oh ROO bi
|Adriamycin PFS™; Adriamycin RDF®;
ADR; Doxorubicin Hydrochloride; Hydroxydaunomycin Hydrochloride|
Antineoplastic Agent, Antibiotic
Treatment of leukemias, lymphomas, multiple myeloma, osseous and nonosseous
sarcomas, mesotheliomas, germ cell tumors of the ovary or testis, and carcinomas
of the head and neck, thyroid, lung, Wilms' tumor, breast, stomach, pancreas,
liver, ovary, bladder, prostate, and uterus, neuroblastoma
Hypersensitivity to doxorubicin or any component, severe congestive heart
failure, cardiomyopathy, pre-existing myelosuppression, patients with impaired
cardiac function, patients who received previous treatment with complete
cumulative doses of doxorubicin, idarubicin, and/or
The U.S. Food and Drug Administration (FDA) currently recommends that
procedures for proper handling and disposal of antineoplastic agents be
considered. Total dose should not exceed 550 mg/m2 or 400
mg/m2 in patients with previous or concomitant treatment (with
daunorubicin, cyclophosphamide, or irradiation of the cardiac region);
irreversible myocardial toxicity may occur as total dosage approaches 550
mg/m2. A baseline cardiac evaluation (EKG, LVEF, +/- ECHO) is
recommended, especially in patients with risk factors for increased cardiac
toxicity. I.V. use only, severe local tissue necrosis will result if
extravasation occurs; reduce dose in patients with impaired hepatic function;
severe myelosuppression is also possible.
Extravasation: Doxorubicin is one of the most notorious vesicants.
Infiltration can cause severe inflammation, tissue necrosis, and ulceration. If
the drug is infiltrated, consult institutional policy, apply ice to the area,
and elevate the limb. Can have ongoing tissue destruction secondary to
propagation of free radicals; may require debridement.
Gastrointestinal: Acute nausea and vomiting may be seen in 21% to 55% of
patients; mucositis, ulceration, and necrosis of the colon, anorexia, and
diarrhea, stomatitis, esophagitis
less than or equal to 20 mg: Moderately low (10% to 30%)
>20 mg or < 60 mg: Moderate (30% to 60%)
greater than or equal to 60 mg: Moderately high (60% to 90%)
Time course for nausea/vomiting: Onset: 1-3 hours; Duration 4-24 hours
Genitourinary: Discoloration of urine (red)
Hematologic: Myelosuppressive: 60% to 80% of patients will have leukopenia;
Onset (days): 7
Nadir (days): 10-14
Recovery (days): 21-28
1% to 10%:
Cardiac toxicity: Dose-limiting and related to cumulative dose; usually a
maximum total lifetime dose of 450-550 mg/m2 is administered;
although, it has been demonstrated that if given by continuous infusion in
breast cancer patients, higher doses may be tolerated. Patients may present with
acute toxicity (arrhythmias, heart block, pericarditis-myocarditis) which may be
fatal. More commonly, chronic toxicity is seen, in which patients present with
signs of congestive heart failure. Treatment includes aggressive management of
CHF with digoxin, diuretics and peripheral vasodilators. Several methods of
monitoring cardiac toxicity have been utilized, including myocardial biopsy
(expensive and hazardous procedure).
Cardiovascular: Facial flushing
Dermatologic: Hyperpigmentation of nail beds, erythematous streaking along
the vein if administered too rapidly
Endocrine & metabolic: Hyperuricemia
<1%: Fever, chills, urticaria, conjunctivitis, allergic reaction,
anaphylaxis; radiation recall noticed in patients who have had prior
irradiation; reactions include redness, warmth, erythema, and dermatitis in the
radiation port. Can progress to severe desquamation and ulceration. Occurs 5-7
days after doxorubicin administration; local therapy with topical
corticosteroids and cooling have given the best relief.
