Due to the fact that Cardioksan is prescribed together with anthracyclines, it is not always possible to evaluate the contribution to the development of undesirable phenomena (NJ) directly by Cardioksan. The most frequent AEs developing against the background of therapy with Cardioksan: anemia, leukopenia, nausea, vomiting, stomatitis, asthenia, alopecia. Myelosupressivny effect of the drug Cardioksan can be additional to the similar effects of chemotherapy. There is evidence of an increased risk of developing secondary malignant diseases (especially acute myeloid leukemia) on the background of therapy with Cardioksan.
Adverse events, observed in clinical trials and probably related to the use of Cardioksan, are presented in Table 2. Here, eight clinical trials are presented in which adult patients treated with Cardiocyan in combination with doxorubicin in a ratio of 20: 1 or epirubicin in proportion 10: 1. For comparison, the table presents data on the frequency of AE in the control group, where patients received only chemotherapy.
To assess the incidence of adverse events, the following criteria were used: "very often" (≥1 / 10), "often" (≥1 / 100, <1/10), "infrequently" (≥1 / 1000, <1/100), "rarely" (≥1 / 10,000, <1/1000), "very rarely" (<1/10 000). Within each group, allocated according to frequency of occurrence, Undesirable phenomena are distributed in order of decreasing importance.
Table 2. Adverse events with Cardioksan and chemotherapy detected in clinical trials
| Adverse events | Cardiocyanate + Chemotherapy (n=375) | Chemotherapy (n=157) | Frequency |
| Infections and invasions |
| Sepsis | 0,5% | 0 | infrequently |
| Other infectious complications | 0,8% | 0 | infrequently |
| Blood disorders |
| Anemia | 14% | 18% | highly often |
| Leukopenia | 18% | 24% | highly often |
| Neutropenia | 9% | 20% | often |
| Febrile neutropenia | 4% | 8% | often |
| Febrile aplasia of the bone marrow | 1,1% | 0,6% | often |
| Thrombocytopenia | 5% | 8% | often |
| Granulocytopenia | 1,1% | 0 | often |
| Decreased leukocyte count | 1,1% | 0,6% | often |
| Decrease in the number of lymphocytes | 0,8% | 0 | infrequently |
| Decrease in the number of monocytes | 0,5% | 0 | infrequently |
| Increased number of eosinophils | 0,5% | 0 | infrequently |
| Increase in the number of leukocytes | 0,5% | 0 | infrequently |
| Increased number of platelets | 0,5% | 0 | infrequently |
| Increased number of neutrophils | 0,5% | 0 | infrequently |
| Disorders from the metabolism and nutrition |
| Anorexia | 2% | 4% | often |
| Disturbances from the nervous system |
| Peripheral Neuropathy | 1,3% | 0,6% | often |
| Paresthesia | 2% | 4% | often |
| Dizziness | 1,1% | 0,6% | often |
| Headache | 1,1% | 4% | often |
| Fainting | 0,5% | 0 | infrequently |
| Hearing disorders and labyrinthine disorders |
| Ear infections | 0,8% | 0 | infrequently |
| Vertigo | 0,8% | 0 | infrequently |
| Heart Disease |
| Decrease in cardiac output fraction | 3% | 10% | often |
| Tachycardia | 1,1% | 0,6% | often |
| Vascular disorders |
| Phlebitis | 7% | 2% | often |
| Venous thrombosis | 0,8% | 0 | infrequently |
| Lymphedema | 0,5% | 0 | infrequently |
| Disturbances from the respiratory system, organs thorax and mediastinum |
| Dyspnea | 2% | 3% | often |
| Pharyngitis | 1,3% | 0,6% | often |
| Respiratory tract infections | 1,3% | 1,3% | often |
| Cough | 1,3% | 3% | often |
| Disorders from the digestive system |
| Nausea | 50% | 54% | highly often |
| Stomatitis | 16% | 34% | highly often |
| Vomiting | 51% | 38% | highly often |
| Diarrhea | 9% | 17% | often |
| Abdominal pain | 2% | 4% | often |
| Dyspepsia | 1,1% | 3% | often |
| Constipation | 4% | 10% | often |
| Gingivitis | 0,5% | 0 | infrequently |
| Candidiasis of the mouth | 0,5% | 0 | infrequently |
| Disorders from the hepatobiliary system |
| Increased transaminase levels | 1,3% | 1,3% | often |
| Disturbances from the skin and subcutaneous tissues |
| Alopecia | 72% | 75% | highly often |
| The defeat of nails | 2% | 3% | often |
| Erythema | 1,1% | 0,6% | often |
| Inflammation of subcutaneous tissue | 0,5% | 0 | infrequently |
| General disorders and disorders in place of introduction |
| Asthenia | 13% | 27% | highly often |
| Inflammation of mucous membranes | 3% | 14% | often |
| Fever | 9% | 13% | often |
| Increased fatigue | 4% | 9% | often |
| Edema | 2,1% | 1,3% | often |
| General malaise | 8% | 1% | often |
| Pain at the injection site | 8% | 1,2% | often |
| Irritation at the site of administration | 1,3% | 0 | often |
| Thrombosis at the site of administration | 0,5% | 0 | infrequently |
| Thirst | 0,5% | 0 | infrequently |
Description of patients who participated in clinical trials
Patients receiving chemotherapy and Cardioksan (n = 375)
- 76% of these patients received treatment for breast cancer, 24% - for other types of advanced cancer.
- The average dose of the drug Kardioksan when combined with doxorubicin was 1010 mg / m2 (median 1,000 mg / m2), when combined with epirubicin - 941 mg / m2 (median 997 mg / m2).
- Patients receiving treatment about breast cancer: 45% were given doxorubicin 50 mg / m2 (mainly in combination with 5-fluorouracil and cyclophosphamide); 17% were given epirubicin, 14% epirubicin in a dose of 60 mg / m2 or 90 mg / m2 in combination with 5-fluorouracil and cyclophosphamide.
Patients who received only chemotherapy (n = 157)
- All patients received treatment for breast cancer.
- 43% of patients received ionotherapy epirubicin in a dose of 120 mg / m2; 33% received combination therapy doxorubicin in a dose of 50 mg / m2 in combination with 5-fluorouracil and cyclophosphamide; 24% combined therapy with epirubicin at a dose of 60 mg / m2 or 90 mg / m2 with 5-fluorouracil and cyclophosphamide.
Adverse events with the use of Cardioksan in clinical practice, identified through individual reports
In view of the fact that data on these AEs are collected due to separate voluntary reports, it is not possible to establish their frequency. AEs are grouped according to the WHO classification. In each group, AEs are distributed in order of decreasing importance.
Benign and malignant neoplasms: acute myeloid leukemia.
Immune system disorders: anaphylactic reactions, hypersensitivity.
Vascular disorders: thromboembolism.
Disturbances from the respiratory system, chest and mediastinal organs: pulmonary embolism.
Descriptions of some undesirable phenomena
Anaphylactic reactions
Anaphylactic reactions in patients treated with Kardioksan together with anthracyclines, mainly included: angioedema, face edema, nasal edema, laryngeal edema, generalized pruritus, macular erythema, dyspnea, cough, bronchospasm, pronounced decrease in blood pressure, asthma status, hypoxia, respiratory failure , stridor, shock / depression of consciousness. Before starting treatment, it is necessary to carefully study the allergic anamnesis to exclude allergies to dexrazoxane, dispersed and / or anthracyclines.
Benign, malignant and unspecified neoplasms
Secondary acute myeloid leukemia (AML) / myelodysplastic syndrome (MDS) has been reported in patients with Hodgkin's lymphoma or acute lymphoblastic leukemia receiving dexrazoxane in combination with chemotherapy. Post-marketing reports document AML cases in adult patients with breast cancer.
Below are the AEs revealed during the prescription of Cardiodoxan in a dose about the maximum tolerated: neutropenia, thrombocytopenia, nausea, vomiting, increased hepatic indicators.
Other toxic effects: malaise, subfebrile condition, increased renal clearance of iron and zinc, anemia, impairment blood coagulability, transient increase in concentration triglycerides, amylases and a transient decrease in serum calcium concentration.
If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.