Key points
- Patients taking phenobarbitone tablets for epilepsy require alerting to the impending brand change and required actions.
- Two appointments with a health-care provider are needed: one before and one after the brand change.
- Serum phenobarbital testing is required to check that concentrations remain at the same level before and after the brand change. Testing is recommended:
- three weeks before the change
- within the week before the change
- within the first week of the change
- one month after the change.
- The brand change necessity may provide health professionals with an opportunity to review patient clinical management.
- Pharmac funding is available to avoid extra patient cost associated with this change.
- Waka Kotahi recommends patients consider a voluntary driving stand-down period of eight weeks following an antiepileptic medication brand change.
The funded brand of phenobarbitone tablets in New Zealand is changing and all patients taking these tablets will need to change brands.
To ensure patients transition safely, prescribers are encouraged to discuss changing brands with their patients as soon as practicable, so the required pre-switch phenobarbital serum level measurements are not missed.
Background
Phenobarbitone (under the PSM brand) 15mg and 30mg tablets, supplied by API Consumer Brands, will soon be replaced with another brand of phenobarbitone tablets in these two strengths.
The new brand will be funded by Pharmac and available from June 1, 2023, ahead of expected depletion of PSM 30mg and 15mg tablets in July and October, respectively.
The closure of the API manufacturing facility in Auckland has necessitated this brand change for phenobarbitone tablets.
Note that the supply of phenobarbitone injection and powder formulations will not be affected.
Phenobarbitone is a barbiturate most often prescribed in this country for managing epilepsy in older people.
In tablet form, it is sometimes used “off-label” for premedication and sedation, and for conditions other than epilepsy, including anxiety, sleeping disorders and cyclic vomiting syndrome.
Phenobarbitone tablets can also be used to manage palliative care, assisted dying, and drug withdrawal/neonatal abstinence.
The advice concerning serum phenobarbital monitoring in this article relates only to people with epilepsy.
Patient group
Around 400 people are dispensed phenobarbitone tablets each year in Aotearoa New Zealand (see table), with most of the dispensing occurring in the community and prescribed by GPs.
Number of people dispensed phenobarbitone from July 1, 2022, to January 20231
| Phenobarbitone | Total | Māori | Pacific peoples |
| 15 mg | 60 | 7 | 2 |
| 30 mg | 374 | 30 | 10 |
It is estimated that around 80 per cent of people currently taking phenobarbitone tablets have epilepsy. Many of these patients (most aged 65 and older) have been on phenobarbitone for a substantial amount of time.1
Recognise vulnerable people
Health services need to be vigilant to ensure people in disability care facilities and aged residential care who are prescribed phenobarbitone are not overlooked for this brand change.
Monitor for change in therapeutic effect
Phenobarbitone is a UK-classified category one epilepsy medicine. Hence, clinically relevant differences between different brands of phenobarbitone may occur, despite bioequivalence having been demonstrated and pharmaceutical formulations being the same between brands.2
During this brand change, it is important for health professionals to monitor serum phenobarbital concentrations in patients with epilepsy (although this is not usual practice), to check that these remain at the same level before and after the medication switch.
Testing timeline
Testing for serum phenobarbital concentration should be performed on samples collected at trough (pre-dose) periods and by the same laboratory, to maintain consistency.
Four occasions are recommended for testing, relative to the time of the patient changing phenobarbitone brands.3
-
- Three weeks before the change (baseline 1).
- Within the week before the change (baseline 2).
- Within the first week of the change – ideally four to 10 days after the first dose of the new brand.
- One month after the change.
Prescribers will need to monitor the results of these blood tests.
Testing outcomes
The formal therapeutic range for serum phenobarbital concentration is derived from group average data, and can differ between laboratories.
Some clinicians may find their patient’s serum phenobarbital concentration is less than the lower limit of this range and therefore may be considered sub-therapeutic.
However, if the patient’s phenobarbitone dose is providing a clinically therapeutic effect and the patient is well-managed, there is no need to increase the dose in order to meet the lower limits of the serum phenobarbital formal therapeutic range.3
A variation of ±10 per cent between the two baseline measurements is considered stable. However, appreciable variation indicates instability and, in this case, a patient will require closer monitoring of their serum phenobarbital concentrations after the brand change, especially early on.3
What to expect if phenobarbital levels are too low or high
Effects of reduced phenobarbital levels include:3
-
- sleep difficulties
- insufficient clinical effects, including seizure activity.
