Gliclazida Winthrop may be available in the countries listed below.
Gliclazide is reported as an ingredient of Gliclazida Winthrop in the following countries:
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Lomesone may be available in the countries listed below.
Alclometasone 17α,21-dipropionate (a derivative of Alclometasone) is reported as an ingredient of Lomesone in the following countries:
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Alfasuly may be available in the countries listed below.
Alfacalcidol is reported as an ingredient of Alfasuly in the following countries:
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Dopamine hydrochloride (a derivative of Dopamine) is reported as an ingredient of Dopamine Hydrochloride in Dextrose in the following countries:
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In the US, K-10 is a member of the drug class minerals and electrolytes and is used to treat Hypokalemia and Prevention of Hypokalemia.
Potassium Chloride is reported as an ingredient of K-10 in the following countries:
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In some countries, this medicine may only be approved for veterinary use.
In the US, Potassium Iodide (potassium iodide systemic) is a member of the following drug classes: antithyroid agents, expectorants and is used to treat Cough, Cutaneous Sporotrichosis, Hyperthyroidism and Radiation Emergency.
US matches:
USP
R05CA02,S01XA04,V03AB21
0007681-11-0
K-I
166
Antidote
Expectorant
Prophylactic, iodine therapy
Potassium iodide (KI)
International Drug Name Search
Glossary
| JAN | Japanese Accepted Name |
| OS | Official Synonym |
| PH | Pharmacopoeia Name |
| USP | Pharmacopoeia of the United States |
Faltidin may be available in the countries listed below.
Famotidine is reported as an ingredient of Faltidin in the following countries:
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Cyclocaps Budesonid may be available in the countries listed below.
Budesonide is reported as an ingredient of Cyclocaps Budesonid in the following countries:
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Félodipine Sandoz may be available in the countries listed below.
Felodipine is reported as an ingredient of Félodipine Sandoz in the following countries:
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Zotrix may be available in the countries listed below.
Ondansetron hydrochloride (a derivative of Ondansetron) is reported as an ingredient of Zotrix in the following countries:
Ondansetron hydrochloride dihydrate (a derivative of Ondansetron) is reported as an ingredient of Zotrix in the following countries:
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In the US, Baci-Rx is a member of the drug class miscellaneous antibiotics and is used to treat Pneumonia.
Bacitracin is reported as an ingredient of Baci-Rx in the following countries:
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Keratinamin Kowa may be available in the countries listed below.
Urea is reported as an ingredient of Keratinamin Kowa in the following countries:
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Mirtaron may be available in the countries listed below.
Mirtazapine is reported as an ingredient of Mirtaron in the following countries:
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MTX medac may be available in the countries listed below.
Methotrexate is reported as an ingredient of MTX medac in the following countries:
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Sedaquin may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Acepromazine maleate (a derivative of Acepromazine) is reported as an ingredient of Sedaquin in the following countries:
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Lattulosio Germed may be available in the countries listed below.
Lactulose is reported as an ingredient of Lattulosio Germed in the following countries:
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Fenoxymethylpenicilline CF may be available in the countries listed below.
Phenoxymethylpenicillin potassium (a derivative of Phenoxymethylpenicillin) is reported as an ingredient of Fenoxymethylpenicilline CF in the following countries:
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Kalliant TP may be available in the countries listed below.
Isosorbide Dinitrate is reported as an ingredient of Kalliant TP in the following countries:
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Marbocyl Bolus may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Marbofloxacin is reported as an ingredient of Marbocyl Bolus in the following countries:
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Coldistan may be available in the countries listed below.
Diphenhydramine hydrochloride (a derivative of Diphenhydramine) is reported as an ingredient of Coldistan in the following countries:
Naphazoline hydrochloride (a derivative of Naphazoline) is reported as an ingredient of Coldistan in the following countries:
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Lanzo may be available in the countries listed below.
Lansoprazole is reported as an ingredient of Lanzo in the following countries:
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Pyricontin may be available in the countries listed below.
Pyridoxine is reported as an ingredient of Pyricontin in the following countries:
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Dosidol may be available in the countries listed below.
Nefopam hydrochloride (a derivative of Nefopam) is reported as an ingredient of Dosidol in the following countries:
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Aspen Vancomycin may be available in the countries listed below.
Vancomycin hydrochloride (a derivative of Vancomycin) is reported as an ingredient of Aspen Vancomycin in the following countries:
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Ciplametazon may be available in the countries listed below.
Beclometasone 17α,21-dipropionate (a derivative of Beclometasone) is reported as an ingredient of Ciplametazon in the following countries:
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Tétrazépam Sandoz may be available in the countries listed below.
Tetrazepam is reported as an ingredient of Tétrazépam Sandoz in the following countries:
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Enalapril Bluepharma may be available in the countries listed below.
