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

ProcedureVolume of drugDose______

Single spray up each nostril at onset of pain0.2 ml10 mcg sufentanil

(2 sprays at time zero)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 pain0.2 ml10 mcg sufentanil

(2 sprays at 10 minutes)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 pain0.2 ml10 mcg sufentanil

(2 sprays at 20 minutes)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

ProcedureVolume of drugDose______

Two sprays up each nostril at onset of pain0.4 ml20 mcg sufentanil

(4 sprays at time zero)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 pain0.4 ml20 mcg sufentanil

(4 sprays at time zero)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 pain0.4 ml20 mcg sufentanil

(4 sprays at time zero)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

ProcedureVolume of drugDose______

Four sprays up each nostril at onset of pain0.8 ml40 mcg sufentanil

(8 sprays at time zero)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 pain0.8 ml40 mcg sufentanil

(8 sprays at time zero)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 pain0.8 ml40 mcg sufentanil

(8 sprays at time zero)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.