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Megestrol

Megestrol

Indications, Uses, Dosage, Drugs Interactions, Side effects
Megestrol
Medicine Type :
Allopathy
Prescription Type:
Prescription Required
Approval :
DCGI (Drugs Controller General of India)
Schedule
Schedule H
Pharmacological Class:
Progestins,
Therapy Class:
Antineoplastic agent, Synthetic hormone,
Approved Countries
India, the United States, Canada, the United Kingdom, Germany, Australia, Japan and Brazil.

Megestrol is a natural hormone/ antineoplastic agent belonging to the pharmacological class of progestins.

Megestrol is FDA-approved for treating cachexia, anorexia,or unexplained weight loss in those patients with acquired immunodeficiency syndrome (AIDS) and for the palliative treatment of advanced breast cancer in postmenopausal women.

Megestrol is variably but well absorbed from the gastrointestinal tract. It enters breast milk and undergoes primarily hepatic metabolism. The major routes of elimination are urine (57-78%) and faeces (8-30%)

Infusion reactions such as swollen face, lips, mouth, tongue or throat and difficulty swallowing or breathing are Megestrol's most common side effects.

Megestrol is available as tablets and oral suspensions.

The molecule is available in India, the United States, Canada, the United Kingdom, Germany, Australia, Japan and Brazil.

Megestrol is a natural hormone/ antineoplastic agent belonging to the pharmacological class of progestins.

Megestrol acetate's progestin antitumor action may include suppressing luteinizing hormone by inhibiting pituitary function, while the exact method by which it has effects in anorexia and cachexia is yet unclear. Additionally, research indicates that the megestrol's ability to stimulate hunger or promote metabolism may have more of an impact on weight gain than its ability to mimic the actions of glucocorticoids or cause oedema. Megestrol may affect metabolic pathways by interfering with the synthesis or function of mediators such as cachectin, a hormone that inhibits the lipogenic enzymes in adipocytes.

Megestrol achieves peak plasma concentration within 1-3 hours when administered as a tablet and within 3-5 hours as a suspension.

Megestrol is available as tablets and oral suspensions.

Tablets: To be swallowed whole with water/liquid. Do not chew, crush or break it.

Oral suspension: Shake well before each use. Measure the dose carefully with the provided device and take it as directed.

The physician recommends taking this medication orally once daily, with or without meals.

  • Anorexia Nervosa
  • Breast cancer
  • Endometrial cancer
  • Breast cancer: Megestrol reduces breast cancer symptoms such as breast lumps, bloody nipple discharge, and changes to the texture or contour of the breast. It functions by modifying the body's synthesis of the hormones necessary for the development and metastasis of breast cancer. To stop the cancer from growing, it may also directly affect the tumour or interact with other hormones.
  • Endometrial cancer: A synthetic hormone called megestrol replicates the effects of progesterone, a hormone that is naturally present in females. It treats the signs and symptoms of endometrial cancer, a kind of cancer that starts in the lining of the womb and includes pain during sex, lower back pain, and irregular vaginal flow. It tampers with hormone synthesis and function, which are critical for the development and metastasis of endometrial cancer. In addition, it could directly affect the tumour to stop its growth or interact with other hormones.
  • Anorexia Nervosa: Patients with acquired immunodeficiency syndrome (AIDS) who have been diagnosed with anorexia, cachexia, or unexplained considerable weight loss are treated with megestrol. It works by facilitating appetite stimulation and weight gain. Its use helps regain weight, addressing nutritional inadequacies and related problems.
  • Megestrol is indicated palliatively to manage recurrent, inoperable, or metastatic breast cancer and endometrial cancer.
  • It is also indicated to treat cachexia, anorexia or unexplained significant weight loss in those patients diagnosed with acquired immunodeficiency syndrome (AIDS).

Orally: Administer megestrol tablets orally with or without food. Swallow the tablets whole with a full glass of water. Shake the oral suspension well before each use. Measure the prescribed dose accurately using the provided device. Take the suspension directly from the measuring device or mix it with a small amount of food or liquid. Do not take extra doses if a dosage is missed; take it as soon as you recall. As directed by the healthcare provider, adhere to the recommended dose standards.

The dosage and duration of treatment should be as per the treating physician's clinical judgment.

  • Tablet: 20mg, 40mg
  • Oral suspension: 200mg/5mL, 625mg/5mL

Megestrol is available as tablets and oral suspensions.

Dose Adjustment in Adult Patients:

Palliative treatment of breast cancer

As tab: 160 mg one day, either as a single dose or divided over a minimum of two months.

Palliative treatment of endometrial cancer

As tab: 40 to 320 mg daily in divided doses for at least two months.

Patients with AIDS or cancer may have anorexia and cachexia.

400–800 mg daily as a tablet or syrup with 40 mg/mL. As susp containing 125 mg/mL: 625 mg once daily. The mg-per-mg equivalents and interchangeability of megestrol suspensions are not included.

AIDS-related weight loss

400–800 mg per day as a tablet or syrup with 40 mg/mL. As susp containing 125 mg/mL: 625 mg once day. The mg-per-mg equivalents and interchangeability of megestrol suspensions are not included.

While on Megestrol, managing side effects is possible through dietary adjustments. A balanced diet should be consumed, and processed meats, fast food, fried foods, refined carbs, and added sugars should be avoided. Prevent constipation by drinking enough water and eating meals high in fibre. Add green vegetables, berries, yoghurt, citrus fruits, fatty fish, apples, peaches, broccoli, cauliflower, cabbage, beans, herbs, and spices to the diet. At the same time, refrain from smoking and limit alcohol consumption.

The dietary restriction should be individualized as per patient requirements.

  • History of severe hypersensitivity to Megestrol or any of the excipients.
  • Pregnancy known or suspected
  • Thrombophilia, breast cancer, and acute thrombophlebitis
  • May induce vaginal bleeding in women
  • Undiagnosed abnormal vaginal bleeding
  • Pregnancy Risk: Megestrol acetate users who are women of childbearing potential should take precautions to avoid becoming pregnant during treatment.
  • History of Thromboembolic Disease: Exercise caution in patients with a history of thromboembolic disease due to potential risks associated with megestrol acetate use.
  • Chronic Megestrol Acetate Use and Cushing's Syndrome: Prolonged use of megestrol acetate is associated with clinical cases of overt Cushing's Syndrome.
  • Adrenal Insufficiency: Clinical cases of adrenal insufficiency have been observed during chronic megestrol acetate use in both stressed and non-stressed states.
  • Diabetes Risk: Megestrol acetate therapy has been linked to the new onset and exacerbation of pre-existing diabetes, as reported in clinical cases.

Alcohol Warning

It is unsafe to consume Megestrol with alcohol.

Breast Feeding Warning

It is unsafe to use Megestrol during breastfeeding.

Pregnancy Warning

It is not recommended for use during pregnancy.

