What are the major drug interactions with ranolazine. How many medications interact with ranolazine. Are there any disease interactions with ranolazine. What is the alcohol interaction with ranolazine.

Overview of Ranolazine Drug Interactions

Ranolazine, marketed under the brand name Ranexa, is an antianginal medication used to treat chronic angina. As with many medications, ranolazine can interact with other drugs, potentially affecting its efficacy or causing adverse effects. Understanding these interactions is crucial for patient safety and optimal treatment outcomes.

According to the comprehensive drug interaction checker on Drugs.com, ranolazine has known interactions with 510 different drugs. These interactions are categorized based on their severity:

• 161 major interactions
• 318 moderate interactions
• 31 minor interactions

Additionally, ranolazine has 3 disease interactions and 1 alcohol/food interaction. This extensive list of potential interactions underscores the importance of careful medication management for patients prescribed ranolazine.

Major Drug Interactions with Ranolazine

Major drug interactions are considered highly clinically significant and should be avoided due to the potential risks outweighing the benefits. Some of the drugs that have major interactions with ranolazine include:

• Ticagrelor (Brilinta)
• Apixaban (Eliquis)
• Sacubitril/Valsartan (Entresto)
• Rivaroxaban (Xarelto)

Why are these interactions considered major? Major interactions can significantly increase the risk of adverse effects or reduce the effectiveness of one or both medications. For example, the combination of ranolazine with certain anticoagulants like apixaban or rivaroxaban may increase the risk of bleeding.

Moderate Drug Interactions with Ranolazine

Moderate interactions, while less severe than major ones, still require careful consideration and potential adjustments to treatment plans. Some medications with moderate interactions include:

• Metoprolol
• Atorvastatin (Lipitor)
• Rosuvastatin (Crestor)
• Clopidogrel (Plavix)

How should moderate interactions be managed? In cases of moderate interactions, healthcare providers may need to adjust dosages, monitor patients more closely, or consider alternative medications. For instance, when combining ranolazine with statins like atorvastatin or rosuvastatin, dose adjustments may be necessary to prevent potential muscle toxicity.

Minor Drug Interactions with Ranolazine

Minor interactions typically have minimal clinical significance but should still be considered in the overall treatment plan. Examples of medications with minor interactions include:

• Acetaminophen (Tylenol)
• Cetirizine (Zyrtec)
• Polyethylene glycol 3350 (MiraLAX)

Do minor interactions require action? While minor interactions may not necessitate changes to the treatment regimen, patients and healthcare providers should still be aware of them. Monitoring for any unexpected side effects or changes in medication efficacy is prudent.

Disease Interactions with Ranolazine

Ranolazine has three known disease interactions that warrant special consideration:

1. Severe hepatic impairment
2. QT prolongation
3. Renal disease

How do these disease interactions affect ranolazine use? In patients with severe liver impairment, ranolazine may accumulate in the body, potentially leading to increased side effects. For those at risk of QT prolongation, ranolazine could further increase this risk, potentially leading to dangerous arrhythmias. In cases of renal disease, dose adjustments may be necessary to prevent drug accumulation.

Alcohol and Food Interactions with Ranolazine

While the specific details of the alcohol/food interaction are not provided in the given information, it’s important to note that such an interaction exists. Patients taking ranolazine should discuss potential dietary restrictions or alcohol consumption guidelines with their healthcare provider.

Can ranolazine be taken with food? Generally, ranolazine can be taken with or without food. However, patients should follow their doctor’s specific instructions regarding the timing of medication in relation to meals.

Commonly Checked Drug Interactions with Ranolazine

Several medications are frequently checked for interactions with ranolazine, indicating their common co-prescription or use. These include:

• Aspirin (including low-strength formulations)
• Metoprolol
• Atorvastatin (Lipitor)
• Clopidogrel (Plavix)
• Nitroglycerin (Nitrostat)
• Furosemide (Lasix)

Why are these interactions frequently checked? Many of these medications are commonly used in patients with cardiovascular conditions, which is also the primary indication for ranolazine. Understanding how these drugs interact is crucial for optimizing treatment and minimizing risks in patients with complex cardiovascular regimens.

