Axibin

Each mL Vial contains Doxorubicin hydrochloride, USP 2 mg.

Pharmacology: Pharmacodynamics: Doxorubicin is an antitumour agent. Tumour cells are probably killed through drug-induced alterations of nucleic acid synthesis although the exact mechanism of action has not yet been clearly elucidated.
Proposed mechanism of action include: DNA intercalation (leading to an inhibition of synthesis of DNA, RNA and proteins), formation of highly reactive free-radicals and superoxides, chelation of divalent cations, the inhibition of Na-K ATPase and the binding of doxorubicin to certain constituents of cell membranes (particularly to the membrane lipids, spectrin and cardiolipin). Highest drug concentrations are attained in the lung, liver, spleen, kidney, heart, small intestine and bone-marrow. Doxorubicin does not cross the blood-brain barrier.
Pharmacokinetics: After IV administration, the plasma disappearance curve of doxorubicin is triphasic with half-lives of 12 minutes, 3.3 hours and 30 hours. The relatively long terminal elimination half-life reflects doxorubicin's distribution into a deep tissue compartment. Only about 33 to 50% of fluorescent or tritiated drug (or degradation products), respectively, can be accounted for in urine, bile and faeces for up to 5 days after IV administration. The remainder of the doxorubicin and degradation products appear to be retained for long periods of time in body tissues.
In cancer patients, doxorubicin is reduced to adriamycinol, which is an active cytotoxic agent. This reduction appears to be catalysed by cytoplasmic and pH-dependent aldo-keto reductases that are found in all tissues and play an important role in determining the overall pharmacokinetics of doxorubicin.
Microsomal glycosidases present in most tissues split doxorubicin and adriamycinol into inactive aglycones. The aglycones may then undergo 0-demethylation, followed by conjugation to sulphate or glucuronide esters, and excretion in the bile.

Malignant lymphoma (lymphomas of both Hodgkin and non Hodgkin types, lymphoma sarcoma) gastric, hepatic, rectal and colic carcinoma, pancreatic carcinoma, acute myeloplastic leukemia, soft-tissue and osteogenic sarcomas, breast, and ovarian carcinoma, lung, and bronchogenic carcinoma, bladder carcinoma, Wilm's carcinoma.

The solution is given via the tubing of a freely running intravenous infusion, taking 2 to 3 minutes over the injection. This technique minimizes the risk of thrombosis or perivenous extravasation which can lead to severe cellulites and vesication.
Calculated on the basis of body surface area: On this basis, 60-75 mg/m² may be given every three weeks when doxorubicin is used alone. If it is used in combination with other antitumor agents having overlapping toxicity, the dosage of doxorubicin may need to be reduced 30-40 mg/m² every three weeks.
Calculated on the basis of body weight: It has been shown that giving doxorubicin as a single dose every three weeks greatly reduces the distressing toxic effect, mucositis; however, there are still some who believe that dividing the dose over three successive days (0.4-0.8 mg/kg or 20-25 mg/m² on each day) gives greater effectiveness though at the cost of higher toxicity.
Combination with other antitumor agents having overlapping toxicity, the dosage of doxorubicin may need to be reduced 30-40 mg/m² every three weeks.
Hepatic function is impaired, doxorubicin dosage should be reduced according to the following table. (See table.)

Click on icon to see table/diagram/image

Total dosage of the drug exceeding the currently recommended limit of 550 mg/m².
It is recommended that Doxorubicin be slowly administered into the tubing of a freely running intravenous infusion of Sodium Chloride Injection, or 5% Dextrose Injection. The tubing should be attached to a needle inserted preferably into a large vein. If possible, avoid veins over joints or in extremities with compromised venous or lymphatic drainage. The rate of administration is dependent on the size of the vein and the dosage. However, the dose should be administered in not less than 2-5 minutes. Local erythematous streaking along the vein as well as facial flushing may be indicative of too rapid administration. A burning or stinging sensation may be indicative of perivenous infiltration and the infusion should be immediately terminated and restarted in another vein. Perivenous infiltration may occur painlessly. Doxorubicin should not be mixed with heparin or other drugs.

Single doses of 250 mg and 500 mg of doxorubicin have proved fatal. Such doses may cause acute myocardial degeneration within 24 hours and severe myelosuppression (mainly leucopenia and thrombocytopenia), the effects of which are greatest between 10 and 15 days after administration. Treatment should aim to support the patient during this period and should utilise such measures as blood transfusions and reverse barrier nursing.
Acute overdose with doxorubicin will result in gastrointestinal toxic effects (mainly mucositis). This generally appears early after drug administration, but most patients recover from this within three weeks.
Delayed cardiac failure may occur up to six months after the overdosage. Patients should be observed carefully and should signs of cardiac failure arise, be treated along conventional lines.

Patients with cardiac failure or pre-existing heart disease.
Patients known to have hypersensitivity to the drug.

Patients with hepatic failure; renal damage; fetal infections have been associated with a combination of doxorubicin; bone marrow depression; chickenpox (fatal systemic disorder may occur).
The elderly.
Initial treatment with doxorubicin requires close observation of the patients and extensive laboratory monitoring. It is recommended, therefore, that patients should be hospitalized at least during the first phase of the treatment.
Special attention must be given to the infection and bleeding tendency exhibited by doxorubicin.
In case of prescription to a child and a patient with generative power, consider effect on sexual gland.
Precaution on Administration: Doxorubicin must not be given by the intramuscular or subcutaneous route.
Avoid intraperitoneal prescribing because of danger of intestinal obstruction.
Since intravenous administration may cause vascular pain, phlebitis, thrombus, site of injection and administration method should be cautioned, and administered as possible as slow.
Induration, necrobiosis may occur due to extravasation of the solution in intravenous injection.
Therefore, intravenous administration should be cautioned not to leak the solution.
Others: Doxorubicin imparts a red coloration to the urine after administration and patients should be advised to expect this during active therapy.
Tumors of the breast have been reported in the animal test with rat intravenously.
Use in children: Use in children should be cautioned about manifestation of adverse effects.

There is conclusive information as to whether doxorubicin may adversely affect human fertility or cause teratogenesis.
Experimental data, however, suggest that doxorubicin may harm the foetus and should, therefore, not be administered to pregnant women or to mothers who are breast feeding.

Cardiogenic: Cardiotoxicity may be manifested in tachycardia, including supraventricular tachycardia, arrhythmia, abdominal pain, and ECG changes. Routine ECG monitoring is recommended and caution should be exercised in patients with impaired cardiac function.
Shock: Rarely, shock may occur. Therefore, it should be sufficiently observed, if necessary, the administration should be discontinued and/or appropriate therapy instituted.
Hematologic: Anemia, bleeding, leukocytopenia, and thrombopenia.
Hypersensitivity: Fever, chills, and urticaria have been reported occasionally. Anaphylaxis may occur.
Hepatic: Hepatic impairment has been reported occasionally.
Renal: Occasionally, proteinuria has been reported.
Gastrointestinal: Acute nausea and vomiting occurs frequently and may be severe. Mucositis (stomatitis and esophagitis) may occur 5 to 10 days after administration. Anorexia and diarrhea have been occasionally reported.
Cutaneous: Reversible complete alopecia occurs in most cases. Hyperpigmentation of nailbeds and dermal creases have been reported in a few cases.
CNS: Fatigue and headache occurs frequently.
Urinary system: Cystic stimulation symptoms (oliguria, urodynia, urocystitis, hematuria) by vesicoclysis therapy.
Respiratory system: Pneumothorax during treat symptom which metastasize to the lungs.
Other: Blennophthalmia, epiphora, amenorrhea, aspermia occur.

Doxorubicin must not be given by the intramuscular or subcutaneous route.
Avoid intraperitoneal prescribing because of danger of intestinal obstruction.
Since intravenous administration may cause vascular pain, phlebitis, thrombus, site of injection and administration method should be cautioned, and administered as possible as slow.
Induration, necrobiosis may occur due to extravasation of the solution in intravenous injection.
Therefore, intravenous administration should be cautioned not to leak the solution.

Preserve in hermetic containers.
Store in a cool and dark place at temperatures between 2 to 8°C.

Cytotoxic Chemotherapy

L01DB01 - doxorubicin ; Belongs to the class of cytotoxic antibiotics, anthracyclines and related substances. Used in the treatment of cancer.

Rx