Trangorex Dosage

• Dosage of Trangorex in details
• Trangorex interactions
• Trangorex reviews

Dosage of Trangorex in details

Trangorex 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 Trangorex is about 1000 mg over the first 24 hours of therapy, delivered by the following infusion regimen:

Trangorex HCI INJECTION DOSE RECOMMENDATIONS

- FIRST 24 HOURS -

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 (Trangorex 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 Trangorex 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 Trangorex 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 Trangorex injection for longer than 3 weeks.

The surface properties of solutions containing injectable Trangorex 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. Trangorex injection must be delivered by a volumetric infusion pump.

Trangorex injection should, whenever possible, be administered through a central venous catheter dedicated to that purpose. An in-line filter should be used during administration.

Trangorex 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.

Trangorex 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, Trangorex injection concentrations should not exceed 2 mg/mL unless a central venous catheter is used.

Trangorex injection infusions exceeding 2 hours must be administered in glass or polyolefin bottles containing D5W. Use of evacuated glass containers for admixing Trangorex injection is not recommended as incompatibility with a buffer in the container may cause precipitation.

It is well known that Trangorex 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 Trangorex 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 Trangorex at higher concentrations and lower flow rates than provided in dosage and Administration.

Intravenous Trangorex does not need to be protected from light during administration.

Trangorex SOLUTION STABILITY

Intravenous to

Oral Transition

Patients whose arrhythmias have been suppressed by intravenous Trangorex may be switched to oral Trangorex. The optimal dose for changing from intravenous to oral administration of Trangorex will depend on the dose of intravenous Trangorex already administered, as well as the bioavailability of oral Trangorex. When changing to oral Trangorex 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 Trangorex when switching from intravenous to oral Trangorex therapy.

Since grapefruit juice is known to inhibit CYP3A4-mediated metabolism of oral Trangorex in the intestinal mucosa, resulting in increased plasma levels of Trangorex, grapefruit juice should not be taken during treatment with oral Trangorex.

The following table provides suggested doses of oral Trangorex to be initiated after varying durations of intravenous Trangorex administration. These recommendations are made on the basis of a comparable total body amount of Trangorex delivered by the intravenous and oral routes, based on 50% bioavailability of oral Trangorex.

RECOMMENDATIONS FOR ORAL DOSAGE AFTER I.V. INFUSION

How supplied

Trangorex Injection, is supplied as:

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 Trangorex?

Many drugs can interact with Trangorex. Not all possible interactions are listed here. Tell your doctor about all your medications and any you start or stop using during treatment with Trangorex, 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 Trangorex. 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.

Trangorex takes a long time to completely clear from your body, and drug interactions are possible for up to several months after you stop using Trangorex 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 Trangorex.

Trangorex interactions

In view of the long and variable half-life of Trangorex, potential for drug interactions exists, not only with concomitant medication, but also with drugs administered after discontinuation of Trangorex.

Pharmacodynamic Interactions

Drugs Inducing TdP or Prolonging QT

Co-administration of Trangorex 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 Trangorex, resulting in bradycardia, sinus arrest, and AV block. Monitor heart rate in patients on Trangorex and concomitant drugs that slow heart rate.

Pharmocokinetic Interactions

Effects Of Other Medicinal Products On Trangorex

Since Trangorex 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 Trangorex. Concomitant use of CYP3A inducers (rifampin, St. John's Wort), may lead to decreased serum concentrations and loss of efficacy. Consider serial measurement of Trangorex serum concentration during concomitant use of drugs affecting CYP3A activity.

Grapefruit juice given to healthy volunteers increased Trangorex AUC by 50% and C by 84%, and decreased DEA to unquantifiable concentrations. Grapefruit juice inhibits CYP3A-mediated metabolism of oral Trangorex in the intestinal mucosa, resulting in increased plasma levels of Trangorex; therefore, grapefruit juice should not be taken during treatment with oral Trangorex. This information should be considered when transitioning from intravenous to oral Trangorex. Cholestyramine reduces enterohepatic circulation of Trangorex thereby increasing its elimination. This results in reduced Trangorex serum levels and half-life.

Effects Of Trangorex On Other Medicinal Products

Trangorex 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 Trangorex 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 Trangorex has been associated with reports of myopathy/rhabdomyolysis. Limit the dose of simvastatin in patients on Trangorex 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 Trangorex may increase the plasma concentration of these drugs.

Digoxin

In patients receiving digoxin therapy, administration of oral Trangorex results in an increase in the serum digoxin concentration. Trangorex taken concomitantly with digoxin increases the serum digoxin concentration by 70% after one day. On initiation of oral Trangorex, 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 Trangorex. Trangorex taken concomitantly with quinidine increases quinidine serum concentration by 33% after two days. Trangorex 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 Trangorex 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 Trangorex. During transition to Trangorex the dose levels of previously administered agents should be reduced by 30 to 50% several days after the addition of Trangorex, when arrhythmia suppression should be beginning. The continued need for the other antiarrhythmic agent should be reviewed after the effects of Trangorex 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 Trangorex is continued. In Trangorex-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 Trangorex resulting in increased lidocaine concentrations. Sinus bradycardia and seizure has been reported in patients receiving concomitant lidocaine and Trangorex.

Anticoagulants

Potentiation of warfarin-type (CYP2C9 and CYP3A substrate) anticoagulant response is almost always seen in patients receiving Trangorex and can result in serious or fatal bleeding. Since the concomitant administration of warfarin with Trangorex 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 Trangorex resulting in ineffective inhibition of platelet aggregation has been reported.

Dabigatran etexilate when taken concomitantly with Trangorex may result in elevated serum concentration of dabigatran.

Fentanyl (CYP3A substrate) in combination with Trangorex may cause hypotension, bradycardia, and decreased cardiac output.

Increased steady-state levels of phenytoin during concomitant therapy with Trangorex have been reported. Monitor phenytoin levels in patients taking both drugs.

Dextromethorphan is a substrate for both CYP2D6 and CYP3A. Trangorex inhibits CYP2D6 and CYP3A. Chronic ( > 2 weeks) Trangorex treatment impairs metabolism of dextromethorphan leading to increased serum concentration.

References

1. 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).
2. MeSH. "Potassium Channel Blockers". https://www.ncbi.nlm.nih.gov/mesh/68... (accessed September 17, 2018).
3. 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).

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