Alexan

Alexan uses

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• References
• Alexan reviews

INDICATIONS AND USAGE

Alexan 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 Alexan is indicated in the prophylaxis and treatment of meningeal leukemia.

CONTRAINDICATIONS

Alexan Injection is contraindicated in those patients who are hypersensitive to the drug.

WARNINGS

( See boxed WARNING )

Alexan 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 Alexan.

Severe and at times fatal CNS, GI and pulmonary toxicity (different from that seen with conventional therapy regimens of Alexan) has been reported following some experimental Alexan 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 Alexan 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 Alexan 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 Alexan 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 Alexan 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 (Category D): Alexan Injection can cause fetal harm when administered to a pregnant woman. Alexan 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.

PRECAUTIONS

1. General Precautions:

Patients receiving Alexan Injection must be monitored closely. Frequent platelet and leukocyte counts and bone marrow examinations are mandatory. Consider suspending or modifying therapy when drug-induced marrow depression has resulted in a platelet count under 50,000 or a polymorphonuclear granulocyte count under 1000/mm³. Counts of formed elements in the peripheral blood may continue to fall after the drug is stopped and reach lowest values after drug-free intervals of 12 to 24 days. When indicated, restart therapy when definite signs of marrow recovery appear. Patients whose drug is withheld until "normal" peripheral blood values are attained may escape from control.

When large intravenous doses are given quickly, patients are frequently nauseated and may vomit for several hours postinjection. This problem tends to be less severe when the drug is infused.

The human liver apparently detoxifies a substantial fraction of an administered dose. In particular, patients with renal or hepatic function impairment may have a higher likelihood of CNS toxicity after high-dose Alexan treatment. Use the drug with caution and possibly at reduced dose in patients whose liver or kidney function is poor.

Periodic checks of bone marrow, liver and kidney functions should be performed in patients receiving Alexan Injection.

Like other cytotoxic drugs, Alexan Injection may induce hyperuricemia secondary to rapid lysis of neoplastic cells. The clinician should monitor the patient's blood uric acid level and be prepared to use such supportive and pharmacologic measures as might be necessary to control this problem.

Acute pancreatitis has been reported to occur in a patient receiving Alexan by continuous infusion and in patients being treated with Alexan who have had prior treatment with L-asparaginase.

2. Information for patient:

Not applicable.

3. Laboratory tests:

See General Precautions .

4. Drug Interactions:

Reversible decreases in steady-state plasma digoxin concentrations and renal glycoside excretion were observed in patients receiving beta-acetyldigoxin and chemotherapy regimens containing cyclophosphamide, vincristine and prednisone with or without Alexan or procarbazine. Steady-state plasma digitoxin concentrations did not appear to change. Therefore, monitoring of plasma digoxin levels may be indicated in patients receiving similar combination chemotherapy regimens. The utilization of digitoxin for such patients may be considered as an alternative.

An in vitro interaction study between gentamicin and Alexan showed a Alexan related antagonism for the susceptibility of K. pneumoniae strains. This study suggests that in patients on Alexan being treated with gentamicin for a K. pneumoniae infection, the lack of a prompt therapeutic response may indicate the need for reevaluation of antibacterial therapy.

Clinical evidence in one patient showed possible inhibition of fluorocytosine efficacy during therapy with Alexan. This may be due to potential competitive inhibition of its uptake.

5. Carcinogenesis, mutagenesis, impairment of fertility:

Extensive chromosomal damage, including chromatoid breaks have been produced by Alexan and malignant transformation of rodent cells in culture has been reported.

6. Pregnancy:

Pregnancy Category D. See WARNINGS . A review of the literature has shown 32 reported cases where Alexan was given during pregnancy, either alone or in combination with other cytotoxic agents.

Eighteen normal infants were delivered. Four of these had first trimester exposure. Five infants were premature or of low birth weight. Twelve of the 18 normal infants were followed up at ages ranging from six weeks to seven years, and showed no abnormalities. One apparently normal infant died at 90 days of gastroenteritis.

Two cases of congenital abnormalities have been reported, one with upper and lower distal limb defects, and the other with extremity and ear deformities. Both of these cases had first trimester exposure.

There were seven infants with various problems in the neonatal period, including pancytopenia; transient depression of the WBC, hematocrit or platelets; electrolyte abnormalities; transient eosinophilia; and one case of increased IgM levels and hyperpyrexia possibly due to sepsis. Six of the seven infants were also premature. The child with pancytopenia died at 21 days of sepsis.

Therapeutic abortions were done in five cases. Four fetuses were grossly normal, but one had an enlarged spleen and another showed Trisomy C chromosome abnormality in the chorionic tissue.

Because of the potential for abnormalities with cytotoxic therapy, particularly during the first trimester, a patient who is or who may become pregnant while on Alexan Injection should be apprised of the potential risk to the fetus and the advisability of pregnancy continuation. There is a definite, but considerably reduced risk if therapy is initiated during the second or third trimester. Although normal infants have been delivered to patients treated in all three trimesters of pregnancy, follow-up of such infants would be advisable.