Effects of increased phenobarbital levels may include:3
-
- headache
- mood changes
- drowsiness
- sedation.
Once phenobarbital serum levels increase above the therapeutic range, the patient is at substantial risk of adverse effects. Symptoms of barbiturate toxicity vary between individuals but commonly include:4
-
- difficulty thinking
- decreased level of consciousness
- bradycardia or rapid and weak pulse
- poor coordination
- vertigo
- nausea
- muscle weakness
- thirst
- oliguria (low urine output)
- decreased temperature
- dilated or contracted pupils.
Deaths have resulted from marked respiratory depression, hypotension and coma.
Extra funding provided to help cover costs
Patients will require two appointments with their health-care provider, one before and one after the brand change, in addition to the testing required to assess serum phenobarbital levels.
To reduce barriers and so that patients pay no extra costs associated with this brand change, Pharmac will fund GP co-payments for the two recommended appointments.
Pharmac will also implement an early brand switch fee (BSF) as support for pharmacists to discuss the brand change with patients, as well as proactively identify those who haven’t yet discussed the change with their prescriber.
To reduce barriers and so that patients pay no extra costs associated with this brand change, Pharmac will fund GP co-payments for the two recommended appointments.
Driving after a brand change
Waka Kotahi, the New Zealand Transport Agency, recognises that health professionals — due to their knowledge of their patient’s medical history and other relevant factors — are best placed to determine the patient’s ability to drive.5
To help clinicians make this determination, Waka Kotahi has developed a guide for health professionals on the medical aspects of fitness to drive,6 and a fact sheet on epilepsy/seizures and driving.7
Waka Kotahi has previously recommended advising patients not to drive during medication changes or withdrawal of antiepileptic drugs, and for six months afterwards.
When changing brands of the same medication, Waka Kotahi advises caution and recommends that patients consider a voluntary driving stand-down period of eight weeks following the change.5,8
Other guidance available
If the patient’s epilepsy is not currently well controlled on phenobarbitone tablets, the necessity to change brands provides an opportunity to review a patient’s clinical management. Switching to an alternative epilepsy medicine could be considered.
Although not a requirement when managing the phenobarbitone brand change, health professionals treating patients with epilepsy may like to discuss the change and seek guidance on switching epilepsy medicines with a neurologist.
Talking with a neurologist may help medical clinicians, practice nurses and pharmacists to understand potential issues with a brand change and the need for serum phenobarbital monitoring. This information will also aid in discussions with patients, so they feel appropriately and accurately informed.
Information for consumers about phenobarbitone, anti-seizure medicines, and a variety of epilepsy topics is also available on Health Navigator.
The Māori Pharmacists’ Association, Ngā Kaitiaki o te Puna Rongoā, has a non-urgent, free phone line, 0800 664 488, to answer questions whānau have about their medicines.
Reviewed by Dr John Mottershead, consultant neurologist at Te Whatu Ora Southern.
References
- Te Whatu Ora. (2023). Pharmaceutical claims collection.
- UK Government Medicines and Healthcare products Regulatory Agency. (2017, Nov 24). Antiepileptic drugs: updated advice on switching between different manufacturers’ products.
- Pharmacology and Therapeutics Advisory Committee (PTAC). (2021). Record of the Neurological Subcommittee of PTAC Meeting held on 29 October 2021.
- Lewis, C. B., & Adams, N. (2022). Phenobarbital. StatPearls. Last update 17 January 2022.
- Waka Kotahi, NZ Transport Agency. (2019). Changes to funded brands of epilepsy medication.
- Waka Kotahi, NZ Transport Agency. (2014). Medical aspects of fitness to drive: A guide for health practitioners.
- Waka Kotahi, NZ Transport Agency. (2018). Epilepsy/seizures and driving. (Fact Sheet 17.)
- New Zealand Formulary. (2023). Control of the epilepsies.