Veterinary medicines

The NZVA has received the following advice from a registered specialist in veterinary neurology on recommended steps to consider when transitioning companion animals from one brand of phenobarbitone to another:

1. Recheck a phenobarbital level (and ideally a CBC/liver profile if it hasn’t been done in the preceding six months) within four to six weeks before the brand change.
2. Recheck the same parameters three to four weeks after the brand change.

While there is no specific evidence to suggest a change in brand may influence the steady state of phenobarbitone, the above steps are precautionary.

We are aware that there will be a significant increase in price for the replacement brand, which may have an impact for some of your clients. Other available treatment options may need to be considered. Please refer to the 2015 ACVIM Small Animal Consensus Statement on Seizure Management in Dogs.

Boehringer Ingelheim Animal Health has shared the below guidelines for transitioning patients from phenobarbitone to imepitoin (PEXION®).

This advice leverages that prepared by the global Canine Epilepsy Advisory Group and is adapted from protocols where there is concern about potential side effects with phenobarbitone. Any decisions to transition a well-controlled patient off phenobarbitone should be made in close consultation with the pet guardian and the veterinarian should explain the potential risks of transitioning a patient from one medication to another (including the possibility that multimodal therapy may be required). Cost as a consideration is an important (but not singular) part of this discussion.

Boehringer Ingelheim Technical services veterinarians understand this is a challenging time for the profession and are happy to take further enquiries on this matter. If you have any questions, please contact Boehringer Ingelheim technical services on 0800 800 822.

Download Boehringer Ingelheim's letter to veterinarians

Download the protocol for transitioning patients from phenobarbitone to imepitoin

Animal Referral Centre Neurologist, Dr Georgina Stewart has shared detailed information on managing the brand change of phenobarbitone tablets. This information was originally posted in private veterinary Facebook groups on 30 August 2023, but Georgina has kindly agreed to share it with NZVA members as well.

Hi everyone, as you are all likely aware there are some changes ahead in regards to availability of phenobarbital in NZ. The 30mg tablets have been approved but so far not the 15mg. Unfortunately the new brand will be significantly more expensive.

This means that many of our patients may need a medication change. There are some guidelines out there on the human medicine front in regard to testing levels before and after a brand change. I personally feel that these are far too intensive for our veterinary patients – I suggest a more reasonable approach as outlined below:

1. Recheck a phenobarbital level (and ideally a CBC/liver profile if it hasn’t been done in the preceding 6 months) within 4-6 weeks prior to the brand change
2. Recheck the same parameters 3-4 weeks after the brand change

In regards to alternative options, several factors need to be kept in mind:

• Not all antiepileptic medications are equal in efficacy
• Phenobarbital needs to be weaned and cannot be stopped rapidly due to the risk of breakthrough seizures

Phenobarbital is one of the most, if not the most, effective antiepileptic medications on the market for veterinary patients. Many of our alternative options such as levetiracetam, imepitoin and zonisamide are not equal in their efficacy – even if they are shiny and new! Based on this, alternative medications need to be chosen very carefully on an individual basis as what works for one will potentially not be suitable for another. Bear in mind that for some dogs, the cost of phenobarbital (even with the price increase) may end up being equivalent to the branded veterinary specific medication such as Pexion – meaning a medication change may not actually be necessary or in the patient’s best interests.

For more severe epileptics (ie dogs with >1 seizure per month, cluster seizures, controlled only with high end serum phenobarbital levels or requires multiple medications) I strongly suggest transitioning onto potassium bromide (dogs ONLY). This medication is my second choice for severe epileptics and is often combined with phenobarbital. Optimus Compounding Labs makes this for ARC and there are many other compounding labs in Auckland and around NZ with the ability to make this medication. Levetiracetam and imepitoin are not indicated as the primary/sole agent for severe epileptic patients.

For less severe epileptics (ie <1 seizure per month or seizures controlled with subtherapeutic or low end serum phenobarbital levels) you have the option of either levetiracetam or Pexion (imepitoin). Levetiracetam needs to be given every 8 hours compared to every 12 hours for imepitoin. If you are planning to use levetiracetam, please ensure you administer a dose rate of at least 20mg/kg every 8 hours. This is a safe medication with limited side effects but it has to be dosed appropriately to be effective.

Transitioning patients safely off phenobarbital and onto an alternative medication does require some overlap so you don’t end up with breakthrough seizures. I suggest starting your secondary agent before weaning phenobarbital to ensure the smoothest transition. Phenobarbital should ideally be weaned over a period of 4-8 weeks if possible, with a 20-25% reduction every 1-2 weeks. Weaning more rapidly than this, especially over less than 1-2 weeks, carries a significant risk of breakthrough seizures which can be life threatening.

If you intend to start potassium bromide as your alternative medication please remember that this drug has a very long half life and can take up to 3 months to reach steady state in the blood. I suggest either allowing 6-8 weeks of KBr administration before you start to taper phenobarbital OR consider a partial loading dose of KBr (in stable patients, I typically double the dose for 1 week before going back down to a maintenance dose of ~15mg/kg BID) prior to tapering phenobarbital.

You may need to warn your clients to expect an increase in sedation or other side effects during the transition between medications.
Our feline patients are slightly more challenging as potassium bromide is not an option (30-50% of cats receiving KBr will develop potentially fatal pneumonitis). There is even less data on cats than in dogs but recent studies suggest that both levetiracetam and imepitoin are well tolerated.

In September 2023, the Agricultural Compounds and Veterinary Medicines (ACVM) team at Ministry for Primary Industries (MPI) issued a notification about the phenobarbitone supply issue for veterinary patients. The notice includes information about what New Zealand Food Safety is doing now, and what they plan to do in the long-term.

If you have any questions about phenobarbitone access, please contact New Zealand Food Safety at approvals@mpi.govt.nz.