Doxorubicine 30 mg – Lyophilized Vial
In individual box.
Chemotherapy drug to canine and feline with cancer.
Use in veterinary medicine
Made in Argentina
Presentation: Lyophilizated vial of 30 mg.
Description: Chemotherapy for dogs and cats. Composition: Doxorubicin: 30 mg Excipients authorized. c.s.
Action: Chemotherapy. The basic idea behind drugs of cancer chemotherapy is for them to reach areas of the body that are inaccessible to surgery and to kill only the cancer cells and leave alone the normal cells of the body. The antineoplastic antibiotics are products of Streptomyces. Doxorubicin, is an important antineoplastic antibiotics. These drugs intercalate and bind to DNA between base pairs on adjacent strands. This causes the DNA helix to uncoil, which destroys the DNA template and inhibits RNA and DNA polymerases. Scission of DNA is thought to be mediated by either the enzyme topoisom-erase II or by generation of free radicals. Intracellular interactions of anthracycline antibiotics result in the formation of semiquinone radical intermediates capable of generating hydrogen peroxide and hydroxyl radicals. Considered cell-cycle nonspecific because of the damage associated with radical formation, these drugs probably have their maximal effect during the S phase of the cell cycle.
Indications: Chemotherapy drug to use in pet with cancer. Doxorubicin has the ability to penetrate the blood/brain barrier, which means it can be used to treat cancers of the nervous system. Also the usual tumors against which doxorubicin is most commonly used are: lymphoma, particularly cutaneous (skin) lymphoma, mast cell tumors, kidney tumors, lung tumors, sarcomas and melanoma.
Dosage: The exact doses should be calculated by a diplomate veterinary oncology. General rule is Dogs: 30 mg/mt2. To dogs more of 10 kg or 1 mg/kg to dog minor of 10 kg. Cats: 1 mg/kg.
Administration: Doxorubicin is a cytotoxic drug that is usually administered to cancer patients by the intravenous and, whenever appropriate, intravesical and intra-arterial routes. Intravenous (IV) Administration: Dosage is usually calculated on the basis of body surface area (mg/m2). The doxorubicin dose-schedule to be delivered may differ depending on the therapeutic indication (e.g. solid tumours or acute leukaemias) as well as on its use within a specific regimen (e.g. as a single agent or in combination with other cytotoxics or as a part of multidisciplinary approaches which include combination with surgery and/or radiotherapy). Intravenous administration of doxorubicin should be performed with caution. It is recommended to administer doxorubicin into the tubing of a freely flowing IV infusion (isotonic sodium chloride or 5% glucose solution) over a period of 30 - 60 minutes. Intravesical Administration: Doxorubicin administered intravesically can be used for the treatment of superficial bladder tumours or as prophylaxis to reduce recurrence after trans-urethral resection. The recommended doxorubicin dose for topical intravesical treatment of superficial bladder cancer is in 15 – 50 mL of saline solution per instillation. In the case of local toxicity (chemical cystitis), the dose should be instilled in 50-100 mL of saline solution. Once the instillation has been completed, the pets should be rotated a quarter turn every fifteen minutes. Generally, the instillate should be retained in the bladder for 1-2 hours. To avoid undue dilution with urine, the pet should be not to drink any fluid in the twelve hours prior to instillation (this should limit urine production to approximately 50 mL/hour). Instillations can be repeated at intervals which can vary from one week to one month, depending on whether the treatment is therapeutic or prophylactic. The systemic absorption of doxorubicin following intravesical instillation is very low. Intra-arterial Administration: Doxorubicin has been also used by the intra-arterial route in an attempt to produce intense local activity with reduced general toxicity in animals with hepatocellular carcinoma. Since this technique is potentially hazardous and can lead to widespread necrosis of the perfused tissue, intra-arterial administration should only be attempted by those veterinary oncology fully trained with this technique. Pets may receive an infusion into the main hepatic artery in doses of 30 mg/m2 at intervals of 3 weeks to 3 months, with higher doses reserved for administration with concurrent extracorporeal drug elimination.
Therapeutic regimen: The interval and numbers of cycles should be indicated by a diplomate veterinary oncology. General rule is between 21 days.
