Megestrol acetate 40 mg liquid

Megace

SIDE EFFECTS

Clinical Adverse Events

Adverse events which occurred in at least 5% of patients in any arm of the two clinical efficacy trials and the open trial are listed below by treatment group. All patients listed had at least one post baseline visit during the 12 study weeks. These adverse events should be considered by the physician when prescribing MEGACE Oral Suspension.

ADVERSE EVENTS

Megestrol Acetate, mg/day
No. of Patients
T rial 1
(N=236)
Trial 2
(N=87)
Open Label Trial
Placebo
0 N=34
100
N=68
400
N=69
800
N=65
Placebo 0
N=38
800
N=49
1200
N=176
Diarrhea 15 13 8 15 8 6 10
Impotence 3 4 6 14 0 4 7
Rash 9 9 4 12 3 2 6
Flatulence 9 0 1 9 3 10 6
Hypertension 0 0 0 8 0 0 4
Asthenia 3 2 3 6 8 4 5
Insomnia 0 3 4 6 0 0 1
Nausea 9 4 0 5 3 4 5
Anemia 6 3 3 5 0 0 0
Fever 3 6 4 5 3 2 1
Libido Decreased 3 4 0 5 0 2 1
Dyspepsia 0 0 3 3 5 4 2
Hyperglycemia 3 0 6 3 0 0 3
Headache 6 10 1 3 3 0 3
Pain 6 0 0 2 5 6 4
Vomiting 9 3 0 2 3 6 4
Pneumonia 6 2 0 2 3 0 1
Urinary Frequency 0 0 1 2 5 2 1

Adverse events which occurred in 1% to 3% of all patients enrolled in the two clinical efficacy trials with at least one follow-up visit during the first 12 weeks of the study are listed below by body system. Adverse events occurring less than 1% are not included. There were no significant differences between incidence of these events in patients treated with megestrol acetate and patients treated with placebo.

Body as a Whole: abdominal pain, chest pain, infection, moniliasis and sarcoma

Cardiovascular System: cardiomyopathy and palpitation

Digestive System: constipation, dry mouth, hepatomegaly, increased salivation and oral moniliasis

Hemic and Lymphatic System: leukopenia

Metabolic and Nutritional: LDH increased, edema and peripheral edema

Nervous System: paresthesia, confusion, convulsion, depression, neuropathy, hypesthesia and abnormal thinking

Respiratory System: dyspnea, cough, pharyngitis and lung disorder

Skin and Appendages: alopecia, herpes, pruritus, vesiculobullous rash, sweating and skin disorder

Special Senses: amblyopia

Urogenital System: albuminuria, urinary incontinence, urinary tract infection and gynecomastia

Postmarketing

Postmarketing reports associated with MEGACE Oral Suspension include thromboembolic phenomena including thrombophlebitis and pulmonary embolism, and glucose intolerance (see WARNINGS AND PRECAUTIONS).

Read the entire FDA prescribing information for Megace (Megestrol Acetate)

CLINICAL PHARMACOLOGY

Several investigators have reported on the appetite enhancing property of megestrol acetate and its possible use in cachexia. The precise mechanism by which megestrol acetate produces effects in anorexia and cachexia is unknown at the present time.

There are several analytical methods used to estimate megestrol acetate plasma concentrations, including gas chromatography-mass fragmentography (GC-MF), high pressure liquid chromatography (HPLC), and radioimmunoassay (RIA). The GC-MF and HPLC methods are specific for megestrol acetate and yield equivalent concentrations. The RIA method reacts to megestrol acetate metabolites and is, therefore, non-specific and indicates higher concentrations than the GC-MF and HPLC methods. Plasma concentrations are dependent, not only on the method used, but also on intestinal and hepatic inactivation of the drug, which may be affected by factors such as intestinal tract motility, intestinal bacteria, antibiotics administered, body weight, diet, and liver function.

The major route of drug elimination in humans is urine. When radiolabeled megestrol acetate was administered to humans in doses of 4 to 90 mg, the urinary excretion within 10 days ranged from 56.5% to 78.4% (mean 66.4%) and fecal excretion ranged from 7.7% to 30.3% (mean 19.8%). The total recovered radioactivity varied between 83.1% and 94.7% (mean 86.2%). Megestrol acetate metabolites which were identified in urine constituted 5% to 8% of the dose administered. Respiratory excretion as labeled carbon dioxide and fat storage may have accounted for at least part of the radioactivity not found in urine and feces.