Enalapril maleate (a derivative of Enalapril) is reported as an ingredient of Enalapril Bluepharma in the following countries:
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Active ingredient (in each teaspoonful(5 mL)) Purpose
Docusate 20 mg . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Stool Softener
| Adults and children over 12 years | 1 to 3 tablespoonfuls |
| Children 12 to under 6 years | 2 teaspoonfuls |
| children under 6 years | Ask a doctor |
alcohol(not more than 1%), citric acid, D&C red no. 33, FD&C red no.6, glycerin, flavor, methylparaben, sodium benzoate, propylene glycol, propylparaben, purified water, sodium citrate, sucrose.
Qualitest Pharmaceuticals
130 Vintage Drive
Huntsville, AL 35811
USA
| DOCQLACE docusate sodium syrup | ||||||||||||||||||||||||||||
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| Marketing Information | |||
| Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
| unapproved drug other | 10/05/1990 | ||
| Labeler - Qualitest Pharmaceuticals (011103059) |
| Registrant - Silarx Pharmaceuticals, Inc (161630033) |
Linco Spectin may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Lincomycin is reported as an ingredient of Linco Spectin in the following countries:
Lincomycin hydrochloride monohydrate (a derivative of Lincomycin) is reported as an ingredient of Linco Spectin in the following countries:
Spectinomycin is reported as an ingredient of Linco Spectin in the following countries:
Spectinomycin sulphate tetrahydrate for veterinary use (a derivative of Spectinomycin) is reported as an ingredient of Linco Spectin in the following countries:
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Balance may be available in the countries listed below.
Chlordiazepoxide is reported as an ingredient of Balance in the following countries:
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Topimax may be available in the countries listed below.
Prednicarbate is reported as an ingredient of Topimax in the following countries:
Topiramate is reported as an ingredient of Topimax in the following countries:
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Pragesol may be available in the countries listed below.
Metamizole sodium anhydrous (a derivative of Metamizole) is reported as an ingredient of Pragesol in the following countries:
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Argatra may be available in the countries listed below.
Argatroban is reported as an ingredient of Argatra in the following countries:
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Cryosid may be available in the countries listed below.
Etoposide is reported as an ingredient of Cryosid in the following countries:
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Anapeine may be available in the countries listed below.
Ropivacaine hydrochloride (a derivative of Ropivacaine) is reported as an ingredient of Anapeine in the following countries:
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Kalléone may be available in the countries listed below.
Kalléone (DCF) is also known as Kallidinogenase (Rec.INN)
International Drug Name Search
Glossary
| DCF | Dénomination Commune Française |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
Aciclovir Topico Kern Pharma may be available in the countries listed below.
Aciclovir is reported as an ingredient of Aciclovir Topico Kern Pharma in the following countries:
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Sali-Decoderm may be available in the countries listed below.
Fluprednidene 21-acetate (a derivative of Fluprednidene) is reported as an ingredient of Sali-Decoderm in the following countries:
Salicylic Acid is reported as an ingredient of Sali-Decoderm in the following countries:
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Tibs may be available in the countries listed below.
Tegaserod is reported as an ingredient of Tibs in the following countries:
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Tripanzym may be available in the countries listed below.
Pancreatin is reported as an ingredient of Tripanzym in the following countries:
Simeticone is reported as an ingredient of Tripanzym in the following countries:
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Irinotecan Mayne may be available in the countries listed below.
Irinotecan hydrochloride trihydrate (a derivative of Irinotecan) is reported as an ingredient of Irinotecan Mayne in the following countries:
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Fluzole may be available in the countries listed below.
Fluconazole is reported as an ingredient of Fluzole in the following countries:
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Corixa may be available in the countries listed below.
Clarithromycin is reported as an ingredient of Corixa in the following countries:
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Gemcitabine Vianex may be available in the countries listed below.
Gemcitabine hydrochloride (a derivative of Gemcitabine) is reported as an ingredient of Gemcitabine Vianex in the following countries:
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Kavelor may be available in the countries listed below.
Simvastatin is reported as an ingredient of Kavelor in the following countries:
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Neuvita may be available in the countries listed below.
Octotiamine is reported as an ingredient of Neuvita in the following countries:
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Venlafaxine EG may be available in the countries listed below.
Venlafaxine hydrochloride (a derivative of Venlafaxine) is reported as an ingredient of Venlafaxine EG in the following countries:
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Novolin 50R may be available in the countries listed below.
Insulin Injection, Biphasic Isophane human (a derivative of Insulin Injection, Biphasic Isophane) is reported as an ingredient of Novolin 50R in the following countries:
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Ciper-Pulvizoo may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Cypermethrin is reported as an ingredient of Ciper-Pulvizoo in the following countries:
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Miridacin may be available in the countries listed below.
