Palonosetron, sold under the brand name Aloxi, is used for the prevention and treatment of

chemotherapy-induced nausea and vomiting Chemotherapy-induced nausea and vomiting (CINV) is a common side-effect of many cancer treatments. Nausea and vomiting are two of the most feared cancer treatment-related side effects for cancer patients and their families. In 1983, Coates et al. f ...

(CINV). It is a 5-HT₃ antagonist. Palonosetron is administered intravenously, or as a single oral capsule. Freely available with registration. It has a longer duration of action than other 5-HT₃ antagonists. The oral formulation was approved on August 22, 2008, for prevention of acute CINV alone, as a large clinical trial did not show oral administration to be as effective as intravenous use against delayed CINV. It is on the World Health Organization's List of Essential Medicines. The oral combination netupitant/palonosetron is approved for both acute and delayed CINV.

Adverse effects

The most common adverse effects are headache, which occurs in 4–11% of patients, and constipation in up to 6% of patients. In less than 1% of patients, other gastrointestinal disorders occur, as well as

sleeplessness Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

, first- and second-degree atrioventricular block, muscle pain and shortness of breath. Palonosetron is similarly well tolerated as other 5-HT₃ antagonists, and slightly less than placebo.

Interactions

Palonosetron does not relevantly inhibit or induce

cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

liver enzymes. There are case reports about serotonin syndrome when the drug is combined with serotonergic substances such as selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs), two common types of antidepressants.

Pharmacology

Mechanism of action

Palonosetron is a 5-HT₃ antagonist, commonly known as a ''setron''. These drugs act by blocking

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

from binding to the 5-HT₃ receptor.

Pharmacokinetics

Orally taken palonosetron is absorbed well from the gut and has a bioavailability of 97%. Highest blood plasma levels are reached after 5.1±1.7 hours, independently of food intake, and plasma protein binding is 62%. 40% of the substance are eliminated in the unchanged form, and a further 45–50% are metabolized by the liver enzyme CYP2D6 and to a lesser extent by

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...

and CYP1A2. The two main metabolites, the ''N''-oxide and a hydroxy derivative, have less than 1% of palonosetron's antagonistic effect and are thus practically inactive. Palonosetron and its metabolites are mainly (to 80–93%) eliminated via the kidney. Biological half-life in healthy persons was 37±12 hours in a study, and 48±19 hours in cancer patients. In 10% of patients, half-life is over 100 hours. Most other marketed setrons have half-lives in the range of about two to 15 hours. Palonosetron metabolites

Chemistry

The substance is solid at room temperature and melts at . The infusions and capsules contain palonosetron hydrochloride, which is also a solid. The hydrochloride is easily soluble in water, soluble in propylene glycol, and slightly soluble in ethanol and isopropyl alcohol. The molecule has two asymmetric carbon atoms. It is used in form of the pure (''S,S'')- stereoisomer.

References

External links

* {{Portal bar , Medicine 5-HT3 antagonists Quinuclidines Isoquinolines Hoffmann-La Roche brands Lactams World Health Organization essential medicines