# Phenobarbital vs Keppra for Dogs: Which Seizure Drug? Phenobarbital and Keppra (levetiracetam) are both used to control seizures in dogs, but they work differently and fit different situations. Phenobarbital is a long-established daily anticonvulsant, while Keppra is often used as an add-on or for emergencies. The right choice depends on your dog's seizure pattern, health, and how well other drugs are working. This article is educational and is not a substitute for veterinary diagnosis or treatment. ## Quick Answer - Phenobarbital and levetiracetam are the two most commonly prescribed first-line seizure drugs in US dogs, at 34.9% and 31.3% of cases in one large primary care study [1]. - Phenobarbital is absorbed quickly and well, so it can be used to stop cluster seizures or status epilepticus and prevent more seizures [2]. - Levetiracetam has limited liver metabolism and is cleared mainly by the kidneys, which is why it is often chosen as an add-on drug [3]. - Both drugs need a veterinarian to set the dose based on your dog's weight and health, and neither should ever be stopped suddenly [4]. - Blood monitoring is part of long-term treatment with either drug, and liver-related lab changes are the most common finding in dogs on anticonvulsants [5]. ## What Each Drug Is and What Veterinarians Use It For Phenobarbital is one of the oldest and most widely used anticonvulsants in veterinary medicine. It is a key anticonvulsant for dogs and remains a standard first choice for long-term seizure control [6]. Because it has high bioavailability and is rapidly absorbed, veterinarians also use it to prevent further seizures in dogs with cluster seizures, reactive seizures, or status epilepticus [2]. Levetiracetam, sold under the brand name Keppra, is a newer anticonvulsant. It is commonly used as an adjunctive (add-on) antiseizure medication in dogs because of its favorable pharmacokinetic profile and limited hepatic metabolism [3]. In other words, it does not lean heavily on the liver to be cleared, which matters for dogs already taking phenobarbital or with liver concerns. In US primary care, phenobarbital and levetiracetam together account for about two-thirds of first-line seizure prescriptions, followed by zonisamide and potassium bromide [1]. So when your vet talks about options, these two are usually the starting point. ## How They Work Phenobarbital works by dampening abnormal electrical activity in the brain. It is a broad-spectrum anticonvulsant, meaning it can help with many seizure types. Its main drawback is that it is metabolized by the liver, and the specific dog liver enzymes involved in breaking it down have been the subject of ongoing research [6]. That liver processing is why long-term phenobarbital use requires periodic bloodwork. Levetiracetam works through a different mechanism and is largely eliminated by the kidneys unchanged [3]. Because it does not rely on the liver, it is often paired with phenobarbital when seizures are not fully controlled on phenobarbital alone. This combination approach is common in dogs with idiopathic epilepsy. If your dog's seizures are not controlled on one drug, your veterinarian may check the drug level in the blood before adding a second medication. If the level is below the therapeutic range, the dose may be increased first. If the level is already at the high end and seizures continue, adding another anticonvulsant may be the next step [4]. ## Dosing Basics ### Who decides the dose Your veterinarian does. The dose is calculated from your dog's body weight, overall health, kidney and liver function, and other medications. Never adjust the dose on your own, and never give a dose meant for another pet or a human. ### How each drug is given Phenobarbital is usually given by mouth for long-term maintenance. In an emergency, it can be given intravenously [2]. Levetiracetam is also typically given by mouth, and a compounded intranasal form has been studied in healthy dogs as a possible option for rapid treatment of cluster seizures and status epilepticus [7]. For any seizure drug, the oral route is ideal for long-term maintenance, but absorption can vary based on the drug, its formulation, other drugs, and even diet [4]. ### What to do about a missed dose If you miss a dose, call your veterinarian's office for guidance. Do not double up unless they tell you to. Abruptly stopping phenobarbital can trigger severe withdrawal seizures, so tapering is essential if the drug is ever discontinued [4]. The same caution applies to benzodiazepines. If your dog vomits a dose or you are unsure whether it was absorbed, ask before giving another. ## Side Effects: What to Watch For | Side effect | How common or serious | What to do | |---|---|---| | Sleepiness, wobbliness, increased appetite, thirst, urination | Common with phenobarbital, especially early or after dose changes | Note the pattern and tell your vet at the next visit. Call sooner if your dog seems sedated or unsteady | | Elevated liver enzymes on bloodwork | Common in dogs on