Lessons from the Literature

Volume 23, Number 9: September 2022

IAHPC Research Advisor Dr. Tania Pastrana selects one article from recently published medical literature and describes why it is worthwhile.

Under My Microscope

Dr. Tania Pastrana. Used with permission.

By Dr. Tania Pastrana
IAHPC Research Advisor

Subcutaneous Drugs and Off-Label Use in Hospice and Palliative Care: A scoping review

Wernli U, Dürr F, Jean-Petit-Matile S, Kobleder A, Meyer-Massetti C. J Pain Symptom Manage 2022. In press. DOI: 10.1016/j.jpainsymman.2022.07.006

The practice of subcutaneous injections began in the mid to late 19th century. In palliative care, it became an established route for the administration of medicines because of poor oral tolerance due to an underlying disease and/or symptoms. About half of authorized medicines prescribed in palliative care are used either for unauthorized indications, by an unauthorized method, or both, as Constanze Rémi and Claudia Bausewein address in their booklet Off-Label-Use in Palliative Medicine.1

A Swiss research team led by Ursina Wernli conducted a scoping review of available data on the tolerability and/or effectiveness of 17 medicines, commonly administered subcutaneously, that are used off-label in Switzerland. They identified 57 studies, most of which were observational. Midazolam was the most researched medicine (n = 14/57, 24.6%), followed by levetiracetam (n = 8/57, 14.0%), haloperidol (n = 8/57, 14.0%), furosemide (n = 7/57, 12.3%), and ketamine (n = 7/57, 12.3%).

This study highlights an important gap in our field. Although we have been using a significant number of medicines off-label throughout the last five decades, we have evidence for only a few of them. More evidence is needed to develop evidence-based guidelines for subcutaneous administration of medicines and medicines commonly used in hospice and palliative care.

  1. Remi C, Bausewein C, editors. Off-Label-Use in Palliative Medicine, 15th edition. 2020.

Link to article

Background: Subcutaneous drug administration is an interesting approach for symptom control in hospice and palliative care. However, most drugs have no marketing authorization for subcutaneous administration and are therefore used off-label. In order to meet the requirements of a safe and effective drug therapy, especially in highly vulnerable patients, it is essential to investigate the scope of evidence of these common practices.

Objectives: The purpose of this scoping review was to provide an overview of available data on the tolerability and/or effectiveness of subcutaneously administered and off-label used drugs.

Method: We performed a scoping review according to the PRISMA extension to identify data available on the tolerability and/or effectiveness of 17 predefined drugs that are commonly administered subcutaneously in Swiss hospices and hospice-like institutions and that have no marketing authorization (off-label use).

Results: The scoping review identified 57 studies with most data available on their tolerability (68% local, 54% systemic), clinical effects (82%), details on dosage (96%) and routes of application (100%). Information on pharmacokinetic properties was mostly missing and only available for fentanyl, levetiracetam, midazolam, and ondansetron. For seven drugs, less than five articles were identified and no studies on codeine or clonazepam were available.

Conclusion: This work provides an overview of current evidence on subcutaneous and off-label used drugs in hospice and palliative care. Although both are common practices, evidence on tolerability and effectiveness, particularly pharmacokinetic data, is limited and the identified information gaps need to be closed. This work establishes a basis for further research in this area.

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