Dosage of Rythma in details
Rythma shows considerable inter-individual variation in response. Thus, although a starting dose adequate to suppress life-threatening arrhythmias is needed, close monitoring with adjustment of dose as needed is essential. The recommended starting dose of intravenous Rythma is about 1000 mg over the first 24 hours of therapy, delivered by the following infusion regimen:
Rythma HCI INJECTION DOSE RECOMMENDATIONS
- FIRST 24 HOURS -
| Loading infusions First Rapid: | 150 mg over the FIRST 10 minutes (15 mg/min). |
| Add 3 mL of Rythma Injection (150 mg) to 100 mL D5W (concentration = 1.5 mg/mL). Infuse 100 mL over 10 minutes. | |
| Followed by Slow: 360 mg over the NEXT 6 hours (1 mg/min). | |
| Add 18 mL of Rythma Injection (900 mg) to 500 mL D5W (concentration = 1.8 mg/mL). | |
| Maintenance infusion | 540 mg over the REMAINING 18 hours (0.5 mg/min). |
| Decrease the rate of the slow loading infusion to 0.5 mg/min. |
After the first 24 hours, the maintenance infusion rate of 0.5 mg/min (720 mg/24 hours) should be continued utilizing a concentration of 1 to 6 mg/mL (Rythma injection concentrations greater than 2 mg/mL should be administered via a central venous catheter). In the event of breakthrough episodes of VF or hemodynamically unstable VT, 150 mg supplemental infusions of Rythma injection mixed in 100 mL of D5W may be administered. Such infusions should be administered over 10 minutes to minimize the potential for hypotension. The rate of the maintenance infusion may be increased to achieve effective arrhythmia suppression.
The first 24-hour dose may be individualized for each patient; however, in controlled clinical trials, mean daily doses above 2100 mg were associated with an increased risk of hypotension. The initial infusion rate should not exceed 30 mg/min.
Based on the experience from clinical studies of Rythma injection, a maintenance infusion of up to 0.5 mg/min can be cautiously continued for 2 to 3 weeks regardless of the patient's age, renal function, or left ventricular function. There has been limited experience in patients receiving Rythma injection for longer than 3 weeks.
The surface properties of solutions containing injectable Rythma are altered such that the drop size may be reduced. This reduction may lead to underdosage of the patient by up to 30% if drop counter infusion sets are used. Rythma injection must be delivered by a volumetric infusion pump.
Rythma injection should, whenever possible, be administered through a central venous catheter dedicated to that purpose. An in-line filter should be used during administration.
Rythma injection loading infusions at much higher concentrations and rates of infusion much faster than recommended have resulted in hepatocellular necrosis and acute renal failure, leading to death.
Rythma injection concentrations greater than 3 mg/mL in D5W have been associated with a high incidence of peripheral vein phlebitis; however, concentrations of 2.5 mg/mL or less appear to be less irritating. Therefore, for infusions longer than 1 hour, Rythma injection concentrations should not exceed 2 mg/mL unless a central venous catheter is used.
Rythma injection infusions exceeding 2 hours must be administered in glass or polyolefin bottles containing D5W. Use of evacuated glass containers for admixing Rythma injection is not recommended as incompatibility with a buffer in the container may cause precipitation.
It is well known that Rythma adsorbs to polyvinyl chloride (PVC) tubing and the clinical trial dose administration schedule was designed to account for this adsorption. All of the clinical trials were conducted using PVC tubing and its use is therefore recommended. The concentrations and rates of infusion provided in DOSAGE AND ADMINISTRATION reflect doses identified in these studies. It is important that the recommended infusion regimen be followed closely.
Intravenous Rythma has been found to leach out plasticizers, including DEHP [di-(2-ethylhexyl) phthalate] from intravenous tubing (including PVC tubing). The degree of leaching increases when infusing intravenous Rythma at higher concentrations and lower flow rates than provided in dosage and Administration.
Intravenous Rythma does not need to be protected from light during administration.
Rythma SOLUTION STABILITY
| Solution | Concentration (mg/mL) | Container | Comments |
| 5% Dextrose in Water (DW | 3 mg/mL | Precipitate |
Intravenous to
Oral Transition
Patients whose arrhythmias have been suppressed by intravenous Rythma may be switched to oral Rythma. The optimal dose for changing from intravenous to oral administration of Rythma will depend on the dose of intravenous Rythma already administered, as well as the bioavailability of oral Rythma. When changing to oral Rythma therapy, clinical monitoring is recommended, particularly for elderly patients.
Since there are some differences between the safety and efficacy profiles of the intravenous and oral formulations, the prescriber is advised to review the package insert for oral Rythma when switching from intravenous to oral Rythma therapy.
Since grapefruit juice is known to inhibit CYP3A4-mediated metabolism of oral Rythma in the intestinal mucosa, resulting in increased plasma levels of Rythma, grapefruit juice should not be taken during treatment with oral Rythma.
