Adverse reactions caused by cytarabine, depend on the dosage, mode of administration and duration of therapy.
On the part of the hematopoiesis system: because the cytarabine is an agent that depresses the bone marrow, as the consequences of its introduction can be expected the development of anemia, leukopenia, thrombocytopenia and megaloblastosis, as well as a reduction in the number of reticulocytes. The decrease in the number of leukocytes is of a two-phase nature, with the first maximum decrease being achieved by 7-9 days.Then there is a short-term rise with a maximum of 12 days. At the second and deeper decline, the minimum number of leukocytes is observed in 15-24 days. In the next 10 days, the number of white blood cells increases rapidly. The decrease in the number of platelets becomes noticeable by day 5, the minimum occurs between 12-15 days. In the next 10 days there is a rapid increase in the number of platelets to the baseline level. The severity of these reactions depends on the dose and the scheme of administration.
From the gastrointestinal tract (GIT): nausea and vomiting most often occur within a few hours after a rapid intravenous injection. These reactions may be less pronounced if the drug is administered as an infusion. When using high doses (2-3 g / m2) ulceration of the gastrointestinal tract can be severe, it is possible to develop necrotic colitis, small intestine necrosis, cystic pneumatosis of the intestine, leading to peritonitis.
From the liver and pancreas: with high-dosage therapy - a violation of liver function with hyperbilirubinemia, sepsis and liver abscess.
There have also been reports of individual cases of pancreatitis in the treatment of high doses of cytarabine in combination with other drugs.
From the nervous system: disorders from the central nervous system are mainly noted in the treatment with high doses, with the most important disorders of the brain, including the cerebellum (nystagmus, dysarthria, ataxia, confusion), including personality changes, drowsiness, and coma. Disorders from the CNS are usually reversible.
Also reported were cases of peripheral motor and sensory neuropathy and late progressive ascending paralysis. In some cases after the intrathecal administration of the drug, nausea, vomiting, dizziness and fever were noted. These complaints can also be caused by lumbar puncture. Cumulative neurotoxicity may also occur, especially with short intervals between dose administrations.
Individual cases of necrotizing leukoencephalopathy, as well as paraplegia and blindness after intrathecal cytarabine injection were described.
From the sense organs: in the treatment of high doses, reversible ulcerative keratitis and hemorrhagic conjunctivitis may occur.
From the cardiovascular and respiratory systems: Cardiomyopathy can sometimes be fatal when using cytarabine in high doses in combination with cyclophosphamide.
Infectious complications: with the use of cytarabine in the form of monotherapy or in combination with other immunosuppressive drugs (when administered at doses that affect cellular or humoral immunity), viral, bacterial, fungal, parasitic or saprophytic infections can be associated in any part of the body (including sepsis). These infections can be mild or moderate, but can be severe and sometimes fatal.
Cytarabine Syndrome: has the following manifestations: fever, muscle pain, bone pain, sometimes pain in the chest, spotty papular rash, conjunctivitis, malaise. These symptoms usually appear 6-12 hours after the administration of the drug. It has been established that glucocorticosteroids are effective in treating or preventing the development of this syndrome.
If the symptoms of cytarabine syndrome are treated as treatable, consideration should be given to the need for glucocorticosteroids, as well as the continuation of cytarabine therapy.
Registered adverse reactions are listed below by category of organ systems according to the dictionary MedDRA and the frequency of manifestation. The frequencies are defined as follows: very often (> 10%), often (> 1%, <10%), infrequently (> 0.1%, <1%), rarely (> 0.01%, <0.1% ) and the frequency is unknown (can not be calculated from available data).
