Patiromer

Last updated

Patiromer
Patiromer skeletal.svg
Clinical data
Trade names Veltassa
Other namesRLY5016
AHFS/Drugs.com Monograph
MedlinePlus a616012
License data
Pregnancy
category
  • AU:B1
Routes of
administration
By mouth (suspension)
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability Not absorbed
Metabolism None
Onset of action 7 hrs
Duration of action 24 hrs
Excretion Feces
Identifiers
CAS Number
PubChem SID
DrugBank
ChemSpider
  • None
UNII
KEGG
ChEMBL
Chemical and physical data
Formula [(C3H3FO2)182·(C10H10)8·(C8H14)10]n
[Ca91(C3H2FO2)182·(C10H10)8·(C8H14)10]n (calcium salt)

Patiromer, sold under the brand name Veltassa, is a medication used to treat high blood potassium. [4] It is taken by mouth. [4] It works by binding potassium in the gut. [5] [2]

Contents

Common side effects include constipation, low blood magnesium, and abdominal pain. [4]

It was approved for medical use in the United States in October 2015, [2] [6] [4] [7] and in the European Union in July 2017. [3]

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. [2] Such a condition needs other kinds of treatment, for example calcium infusions, insulin plus glucose infusions, salbutamol inhalation, and hemodialysis. [8]

Typical reasons for hyperkalemia are chronic kidney disease and application of drugs that inhibit the renin–angiotensin–aldosterone system (RAAS) – e.g. ACE inhibitors, angiotensin II receptor antagonists, or potassium-sparing diuretics – or that interfere with kidney function in general, such as nonsteroidal anti-inflammatory drugs (NSAIDs). [9] [10]

Adverse effects

Patiromer was generally well tolerated in studies. Side effects that occurred in more than 2% of patients included in clinical trials were mainly gastro-intestinal problems such as constipation, diarrhea, nausea, and flatulence, and also hypomagnesemia (low levels of magnesium in the blood) in 5% of patients, because patiromer binds magnesium in the gut as well. [2] [11]

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, [2] wherefore patiromer has received a boxed warning by the US Food and Drug Administration (FDA), telling patients to wait for at least six hours between taking patiromer and any other oral drugs. [7]

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. [12]

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 boxed warning 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. [2]

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. The net effect is a reduction of potassium levels in the blood serum. [2] [9]

Lowering of potassium levels is detectable seven 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. [2]

Pharmacokinetics

Patiromer is not absorbed from the gut, is not metabolized, and is excreted in unchanged form with the feces. [2]

Chemistry

The substance is a cross-linked polymer of 2-fluoroacrylic acid with divinylbenzenes and 1,7-octadiene. It is used in form of its calcium salt (ratio 2:1) and with sorbitol (one molecule per two calcium ions or four fluoroacrylic acid units), a combination called patiromer sorbitex calcium. [2]

Patiromer sorbitex calcium is an off-white to light brown, amorphous, free-flowing powder. It is insoluble in water, 0.1  M hydrochloric acid, heptane, and methanol. [2]

History

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 of 107 responders into a group receiving continued patiromer treatment and a placebo group, re-occurrence of hyperkalemia was 15% versus 60%, respectively. [13]

Society and culture

The US FDA approved patiromer in October 2015. [7] It was approved for use in the European Union in July 2017. [3]

Related Research Articles

<span class="mw-page-title-main">ACE inhibitor</span> Class of medications used primarily to treat high blood pressure

Angiotensin-converting-enzyme inhibitors are a class of medication used primarily for the treatment of high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart.

<span class="mw-page-title-main">Renin–angiotensin system</span> Hormone system

The renin–angiotensin system (RAS), or renin–angiotensin–aldosterone system (RAAS), is a hormone system that regulates blood pressure, fluid and electrolyte balance, and systemic vascular resistance.

<span class="mw-page-title-main">Captopril</span> Chemical compound

Captopril, sold under the brand name Capoten among others, is an angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first oral ACE inhibitor found for the treatment of hypertension. It does not cause fatigue as associated with beta-blockers. Due to the adverse drug event of causing hyperkalemia, as seen with most ACE Inhibitors, the medication is usually paired with a diuretic.

Antihypertensives are a class of drugs that are used to treat hypertension. Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34% and of ischaemic heart disease by 21%, and can reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease. There are many classes of antihypertensives, which lower blood pressure by different means. Among the most important and most widely used medications are thiazide diuretics, calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists (ARBs), and beta blockers.