Ranolazine and Cardiovascular Medications

Given ranolazine’s use in treating chronic angina, it’s not surprising that many of its potential interactions involve other cardiovascular medications. Some key points to consider include:

• Beta-blockers (e.g., metoprolol): May have additive effects on heart rate and blood pressure
• Statins (e.g., atorvastatin, rosuvastatin): Potential for increased risk of muscle-related side effects
• Antiplatelet agents (e.g., clopidogrel, ticagrelor): May affect bleeding risk or drug efficacy
• Anticoagulants (e.g., apixaban, rivaroxaban): Increased risk of bleeding complications

How should these cardiovascular drug interactions be managed? Close monitoring, dose adjustments, and in some cases, consideration of alternative medications may be necessary. The specific approach will depend on the individual patient’s condition, overall medication regimen, and risk factors.

Importance of Medication Reconciliation and Monitoring

The extensive list of potential interactions with ranolazine highlights the critical importance of thorough medication reconciliation and ongoing monitoring for patients prescribed this drug. Healthcare providers should:

1. Conduct a comprehensive review of all medications, including over-the-counter drugs and supplements
2. Use drug interaction checkers and clinical decision support tools
3. Regularly reassess the medication regimen for potential interactions
4. Monitor patients for signs of adverse effects or changes in drug efficacy
5. Educate patients about potential interactions and signs to watch for

Why is ongoing monitoring crucial? Medication regimens often change over time, and new interactions may arise as treatments are adjusted. Regular review and monitoring help ensure continued safety and efficacy of the overall treatment plan.

Patient Education and Communication

Effective management of ranolazine interactions relies heavily on patient education and open communication between patients and healthcare providers. Key points for patient education include:

• The importance of informing all healthcare providers about ranolazine use
• The need to consult a healthcare provider before starting any new medications, including over-the-counter drugs and supplements
• Awareness of potential signs of drug interactions or adverse effects
• The importance of adherence to the prescribed medication regimen and follow-up appointments

How can patients contribute to safe medication use? By staying informed, maintaining open communication with their healthcare team, and promptly reporting any unusual symptoms or concerns, patients play a crucial role in preventing and managing potential drug interactions.

Emerging Research and Future Considerations

As with many areas of pharmacology, research into drug interactions is ongoing. Future studies may reveal new interactions or provide more detailed insights into known interactions. Healthcare providers should stay informed about the latest research and guidelines related to ranolazine use and potential interactions.

What areas of research are important for ranolazine interactions? Some key areas for future investigation include:

• Long-term effects of combined use with commonly co-prescribed medications
• Genetic factors that may influence drug interactions
• Development of more sophisticated drug interaction prediction models
• Exploration of potential beneficial interactions that could enhance therapeutic outcomes

As our understanding of drug interactions continues to evolve, so too will strategies for managing these interactions and optimizing patient care. The complex landscape of ranolazine interactions underscores the importance of personalized medicine approaches and the need for ongoing vigilance in medication management.

Ranolazine Interactions Checker – Drugs.com

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There are 510 drugs known to interact with
ranolazine, along with
3 disease interactions, and 1 alcohol/food interaction.

Of the total drug interactions,
161 are major, 318 are moderate, and 31 are minor.

Does ranolazine interact with my other drugs?

Enter other medications to view a detailed report.

• View all 510 medications that may interact with ranolazine
• View ranolazine alcohol/food interactions (1)
• View ranolazine disease interactions (3)

Most frequently checked interactions

View interaction reports for ranolazine and the medicines listed below.