7. Labor and delivery:

Not applicable.

8. Nursing mothers:

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Alexan, 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.

9. Pediatric use:

See INDICATIONS AND USAGE .

ADVERSE REACTIONS

Expected Reactions: Because Alexan is a bone marrow suppressant, anemia, leukopenia, thrombocytopenia, megaloblastosis and reduced reticulocytes can be expected as a result of administration with Alexan. 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/m² to 600 mg/m², 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 7-9. This is followed by a brief rise which peaks around the twelfth day. A second and deeper fall reaches nadir at days 15-24. 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 12-15. 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 Alexan 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 Alexan (Ara-C) Syndrome: A Alexan 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 6-12 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 Alexan Injection.

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.

Experimental Doses: Severe and at times fatal CNS, GI and pulmonary toxicity (different from that seen with conventional therapy regimens of Alexan) has been reported following some experimental dose schedules of Alexan. 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 Alexan 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 Alexan 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 Alexan 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 Alexan, daunorubicin, and asparaginase. Patients treated with high-dose Alexan 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 Alexan (1 g/m²) 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 Alexan.

Two cases of pancreatitis have been reported following experimental doses of Alexan and numerous other drugs. Alexan could have been the causative agent.

OVERDOSAGE

There is no antidote for Alexan overdosage. Doses of 4.5 g/m² by intravenous infusion over 1 hour every 12 hours for 12 doses has caused an unacceptable increase in irreversible CNS toxicity and death.

Single doses as high as 3 g/m² have been administered by rapid intravenous infusion without apparent toxicity.

DOSAGE AND ADMINISTRATION

Alexan Injection (non-preserved) can be administered by intravenous injection or infusion, subcutaneously, or intrathecally. However, the intent of this Pharmacy Bulk Package is for the preparation of solutions for IV infusion only. Intrathecal use of Alexan requires the use of single-dose, unpreserved solutions only.

Alexan Injection is not active orally. The schedule and method of administration varies with the program of therapy to be used. While Alexan Injection may be given by intravenous infusion or injection, or subcutaneously or intrathecally, THE PURPOSE OF THE PHARMACY BULK PACKAGE IS FOR THE PREPARATION OF INTRAVENOUS INFUSIONS. Thrombophlebitis has occurred at the site of drug injection or infusion in some patients, and rarely patients have noted pain and inflammation at subcutaneous injection sites. In most instances, however, the drug has been well tolerated.

Patients can tolerate higher total doses when they receive the drug by rapid intravenous injection as compared with slow infusion. This phenomenon is related to the drug's rapid inactivation and brief exposure of susceptible normal and neoplastic cells to significant levels after rapid injection. Normal and neoplastic cells seem to respond in somewhat parallel fashion to these different modes of administration and no clear-cut clinical advantage has been demonstrated for either.

In the induction therapy of acute non-lymphocytic leukemia, the usual Alexan dose in combination with other anti-cancer drugs is 100 mg/m²/day by continuous IV infusion (Days 1-7) or 100 mg/m² IV every 12 hours (Days 1-7).

The literature should be consulted for the current recommendations for use in acute lymphocytic leukemia.

Intrathecal Use in Meningeal Leukemia: Alexan has been used intrathecally in acute leukemia in doses ranging from 5 mg/m² to 75 mg/m² of body surface area. The frequency of administration varied from once a day for 4 days to once every 4 days. The most frequently used dose was 30 mg/m² every 4 days until cerebrospinal fluid findings were normal, followed by one additional treatment. The dosage schedule is usually governed by the type and severity of central nervous system manifestations and the response to previous therapy.

If used intrathecally, do not use a solution containing benzyl alcohol. This pharmacy bulk package is not intended to be used for the preparation of intrathecal doses.

Alexan given intrathecally may cause systemic toxicity and careful monitoring of the hemopoietic system is indicated. Modification of other anti-leukemia therapy may be necessary. Major toxicity is rare. The most frequently reported reactions after intrathecal administration were nausea, vomiting and fever; these reactions are mild and self-limiting. Paraplegia has been reported. Necrotizing leukoencephalopathy occurred in 5 children; these patients had also been treated with intrathecal methotrexate and hydrocortisone, as well as by central nervous system radiation. Isolated neurotoxicity has been reported. Blindness occurred in two patients in remission whose treatment had consisted of combination systemic chemotherapy, prophylactic central nervous system radiation and intrathecal Alexan.

When Alexan is administered both intrathecally and intravenously within a few days, there is an increased risk of spinal cord toxicity, however, in serious life-threatening disease, concurrent use of intravenous and intrathecal Alexan is left to the discretion of the treating physician.

Focal leukemic involvement of the central nervous system may not respond to intrathecal Alexan and may better be treated with radiotherapy.