<span class="mw-page-title-main">Hyperkalemia</span> Medical condition with excess potassium

Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0 mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5 mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasionally when severe it can cause palpitations, muscle pain, muscle weakness, or numbness. Hyperkalemia can cause an abnormal heart rhythm which can result in cardiac arrest and death.

<span class="mw-page-title-main">Angiotensin II receptor blocker</span> Group of pharmaceuticals that modulate the renin–angiotensin system

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 that bind to and inhibit the angiotensin II receptor type 1 (AT1) and thereby block the arteriolar contraction and sodium retention effects of renin–angiotensin system.

<span class="mw-page-title-main">Loop diuretic</span> Diuretics that act at the ascending limb of the loop of Henle in the kidney

Loop diuretics are diuretics that act on the Na-K-Cl cotransporter along the thick ascending limb of the loop of Henle in nephrons of the kidneys. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure or chronic kidney disease. While thiazide diuretics are more effective in patients with normal kidney function, loop diuretics are more effective in patients with impaired kidney function.

<span class="mw-page-title-main">Amiloride</span> Medication

Amiloride, sold under the trade name Midamor among others, is a medication typically used with other medications to treat high blood pressure or swelling due to heart failure or cirrhosis of the liver. Amiloride is classified as a potassium-sparing diuretic. Amiloride is often used together with another diuretic, such as a thiazide or loop diuretic. It is taken by mouth. Onset of action is about two hours and it lasts for about a day.

<span class="mw-page-title-main">Lisinopril</span> Medication used to treat high blood pressure and heart failure

Lisinopril is a medication of the angiotensin-converting enzyme (ACE) inhibitor and is used to treat high blood pressure, heart failure, and after heart attacks. For high blood pressure it is usually a first-line treatment. It is also used to prevent kidney problems in people with diabetes mellitus. Lisinopril is taken by mouth. Full effect may take up to four weeks to occur.

<span class="mw-page-title-main">Ramipril</span> ACE inhibitor

Ramipril, sold under the brand name Altace among others, is an ACE inhibitor type medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It can also be used as a preventative medication in patients over 55 years old to reduce the risk of having a heart attack, stroke or cardiovascular death in patients shown to be at high risk, such as some diabetics and patients with vascular disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth.

<span class="mw-page-title-main">Gitelman syndrome</span> Medical condition

Gitelman syndrome (GS) is an autosomal recessive kidney tubule disorder characterized by low blood levels of potassium and magnesium, decreased excretion of calcium in the urine, and elevated blood pH. It is the most frequent hereditary salt-losing tubulopathy. Gitelman syndrome is caused by disease-causing variants on both alleles of the SLC12A3 gene. The SLC12A3 gene encodes the thiazide-sensitive sodium-chloride cotransporter, which can be found in the distal convoluted tubule of the kidney.

<span class="mw-page-title-main">Potassium-sparing diuretic</span> Drugs that cause diuresis without causing potassium loss in the urine and leading to hyperkalemia

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 antagonists can also be used for treatment of primary hyperaldosteronism. Spironolactone, a steroidal aldosterone antagonist, is also used in management of female hirsutism and acne from PCOS or other causes.

<span class="mw-page-title-main">Benazepril</span> Chemical compound

Benazepril, sold under the brand name Lotensin among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combinations benazepril/hydrochlorothiazide and benazepril/amlodipine.

<span class="mw-page-title-main">Losartan</span> Blood pressure medication

Losartan, sold under the brand name Cozaar among others, is a medication used to treat high blood pressure (hypertension). It is in the angiotensin receptor blocker (ARB) family of medication, and is considered protective of the kidneys. Besides hypertension, it is also used in diabetic kidney disease, heart failure, and left ventricular enlargement. It comes as a tablet that is taken by mouth. It may be used alone or in addition to other blood pressure medication. Up to six weeks may be required for the full effects to occur.

<span class="mw-page-title-main">Polystyrene sulfonate</span>

Polystyrene sulfonates are a group of medications used to treat high blood potassium. Effects generally take hours to days. They are also used to remove potassium, calcium, and sodium from solutions in technical applications.

<span class="mw-page-title-main">Valsartan</span> Angiotensin II receptor antagonist

Valsartan, sold under the brand name Diovan among others, is a medication used to treat high blood pressure, heart failure, and diabetic kidney disease. It belongs to a class of medications referred to as angiotensin II receptor blockers (ARBs). It is a reasonable initial treatment for high blood pressure. It is taken by mouth. Versions are available as the combination valsartan/hydrochlorothiazide, valsartan/amlodipine, valsartan/amlodipine/hydrochlorothiazide, or valsartan/sacubitril.

