Megestrol

Warning

H361fd (100%): Suspected of damaging fertility; Suspected of damaging the unborn child [Warning Reproductive toxicity]

P203, P280, P318, P405, and P501 (click each P-code to see the statement)

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Megestrol acetate tablets. ... The drug is used in female dogs for the postponement of estrus and the alleviation of false pregnancy. /Megestrol acetate/

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including megestrol acetate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Megestrol acetate/

The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Megestrol acetate is included on this list. /Megestrol acetate/

Lonning PE et al; Clinical Pharmacokinetics of Endocrine Agents Used in Advanced Breast Cancer; Clin Pharmacokinet 22 (5): 327-58 (1992).

Schacter L et al; Megestrol Acetate: Clinical Experience; Cancer Treat Rev 16 (1): 49-63 (1989)

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Methods for transporting hazardous drugs to the health-care setting should be consistent with environmental protection and national or local regulations for transporting hazardous substances. When hazardous drugs are being transported to the home-care setting, appropriate containers (eg, lined cardboard boxes) and procedures should be used to prevent breakage and contain leakage. ... The drugs must be securely capped or sealed and properly packaged and protected during transport to reduce further the chance of breakage and spillage in a public area such as a corridor or elevator. /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/

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

/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/

For more Disposal Methods (Complete) data for MEGESTROL (9 total), please visit the HSDB record page.

/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 MEGESTROL (19 total), please visit the HSDB record page.

/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/

Progestins may cause amenorrhea and/or galactorrhea, interfering with effects of bromocriptine; concurrent use is not recommended. /Progestins/

/Investigators/ evaluated the multidrug resistance modulating effects of progesterone and an orally active, structurally related compound, megestrol acetate, in several multidrug resistance human cell lines. At 100 uM, both steroids inhibited the binding of a Vinca alkaloid photoaffinity analog to p-glycoprotein in multidrug resistance human neuroblastic SH-SY5Y/VCR cells (which show treater than 1500 fold resistance to vincristine in the tetrazolium dye assay). However, 100 uM markedly enhanced the binding of (3)H azidopine to p-glycoprotein. Megestrol acetate at low doses was more effective than progesterone in sensitizing cells to vincristine and enhancing their accumulation of (3)H vincristine. The highly resistant SH-SY5Y/VCR subline exhibited significant collateral sensitivity to both steroids. These data suggest that megestrol acetate may be a clinically useful modulator of multidrug resistance.

The most common side effects of megestrol are weight gain and an increase in appetite. Adverse effects include nausea, vomiting, rash, diarrhea, vaginal bleeding, edema, dyspnea, hypogonadism, hyperglycemia, fluid retention, loss of libido, and hypertension. A severe adverse effect is an increased risk for venous thromboembolic events such as thrombophlebitis and deep venous thrombosis due to increased coagulopathy.

Generally, toxicity to megestrol is very mild, rated on a scale of Grade 0 or 1. No serious adverse drug reactions have resulted from megestrol acetate administered in dosages as high as 1200 mg/day. Clinicians should properly adjust the dosage of megestrol to prevent toxicity for patients with comorbidities involving hepatic and cardiovascular disease. Secondary adrenal insufficiency also serves as an indicator of toxicity after the withdrawal of long-term treatment. No antidote currently exists for an overdose of megestrol. Supportive treatment should be provided to patients experiencing overdose symptoms such as diarrhea, nausea, and shortness of breath. According to product labeling, it is unknown whether megestrol can be removed by dialysis or not, but due to low solubility, it is hypothesized that it is potentially dialyzable.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ There is no method available for routine monitoring of personnel for evidence of hazardous drug exposure. Tests for the presence of mutagens or chromosomal damage are not drug specific and are of value only in controlled studies. Chemical analysis of urine for the presence of hazardous drugs at the sensitivity level needed to detect occupational exposure is limited to a few drugs and is not yet commercially available. /Antineoplastic agents/

/HUMAN EXPOSURE STUDIES/ ... Little is known about the acute effects of megestrol on the hypothalamic-pituitary-adrenal (HPA) axis. As part of an endocrine study, /investigators/ evaluated the acute effects of megestrol, hydrocortisone and placebo on morning cortisol and ACTH levels. Using a balanced double-blind design, ten healthy male subjects were treated at 11:00 p.m. and 8:00 a.m. with megestrol (total dose 320 mg), hydrocortisone (total dose 30 mg) or placebo. After 1 hr of rest, blood was drawn at 10:00 a.m. and 10:30 a.m. for determination of cortisol and ACTH levels. Compared to placebo, acute administration of megestrol resulted in a significant decrease in morning ACTH and cortisol levels. The suppression of ACTH after pretreatment with megestrol was less pronounced than after pretreatment with hydrocortisone. /These/ results suggest that megestrol exerts glucocorticoid-like effects and has an acute depressing effect on the HPA axis. Therefore alterations in the steroid system should be included in the differential diagnosis of all subjects under treatment with megestrol.

/SIGNS AND SYMPTOMS/ No serious unexpected adverse effects were reported in patients with AIDS-related cachexia or with breast cancer receiving megestrol acetate dosages up to 1200 or 1600 mg daily, respectively. It is not known if megestrol acetate is removed by dialysis; however, the manufacturer states that because of the low solubility of the drug, megestrol acetate probably is not removed by this procedure.

/CASE REPORTS/ ... An 80-year-old woman with worsening dyspnea was transferred to our university-affiliated community medical center from an inpatient psychiatric facility, where she was being treated for major depressive disorder with psychotic features. She had undergone a general decline in physical function accompanied by some weight loss and anorexia consistent with failure to thrive and, 1 month earlier, had been started on MA 400 mg/d to stimulate her appetite and improve her nutrition. During hospitalization at our center, the patient's dyspnea worsened and she was transferred to the intensive care unit, where she was intubated. While in the intensive care unit, the patient developed hypotension. Infectious, cardiac, and neurologic causes of hypotension having been ruled out, a cosyntropin stimulation test was performed to rule out adrenal insufficiency. Cortisol levels before, 30 minutes after, and 60 minutes after administration of cosyntropin were 1.6, 7.1, and 9.8 ug/dL, respectively, indicating a suboptimal response. The adrenocorticotropic hormone level was 8 pg/mL (normal, 10-60 pg/mL). Based on these findings suggesting adrenal insufficiency, MA was discontinued and steroid replacement was initiated. The patient's blood pressure normalized and she improved slowly. She was weaned from the ventilator several weeks later and was discharged to a skilled nursing facility. At 2-month follow-up, the patient's strength and respiratory function were improved, and the results of a repeat cosyntropin stimulation test were normal (cortisol response before, 30 minutes after, and 60 minutes after cosyntropin administration: 15.4, 22.6, and 25.2 ug/dL, respectively). The Naranjo score for this case was 7, indicating a probable correlation between MA use and adrenal insufficiency. ...

/CASE REPORTS/ ... /The authors/ describe 2 patients who recently presented to our Metabolic Bone Disease Clinic with severe osteoporosis complicated by multiple vertebral fractures experienced while the patients were receiving high-dose megestrol therapy. The patients had evidence of adrenal axis suppression but recovered fully after megestrol was discontinued. /Investigators/ speculate that megestrol was an important factor in the development of osteoporosis and subsequent fractures. Further study is warranted to clarify the relationship between megestrol and its potential for adversely affecting the skeleton.

For more Human Toxicity Excerpts (Complete) data for MEGESTROL (14 total), please visit the HSDB record page.

/LABORATORY ANIMALS: Acute Exposure/ Oral administration of large, single doses of megestrol acetate (5 g/kg) did not produce toxic effects in mice.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In female beagles receiving megestrol acetate dosages of 0.01, 0.1, or 0.25 mg/kg daily for 7 years, both benign and malignant breast tumors occurred. No tumors were reported in female monkeys receiving megestrol acetate dosages of 0.01, 0.1, or 0.5 mg/kg daily for 10 years. Pituitary tumors were observed in female rats receiving megestrol acetate dosages of 3.9 or 10 mg/kg daily for 2 years.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ A 4-year evaluation of the chronic toxicity of megestrol acetate in dogs is reported. 0.01, 0.1 or 0.25 mg of megestrol acetate/kg/day or 0.25 mg of chlormadinone acetate/kg/day was administered orally for 4 years to female beagle dogs. The hormone-treated dogs tended to gain more weight than did the controls (controls vs. 0.25 mg megestrol acetate every month after the 3rd p less than 0.01). All treated dogs revealed decreased evidence of estrus. Mucoid vaginal discharges were more prevalent among the middle and high dose groups. Mean hemoglobin, packed cell volume and total erythrocyte values were slightly decreased while mean total leucocyte count and erythrocyte sedimentation rates were slightly increased in the middle and high dose groups. Clotting mechanism did not reveal any disturbances. Evidence of diabetes consisting of bilateral cataracts, elevated serum glucose concentrations and glycosuria after 4 years in 2 of 16 high-dose megestrol acetate and in 6 of 15 chlormadinone acetate-treated dogs was revealed. It is concluded that the effects of megestrol acetate were similar but less severe than those of chlormadinone acetate.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Reproduction studies in female rats using megestrol acetate dosages of 0.05-12.5 mg/kg daily (lower than the recommended (13.3 mg/kg daily) dosages in humans) have revealed evidence of impaired fertility in male offspring of mothers receiving megestrol acetate; similar results were obtained in dogs.

For more Non-Human Toxicity Excerpts (Complete) data for MEGESTROL (9 total), please visit the HSDB record page.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

Megestrol acetate tablets. ... The drug is used in female dogs for the postponement of estrus and the alleviation of false pregnancy. /Megestrol acetate/

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including megestrol acetate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Megestrol acetate/

The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Megestrol acetate is included on this list. /Megestrol acetate/

L02AB01

G - Genito urinary system and sex hormones

L - Antineoplastic and immunomodulating agents

G - Genito urinary system and sex hormones

QG - Genito urinary system and sex hormones

QL - Antineoplastic and immunomodulating agents

Megestrol acetate shares the actions of the progestins: induction of secretory changes in the endometrium, increase in basal body temperature, pituitary inhibition, and production of withdrawal bleeding in the presence of estrogen. In animals, the drug suppresses ovulation and produces antigonadotrophic, antiuterotrophic and antiandrogenic/antimyotrophic effects. It has slight glucocorticoid activity and a very slight degree of mineralocorticoid activity. Megestrol acetate has no estrogenic, androgenic, or anabolic activity.

While the precise mechanism by which megestrol acetate produces its antineoplastic effects against endometrial carcinoma is unknown at the present time, inhibition of pituitary gonadotrophin production and resultant decrease in estrogen secretion may be factors. There is evidence to suggest a local effect as a result of the marked changes brought about by the direct instillation of progestational agents into the endometrial cavity. The antineoplastic action of megestrol acetate on carcinoma of the breast is effected by modifying the action of other steroid hormones and by exerting a direct cytotoxic effect on tumor cells. In metastatic cancer, hormone receptors may be present in some tissues but not others. The receptor mechanism is a cyclic process whereby estrogen produced by the ovaries enters the target cell, forms a complex with cytoplasmic receptor and is transported into the cell nucleus. There it induces gene transcription and leads to the alteration of normal cell functions. Pharmacologic doses of megestrol acetate not only decrease the number of hormone-dependent human breast cancer cells but also are capable of modifying and abolishing the stimulatory effects of estrogen on these cells. It has been suggested that progestins may inhibit in one of two ways: by interfering with either the stability, availability, or turnover of the estrogen receptor complex in its interaction with genes or in conjunction with the progestin receptor complex, by interacting directly with the genome to turn off specific estrogen-responsive genes.

The precise mechanism for megestrol-induced weight gain has not been clearly established; however, evidence from clinical studies indicates that the increase in body weight observed during megestrol therapy is related to the drug's appetite-stimulant or metabolic effects rather than its glucocorticoid-like effects or the production of edema. It has been suggested that megestrol and/or its metabolites may, either directly or indirectly, stimulate appetite resulting in weight gain or may alter metabolic pathways via interference with the production or action of mediators such as cachectin (a hormone that inhibits adipocyte lipogenic enzymes).

Splenic macrophage Fc gamma receptors participate in the pathophysiology of immune cytopenias, and in such disorders, the beneficial effects of glucocorticoids are in part mediated by decreased expression of macrophage Fc gamma receptors. In the animal model, progesterones, like glucocorticoids, inhibit expression of these receptors. Megestrol acetate (MA) is a progesterone frequently used for treating human immunodeficiency virus (HIV)-associated anorexia-cachexia. Twenty-eight patients with HIV-associated thrombocytopenia with shortened platelet survival and increased platelet-associated immunoglobulin G (IgG) who were being treated with MA for anorexia-cachexia were prospectively studied for a 6-month period to assess the potential role of progesterones in the treatment of immune thrombocytopenia. Treatment with MA for non-consecutive periods of 2 months and 1 month significantly increased platelet count and platelet survival without significant alteration of platelet-associated immunoglobulin levels. Of the 28 patients studied, 22 presented a complete response, 19 presented a complete response 1 month after finishing the MA treatment regimen, and 12 remained in complete response for a further month. Expression of Fc gamma receptors (Fc gamma RI and Fc gamma RII) by peripheral blood monocytes and the in vitro recognition of IgG-sensitized cells by monocytes were significantly decreased by the MA treatment. Decreased expression and functioning of these receptors significantly correlated with platelet counts and survival times, but no relationship was found with platelet-associated immunoglobulin, circulating immune complexes, body mass index, plasma HIV load, or CD4 lymphocyte levels. These results suggest that treatment with progesterones, like MA, may be an alternative therapy for immune cytopenias, with few side effects.