Proglumetacin dimaleate (a derivative of Proglumetacin) is reported as an ingredient of Miridacin in the following countries:
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Apo-Pioglitazone may be available in the countries listed below.
Pioglitazone is reported as an ingredient of Apo-Pioglitazone in the following countries:
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Fluconazol La Santé may be available in the countries listed below.
Fluconazole is reported as an ingredient of Fluconazol La Santé in the following countries:
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Vilbine may be available in the countries listed below.
Vinorelbine is reported as an ingredient of Vilbine in the following countries:
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The following drugs and medications are in some way related to, or used in the treatment of Photoaging of the Skin. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.
Vincamin-ratiopharm may be available in the countries listed below.
Vincamine is reported as an ingredient of Vincamin-ratiopharm in the following countries:
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Oxaltina may be available in the countries listed below.
Oxaliplatin is reported as an ingredient of Oxaltina in the following countries:
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Megacin may be available in the countries listed below.
Cefradine is reported as an ingredient of Megacin in the following countries:
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Silarine may be available in the countries listed below.
Silibinin is reported as an ingredient of Silarine in the following countries:
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Anavan may be available in the countries listed below.
Diclofenac sodium salt (a derivative of Diclofenac) is reported as an ingredient of Anavan in the following countries:
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In the US, Kerasal (ammonium lactate/urea topical) is a member of the drug class topical emollients and is used to treat Foot Care.
US matches:
Salicylic Acid is reported as an ingredient of Kerasal in the following countries:
Urea is reported as an ingredient of Kerasal in the following countries:
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Dihormon may be available in the countries listed below.
Estradiol 17ß-valerate (a derivative of Estradiol) is reported as an ingredient of Dihormon in the following countries:
Testosterone 17ß-enantate (a derivative of Testosterone) is reported as an ingredient of Dihormon in the following countries:
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Adebit may be available in the countries listed below.
Buformin hydrochloride (a derivative of Buformin) is reported as an ingredient of Adebit in the following countries:
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Phendimétrazine may be available in the countries listed below.
Phendimétrazine (DCF) is known as Phendimetrazine in the US.
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Glossary
| DCF | Dénomination Commune Française |
Tonocalcin may be available in the countries listed below.
Calcitonin is reported as an ingredient of Tonocalcin in the following countries:
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Rixapen may be available in the countries listed below.
Clometocillin potassium salt (a derivative of Clometocillin) is reported as an ingredient of Rixapen in the following countries:
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Augmentin-BID may be available in the countries listed below.
Amoxicillin is reported as an ingredient of Augmentin-BID in the following countries:
Amoxicillin trihydrate (a derivative of Amoxicillin) is reported as an ingredient of Augmentin-BID in the following countries:
Clavulanic Acid is reported as an ingredient of Augmentin-BID in the following countries:
Clavulanic Acid potassium (a derivative of Clavulanic Acid) is reported as an ingredient of Augmentin-BID in the following countries:
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Dexrazoxane for injection is a sterile, pyrogen-free lyophilizate intended for intravenous administration. It is a cardioprotective agent for use in conjunction with doxorubicin.
Chemically, Dexrazoxane is (S)-4,4'-(1-methyl-1,2-ethanediyl)bis-2,6piperazinedione.The structural formula is as follows:
C11H16N4O4 M.W. 268.28
Dexrazoxane, a potent intracellular chelating agent is a derivative of EDTA. Dexrazoxane is a whitish crystalline powder which melts at 191° to 197°C. It is sparingly soluble in water and 0.1 N HCl, slightly soluble in ethanol and methanol and practically insoluble in nonpolar organic solvents. The pKa is 2.1. Dexrazoxane has an octanol/water partition coefficient of 0.025 and degrades rapidly above a pH of 7.0.
Dexrazoxane for injection is available in 250 mg and 500 mg single use only vials.
Each 250 mg vial contains Dexrazoxane hydrochloride equivalent to 250 mg Dexrazoxane. Hydrochloric Acid, NF is added for pH adjustment. When reconstituted as directed with the 25 mL vial of 0.167 Molar (M/6) Sodium Lactate Injection, USP diluent provided, each mL contains: 10 mg Dexrazoxane. The pH of the resultant solution is 3.5 to 5.5.
Each 500 mg vial contains Dexrazoxane hydrochloride equivalent to 500 mg Dexrazoxane. Hydrochloric Acid, NF is added for pH adjustment. When reconstituted as directed with the 50 mL vial of 0.167 Molar (M/6) Sodium Lactate Injection, USP diluent provided, each mL contains: 10 mg Dexrazoxane. The pH of the resultant solution is 3.5 to 5.5.