Table of unwanted reactions
| Infectious and parasitic diseases |
| Often | Sepsis, pneumonia and infectiona |
| Frequency unknown | Inflammation of subcutaneous tissue at the injection site |
| Violations of the blood and lymphatic system |
| Often | Insufficiency of bone marrow function, thrombocytopenia, anemia, megaloblastic anemia, leukopenia and a decrease in the number of reticulocytes |
| Immune system disorders |
| Frequency unknown | Anaphylactic reaction, allergic edema |
| Metabolic and nutritional disorders |
| Frequency unknown | Reduced appetite (until loss of appetite) |
| Disturbances from the nervous system |
| Frequency unknown | Neurotoxicity, neuritis, dizziness and headache |
| Disturbances on the part of the organ of sight |
| Frequency unknown | Conjunctivitisb |
| Heart Disease |
| Frequency unknown | Pericarditis |
| Vascular disorders |
| Frequency unknown | Thrombophlebitis |
| Disturbances from the respiratory system, chest and mediastinal organs |
| Frequency unknown | Shortness of breath, pain in the oropharynx, apnea, pneumonia, diffuse interstitial pneumonitis |
| Disorders from the gastrointestinal tract |
| Often | Stomatitis, oral ulcer, anal ulcer, inflammation in the anus, diarrhea, vomiting, nausea and abdominal pain |
| Frequency unknown | Pancreatitis, ulcer of esophagus, esophagitis |
| Disturbances from the liver and bile ducts |
| Often | Deviation from the norm of liver function indices |
| Frequency unknown | Jaundice |
| Disturbances from the skin and subcutaneous tissues |
| Often | Alopecia, rash |
| Often | Cutaneous ulcer |
| Frequency unknown | Syndrome of palmar-plantar erythrodysesthesia, hives, itching and lentigo (pigment spots) |
| Disturbances from the skeletal musculature, bones and connective tissue |
| Often | Cytarabine Syndrome |
| Disorders from the kidneys and urinary tract |
| Frequency unknown | Violation of kidney function, urinary retention, hyperuricemia, urate nephropathy |
| General disorders and reactions at the injection site |
| Often | Fever |
| Frequency unknown | Pain in the chest, reaction at the injection siteat |
| Laboratory and instrumental data |
| Often | Deviation from the norm of the bone marrow biopsy result, the result of the blood smear analysis |
a It can be mild, but can be severe and in some cases lethal
b It can occur with a rash, when using the drug in high doses can be hemorrhagic
at Pain and inflammation at the site of subcutaneous injection
The following table includes undesirable reactions recorded with high-dose therapy.
Table of adverse reactions (high dose therapy)
| Infectious and parasitic diseases |
| Frequency unknown | Abscess of liver |
| Mental disorders |
| Frequency unknown | Change of personalitya |
| Disturbances from the nervous system |
| Often | Brain injury, cerebellar involvement, drowsiness |
| Frequency unknown | Coma, convulsions,peripheral motor neuropathy and peripheral sensory neuropathy |
| Disturbances on the part of the organ of sight |
| Often | Corneal damage |
| Heart Disease |
| Frequency unknown | Cardiomyopathy6 |
| Disturbances from the respiratory system, chest and mediastinal organs |
| Often | Acute respiratory distress syndrome, pulmonary edema |
| Disorders from the gastrointestinal tract |
| Often | Necrotizing Colitis |
| Frequency unknown | Gastrointestinal necrosis, gastrointestinal ulcer, intestinal pneumonitis and peritonitis |
| Disturbances from the liver and bile ducts |
| Frequency unknown | Liver involvement, hyperbilirubinemia |
| Disturbances from the skin and subcutaneous tissues |
| Often | Skin peeling |
a The change in personality was recorded in combination with dysfunction of the brain and cerebellum
b With the subsequent lethal outcome
Other undesirable reactions
In patients who received experimental therapy with average doses of cytarabine (1 g / m2) in combination with other chemotherapeutic drugs (M-AMCA, daunorubicin, VP-16) and in the form of monotherapy, diffuse interstitial pneumonitis was registered without an obvious cause, possibly associated with cytarabine.
After experimental therapy with high doses of cytarabine for recurrent leukemia, a sudden development of respiratory distress syndrome with rapid progression to pulmonary edema and radiographically confirmed cardiomegaly was recorded; the lethal outcome was recorded.
Intrathecal application
The most frequently reported reactions occurring after intrathecal administration were nausea, vomiting, and fever; such reactions are characterized by mild severity and pass on their own. There have been reports of paraplegia. There were also cases of necrotizing leukoencephalopathy with seizures and without them; in some cases, patients also received therapy in the form of intrathecal administration of methotrexate and / or hydrocortisone, as well as irradiation of the central nervous system. Isolated neurotoxicity was recorded. Two patients who were in remission, whose treatment included combined systemic chemotherapy, preventive irradiation of the central nervous system and intrathecal administration of cytarabine, developed blindness.