In the absence of compatibility studies, Slentrol should not be physically mixed with other veterinary medicinal products. Interactions with other drug types have not been specifically investigated. Therefore, for dogs receiving treatments in addition to Slentrol, drug interactions should be monitored closely.

Oral dosing devices may be cleaned with water but must be dried before re-use. The product is not miscible with water.

Overdose up to 10 times the maximum dose of 1 mg/kg current body weight may produce vomiting, diarrhoea or increased ALT/AST levels. These signs will resolve spontaneously following discontinuation of product administration.

Fertility studies have not been conducted in the target species. Use in dogs intended for breeding should be subject to a risk-benefit analysis by the attending veterinary surgeon. MTP inhibitors (microsomal triglyceride transfer protein inhibitors) as a class have the potential to disrupt yolk sac development and laboratory studies on rats and rabbits have shown evidence of embryolethality, teratogenicity, and developmental toxicity.

In clinical trials, treated animals rapidly regained weight following cessation of treatment when diet was not restricted. In order to avoid this rebound weight gain, it is necessary to feed the animals to maintenance energy requirements. Thus, during treatment or at the end of treatment at the latest, an appropriate feeding and exercise regimen should be implemented in order to ensure long term maintenance of the body weight.

During treatment, because food intake is reduced as when using a traditional non-medical calorie restriction method, care must be taken to ensure that protein, vitamins, essential fatty acids and minerals supplied by the daily food ration meet minimal recommended requirements in order to ensure a complete and balanced nutritional supply.

The liver function of dogs suspected of suffering from a liver disease or dysfunction should be evaluated, before commencing treatment with the product.

Any clinical suspicion of liver disease or dysfunction during treatment should be investigated through the evaluation of liver function. Any indication of progressive liver damage or of dysfunction should result in the discontinuation of the treatment. Sporadic and mild serum ALT elevations up to 4 times the upper reference range are not a reason for discontinuing therapy in the absence of any indication of liver dysfunction.

Dirlotapide is a potent selective inhibitor of the microsomal triglyceride transfer protein (MTP). The microsomal triglyceride transfer protein (MTP) is pivotal for the absorption and distribution of fat. The inhibition of intestinal and hepatic MTP reduces plasma cholesterol and triglyceride concentration. The selective inhibition of intestinal MTP also reduces intestinal fat absorption.

Clinical and pharmacodynamic data strongly suggest that the efficacy of dirlotapide results from a primary local action in the gut after oral administration. This is consistent with in vivo data generated in mice which shows that dirlotapide has selectivity for intestinal MTP. The effect is mainly mediated indirectly due to reduced feed intake during therapy.

As a consequence of reducing intestinal fat absorption, dirlotapide reduces food intake in dogs in a dose dependent manner. This food inhibitory effect of dirlotapide results from a primary local effect on the gastrointestinal tract following oral administration, and is not a result of systemic exposure.

The efficacy of dirlotapide has been demonstrated with various types of diets, representing the whole range of fat contents available in commercial diets.

In a radiolabeled metabolism study, the primary route for excretion was via the faeces with minimal excretion via urine (<1%). Additionally, dirlotapide is highly protein bound (>99%) in dog plasma.