Pharmacokinetics / Absorption: Doxorubicin is not absorbed by the gastrointestinal tract. Since the drug is extremely irritating to tissues, it has to be administered by intravascular routes (intravenous or intra-arterial). Intravesical administration has been demonstrated as feasible; following such administration, drug passage to the systemic circulation is minimal.Distribution: Doxorubicin is quickly and widely distributed into the extravascular compartments, as indicated by a rapid initial plasma half-life and by a steady-state distribution volume in excess. However, doxorubicin does not cross the blood-brain barrier in detectable amounts. Binding of doxorubicin to plasma protein is about 75%, and is not dependent on plasma concentrations up to 2 µM. Metabolism: Doxorubicin is metabolized to a significant extent, mainly by the liver. The major metabolite of doxorubicin is 13-OH-doxorubicinol, produced by aldo-keto reductases, which possesses a certain degree of antitumour activity. Doxorubicin and 13-OH-doxorubicinol predominate also in urine and in the bile. Other metabolites present in detectable amounts in plasma are the aglycones of doxorubicin and 13-OH-doxorubicinol.Excretion: Following IV administration, plasma levels of doxorubicin follow a multiphasic decline, with a terminal half-life reported in the 20 to 48 hour range. The terminal half-life of 13-OH-doxorubicinol is similar to that of doxorubicin. Plasma clearance is in the range of 8 to 20 ml/min/kg, and is mainly due to metabolism and biliary excretion. This slow elimination from plasma might be further prolonged in patients with impaired liver function. The clearance of doxorubicin occurs to a substantial extent by metabolic conversion to a number of less active or inactive products. Forty to fifty percent of the administered dosage is recovered in the bile or in the faeces in seven days. Renal excretion is modest, accounting for only 5% to 10% of the administered dose in 5 days.
Side effects: Because doxorubicin targets rapidly dividing cells, the cells of the bone marrow are vulnerable whether or not there is any cancer. The bone marrow is where blood cells are produced and special attention is generally paid to white blood cells, whose numbers typically drop about a week after the doxorubicin dose is given. Often antibiotics are given during the week where the white count drops to at least in part make up for the blow to the immune system caused by the drug. Platelets, cells involved in blood clotting, also drop in number with doxorubicin but generally recover by the time for the next dose. If they have not, the dose may be delayed. Bone marrow effects are more pronounced in cats, thus lower doses of doxorubicin are typically used. Doxorubicin is harsh on the patient’s liver as well. Liver disease first manifests as a change in laboratory testing before the patient actually feels ill. To prevent a patient from developing serious liver disease, an enzyme called alanine aminotransferase (ALT) is monitored before each doxorubicin dose. If there is any elevation, the doxorubicine treatments are discontinued. Kidney damage from doxorubicin is common in cats. Kidney function is usually included in the monitoring about both species. Normal intestinal cells are also rapidly dividing and most chemotherapy agents targeting rapid cell division generally cause an upset stomach.
Interactions with Other Drugs: Doxorubicine is removed from the body by the liver’s detoxification processes within hours of administration. Phenobarbital, the most common oral anti-convulsant in pets, enhances the enzymes involved, which means that pets on phenobarbital will remove doxorubicine from their bodies faster than they normally would and doxorubicine will not work as well. Any time two drugs with potential to suppress the bone marrow are used together, the risk of marrow suppression becomes greater. Such drugs would include other agents of chemotherapy, chloramphenicol, possibly methimazole, etc. Any time two drugs that have potential to suppress immune function are used together, the risk of infection becomes greater. Such drugs would include other agents of chemotherapy and corticosteroids.
Concerns and Cautions: As with all chemotherapy agents, doxorubicin should not be used in pregnancy, lactation, or in animals to be used for breeding. Live vaccinations should not be given while the patient is on doxorubicine. The anthracycline antibiotics are given IV; they are severe vesicants if administered perivascularly and may cause a severe, delayed phlebitis. Administration of a free radical inhibitor, dexrazoxane, may limit the extent of tissue damage seen with extravasation of this drug.
Contraindications: Hypersensitivity to doxorubicin or any other component of the product, other anthracyclines or anthracenediones. Adriamycin therapy is also contraindicated in pregnancy and lactation.
Protective measures: The following protective recommendations are given due to the toxic nature of this substance. Personnel should be trained in good technique and handling; pregnant staff should be excluded from working with this drug; personnel handling doxorubicin should wear protective clothing: goggles, gowns and disposable gloves and masks; A designated area should be defined for reconstitution (preferably under a laminar flow system). The work surface should be protected by disposable, plastic-backed, absorbent paper. All items used for, administration or cleaning, including gloves, should be placed in high-risk waste-disposal bags for high-temperature incineration. Spillage or leakage should be treated with dilute sodium hypochlorite (1% available chlorine) solution, preferably by soaking, and then water. All cleaning materials should be disposed of as indicated previously. In case of skin contact thoroughly wash the affected area with soap and water or sodium bicarbonate solution. However, do not abrade the skin by using a scrub brush. In case of contact with the eye(s), hold back the eyelid(s) and flush the affected eye(s) with copious amounts of water for at least 15 minutes. Then seek medical evaluation by a physician. Always wash hands after removing gloves.
Storage: Storage of the doxorrubicin solution at refrigerated conditions can result in the formation of a gelled product. This gelled product will return to a slightly viscous to mobile solution after two to a maximum of four hours equilibration at controlled room temperature (15 - 25 o C).
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