Cytarabine
Generic: CYTARABINE
Basic Information
Manufacturer
Meitheal Pharmaceuticals Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
1be2668b-d76f-4c65-aea9-86c5c40889a2
Indications & Usage
INDICATIONS AND USAGE Cytarabine Injection in combination with other approved anticancer drugs is indicated for remission induction in acute non-lymphocytic leukemia of adults and children.
It has also been found useful in the treatment of acute lymphocytic leukemia and the blast phase of chronic myelocytic leukemia.
Intrathecal administration of Cytarabine Injection is indicated in the prophylaxis and treatment of meningeal leukemia.
It has also been found useful in the treatment of acute lymphocytic leukemia and the blast phase of chronic myelocytic leukemia.
Intrathecal administration of Cytarabine Injection is indicated in the prophylaxis and treatment of meningeal leukemia.
Warnings
WARNINGS ( See boxed WARNING ) Cytarabine is a potent bone marrow suppressant.
Therapy should be started cautiously in patients with pre-existing drug-induced bone marrow suppression.
Patients receiving this drug must be under close medical supervision and, during induction therapy, should have leucocyte and platelet counts performed daily.
Bone marrow examinations should be performed frequently after blasts have disappeared from the peripheral blood.
Facilities should be available for management of complications, possibly fatal, of bone marrow suppression (infection resulting from granulocytopenia and other impaired body defenses, and hemorrhage secondary to thrombocytopenia).
One case of anaphylaxis that resulted in acute cardiopulmonary arrest and required resuscitation has been reported.
This occurred immediately after the intravenous administration of cytarabine.
Severe and at times fatal CNS, GI and pulmonary toxicity (different from that seen with conventional therapy regimens of cytarabine) has been reported following some experimental cytarabine dose schedules.
These reactions include reversible corneal toxicity, and hemorrhagic conjunctivitis, which may be prevented or diminished by prophylaxis with a local corticosteroid eye drop; cerebral and cerebellar dysfunction, including personality changes, somnolence and coma, usually reversible; severe gastrointestinal ulceration, including pneumatosis cystoides intestinalis leading to peritonitis; sepsis and liver abscess; pulmonary edema, liver damage with increased hyperbilirubinemia; bowel necrosis; and necrotizing colitis.
Rarely, severe skin rash, leading to desquamation has been reported.
Complete alopecia is more commonly seen with experimental high dose therapy than with standard cytarabine treatment programs.
If experimental high dose therapy is used, do not use a diluent containing benzyl alcohol.
Cases of cardiomyopathy with subsequent death has been reported following experimental high dose therapy with cytarabine in combination with cyclophosphamide when used for bone marrow transplant preparation.
A syndrome of sudden respiratory distress, rapidly progressing to pulmonary edema and radiographically pronounced cardiomegaly has been reported following experimental high dose therapy with cytarabine used for the treatment of relapsed leukemia from one institution in 16/72 patients.
The outcome of this syndrome can be fatal.
Two patients with childhood acute myelogenous leukemia who received intrathecal and intravenous cytarabine at conventional doses (in addition to a number of other concomitantly administered drugs) developed delayed progressive ascending paralysis resulting in death in one of the two patients.
Use in Pregnancy Cytarabine can cause fetal harm when administered to a pregnant woman.
Cytarabine causes abnormal cerebellar development in the neonatal hamster and is teratogenic to the rat fetus.
There are no adequate and well-controlled studies in pregnant women.
Women of childbearing potential should be advised to avoid becoming pregnant.
Therapy should be started cautiously in patients with pre-existing drug-induced bone marrow suppression.
Patients receiving this drug must be under close medical supervision and, during induction therapy, should have leucocyte and platelet counts performed daily.
Bone marrow examinations should be performed frequently after blasts have disappeared from the peripheral blood.
