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Dexrazoxane | CAS No: 24584-09-6 | GMP-certified suppliers
A medication that reduces cardiomyopathy risk in metastatic breast cancer patients receiving doxorubicin and treats anthracycline-induced extravasation, supporting cardioprotection during cancer therapy.
Therapeutic categories
Primary indications
- 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
Product Snapshot
- Dexrazoxane is an injectable small molecule formulated as a powder or solution for intravenous and parenteral administration
- It is indicated primarily for cardioprotection in patients receiving doxorubicin chemotherapy and for treating extravasation caused by intravenous anthracyclines
- The product holds approved status in key regulatory markets including the US, Canada, and the EU, with some instances of withdrawal
Clinical Overview
Pharmacologically, dexrazoxane functions as a cardioprotective agent by mitigating the cardiotoxic effects of anthracyclines, which are known to induce multiple forms of cardiotoxicity: acute, chronic/subacute, and late-onset, particularly in pediatric patients. Anthracycline-induced cardiotoxicity mechanisms include inhibition of cardiac muscle gene expression, calcium overload, disruption of myocardial adrenergic function, and generation of free radicals through drug-metal complex formation. Cardiac cells are particularly vulnerable due to limited endogenous antioxidant enzyme systems.
Dexrazoxane’s mechanism involves intracellular conversion from a prodrug to a bidentate iron chelator, thereby interfering with iron-mediated free radical formation implicated in anthracycline cardiotoxicity. It is a cyclic derivative of EDTA capable of penetrating cell membranes. Evidence also suggests dexrazoxane may inhibit topoisomerase II, which could contribute to its cardioprotective effects.
Key pharmacokinetic characteristics include primary renal excretion, consistent with its classification among drugs mainly cleared by the kidneys. Safety considerations focus on monitoring for myelosuppression and potential immunosuppressive effects due to its pharmacological profile. Given its clinical use and mechanism, awareness of drug interactions and dose adjustments in renal impairment may be necessary.
Dexrazoxane is marketed under various brand names globally and holds orphan drug designation by the U.S. Food and Drug Administration for cardiomyopathy prevention in anthracycline-treated patients. Procurement of dexrazoxane APIs necessitates stringent quality control to ensure chirality, purity, and compliance with regulatory standards due to its complex synthetic profile and clinical criticality. Reliable sourcing from certified manufacturers with validated processes is recommended to maintain consistent API quality for pharmaceutical formulations.
Identification & chemistry
| Generic name | Dexrazoxane |
|---|---|
| Molecule type | Small molecule |
| CAS | 24584-09-6 |
| UNII | 048L81261F |
| DrugBank ID | DB00380 |
Pharmacology
| Summary | Dexrazoxane acts as a cardioprotective agent primarily by chelating intracellular free iron, thereby reducing iron-mediated free radical formation associated with anthracycline-induced cardiotoxicity. Additionally, it inhibits DNA topoisomerase II isoforms, which may contribute to its protective effects. Its therapeutic application centers on mitigating the incidence and severity of cardiomyopathy in patients receiving cumulative doses of doxorubicin. |
|---|---|
| Mechanism of action | The mechanism by which dexrazoxane 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 (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. |
| Pharmacodynamics | Dexrazoxane 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. |
Targets
| Target | Organism | Actions |
|---|---|---|
| DNA topoisomerase 2-alpha | Humans | inhibitor |
| DNA topoisomerase 2-beta | Humans |
ADME / PK
| Absorption | IV administration results in complete bioavailability. |
|---|---|
| Half-life | 2.5 hours |
| Protein binding | Very low (< 2%) |
| Metabolism | Dexrazoxane is hydrolysed by the enzyme dihydropyrimidine amidohydrolase in the liver and kidney to active metabolites that are capable of binding to metal ions. |
| Route of elimination | 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. |
| Volume of distribution | * 9 to 22.6 L/m^2 |
| Clearance | * 7.88 L/h/m2 [dose of 50 mg/m2 Doxorubicin and 500 mg/m2 Dexrazoxane] * 6.25 L/h/m2 [dose of 60 mg/m2 Doxorubicin and 600 mg/m2 Dexrazoxane] |
Formulation & handling
- Dexrazoxane is a small molecule API formulated primarily for intravenous or parenteral administration as lyophilized powder or solution. Its high water solubility and negative LogP indicate hydrophilic properties, influencing formulation in aqueous media. Handling requires attention to sterility and proper reconstitution for injectable use; stability considerations may include protection from moisture before reconstitution.