<span class="mw-page-title-main">Hypoaldosteronism</span> Medical condition

Hypoaldosteronism is an endocrinological disorder characterized by decreased levels of the hormone aldosterone. Similarly, isolated hypoaldosteronism is the condition of having lowered aldosterone without corresponding changes in cortisol.

<span class="mw-page-title-main">Aliskiren</span> Medication

Aliskiren is the first in a class of drugs called direct renin inhibitors. It is used for essential (primary) hypertension. While used for high blood pressure, other better studied medications are typically recommended due to concerns of higher side effects and less evidence of benefit.

<span class="mw-page-title-main">Renin inhibitor</span> Compound inhibiting the activity of renin

Renin inhibitors are pharmaceutical drugs inhibiting the activity of renin that is responsible for hydrolyzing angiotensinogen to angiotensin I, which in turn reduces the formation of angiotensin II that facilitates blood pressure.

<span class="mw-page-title-main">Azilsartan</span> Chemical compound

Azilsartan is an angiotensin II receptor antagonist used in the treatment of hypertension, developed by Takeda. It is marketed in tablet form under the brand name Edarbi as the prodrug azilsartan medoxomil.

References

  1. "Summary Basis of Decision (SBD) for Veltassa". Health Canada . 23 October 2014. Archived from the original on 31 May 2022. Retrieved 29 May 2022.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 "Veltassa- patiromer powder, for suspension". DailyMed. 23 October 2019. Archived from the original on 20 October 2020. Retrieved 18 October 2020.
  3. 1 2 3 "Veltassa EPAR". European Medicines Agency (EMA). 17 September 2018. Archived from the original on 21 October 2020. Retrieved 18 October 2020.
  4. 1 2 3 4 "Patiromer Sorbitex Calcium Monograph for Professionals". Drugs.com. February 2017. Archived from the original on 13 November 2019. Retrieved 13 November 2019.
  5. Henneman A, Guirguis E, Grace Y, Patel D, Shah B (January 2016). "Emerging therapies for the management of chronic hyperkalemia in the ambulatory care setting". American Journal of Health-System Pharmacy. 73 (2): 33–44. doi:10.2146/ajhp150457. PMID   26721532.
  6. "Veltassa (Patiromer) Powder for Oral Suspension". U.S. Food and Drug Administration (FDA). 25 November 2015. Archived from the original on 4 May 2022. Retrieved 24 February 2023.
  7. 1 2 3 "FDA approves new drug to treat hyperkalemia" (Press release). U.S. Food and Drug Administration (FDA). 21 October 2015. Archived from the original on 7 November 2015. Retrieved 24 February 2023.
  8. Vanden Hoek TL, Morrison LJ, Shuster M, Donnino M, Sinz E, Lavonas EJ, et al. (November 2010). "Part 12: cardiac arrest in special situations: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care". Circulation. 122 (18 Suppl 3): S829-861. doi: 10.1161/CIRCULATIONAHA.110.971069 . PMID   20956228.
  9. 1 2 Esteras R, Perez-Gomez MV, Rodriguez-Osorio L, Ortiz A, Fernandez-Fernandez B (August 2015). "Combination use of medicines from two classes of renin-angiotensin system blocking agents: risk of hyperkalemia, hypotension, and impaired renal function". Therapeutic Advances in Drug Safety. 6 (4): 166–176. doi:10.1177/2042098615589905. PMC   4530349 . PMID   26301070.
  10. Rastegar A, Soleimani M, Rastergar A (December 2001). "Hypokalaemia and hyperkalaemia". Postgraduate Medical Journal. 77 (914): 759–764. doi:10.1136/pmj.77.914.759. PMC   1742191 . PMID   11723313.
  11. Tamargo J, Caballero R, Delpón E (November 2014). "New drugs for the treatment of hyperkalemia in patients treated with renin-angiotensin-aldosterone system inhibitors -- hype or hope?". Discovery Medicine. 18 (100): 249–254. PMID   25425465.
  12. Pharmabiz: US FDA approves removal of boxed warning on Relypsa's hyperkalemia drug, Veltassa Archived 21 December 2016 at the Wayback Machine .
  13. Weir MR, Bakris GL, Bushinsky DA, Mayo MR, Garza D, Stasiv Y, et al. (January 2015). "Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors". The New England Journal of Medicine. 372 (3): 211–221. doi: 10.1056/NEJMoa1410853 . PMID   25415805. S2CID   205097243.