Facilities should be available for management of complications, possibly fatal, of bone marrow suppression (infection resulting from granulocytopenia and other impaired body defenses, and hemorrhage secondary to thrombocytopenia).
One case of anaphylaxis that resulted in acute cardiopulmonary arrest and required resuscitation has been reported.
This occurred immediately after the intravenous administration of cytarabine.
Severe and at times fatal CNS, GI and pulmonary toxicity (different from that seen with conventional therapy regimens of cytarabine) has been reported following some experimental cytarabine dose schedules.
These reactions include reversible corneal toxicity, and hemorrhagic conjunctivitis, which may be prevented or diminished by prophylaxis with a local corticosteroid eye drop; cerebral and cerebellar dysfunction, including personality changes, somnolence and coma, usually reversible; severe gastrointestinal ulceration, including pneumatosis cystoides intestinalis leading to peritonitis; sepsis and liver abscess; pulmonary edema, liver damage with increased hyperbilirubinemia; bowel necrosis; and necrotizing colitis.
Rarely, severe skin rash, leading to desquamation has been reported.
Complete alopecia is more commonly seen with experimental high dose therapy than with standard cytarabine treatment programs.
If experimental high dose therapy is used, do not use a diluent containing benzyl alcohol.
Cases of cardiomyopathy with subsequent death has been reported following experimental high dose therapy with cytarabine in combination with cyclophosphamide when used for bone marrow transplant preparation.
A syndrome of sudden respiratory distress, rapidly progressing to pulmonary edema and radiographically pronounced cardiomegaly has been reported following experimental high dose therapy with cytarabine used for the treatment of relapsed leukemia from one institution in 16/72 patients.
The outcome of this syndrome can be fatal.
Two patients with childhood acute myelogenous leukemia who received intrathecal and intravenous cytarabine at conventional doses (in addition to a number of other concomitantly administered drugs) developed delayed progressive ascending paralysis resulting in death in one of the two patients.
Use in Pregnancy Cytarabine can cause fetal harm when administered to a pregnant woman.
Cytarabine causes abnormal cerebellar development in the neonatal hamster and is teratogenic to the rat fetus.
There are no adequate and well-controlled studies in pregnant women.
Women of childbearing potential should be advised to avoid becoming pregnant.
Adverse Reactions
ADVERSE REACTIONS Expected Reactions Because cytarabine is a bone marrow suppressant, anemia, leukopenia, thrombocytopenia, megaloblastosis and reduced reticulocytes can be expected as a result of administration with cytarabine.
The severity of these reactions are dose and schedule dependent.
Cellular changes in the morphology of bone marrow and peripheral smears can be expected.
Following 5-day constant infusions or acute injections of 50 mg/m 2 to 600 mg/m 2 , white cell depression follows a biphasic course.
Regardless of initial count, dosage level, or schedule, there is an initial fall starting the first 24 hours with a nadir at days 7 to 9.
This is followed by a brief rise which peaks around the twelfth day.
A second and deeper fall reaches nadir at days 15 to 24.
Then there is a rapid rise to above baseline in the next 10 days.
Platelet depression is noticeable at 5 days with a peak depression occurring between days 12 to 15.
Thereupon, a rapid rise to above baseline occurs in the next 10 days.
Infectious Complications Infection Viral, bacterial, fungal, parasitic, or saprophytic infections, in any location in the body may be associated with the use of cytarabine alone or in combination with other immunosuppressive agents following immunosuppressant doses that affect cellular or humoral immunity.
These infections may be mild, but can be severe and at times fatal.
The Cytarabine (Ara-C) Syndrome A cytarabine syndrome has been described by Castleberry.
It is characterized by fever, myalgia, bone pain, occasionally chest pain, maculopapular rash, conjunctivitis and malaise.
It usually occurs 6 to 12 hours following drug administration.
Corticosteroids have been shown to be beneficial in treating or preventing this syndrome.
If the symptoms of the syndrome are deemed treatable, corticosteroids should be contemplated as well as continuation of therapy with cytarabine.