The mechanism by which Dexrazoxane for injection exerts its cardioprotective activity is not fully understood. Dexrazoxane is a cyclic derivative of EDTA that readily penetrates cell membranes. Results of laboratory studies suggest that Dexrazoxane is converted intracellularly to a ring-opened chelating agent that interferes with iron-mediated free radical generation thought to be responsible, in part, for anthracycline induced cardiomyopathy.
The pharmacokinetics of Dexrazoxane have been studied in advanced cancer patients with normal renal and hepatic function. Generally, the pharmacokinetics of Dexrazoxane can be adequately described by a two-compartment open model with first-order elimination. Dexrazoxane has been administered as a 15 minute infusion over a dose-range of 60 to 900 mg/m2 with 60 mg/m2 of doxorubicin, and at a fixed dose of 500 mg/m2 with 50 mg/m2 doxorubicin. The disposition kinetics of Dexrazoxane are dose-independent, as shown by linear relationship between the area under plasma concentration-time curves and administered doses ranging from 60 to 900 mg/m2. The mean peak plasma concentration of Dexrazoxane was 36.5 mcg/mL at the end of the 15 minute infusion of a 500 mg/m2 dose of Dexrazoxane for injection administered 15 to 30 minutes prior to the 50 mg/m2 doxorubicin dose. The important pharmacokinetic parameters of Dexrazoxane are summarized in the following table.
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| Dose Doxorubicin (mg/m2) | Dose Dexrazoxane (mg/m2) | Number of Subjects | Elimination Half-Life (h) | Plasma Clearance (L/h/m2) | Renal Clearance (L/h/m2) | †Volume of Distribution (L/m2) |
| 50 | 500 | 10 | 2.5 (16) | 7.88 (18) | 3.35 (36) | 22.4 (22) |
| 60 | 600 | 5 | 2.1 (29) | 6.25 (31) | --- | 22 (55) |
Following a rapid distributive phase (~ 0.2 to 0.3 hours), Dexrazoxane reaches post-distributive equilibrium within 2 to 4 hours. The estimated steady-state volume of distribution of Dexrazoxane suggests its distribution primarily in the total body water (25 L/m2). The mean systemic clearance and steady-state volume of distribution of Dexrazoxane in two Asian female patients at 500 mg/m2 Dexrazoxane along with 50 mg/m2 doxorubicin were 15.15 L/h/m2 and 36.27 L/m2, respectively, but their elimination half-life and renal clearance of Dexrazoxane were similar to those of the ten Caucasian patients from the same study. Qualitative metabolism studies with Dexrazoxane for injection have confirmed the presence of unchanged drug, a diacid-diamide cleavage product, and two monoacid-monoamide ring products in the urine of animals and man. The metabolite levels were not measured in the pharmacokinetic studies.
Urinary excretion plays an important role in the elimination of Dexrazoxane. Forty-two percent of the 500 mg/m2 dose of Dexrazoxane for injection was excreted in the urine.
In vitro studies have shown that Dexrazoxane for injection is not bound to plasma proteins.
The pharmacokinetics of Dexrazoxane for injection have not been evaluated in pediatric patients.
Analysis of pooled data from two pharmacokinetic studies indicate that male patients have a lower mean clearance value than female patients (110 mL/min/m2 versus 133 mL/min/m2). This gender effect is not clinically relevant.
The pharmacokinetics of Dexrazoxane for injection were assessed following a single 15 minute IV infusion of 150 mg/m2 of Dexrazoxane in male and female subjects with varying degrees of renal dysfunction as determined by creatinine clearance (CLCR) based on a 24-hour urinary creatinine collection. Dexrazoxane clearance was reduced in subjects with renal dysfunction. Compared with controls, the mean AUC0–inf value was 2-fold greater in subjects with moderate (CLCR 30 to 50 mL/min) to severe (CLCR < 30 mL/min) renal dysfunction. Modeling demonstrated that equivalent exposure (AUC0–inf) could be achieved if dosing were reduced by 50% in subjects with creatinine clearance values < 40 mL/min compared with control subjects (CLCR >80 mL/min) (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).
The pharmacokinetics of Dexrazoxane for injection have not been evaluated in patients with hepatic impairment. The Dexrazoxane for injection dose is dependent upon the dose of doxorubicin (see DOSAGE AND ADMINISTRATION). Since a doxorubicin dose reduction is recommended in the presence of hyperbilirubinemia, the Dexrazoxane for injection dosage is proportionately reduced in patients with hepatic impairment.
There was no significant change in the pharmacokinetics of doxorubicin (50 mg/m2) and its predominant metabolite, doxorubicinol, in the presence of Dexrazoxane (500 mg/m2) in a crossover study in cancer patients.
