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DRUGS & SUPPLEMENTS
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Neozine
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Neozine uses
- Indications and usage
- Contraindications
- Warnings
- Precautions
- Adverse reactions
- Overdosage
- Dosage and administration
- How supplied
- References
INDICATIONS AND USAGE
Neozine is indicated for use in combination with other anticancer drugs for the treatment of Stage III and IV Hodgkin's disease. Neozine is used as part of the MOPP (nitrogen mustard, vincristine, Neozine, prednisone) regimen.
CONTRAINDICATIONS
Neozine is contraindicated in patients with known hypersensitivity to the drug or inadequate marrow reserve as demonstrated by bone marrow aspiration. Due consideration of this possible state should be given to each patient who has leukopenia, thrombocytopenia or anemia.
WARNINGS
To minimize CNS depression and possible potentiation, barbiturates, antihistamines, narcotics, hypotensive agents or phenothiazines should be used with caution. Ethyl alcohol should not be used since there may be an Antabuse -like reaction. Because Neozine exhibits some monoamine oxidase inhibitory activity, sympathomimetic drugs, tricyclic antidepressant drugs (eg, amitriptyline HCI, imipramine HCI) and other drugs and foods with known high tyramine content, such as wine, yogurt, ripe cheese and bananas, should be avoided. A further phenomenon of toxicity common to many hydrazine derivatives is hemolysis and the appearance of Heinz-Ehrlich inclusion bodies in erythrocytes.
Pregnancy
Teratogenic Effects
Pregnancy Category D. Neozine hydrochloride can cause fetal harm when administered to a pregnant woman. While there are no adequate and well-controlled studies with Neozine hydrochloride in pregnant women, there are case reports of malformations in the offspring of women who were exposed to Neozine hydrochloride in combination with other antineoplastic agents during pregnancy. Neozine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 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 hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant. Neozine hydrochloride is teratogenic in the rat when given at doses approximately 4 to 13 times the maximum recommended human therapeutic dose of 6 mg/kg/day.
Nonteratogenic Effects
Neozine hydrochloride has not been adequately studied in animals for its effects on peri- and postnatal development. However, neurogenic tumors were noted in the offspring of rats given intravenous injections of 125 mg/kg of Neozine hydrochloride on day 22 of gestation. Compounds which inhibit DNA, RNA and protein synthesis might be expected to have adverse effects on peri- and postnatal development.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
The carcinogenicity of Neozine hydrochloride in mice, rats and monkeys has been reported in a considerable number of studies. Instances of a second nonlymphoid malignancy, including lung cancer and acute myelocytic leukemia, have been reported in patients with Hodgkin's disease treated with Neozine in combination with other chemotherapy and/or radiation. The risks of secondary lung cancer from treatment appear to be multiplied by tobacco use. The International Agency for Research on Cancer considers that there is “sufficient evidence” for the human carcinogenicity of Neozine hydrochloride when it is given in intensive regimens which include other antineoplastic agents but that there is inadequate evidence of carcinogenicity in humans given Neozine hydrochloride alone.
Mutagenesis
Neozine hydrochloride has been shown to be mutagenic in a variety of bacterial and mammalian test systems.
Impairment of Fertility
Azoospermia and antifertility effects associated with Neozine hydrochloride administration in combination with other chemotherapeutic agents for treating Hodgkin's disease have been reported in human clinical studies. Since these patients received multicombination therapy, it is difficult to determine to what extent Neozine hydrochloride alone was involved in the male germ-cell damage. The usual Segment I fertility/reproduction studies in laboratory animals have not been carried out with Neozine hydrochloride. However, compounds which inhibit DNA, RNA and/or protein synthesis might be expected to have adverse effects on gametogenesis. Unscheduled DNA synthesis in the testis of rabbits and decreased fertility in male mice treated with Neozine hydrochloride have been reported.
PRECAUTIONS
General
Undue toxicity may occur if Neozine is used in patients with impairment of renal and/or hepatic function. When appropriate, hospitalization for the initial course of treatment should be considered.
If radiation or a chemotherapeutic agent known to have marrow-depressant activity has been used, an interval of one month or longer without such therapy is recommended before starting treatment with Neozine. The length of this interval may also be determined by evidence of bone marrow recovery based on successive bone marrow studies.
Prompt cessation of therapy is recommended if any one of the following occurs:
- Central nervous system signs or symptoms such as paresthesias, neuropathies or confusion.
- Leukopenia.
- Thrombocytopenia (platelets under 100,000).
- Hypersensitivity reaction.
- Stomatitis - The first small ulceration or persistent spot soreness around the oral cavity is a signal for cessation of therapy.
- Diarrhea - Frequent bowel movements or watery stools.
- Hemorrhage or bleeding tendencies.
Bone marrow depression often occurs 2 to 8 weeks after the start of treatment. If leukopenia occurs, hospitalization of the patient may be needed for appropriate treatment to prevent systemic infection.
Information for Patients
Patients should be warned not to drink alcoholic beverages while on Neozine therapy since there may be an Antabuse (disulfiram)-like reaction. They should also be cautioned to avoid foods with known high tyramine content such as wine, yogurt, ripe cheese and bananas. Over-the-counter drug preparations which contain antihistamines or sympathomimetic drugs should also be avoided. Patients taking Neozine should also be warned against the use of prescription drugs without the knowledge and consent of their physician. Patients should be advised to discontinue tobacco use.
Laboratory Tests
Baseline laboratory data should be obtained prior to initiation of therapy. The hematologic status as indicated by hemoglobin, hematocrit, white blood count, differential, reticulocytes and platelets should be monitored closely - at least every 3 or 4 days.
Hepatic and renal evaluation are indicated prior to beginning therapy. Urinalysis, transaminase, alkaline phosphatase and blood urea nitrogen tests should be repeated at least weekly.
Drug Interactions
No cross-resistance with other chemotherapeutic agents, radiotherapy or steroids has been demonstrated.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Pregnancy
Pregnancy Category D. See WARNINGS section.
Nursing Mothers
It is not known whether Neozine is excreted in human milk. Because of the potential for tumorigenicity shown for Neozine hydrochloride in animal studies, mothers should not nurse while receiving this drug.
Pediatric Use
Undue toxicity, evidenced by tremors, coma and convulsions, has occurred in a few cases. Dosage, therefore, should be individualized. Very close clinical monitoring is mandatory.
ADVERSE REACTIONS
Leukopenia, anemia and thrombopenia occur frequently. Nausea and vomiting are the most commonly reported side effects.
Other adverse reactions are:
Hematologic
Pancytopenia; eosinophilia; hemolytic anemia; bleeding tendencies such as petechiae, purpura, epistaxis and hemoptysis.
Gastrointestinal
Hepatic dysfunction, jaundice, stomatitis, hematemesis, melena, diarrhea, dysphagia, anorexia, abdominal pain, constipation, dry mouth.
Neurologic
Coma, convulsions, neuropathy, ataxia, paresthesia, nystagmus, diminished reflexes, falling, foot drop, headache, dizziness, unsteadiness.
Cardiovascular
Hypotension, tachycardia, syncope.
Ophthalmic
Retinal hemorrhage, papilledema, photophobia, diplopia, inability to focus.
Respiratory
Pneumonitis, pleural effusion, cough.
Dermatologic
Herpes, dermatitis, pruritus, alopecia, hyperpigmentation, rash, urticaria, flushing.
Allergic
Generalized allergic reactions.
Genitourinary
Hematuria, urinary frequency, nocturia.
Musculoskeletal
Pain, including myalgia and arthralgia; tremors.
Psychiatric
Hallucinations, depression, apprehension, nervousness, confusion, nightmares.
Endocrine
Gynecomastia in prepubertal and early pubertal boys.
Miscellaneous
Intercurrent infections, hearing loss, pyrexia, diaphoresis, lethargy, weakness, fatigue, edema, chills, insomnia, slurred speech, hoarseness, drowsiness.
Second nonlymphoid malignancies (including lung cancer, acute myelocytic leukemia and malignant myelosclerosis) and azoospermia have been reported in patients with Hodgkin's disease treated with Neozine in combination with other chemotherapy and/or radiation. The risks of secondary lung cancer from treatment appear to be multiplied by tobacco use.
OVERDOSAGE
The major manifestations of overdosage with Neozine would be anticipated to be nausea, vomiting, enteritis, diarrhea, hypotension, tremors, convulsions and coma. Treatment should consist of either the administration of an emetic or gastric lavage. General supportive measures such as intravenous fluids are advised. Since the major toxicity of Neozine hydrochloride is hematologic and hepatic, patients should have frequent complete blood counts and liver function tests throughout their period of recovery and for a minimum of two weeks thereafter. Should abnormalities appear in any of these determinations, appropriate measures for correction and stabilization should be immediately undertaken.
