# S-Adenosylmethionine (SAMe): veterinary dose and monograph

> S-Adenosylmethionine (SAMe) is a veterinary gastrointestinal drug. A naturally occurring molecule (ademetionine) and the leading nutraceutical HEPATOPROTECTANT — it is the precursor for glutathione (the liver's main antioxidant) and for transmethylation/transsulphuration reactions, so it raises hepatic… Indications include 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. This monograph lists 4 reference doses for dogs and cats, each with route, frequency and source.

Source: https://vetmasterji.com/drugs/sam-e · Last reviewed: 2026-10-01

## 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

*S-Adenosylmethionine (SAMe) doses for dogs*

| Indication | Dose | Route | Frequency | Duration |
| --- | --- | --- | --- | --- |
| Hepatoprotection / hepatopathy | 18–20 mg/kg | PO | q24h on empty stomach | — |
| Paracetamol (acetaminophen) toxicity (adjunct) | 40 mg/kg | PO | once, then 20 mg/kg q24h for 7 days | — |

- 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

*S-Adenosylmethionine (SAMe) doses for cats*

| Indication | Dose | Route | Frequency | Duration |
| --- | --- | --- | --- | --- |
| Hepatic lipidosis / cholangitis / hepatoprotection | 18–20 mg/kg | PO | q24h on empty stomach | — |
| Paracetamol (acetaminophen) exposure (adjunct) | 180 mg per cat PO q12h for 3 days, then 90 mg q12h for 11 days | PO | q12h | 14 days |

- 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

> **Caution:** 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

> **Caution:** 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

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- [Pantoprazole](https://vetmasterji.com/drugs/pantoprazole)
- [Ranitidine](https://vetmasterji.com/drugs/ranitidine)
- [Silymarin (Milk Thistle / Silybin)](https://vetmasterji.com/drugs/silymarin)
- [Sucralfate](https://vetmasterji.com/drugs/sucralfate)
- [Sulfasalazine](https://vetmasterji.com/drugs/sulfasalazine)
- [Tylosin](https://vetmasterji.com/drugs/tylosin)

## Frequently asked questions

### What is the dose of S-Adenosylmethionine (SAMe) for dogs?

Reference doses for S-Adenosylmethionine (SAMe) in dogs: 18–20 mg/kg PO q24h on empty stomach (Hepatoprotection / hepatopathy); 40 mg/kg PO once, then 20 mg/kg q24h for 7 days (Paracetamol (acetaminophen) toxicity (adjunct)). Confirm against the label and the patient before use.

### What is the dose of S-Adenosylmethionine (SAMe) for cats?

Reference doses for S-Adenosylmethionine (SAMe) in cats: 18–20 mg/kg PO q24h on empty stomach (Hepatic lipidosis / cholangitis / hepatoprotection); 180 mg per cat PO q12h for 3 days, then 90 mg q12h for 11 days PO q12h for 14 days (Paracetamol (acetaminophen) exposure (adjunct)). Confirm against the label and the patient before use.

### When should S-Adenosylmethionine (SAMe) not be used?

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).

### What are the side effects of S-Adenosylmethionine (SAMe) in animals?

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

## Sources

- Plumb's Veterinary Drug Handbook
- Merck Veterinary Manual, 11th edition
- Papich, Papich Handbook of Veterinary Drugs, 5th edition

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VetMasterJi is a clinical decision-support and education platform for veterinary professionals and students. It does not provide veterinary advice, diagnosis or treatment for specific animals. All drug doses, calculators and differentials are references that must be independently verified before clinical use; the attending registered veterinarian remains solely responsible for every clinical decision.