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 Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...

, 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 WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...

. The oral combination

netupitant/palonosetron Netupitant/palonosetron, sold under the brand name Akynzeo, is a fixed-dose combination medication used for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. It is marketed and distributed by Helsinn Therapeutics. Netu ...

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 disorder Gastrointestinal diseases (abbrev. GI diseases or GI illnesses) refer to diseases involving the Human gastrointestinal tract, gastrointestinal tract, namely the oesophagus, stomach, small intestine, large intestine and rectum, and the accessory org ...

s occur, as well as sleeplessness, first- and

second-degree atrioventricular block Second-degree atrioventricular block (AV block) is a disease of the electrical conduction system of the heart. It is a conduction block between the atria and ventricles. The presence of second-degree AV block is diagnosed when one or more (but n ...

muscle pain Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likel ...

and

shortness of breath Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing disc ...

. Palonosetron is similarly well tolerated as other 5-HT₃ antagonists, and slightly less than

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures. In general ...

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 Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The degree of symptoms can range from mild to severe, including a potentiality of death. Symptoms in mild cases include high ...

when the drug is combined with

serotonergic Serotonergic () or serotoninergic () means "pertaining to or affecting serotonin". Serotonin is a neurotransmitter. A synapse is serotonergic if it uses serotonin as its neurotransmitter. A serotonergic neuron ''produces'' serotonin. A substance is ...

substances such as

selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracell ...

s (SSRIs) and

serotonin–norepinephrine reuptake inhibitor Serotonin–norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant drugs used to treat major depressive disorder (MDD), anxiety disorders, obsessive–compulsive disorder (OCD), social phobia, attention-deficit hyperactivity dis ...

s (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 In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

of 97%. Highest blood plasma levels are reached after 5.1±1.7 hours, independently of food intake, and

plasma protein binding Plasma protein binding refers to the degree to which medications attach to proteins within the blood. A drug's efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse or diffuse th ...

is 62%. 40% of the substance are eliminated in the unchanged form, and a further 45–50% are metabolized by the liver enzyme

CYP2D6 Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the ''CYP2D6'' gene. ''CYP2D6'' is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra. CYP2D ...

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 Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene. Function ...

. 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 Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

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 In chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (e.g. an amine). An alternative name is chlorhydrate, which comes from French. An archaic alternative na ...

, which is also a solid. The hydrochloride is easily soluble in water, soluble in

propylene glycol Propylene glycol (IUPAC nomenclature, IUPAC name: propane-1,2-diol) is a viscous, colorless liquid, which is nearly odorless but possesses a faintly sweet taste. Its chemical formula is CH3CH(OH)CH2OH. Containing two Alcohol (chemistry), alcoho ...

, and slightly soluble in

ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...

and

isopropyl alcohol Isopropyl alcohol (IUPAC name propan-2-ol and also called isopropanol or 2-propanol) is a colorless, flammable organic compound with a pungent alcoholic odor. As an isopropyl group linked to a hydroxyl group (chemical formula ) it is the simple ...

. The molecule has two

asymmetric carbon An asymmetric carbon atom (chiral carbon) is a carbon atom that is attached to four different types of atoms or groups of atoms. Le Bel-van't Hoff rule states that the number of stereoisomers of an organic compound is 2n, where n represents the num ...

atoms. It is used in form of the pure (''S,S'')-

stereoisomer In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in ...

References

External links

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