The estimated mean lethal dose of Neozine hydrochloride in laboratory animals varied from approximately 150 mg/kg in rabbits to 1300 mg/kg in mice.
DOSAGE AND ADMINISTRATION
The following doses are for administration of the drug as a single agent. When used in combination with other anticancer drugs, the Neozine dose should be appropriately reduced, eg, in the MOPP regimen, the Neozine dose is 100 mg/m2 daily for 14 days. All dosages are based on the patient's actual weight. However, the estimated lean body mass (dry weight) is used if the patient is obese or if there has been a spurious weight gain due to edema, ascites or other forms of abnormal fluid retention.
Adults: To minimize the nausea and vomiting experienced by a high percentage of patients beginning Neozine therapy, single or divided doses of 2 to 4 mg/kg/day for the first week are recommended. Daily dosage should then be maintained at 4 to 6 mg/kg/day until maximum response is obtained or until the white blood count falls below 4000/cmm or the platelets fall below 100,000/cmm. When maximum response is obtained, the dose may be maintained at 1 to 2 mg/kg/day. Upon evidence of hematologic or other toxicity, the drug should be discontinued until there has been satisfactory recovery. After toxic side effects have subsided, therapy may then be resumed at the discretion of the physician, based on clinical evaluation and appropriate laboratory studies, at a dosage of 1 to 2 mg/kg/day.
Pediatric Patients: Very close clinical monitoring is mandatory. Undue toxicity, evidenced by tremors, coma and convulsions, has occurred in a few cases. Dosage, therefore, should be individualized. The following dosage schedule is provided as a guideline only.
Fifty (50) mg per square meter of body surface per day is recommended for the first week. Dosage should then be maintained at 100 mg per square meter of body surface per day until maximum response is obtained or until leukopenia or thrombocytopenia occurs. When maximum response is attained, the dose may be maintained at 50 mg per square meter of body surface per day. Upon evidence of hematologic or other toxicity, the drug should be discontinued until there has been satisfactory recovery, based on clinical evaluation and appropriate laboratory tests. After toxic side effects have subsided, therapy may then be resumed.
Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.1-6 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
HOW SUPPLIED
Capsules, ivory, containing the equivalent of 50 mg Neozine as the hydrochloride; in bottles of 100 (NDC 54482-053-01). Imprint on capsules: Neozine σ sigma-tau.
REFERENCES
- Recommendations for the safe handling of parenteral antineoplastic drugs. Washington, DC: U.S. Government Printing Office NIH Publication No. 83-2621.
- AMA Council Report. Guidelines for handling parenteral antineoplastics. JAMA. Mar 15, 1985; 253:1590-1592.
- National Study Commission on Cytotoxic Exposure: Recommendations for handling cytotoxic agents. Available from Louis P. Jeffrey, ScD, Director of Pharmacy Services, Rhode Island Hospital, 593 Eddy Street, Providence, Rhode Island 02902.
- Clinical Oncological Society of Australia: Guidelines and recommendations for safe handling of antineoplastic agents. Med J Aust. Apr 30,1983; 1:426-428.
- Jones RB, Frank R, Mass T: Safe handling of chemotherapeutic agents: a report from the Mount Sinai Medical Center. CA. Sept-Oct 1983; 33:258-263.
- ASHP technical assistance bulletin on handling cytotoxic drugs in hospitals. Am J Hosp Pharm. Jan 1985; 42:131-137.
NDC 54482-053-01
Neozine®
(PROCARBAZINE HYDROCHLORIDE)
50 mg
Each capsule contains 50 mg Neozine
in the form of the hydrochloride salt.
Rx only
100 Capsules
sigma-tau
Dispense in tight, light-resistant containers as
defined in USP/NF.
Store at 59° to 86°F (15° to 30°C).
LOT EXP.
M7-07/16 PC3986C
Usual
Dosage: See package insert.
Mfd. for: Sigma-Tau Pharmaceuticals, Inc.,
Gaithersburg, MD 20878 Mfd. by: Alcami Corporation
1726 North 23rd St., Wilmington, NC 28405
Bottle Label
Neozine pharmaceutical active ingredients containing related brand and generic drugs:
Neozine available forms, composition, doses:
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.