The ability of Dexrazoxane for injection to prevent/reduce the incidence and severity of doxorubicin-induced cardiomyopathy was demonstrated in three prospectively randomized placebo-controlled studies. In these studies, patients were treated with a doxorubicin-containing regimen and either Dexrazoxane for injection or placebo starting with the first course of chemotherapy. There was no restriction on the cumulative dose of doxorubicin. Cardiac function was assessed by measurement of the left ventricular ejection fraction (LVEF), utilizing resting multigated nuclear medicine (MUGA) scans, and by clinical evaluations. Patients receiving Dexrazoxane for injection had significantly smaller mean decreases from baseline in LVEF and lower incidences of congestive heart failure than the control group. The difference in decline from baseline in LVEF was evident beginning with a cumulative doxorubicin dose of 150 mg/m2 and reached statistical significance in patients who received ≥ 400 mg/m2 of doxorubicin. In addition to evaluating the effect of Dexrazoxane for injection on cardiac function, the studies also assessed the effect of the addition of Dexrazoxane for injection on the antitumor efficacy of the chemotherapy regimens. In one study (the largest of three breast cancer studies) patients with advanced breast cancer receiving fluorouracil, doxorubicin and cyclophosphamide (FAC) with Dexrazoxane for injection had a lower response rate (48% vs. 63%; p = 0.007) and a shorter time to progression than patients who received FAC + placebo, although the survival of patients who did or did not receive Dexrazoxane for injection with FAC was similar.
Two of the randomized breast cancer studies evaluating the efficacy and safety of FAC with either Dexrazoxane for injection or placebo were amended to allow patients on the placebo arm who had attained a cumulative dose of doxorubicin of 300 mg/m2 (six courses of FAC) to receive FAC with open-label Dexrazoxane for injection for each subsequent course. This change in design allowed examination of whether there was a cardioprotective effect of Dexrazoxane for injection even when it was started after substantial exposure to doxorubicin.
Retrospective historical analyses were then performed to compare the likelihood of heart failure in patients to whom Dexrazoxane for injection was added to the FAC regimen after they had received six (6) courses of FAC (and who then continued treatment with FAC therapy) with the heart failure rate in patients who had received six (6) courses of FAC and continued to receive this regimen without added Dexrazoxane for injection. These analyses showed that the risk of experiencing a cardiac event (see Table 1 for definition) at a given cumulative dose of doxorubicin above 300 mg/m2 was substantially greater in the 99 patients who did not receive Dexrazoxane for injection beginning with their seventh course of FAC than in the 102 patients who did receive Dexrazoxane for injection (see Figure 1).
Table 1: The Development of Cardiac Events is Shown by:
Figure 1 displays the risk of developing congestive heart failure by cumulative dose of doxorubicin in patients who received Dexrazoxane for injection starting with their seventh course of FAC compared to patients who did not. Patients unprotected by Dexrazoxane for injection had a 13 times greater risk of developing congestive heart failure. Overall, 3% of patients treated with Dexrazoxane for injection developed CHF compared with 22% of patients not receiving Dexrazoxane for injection.
Because of its cardioprotective effect, Dexrazoxane for injection permitted a greater percentage of patients to be treated with extended doxorubicin therapy. Figure 2 shows the number of patients still on treatment at increasing cumulative doses.
In addition to evaluating the cardioprotective efficacy of Dexrazoxane for injection in this setting, the time to tumor progression and survival of these two groups of patients were also compared. There was a similar time to progression in the two groups and survival was at least as long for the group of patients that received Dexrazoxane for injection starting with their seventh course, i.e., starting after a cumulative dose of doxorubicin of 300 mg/m2. These time to progression and survival data should be interpreted with caution, however, because they are based on comparisons of groups entered sequentially in the studies and are not comparisons of prospectively randomized patients.
Dexrazoxane for injection is indicated for reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin dose of 300 mg/m2 and who will continue to receive doxorubicin therapy to maintain tumor control. It is not recommended for use with the initiation of doxorubicin therapy (see WARNINGS).
Dexrazoxane for injection should not be used with chemotherapy regimens that do not contain an anthracycline.
Dexrazoxane for injection may add to the myelosuppression caused by chemotherapeutic agents.
There is some evidence that the use of Dexrazoxane concurrently with the initiation of fluorouracil, doxorubicin and cyclophosphamide (FAC) therapy interferes with the antitumor efficacy of the regimen, and this use is not recommended. In the largest of three breast cancer trials, patients who received Dexrazoxane starting with their first cycle of FAC therapy had a lower response rate (48% vs. 63%; p = 0.007) and shorter time to progression than patients who did not receive Dexrazoxane (see CLINICAL PHARMACOLOGY: Clinical Studies). Therefore, Dexrazoxane for injection should only be used in those patients who have received a cumulative doxorubicin dose of 300 mg/m2 and are continuing with doxorubicin therapy.