Chemical Stability of Infusion Solutions: Chemical stability studies were performed by a stability indicating HPLC assay on Alexan Injection in infusion solutions. These studies showed that when Alexan Injection was diluted with Water for Injection, 5% Dextrose Injection or Sodium Chloride Injection, in both glass and plastic infusion bags, 97-100% of the Alexan was present after 8 days storage at room temperature.

This chemical stability information in no way indicates that it would be acceptable practice to infuse a Alexan admixture well after the preparation time. Good professional practice suggests that administration of an admixture should be as soon after preparation as feasible.

Parenteral drugs should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Handling and Disposal: Procedures for proper handling and disposal of anti-cancer drugs should be considered. Several guidelines on this subject have been published.^1-7 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

Direction for Dispensing From Pharmacy Bulk Package: The 50 mL Pharmacy Bulk Package is for use in the Pharmacy Admixtures Service only. The vials should be inserted into the plastic handling device provided, suspended as a unit in the laminar flow hood.

A single entry through the vial closure should be made with a sterile dispensing set or transfer device. Transfer individual doses to appropriate intravenous infusion solutions. Use of a syringe with needle is not recommended. Multiple entries will increase the potential of microbial and particulate contamination.

The above process should be carried out under a laminar flow hood using aseptic technique. Care should be exercised to protect personnel from aerosolized drug (see DOSAGE AND ADMINISTRATION, REFERENCES ). Discard any unused portion within 4 hours after initial closure entry.

HOW SUPPLIED

Alexan Injection, PHARMACY BULK PACKAGE. Sterile, Isotonic Solution. Preservative Free. NDC No. 61703-303-46.

Protect from light. Retain in carton until time of use.

Alexan Injection 20 mg/mL (1000 mg) in a 50 mL flip-top vial (green cap), packaged individually.

Store at 20°C to 25°C (68°F to 77°F) [USP Controlled Room Temperature].

REFERENCES

• Recommendations for the Safe handling of Parenteral Antineoplastic Drugs, NIH Publications No. 83-2621. For sale by the Superintendent of Documents, U.S. Government Printing Office, Washington, D.C. 20402.
• AMA Council Report, Guidelines for Handling Parenteral Antineoplastics, JAMA, 1985; 2.53 (11): 1590-1592.
• National Study Commission on Cytotoxic Exposure - Recommendations for Handling Cytotoxic Agents. Available from Louis P. Jeffrey, ScD., Chairman, National Study Commission on Cytotoxic Exposure, Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, Massachusetts 02115.
• Clinical Oncological Society of Australia, Guidelines and Recommendations for Safe handling of Antineoplastic Agents. Med J Australia, 1983; 1:426-428.
• Jones RB, et al: Safe Handling of Chemotherapeutic Agents: A Report from the Mount Sinai Medical Center. CA-A Cancer Journal of Clinicians, 1983; (Sept/Oct) 258-263.
• American Society of Hospital Pharmacists Technical Assistance Bulletin on Handling Cytotoxic and Hazardous Drugs. Am J. Hosp. Pharm, 1990; 47:1033-1049.
• Controlling Occupational Exposure to Hazardous Drugs. (OSHA Work Practice Guidelines), Am J. Health- Syst Pharm, 1996; 53: 1669-1685.

Manufactured by Zydus Hospira Oncology Private Ltd.

Ahmedabad 382-213, Gujarat, India

for Hospira, Inc. Lake Forest, IL 60045 USA

Made in India

GUJ-DRUGS/G/28/1267

EN-4358

7/2016

Hospira logo

50 mL Vial

NDC 61703-303-46

Sterile

Rx only

Alexan Injection

1000 mg/ 50 mL

20 mg/mL

For Intravenous and Subcutaneous Use*

Pharmacy Bulk Package

Not for Direct Infusion

Cytotoxic Agent

Alexan pharmaceutical active ingredients containing related brand and generic drugs:

• Cytarabine

Alexan available forms, composition, doses:

• Injectable; Infusion; Cytarabine 20 mg / ml
• Injectable; Infusion; Cytarabine 50 mg / ml

Alexan destination | category:

• Human:
• Antineoplastic agents
• Cytotoxic chemotherapy

Alexan Anatomical Therapeutic Chemical codes:

• L01BC01 - Cytarabine

Alexan pharmaceutical companies:

• Boots
• Byk
• Ebewe Pharma
• Eczacibasi
• EuroCept
• Ferraz Lynce
• Heinrich Mack Nachfolger
• Intramed
• Keri Pharma
• Neocorp
• Nycomed
• Pfizer
• Sandoz
• Schumit 1967
• Summit
• Zuellig Pharma

References

1. Dailymed."CYTARABINE INJECTION, SOLUTION [HOSPIRA, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
2. "cytarabine". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Depending on the reaction of the Alexan after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Alexan not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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The information was verified by Dr. Rachana Salvi, MD Pharmacology