Most Frequent Adverse Reactions Anorexia, hepatic dysfunction, nausea, fever, vomiting, rash, diarrhea, thrombophlebitis, oral and anal inflammation or ulceration, bleeding (all sites).
Nausea and vomiting are most frequent following rapid intravenous injection.
Less Frequent Adverse Reactions Sepsis, abdominal pain, pneumonia, freckling, cellulitis at injection site, jaundice, skin ulceration, conjunctivitis (may occur with rash), urinary retention, dizziness, renal dysfunction, alopecia, neuritis, anaphylaxis (see WARNINGS ), neural toxicity, allergic edema, sore throat, pruritus, esophageal ulceration, shortness of breath, esophagitis, urticaria, chest pain, pericarditis, headache, bowel necrosis, pancreatitis, sinus bradycardia.
Experimental Doses Severe and at times fatal CNS, GI and pulmonary toxicity (different from that seen with conventional therapy regimens of cytarabine) has been reported following some experimental dose schedules of cytarabine.
These reactions include reversible corneal toxicity and hemorrhagic conjunctivitis, which may be prevented or diminished by prophylaxis with a local corticosteroid eye drop; cerebral and cerebellar dysfunction, including personality changes, somnolence and coma, usually reversible; severe gastrointestinal ulceration, including pneumatosis cystoides intestinalis leading to peritonitis; sepsis and liver abscess; pulmonary edema, liver damage with increased hyperbilirubinemia; bowel necrosis; and necrotizing colitis.
Rarely, severe skin rash, leading to desquamation has been reported.
Complete alopecia is more commonly seen with experimental high dose therapy than with standard cytarabine treatment programs.
If experimental high dose therapy is used, do not use a diluent containing benzyl alcohol.
Cases of cardiomyopathy with subsequent death has been reported following experimental high dose therapy with cytarabine in combination with cyclophosphamide when used for bone marrow transplant preparation.
This cardiac toxicity may be schedule dependent.
A syndrome of sudden respiratory distress, rapidly progressing to pulmonary edema and radiographically pronounced cardiomegaly has been reported following experimental high dose therapy with cytarabine used for the treatment of relapsed leukemia from one institution in 16/72 patients.
The outcome of this syndrome can be fatal.
Two patients with adult acute non-lymphocytic leukemia developed peripheral motor and sensory neuropathies after consolidation with high-dose cytarabine, daunorubicin, and asparaginase.
Patients treated with high-dose cytarabine should be observed for neuropathy since dose schedule alterations may be needed to avoid irreversible neurologic disorders.
Ten patients treated with experimental intermediate doses of cytarabine (1 g/m 2 ) with and without other chemotherapeutic agents (meta-AMSA, daunorubicin, etoposide) at various dose regimens developed a diffuse interstitial pneumonitis without clear cause that may have been related to the cytarabine.
Two cases of pancreatitis have been reported following experimental doses of cytarabine and numerous other drugs.
Cytarabine could have been the causative agent.
To report SUSPECTED ADVERSE REACTIONS, contact Meitheal Pharmaceuticals Inc.
at 1-844-824-8426 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
The severity of these reactions are dose and schedule dependent.
Cellular changes in the morphology of bone marrow and peripheral smears can be expected.
Following 5-day constant infusions or acute injections of 50 mg/m 2 to 600 mg/m 2 , white cell depression follows a biphasic course.
Regardless of initial count, dosage level, or schedule, there is an initial fall starting the first 24 hours with a nadir at days 7 to 9.
This is followed by a brief rise which peaks around the twelfth day.
A second and deeper fall reaches nadir at days 15 to 24.
Then there is a rapid rise to above baseline in the next 10 days.
Platelet depression is noticeable at 5 days with a peak depression occurring between days 12 to 15.
Thereupon, a rapid rise to above baseline occurs in the next 10 days.