Although clinical studies have shown that patients receiving FAC with Dexrazoxane for injection may receive a higher cumulative dose of doxorubicin before experiencing cardiac toxicity than patients receiving FAC without Dexrazoxane for injection, the use of Dexrazoxane for injection in patients who have already received a cumulative dose of doxorubicin of 300 mg/m2 without Dexrazoxane for injection, does not eliminate the potential for anthracycline induced cardiac toxicity. Therefore, cardiac function should be carefully monitored.
Secondary malignancies (primarily acute myeloid leukemia) have been reported in patients treated chronically with oral razoxane. Razoxane is the racemic mixture, of which Dexrazoxane is the S(+)-enantiomer. In these patients, the total cumulative dose of razoxane ranged from 26 to 480 grams and the duration of treatment was from 42 to 319 weeks. One case of T-cell lymphoma, a case of B-cell lymphoma and six to eight cases of cutaneous basal cell or squamous cell carcinoma have also been reported in patients treated with razoxane.
Doxorubicin should not be given prior to the intravenous injection of Dexrazoxane. Dexrazoxane for injection should be given by slow I.V. push or rapid drip intravenous infusion from a bag. Doxorubicin should be given within 30 minutes after beginning the infusion with Dexrazoxane for injection. (See DOSAGE AND ADMINISTRATION.)
As Dexrazoxane for injection will always be used with cytotoxic drugs, patients should be monitored closely. While the myelosuppressive effects of Dexrazoxane for injection at the recommended dose are mild, additive effects upon the myelosuppressive activity of chemotherapeutic agents may occur.
Greater exposure to Dexrazoxane may occur in patients with compromised renal function. The Dexrazoxane for injection dose should be reduced by 50% in patients with creatinine clearance values < 40 mL/min (see DOSAGE AND ADMINISTRATION).
As Dexrazoxane for injection may add to the myelosuppressive effects of cytotoxic drugs, frequent complete blood counts are recommended. (See ADVERSE REACTIONS.)
Dexrazoxane for injection does not influence the pharmacokinetics of doxorubicin.
(see WARNINGS section for information on human carcinogenicity) - No long-term carcinogenicity studies have been carried out with Dexrazoxane in animals. Dexrazoxane was not mutagenic in the Ames test but was found to be clastogenic to human lymphocytes in vitro and to mouse bone marrow erythrocytes in vivo (micronucleus test).
The possible adverse effects of Dexrazoxane for injection on the fertility of humans and experimental animals, male or female, have not been adequately studied. Testicular atrophy was seen with Dexrazoxane administration at doses as low as 30 mg/kg weekly for 6 weeks in rats (1/3 the human dose on a mg/m2 basis) and as low as 20 mg/kg weekly for 13 weeks in dogs (approximately equal to the human dose on a mg/m2 basis).
Dexrazoxane was maternotoxic at doses of 2 mg/kg (1/40 the human dose on a mg/m2 basis) and embryotoxic and teratogenic at 8 mg/kg (approximately 1/10 the human dose on a mg/m2 basis) when given daily to pregnant rats during the period of organogenesis. Teratogenic effects in the rat included imperforate anus, microphthalmia, and anophthalmia. In offspring allowed to develop to maturity, fertility was impaired in the male and female rats treated in utero during organogenesis at 8 mg/kg. In rabbits, doses of 5 mg/kg (approximately 1/10 the human dose on a mg/m2 basis) daily during the period of organogenesis were maternotoxic and dosages of 20 mg/kg (1/2 the human dose on a mg/m2 basis) were embryotoxic and teratogenic. Teratogenic effects in the rabbit included several skeletal malformations such as short tail, rib and thoracic malformations, and soft tissue variations including subcutaneous, eye and cardiac hemorrhagic areas, as well as agenesis of the gallbladder and of the intermediate lobe of the lung. There are no adequate and well controlled studies in pregnant women. Dexrazoxane for injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
It is not known whether Dexrazoxane is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants exposed to Dexrazoxane, mothers should be advised to discontinue nursing during Dexrazoxane therapy.
Safety and effectiveness of Dexrazoxane in pediatric patients have not been established.
Clinical studies of Dexrazoxane for injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, elderly patients should be treated with caution due to the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.
