Savene
Savene Uses, Dosage, Side Effects, Food Interaction and all others data.
An antimitotic agent with immunosuppressive properties. Savene, the (+)-enantiomorph of razoxane, provides cardioprotection against anthracycline toxicity. It appears to inhibit formation of a toxic iron-anthracycline complex. [PubChem]The Food and Drug Administration has designated dexrazoxane as an orphan drug for use in the prevention or reduction in the incidence and severity of anthracycline-induced cardiomyopathy.
Savene is a cardioprotective agent for use in conjunction with doxorubicin 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. Patients receiving anthracycline-derivative antineoplastic agents may experience three types of cardiotoxicity: acute transient type; chronic, subacute type (related to cumulative dose and has a more indolent onset later on); and a late-onset type that manifests years after therapy, mainly in patients that have been exposed to the drug as a child. Although the exact mechanism of anthracycline-induced cardiotoxicity is not known, it has shown to exert a variety of actions that may result in the development of cardiotoxicity. In animals, anthracyclines cause a selective inhibition of cardiac muscle gene expression for α-actin, troponin, myosin light-chain 2, and the M isoform of creatine kinase. This may lead to myofibrillar loss associated with anthracycline-induced cardiotoxicity. Anthracyclines may also cause myocyte damage via calcium overload, altered myocardial adrenergic function, release of vasoactive amines, and proinflammatory cytokines. Furthermore, it has been suggested that the main cause of anthracycline-induced cardiotoxicity is associated with free-radical damage to DNA. The drugs intercalate DNA, chelate metal ions to produce drug-metal complexes, and generate superoxide radicals via oxidation-reduction reactions. Anthracyclines also contain a quinone structure that can undergo reduction via NADPH-dependent reactions to produce a semiquinone free radical that initiates a cascade of superoxide and hydroxide radical generation. Chelation of metal ions, particularly iron, by anthracyclines results in an anthracycline-metal complex that catalyzes the generation of reactive oxygen free radicals. This complex is a powerful oxidant that can initiate lipid peroxidation in the absence of oxygen free radicals. The toxicity induced by antrhacyclines may be exacerbated in cardiac cells, as these cells do not possess sufficient amounts of certain enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase) involved in detoxifying free radicals and protecting the cells from subsequent damage.
| Trade Name | Savene |
| Availability | Prescription only |
| Generic | Dexrazoxane |
| Dexrazoxane Other Names | Dexrazoxan, Dexrazoxane, Dexrazoxano, Dexrazoxanum, Dextrorazoxane |
| Related Drugs | hyaluronidase, Zinecard, Amphadase, Hylenex, Vitrase, Hydase |
| Type | infusion |
| Formula | C11H16N4O4 |
| Weight | Average: 268.2691 Monoisotopic: 268.11715502 |
| Protein binding | Very low (< 2%) |
| Groups | Approved, Withdrawn |
| Therapeutic Class | |
| Manufacturer | Clinigen Healthcare Ltd, Spepharm Holding Bv |
| Available Country | United Kingdom, France, Italy, Portugal, Spain, |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Savene is a cytoprotective drug used to prevent and improve cardiomyopathy associated with doxorubicin treatment for metastatic breast cancer.
For reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin hydrochloride dose of 300 mg/m^2 and would benefit from continued doxorubicin therapy. Also approved for the treatment of extravasation from intravenous anthracyclines.
Savene is also used to associated treatment for these conditions: Cardiomyopathy
How Savene works
The mechanism by which dexrazoxane exerts its cardioprotective activity is not fully understood. Savene is a cyclic derivative of EDTA that readily penetrates cell membranes. Results of laboratory studies suggest that dexrazoxane (a prodrug) is converted intracellularly to a ring-opened bidentate chelating agent that chelates to free iron and interferes with iron-mediated free radical generation thought to be responsible, in part, for anthracycline-induced cardiomyopathy. It should be noted that dexrazoxane may also be protective through its inhibitory effect on topoisomerase II.
Toxicity
Intraperitoneal, mouse LD10 = 500 mg/kg. Intravenous, dog LD10 = 2 gm/kg.
Food Interaction
No interactions found.Savene Drug Interaction
Unknown: 5-hydroxytryptophan, 5-hydroxytryptophan, aripiprazole, aripiprazole, sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprim, meperidine, meperidine, glucose, glucose, diltiazem, diltiazem, metoprolol, metoprolol, metoprolol, metoprolol, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol
Volume of Distribution
- 9 to 22.6 L/m^2
Elimination Route
IV administration results in complete bioavailability.
Half Life
2.5 hours
Clearance
- 7.88 L/h/m2 [dose of 50 mg/m2 Doxorubicin and 500 mg/m2 Savene]
- 6.25 L/h/m2 [dose of 60 mg/m2 Doxorubicin and 600 mg/m2 Savene]
Elimination Route
Urinary excretion plays an important role in the elimination of dexrazoxane. Forty-two percent of the 500 mg/m2 dose of dexrazoxane was excreted in the urine.
Innovators Monograph
You find simplified version here Savene