Symptoms of overdose include myelosuppression, nausea, vomiting, myocardial
CYP3A3/4 enzyme substrate; CYP2D6 enzyme inhibitor
Doxorubicin may decrease digoxin plasma levels and renal excretion
Phenobarbital increases elimination of doxorubicin
Phenytoin levels decreased by doxorubicin
Cyclosporine may induce coma or seizures. The addition of cyclosporine to
doxorubicin may result in increases in AUC for both doxorubicin and
doxorubicinol possibly due to a decrease in clearance of parent drug and a
decrease in metabolism of the doxorubicinol. Literature reports suggest that
adding cyclosporine to doxorubicin results in more profound and prolonged
hematologic toxicity than doxorubicin alone.
Cyclophosphamide enhances the cardiac toxicity of doxorubicin by producing
additional myocardial cell damage
Mercaptopurine increases toxicities
Paclitaxel: Two published studies report that initial administration of
paclitaxel infused over 24 hours followed by doxorubicin administered over 48
hours resulted in a significant decrease in doxorubicin clearance with more
profound neutropenic and stomatitis episodes than the reverse sequence
Progesterone: Enhanced doxorubicin-induced neutropenia and thrombocytopenia
were observed with progesterone given intravenously to patients with advanced
malignancies at high doses concomitantly with a fixed doxorubicin dose (60
mg/m2) via bolus.
Streptozocin greatly enhances leukopenia and thrombocytopenia by inhibiting
Verapamil alters the cellular distribution of doxorubicin; may result in
increased cell toxicity by inhibition of the P-glycoprotein pump
Store intact vials of solution under refrigeration (2°C
to 8°C) and protect from light; store intact vials of
lyophilized powder at room temperature (15°C to
30°C). Gensia formulation of generic doxorubicin is stable
for up to 30 days at room temperature.
Reconstitute lyophilized powder with SWI or NS to a final concentration of 2
mg/mL as follows. Reconstituted solution is stable for 7 days at room
temperature (25°C) and 15 days under refrigeration
(5°C) when protected from light.
10 mg vial = 5 mL
20 mg vial = 10 mL
50 mg vial = 25 mL
Further dilution in D5W or NS is stable for 48 hours at room
temperature (25°C) when protected from light
Unstable in solutions with a pH <3 or >7; avoid aluminum needles and
bacteriostatic diluents as precipitation occurs; decomposing drug turns purple;
protect from direct sunlight
Incompatible with aminophylline, cephalothin, dexamethasone,
diazepam, fluorouracil, furosemide, heparin, hydrocortisone, sodium bicarbonate
Y-site compatible with bleomycin, cyclophosphamide, dacarbazine,
Standard I.V. dilution:
I.V. push: Dose/syringe (concentration: 2 mg/mL)
Maximum syringe size for IVP is a 30 mL syringe and syringe should be less
than or equal to 75% full
Syringes are stable for 7 days at room temperature
(25°C) and 15 days under refrigeration
(5°C) when protected from light
IVPB: Dose/50-100 mL D5W or NS
IVPB solutions are stable for 48 hours at room temperature
(25°C) when protected from light
Doxorubicin works through inhibition of topoisomerase-II at the point of DNA
cleavage. A second mechanism of action is the production of free radicals (the
hydroxy radical OH) by doxorubicin, which in turn can destroy DNA and cancerous
cells. Doxorubicin is also a very powerful iron chelator, equal to deferoxamine.
The iron-doxorubicin complex can bind DNA and cell membranes rapidly and produce
free radicals that immediately cleave the DNA and cell membranes. Inhibits DNA
and RNA synthesis by intercalating between DNA base pairs and by steric
obstruction; active throughout entire cell cycle.
Absorption: Oral: Poor, <50%
Distribution: Vd: 25 L/kg; rapidly distributed into the liver,
spleen, kidney, lung and heart, also distributes into breast milk
Protein binding: 70% bound to plasma proteins
Metabolism: In both the liver and in plasma to both active and inactive
Half-life, triphasic: Primary: 30 minutes; Secondary: 3-3.5 hours for
metabolites; Terminal: 17-30 hours for doxorubicin and its metabolites
Elimination: Triphasic; 80% eventually excreted in bile and feces; clearance
has been shown to be significantly reduced in obese women with weight >130%
Refer to individual protocols
Children: 35-75 mg/m2 as a single dose, repeat every 21 days;
or 20-30 mg/m2 once weekly; or 60-90 mg/m2
given as a continuous infusion over 96 hours every 3-4 weeks
Adults: 60-75 mg/m2 as a single dose, repeat every 21 days
or other dosage regimens like 20-30 mg/m2/day for 2-3 days,
repeat in 4 weeks or 20 mg/m2 once weekly
The lower dose regimen should be given to patients with decreased bone marrow
reserve, prior therapy or marrow infiltration with malignant cells
Currently the maximum cumulative dose is 550 mg/m2 or 450
mg/m2 in patients who have received RT to the mediastinal areas; a
baseline MUGA should be performed prior to initiating treatment. If the LVEF is
<30% to 40%, therapy should not be instituted; LVEF should be monitored
Doxorubicin has also been administered intraperitoneal (phase I in refractory
ovarian cancer patients) and intra-arterially.
Dosing adjustment in renal impairment: Adjustments not required in
mild to moderate renal failure
Clcr <10 mL/minute: Reduce dose to 75% of normal dose in severe
Hemodialysis: Supplemental dose is not necessary
Dosing adjustment in hepatic impairment:
Bilirubin 1.2-3 mg/dL: Administer 50% of dose
Bilirubin 3.1-5 mg/dL: Administer 25% of dose
Bilirubin >5 mg/dL: Avoid use
CBC with differential and platelet count, echocardiogram, liver function
|Mental Health: Effects
on Mental Status|
Effects on Psychiatric
Myelosuppression is common; use caution with clozapine and
|Dental Health: Local
No information available to require special precautions
Effects on Dental Treatment|
No effects or complications reported
This medication can only be administered I.V. During therapy, do not use
alcohol, aspirin-containing products, and OTC medications without consulting
prescriber. It is important to maintain adequate nutrition and hydration (2-3
L/day of fluids unless instructed to restrict fluid intake) during therapy;
frequent small meals may help. You may experience nausea or vomiting (frequent
small meals, frequent mouth care, sucking lozenges, or chewing gum may help).
You may experience loss of hair (reversible); you will be more susceptible to
infection (avoid crowds and exposure to infection as much as possible). Urine
may turn red-brown (normal). Yogurt or buttermilk may help reduce diarrhea (if
unresolved, contact prescriber for medication relief). Frequent mouth care and
use of a soft toothbrush or cotton swabs may reduce mouth sores. May discolor
urine (red/pink). Report fever, chills, unusual bruising or bleeding, signs of
infection, abdominal pain or blood in stools, excessive fatigue, yellowing of
eyes or skin, swelling of extremities, difficulty breathing, or unresolved
diarrhea. Pregnancy/breast-feeding precautions: Do not get pregnant or
cause a pregnancy (males) while taking this medication; use appropriate barrier
contraceptive measures for at least 1 month following therapy. Do not
Local erythematous streaking along the vein and/or facial flushing may
indicate too rapid a rate of administration
Apply ice immediately for 30-60 minutes; then alternate off/on every 15
minutes for one day
Topical cooling may be achieved using ice packs or cooling pad with
circulating ice water. Cooling of site for 24 hours as tolerated by the patient.
Elevate and rest extremity 24-48 hours, then resume normal activity as
tolerated. Application of cold inhibits vesicant's cytotoxicity.
Application of heat or sodium bicarbonate can be harmful and is
If pain, erythema, and/or swelling persist beyond 48 hours, refer patient
immediately to plastic surgeon for consultation and possible debridement
Injection, as hydrochloride:
Aqueous, with NS: 2 mg/mL (5 mL, 10 mL, 25 mL)
Preservative free: 2 mg/mL (5 mL, 10 mL, 25 mL, 100 mL)
Powder for injection, as hydrochloride, lyophilized: 10 mg, 20 mg, 50 mg, 100
Powder for injection, as hydrochloride, lyophilized, rapid dissolution
formula: 10 mg, 20 mg, 50 mg, 150 mg
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