Pharmacology Notes

Fentanyl is a very potent synthetic opioid, with a short duration of action. It is indicated for use in both acute and chronic pain management. Fentanyl can be administered via the oral mucosa (lozenge), parenterally (IM, IV, SC, intrathecal, epidural), transdermally (patch) and intranasally.

Fentanyl is metabolised in the liver to inactive products and is suitable for patients with renal failure. It can be used in haemodynamically compromised patients.

The adverse effects of fentanyl are similar to those of morphine but with a slightly lower incidence of constipation and confusion; use does not obviate the need for laxatives. See also Table 1.5.

Fentanyl patches are not indicated for acute pain, and are suitable only for patients with relatively stable pain. Fentanyl patches are unsuitable and potentially unsafe for use by opioid-naive patients, or for rapid dose titration. Transdermal dosing using a patch produces a reservoir in the underlying skin and consequent continued absorption. Patches are usually changed every 3 days (72 hours). A patient who has breakthrough pain while using a fentanyl patch should be managed in a similar manner to patients with breakthrough pain while on other sustained-release analgesics. The amount of additional analgesic is used as a guide for an increased strength of patch. A small number of patients, particularly if on lower-dose patches, may not tolerate the increase to the next patch size. In this situation, it may be necessary to change to fentanyl by subcutaneous infusion while adjusting doses, or to change to another opioid. Care should be taken not to ‘overshoot’ with dose increases, as this can cause patients distress.

Absorption may be a problem in a very small number of people who may require the patch to be changed at 60 or even 48 hours to maintain analgesia. After the patch is removed, the half-life of fentanyl in the blood is 15 to 20 hours. Continuous analgesia can also be provided using fentanyl by subcutaneous infusion or the intrathecal route.

Where a fentanyl patch is substituted for another opioid, the total daily dose of the opioid should first be converted to mg per day of morphine. Table 10.7 and Table 10.9 give some data for conversion. Fentanyl patches may have variable rates of delivery in some situations (eg sweaty skin in hot climates); consequently the tables suggest a range for conversion. Fentanyl blood concentrations increase slowly over 18 to 24 hours, so other forms of analgesia should be continued during this period. Likewise, fentanyl concentrations decrease slowly following removal of a patch, falling to 50% after about 17 hours. Replacement with other opioids should therefore be gradual. For breakthrough pain, an alternative route of administration needs to be used; morphine or an alternative opioid can be prescribed.

Patches should not be cut or altered, and must be applied directly to the skin. Cut the hair on the skin rather than shaving it prior to applying the patch, as shaving may increase the rate of absorption by disrupting the outer layers of the skin.

Fentanyl is a highly lipophilic opioid that is well absorbed into the highly vascular nasal mucosa, thus bypassing first pass metabolism. This route of administration has a bioavailability of approximately 70% compared with intravenous administration. Intranasal administration has been evaluated as an alternative to intravenous administration in burns, paediatric emergency and postoperative patients. It is also widely used by paramedics in the prehospital setting. An intranasal delivery device is required to deliver a fine mist of solution quickly into the nasal cavity. A number of devices may be used, but the most widely used currently is the mucosal atomisation device (MAD). Fentanyl is widely available as a 100 microgram in 2 mL ampoule. A 3 mL product containing 300 micrograms/mL is commercially available and some centres manufacture other concentrations extemporaneously. The advantage of the more concentrated formulations is that smaller volumes can be administered, resulting in reduced risk of sneezing and possibly improved absorption due to reduced loss from swallowing. Intranasal administration has the advantage that it may be able to provide more rapid analgesia than intravenous administration and it may avoid the need for intravenous cannulation. This route of administration should be avoided in patients with nasal congestion, occlusion or epistaxis.

Alfentanil, remifentanil and sufentanil are newer drugs that have a more rapid onset, smaller volume of distribution, and more rapid redistribution and clearance compared with fentanyl. They should only be used by those experienced in their use. The peak effect of analgesia is usually 1 to 2 minutes after intravenous administration, while the onset of peak effect observed after intravenous administration of fentanyl is 3 to 4 minutes, and of morphine is 20 minutes. The duration of action is dose-related, but is shorter than that of fentanyl. For longer duration of analgesia they are given by continuous infusion.

Sufentanil can be used in haemodynamically compromised patients. Short-acting remifentanil offers several advantages in patients requiring prolonged infusions. The organ-independent metabolism of remifentanil may be valuable in patients with multiple organ failure.