Regulatory status
| Lifecycle | The active pharmaceutical ingredient is in a mature market phase in the US, with patents expired as of 2010 and 2020, and is available in other established markets including Canada and the EU. Generic competition is likely present or emerging across these regions. |
|---|
| Markets | US, Canada, EU |
|---|
Supply Chain
| Supply chain summary | Dexrazoxane is manufactured by multiple originator companies supplying both US and EU markets. The product is marketed under several branded names across the US, Canada, and Europe, indicating established global presence. Patent expirations, with the latest in 2020, suggest that generic competition is currently present or emerging in the marketplace. |
|---|
Safety
| Toxicity | Intraperitoneal, mouse LD<sub>10</sub> = 500 mg/kg. Intravenous, dog LD<sub>10</sub> = 2 gm/kg. |
|---|
- Handle with appropriate personal protective equipment to minimize exposure due to moderate acute toxicity observed in animal studies
- Avoid inhalation and skin contact
- Ensure proper ventilation and containment during manufacturing processes
Dexrazoxane is a type of Antineoplastics
Antineoplastics are a crucial category of pharmaceutical active pharmaceutical ingredients (APIs) primarily used in the treatment of cancer. These powerful substances inhibit or destroy the growth of cancer cells, thus impeding the progression of malignancies.
Antineoplastics exert their therapeutic effects through various mechanisms. Some APIs interfere with DNA replication, inhibiting the division and proliferation of cancer cells. Others target specific proteins or enzymes involved in tumor growth, effectively blocking their function. Additionally, certain antineoplastic agents induce programmed cell death, known as apoptosis, in cancer cells.
These APIs find application in a wide range of cancer treatments, including chemotherapy, targeted therapy, immunotherapy, and hormone therapy. They are often administered in combination with other drugs to optimize therapeutic outcomes and minimize drug resistance.
Antineoplastics are typically synthesized through complex chemical processes, ensuring high purity and potency. Stringent quality control measures are implemented throughout manufacturing to meet regulatory standards and ensure patient safety.
Although antineoplastics offer significant benefits in treating cancer, they can also cause adverse effects due to their cytotoxic nature. Common side effects include bone marrow suppression, gastrointestinal disturbances, hair loss, and immune system suppression. Close monitoring and supportive care are essential to manage these side effects effectively.
In conclusion, antineoplastics are a vital category of pharmaceutical APIs used in the treatment of cancer. Through their diverse mechanisms of action, these compounds play a critical role in combating malignancies and improving patient outcomes.
Dexrazoxane API manufacturers & distributors
Compare qualified Dexrazoxane API suppliers worldwide. We currently have 3 companies offering Dexrazoxane API, with manufacturing taking place in 2 different countries. Use the table below to review supplier type, countries of origin, certifications, product portfolio and GMP audit availability.
| Supplier | Type | Country | Product origin | Certifications | Portfolio |
|---|---|---|---|---|---|
| ALCAMI | Producer | United States | United States | CoA, USDMF | 5 products |
| Lundbeck Pharma | Producer | Italy | Italy | CoA, GMP | 15 products |
| Sicor | Producer | Italy | Italy | CoA, GMP | 47 products |
When sending a request, specify which Dexrazoxane API quality you need: for example EP (Ph. Eur.), USP, JP, BP, or another pharmacopoeial standard, as well as the required grade (base, salt, micronised, specific purity, etc.).
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