Patiromer, sold under the brand name Veltassa, is a medication used to treat

high blood potassium Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0mmol/L (3.5 and 5.0mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasi ...

. It is taken by mouth. Common side effects include

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...

low blood magnesium Magnesium deficiency is an electrolyte disturbance in which there is a low level of magnesium in the body. It can result in multiple symptoms. Symptoms include tremor, poor coordination, muscle spasms, loss of appetite, personality changes, and ...

, and abdominal pain. It works by binding potassium in the gut. It was approved for medical use in the United States in 2015.

Medical uses

Patiromer is used for the treatment of hyperkalemia, but not as an emergency treatment for life-threatening hyperkalemia, as it acts relatively slowly. Such a condition needs other kinds of treatment, for example

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...

infusions,

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...

plus

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...

infusions,

salbutamol Salbutamol, also known as albuterol and sold under the brand name Ventolin among others, is a medication that opens up the medium and large airways in the lungs. It is a short-acting β2 adrenergic receptor agonist which works by causing rel ...

inhalation, and

hemodialysis Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatinin ...

. Typical reasons for hyperkalemia are

chronic kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...

and application of drugs that inhibit the renin–angiotensin–aldosterone system (RAAS) – e.g.

ACE inhibitor Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of hypertension, high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease i ...

angiotensin II receptor antagonist Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals tha ...

s, or

potassium-sparing diuretic Potassium-sparing diuretics refers to drugs that cause diuresis without causing potassium loss in the urine. They are typically used as an adjunct in management of hypertension, cirrhosis, and congestive heart failure. The steroidal aldosterone ...

s – or that interfere with

renal The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

function in general, such as

nonsteroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...

s (NSAIDs).

Adverse effects

Patiromer was generally well tolerated in studies. Side effects that occurred in more than 2% of patients included in

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

s were mainly

gastro-intestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

problems such as constipation, diarrhea, nausea, and

flatulence Flatulence, in humans, is the expulsion of gas from the intestines via the anus, commonly referred to as farting. "Flatus" is the medical word for gas generated in the stomach or bowels. A proportion of intestinal gas may be swallowed environm ...

, and also

hypomagnesemia Magnesium deficiency is an electrolyte disturbance in which there is a low level of magnesium in the body. It can result in multiple symptoms. Symptoms include tremor, poor coordination, muscle spasms, loss of appetite, personality changes, an ...

(low levels of

magnesium Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ta ...

in the blood) in 5% of patients, because patiromer binds magnesium in the gut as well.

Interactions

Patiromer was tested for drug-drug interactions with 28 drugs and showed binding or interaction with 14 of these drugs. This could reduce their availability and thus effectiveness, wherefore patiromer has received a

boxed warning In the United States, a boxed warning (sometimes "black box warning", colloquially) is a type of warning that appears on the package insert for certain prescription drugs, so called because the U.S. Food and Drug Administration specifies that it ...

by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA), telling patients to wait for at least six hours between taking patiromer and any other oral drugs. Of the 14 drugs that did show an interaction in vitro, 12 were selected for further testing in phase 1 studies in healthy volunteers to assess whether the results seen in vitro translated into an effect in people. These studies showed patiromer did not alter the absorption of nine of the 12 drugs when co-administered. Patiromer reduced absorption of three drugs when co-administered, however, there was no interaction when patiromer and these three drugs were taken 3 hours apart. This information was submitted to the FDA in the form of a supplemental New Drug Application (sNDA) and as a result, in November 2016 the FDA approved the removal of the

regarding the separation of patiromer and other oral medications. The updated label recommends patients take patiromer at least three hours before or three hours after other oral medications.

Pharmacology

Mechanism of action

Patiromer works by binding free potassium ions in the gastrointestinal tract and releasing calcium ions for exchange, thus lowering the amount of potassium available for absorption into the bloodstream and increasing the amount that is excreted via the

feces Feces ( or faeces), known colloquially and in slang as poo and poop, are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the large intestine. Feces contain a relati ...

. The net effect is a reduction of potassium levels in the

blood serum Serum () is the fluid and solute component of blood which does not play a role in clotting. It may be defined as blood plasma without the clotting factors, or as blood with all cells and clotting factors removed. Serum includes all proteins not u ...

. Lowering of potassium levels is detectable 7 hours after administration. Levels continue to decrease for at least 48 hours if treatment is continued, and remain stable for 24 hours after administration of the last dose. After this, potassium levels start to rise again over a period of at least four days.

Pharmacokinetics

Patiromer is not absorbed from the gut, is not

metabolize Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

d, and is excreted in unchanged form with the feces.

Chemistry

The substance is a cross-linked

polymer A polymer (; Greek '' poly-'', "many" + ''-mer'', "part") is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...

of 2-fluoro

acrylic acid Acrylic acid (IUPAC: propenoic acid) is an organic compound with the formula CH2=CHCOOH. It is the simplest unsaturated carboxylic acid, consisting of a vinyl group connected directly to a carboxylic acid terminus. This colorless liquid has a ...

with

divinylbenzene Divinylbenzene (DVB) consists of a benzene ring bonded to two vinyl groups. It is related to styrene (vinylbenzene) by the addition of a second vinyl group.CRC Handbook of Chemistry and Physics 65Th Ed. It is a colorless liquid manufactured by ...

s and 1,7- octadiene. It is used in form of its

salt (ratio 2:1) and with

sorbitol Sorbitol (), less commonly known as glucitol (), is a sugar alcohol with a sweet taste which the human body metabolizes slowly. It can be obtained by reduction of glucose, which changes the converted aldehyde group (−CHO) to a primary alcohol g ...

(one molecule per two calcium ions or four fluoroacrylic acid units), a combination called ''patiromer sorbitex calcium''. File:2-Fluoroacrylic acid.svg, 2-fluoroacrylic acid File:Divinylbenzene12.PNG, ''o''-divinylbenzene File:Divinylbenzene14.PNG, ''p''-divinylbenzene File:1,7-Octadiene.svg, 1,7-octadiene Patiromer sorbitex calcium is an off-white to light brown, amorphous, free-flowing powder. It is insoluble in water, 0.1 M

hydrochloric acid Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid Acid strength is the tendency of an acid, symbol ...

heptane Heptane or ''n''-heptane is the straight-chain alkane with the chemical formula H3C(CH2)5CH3 or C7H16. When used as a test fuel component in anti-knock test engines, a 100% heptane fuel is the zero point of the octane rating scale (the 100 point ...

, and

methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical and the simplest aliphatic alcohol, with the formula C H3 O H (a methyl group linked to a hydroxyl group, often abbreviated as MeOH). It is a ...

History

Studies

In a Phase III multicenter clinical trial including 237 patients with hyperkalemia under RAAS inhibitor treatment, 76% of participants reached normal serum potassium levels within four weeks. After subsequent

randomization Randomization is the process of making something random. Randomization is not haphazard; instead, a random process is a sequence of random variables describing a process whose outcomes do not follow a deterministic pattern, but follow an evolution d ...

of 107 responders into a group receiving continued patiromer treatment and a

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 ...

group, re-occurrence of hyperkalemia was 15% versus 60%, respectively.

Society and culture

Legal status

The US FDA approved patiromer in October 2015. It was approved for use in the European Union in July 2017.

References

External links

* * {{Portal bar , Medicine Nephrology procedures Potassium Organic polymers