Food Warning

Consume leafy vegetables and fruits; avoid smoking, alcohol, and processed foods.
The adverse reactions related to Megestrol can be categorized as:
  • Common Adverse Effects: Weight gain, fluid retention, and increased appetite.
  • Less Common Adverse Effects: Nausea, insomnia, elevated blood sugar levels, mood changes and changes in libido.
  • Rare Adverse Effects: Severe allergic reactions, liver problems, or blood clots.
Reports on Postmarketing
Impotence, rash, and asthenia
The clinically relevant drug interactions of Megestrol are briefly summarized here.
  • This may lessen the anticoagulant and antidiabetic agent's therapeutic efficacy.
  • When coadministering with megestrol acetate, administration of a more significant dose of indinavir should be considered due to a considerable decrease in indinavir exposure.
The common side effects of Megestrol include
Increased appetite
Weight gain
Constipation
Increased glucose level in the blood
Shortness of breath
Reddening of the face and neck, or hot flushes
High blood pressure
Increased blood sugar levels
Rounded face
Swelling of a vein due to a blood clot
Pregnancy
ROUTE(S): PO: D For tablet; Use in cases where no safer medication is available, and life is in danger. Positive evidence of prenatal risk in humans.
ROUTE(S): PO: X For oral suspension; When pregnant, avoid using. The risks outweigh the potential benefits. There are safer alternatives available.
Before starting therapy, take a pregnancy test from women who are capable of bearing children. Tell women who are capable of bearing children to use an effective form of contraception while taking medication.
Advise a pregnant woman of potential danger to the fetus since there are no human data available to assess drug-associated risks of miscarriage, birth abnormalities, or severe maternal or fetal outcomes.
Before starting therapy, a pregnancy test is advised.
Advise women who are capable of bearing children to utilize an effective form of contraception while undergoing therapy, as it may cause damage to the fetus if given during pregnancy.
Animal data
Pregnant rats treated with low doses showed reductions in the weight of the fetus and number of live births, as well as feminization of male fetuses at doses below the maximum recommended clinical dosing based on body surface area. In addition, animal data suggest that megestrol acetate may cause potential harm to the fetus when administered to a pregnant woman and is contraindicated during pregnancy.
  • Nursing Mothers
Nursing should be stopped due to the possibility of adverse effects on the newborn.
The drug is present in human milk; there is no information on how the drug affects a breastfed infant or milk production; mothers receiving therapy are advised not to breastfeed due to the risk of HIV-1 transmission and the potential for adverse effects on a breastfed infant.
  • Pediatric Use
As per FDA, the safety and effectiveness of Megestrol in pediatric patients have not been established.
Dose Adjustment in Kidney Impairment Patients:
When renal function is normal, 57–78% of the medication is eliminated in the urine after ten days, so use cautiously.
Dose Adjustment in Hepatic Impairment Patients:
Megestrol should be used with caution in patients with severe liver disease. Dose adjustment may be needed.
The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of Megestrol.
Signs and Symptoms
Overconsumption of Megestrol could lead to diarrhoea, cough, unsteady gait, nausea, abdominal pain, shortness of breath, listlessness, and chest pain.
Management
There is no specific antidote for overdose with megestrol. In case of an overdose, appropriate supportive measures should be taken immediately. Megestrol has not been tested for dialyzability; however, due to its low solubility, it is indicated that dialysis would not be an effective method of treating overdose.
Pharmacodynamics:
The physiologic effects of megestrol, a synthetic progestin, are identical to natural progesterone. The effects include generating secretory alterations in the endometrium, elevation of basal body temperature, suppression of the pituitary gland, and induction of withdrawal bleeding when estrogen is present. Mestrogel has minimal mineralocorticoid action in addition to very slight glucocorticoid activity. This medication lacks any anabolic, androgenic, or estrogenic properties.
Pharmacokinetics:
  • Absorption: Although absorption might vary, megestrol is well absorbed from the gastrointestinal system.
  • Distribution: It may affect nursing infants as it enters into breast milk.
  • Metabolism: It primarily takes place in the liver. About 5–8% of the given dosage shows up in urine as recognized metabolites. No apparent active metabolites have been found.
  • Excretion: In humans, urine accounts for 57–78% of elimination (including 5-8% as metabolites) and faeces (8–30%) for most of elimination. For tablets, the elimination half-life is around 15-20 hours, while for suspension, it is 20–50 hours.
  • Ruiz-García V, López-Briz E, Carbonell-Sanchis R, Bort-Martí S, Gonzálvez-Perales JL. Megestrol acetate for cachexia-anorexia syndrome. A systematic review. J Cachexia Sarcopenia Muscle. 2018 Jun;9(3):444-452. doi: 10.1002/jcsm.12292. Epub 2018 Mar 14. PMID: 29542279; PMCID: PMC5989756.
  • Westman G, Bergman B, Albertsson M, Kadar L, Gustavsson G, Thaning L, Andersson M, Straumits A, Jeppson B, Lindén CJ, Ewers SB, Andersson H, Mercke C, Hafström L, Birck O, Orgum P. Megestrol acetate in advanced, progressive, hormone-insensitive cancer. Effects on the quality of life: a placebo-controlled, randomised, multicentre trial. Eur J Cancer. 1999 Apr;35(4):586-95. doi: 10.1016/s0959-8049(98)00398-0. PMID: 10492632.
  • De Conno F, Martini C, Zecca E, Balzarini A, Venturino P, Groff L, Caraceni A. Megestrol acetate for anorexia in patients with far-advanced cancer: a double-blind controlled clinical trial. Eur J Cancer. 1998 Oct;34(11):1705-9. doi: 10.1016/s0959-8049(98)00219-6. PMID: 9893656.
  • Vadell C, Seguí MA, Giménez-Arnau JM, Morales S, Cirera L, Bestit I, Batiste E, Blanco R, Jolis L, Boleda M, Antón I. Anticachectic efficacy of megestrol acetate at different doses and versus placebo in patients with neoplastic cachexia. Am J Clin Oncol. 1998 Aug;21(4):347-51. doi: 10.1097/00000421-199808000-00006. PMID: 9708631.
  • https://www.ncbi.nlm.nih.gov/books/NBK559205/
  • US Food and Drug Administration (FDA) [Internet]. Maryland. USA; Package leaflet information for the user; Megace (megestrol acetate)
  • https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020264s017lbl.pdf
  • April Hazard Vallerand, Cynthia A. Sanoski. [link]. Sixteenth Edition. Philadelphia, China: F. A. Davis Company; 2019: Page No 808-809
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Chumbeni
Dr. Chumbeni E Lotha has completed her Bachelor of Pharmacy from RIPANS, Mizoram and Doctor of Pharmacy from SGRRU,Dehradun. She can be reached at editorial@medicaldialogues.in
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Dr JUHI SINGLA
Dr JUHI SINGLA has completed her MBBS from Era’s Lucknow Medical college and done MD pharmacology from SGT UNIVERSITY Gurgaon. She can be contacted at editorial@medicaldialogues.in. Contact no. 011-43720751
Published on: 28 Jan 2024 7:59 AM GMT
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