Table 2.

Potential advantages and disadvantages of different routes for available breakthrough pain treatments (adapted from Nicholson and Agarwala⁷⁵ and product prescribing information)²²,²⁸–³⁰,³²,³³

Administration route Available formulations	Advantages	Disadvantages	Pivotal clinical trials
Oral transmucosal Oral transmucosal fentanyl citrate (ACTiQ®)	The mucosally absorbed dose (25%) bypasses hepatic first-pass metabolism Rapid onset of action Cessation of drug administration is feasible if toxicity develops Can be used for pediatric and geriatric patientsa Can be used by patients who are unable to swallow or find medications difficult to swallow due to nausea/vomiting	Relatively low surface area for absorption May be difficult for patients with dry mouth/mucositis The “lollipop” may be perceived as childish Potential for dental decay with prolonged use Absorption can be variable Patients may require training on correct use Takes time to dissolve	Farrar et al37
Transbuccal Fentanyl buccal tablets (FENTORA®) Fentanyl buccal soluble film (ONSOLIS®)	The mucosally absorbed dose (48% with buccal tablets; 51% with soluble film) bypasses hepatic first-pass metabolism Rapid onset of action Greater bioavailability than oral transmucosal products Can be used by patients who are unable to swallow or find medications difficult to swallow due to nausea/vomiting	Lower permeability via buccal membrane compared with sublingual membrane Smaller surface area for absorption May be difficult for patients with dry mouth/mucositis	Portenoy et al (FENTORA®)51 Rauck et al (ONSOLIS®)63
Sublingual Sublingual fentanyl tablet (ABSTRAL®) Sublingual fentanyl spray (SUBSYSTM)	The mucosally absorbed dose bypasses hepatic first-pass metabolism Rapid onset of action Can be used by patients who are unable to swallow or find medications difficult to swallow due to nausea/vomiting	May be difficult for patients with dry mouth/mucositis Drug and delivery system may be ingestedin saliva May be limited to lower doses	Rauck et al (ABSTRAL®)65 Rauck et al (SUBSYS™)67
Intranasal intranasal fentanyl spray (instanyl®) Fentanyl pectin nasal spray (Lazanda®)	The systemically absorbed dose bypasses hepatic first-pass metabolism Can be administered by caregivers Rapid onset of actionConvenient Can be used by patients who are unable to swallow or find medications difficult to swallow due to nausea/vomiting	Patients may require training in the correct administration technique for intranasal sprays Potential for application-site adverse effects including nasal irritation Potentially unsuitable for patients with colds or illnesses that result in changes to the nasal mucosa Quantity of drug absorbed may be variable Nasal drip or swallowing can affect absorption May be difficult for patients lacking manual dexterity Dose limited to <0.2 mL	Kress et al (Instanyl®)68 Portenoy et al (Lazanda®)72

Note: ^aACTIQ is not indicated for use in pediatric patients.