Infectious Complications Infection Viral, bacterial, fungal, parasitic, or saprophytic infections, in any location in the body may be associated with the use of cytarabine alone or in combination with other immunosuppressive agents following immunosuppressant doses that affect cellular or humoral immunity.
These infections may be mild, but can be severe and at times fatal.
The Cytarabine (Ara-C) Syndrome A cytarabine syndrome has been described by Castleberry.
It is characterized by fever, myalgia, bone pain, occasionally chest pain, maculopapular rash, conjunctivitis and malaise.
It usually occurs 6 to 12 hours following drug administration.
Corticosteroids have been shown to be beneficial in treating or preventing this syndrome.
If the symptoms of the syndrome are deemed treatable, corticosteroids should be contemplated as well as continuation of therapy with cytarabine.
Most Frequent Adverse Reactions Anorexia, hepatic dysfunction, nausea, fever, vomiting, rash, diarrhea, thrombophlebitis, oral and anal inflammation or ulceration, bleeding (all sites).
Nausea and vomiting are most frequent following rapid intravenous injection.
Less Frequent Adverse Reactions Sepsis, abdominal pain, pneumonia, freckling, cellulitis at injection site, jaundice, skin ulceration, conjunctivitis (may occur with rash), urinary retention, dizziness, renal dysfunction, alopecia, neuritis, anaphylaxis (see WARNINGS ), neural toxicity, allergic edema, sore throat, pruritus, esophageal ulceration, shortness of breath, esophagitis, urticaria, chest pain, pericarditis, headache, bowel necrosis, pancreatitis, sinus bradycardia.
Experimental Doses Severe and at times fatal CNS, GI and pulmonary toxicity (different from that seen with conventional therapy regimens of cytarabine) has been reported following some experimental dose schedules of cytarabine.
These reactions include reversible corneal toxicity and hemorrhagic conjunctivitis, which may be prevented or diminished by prophylaxis with a local corticosteroid eye drop; cerebral and cerebellar dysfunction, including personality changes, somnolence and coma, usually reversible; severe gastrointestinal ulceration, including pneumatosis cystoides intestinalis leading to peritonitis; sepsis and liver abscess; pulmonary edema, liver damage with increased hyperbilirubinemia; bowel necrosis; and necrotizing colitis.
Rarely, severe skin rash, leading to desquamation has been reported.
Complete alopecia is more commonly seen with experimental high dose therapy than with standard cytarabine treatment programs.
If experimental high dose therapy is used, do not use a diluent containing benzyl alcohol.
Cases of cardiomyopathy with subsequent death has been reported following experimental high dose therapy with cytarabine in combination with cyclophosphamide when used for bone marrow transplant preparation.
This cardiac toxicity may be schedule dependent.
A syndrome of sudden respiratory distress, rapidly progressing to pulmonary edema and radiographically pronounced cardiomegaly has been reported following experimental high dose therapy with cytarabine used for the treatment of relapsed leukemia from one institution in 16/72 patients.
The outcome of this syndrome can be fatal.
Two patients with adult acute non-lymphocytic leukemia developed peripheral motor and sensory neuropathies after consolidation with high-dose cytarabine, daunorubicin, and asparaginase.
Patients treated with high-dose cytarabine should be observed for neuropathy since dose schedule alterations may be needed to avoid irreversible neurologic disorders.
Ten patients treated with experimental intermediate doses of cytarabine (1 g/m 2 ) with and without other chemotherapeutic agents (meta-AMSA, daunorubicin, etoposide) at various dose regimens developed a diffuse interstitial pneumonitis without clear cause that may have been related to the cytarabine.
Two cases of pancreatitis have been reported following experimental doses of cytarabine and numerous other drugs.
Cytarabine could have been the causative agent.
To report SUSPECTED ADVERSE REACTIONS, contact Meitheal Pharmaceuticals Inc.
at 1-844-824-8426 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .