S-Adenosylmethionine (SAMe): veterinary dose and monograph

At a glance

Drug class

Gastrointestinal

Also known as

SAMe, Denosyl, Zentonil, Ademetionine

Species with doses

Dogs and Cats

General dose range

18–20 mg/kg PO q24h (empty stomach) — check the species tables for the indication

Routes

PO

Last reviewed

1 October 2026

Indications

• Chronic hepatitis / cholangitis and cholestatic liver disease (hepatoprotection)
• Toxic / drug-induced hepatopathy (acetaminophen, NSAID, xylitol, mushroom, etc.) — antioxidant support
• Vacuolar/steroid hepatopathy; supportive care in any oxidative hepatic injury
• Cognitive dysfunction support in older dogs (off-label)

S-Adenosylmethionine (SAMe) dose by species

Doses are per administration unless stated. mg/kg doses scale with body weight; per-animal, per-quarter and infusion-rate doses are shown as the reference writes them.

Dogs

• Hepatoprotection / hepatopathy: Papich 5e: 20 mg/kg per day PO (or 90 mg small, 225 mg medium, 425 mg large dogs). Plumb’s p.1051: 18 mg/kg/day rounded to tablet size (label); 20 mg/kg once daily for necro-inflammatory, cholestatic or vacuolar hepatopathy (Center). Give on an empty stomach at least 1 h before food; swallow enteric tablets whole.
• Paracetamol (acetaminophen) toxicity (adjunct): Papich 5e: 40 mg/kg PO loading dose, then 20 mg/kg q24h for 7 days. Acetylcysteine is the more reliable antidote.

Cats

• Hepatic lipidosis / cholangitis / hepatoprotection: Plumb’s p.1051: 18–20 mg/kg PO once daily on an empty stomach (label; Center — feline hepatic lipidosis). Papich 5e: 90 mg per cat per day for cats up to 5 kg.
• Paracetamol (acetaminophen) exposure (adjunct): Papich 5e. Acetylcysteine is the more reliable antidote.

Contraindications

Known hypersensitivity. (Few true contraindications — it is a well-tolerated nutraceutical.) Do not crush/split enteric-coated tablets (acid degrades the active). Give on an empty stomach (food reduces absorption).

Species-specific warnings

Cats: A useful antioxidant adjunct in feline hepatic lipidosis/cholangitis — but nutritional support (assisted feeding) remains the cornerstone; SAMe is supportive.

Adverse effects

• Very well tolerated
• Occasional GI upset (vomiting) — rare
• No significant organ toxicity

Drug interactions

• Complementary with silybin/milk thistle and N-acetylcysteine (combined antioxidant hepatoprotection)
• Theoretical serotonergic interaction at high doses (SAMe affects neurotransmitter methylation) — caution with strong serotonergic drugs
• No major adverse pharmacokinetic interactions

Pregnancy and lactation

Considered low-risk (a physiological molecule); use if clearly indicated.

Monitoring

• Liver enzymes / bilirubin trends and clinical response
• Correct administration (empty stomach, whole tablet) — the commonest cause of poor response
• Part of a broader hepatic plan (nutrition, treating the underlying disease)

Toxicity and overdose

Very wide safety margin — overdose typically causes at most mild GI upset. No characteristic organ toxicity. The main "failure mode" is reduced efficacy from incorrect administration (with food, or a crushed/degraded tablet).

Management: Supportive only; no specific antidote needed (wide margin). Manage any GI upset symptomatically.

Clinical pearls

• The go-to nutraceutical hepatoprotectant — it refuels hepatocyte glutathione, the liver's antioxidant; valuable in chronic hepatitis, toxic hepatopathy and feline hepatic lipidosis
• Administration is everything: EMPTY stomach (≥1 h before food) and swallow the enteric tablet WHOLE — crushing or feeding with it wrecks absorption
• Frequently combined with silybin (Denamarin) and/or NAC for layered antioxidant support
• Very safe — but it supports the liver; you still must diagnose and treat the underlying disease

Mechanism of action

SAMe is a central metabolic intermediate: as the principal methyl donor (transmethylation) it supports membrane and protein function, and via the transsulphuration pathway it is the precursor of cysteine and GLUTATHIONE — the liver's major intracellular antioxidant. By replenishing hepatocyte glutathione it protects liver cells from oxidative and toxic damage, supports mitochondrial function and bile flow, and may have anti-apoptotic and (centrally) mood/cognition-supportive effects.

Formulations and products

• 90 / 225 / 425 mg enteric-coated tablet (Denosyl)
• SAMe + silybin combination tablet (Denamarin)
• Denosyl / Denamarin (Nutramax) — SAMe 90/225/425 mg (± silybin), Enteric-coated tablet
• Zentonil (Vetoquinol) — SAMe (ademetionine) tablet, Tablet

Storage

Enteric tablets: 15–30 °C, KEEP IN BLISTER until use (moisture/acid-sensitive); do not crush/split. Protect from light/moisture.

Before you use this dose

Reference doses for veterinary professionals. Confirm the dose against the product label, the patient’s condition, current guidance and local regulations before use; the attending veterinarian remains responsible for every clinical decision.

Other gastrointestinal drugs

• Misoprostol
• Omeprazole
• Pantoprazole
• Ranitidine
• Silymarin (Milk Thistle / Silybin)
• Sucralfate
• Sulfasalazine
• Tylosin

Frequently asked questions