For more Mechanism of Action (Complete) data for MEGESTROL (6 total), please visit the HSDB record page.

Megestrol acetate appears to be completely metabolized in the liver to free steroids and glucuronide conjugates of 17alpha-acetoxy-2alpha-hydroxy-6-methylpregna-4,6-diene-3,20-dione, 17alpha-acetoxy-6-hydroxymethylpregna-4,6-diene-3,20-dione, and 17alpha-acetoxy-2alpha-hydroxy-6-hydroxymethylpregna-4,6-diene-3,20-dione.

Completely metabolized in liver to free steroids and glucuronide conjugates of 17alpha-acetoxy-2alpha-hydroxy-6-methylpregna-4,6-diene-3,20-dione, 17alpha-acetoxy-6-hydroxymethylpregna-4,6-diene-3,20-dione, & 17alpha-acetoxy-2alpha-hydroxy-6-hydroxymethylpregna-4,6-diene-3,20-dione /Human, oral/

EA6LD1M70M

MEGESTROL

Chemical Structure [CS] - Progesterone Congeners

Established Pharmacologic Class [EPC] - Progestin

Megestrol is a Progestin.

Oral contraceptives which owe their effectiveness to hormonal preparations.

Oral contraceptives which owe their effectiveness to synthetic preparations.

Antineoplastic agents that are used to treat hormone-sensitive tumors. Hormone-sensitive tumors may be hormone-dependent, hormone-responsive, or both. A hormone-dependent tumor regresses on removal of the hormonal stimulus, by surgery or pharmacological block. Hormone-responsive tumors may regress when pharmacologic amounts of hormones are administered regardless of whether previous signs of hormone sensitivity were observed. The major hormone-responsive cancers include carcinomas of the breast, prostate, and endometrium; lymphomas; and certain leukemias. (From AMA Drug Evaluations Annual 1994, p2079)

Megestrol acetate appears to be well absorbed from the GI tract. The relative oral bioavailability of megestrol acetate suspensions and tablets has not been evaluated.

Plasma megestrol acetate concentrations achieved with a 625-mg dose of the more concentrated oral suspension (Megace ES 625 mg/5 mL) are equivalent to those achieved with an 800-mg dose of the original formulation (200 mg/5 mL) under fed conditions.

The effect of food on the bioavailability of Megestrol Acetate Oral Suspension has not been evaluated.

Peak concentrations and AUC were 54.8 and 43.3% higher, respectively, under fed conditions compared with fasting for the concentrated suspension and were 12.9 and 24.4% higher, respectively, under fed conditions compared with fasting for the original formulation.

For more Absorption, Distribution and Excretion (Complete) data for MEGESTROL (13 total), please visit the HSDB record page.

MEDICATION

MEDICATION (VET)

Use (kg; approx.) in Germany (2009): >25

Reported impurities include: 6,17a-dimethyl-3,17-dioxo-D-homoandrosta-4,6-dien-17aalpha-yl acetate (D-homo megestrol acetate), 6alpha-methyl-3,20-dioxopregn-4-en-17-yl acetate (medroxyprogesterone acetate), 6-methyl-3,20-dioxopregna-1,4,6-trien-17-yl acetate, 6-methylene-3,20-dioxopregn-4-en-17-yl acetate (6-methylene hydroxyprogesterone acetate) and 6-methyl-17-hydroxypregna-4,6-diene-3,20-dione (megestrol). /Megestrol acetate/

Megestrol acetate is commercially available as oral tablets and as oral suspensions; the 2 concentrations of the oral suspensions differ in formulation and are not bioequivalent.

NIAGESTIN, OVABAN. MIXT WITH ETHYNYLESTRADIOL: CO-ERVONUM, KOMBIQUENS, NOVAL, NUVACON, OVEX, PLANOVIN, TRI-ERVONUM, VOLIDAN, WERADYS; MIXT WITH MESTRANOL: DELPREGNIN. /MEGESTROL ACETATE/

MEGESTROL ACETATE (MEGACE) IS AVAIL IN 20-MG TABLETS. /ACETATE/

Oral: Suspension: 40 mg of micronized megestrol acetate per mL, Megestrol (STAT RX USA LLC)

Oral: Tablets: 20 mg or 40 mg megestrol acetate, Megestrol Acetate (Barr Laboratories Inc).