Pipobroman

356.058

356.05

6Q99RDT97R

758461|25154

DTXSID7023485

C750

CRYSTALS|WHITE OR PRACTICALLY WHITE, CRYSTALLINE POWDER

L - Antineoplastic and immunomodulating agents

2933599090

40.6

1.1

Solid

1.691g/cm3

106-107 °C

487.1ºC at 760mmHg

248.4ºC

1.566

2.24e+00 g/L

LD50 orl-rat: 220 mg/kg IYKEDH 4,467,73

SLIGHTLY SHARP, FRUITY ODOR

SLIGHT BITTER TASTE

STABLE IN LIGHT & AIR

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All contaminated disposables should be contained in sealable bags for transfer to larger waste containers. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All bottles must be discarded as contaminated waste after decontamination of the biohazard cabinet. All protective apparel (gown, gloves, goggles, and respirator) should be discarded as contaminated waste. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The contaminated filters must be removed, bagged in thick plastic and prepared for disposal in a hazardous waste dump site or incinerator licensed by the Environmental Protection Agency (EPA). /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The gown should be removed and placed in a sealable container before removal of the inner gloves. The inner gloves should be removed last and placed in the container with the gown. /Antineoplastic agents/|For more Disposal Methods (Complete) data for PIPOBROMAN (7 total), please visit the HSDB record page.

