Description

Simple

A medication used to manage continual pain or pressure in the chest.

Clinical

An anti-anginal drug used for the treatment of chronic angina.

Overview

Chronic angina is a common cardiovascular condition affecting millions worldwide and causes significant disability while interfering with daily activities.[11] Ranolazine is a well-tolerated piperazine derivative used for the management of this condition, offering relief from uncomfortable and debilitating symptoms.[17] With a mechanism of action different from drugs used to treat the same condition, ranolazine is a promising anti-anginal therapy. It was originally approved by the FDA in 2006.[15]

Pharmacology

Indication

Ranolazine is indicated for the treatment of chronic angina. It can be used alone or in conjunction with nitrates, beta-blockers, angiotensin receptor blockers, anti-platelet drugs, calcium channel blockers, lipid-lowering drugs, and ACE inhibitors.[ Read more

Pharmacodynamic

Ranolazine exerts both antianginal and ischemic effects independent from lowering heart rate or blood pressure.[ Read more

Mechanism of action

Myocardial ischemia exerts effects on adenosine triphosphate flux, leading to a decrease in the energy available for contraction and relaxation of the heart muscle. Electrolyte balance of sodium and potassium is necessary for maintaining normal cardiac contraction and relaxation. Disruption of adequ... Read more

Absorption

The time to reach peak serum concentration is quite variable but has been observed to be in the range of 2-6 hours, with steady-state within 3 days.[ Read more

Protein binding

Approximately 62% of the administered dose of ranolazine is bound to plasma proteins.[ Read more

Volume of distribution

The mean apparent volume of distribution of ranolazine is reported to be 53.2 L[16] and the average steady-state volume of distribution is estimated to range from 85 to 180 L.[ Read more

Clearance

The reported clearance rate of orally administered ranolazine is of 45 L/h when administered at a dose of 500 mg twice daily.[ Read more

Half life

The apparent terminal half-life of ranolazine is 7 hours.[ Read more

Route of elimination

From the administered dose, about 3/4 of the dose is excreted renally, while 1/4 of the dose is excreted in the feces. An estimated 5% of an ingested dose is excreted as unchanged drug.[ Read more

Toxicity

The reported LD50 of oral ranolazine in the rat is 980 mg/kg.[MSDS] High oral doses of ranolazine have led to dizziness, nausea, and vomiting. These effects have been shown to be dose related. High intravenous doses can cause diplopia, confusion, paresthesia, in addition to syncope. In
the case of... Read more

Adverse Effects

Contraindications

  • Regions: US
  • Patient Conditions:
      • Name: Taking strong inhibitors of CYP3A
      • Drugbank Id: DBCOND0107517
  • Regions: US
  • Patient Conditions:
      • Name: Clinically significant hepatic impairment
      • Drugbank Id: DBCOND0107519
  • Regions: US
  • Patient Conditions:
      • Name: Taking inducers of CYP3A
      • Drugbank Id: DBCOND0107518

Food Interactions

  • Avoid grapefruit products.
  • Take with or without food. The absorption is unaffected by food.

