A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Adria Side Effects, and Drug Interactions - Doxorubicin hydrochloride
Adria Side Effects, and Drug Interactions - Doxorubicin hydrochloride
SIDE EFFECTS
Dose limiting toxicities of therapy are myelosuppression and
cardiotoxicity. Other reactions reported are:
Cardiotoxicity – (See WARNINGS.)
Cutaneous – Reversible complete alopecia occurs in most
cases. Hyperpigmentation of nailbeds and dermal crease, primarily in pediatric
patients, and onycholysis have been reported in a few cases. Recall of skin
reaction due to prior radiotherapy has occurred with doxorubicin administration.
Gastrointestinal – Acute nausea and vomiting occurs
frequently and may be severe. This may be alleviated by antiemetic therapy.
Mucositis (stomatitis and esophagitis) may occur 5 to 10 days after administration.
The effect may be severe leading to ulceration and represents a site of origin
for severe infections. The dosage regimen consisting of administration of doxorubicin
on three successive days results in greater incidence and severity of mucositis.
Ulceration and necrosis of the colon, especially the cecum, may occur leading
to bleeding or severe infections which can be fatal. This reaction has been
reported in patients with acute non-lymphocytic leukemia treated with a 3-day
course of doxorubicin combined with cytarabine. Anorexia and diarrhea have been
occasionally reported.
Vascular – Phlebosclerosis has been reported especially
when small veins are used or a single vein is used for repeated administration.
Facial flushing may occur if the injection is given too rapidly.
Local – Severe cellulitis, vesication and tissue necrosis
will occur if extravasation of doxorubicin occurs during administration. Erythematous
streaking along the vein proximal to the site of injection had been reported
(see DOSAGE AND ADMINISTRATION).
Hematologic – The occurrence of secondary acute myeloid
leukemia with or without a preleukemic phase has been reported rarely in patients
concurrently treated with doxorubicin in association with DNA-damaging antineoplastic
agents. Such cases could have a short (1-3 years) latency period. Pediatric
patients are also at risk of developing secondary acute myeloid leukemia.
Hypersensitivity – Fever, chills and urticaria have
been reported occasionally. Anaphylaxis may occur. A case of apparent cross
sensitivity to lincomycin has been reported.
Neurological – Peripheral neurotoxicity in the form
of local-regional sensory and/or motor disturbances have been reported in patients
treated intra-arterially with doxorubicin, mostly in combination with cisplatin.
Animal studies have demonstrated seizures and coma in rodents and dogs treated
with intra-carotid doxorubicin. Seizures and coma have been reported in patients
treated with doxorubicin in combination with cisplatin or vincristine.
Other – Conjunctivitis and lacrimation occur rarely.
DRUG INTERACTIONS
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 of administration.
Progesterone: In a published study, progesterone was given intravenously to patients with advanced malignancies (ECOG PS < 2) at high doses (up to 10 g over 24 hours) concomitantly with a fixed doxorubicin dose (60 mg/m2) via bolus. Enhanced doxorubicin-induced neutropenia and thrombocytopenia were observed. Verapamil: A study of the effects of verapamil on the acute toxicity of doxorubicin in mice revealed higher initial peak concentrations of doxorubicin in the heart with a higher incidence and severity of degenerative changes in cardiac tissue resulting in a shorter survival.
Cyclosporine: 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 doxorubicinol. Literature reports suggest that adding cyclosporine to doxorubicin results in more profound and prolonged hematologic toxicity than doxorubicin alone. Coma and/or seizures have also been described. Literature reports have also described the following drug interactions: phenobarbital increases the elimination of doxorubicin, phenytoin levels may be decreased by doxorubicin, streptozocin (Zanosar®) may inhibit hepatic metabolism of doxorubicin, and administration of live vaccines to immunosuppressed patients including those undergoing cytotoxic chemotherapy may be hazardous.
Laboratory Tests
Initial treatment with doxorubicin requires observation of
the patient and periodic monitoring of complete blood counts, hepatic function
tests, and radionuclide left ventricular ejection fraction. (See WARNINGS).
Like other cytotoxic drugs, doxorubicin may induce "tumor lysis syndrome"
and hyperuricemia in patients with rapidly growing tumors. Appropriate supportive
and pharmacologic measures may prevent or alleviate this complication.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Formal long-term carcinogenicity studies have not been conducted with doxorubicin. Doxorubicin and related compounds have been shown to have mutagenic and carcinogenic properties when tested in experimental models (including bacterial systems, mammalian cells in culture, and female Sprague-Dawley rats).
The possible adverse effect on fertility in males and females in humans or experimental animals have not been adequately evaluated. Testicular atrophy was observed in rats and dogs.
A variant of chemotherapy-related acute non-lymphocytic leukemia has been reported to occur infrequently a few years after multiple drug treatment of some neoplasms, which sometimes included doxorubicin. The exact role of doxorubicin has not been elucidated. Pediatric patients treated with doxorubicin or other topoisomerase II inhibitors are at a risk for developing acute myelogenous leukemia and other neoplasms. The extent of increased risk associated with doxorubicin has not been precisely quantified.
Pregnancy Category D
(See WARNINGS.)
Nursing Mothers:
Because of the potential for serious adverse reactions in nursing infants from doxorubicin, mothers should be advised to discontinue nursing during doxorubicin therapy.
Pediatric Use:
Pediatric patients are at increased risk for developing delayed
cardiotoxicity. Follow-up cardiac evaluations are recommended periodically to
monitor for this delayed cardiotoxicity (see WARNINGS).
Doxorubicin, as a component of intensive chemotherapy regimens
administered to pediatric patients, may contribute to prepubertal growth failure.
It may also contribute to gonadal impairment, which is usually temporary.
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