Plasma steady-state pharmacokinetics of megestrol acetate were evaluated in 10 adult, cachectic male patients with acquired immunodeficiency syndrome (AIDS) and an involuntary weight loss greater than 10% of baseline. Patients received single oral doses of 800 mg/day of MEGACE Oral Suspension for 21 days. Plasma concentration data obtained on day 21 were evaluated for up to 48 hours past the last dose.

Mean (±1SD) peak plasma concentration (Cmax) of megestrol acetate was 753 (±539) ng/mL. Mean area under the concentration-time-curve (AUC) was 10476 (±7788) ng × hr/mL. Median Tmax value was five hours. Seven of 10 patients gained weight in three weeks.

Additionally, 24 adult, asymptomatic HIV seropositive male subjects were dosed once daily with 750 mg of MEGACE Oral Suspension. The treatment was administered for 14 days. Mean Cmax and AUC values were 490 (±238) ng/mL and 6779 (±3048) ng × hr/mL respectively. The median Tmax value was three hours. The mean Cmin value was 202 (±101) ng/mL. The mean percent of fluctuation value was 107 (±40).

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

Description Of Clinical Studies

The clinical efficacy of MEGACE Oral Suspension was assessed in two clinical trials. One was a multicenter, randomized, double-blind, placebo-controlled study comparing megestrol acetate (MA) at doses of 100 mg, 400 mg, and 800 mg per day versus placebo in AIDS patients with anorexia/cachexia and significant weight loss. Of the 270 patients entered on study, 195 met all inclusion/exclusion criteria, had at least two additional post baseline weight measurements over a 12-week period, or had one post baseline weight measurement but dropped out for therapeutic failure. The percent of patients gaining five or more pounds at maximum weight gain in 12 study weeks was statistically significantly greater for the 800 mg (64%) and 400 mg (57%) MA-treated groups than for the placebo group (24%). Mean weight increased from baseline to last evaluation in 12 study weeks in the 800 mg MA-treated group by 7.8 pounds, the 400 mg MA group by 4.2 pounds, the 100 mg MA group by 1.9 pounds, and decreased in the placebo group by 1.6 pounds. Mean weight changes at 4, 8, and 12 weeks for patients evaluable for efficacy in the two clinical trials are shown graphically. Changes in body composition during the 12 study weeks as measured by bioelectrical impedance analysis showed increases in nonwater body weight in the MA-treated groups (see Clinical Studies table). In addition, edema developed or worsened in only 3 patients.

Greater percentages of MA-treated patients in the 800 mg group (89%), the 400 mg group (68%), and the 100 mg group (72%), than in the placebo group (50%), showed an improvement in appetite at last evaluation during the 12 study weeks. A statistically significant difference was observed between the 800 mg MA-treated group and the placebo group in the change in caloric intake from baseline to time of maximum weight change. Patients were asked to assess weight change, appetite, appearance, and overall perception of well-being in a 9-question survey. At maximum weight change, only the 800 mg MAtreated group gave responses that were statistically significantly more favorable to all questions when compared to the placebo-treated group. A dose response was noted in the survey with positive responses correlating with higher dose for all questions.

The second trial was a multicenter, randomized, double-blind, placebo-controlled study comparing megestrol acetate 800 mg/day versus placebo in AIDS patients with anorexia/cachexia and significant weight loss. Of the 100 patients entered on study, 65 met all inclusion/exclusion criteria, had at least two additional post baseline weight measurements over a 12-week period or had one post baseline weight measurement but dropped out for therapeutic failure. Patients in the 800 mg MA-treated group had a statistically significantly larger increase in mean maximum weight change than patients in the placebo group. From baseline to study week 12, mean weight increased by 11.2 pounds in the MA-treated group and decreased 2.1 pounds in the placebo group. Changes in body composition as measured by bioelectrical impedance analysis showed increases in non-water weight in the MA-treated group (see Clinical Studies table). No edema was reported in the MA-treated group. A greater percentage of MA-treated patients (67%) than placebo-treated patients (38%) showed an improvement in appetite at last evaluation during the 12 study weeks; this difference was statistically significant. There were no statistically significant differences between treatment groups in mean caloric change or in daily caloric intake at time to maximum weight change. In the same 9-question survey referenced in the first trial, patients’ assessments of weight change, appetite, appearance, and overall perception of well-being showed increases in mean scores in MA-treated patients as compared to the placebo group.