anticonvulsants, often adaptive instead of true disease [5] | Keep scheduled monitoring appointments. Your vet will interpret the numbers in context | | Blood cell changes (anemia or low cell counts) | Less common than liver changes, but possible [5] | Routine bloodwork catches these. Report pale gums, weakness, or unusual bruising right away | | Kidney biomarker changes with levetiracetam | In one 4-week study of dogs on phenobarbital plus levetiracetam, no significant changes were found in SDMA, creatinine, BUN, phosphorus, or albumin [3] | Still worth periodic monitoring, especially in dogs with kidney disease | | Increased seizures after stopping a drug suddenly | Serious and preventable | Never stop phenobarbital or a benzodiazepine abruptly. Taper only under veterinary direction [4] | Most dogs adjust to phenobarbital over the first few weeks. If sedation or wobbliness does not improve, or if your dog seems painful, confused, or unable to stand, call your veterinarian. ## Who Should Not Take These Drugs and What Interacts With Them Phenobarbital is processed by liver enzymes, so it can interact with other drugs that use the same pathways. This is a real concern in dogs taking multiple medications. If your dog is on other anticonvulsants, heart medications, antibiotics, or pain drugs, your veterinarian needs the full list. For a deeper look at managing multiple medications, see [Drug Interactions with Antiepileptic Drugs in Veterinary Patients: Managing Polypharmacy](/knowledge/veterinary-medicine/clinical-pharmacology/drug-interactions-antiepileptic-veterinary). Levetiracetam is cleared by the kidneys, so dogs with kidney disease may need dose adjustments or closer monitoring [3]. It is often chosen when liver concerns make phenobarbital less appealing. Dogs with certain metabolic or hormonal conditions, pregnant or nursing dogs, and dogs with known sensitivity to a drug should be discussed with your veterinarian before starting or changing therapy. There is no single rule that fits every dog. If your dog has seizures caused by low blood sugar from insulin, long-term anticonvulsant therapy is often not needed. In one study of 49 dogs with insulin-induced hypoglycemic seizures, only 3 of 34 dogs with seizures required long-term management [8]. That is a good example of why finding the underlying cause matters before committing to a daily seizure drug. For help understanding how drug levels are checked and what the numbers mean, see [Therapeutic Monitoring of Antiepileptic Drugs in Dogs and Cats](/knowledge/veterinary-medicine/veterinary-pathology-microbiology/therapeutic-monitoring-antiepileptic-drugs-dogs-cats). ## Overdose and When to Call for Help Signs of phenobarbital overdose include extreme sedation, inability to stand, slow breathing, and unresponsiveness. Levetiracetam overdose can cause severe drowsiness, vomiting, and unsteadiness. If you think your dog got too much of either drug, call your veterinarian or an animal poison control hotline immediately. Do not wait for symptoms to worsen. Bring the medication bottle with you or have it nearby so you can tell the veterinarian exactly what was given and when. If your dog is having trouble breathing, is unconscious, or is having continuous seizures, go to the nearest emergency veterinary hospital right away. ## Limitations and When to Contact a Veterinarian No article can tell you which drug is right for your dog. That decision needs a veterinarian who knows your dog's history, lab work, and seizure pattern. Call your veterinarian the same day if your dog has more seizures than usual, seems sedated or unsteady after a dose change, vomits a dose, or has a change in appetite or water intake. Go to an emergency clinic now if a seizure lasts more than a few minutes, if seizures keep coming back without your dog fully recovering between them, if your dog is having trouble breathing, or if your dog cannot stand or wake up after a seizure. Keep routine monitoring visits even when your dog seems fine. Bloodwork is how problems get caught early, and liver-related changes are the most common lab finding in dogs on anticonvulsants [5]. Your veterinarian will decide how often to check levels and organ function based on your dog's drug, dose, and response. ## Frequently Asked Questions ### Is Keppra or phenobarbital better for dogs? Neither is universally better. Phenobarbital is a proven first-line drug for many seizure types and is also used in emergencies [2]. Levetiracetam is often chosen as an add-on because it does not rely on the liver [3]. Your veterinarian will match the drug to your dog's seizure pattern and health. ### Can my dog take phenobarbital and Keppra together? Yes, this combination is common. Levetiracetam is frequently used as an adjunctive medication in dogs already receiving phenobarbital [3]. The goal is better seizure control with manageable side effects. ### Does Keppra work fast enough for a seizure emergency? An intranasal compounded levetiracetam product has been studied in healthy dogs and reached target blood concentrations, but this is not the same as proven emergency use in every dog [7]. For status epilepticus and cluster seizures, injectable phenobarbital is a standard option because of its rapid absorption [2]. Ask your veterinarian what plan is right for your dog. ### Will my dog need blood tests on these drugs? Yes, monitoring is expected with long-term anticonvulsant therapy. Drug levels may be checked when seizures are not controlled, and routine lab work looks for liver and blood changes [4][5]. Your veterinarian sets the schedule. ### Can I stop my dog's seizure medication if the seizures stop? No. Stopping suddenly can cause severe withdrawal seizures, especially with phenobarbital [4]. If your veterinarian decides to discontinue a drug, the dose is tapered gradually over a few weeks [4]. Always talk to your vet first. For more on choosing and monitoring seizure drugs, see [Canine Epilepsy: Antiepileptic Drug Selection and Monitoring](/knowledge/veterinary-medicine/clinical-internal-medicine/canine-epilepsy-antiepileptic-drug-selection-monitoring) and [What Are the Side Effects of Seizure Medication in Dogs?](/knowledge/veterinary-medicine/pet-medication-guide/seizure-medication-side-effects-dogs). ## Related Articles - [Canine Epilepsy: Antiepileptic Drug Selection and Monitoring](/knowledge/veterinary-medicine/clinical-internal-medicine/canine-epilepsy-antiepileptic-drug-selection-monitoring) - [Canine Epilepsy: Diagnosis and Antiepileptic Drug Management](/knowledge/veterinary-medicine/clinical-methods/canine-epilepsy-diagnosis-antiepileptic-management) - [Therapeutic Monitoring of Antiepileptic Drugs in Dogs and Cats](/knowledge/veterinary-medicine/veterinary-pathology-microbiology/therapeutic-monitoring-antiepileptic-drugs-dogs-cats) - [What Are the Side Effects of Seizure Medication in Dogs?](/knowledge/veterinary-medicine/pet-medication-guide/seizure-medication-side-effects-dogs) - [Drug Interactions with Antiepileptic Drugs in Veterinary Patients: Managing Polypharmacy](/knowledge/veterinary-medicine/clinical-pharmacology/drug-interactions-antiepileptic-veterinary) - [Therapeutic Drug Monitoring in Epileptic Dogs: Antiepileptic Drug Levels](/knowledge/veterinary-medicine/clinical-pharmacology/therapeutic-drug-monitoring-epileptic-dogs-antiepileptic-drug-levels) - [Phenobarbital for Dogs: Side Effects and Overdose Signs](/knowledge/veterinary-medicine/pet-medication-guide/phenobarbital-dogs-side-effects-overdose) - [Keppra for Dogs: Side Effects and Effectiveness](/knowledge/veterinary-medicine/pet-medication-guide/keppra-dogs-side-effects-effectiveness) - [Keppra for Dogs With Seizures or Brain Tumors](/knowledge/veterinary-medicine/pet-medication-guide/keppra-dogs-seizures-brain-tumor) ## References 1. [Retrospective study on canine idiopathic epilepsy treatment in primary care practices in the United States](https://pubmed.ncbi.nlm.nih.gov/41737686/). Frontiers in veterinary science, 2026. 2. [Anticonvulsants for Emergency Treatment of Seizures in Dogs and Cats - Pharmacology](https://www.merckvetmanual.com/pharmacology/systemic-pharmacotherapeutics-of-the-nervous-system/anticonvulsants-for-emergency-treatment-of-seizures-in-dogs-and-cats). Merck Veterinary Manual. 3. [Short-Term Renal Effects of Add-On Levetiracetam in Client-Owned Dogs with Idiopathic Epilepsy Receiving Phenobarbital: A Four-Week Prospective Study](https://pubmed.ncbi.nlm.nih.gov/42797888/). Veterinary sciences, 2026. 4. [Anticonvulsants for Treatment of Animals - Pharmacology](https://www.merckvetmanual.com/pharmacology/systemic-pharmacotherapeutics-of-the-nervous-system/anticonvulsants-for-treatment-of-animals). Merck Veterinary Manual. 5. [Antiepileptic drug therapy in companion animals: New perspectives on clinical pathology monitoring](https://pubmed.ncbi.nlm.nih.gov/42571377/). Veterinary and animal science, 2026. 6. [Different Roles of Canine Cytochrome P450 2C and 3A Enzymes Involved in the Oxidative Metabolism of Phenobarbital, a Key Anticonvulsant for Dogs: Comparison With Human P450 Enzymes](https://pubmed.ncbi.nlm.nih.gov/42410958/). Journal of veterinary pharmacology and therapeutics, 2026. 7. [Single-Dose Pharmacokinetics of Intranasal Levetiracetam in Healthy Dogs](https://pubmed.ncbi.nlm.nih.gov/41557509/). Journal of veterinary pharmacology and therapeutics, 2026. 8. [Long-term antiepileptic therapy is often not required in dogs with insulin-induced hypoglycemic seizures: a multicenter retrospective study of 49 dogs](https://pubmed.ncbi.nlm.nih.gov/41237494/). Journal of the American Veterinary Medical Association, 2026. ## Further Reading - [Epilepsy in Small Animals - Nervous System (Merck Veterinary Manual)](https://www.merckvetmanual.com/nervous-system/epilepsy-in-small-animals/epilepsy-in-small-animals) - [American Veterinary Medical Association: First Aid Tips for Pet Owners](https://www.avma.org/resources-tools/pet-owners/emergencycare/first-aid-tips-pet-owners) - [Merck Veterinary Manual: Dog Owners](https://www.merckvetmanual.com/dog-owners)