fentanyl or standard generic sufentanil, if
appropriate repeat with more concentrated fentanyl until appropriate dose is determined or side effects
are intolerable.
Phase 1
Procedure
Volume of drug
Dose_______________
Single spray up each nostril at onset of pain
(2 sprays at time zero)
0.2 ml
10 mcg sufentanil
100 mcg fentanyl
Wait 10 minutes are reassess pain and drowsiness – if pain still significant and not drowsy, repeat dose
Single spray up each nostril at onset of pain
(2 sprays at 10 minutes)
0.2 ml
10 mcg sufentanil
100 mcg fentanyl
Wait 10 minutes are reassess pain and drowsiness – if pain still significant and not drowsy, repeat dose
Single spray up each nostril at onset of pain
(2 sprays at 20 minutes)
0.2 ml
10 mcg sufentanil
100 mcg fentanyl

If pain is adequately controlled at any point during this phase, then the number of spray administered
should be use all at the same time for the next breakthrough pain spell to determine if in fact it is
adequate and safe. If too much sedation occurs – back off by 1-2 sprays until the safe and effective dose
is found. If effective 75% of the time or more – this is the dose the patient should use for all further
breakthrough pain spells.

At 30 minutes if pain is not controlled, provide usual breakthrough pain medication and wait until next
spell of breakthrough pain – using Phase II
Phase II – Proceed to this step only if you failed to determine appropriate dose during phase 1
Procedure
Volume of drug
Dose_______________
Two sprays up each nostril at onset of pain
(4 sprays at time zero)
0.4 ml
20 mcg sufentanil
200 mcg fentanyl
Wait 10 minutes are reassess pain and drowsiness – if pain still significant and not drowsy, repeat dose
Two sprays up each nostril at onset of pain
(4 sprays at time zero)
0.4 ml
20 mcg sufentanil
200 mcg fentanyl
Wait 10 minutes are reassess pain and drowsiness – if pain still significant and not drowsy, repeat dose
Two sprays up each nostril at onset of pain
(4 sprays at time zero)
0.4 ml
20 mcg sufentanil
200 mcg fentanyl

If pain is adequately controlled at any point during this phase, then the number of spray administered
should be use all at the same time for the next breakthrough pain spell to determine if in fact it is
adequate and safe. If too much sedation occurs – back off by 1-2 sprays until the safe and effective dose
is found. If effective 75% of the time or more – this is the dose the patient should use for all further
breakthrough pain spells.

At 30 minutes if pain is not controlled, provide usual breakthrough pain medication and wait until next
spell of breakthrough pain – using Phase III
Phase III – Proceed to this step only if you failed to determine appropriate dose during phase II
Procedure
Volume of drug
Dose_______________
Four sprays up each nostril at onset of pain
(8 sprays at time zero)
0.8 ml
40 mcg sufentanil
400 mcg fentanyl
Wait 10 minutes are reassess pain and drowsiness – if pain still significant and not drowsy, repeat dose
Four sprays up each nostril at onset of pain
(8 sprays at time zero)
0.8 ml
40 mcg sufentanil
400 mcg fentanyl
Wait 10 minutes are reassess pain and drowsiness – if pain still significant and not drowsy, repeat dose
Four sprays up each nostril at onset of pain
(8 sprays at time zero)
0.8 ml
40 mcg sufentanil
400 mcg fentanyl

If pain is adequately controlled at any point during this phase, then the number of spray administered
should be use all at the same time for the next breakthrough pain spell to determine if in fact it is
adequate and safe. If too much sedation occurs – back off by 1-2 sprays until the safe and effective dose
is found. If effective 75% of the time or more – this is the dose the patient should use for all further
breakthrough pain spells.

At 30 minutes if pain is not controlled, provide usual breakthrough pain medication and re-evaluate
whether this patient can have their pain controlled via this mechanism. If still interested, consider
highly concentrated fentanyl compounded to 2 or 4 times the potency of the current formulation
References:
1.
Good P, Jackson K, Brumley D, Ashby M. Intranasal sufentanil for cancer-associated
breakthrough pain. Palliat Med 2009;23(1):54-8.
2.
Kress HG, Oronska A, Kaczmarek Z, Kaasa S, Colberg T, Nolte T. Efficacy and tolerability of
intranasal fentanyl spray 50 to 200 microg for breakthrough pain in patients with cancer: a phase III,
multinational, randomized, double-blind, placebo-controlled, crossover trial with a 10-month, open-label
extension treatment period. Clin Ther 2009;31(6):1177-91.
3.
Mercadante S, Radbruch L, Davies A, et al. A comparison of intranasal fentanyl spray with oral
transmucosal fentanyl citrate for the treatment of breakthrough cancer pain: an open-label, randomised,
crossover trial. Current medical research and opinion 2009;25(11):2805-15.