In both trials, patients tolerated the drug well and no statistically significant differences were seen between the treatment groups with regard to laboratory abnormalities, new opportunistic infections, lymphocyte counts, T4 counts, T8 counts, or skin reactivity tests (see ADVERSE REACTIONS).

MEGACE (megestrol acetate, USP) Oral Suspension Clinical Efficacy Trials

Trial 1 Study Accrual Dates 11/88 to 12/90 Trial 2 Study Accrual Dates 5/89 to 4/91
Megestrol Acetate, mg/day 0 100 400 800 0 800
Entered Patients 38 82 75 75 48 52
Evaluable Patients 28 61 53 53 29 36
Mean Change in Weight (lb.)
Baseline to 12 Weeks 0.0 2.9 9.3 10.7 -2.1 11.2
% Patients > 5-Pound Gain at Last Evaluation in 12 Weeks 21 44 57 64 28 47
Mean Changes in Body Composition*
Fat Body Mass (lb.) 0.0 2.2 2.9 5.5 1.5 5.7
Lean Body Mass (lb.) -1.7 -0.3 1.5 2.5 -1.6 -0.6
Water (liters) -1.3 -0.3 0.0 0.0 -0.1 -0.1
% Patients With Improved Appetite
At Time of Maximum Wt. Change
At Last Evaluation in 12 50 72 72 93 48 69
Weeks 50 72 68 89 38 67
Mean Change in Daily Caloric Intake:
Baseline to Time of Maximum
Weight Change -107 326 308 646 30 464
* Based on bioelectrical impedance analysis determinations at last evaluation in 12 weeks

Presented below are the results of mean weight changes for patients evaluable for efficacy in Trials 1 and 2.

Animal Toxicology

Long-term treatment with MEGACE may increase the risk of respiratory infections. A trend toward increased frequency of respiratory infections, decreased lymphocyte counts, and increased neutrophil counts was observed in a 2-year chronic toxicity/carcinogenicity study of megestrol acetate conducted in rats.

Megestrol by AA Pharma

How does this medication work? What will it do for me?

Megestrol belongs to a group of medications known as progestogens. Megestrol is used to treat prostate cancer because testosterone is needed by prostate cancer cells for growth. It prevents the release of a hormone required for production of testosterone in the testicles.

Megestrol also slows the growth of breast and endometrium (lining of the uterus) cancer cells by interfering with other hormones and proteins that are required for growth of the cancer cells. It is also used to treat appetite loss and severe weight or muscle loss in people with cancer or acquired immunodeficiency syndrome (AIDS). It helps these conditions by promoting the production of certain proteins that increase appetite and weight gain.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor. Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

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What form(s) does this medication come in?

40 mg
Each light blue, round, flat-faced, bevelled-edged, scored tablet, engraved “40” on one side, contains megestrol acetate 40 mg. Nonmedicinal ingredients: colloidal silicon dioxide, croscarmellose sodium, lactose, magnesium stearate, microcrystalline cellulose, and Brilliant Blue FCF Lake 12% (dye).

160 mg
Each white, oval, biconvex, scored tablet engraved “160” on one side, contains megestrol acetate 160 mg. Nonmedicinal ingredients: colloidal silicon dioxide, croscarmellose sodium, lactose, magnesium stearate, and microcrystalline cellulose.

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How should I use this medication?

The recommended dose depends on the condition being treated and body weight.

For people with prostate cancer, the recommended dose is 120 mg taken as a single daily dose in combination with diethylstilbestrol 0.1 mg.

For people with breast cancer, the usual dose is 160 mg daily. This dose may be divided into 4 equal doses of 40 mg.

For people with cancer of the endometrium, the usual dose is 80 mg to 320 mg daily, which can be divided into 40 mg tablets taken 2 to 4 times daily, or 160 mg tablets taken 1 to 2 times daily.

For people with cancer or AIDS and appetite loss, muscle wasting, or significant weight loss, the usual adult dose is 400 mg to 800 mg as a single daily dose. People with AIDS usually use the liquid form of this medication. Shake the liquid well before measuring the dose.

The effectiveness of megestrol acetate can be assessed after 2 months have passed following the start of therapy.

Many things can affect the dose of a medication that a person needs, such as body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones listed here, do not change the way that you are taking the medication without consulting your doctor.

Megestrol can be taken with or without food.

Use an oral syringe to measure each dose of the liquid, as it gives a more accurate measurement than household teaspoons.

