DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Depocyt (Cytarabine) - Warnings and Precautions

 
 



WARNING: CHEMICAL ARACHNOIDITIS

Chemical arachnoiditis, a syndrome manifested primarily by nausea, vomiting, headache and fever, was a common adverse event in all clinical studies. If left untreated, chemical arachnoiditis may be fatal. Patients receiving DepoCyt should be treated concurrently with dexamethasone to mitigate the symptoms of chemical arachnoiditis. [see Warnings and Precautions (5.1, 5.2)]

 

WARNINGS AND PRECAUTIONS

Chemical Arachnoiditis

Chemical arachnoiditis, a syndrome manifested primarily by nausea, vomiting, headache and fever, has been a common adverse event in all studies. If chemical arachnoiditis is suspected, exclude other inflammatory, infectious, or neoplastic conditions. If left untreated, chemical arachnoiditis may be fatal. The incidence and severity of chemical arachnoiditis can be reduced by coadministration of dexamethasone. Patients receiving DepoCyt should be treated concurrently with dexamethasone to mitigate the symptoms of chemical arachnoiditis [see Dosage and Administration (2)].

Toxic effects may be related to a single dose or to cumulative administration. Because toxic effects can occur at any time during therapy (although they are most likely to occur within 5 days of drug administration), patients receiving intrathecal therapy with DepoCyt should be monitored continuously for the development of neurotoxicity. If patients develop neurotoxicity, reduce subsequent doses of DepoCyt. If neurotoxicity persists, discontinue DepoCyt [see Warnings and Precautions (5.3)]

Hydrocephalus has also been reported, possibly precipitated by arachnoiditis.

Arachnoiditis is an expected and well-documented side effect of both neoplastic meningitis and of intrathecal chemotherapy. The incidence of severe and life-threatening arachnoiditis in patients receiving DepoCyt was 19% (48/257) in all patients and 30% (10/33) in patients with lymphomatous meningitis. In the early dose-finding study, chemical arachnoiditis was observed in 100% of cycles without dexamethasone prophylaxis. When concurrent dexamethasone was administered, chemical arachnoiditis was observed in 33% of cycles.

Neurotoxicity

Intrathecal administration of cytarabine may cause myelopathy and other neurologic toxicity and can rarely lead to a permanent neurologic deficit. Administration of intrathecal cytarabine in combination with other chemotherapeutic agents or with cranial/spinal irradiation may increase this risk of neurotoxicity.

Blockage to CSF flow may result in increased free cytarabine concentrations in the CSF and an increased risk of neurotoxicity. Therefore, as with any intrathecal cytotoxic therapy, consideration should be given to the need for assessment of CSF flow before treatment is started.

Following intrathecal administration of DepoCyt, central nervous system toxicity, including persistent extreme somnolence, hemiplegia, visual disturbances including blindness which may be total and permanent, deafness and cranial nerve palsies have been reported. Symptoms and signs of peripheral neuropathy, such as pain, numbness, paresthesia, weakness, and impaired bowel and bladder control have also been observed. In some cases, a combination of neurological signs and symptoms has been reported as Cauda Equina Syndrome.

If patients develop neurotoxicity, reduce subsequent doses of DepoCyt or discontinue DepoCyt Headache, nausea, and fever are expected in early signs of neurotoxicity.

Transient Elevations in CSF Protein and CSF White Blood Cells

Transient elevations in CSF protein and white blood cell counts have been observed in patients following DepoCyt administration.

Embryo-fetal Toxicity

Cytarabine, the active component of DepoCyt, can cause fetal harm if a pregnant woman is exposed to the drug systemically. The systemic exposure of cytarabine following intrathecal administration of DepoCyt is negligible. Cytarabine was teratogenic in mice and rats. Cytarabine was embryotoxic in mice when administered during the period of organogenesis. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to a fetus. [See Use in Specific Populations, Sec. 8.1 ]

USE IN SPECIFIC POPULATIONS

Pregnancy Category D

[see Warnings and Precautions]

Risk Summary

There are no studies assessing the reproductive toxicity of DepoCyt. The systemic exposure of cytarabine following intrathecal administration of DepoCyt is negligible. Cytarabine can cause fetal harm if a pregnant woman is exposed to the drug systemically. Three anecdotal cases of major limb malformations have been reported in infants after their mothers received intravenous cytarabine, alone or in combination with other agents, during the first trimester. Advise women of childbearing potential to avoid becoming pregnant while receiving DepoCyt. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to a fetus.

Animal Data

Cytarabine was teratogenic in mice (cleft palate, phocomelia, deformed appendages, skeletal abnormalities) when doses ≥2 mg/kg/day were administered IP during the period of organogenesis (about 0.2 times the recommended human dose on a mg/m2 basis), and in rats (deformed appendages) when 20 mg/kg was administered as a single IP dose on day 12 of gestation (about 4 times the recommended human dose on a mg/m2 basis). Single IP doses of 50 mg/kg in rats (about 10 times the recommended human dose on a mg/m2 basis) on day 14 of gestation reduced prenatal and postnatal brain size and permanent impairment of learning ability.

Cytarabine was embryotoxic in mice when administered during the period of organogenesis. Embryotoxicity was characterized by decreased fetal weight at 0.5 mg/kg/day (about 0.05 times the recommended human dose on mg/m2 basis), and increased early and late resorptions and decreased live litter sizes at 8 mg/kg/day (approximately equal to the recommended human dose on mg/m2 basis).

Nursing Mothers

It is not known whether cytarabine is excreted in human milk following intrathecal DepoCyt administration. The systemic exposure to free cytarabine following intrathecal treatment with DepoCyt was negligible. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and efficacy of DepoCyt in pediatric patients has not been established.

Hepatic and Renal Impairment

The effects of hepatic or renal impairment on the pharmacokinetics of DepoCyt have not been studied.

Page last updated: 2015-01-02

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017