• Major
• Moderate
• Minor
• Unknown

• Aspir 81 (aspirin)
• Aspirin Low Strength (aspirin)
• Brilinta (ticagrelor)
• CoQ10 (ubiquinone)
• Crestor (rosuvastatin)
• Eliquis (apixaban)
• Entresto (sacubitril / valsartan)
• Farxiga (dapagliflozin)
• Fish Oil (omega-3 polyunsaturated fatty acids)
• Jardiance (empagliflozin)
• Lantus (insulin glargine)
• Lasix (furosemide)
• Lipitor (atorvastatin)
• Lyrica (pregabalin)
• Metoprolol Succinate ER (metoprolol)
• Metoprolol Tartrate (metoprolol)
• MiraLAX (polyethylene glycol 3350)
• Nitrostat (nitroglycerin)
• Norco (acetaminophen / hydrocodone)
• Ozempic (semaglutide)
• Plavix (clopidogrel)
• Protonix (pantoprazole)
• Repatha (evolocumab)
• Trulicity (dulaglutide)
• Tylenol (acetaminophen)
• Vitamin B12 (cyanocobalamin)
• Vitamin C (ascorbic acid)
• Vitamin D3 (cholecalciferol)
• Xarelto (rivaroxaban)
• Zyrtec (cetirizine)

Ranolazine alcohol/food interactions

There is 1 alcohol/food interaction with ranolazine.

Ranolazine disease interactions

There are 3 disease interactions with ranolazine which include:

• severe hepatic impairment
• QT prolongation
• renal disease

Report options

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• ranolazine consumer information
• Compare alternatives
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• Reviews (83)
• Drug images
• Side effects
• Dosage information
• During pregnancy
• Drug class: antianginal agents
• En español

Related treatment guides

• Angina

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.

Major	Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate	Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor	Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown	No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer

Ranexa Interactions Checker – Drugs.com

Print

Save

There are 510 drugs known to interact with
Ranexa (ranolazine), along with
3 disease interactions, and 1 alcohol/food interaction.

Of the total drug interactions,
161 are major, 318 are moderate, and 31 are minor.

Does Ranexa interact with my other drugs?

Enter other medications to view a detailed report.

• View all 510 medications that may interact with Ranexa
• View Ranexa alcohol/food interactions (1)
• View Ranexa disease interactions (3)

Most frequently checked interactions

View interaction reports for Ranexa (ranolazine) and the medicines listed below.

• Major
• Moderate
• Minor
• Unknown

• amlodipine
• Aspir 81 (aspirin)
• aspirin
• Aspirin Low Strength (aspirin)
• atorvastatin
• carvedilol
• clopidogrel
• Crestor (rosuvastatin)
• furosemide
• gabapentin
• Imdur (isosorbide mononitrate)
• isosorbide mononitrate
• Lasix (furosemide)
• levothyroxine
• Lipitor (atorvastatin)
• lisinopril
• losartan
• metformin
• metoprolol
• Metoprolol Succinate ER (metoprolol)
• Metoprolol Tartrate (metoprolol)
• nitroglycerin
• Nitrostat (nitroglycerin)
• omeprazole
• pantoprazole
• Plavix (clopidogrel)
• potassium chloride
• simvastatin
• Vitamin B12 (cyanocobalamin)
• Vitamin D3 (cholecalciferol)

Ranexa alcohol/food interactions

There is 1 alcohol/food interaction with Ranexa (ranolazine).

Ranexa disease interactions

There are 3 disease interactions with Ranexa (ranolazine) which include:

• severe hepatic impairment
• QT prolongation
• renal disease

Report options

Loading…

QR code containing a link to this page

More about Ranexa (ranolazine)

• Ranexa consumer information
• Compare alternatives
• Pricing & coupons
• Reviews (67)
• Drug images
• Side effects
• Dosage information
• During pregnancy
• FDA approval history
• Drug class: antianginal agents
• En español

Related treatment guides

• Angina

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.

Major	Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate	Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor	Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown	No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer

Mechanism of action and use of ranolazine in ischemic heart disease and atrial fibrillation | Gurevich M.A., Agababyan D.A., Kuzmenko N.

A.

Cardiovascular disease remains the leading cause of death in many parts of the world. In the last decades of the last century in economically developed countries, there was a certain decrease in mortality from diseases of the circulatory system (CVD), including coronary heart disease (CHD). In recent years, a similar dynamics of mortality from CSD has also been observed in our country. In Russia, the gradual decline in mortality in 2011 reached 18.8%. It should be noted that, despite this positive trend, mortality from coronary artery disease in our country is 3 times higher than in the United States [1–3].

The prevalence of IHD in our country is 13.5%, in the USA it is almost 2 times lower – 7% [3, 4]. It should be noted that an increase in the prevalence of CSD in the world is expected. According to P. Heidenreich et al. (2011), the prevalence of IHD by 2030 will increase by 9.3%, and direct medical costs will increase by 198% compared to those in 2010. Thus, IHD remains the main cause of death and disability in the population. Obviously, the current situation necessitates the improvement of therapeutic and preventive measures for this disease.

Currently, there has been undoubted progress in the treatment of patients with coronary artery disease, which is associated both with the emergence of new groups of drugs (antiplatelet agents, lipid-lowering and antianginal drugs), and with an increase in the frequency of use of coronary revascularization procedures. The presence of a large arsenal of funds contributes to the primary and secondary prevention of vascular complications. It should be noted that 25% of patients after successful myocardial revascularization, even when taking all the recommended drugs, experience symptoms of ischemia again after 5 years [5]. At the same time, it remains relevant to conduct adequate drug therapy for stable coronary artery disease, aimed at stopping and preventing the main clinical symptoms of the disease, improving the quality of life of patients and increasing exercise tolerance. Antianginal drugs, by preventing myocardial ischemia, significantly improve the well-being of patients and increase their exercise tolerance.

Currently, 7 groups of antianginal drugs are recommended for use: β-blockers, calcium antagonists, nitrates, sinus node cell If-channel inhibitors, metabolic drugs, nicorandil and ranolazine.

The modern strategy of managing patients with coronary artery disease for the prevention of cardiovascular complications requires the mandatory prescription of antiplatelet agents, lipid-lowering drugs (statins, PUFAs) and β-blockers. The addition of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers to all patients with stable coronary artery disease, including those without signs of heart failure, reduces the risk of developing MI, which contributes to a marked improvement in the prognosis in this category of patients.
Antianginal drugs that prevent an attack of angina pectoris by preventing myocardial ischemia significantly improve the well-being of patients and increase their exercise tolerance.
Noteworthy is the potassium channel activator nicorandil, which simultaneously has the properties of organic nitrates and activates ATP-dependent potassium channels. The drug is used to prevent and treat angina attacks.

Ranolazine, a relatively new for our country drug for the treatment of stable angina pectoris, is no less interesting. It is a selective inhibitor of late sodium current, which reduces ventricular repolarization and contractility disorders associated with myocardial ischemia [6].

Pharmacokinetics and mechanism of action of ranolazine
Ranolazine is an inhibitor of the late current of sodium ions into myocardial cells. A decrease in intracellular accumulation of sodium leads to a decrease in the excess of intracellular calcium ions. This reduces intracellular ion imbalance during ischemia. Reduction of excess intracellular calcium promotes relaxation of the myocardium and thus reduces the diastolic tension of the ventricular wall. Clinical evidence for inhibition of late sodium current by ranolazine is a significant shortening of the QTc interval (QTc is the corrected QT value based on heart rate) and a positive effect on diastolic relaxation, revealed in an open study in patients with long QT syndrome (patients with LQT-3 syndrome). having mutations in the SCN5A ΔKPQ gene). These effects of the drug do not depend on changes in heart rate, blood pressure or the degree of vasodilation.