Interactions

Type in a drug name to check for interaction with Ranolazine
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  • Paracetamol(acetaminophen)
  • Paxil(paroxetine)
  • Pamelor(nortriptyline)
  • Panadol(acetaminophen)
  • Patanol(olopatadine ophthalmic)
  • Pataday(olopatadine ophthalmic)
  • Parnate(tranylcypromine)
  • Pazeo(olopatadine ophthalmic)
(R)-warfarin
The serum concentration of (R)-warfarin can be increased when it is combined with Ranolazine.
(S)-Warfarin
The serum concentration of (S)-Warfarin can be increased when it is combined with Ranolazine.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine
The metabolism of Ranolazine can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
4-hydroxycoumarin
The metabolism of 4-hydroxycoumarin can be decreased when combined with Ranolazine.
4-Methoxyamphetamine
The serum concentration of 4-Methoxyamphetamine can be increased when it is combined with Ranolazine.
5-methoxy-N,N-dimethyltryptamine
The serum concentration of 5-methoxy-N,N-dimethyltryptamine can be increased when it is combined with Ranolazine.
9-aminocamptothecin
The metabolism of 9-aminocamptothecin can be decreased when combined with Ranolazine.
Abacavir
Ranolazine may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abatacept
The metabolism of Ranolazine can be increased when combined with Abatacept.
Abexinostat
The risk or severity of QTc prolongation can be increased when Ranolazine is combined with Abexinostat.
Abiraterone
The metabolism of Ranolazine can be decreased when combined with Abiraterone.
Acarbose
Ranolazine may decrease the excretion rate of Acarbose which could result in a higher serum level.
Acebutolol
The serum concentration of Ranolazine can be increased when it is combined with Acebutolol.
Aceclofenac
Aceclofenac may decrease the excretion rate of Ranolazine which could result in a higher serum level.
Acemetacin
Acemetacin may decrease the excretion rate of Ranolazine which could result in a higher serum level.
Acenocoumarol
The serum concentration of Acenocoumarol can be increased when it is combined with Ranolazine.
Aceprometazine
The risk or severity of QTc prolongation can be increased when Ranolazine is combined with Aceprometazine.
Acetaminophen
The metabolism of Acetaminophen can be increased when combined with Ranolazine.
Acetazolamide
Acetazolamide may increase the excretion rate of Ranolazine which could result in a lower serum level and potentially a reduction in efficacy.
Acetyldigoxin
The serum concentration of Acetyldigoxin can be increased when it is combined with Ranolazine.
19 References
  1. 1 . Rayner-Hartley E, Sedlak T: Ranolazine: A Contemporary Review. J Am Heart Assoc. 2016 Mar 15;5(3):e003196. doi: 10.1161/JAHA.116.003196.PubMed: 26979079
  2. 2 . Saad M, Mahmoud A, Elgendy IY, Richard Conti C: Ranolazine in Cardiac Arrhythmia. Clin Cardiol. 2016 Mar;39(3):170-8. doi: 10.1002/clc.22476. Epub 2015 Oct 13.PubMed: 26459200
  3. 3 . Reed M, Nicolas D: Ranolazine .PubMed: 29939605
  4. 4 . Mezincescu A, Karthikeyan VJ, Nadar SK: Ranolazine: A true pluripotent cardiovascular drug or jack of all trades, master of none? Sultan Qaboos Univ Med J. 2018 Feb;18(1):e13-e23. doi: 10.18295/squmj.2018.18.01.003. Epub 2018 Apr 4.PubMed: 29666676
  5. 5 . Codolosa JN, Acharjee S, Figueredo VM: Update on ranolazine in the management of angina. Vasc Health Risk Manag. 2014 Jun 24;10:353-62. doi: 10.2147/VHRM.S40477. eCollection 2014.PubMed: 25028555
  6. 6 . Jerling M: Clinical pharmacokinetics of ranolazine. Clin Pharmacokinet. 2006;45(5):469-91. doi: 10.2165/00003088-200645050-00003.PubMed: 16640453
  7. 7 . Thomas D, Karle CA, Kiehn J: The cardiac hERG/IKr potassium channel as pharmacological target: structure, function, regulation, and clinical applications. Curr Pharm Des. 2006;12(18):2271-83. doi: 10.2174/138161206777585102.PubMed: 16787254
  8. 8 . Balestrini S, Sisodiya SM: Pharmacogenomics in epilepsy. Neurosci Lett. 2018 Feb 22;667:27-39. doi: 10.1016/j.neulet.2017.01.014. Epub 2017 Jan 10.PubMed: 28082152
  9. 9 . Gomberg-Maitland M, Schilz R, Mediratta A, Addetia K, Coslet S, Thomeas V, Gillies H, Oudiz RJ: Phase I safety study of ranolazine in pulmonary arterial hypertension. Pulm Circ. 2015 Dec;5(4):691-700. doi: 10.1086/683813.PubMed: 26697176
  10. 10 . Zweiker R, Aichinger J, Metzler B, Lang I, Wallner E, Delle-Karth G: Ranolazine: impact on quality of life in patients with stable angina pectoris, results from an observational study in Austria - the ARETHA AT study. Wien Klin Wochenschr. 2019 Apr;131(7-8):165-173. doi: 10.1007/s00508-019-1481-x. Epub 2019 Apr 8.PubMed: 30963332
  11. 11 . Reddy BM, Weintraub HS, Schwartzbard AZ: Ranolazine: a new approach to treating an old problem. Tex Heart Inst J. 2010;37(6):641-7.PubMed: 21224931
  12. 12 . Bhandari B, Subramanian L: Ranolazine, a partial fatty acid oxidation inhibitor, its potential benefit in angina and other cardiovascular disorders. Recent Pat Cardiovasc Drug Discov. 2007 Jan;2(1):35-9. doi: 10.2174/157489007779606095.PubMed: 18221101
  13. 13 . Chaitman BR: Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation. 2006 May 23;113(20):2462-72. doi: 10.1161/CIRCULATIONAHA.105.597500.PubMed: 16717165
  14. 14 . FDA approvals Link
  15. 15 . FDA approvals Link
  16. 16 . Australian Assessment Report Link
  17. 17 . Ranolazine FDA Label Link
  18. 18 . Angina: Mayo clinic Link
  19. 19 . RANEXA (ranolazine) Australian report File