It is important to take this medication exactly as prescribed by your doctor. If you miss a dose, take it as soon as possible and continue with your regular schedule. If it is almost time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

The tablets and liquid should be stored at room temperature in a cool, dry place.

Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

Who should NOT take this medication?

Do not take megestrol if you:

  • are allergic to megestrol acetate or any ingredients of the medication
  • are or may be pregnant (first 4 months)

What side effects are possible with this medication?

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

  • constipation
  • diarrhea
  • hair loss
  • increased appetite
  • mild blood pressure increase
  • mood changes
  • nausea or vomiting
  • swelling of the face, ankles, or feet
  • weight gain

Although most of the side effects listed below don’t happen very often, they could lead to serious problems if you do not check with your doctor or seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

  • breast enlargement
  • changes in vaginal bleeding
  • decreased hearing
  • decreased interest or ability in sexual activity
  • depression
  • filling or rounding out of face
  • hot flushes
  • impotence
  • increased flow of breast milk
  • increased urination
  • loss of appetite
  • mood changes
  • rash
  • shortness of breath
  • symptoms of high blood sugar (e.g., frequent urination, increased thirst, excessive eating, unexplained weight loss, poor wound healing, infections, fruity breath odour)
  • unusual tiredness or weakness

Stop taking the medication and seek immediate medical attention if any of the following occur:

  • signs of stroke (e.g., sudden or severe headache; sudden loss of coordination; vision changes; sudden slurring of speech; or unexplained weakness, numbness, or pain in arm or leg)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Are there any other precautions or warnings for this medication?

Before you begin taking a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should take this medication.

Blood clots: This medication may increase the chance of blood clot formation, which will cause blood flow to organs or to the extremities to be reduced.

If you have a history of clotting, you may be at increased risk of experiencing blood clot-related problems such as heart attack, stroke, or clots in the deep veins of your leg. Discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

If you experience symptoms such as sharp pain and swelling in the leg, difficulty breathing, chest pain, blurred vision or difficulty speaking, contact your doctor immediately.

Diabetes: Megestrol acetate may cause a loss of control of diabetes by increasing blood sugar levels and changing glucose tolerance. If you have diabetes, you may find it necessary to monitor your blood sugar more frequently while using this medication.

If you have diabetes or are at risk for developing diabetes, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. You may need to check your blood glucose levels more often.

Kidney disease: Kidney disease or reduced kidney function may cause this medication to build up in the body, causing side effects. If you have kidney problems, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. Your doctor may want to test your liver function regularly with blood tests while you are taking this medication.

Osteoporosis: Long-term use of this medication can increase the risk of osteoporosis (brittle bones). Talk to your doctor about ways to help prevent osteoporosis. Your doctor will monitor your bone density if you take this medication for a long period of time.

Pregnancy: Megestrol acetate is not recommended for use during the first 4 months of pregnancy. Women should use effective birth control when taking megestrol. If you become pregnant while taking megestrol, tell your doctor right away.

Breast-feeding: This medication may pass into breast milk. If you are a breast-feeding mother and are taking megestrol acetate, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children: The safety and effectiveness of using this medication have not been established for children.

What other drugs could interact with this medication?

There may be an interaction between megestrol acetate and any of the following:

  • apixaban
  • cyclosporine
  • dabigatran
  • diabetes medications (e.g., chlorpropamide, glipizide, glyburide, insulin, metformin, nateglinide, rosiglitazone)
  • dofetilide
  • heparin and low-molecular weight heparins (e.g., dalteparin, tinzaparin)
  • rivaroxaban
  • testosterone and androgens(for men taking megestrol to treat prostate cancer)
  • estrogen (for women taking megestrol for breast or endometrial cancer)
  • ulipristal
  • warfarin

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

  • stop taking one of the medications,
  • change one of the medications to another,
  • change how you are taking one or both of the medications, or
  • leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

All material copyright MediResource Inc. 1996 – 2020. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Source: www.medbroadcast.com/drug/getdrug/Megestrol-by-AA-Pharma

Should we use appetite stimulants for malnourished elderly patients?

EVIDENCE-BASED ANSWER

Probably not. Only 1 appetite stimulate, megestrol acetate oral suspension (Megace) at 400 mg or 800 mg daily, has been studied in this population. The data show only limited benefit, mixed outcomes, and potential harm (strength of recommendation: B, based on small, randomized, controlled trials).

Clinical commentary

Good advice for a common problem
Kayleen P. Papin, MD
Medical College of Wisconsin, Milwaukee

This question hits home for me. I recently sat down with the husband, and main caregiver, of a woman with advanced dementia. The woman eats very little and is losing weight despite her husband’s great efforts at encouraging her to eat. Under the care of another physician, she had been given megestrol acetate and there had been some improvement. Her visit to my office was an opportunity to continue an ongoing conversation with her husband about his wife’s overall decline, her advancing dementia, and the sorrow he was feeling over her failing health.

Should we use appetite stimulants in malnourished elderly patients? “probably not.” that is a good place to start to avoid harm to our most frail, declining, elderly patients for whom we care. That leaves open flexibility to patient, family, and caregiver preferences, but reminds us that the most important part of caring for these patients and their families is clear, compassionate communication regarding goals and expectations.

Evidence summary

Although a number of studies have evaluated various appetite stimulants—megestrol, dronabinol (Marinol), cyproheptadine (Periactin), thalidomide (Thalomid), pentoxifylline (Pentoxil/Trental), nandrolone decanoate (DecaDurabolin), oxandrolone (Oxandrin), and corticosteroids—in patients with AIDS, anorexia cachexia syndrome, and advanced cancer, only megestrol has been studied in malnourished elderly patients.

Two studies, mixed results

One placebo-controlled randomized clinical trial studied 45 malnourished patients who were recently discharged from an acute care hospital to a nursing home. The patients (predominately female, with a mean age of 83) were randomized into 4 treatment arms (placebo or megestrol 200 mg, 400 mg, or 800 mg daily) and followed for 63 days.

Only those receiving megestrol (400 mg or 800 mg daily) demonstrated a statistically significant increase in patient appetite and a dose-responsive increase in prealbumin level at the 20 day interim analysis (7.5 and 9.0 mg/dL, respectfully). But at the final assessment (63 days), only the 400-mg dose maintained a statistically significant increase in prealbumin over placebo. However, there was no significant improvement in serum albumin or clinical endpoints (weight, functional status, or health-related quality of life).1

In contrast, an earlier Veterans Administration (and predominantly male) study showed 13/21 of those treated with megestrol (800 mg daily for 12 weeks) noted weight gain (≥4 lb sustained at 3 months post-treatment), compared with 5/23 of those receiving placebo (number needed to treat =2.5).2 Of note, only 9/26 patients had sustained weight gain in the megestrol group at the 12-month endpoint post-treatment, comparable with 7/25 in the placebo group.

Some small, but statistically significant, score improvements were noted during the treatment period in appetite and enjoyment of life; however, no differences were noted in scores on the more widely accepted Geriatric Depression Scale.

Adverse effects

As in all therapeutic interventions, benefit must be balanced against risk. The Megace ES package insert notes the following potential adverse effects: diarrhea, cardiomyopathy, palpitation, hepatomegaly, leukopenia, edema, paresthesia, confusion, convulsion, depression, neuropathy, hypesthesia and abnormal thinking, thrombophlebitis, pulmonary embolism, and glucose intolerance.3

To date, the prevalence rates of these potential adverse effects have only been studied in patients with AIDS. No data reflecting potential rates in elderly patients have been published.

Recommendations from others

The American Geriatric Society4 made 3 comments on appetite stimulation:

  1. There are no FDA-approved drugs available for the promotion of weight gain in older adults.
  2. A minority of patients receiving mirtazapine report appetite stimulation and weight gain.
  3. All drugs used for appetite have substantial potential adverse events.

We found only 1 national guideline on this topic: Unintentional Weight Loss in the Elderly from the University of Texas School of Nursing.5 The guideline indicates that drugs should not be used as first-line intervention in the elderly, as there has been inadequate testing in this population. Benefits are restricted to small weight gains without indication of decreased morbidity or mortality, improved quality of life, or improved functional ability.

Acknowledgments

The opinions and assertions contained herein are the private views of the author and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.

Unintentional Weight Loss and Appetite Stimulants

May/June 2013

By Mark D. Coggins, PharmD, CGP, FASCP
Today’s Geriatric Medicine
Vol. 6 No. 3 P. 10

Unintentional weight loss, defined as a loss of 5% of body weight in one month or 10% in six months, is of significant concern in older adults.1,2 It’s a predictor of mortality, with 9% to 38% of older adults dying within one to 2 1/2 years of onset3 and the risk increasing four times with a 5% weight loss in one month.

In the frail elderly, even small amounts of weight loss can have negative consequences, and all elderly patients are encouraged to maintain their nutrition and weight over the years as even voluntary weight loss has been associated with increased risk of death and hip fracture.3

Complications of unintentional weight loss include anemia, decreased cognition and quality of life, edema, falls, hospitalizations, hip fractures, infections, nursing home placement, osteoporosis, and pressure ulcers.1-3

Common Causes of Unintended Weight Loss
Causes of unintentional weight loss can be divided into three main categories:

• physiological (eg, diseases, cancer, dental problems, pain);

• psychological (eg, depression, dementia); and

• socioeconomic (eg, isolation, financial).

Health care providers can use the mnemonic “Meals on Wheels” (see below) to identify common treatable causes of unintentional weight loss.

Elderly patients experiencing weight loss should be screened for depression (eg, Geriatric Depression Scale), as the incidence of depression is high among these patients in both community and nursing home settings. 3,4

There’s a possible link between rapid weight loss and the onset of Alzheimer’s disease, with one study finding that twice as many patients with Alzheimer’s disease experienced a weight loss of 5% or greater compared with the study’s control patients. Screening for Alzheimer’s disease or dementia in elderly patients with unintended weight loss using a tool such as the Mini-Mental State Exam or Clock Drawing Test may help with earlier identification earlier of the condition and allow for the consideration of available treatments, such as acetylcholinesterase inhibitors (eg, Aricept, Exelon) and/or memantine (Namenda), to potentially slow cognitive decline.

Medication side effects (see Table 1 below) often contribute to weight loss because of side effects such as anorexia, dry mouth, taste or smell disturbances, swallowing difficulties, and nausea or vomiting.3 A retrospective chart review in a 718-bed long term care facility found that more than 75% of the 41 patients with recent weight loss had received at least one medication known to potentially contribute to weight loss.5 Also, when health care providers had reviewed for possible causes of the weight loss, no changes in medication therapy had been attempted to evaluate the medications as an underlying cause. Instead, many of these patients were placed on additional medications in an attempt to stimulate appetite, contributing to the problem of polypharmacy.5

Managing Unintended Weight Loss
Currently there are no FDA-approved medications for appetite stimulation in the elderly.1 Most studies have failed to demonstrate that the medications commonly used off label to stimulate appetite also decrease morbidity and mortality or improve function or quality of life. As a result, appetite stimulants should not be considered as a first-line treatment for unintended weight loss in the elderly because of the lack of clear evidence of their benefit and the potential for significant medication-related side effects.

Instead, nutritional intervention and the treatment of underlying conditions that contribute to weight loss are the keys to managing this condition. Failing to appropriately treat the underlying cause of the weight loss cannot be corrected with appetite stimulants. For example, appetite stimulant medications will do little to increase food intake if a patient’s underlying problem is poorly fitting dentures or inadequately treated depression or pain.

Pharmacological Agents
Only after nonpharmacological interventions have been attempted and found ineffective should appetite stimulants be considered, and even then, the use of these agents should occur only after their benefit-to-risk ratio has been carefully considered.

Megesterol acetate is commonly used as an appetite stimulant and is FDA approved only for AIDS-associated weight loss. The branded product Megace ES has been heavily promoted in long term care for weight loss despite the lack of indication for this use in the elderly. In March, Par Pharmaceutical, the maker of Megace ES, settled a multimillion dollar federal and multistate lawsuit in which the company was accused of inappropriately marketing Megace ES for use in elderly nursing home patients. The lawsuit claimed Par marketed the product despite knowledge of megesterol acetate’s adverse side effects, including deep vein thrombosis, toxic reactions in elderly patients with impaired renal function, and mortality.6

Studies of megesterol acetate in elderly patients who experience weight loss are limited and of poor quality. Most show minimal or no weight gain, with no nutritional or clinically significant beneficial outcomes observed. Megesterol acetate use also has been associated with significantly increased mortality without significant weight gain.

In some cases, a trial of megesterol acetate may be initiated but only after all other nonpharmacological interventions have been attempted and found to be ineffective. Evaluation of weight gain should occur at least every four weeks, and therapy should be discontinued if no benefit is achieved or adverse events are noted. Megesterol acetate should not be used for more than 12 weeks because of the increased risk of deep vein thrombosis.

The use of megesterol acetate in elderly patients with weight loss often is seen in those who have been hospitalized and then discharged to a nursing facility. These patients should be evaluated closely to ensure the use is appropriate. This practice in hospitals may indicate the need for increased education for dietitians and other health care professionals about the associated risk.

The antidepressant mirtazapine (Remeron) has been used to help increase appetite and weight gain in depressed elderly patients. Mirtazapine should be given at bedtime because of its sedating properties and to minimize the risk of other side effects, including the risk of falls due to sedation, dizziness, and orthostatic hypotension. Studies involving the use of mirtazapine for weight gain in nondepressed elderly patients are lacking. With appropriate monitoring for side effects and weight gain, mirtazapine may be a drug of choice for elderly patients experiencing weight loss who also have coexisting depression.7

Additional Considerations
Weight loss with increasing age is believed to be due in part to decreased growth hormone production. The use of recombinant human growth hormone has been shown to help increase lean body weight, improve walking time, and increase serum albumin when elderly patients are given low doses (0.09 IU/kg) three times weekly for four weeks. However, its use should be limited due to evidence coming from small study sizes, its significant expense, and the potential risk of glucose intolerance, hypertension, hyperlipidemia, gynecomastia, edema, carpal tunnel syndrome, and arthralgia.8

The antihistamine cyproheptadine (Periactin) has been used to increase weight in various disease states. However, it has not been studied specifically for unintended weight loss in the elderly. Ultimately, it’s not recommended for use in older adults because of anticholinergic side effects, including dizziness, sedation, and dry mouth.7

Dronabinol (Marinol) has been shown to increase weight in a small placebo control study of Alzheimer’s patients,7 but its use is limited because of the risk of seizures, confusion, sleepiness, and euphoria.

Multidisciplinary Approach to Weight Loss
Improved management of unintended weight loss in the elderly can best be achieved through an interdisciplinary approach. Physicians should work closely with other members of the care team to identify and treat the underlying causes contributing to weight loss.

Dietitians are valuable resources in assessing food needs, recognizing changes in eating environment, and recommending nutritional supplementation, while social workers can identify socioeconomic factors (eg, living arrangements, financial concerns) contributing to unintended weight loss. Speech and occupational therapists can help assess swallowing and oral issues, while physical therapists can implement exercise programs to stimulate appetite and weight gain. Consult pharmacists to help identify medications that may contribute to weight loss and provide education on the appropriate use of appetite stimulant medications to limit unnecessary polypharmacy and medication-related adverse effects.

— Mark D. Coggins, PharmD, CGP, FASCP, is a director of pharmacy services for more than 300 skilled nursing centers operated by Golden Living and a director on the board of the American Society of Consultant Pharmacists. He was recognized by the Commission for Certification in Geriatric Pharmacy with the 2010 Excellence in Geriatric Pharmacy Practice Award.

1. Huffman GB. Evaluating and treating unintentional weight loss in the elderly. Am Fam Physician. 2002;65(4):640-651.

2. Stajkovic S, Aitken EM, Holroyd-Leduc J. Unintentional weight loss in older adults. CMAJ. 2011;183(4):443-449.

4. Alzheimer’s Association, National Chronic Care Consortium. Tools for Early Identification, Assessment, and Treatment for People With Alzheimer’s Disease and Dementia. http://www.alz.org/national/documents/brochure_toolsforidassesstreat.pdf. Revised June 2003. Accessed April 6, 2013.

5. Goldeberg RJ, Kaplan LA, Boucher LJ. Physicians’ attentiveness to medication use as etiology of weight loss. Long Term Care Interface. 2005;6:20-23.

7. Rudolph DM. Appetite stimulants in long term care: a literature review. Internet J Adv Nur Practice. 2010;11(1).

8. Treatment of unintentional weight loss in the elderly. Pharmacist’s Letter/Prescriber’s Letter. 2009;25(6):250610.

‘Meals on Wheels’ Mnemonic1

M

edication effects

E

motional problems, especially depression

A

norexia nervosa, alcoholism

L

ate-life paranoia

S

wallowing disorders

O

ral factors (eg, poor-fitting dentures, caries)

N

o money

W

andering and other dementia-related behaviors

H

yperthyroidism, hypothyroidism, hyperparathyroidism, hypoadrenalism

E

nteric problems (eg, malabsorption)

E

ating problems (eg, inability to feed self)

L

ow-salt, low-cholesterol diet

S

tones, social problems (eg, isolation, inability to obtain preferred foods)

Table 1: Medication-Related Side Effects Causing Weight Loss3

Anorexia

amantadine, amphetamines, antibiotics, anticonvulsants, benzodiazepines, decongestants, digoxin, gold, levodopa, metformin, neuroleptics, nicotine, opiates, SSRIs, theophylline, tricyclics