Dexrazoxane for injection at a dose of 500 mg/m2 has been administered in combination with FAC in randomized, placebo-controlled, double-blind studies to patients with metastatic breast cancer. The dose of doxorubicin was 50 mg/m2 in each of the trials. Courses were repeated every three weeks, provided recovery from toxicity had occurred. Table 2 below lists the incidence of adverse experiences for patients receiving FAC with either Dexrazoxane for injection or placebo in the breast cancer studies. Adverse experiences occurring during courses 1 through 6 are displayed for patients receiving Dexrazoxane for injection or placebo with FAC beginning with their first course of therapy (column 1 and 3, respectively). Adverse experiences occurring at course 7 and beyond for patients who received placebo with FAC during the first six courses and who then received either Dexrazoxane for injection or placebo with FAC are also displayed (column 2 and 4, respectively).
| Adverse Experience | Percentage (%) of Breast Cancer Patients with Adverse Experience | |||
| FAC + Dexrazoxane | FAC + Placebo | |||
Courses 1 to 6 N = 413 | Courses ≥ 7 N = 102 | Courses 1 to 6 N = 458 | Courses ≥ 7 N = 99 | |
| Alopecia | 94 | 100 | 97 | 98 |
| Nausea | 77 | 51 | 84 | 60 |
| Vomiting | 59 | 42 | 72 | 49 |
| Fatigue/Malaise | 61 | 48 | 58 | 55 |
| Anorexia | 42 | 27 | 47 | 38 |
| Stomatitis | 34 | 26 | 41 | 28 |
| Fever | 34 | 22 | 29 | 18 |
| Infection | 23 | 19 | 18 | 21 |
| Diarrhea | 21 | 14 | 24 | 7 |
| Pain on Injection | 12 | 13 | 3 | 0 |
| Sepsis | 17 | 12 | 14 | 9 |
| Neurotoxicity | 17 | 10 | 13 | 5 |
| Streaking/Erythema | 5 | 4 | 4 | 2 |
| Phlebitis | 6 | 3 | 3 | 5 |
| Esophagitis | 6 | 3 | 7 | 4 |
| Dysphagia | 8 | 0 | 10 | 5 |
| Hemorrhage | 2 | 3 | 2 | 1 |
| Extravasation | 1 | 3 | 1 | 2 |
| Urticaria | 2 | 2 | 2 | 0 |
| Recall Skin Reaction | 1 | 1 | 2 | 0 |
The adverse experiences listed above are likely attributable to the FAC regimen with the exception of pain on injection that was observed mainly on the Dexrazoxane for injection arm.
Patients receiving FAC with Dexrazoxane for injection experienced more severe leucopenia, granulocytopenia and thrombocytopenia at nadir than patients receiving FAC without Dexrazoxane for injection, but recovery counts were similar for the two groups of patients.
Some patients receiving FAC + Dexrazoxane for injection or FAC + placebo experienced marked abnormalities in hepatic or renal function tests, but the frequency and severity of abnormalities in bilirubin, alkaline phosphatase, BUN, and creatinine were similar for patients receiving FAC with or without Dexrazoxane for injection.
There have been no instances of drug overdose in the clinical studies sponsored by the National Cancer Institute. The maximum dose administered during the cardioprotective trials was 1000 mg/m2 every 3 weeks.
Disposition studies with Dexrazoxane for injection have not been conducted in cancer patients undergoing dialysis, but retention of a significant dose fraction (> 0.4) of the unchanged drug in the plasma pool, minimal tissue partitioning or binding, and availability of greater than 90% of the systemic drug levels in the unbound form suggest that it could be removed using conventional peritoneal or hemodialysis.
There is no known antidote for Dexrazoxane. Instances of suspected overdose should be managed with good supportive care until resolution of myelosuppression and related conditions is complete. Management of overdose should include treatment of infections, fluid regulation, and maintenance of nutritional requirements.
The recommended dosage ratio of Dexrazoxane for injection:doxorubicin is 10:1 (e.g., 500 mg/m2 Dexrazoxane for injection:50 mg/m2 doxorubicin). In patients with moderate to severe renal dysfunction (creatinine clearance values < 40 mL/min), the recommended dosage ratio of Dexrazoxane for injection:doxorubicin is 5:1 (eg. 250 mg/m2 Dexrazoxane for injection:50 mg/m2 doxorubicin). Creatinine clearance can be determined from a 24-hour urinary creatinine collection or estimated using the Crockroft-Gault equation (assuming stable renal function):
Since a doxorubicin dose reduction is recommended in the presence of hyperbilirubinemia, the Dexrazoxane for injection dosage should be proportionately reduced (maintaining the 10:1 ratio) in patients with hepatic impairment. Dexrazoxane for injection must be reconstituted with 0.167 Molar (M/6) sodium lactate injection, USP, to give a concentration of 10 mg Dexrazoxane for injection for each mL of sodium lactate. The reconstituted solution should be given by slow I.V. push or rapid drip intravenous infusion from a bag. After completing the infusion of Dexrazoxane for injection, and prior to a total elapsed time of 30 minutes (from the beginning of the Dexrazoxane for injection infusion), the intravenous injection of doxorubicin should be given.