|Danger|H315 (100%): Causes skin irritation [Warning Skin corrosion/irritation]|P201, P202, P261, P264, P271, P280, P281, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Protective apparel: Disposable closed-front gown or coveralls, disposable utility gloves over disposable latex gloves, NIOSH-approved air-purifying half-mask respirator equipped with a high efficiency filter, and eye protection should be worn. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Class 100 clean-air work stations, both horizontal and vertical airflow (with no containment characteristics), are inappropriate engineering controls for handling hazardous drugs because they provide no personnel protection and permit environmental contamination. Although there are no engineering controls designed specifically for the safe handling of hazardous chemicals as sterile products, Class II contained vertical-flow biological safety cabinets (biohazard cabinets) have been adopted for this use. Biohazard cabinetry is, however, designed for the handling of infectious agents, not hazardous chemicals. ... Based on design, ease of use, and cost considerations, Class II contained-vertical-flow biohazard cabinetry is currently recommended for use in preparing sterile doses of hazardous drugs. Class II cabinetry design and performance specifications are defined in NSF Standard 49. Biological safety cabinets selected for use with hazardous drugs should meet NSF Standard 49 specifications to ensure the maximum protection from these engineering controls. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers should wear powder free, disposable surgical latex gloves of good quality when preparing hazardous drugs. Selection criteria for gloves should include thickness (especially at the fingertips where stress is the greatest), fit, length, and tactile sensation. ... The practice of double gloving is supported by research that indicates that many glove materials vary in drug permeability even within lots; therefore, double gloving is recommended. ... In general, surgical latex gloves fit better, have appropriate elasticity for double gloving and maintaining the integrity of the glove-gown interface, and have sufficient tactile sensation (even during double gloving) for stringent aseptic procedures. ... Powdered gloves should be avoided. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers who are not protected by the containment environment of a biohazard cabinet should use respiratory protection when handling hazardous drugs. Respiratory protection should be an adjunct to and not a substitute for engineering controls. Surgical masks of all types provide no respiratory protection against powdered or liquid aerosols of hazardous drugs. In situations where workers may be exposed to potential eye contact with hazardous drugs, an appropriate plastic face shield or splash goggles should be worn. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ During compounding of hazardous drugs (eg, crushing, dissolving, and preparing an ointment), workers should wear low permeability gowns and double gloves. Compounding should take place in a protective area such as a disposable glove box. If compounding must be done in the open, an area away from drafts and traffic must be selected, and the worker should use appropriate respiratory protection. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Spill kits containing all materials needed to clean up spills of hazardous drugs should be assembled or purchased. These kits should be readily available in all areas where hazardous drugs are routinely handled. If hazardous drugs are being prepared or administered in a nonroutine area (home setting or unusual patient-care area), a spill kit should be obtained by the drug handler. The kit should include two pairs of disposable gloves (one outer pair of utility gloves and one inner latex pair); low-permeability, disposable protective garments (coveralls or gown and shoe covers); safety glasses or splash goggles; respirator; absorbent, plastic-backed sheets or spill pads; disposable toweling; at least 2 sealable thick plastic hazardous waste disposal bags (prelabeled with an appropriate warning label); a disposable scoop for collecting glass fragments; and a puncture-resistant container for glass fragments. All individuals who routinely handle hazardous drugs must be trained in proper spill management and cleanup procedures. Spills and breakages must be cleaned up immediately according to the following procedures. If the spill is not located in a confined space, the spill area should be identified and other people should be prevented from approaching and spreading the contamination. Wearing protective apparel from the spill kit, workers should remove any broken glass fragments and place them in the puncture-resistant container. Liquids should be absorbed with a spill pad; powder should be removed with damp disposable gauze pads or soft toweling. The hazardous material should be completely removed and the area rinsed with water and then cleaned with detergent. The spill cleanup should proceed progressively from areas of lesser to greater contamination. The detergent should be thoroughly rinsed and removed. All contaminated materials should be placed in the disposal bags provided and sealed and transported to a designated containment receptacle. Spills occurring in the biohazard cabinet should be cleaned up immediately; a spill kit should be used if the volume exceeds 150 ml or the contents of one drug vial or ampule. If there is broken glass, utility gloves should be worn to remove it and place it in the puncture-resistant container located in the biohazard cabinet. The biological safety cabinet, including the drain spillage trough, should be thoroughly cleaned. If the spill is not easily and thoroughly contained, the biological safety cabinet should be decontaminated after cleanup. If the spill contaminates the high efficiency particulate air filter, use of the biological safety cabinet should be suspended until the cabinet has been decontaminated and the high efficiency particulate air filter replaced. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ If hazardous drugs are routinely prepared or administered in carpeted areas, special equipment is necessary to remove the spill. Absorbent powder should be substituted for pads or sheets and left in place on the spill for the time recommended by the manufacturer. The powder should then be picked up with a small vacuum unit reserved for hazardous drug cleanup. The carpet should then be cleaned according to usual procedures. The vacuum bag should be removed and discarded or cleaned, and the exterior of the vacuum cleaner should be washed with detergent and rinsed before being covered and stored. The contaminated powder should be discarded into a sealable plastic bag and segregated with other contaminated waste materials. Alternatively, inexpensive wet or dry vacuum units may be purchased for this express use and used with appropriate cleaners. All such units are contaminated, once used, and must be cleaned, stored, and ultimately discarded /properly/ ... The circumstances and handling of spills should be documented. Health-care personnel exposed during spill management should also complete an incident report or exposure form. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Accidental contamination of the health-care environment, resulting in exposure of personnel, patients, visitors, and family members to hazardous substances, is prevented by maintaining the physical integrity and security of packages of hazardous drugs. 1. Access to all areas where hazardous drugs are stored is limited to specified authorized staff. 2. A method should be present for identifying to personnel those drugs that require special precautions (eg, cytotoxics). One way to accomplish this is to apply appropriate warning labels to all hazardous drug containers, shelves, and bins where the drug products are stored. ... 3. A method of identifying, for patients and family members, those drugs that require special precautions in the home should be in place. This may be accomplished in the health-care setting, by providing specific labeling for discharge medications, along with written instructions. 4. Methods for identifying shipping cartons of hazardous drugs should be required from manufacturers and distributors of these drugs. 5. Written procedures for handling damaged packages of hazardous drugs should be maintained. Personnel involved in shipping and receiving hazardous drugs should be trained in these procedures, including the proper use of protective garments and equipment. Damaged shipping cartons of hazardous drugs should be received and opened in an isolated area (eg, in a laboratory fume hood, if available, not in a vertical laminar airflow biological safety cabinet used for preparing sterile products). /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Facilities (eg, shelves, carts, counters, and trays) for storing hazardous drugs are designed to prevent breakage and to limit contamination in the event of leakage. Bins, shelves with barriers at the front, or other design features that reduce the chance of drug containers falling to the floor should be used. Hazardous drugs requiring refrigeration should be stored separately from nonhazardous drugs in individual bins designed to prevent breakage and to contain leakage. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Until the reproductive risks (or lack thereof) associated with handling hazardous drugs within a safety program have been substantiated, staff who are pregnant or breast-feeding should be allowed to avoid contact with these drugs. Policies should be in effect that provide these individuals with alternative tasks or responsibilities if they so desire. /Antineoplastic agents/|/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The pharmacy should provide access to information on toxicity, treatment of acute exposure (if available), chemical inactivators, solubility and stability of hazardous drugs (including investigational agents) used in the workplace. /Antineoplastic agents/|For more Preventive Measures (Complete) data for PIPOBROMAN (19 total), please visit the HSDB record page.

Symptoms of overdose include hematologic toxicity, especially with chronic overdosage.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The danger to health-care personnel from handling a hazardous drug stems from a combination of its inherent toxicity and the extent to which workers are exposed to the drug in the course of carrying out their duties. This exposure may be through inadvertent ingestion of the drug on foodstuffs (eg, workers' lunches), inhalation of drug dusts or droplets or direct skin contact. /Antineoplastic agents/

For the treatment of polycythaemia vera and refractory chronic myeloid leukaemia.

