Chemical formula: C₁₁H₁₆N₄O₄ Molecular mass: 268.269 g/mol PubChem compound: 71384
Dexrazoxane interacts in the following cases:
Concomitant use of dexrazoxane with other live attenuated vaccines not recommended: risk of systemic, possible fatal disease. This risk is increased in subjects who are already immunosuppressed by their underlying disease or by concomitant chemotherapy. Use an inactivated vaccine where this exists (poliomyelitis).
In patients with moderate to severe renal impairment (creatinine clearance <40 mL/min) the dexrazoxane dose should be reduced by 50%.
There are limited fertility data from animal studies available, but testicular changes were observed in rats and rabbits following repeat dosing.
Excessive immunosuppression with risk of lymphoproliferative disease.
Dimethylsulfoxide (DMSO) should not be used in patients who are administered dexrazoxane to treat anthracycline extravasation.
Co-administration of doxorubicin (50 to 60 mg/m²) or epirubicin (60 to 100 mg/m²) did not affect dexrazoxane pharmacokinetics significantly. In studies, dexrazoxane did not affect the pharmacokinetics of doxorubicin. There is limited evidence from studies that suggests epirubicin clearance may be increased when dexrazoxane is pre-administered, this occurred at high doses of epirubicin (120-135 mg/m²). Note that in these studies dexrazoxane was administered prior to anthracyline administration.
Cytotoxic agents may reduce the absorption of phenytoin leading to an exacerbation of convulsions. Dexrazoxane is not recommended in combination with phenytoin.
Anaphylactic reaction including angioedema, skin reactions, bronchospasm, respiratory distress, hypotension and loss of consciousness have been observed in patients treated with dexrazoxane and anthracyclines. Previous history of allergy to dexrazoxane should be carefully considered prior to administration.
There are no data from the use of dexrazoxane in pregnant women. Dexrazoxane may cause foetal harm when administered to pregnant women. Studies in animals have shown reproductive toxicity. Dexrazoxane should not be administered to pregnant women unless clearly necessary.
It is not known whether dexrazoxane is excreted in human milk. Because of the potential for serious adverse reactions in breast-fed infants exposed to dexrazoxane, breast-feeding is contraindicated during dexrazoxane therapy.
Since dexrazoxane possesses mutagenic activity and is used with anthracyclines known to have cytotoxic, mutagenic and embryotoxic properties, both sexually active men and women of childbearing potential should be advised not to father a child/become pregnant and must use effective contraceptive measures during and up to 6 months after treatment. Women must inform their doctor immediately if they become pregnant.
There are limited fertility data from animal studies available, but testicular changes were observed in rats and rabbits following repeat dosing.
Dizziness, somnolence and syncope have been reported in a few patients included in dexrazoxane studies. Dexrazoxane has minor influence on the ability to drive and use machines.
A number of published reports comprising more than 1000 patients have demonstrated a uniform pattern of dose dependent adverse reactions. Most common adverse reactions are nausea/vomiting, bone marrow suppression (neutropenia, thrombocytopenia), injection site reactions, diarrhoea, stomatitis and increase in hepatic transaminases (ALT/AST). All adverse reactions have been rapidly reversible.
The following information is based on two clinical studies, TT01 and TT02, of dexrazoxane administered to extravasation patients already receiving cycles of chemotherapeutic agents.
The adverse reactions were those typically seen with standard chemotherapy and also with dexrazoxane: Nausea/vomiting in about one third of the patients, neutropenia and thrombocytopenia in about half of the patients, more rarely increased concentration of liver enzymes (ALT/AST). Adverse reactions observed in the two studies are listed below.
Incidence of adverse reactions (MedDRA) in studies TT01 and TT02 (n=80 patients):
(Note that numbers for Blood and Lymphatic System Disorders are described in a separate table of laboratory examinations)
Adverse reactions reported are listed according to the following frequency: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000).
Very common: Postoperative infection
Common: Infection, Neutropenic infection
Not known: Anaphylactic reactions, Hypersensitivity
Common: Decreased appetite
Common: Dizziness, Sensory loss, Syncope, Tremor
Common: Phlebitis, Superficial thrombophlebitis, Venous thrombosis limb
Common: Dyspnoea, Pneumonia
Very common: Nausea
Common: Vomiting, Diarrhoea, Stomatitis, Dry mouth
Common: Alopecia, Pruritus
Common: Myalgia
Common: Vaginal haemorrhage
Very common: Injection site pain
Common: Pyrexia, Injection site phlebitis, Injection site erythema, Fatigue, Injection site induration, Injection site swelling, Peripheral oedema, Somnolence
Common: Weight decreased
Common: Wound complication
Incidence of laboratory abnormalities in TT01 and TT02 (n=80 patients):
| Lab test | No of patients with post baseline value | CTC grade 3-4 | |
|---|---|---|---|
| N | % | ||
| Haemoglobin | 80 | 2 | 2.5% |
| WBC | 80 | 36 | 45.0% |
| Neutrophils | 78 | 36 | 46.2% |
| Platelets | 80 | 17 | 21.3% |
| Sodium (Hypo) | 79 | 5 | 6.3% |
| Potassium (Hypo) | 79 | 2 | 2.5% |
| Potassium (Hyper) | 79 | 0 | 0.0% |
| Alkaline Phosphatase | 77 | 0 | 0.0% |
| Bilirubin | 77 | 1 | 1.3% |
| AST | 57 | 2 | 3.5% |
| ALT | 71 | 3 | 3.9% |
| Creatinine | 76 | 2 | 2.6% |
| LDH | 78 | 0 | 0.0% |
| Calcium Total (Hypo) | 28 | 2 | 7.1% |
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