Reconstituted Dexrazoxane for injection, when transferred to an empty infusion bag, is stable for 6 hours from the time of reconstitution when stored at controlled room temperature, 20° to 25°C (68° to 77°F) or under refrigeration, 2° to 8°C (36° to 46°F). DISCARD UNUSED SOLUTIONS.
The reconstituted Dexrazoxane for injection solution may be diluted with either 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to a concentration range of 1.3 to 5 mg/mL in intravenous infusion bags. The resultant solutions are stable for 6 hours when stored at controlled room temperature, 20° to 25°C (68° to 77°F) or under refrigeration, 2° to 8°C (36° to 46°F). DISCARD UNUSED SOLUTIONS.
Dexrazoxane for injection should not be mixed with other drugs.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Caution in the handling and preparation of the reconstituted solution must be exercised and the use of gloves is recommended. If Dexrazoxane for injection powder or solutions contact the skin or mucosae, immediately wash thoroughly with soap and water.
Procedures normally used for proper handling and disposal of anticancer drugs should be considered for use with Dexrazoxane for injection. Several guidelines on this subject have been published.1–8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
Dexrazoxane for Injection is available in the following strengths as sterile, pyrogen-free lyophilizates.
NDC 67457-207-25
250 mg single dose vial with a green flip-top seal, packaged in single vial packs. (This package also contains a 25 mL vial of 0.167 Molar (M/6) Sodium Lactate Injection, USP.)
NDC 67457-208-50
500 mg single dose vial with a blue flip-top seal, packaged in single vial packs. (This package also contains a 50 mL vial of 0.167 Molar (M/6) Sodium Lactate Injection, USP.)
Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Reconstituted solutions of Dexrazoxane for injection are stable for 6 hours at controlled room temperature or under refrigeration, 2° to 8°C (36° to 46°F). DISCARD UNUSED SOLUTIONS.
Manufactured for:
Mylan Institutional LLC
Rockford, IL 61103 U.S.A.
Made in India
M.L.: 103/AP/RR/97/F/R
JUNE 2011
MI:DEXRIJ:R1
PRINCIPAL DISPLAY PANEL - 250 mg
NDC 67457-207-25
For Intravenous Use Only
Dexrazoxane for Injection
250 mg and
0.167M (M/6)
Sodium Lactate Injection, USP
Sterile, pyrogen-free lyophilizate
Rx only
1 x 250 mg single dose vial Dexrazoxane
1 x 25 mL vial sodium lactate injection, USP as diluent
Each vial contains:
Dexrazoxane hydrochloride equivalent
to 250 mg Dexrazoxane.
The pH is adjusted with hydrochloric
acid, NF.
This package also contains one 25 mL
vial of 0.167M (M/6) sodium lactate
injection, USP, as diluent.
Upon reconstitution with 25 mL vial of
0.167M (M/6) sodium lactate injection,
USP, the pH of the resultant solution is
3.5 to 5.5.
Reconstituted solutions are stable for 6
hours at controlled room temperature
or under refrigeration, 2° to 8°C (36° to
46°F).
Discard unused solutions.
Usual Dosage: See accompanying
prescribing information.
Store at 20° to 25°C (68° to 77°F).
[See USP Controlled Room
Temperature.]
Manufactured for:
Mylan Institutional LLC
Rockford, IL 61103 U.S.A.
Made in India
M.L.: 103/AP/RR/97/F/R
MI:207:2KC:R2
www.mylan.com
PRINCIPAL DISPLAY PANEL - 500 mg
NDC 67457-208-50
For Intravenous Use Only
Dexrazoxane for Injection
500 mg and
0.167M (M/6)
Sodium Lactate Injection, USP
Sterile, pyrogen-free lyophilizate
Rx only
1 x 500 mg single dose vial Dexrazoxane
1 x 50 mL vial sodium lactate injection, USP as diluent
Each vial contains:
Dexrazoxane hydrochloride equivalent to
500 mg Dexrazoxane.
The pH is adjusted with hydrochloric
acid, NF.
This package also contains one 50 mL
vial of 0.167M (M/6) sodium lactate
injection, USP, as diluent.
Upon reconstitution with 50 mL vial of
0.167M (M/6) sodium lactate injection,
USP, the pH of the resultant solution is
3.5 to 5.5.
Reconstituted solutions are stable for 6
hours at controlled room temperature or
under refrigeration, 2° to 8°C (36° to
46°F).
Discard unused solutions.
Usual Dosage: See accompanying
prescribing information.
Store at 20° to 25°C (68° to 77°F).
[See USP Controlled Room
Temperature.]
Manufactured for:
Mylan Institutional LLC
Rockford, IL 61103 U.S.A.
Made in India
M.L.: 103/AP/RR/97/F/R
MI:208:2KC:R2
www.mylan.com
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