Ranolazine significantly reduces the frequency of angina attacks per week and the consumption of short-acting nitroglycerin compared with placebo, regardless of the sex of patients. The multicenter crossover study MARISА (Monotherapy Assessment of Ranolazine In Stable Angina) showed the effectiveness of ranolazine monotherapy for the prevention of angina attacks [7]. This study (n=191) included patients with exertional angina treated with β-blockers, calcium antagonists and/or organic nitrates. Before the start of the study, all anti-ischemic drugs, except for on-demand nitroglycerin, were discontinued. Further, patients received 500, 1000, 1500 mg of ranolazine or placebo 2 times a day for 1 week, after which they conducted a study using a treadmill test. Monotherapy with ranolazine at all dosages was well tolerated and proved to be effective: the duration of physical activity increased by 9, respectively. 4, 103 and 116 s for ranolazine doses of 500, 750 and 1000 mg bid (p<0.005 vs. placebo). Hemodynamic parameters (BP, heart rate) did not practically change against the background of ranolazine. During treatment, the development of tolerance to ranolazine was not observed. Discontinuation of ranolazine did not increase or increase the frequency of angina attacks. These data indicate ranolazine as an active antianginal drug.
Ranolazine has a significant advantage compared with placebo in increasing the time to the onset of an angina attack and the onset of ST segment depression by 1 mm when taken at a dose of 500–1000 mg 2 r./day. The drug significantly improves exercise tolerance. For ranolazine, a dose-effect relationship was recorded: when taking the drug at a higher dose, the antianginal effect was higher than when taking a lower dose.

Effects detected by ECG: in patients taking ranolazine, there were dose- and plasma concentration-dependent levels of QTc prolongation (about 6 ms when taking 1000 mg 2 r. /day), a decrease in the amplitude of the T wave and, in in some cases, bihumped T waves. ECG findings in patients taking ranolazine are the result of drug inhibition of both fast rectifying potassium current, which lengthens the ventricular action potential, and late sodium current, which shortens the ventricular action potential. A population analysis showed that the use of ranolazine in both patients with stable angina and healthy volunteers leads to an increase in QTc relative to baseline by an average of 2.4 ms at a plasma concentration of ranolazine of 1000 ng / ml. In the case of patients with significant liver failure, the rate of QTc elongation was higher.

One study investigated the association between prolonged QTc and the risk of sudden cardiac death (SCD) and exposure to ranolazine. A total of 6492 patients with non-ST elevation acute coronary syndrome (ACS) (NSTEACS) randomized to placebo or ranolazine in MERLIN-TIMI 36 were studied. women) was associated with a twofold increase in the risk of SCD (hazard ratio HR, 2. 3, p=0.005) after adjusting for other risk factors. In the ranolazine group, the association between abnormal QTc and SCD was comparable to that in the placebo group (HR 1.8, p=0.074). Thus, there were no significant differences in the risk of SCD between the placebo and ranolazine groups in patients with QTc pathology (HR 0.78, p=0.48). QTc prolongation was an independent predictor of SCD [8].
During therapy with ranolazine, there was a significantly lower incidence of arrhythmias compared with placebo, including torsades de pointes ≥8 beats per episode. In patients treated with ranolazine as monotherapy or in combination with other antianginal agents, an effect on hemodynamics was revealed in the form of a slight decrease in heart rate (<2 bpm) and a decrease in systolic blood pressure (<3 mm Hg). Additional intake of ranolazine reduces the frequency of angina attacks. The positive effect of the drug is not accompanied by the development of side effects or worsening of the long-term prognosis [7].
Due to the partial inhibition of fatty acid oxidation, ranolazine increases the efficiency of oxygen utilization and potentiates the action of β-blockers and calcium antagonists.
The Combination Assessment of Ranolizine in Stable Angina (CARISA) study included 823 patients with stable angina treated with atenolol 50 mg, amlodipine 5 mg, or diltiazem 180 mg. Within 12 weeks. participants randomly received placebo (269 people), ranolazine 750 mg 2 r./day (279people) or ranolazine 1000 mg twice a day (275 people) [9].

When added to current therapy, the drug reduced the mean number of angina attacks from 3.3 per week (placebo group) to 2.5 (ranolazine 1500 mg/day group) and 2.1 (ranolazine 2000 mg/day group), respectively. Ranolazine has been shown to be superior to placebo in duration of exercise for both doses studied (24 seconds longer than placebo). There were no differences in the duration of exercise tolerance between the two doses of ranolazine. The duration of the treadmill test increased in both active treatment groups compared to the control (p=0. 01). These differences reached statistical significance as early as the 2nd week. reception.

Interactions with calcium antagonists have also been investigated in Antianginal Efficacy of Ranolazine When Added to Treatment with Amlodipine (ERICA). It included 565 patients with verified coronary artery disease who took the maximum dose of amlodipine, who were randomized to receive 1000 mg of ranolazine and placebo 2 times a day for 6 weeks. The results of the study demonstrated that ranolazine in combination with amlodipine significantly reduced the frequency of attacks compared with that of amlodipine alone (mean frequency of attacks per week – 2.88 vs. 3.31, p = 0.028; average need for nitroglycerin per week – 2 03 versus 2.68, p=0.014) [10].

Ranolazine was not accompanied by side effects and did not affect the levels of blood pressure and heart rate. The drug is suitable for patients with hypotension and bradycardia, in whom a further increase in the dose of “classic” antianginal drugs may adversely affect hemodynamics. Ranolazine is indicated primarily for patients who cannot perform revascularization.
Many patients prefer to take drugs every day if it reduces the severity and number of angina attacks than to undergo percutaneous coronary intervention, in which the 30-day risk of serious complications reaches 2-3% [11].

Speaking about the drug therapy of patients with angina pectoris and diabetes, mention should be made of the effect of ranolazine on the level of glycated hemoglobin and improvement of glycemic control. When taken for 4 months. the incidence of new cases of increased levels of glycated hemoglobin is significantly reduced by 32% and the number of angina attacks is reduced [12].

Effect of ranolazine on atrial fibrillation
Ranolazine is also a drug for the treatment of atrial fibrillation (AF). It was originally developed as an antianginal drug that inhibits a range of ion currents important in the genesis of transmembrane cardiac action potentials; then its antiarrhythmic action was discovered.
The MERLIN-TIMI 36 study [13] included 6560 patients, of whom more than 3500 had ACS without ST elevation and previous episodes of stable angina, who were randomized to ranolazine groups (intravenous administration followed by oral administration of 1000 mg 2 r. / day) and placebo in addition to standard medical therapy. Initially, there was no significant improvement in the primary endpoints (death and recurrent ischemic events) in the ranolazine group, but with continuous ambulatory ECG recording during the first days, there was a decrease in the number of some arrhythmias, including new episodes of AF: compared with placebo ranolazine therapy led to a decrease in the number of episodes of ventricular tachycardia (5.3% vs. 8.3%, p<0.001) and supraventricular tachycardia (44.7% vs. 2.4%, p=0.08).

In the ventricles, ranolazine has been shown to inhibit the late phase of internal sodium current (late INa). The effect is to reduce the AP and reduce the delay in the activation of the fast retrifi- cation current of potassium (IKr), lengthening the duration of the AP. In the atria, in addition to blocking late INa and IKr, ranolazine slows down the peak of Na channel flow (INa peak) and also has some effect on other currents such as ICaL, INa–Ca, and IKs [14].

In the atria, ranolazine is able to suppress atrial tachyarrhythmias and AF, probably due to its multichannel blocking properties. Ranolazine causes an atrial-selective, frequency-dependent decrease in parameters depending on Na-channel functions, such as depolarization rate, diastolic excitation threshold, and post-repolarizing refractoriness [15]. It was noted that in the atrial myocytes of patients with persistent AF, the inhibitory effect of ranolazine on late INa was stronger in patients with AF than in patients with sinus rhythm. Ranolazine also suppresses premature contraction in the right atrium and reduces diastolic tension [16].

In a small study in 7 patients, ranolazine was given shortly after onset of AF (500–1000 mg bid) and discontinuation of any other antiarrhythmic therapy and was effective in maintaining sinus rhythm: most of these patients had structural heart disease, and conventional antiarrhythmic drugs were not used [17]. The same authors proposed the use of ranolazine as a drug to stop AF when using the “pill in the pocket” tactics [18].

Ranolazine (2000 mg) was given orally to 18 patients with new-onset or paroxysmal AF lasting less than 48 hours: 13 of 18 patients were restored to sinus rhythm within 6 hours of initiation, 72% rate conversion compared with other results of the pill-in-pocket protocols “. These results appear promising despite the small amount of research data.
Ranolazine and amiodarone were compared for the prevention of AF after coronary artery bypass grafting (CABG) in 393 patients (mean age – 65±10 years, 72% men): amiodarone – 400 mg before surgery, then 200 mg 2 times a day for 10-14 days, ranolazine – 1500 mg before surgery, then 1000 mg 2 r./day for 10–14 days [19]. AF was reported in 26.5% of patients treated with amiodarone compared with 17.5% of patients treated with ranolazine (p = 0.035). The use of ranolazine was associated with a significant reduction in the number of episodes of AF compared with the use of amiodarone after CABG, with no significant difference in the incidence of side effects. It remains to be clarified whether the reduction in supraventricular tachycardia and new-onset AF during ranolazine therapy is actually the result of a direct effect on atrial electrophysiology by improving atrial metabolism or LV function (thus indirectly suppressing atrial arrhythmogenesis) [20].

In a study of ranolazine, it was shown that it prevents the effects of myocardial ischemia, improves cardiac function in response to various stress stimuli compared with new inhibitors of essential acid oxidants [21]. It appears that this metabolic role of ranolazine is more related to ischemic protection than inhibition of fatty acid oxidants and may play a role in protection against arrhythmias. The drug concentration required to inhibit β-oxidant fatty acid synthesis (>100 µM) is much higher than the therapeutic concentration (<10 µM). This suggests that the inhibition of fatty acid metabolism cannot explain the mechanism of action of ranolazine. It is currently believed that the anti-ischemic effect is mainly due to the blocking effect of ranolazine on late INaL, which interrupts the initial pathway of the ischemic cascade. However, doubts about the direct electrophysiological effects of ranolazine were eliminated by the results of a study that clearly showed the electrophysiological effects of the drug in the prevention and suppression of atrial arrhythmias in a mouse model with genetic QT syndrome [22]. Therefore, ranolazine has a direct electrophysiological effect in addition to the metabolic effect, which is important in the suppression of arrhythmias.

According to a number of researchers [14], ranolazine has an antiarrhythmic effect, affecting the atria and ventricles. In the ventricles, it can suppress arrhythmia associated with ACS, long QT syndrome, chronic heart failure, ischemia and reperfusion. In the atrium, ranolazine effectively suppresses atrial tachyarrhythmia and AF. The mechanism underlying the antiarrhythmic activity is likely due to inhibition of late INa in the ventricles and frequency-dependent inhibition of the INa and IKr peak in the atrium. The short-term and long-term safety of ranolazine, demonstrated in the clinic, allows the use of this drug in patients with structural changes in the heart, with AF, directly affecting late INa.

It has been demonstrated in an experimental model that suppression of AF can be achieved with low doses of dronedarone and ranolazine using their combination [23]. The authors studied in vitro individual and combined effects of drugs (dronedarone 10 µmol/l and ranolazine 5 µmol/l): ranolazine increased the effective refractory period and post-repolarization refractoriness (PRR) to a greater extent than dronedarone. Similarly, ranolazine prevented AF induction more frequently than dronedarone (29% versus 17%). In combination, dronedarone and ranolazine appear to act synergistically to significantly increase PRR. The success rate for preventing AF was also increased (9 out of 10). In addition, persistent AF was cured and reinduction was prevented in 6 out of 10 cases, and in 6 out of 6 when the drugs were used in combination. The results of this study support the hypothesis of the efficacy of a combination of predominantly open and inactivated sodium channel blockers that can arrest and prevent the induction and reinduction of AF. However, the extrapolation of in vitro results to clinical practice should be done with great caution. The absence of autonomic and hormonal influences that can significantly modulate cardiac electrophysiology and thus pharmacological responses to drugs is one of the limitations of in vitro drugs. In addition, experiments were performed “using” healthy atria and ventricles, and AF usually develops in the presence of structural and electrical remodeling. Atrial remodeling can significantly affect the pharmacological response.
To date, the Phase 2 HARMONY study (A Study to Evaluate the Effect Of Ranolazine and Dronedarone When Given Alone and in Combination) has been completed. It included 134 patients with paroxysmal AF and a dual-chamber pacemaker with the ability to detect AF and record and store an electrocardiogram, who were randomly assigned to one of 5 groups: placebo; ranolazine 750 mg 2 times a day; dronedarone 225 mg bid; ranolazine 750 mg and dronedarone 225 mg bid; or ranolazine 750 mg and dronedarone 150 mg bid.

Compared to the placebo group, the ranolazine 750 mg and dronedarone 225 mg group had a greater percentage change in AF from baseline at 12 weeks. (p=0.008). The ranolazine 750 mg and dronedarone 150 mg (p = 0.072) groups treated with ranolazine 750 mg alone (p = 0.49) showed no significant reduction in AF compared with placebo. In the dronedarone 225 mg alone group, there was no difference in percentage change in AF compared to the placebo group, with a non-significant increase in AF (p=0.78). No serious side effects were found. At the moment, the study is in the 3rd phase, which will be crucial in determining the order of application of this combination [24].

Conclusion
These materials indicate that ranolazine is one of the most active modern anti-ischemic agents. In addition, its antiarrhythmic effect has been objectively shown. It is equally important that the drug is well tolerated, the main side effects (constipation, dizziness, headache) are rare, and the incidence of syncope is less than 1%.

Literature
1. Ford E.S., Ajani U.A., Croft J.B., Critchley J.A., Labarthe D.R., Kottke T.E. et al. Explaining the Decrease in U.S. Deaths from Coronary Disease, 1980-2000 // N Engl J Med. 2007 Vol. 356. R. 2388-2398.
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Ranolazine for patients with stable angina

Review question

We wanted to find out if ranolazine (a drug that prevents angina) is more effective than placebo or other drugs for treating stable angina.

Relevance

Angina presents with sudden chest pain caused by insufficient oxygen supply to the heart or other stressors. People with stable angina have a predictable pattern of symptoms. Symptoms of angina worsen with physical exertion and subside during rest or after taking certain medications. Ranolazine is a relatively new drug for people with angina who are already taking other medications for the condition. 0003

Search date

Evidence is current to February 2016.

Research funding sources

Most studies were fully (9 out of 17) or partially (3 out of 17) funded by pharmaceutical companies. Two studies did not receive external funding, and three did not specify a source of funding.

Study profile

We included 17 studies with a total of 9 participants.975 adults. The studies lasted from 1 to 92 weeks.

Main results

We only compared ranolazine and placebo as little data was collected for other comparisons. Evidence is uncertain whether ranolazine 1000 mg twice daily as monotherapy for people with stable angina affects the likelihood of death from heart-related causes. No evidence was found that ranolazine changed the risk of death from non-cardiac causes.

Despite uncertainties about the effects of ranolazine 1000 mg twice daily as monotherapy on all-cause death, quality of life, heart attack, and angina, ranolazine plus other antianginal drugs slightly reduced the number of angina attacks in week. Ranolazine 1000 mg twice daily increases the risk of dizziness, nausea and constipation (moderate side effects)

Quality of evidence

Overall, the quality of the evidence for the likelihood of moderate side effects (for people treated with ranolazine monotherapy) was rated as very low. The quality of the evidence was low in assessing the likelihood of death from cardiac causes (with ranolazine monotherapy), as well as in assessing the likelihood of death from any cause, the likelihood of a heart attack, and changes in the frequency of angina attacks (with ranolazine monotherapy). We found moderate-quality evidence for quality of life, frequency of angina attacks, and the likelihood of moderate side effects (for people who took ranolazine along with other antianginal drugs).

The low quality of the evidence is due to methodological problems in research and reporting, as well as a lack of data for an accurate assessment.

Translation notes:

Translation: Regina Bayazitova.