Overview
11 DESCRIPTION NEREUS (tradipitant) is a substance P/neurokinin-1 (NK-1) receptor antagonist designated by the chemical name, as {2-[1-(3,5-Bistrifluoromethylbenzyl)-5-pyridin-4-yl-1H-[1,2,3]triazol-4- yl]-pyridin-3-yl}-(2-chlorophenyl)-methanone, with molecular formula C 28 H 16 C l F 6 N 5 O, and molecular weight 587.9.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Tradipitant is a selective, high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors. Tradipitant does not have affinity for NK2 and NK3 receptors, serotonin (5-HT3), dopamine (D2), cholinergic, or histamine (H1) receptors. Tradipitant has been shown in animal models to inhibit drug induced emesis. Human Positron Emission Tomography (PET) studies with tradipitant have shown that tradipitant crosses the blood brain barrier and occupies brain NK-1 receptors. The exact mechanism by which tradipitant exerts its therapeutic effect is not fully established. 12.2 Pharmacodynamics Tradipitant inhibits the NK1 receptor with a K i of 0.062 ± 0.
Indications
- 1 INDICATIONS AND USAGE NEREUS is indicated for the prevention of vomiting induced by motion in adults. NEREUS is a substance P/neurokinin 1 (NK1) receptor antagonist indicated for the prevention of vomiting induced by motion in adults. ( 1 )
Common Doses
- 85 mg
- 170 mg
Dosage
2 DOSAGE AND ADMINISTRATION The recommended dosage of NEREUS is 85 mg or 170 mg as a single oral dose approximately 60 minutes before an event expected to cause vomiting induced by motion. The safety of NEREUS for the prevention of vomiting induced by motion in adults for more than 90 doses has not been established in clinical trials. ( 2.1 ) The maximum dosage in a 24-hour period is a single dose of 85 mg or 170 mg. ( 2.1 ) Administer on an empty stomach, at least 1 hour prior to or 2 hours after a full meal. ( 2.1 ) 2.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS Most common adverse reactions (incidence ≥5%) are: somnolence, headache, and fatigue. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Vanda Pharmaceuticals Inc. at 1-844-GO-VANDA (1-844-468-2632) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Interactions
- 7 DRUG INTERACTIONS Strong CYP3A4 Inhibitors: May increase tradipitant exposure and the risk of adverse reactions. ( 7.1 ) 7.1 Effects of Other Drugs on NEREUS Strong CYP3A4 Inhibitors Tradipitant is a CYP3A4 substrate. Strong CYP3A4 inhibitors may increase tradipitant exposure, which may increase the risk of adverse reactions to NEREUS.