The following table provides suggested doses of oral Rythma to be initiated after varying durations of intravenous Rythma administration. These recommendations are made on the basis of a comparable total body amount of Rythma delivered by the intravenous and oral routes, based on 50% bioavailability of oral Rythma.
RECOMMENDATIONS FOR ORAL DOSAGE AFTER I.V. INFUSION
| Duration of Rythma injection Infusion# | Initial Daily Dose ofOral Rythma |
| < 1 week | 800-1600 mg |
| 1-3 weeks | 600-800 mg |
| > 3 weeks* | 400 mg |
| # Assuming a 720 mg/day infusion (0.5 mg/min). * Rythma Injection is not intended for maintenance treatment. |
How supplied
Rythma Hydrochloride Injection, is supplied as:
| NDC | Syringe | Packaging Factor |
| 25021-302-73 | Rythma Hydrochloride Injection 150 mg/3 mL (50 mg/mL) in 3 mL Single Use Syringe | 10 Single Use Syringes per Carton |
Store at 20° to 25°C (68° to 77°F). Protect from light. Avoid excessive heat. Do not freeze.
Use carton to protect contents from light until used. LATEX-FREE
Mfg. for SAGENT Pharmaceuticals, Schaumburg, IL 60195 (USA). Mfg. by Gland Pharma, India. April 2008. FDA revision date: 2/4/2004
What other drugs will affect Rythma?
Many drugs can interact with Rythma. Not all possible interactions are listed here. Tell your doctor about all your medications and any you start or stop using during treatment with Rythma, especially:
-
an antibiotic--azithromycin, ciprofloxacin, clarithromycin, erythromycin, levofloxacin, moxifloxacin, pentamidine, and others;
-
an antidepressant--amitriptyline, citalopram, desipramine, doxepin, imipramine, maprotiline, nortriptyline, and others;
-
cancer medicines;
-
a diuretic or "water pill";
-
heart rhythm medication--dofetilide, dronedarone, ibutilide, propafenone, sotalol;
-
HIV or AIDS medication--indinavir, nelfinavir, rilpivirine, ritonavir, saquinavir; OR
-
medicine to treat mental illness--chlorpromazine, fluphenazine, haloperidol, lithium, pimozide, promethazine, thioridazine, ziprasidone, and others.
This list is not complete and many other drugs can interact with Rythma. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.
Rythma takes a long time to completely clear from your body, and drug interactions are possible for up to several months after you stop using Rythma injection. Talk to your doctor before taking any medication during this time. Keep track of how long it has been since your last dose of Rythma.
Rythma interactions
In view of the long and variable half-life of Rythma, potential for drug interactions exists, not only with concomitant medication, but also with drugs administered after discontinuation of Rythma.
Pharmacodynamic Interactions
Drugs Inducing TdP or Prolonging QT
Co-administration of Rythma with drugs known to prolong the QT interval (such as class I and III antiarrhythmics, lithium, certain phenothiazines, tricyclic antidepressants, certain fluoroquinolone and macrolide antibiotics, IV pentamidine, and azole antifungals) increases the risk of Torsades de Points. Avoid concomitant use of drugs that prolong the QT interval.
Drugs Lowering Heart Rate Or Causing Automaticity Or Conduction Disorders
Concomitant use of drugs with depressant effects on the sinus and AV node (e.g., digoxin, beta blockers, verapamil, diltiazem, clonidine) can potentiate the electrophysiologic and hemodynamic effects of Rythma, resulting in bradycardia, sinus arrest, and AV block. Monitor heart rate in patients on Rythma and concomitant drugs that slow heart rate.
Pharmocokinetic Interactions
Effects Of Other Medicinal Products On Rythma
Since Rythma is a substrate for CYP3A and CYP2C8, drugs/substances that inhibit CYP3A (e.g., certain protease inhibitors, loratadine, cimetidine, trazodone) may decrease the metabolism and increase serum concentrations of Rythma. Concomitant use of CYP3A inducers (rifampin, St. John's Wort), may lead to decreased serum concentrations and loss of efficacy. Consider serial measurement of Rythma serum concentration during concomitant use of drugs affecting CYP3A activity.
Grapefruit juice given to healthy volunteers increased Rythma AUC by 50% and C by 84%, and decreased DEA to unquantifiable concentrations. Grapefruit juice inhibits CYP3A-mediated metabolism of oral Rythma in the intestinal mucosa, resulting in increased plasma levels of Rythma; therefore, grapefruit juice should not be taken during treatment with oral Rythma. This information should be considered when transitioning from intravenous to oral Rythma. Cholestyramine reduces enterohepatic circulation of Rythma thereby increasing its elimination. This results in reduced Rythma serum levels and half-life.
Effects Of Rythma On Other Medicinal Products
Rythma inhibits P-glycoprotein and certain CYP450 enzymes, including CYP1A2, CYP2C9, CYP2D6, and CYP3A. This inhibition can result in unexpectedly high plasma levels of other drugs which are metabolized by those CYP450 enzymes or are substrates of P-glycoprotein. Reported examples of this interaction include the following:
Cyclosporine (CYP3A substrate) administered in combination with oral Rythma has been reported to produce persistently elevated plasma concentrations of cyclosporine resulting in elevated creatinine, despite reduction in dose of cyclosporine. Monitor cyclosporine drug levels and renal function in patients taking both drugs.
HMG-Co A Reductase Inhibitors
The use of HMG-CoA reductase inhibitors that are CYP3A substrates in combination with Rythma has been associated with reports of myopathy/rhabdomyolysis. Limit the dose of simvastatin in patients on Rythma to 20 mg daily. Limit the daily dose of lovastatin to 40 mg. Lower starting and maintenance doses of other CYP3A substrates (e.g., atorvastatin) may be required as Rythma may increase the plasma concentration of these drugs.
Digoxin
In patients receiving digoxin therapy, administration of oral Rythma results in an increase in the serum digoxin concentration. Rythma taken concomitantly with digoxin increases the serum digoxin concentration by 70% after one day. On initiation of oral Rythma, the need for digitalis therapy should be reviewed and the dose reduced by approximately 50% or discontinued. If digitalis treatment is continued, serum levels should be closely monitored and patients observed for clinical evidence of toxicity.
Antiarrhythmics
The metabolism of quinidine, procainamide, flecainide can be inhibited by Rythma. Rythma taken concomitantly with quinidine increases quinidine serum concentration by 33% after two days. Rythma taken concomitantly with procainamide for less than seven days increases plasma concentrations of procainamide and n-acetyl procainamide by 55% and 33%, respectively. In general, any added antiarrhythmic drug should be initiated at a lower than usual dose with careful monitoring.
Combination of Rythma with other antiarrhythmic therapy should be reserved for patients with lifethreatening ventricular arrhythmias who are incompletely responsive to a single agent or incompletely responsive to Rythma. During transition to Rythma the dose levels of previously administered agents should be reduced by 30 to 50% several days after the addition of Rythma, when arrhythmia suppression should be beginning. The continued need for the other antiarrhythmic agent should be reviewed after the effects of Rythma have been established, and discontinuation ordinarily should be attempted. If the treatment is continued, these patients should be particularly carefully monitored for adverse effects, especially conduction disturbances and exacerbation of tachyarrhythmias, as Rythma is continued. In Rythma-treated patients who require additional antiarrhythmic therapy, the initial dose of such agents should be approximately half of the usual recommended dose.
Metabolism of lidocaine (CYP3A substrate) can be inhibited by Rythma resulting in increased lidocaine concentrations. Sinus bradycardia and seizure has been reported in patients receiving concomitant lidocaine and Rythma.
Anticoagulants
Potentiation of warfarin-type (CYP2C9 and CYP3A substrate) anticoagulant response is almost always seen in patients receiving Rythma and can result in serious or fatal bleeding. Since the concomitant administration of warfarin with Rythma increases the prothrombin time by 100% after 3 to 4 days, the dose of the anticoagulant should be reduced by one-third to one-half, and prothrombin times should be monitored closely.
A potential interaction between clopidogrel and Rythma resulting in ineffective inhibition of platelet aggregation has been reported.
Dabigatran etexilate when taken concomitantly with Rythma may result in elevated serum concentration of dabigatran.
Fentanyl (CYP3A substrate) in combination with Rythma may cause hypotension, bradycardia, and decreased cardiac output.
Increased steady-state levels of phenytoin during concomitant therapy with Rythma have been reported. Monitor phenytoin levels in patients taking both drugs.
Dextromethorphan is a substrate for both CYP2D6 and CYP3A. Rythma inhibits CYP2D6 and CYP3A. Chronic ( > 2 weeks) Rythma treatment impairs metabolism of dextromethorphan leading to increased serum concentration.
References
- FDA/SPL Indexing Data. "N3RQ532IUT: The UNique Ingredient Identifier (UNII) is an alphanumeric substance identifier from the joint FDA/USP Substance Registration System (SRS).". https://www.fda.gov/ForIndustry/Data... (accessed September 17, 2018).
- MeSH. "Potassium Channel Blockers". https://www.ncbi.nlm.nih.gov/mesh/68... (accessed September 17, 2018).
- European Chemicals Agency - ECHA. "Amiodarone: The information provided here is aggregated from the "Notified classification and labelling" from ECHA's C&L Inventory. ". https://echa.europa.eu/information-o... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Rythma are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Rythma. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
Consumer reported frequency of use
No survey data has been collected yetConsumer reported doses
No survey data has been collected yetConsumer reviews
There are no reviews yet. Be the first to write one! |
Information checked by Dr. Sachin Kumar, MD Pharmacology