Antineoplastic Agents, Alkylating|...ANTINEOPLASTIC DRUG OF ALKYLATING TYPE. @ PRESENT ITS USE IS MAINLY LIMITED TO TREATMENT OF POLYCYTHEMIA VERA & CHRONIC GRANULOCYTIC LEUKEMIA. EVEN IN THESE DISORDERS...PIPOBROMAN IS GENERALLY NOT AS EFFECTIVE AS OLDER MODES OF TREATMENT.|...PIPOBROMAN IS HELD IN RESERVE FOR USE IN PATIENTS THAT HAVE BECOME REFRACTORY TO X-IRRADIATION & BUSULFAN IN CASE OF LEUKEMIA & PHLEBOTOMY & RADIOPHOSPHATE IN CASE OF POLYCYTHEMIA VERA.|Pipobroman is indicated mainly in the treatment of polycythemia vera. In the limited number of studies reported, there seems to be no difference in the therapeutic response between patients who had been under prior treatment with other drugs and those who had not. There are insufficient data available to provide a comparison of the effectiveness of pipobroman with conventional forms of treatment (radioactive phosphorus, phlebotomy, or other alkylating agents); however, it may be effective in patients with polycythemia vera who are refractory to these forms of therapy.|Although pipobroman has produced remission in chronic myelocytic (granulocytic) leukemia, the number of reported cases is too few to permit evaluation of the drug for this condition and its use is therefore reserved for patients whose disease is resistant to other therapy.

PATIENTS IN WHOM BONE MARROW FUNCTION IS STILL DEPRESSED FROM PREVIOUS IRRADIATION OR OTHER CYTOTOXIC CHEMOTHERAPY SHOULD NOT RECEIVE PIPOBROMAN. CLINICAL EXPERIENCE WITH THIS DRUG IS INSUFFICIENT TO RECOMMEND ITS USE IN CHILDREN UNDER 15 YR OF AGE.|PIPOBROMAN...SHOULD NOT BE ADMIN DURING PREGNANCY, SINCE THERE IS NO INFORMATION ON ITS POTENTIAL TERATOGENICITY.|Rash and adverse GI effects such as nausea, vomiting, abdominal cramping, diarrhea, and anorexia may occur. These adverse effects are usually transient, but may persist and necessitate cessation of therapy.|Pipobroman should not be administered to patients with bone marrow depression resulting from radiation therapy or cytotoxic chemotherapy.

Pipobroman is an antineoplastic agent. Specifically it is a piperazine derivative with a chemical structure close to that of many DNA alkylating agents. Pipobroman has well documented clinical activity against polycythemia vera and essential thrombocythemia.

A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026) (See all compounds classified as Antineoplastic Agents, Alkylating.)

Well absorbed from the GI tract.|The drug is well absorbed following oral administration. Studies of its distribution and fate in man have not been reported.

The mechanism of action is uncertain but pipobroman is thought to alkylate DNA leading to disruption of DNA synthesis and eventual cell death.|Pipobroman has been classified as a polyfunctional alkylating agent, but its precise mechanism of action is not known.

ADVERSE EFFECTS INCL SEVERE ANEMIA, IN PART OF HEMOLYTIC NATURE, & RETICULOCYTOSIS. LEUKOPENIA & THROMBOCYTOPENIA, OF COURSE, ARE RESULT OF INTENDED ACTION OF DRUG, BUT LEUKOCYTE COUNT SHOULD BE KEPT ABOVE 3000/CU MM & PLATELET COUNT ABOVE 100,000/CU MM.|ADVERSE GI REACTIONS (TRANSIENT NAUSEA, VOMITING, ABDOMINAL CRAMPS, & DIARRHEA) HAVE BEEN REPORTED INFREQUENTLY. RASH HAS BEEN OBSERVED IN A FEW PATIENTS.|Pipobroman is a highly toxic drug with a low therapeutic index, and a therapeutic response is not likely to occur without some evidence of toxicity. The drug must be used only under constant supervision by physicians experienced in therapy with cytotoxic agents.|Pipobroman's principal toxic effect is bone marrow depression resulting in leukopenia, thrombocytopenia, and anemia manifested by a reduction in hemoglobin of at least 2 g/dl. Depression of the bone marrow may not occur for 4 weeks or more after treatment is initiated. Usually, the temporary discontinuance of therapy with the drug has been effective in controlling toxicity; however, persistent cytopenia has been reported. Anemia may occur with total pipobroman dosage as low as 30 mg/kg and may be more severe at higher dosage. In most instances, leukopenia accompanies the anemia. Anemia usually has responded to dosage reduction and to blood transfusions in amounts sufficient to produce a hemoglobin level of at least 10 g/dl. A hemolytic process suggested by a rapid drop in hemoglobin, increased bilirubin concentrations, and reticulocytosis has been observed in several patients. If evidence of this hemolytic process develops, pipobroman therapy should be discontinued.

Pipobroman

DOSAGE FORMS--TABLETS NF: 10 & 25 MG.

DETERMINATION OF PIPERAZINE IN DRUGS BY GAS CHROMATOGRAPHY.|Method #961.17. Determination of piperazine in drugs by gravimetric method. /Piperazine/|Method #966.25. Determination of piperazine in drugs by near-infrared spectrophotometry. /Piperazine/

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients