Patiromer

Patiromer
Systematic (IUPAC) name
2-Fluoropropenoic acid, cross-linked polymer with diethenylbenzene and 1,7-octadiene
Clinical data
Trade names Veltassa
AHFS/Drugs.com entry
Routes of
administration		 Oral suspension
Legal status
Pharmacokinetic data
Bioavailability Not absorbed
Metabolism None
Onset of action 7 hrs
Duration of action 24 hrs
Excretion Feces
Identifiers
CAS Number 1260643-52-4
1208912-84-8 (calcium salt)
ATC code None
PubChem SID 135626866
DrugBank DB09263
ChemSpider None
UNII 1FQ2RY5YHH
KEGG D10148
ChEMBL CHEMBL2107875
Synonyms RLY5016
Chemical data
Formula

[(C3H3FO2)182·(C10H10)8·(C8H14)10]n

[Ca91(C3H2FO2)182·(C10H10)8·(C8H14)10]n (calcium salt)

Patiromer (USAN, trade name Veltassa) is a drug used for the treatment of hyperkalemia (elevated blood potassium levels), a condition that may lead to palpitations and arrhythmia (irregular heartbeat). It works by binding potassium in the gut.[1][2]

Medical uses

Patiromer is used for the treatment of hyperkalemia, but not as an emergency treatment for life-threatening hyperkalemia, because 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.[3]

Typical reasons for hyperkalemia are renal insufficiency 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 renal function in general, such as nonsteroidal anti-inflammatory drugs (NSAIDs).[4][5]

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][6]

Interactions

No interaction studies have been done in humans. Patiromer binds to many substances besides potassium, including numerous orally administered drugs (about half of those tested in vitro). 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]

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][4]

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.[2]

Pharmacokinetics

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

Physical and chemical properties

The substance is a cross-linked polymer of 2-fluoroacrylic acid (91% in terms of amount of substance) with divinylbenzenes (8%) and 1,7-octadiene (1%). 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.[8]

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][8]

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 of 107 responders into a group receiving continued patiromer treatment and a placebo group, re-occurrence of hyperkalemia was 15% versus 60%, respectively.[9]

Approval

The US FDA approved patiromer in October 2015.[7] The drug is not approved in Europe as of January 2016.

See also

References

  1. ↑ Henneman, A; Guirguis, E; Grace, Y; Patel, D; Shah, B (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.
  2. 1 2 3 4 5 6 7 8 FDA Professional Drug Information for Veltassa.
  3. ↑ Vanden Hoek TL, Morrison LJ, Shuster M, Donnino M, Sinz E, Lavonas EJ, Jeejeebhoy FM, Gabrielli A; Morrison; Shuster; Donnino; Sinz; Lavonas; Jeejeebhoy; Gabrielli (2010-11-02). "Part 12: cardiac arrest in special situations: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care". Circulation 122 (18 Suppl 3): S829–61. doi:10.1161/CIRCULATIONAHA.110.971069. PMID 20956228.
  4. 1 2 Esteras, R.; Perez-Gomez, M. V.; Rodriguez-Osorio, L.; Ortiz, A.; Fernandez-Fernandez, B. (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. doi:10.1177/2042098615589905. PMID 26301070.
  5. ↑ Rastegar, A; Soleimani, M (2001). "Hypokalaemia and hyperkalaemia". Postgraduate Medical Journal 77 (914): 759–64. doi:10.1136/pmj.77.914.759. PMC 1742191. PMID 11723313.
  6. ↑ Tamargo, J; Caballero, R; Delpón, E (2014). "New drugs for the treatment of hyperkalemia in patients treated with renin-angiotensin-aldosterone system inhibitors -- hype or hope?". Discovery medicine 18 (100): 249–54. PMID 25425465.
  7. 1 2 "FDA approves new drug to treat hyperkalemia". FDA. 21 October 2015.
  8. 1 2 RxList: Veltassa.
  9. ↑ Weir, Matthew R.; Bakris, George L.; Bushinsky, David A.; Mayo, Martha R.; Garza, Dahlia; Stasiv, Yuri; Wittes, Janet; Christ-Schmidt, Heidi; Berman, Lance; Pitt, Bertram (2015). "Patiromer in Patients with Kidney Disease and Hyperkalemia Receiving RAAS Inhibitors". New England Journal of Medicine 372 (3): 211. doi:10.1056/NEJMoa1410853. PMID 25415805.
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