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Novel formulations and routes of administration for opioids in the treatment of breakthrough pain

Lona Louring Christrup, Lena Lundorff and Mads Werner

The interest for assessment and treatment of breakthrough pain (BTP) has been increasing, probably due to a growing attentiveness towards the problems associated with BTP, but also encouraged by the development of novel pharmaceutical formulations specially intended for the treatment of BTP. BTP can be described as ‘an episodic increase in pain intensity over a stable and adequately managed baseline pain’. BTP is a heterogeneous condition, and the most optimal treatment is influenced by a number of different pain-related factors, including the etiology of the pain (cancer or noncancer pain), the pathophysiology of the pain (nociceptive or neuropathic), the characteristics of the pain (type, frequency, and duration). Furthermore, it will depend on various patient-related conditions, such as stage of disease, performance status, compliance and the acceptability of different interventions. Treatment of BTP should be individualized to fit the special needs of the single individual patient. The optimal opioid formulation for the treatment of BTP possesses a pharmacological profile that closely mirrors the intensity–time profile of the BTP episode. Thus, a short onset of action (to relieve pain as quickly as possible) and a relatively short duration of action (to prevent side effects) are preferable. Factors that influence the pharmacological profile of a drug are the physicochemical, pharmaco-kinetic and -dynamic properties of the drug substance, the pharmaceutical formulation and the route of administration. To date, only few formulations specially designed and intended for the treatment of BTP are available. However, many are currently under development and clinical assessment, and some of these are very close to reaching the market.