Dry mouth

anticholinergics, antihistamines, clonidine, levodopa, loop diuretics, neuroleptics, opiates, selegiline

Dysguesia, dysomia

ACE inhibitors, acetazolamide, alcohol, allopurinol, amphetamines, antibiotics, anticholinergics, antihistamines, anticonvulsants, antineoplastics, calcium channel blockers, chloral hydrate, cocaine, gold, hydralazine, hydrochlorothiazides, iron, levodopa, lithium, metformin, metronidazole, nasal vasoconstrictors, nitroglycerin, opiates, penicillamine, propranolol, statins, terbinafine, tricyclics

Dysphagia

antibiotics, anticholinergics, antineoplastics, bisphosphonates, corticosteroids, gold, levodopa, NSAIDs, potassium, quinidine, theophylline

Nausea and vomiting

amantadine, antibiotics, anticonvulsants, antineoplastics, bisphosphonates, digoxin, dopamine agonists, hormone replacement therapy, iron, metformin, metronidazole, nitroglycerin, opiates, potassium, selegiline, SSRIs, statins, theophylline, tricyclics

Table 2: Examples of Medications Known to Cause Weight Loss2

Cardiac

digoxin, aspirin, ACE inhibitors, calcium channel blockers, hydralazine, loop diuretics, hydrochlorothiazides, spironolactone, statins, nitroglycerin

Neurologic and psychiatric

SSRIs, tricyclic antidepressants, neuroleptics, benzodiazepines, anticonvulsants, lithium, levodopa, dopamine agonists, donepezil, memantine

Bones and joints (including pain medications)

bisphosphonates, NSAIDs (including COX-2 inhibitors), opiates, allopurinol, colchicine, gold, hydroxychloroquine

Endocrine

levothyroxine, metformin

Other

anticholinergics, antibiotics, decongestants, antihistamines, iron, potassium, alcohol, nicotine

Megace is the brand name of the prescription drug megestrol, which is used to treat advanced breast cancer and advanced endometrial cancer.

The medicine is given in a concentrated liquid form (Megace ES) to prevent weight loss and improve appetite in people with acquired immunodeficiency syndrome (AIDS).

It’s also sometimes used to relieve symptoms of other cancers, an enlarged prostate, endometriosis (a condition where tissue that lines the uterus grows in other places), or endometrial hyperplasia (overgrowth of the lining of the uterus).

Megace is a man-made form of the human hormone progesterone.

It helps breast and endometrial cancers by affecting the hormones involved in cancer growth. It helps AIDS patients gain weight by increasing appetite.

The Food and Drug Administration (FDA) first approved the medicine in 1971. Megace is manufactured by Bristol-Myers Squibb and Megace ES by Par Pharmaceutical Companies, Inc.

Megace Warnings

Megace shouldn’t be given to prevent weight loss or improve appetite in people who don’t have AIDS or those who haven’t yet developed the disease.

Before taking Megace, tell your doctor if you have or have ever had:

  • An adrenal gland disorder
  • Diabetes
  • Stroke
  • Blood clot
  • Liver disease
  • Kidney disease
  • Allergies to medications

Megace may cause changes in a woman’s normal menstrual period. Talk to your doctor if this is a concern.

Tell your doctor you’re taking this drug before having any type of surgery, including a dental procedure.

Your dose of Megace may need to be changed if you have surgery, become ill, have an infection, or are under a lot of stress. Don’t change your dose without first talking to your physician.

Megace can pass into body fluids such as urine, feces, vomit, semen, and vaginal fluid. Wear rubber gloves when cleaning up these fluids or changing a diaper. Wash your hands before and after.

Pregnancy and Megace

Megace can harm an unborn baby or cause birth defects. Don’t take this medicine if you’re pregnant.

Also, pregnant women shouldn’t handle the body fluids of someone who takes Megace.

Be sure to use effective birth control methods to prevent pregnancy while taking Megace. Talk to your doctor about birth control options.

It’s not known whether the medicine passes into breast milk or could harm a breastfeeding baby. Don’t breastfeed while taking Megace without talking to your doctor first.

Megace for Dogs and Cats

The medicine is sometimes used in dogs and cats to treat certain medical conditions. It’s prescribed by veterinarians under the brand name Ovaban.

The drug is used to help control heat cycles in dogs and cats.

It’s also used to treat false pregnancies, behavioral problems, skin disorders, and other health issues in pets.

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