Clonazepam oral liquid: confusion between drops, milligrams and millilitres

Case

A 21-year-old male with a neurodegenerative syndrome classified as ‘Leigh-like syndrome with complex 1 deficiency’ was admitted to hospice care for elective respite. The patient’s medical history included seizures, severe scoliosis, chronic faecal loading, urinary retention, global developmental delay, and impaired vision. His regular medications included gabapentin, lamotrigine, levetiracetam, macrogol and nitrazepam (administered via a percutaneous endoscopic gastrostomy [PEG] tube), and fentanyl (transdermal patch). As-needed medications included morphine and paracetamol (via PEG tube) and sodium phosphate enema (rectal). His seizure management plan included as-needed clonazepam (0.6 mg via PEG tube) and as-needed midazolam (10 mg intranasally).

On the electronic medication chart, clonazepam oral liquid 2.5 mg/mL was prescribed with the following directions: ‘6 drops PEG solution when required for seizures’. In the comments field, ‘1 drop = 0.1 mg’ was auto-populated. The patient was given 0.6 mL of the 2.5 mg/mL solution (that is, 1.5 mg clonazepam), drawn up in a syringe and diluted with water, instead of 0.6 mg (6 drops); this meant the patient received 2.5 times the prescribed dose. This occurred on 2 occasions, with 2 registered nurses checking the dose each time. The error was detected after the second administration, where review of documentation and discussion with the nursing team showed the error had also happened with the first dose. There was no evidence of harm to the patient, with no respiratory or central nervous system depression noted. An open disclosure regarding the medication error was provided to the patient's family.

 

Comment

Clonazepam is a benzodiazepine used to manage seizures as well as other symptoms in people receiving palliative care, including anxiety and distress, poor sleep and terminal delirium. Incorrect administration of clonazepam presents a risk due to the potential for increased sedation or respiratory depression.

This case highlights a significant issue in medication safety related to the lack of standardisation in prescribing and administering clonazepam oral liquid. Most enteral liquid medications are prescribed in milligrams, and measured and administered in millilitres using an oral dispenser or enteral syringe (e.g. ENFit™). Clonazepam oral liquid is an exception. The manufacturer of the only registered product in Australia (Rivotril 2.5 mg/mL) recommends prescribing and measuring clonazepam doses as drops only, rather than milligrams and millilitres.¹ They recommend administering the dose by counting the drops onto a spoon using the dropper attached to the lid of the bottle, and have advised that using an oral syringe for measurement would be an off-label practice (personal communication with Pharmaco Australia Ltd, 20 November 2023). However, prescribing and administering clonazepam liquid in drops is not universally followed.

An unpublished audit of clonazepam oral liquid administration errors at 5 healthcare facilities, conducted by the authors using NSW Health’s Incident Management System, revealed 10 errors over a 12-month period. The NSW Government Clinical Excellence Commission is currently developing an advisory on the safe use of clonazepam oral liquid.

SA Health and the Victorian Therapeutics Advisory Group have issued alerts for health professionals about the safe prescribing and administration of clonazepam oral liquid. Both alerts emphasise the need to prescribe clonazepam doses in number of DROPS, with number of milligrams (mg) in brackets, and to measure clonazepam oral liquid doses in DROPS (Box 1).^2,3

Clonazepam in Australia is included in Appendix D of the Poisons Standard. Appendix D places additional controls on the possession or supply of selected Schedule 4 poisons. Health services may require clonazepam to be stored in a restricted drug cupboard with a drug register. A factor that may have contributed to the incident described in this report was that the clonazepam oral liquid balance, and the amount removed for each dose, was documented in the ward’s drug register in millilitres rather than drops, which was potentially confusing.

From an administration perspective, nursing staff face many challenges when administering clonazepam liquid as drops in a spoon (when not given via an enteral access device). Transferring clonazepam in a spoon from the drug cupboard to the bedside for administration is impractical and unsafe. The NSW Health Medication Handling Policy allows Schedule 4 Appendix D drugs to be moved to a medication trolley for dose preparation, but this approach is also not ideal from a logistical, security and safety perspective. Transporting the measured dose to the bedside in a medicine cup or oral dispenser (diluted with water or juice) may overcome these issues and reduce the risk of errors.

Prescribers and nurses may have differing levels of knowledge about best-practice prescribing and administration of clonazepam drops, further contributing to the risk of errors. Some nursing staff at the hospice were not familiar with clonazepam oral liquid prior to this patient’s admission, highlighting the need for education and clear, consistent guidelines.

 

Conclusion and recommendations

Standardising the units used for prescribing and administering clonazepam oral liquid is essential to prevent medication errors. Recommendations to reduce the risk of errors include:

1.    In hospitals and aged-care facilities, the clonazepam oral liquid dose should be prescribed in drops on the medication chart (with the milligram dose specified in brackets) to emphasise that this medication is to be measured in drops. In facilities with an electronic medication chart, ‘1 drop = 0.1 mg’ should automatically be populated (e.g. in the ‘order comments’ field) for clonazepam oral liquid orders.

2.    Records in the drug register should be made as drops, not millilitres, to maintain consistency between prescribing, administration and documentation. To facilitate this, it would be helpful if the manufacturer updated the packaging of clonazepam liquid to indicate on the bottle that 10 mL (the pack size) is equivalent to 250 drops.

3.    In the community, clonazepam oral liquid doses should be prescribed in drops, and the pharmacy dispensing label should describe the dose in drops. Patients and caregivers should receive clear education on the correct administration of clonazepam oral liquid using the supplied dropper.

By standardising the prescribing, measuring, and documenting of clonazepam liquid in drops, we can improve patient safety.

Patient consent for publication of this case study was obtained by the author(s).

Conflicts of interest: none declared

Acknowledgements: The authors would like to thank the nursing team at the Adolescent and Young Adult Hospice for their review and comments on this article.

This article is peer reviewed.

 

References

1. Therapeutic Goods Administration. Australian Product Information - Rivotril (clonazepam) oral liquid. Department of Health and Aged Care; 2025. [cited 2025 Feb 17]
2. SA Health. Clonazepam Oral Liquid – Dose Errors. Medication Safety Alert 01/2018. Government of South Australia; 2018. [cited 2024 Dec 8]
3. Victorian Therapeutics Advisory Group. Clonazepam oral liquid. VicTAG Quality Use of Medicines. 2023. [cited 2024 Dec 8]