Aminoglutethimide (Oral)

Aminoglutethimide is used as a treatment for certain types of cancer that affect the adrenal cortex and is sometimes used in cases where the adrenal cortex is overactive but not cancerous.

Overview

It works on the part of the body known as the adrenal cortex by affecting the production of steroids, since it is an adrenal steroid inhibitor. It works by restraining the production of an array of hormones, including androgens, mineralocorticoids, glucocorticoids, and estrogens. It also inhibits the aromatase enzyme; a potent aromatase inhibitor.

Clinically, cytadren is used to treat metastatic breast cancer as well as breast cancer. However, the medication was approved for the treatment of Cushing's syndrome.

In the U.S. the brand name of aminoglutethimide is cytadren. Aminoglutethimide should only be prescribed by a doctor and is taken orally as a pill. Upon withdrawal of medication with aminoglutethimide, the capability of the adrenal glands to produce steroid returns within 72 hours.

Conditions treated

  • Metastatic prostate cancer
  • Breast cancer in menopausal women

Types of medicine

  • Aromatase inhibitor

Side effects

It is essential to put in mind the following points about the side effects of aminoglutethimide:

  • Most individuals do not experience all of the side effects stated below.
  • The side effects mentioned take into account their inception, extent, and severity.
  • Side effects are often almost reversible and will eventually disappear after completing the medication.
  • There are numerous options to aid, lessen or avert side effects.
  • It is also important to note that there is entirely no connection between the occurrence or severity of side effects and the efficiency of the medication.

The following side effects are less common when taking aminoglutethimide pills:

  • Mental depression
  • Indistinct speech
  • Lightheadedness or dizziness (mainly when getting up from a sitting/lying position)
  • Fast heartbeat
  • Uninhibited eye movements
  • Shakiness
  • Unusual weakness or tiredness

Common side effects include:

  • Dizziness and shortness of breath
  • Decreased coordination that leads to clumsiness

Rare side effects

  • Black, tarry stools
  • Blood in stool or urine
  • Side or lower back pain, accompanied by chills or fever
  • Unusual bleeding or bruising
  • Hoarseness or a cough that is accompanied by chills or fever
  • Chills or fever
  • Difficult or painful urination, accompanied by chills or fever
  • Pinpoint red spots on the skin
  • Eyes or the skin turning yellow

Visit a doctor as soon as possible when you see any of the symptoms mentioned above. The drug may also lead to the following side effects that your doctor may watch out for:

  • A low white blood cell count
  • A low red blood cell count

Check with a medical practitioner, especially a doctor, if the following side effects lead to discomfort.

More common

  • Loss of appetite
  • Nausea

Less common

  • Irregular menstrual periods
  • Female voice deepening
  • Increased hair growth in females
  • Vomiting
  • Muscle pain
  • Headache

Dosage

Aminoglutethimide should be taken as prescribed by the doctor, making sure to follow the instructions on the prescription packaging carefully.

The Aminoglutethimide dose that the doctor will recommend will be based on:

  • The other medical conditions that a patient has
  • The medical condition being treated
  • The other medications a patient is taking
  • How a patient responds to this drug

Other factors to be considered include a patient's weight, height and age, as well as gender.

Adult dosage

  • Medication should be administered in the hospital until a constant dosage schedule is achieved.
  • Therapy should be kicked off with 250mg oral pills four times a day daily, if possible at 6-hour intervals.
  • The adrenocortical reaction should be tracked by carefully monitoring the plasma cortisol level awaiting the desired level of inhibition to be achieved. If the stage of cortisol suppression is insufficient, the dosage amount may be added in increments of 250mg every day at intervals of 1-2 weeks to a sum of a daily dose of 2g.
  • Temporary discontinuation or dosage reduction of treatment may be necessary for the event of unpleasant effects, including severe skin rash, extreme drowsiness or deficient cortisol levels.
  • When skin rash persists for more than 5-8 days or becomes brutal, the medication should be stopped
  • It is possible to restore therapy at smaller doses after the fading of a moderate or mild rash.
  • Mineralocorticoid replacement such as fludrocortisone is necessary.
  • If glucocorticoid replacement therapy is required, 20-30mg of hydrocortisone administered orally every morning will restore endogenous secretion.

Children dosage

Smaller doses are used for younger patients. For example, 2 1/2-year-olds receive 0.5-0.75g daily. 3 1/2-year-olds receive 0.5g daily, while all others aged over 10 years receive 0.75-1.5g daily.

Most young patients show a decrease in urinary or plasma steroids at some point while taking this medication. These may, however, be due to other therapeutic modalities or their grouping.

Self-care dosage tips

  • Nausea can be reduced when the drug is taken with food.
  • Unless instructed otherwise a patient should take at least two quarts of water every 24 hours.
  • A patient is likely to experience dizziness and is therefore advised to refrain from driving or handling machines.
  • When a patient experiences symptoms of side effects, they are urged to contact their doctor or medical team so that they can be given ways to counter such problems.

Drug interactions

The following drugs may cause interactions with Aminoglutethimide:

  • A combination of Docetaxel and Aminoglutethimide increase the risk of adverse effects.
  • Gitoformate may reduce the cardiotoxic actions of Aminoglutethimide.
  • The serum concentration of Methadone can be amplified when combined with Aminoglutethimide.
  • Metildigoxin may reduce the cardiotoxic actions of Aminoglutethimide.
  • Oleandrin may reduce the cardiotoxic actions of Aminoglutethimide.
  • Ouabain may lessen the cardiotoxic actions of Aminoglutethimide.
  • The danger of adverse effects can be amplified when Paclitaxel is pooled with Aminoglutethimide.
  • Peruvoside may reduce the cardiotoxic actions of Aminoglutethimide.
  • Proscillaridin may reduce the cardiotoxic actions of Aminoglutethimide.
  • The serum concentration of Saxagliptin can be reduced when it is pooled with Aminoglutethimide.
  • Trastuzumab may amplify the cardiotoxic actions of Aminoglutethimide.
  • The ruthlessness of unpleasant effects can be amplified when Docetaxel is pooled with Aminoglutethimide.
  • Gitoformate may reduce the cardiotoxic actions of Aminoglutethimide.
  • Lanatoside C may reduce the cardiotoxic actions of Aminoglutethimide.
  • The serum concentration of Methadone can be amplified when it is pooled with Aminoglutethimide.
  • Metildigoxin may reduce the cardiotoxic actions of Aminoglutethimide.
  • Oleandrin may lessen the cardiotoxic behavior of Aminoglutethimide.
  • Ouabain may lessen the cardiotoxic behavior of Aminoglutethimide.
  • The ruthlessness of unpleasant effects can be amplified when Paclitaxel is pooled with Aminoglutethimide.

There are brutal signs of allergic reaction to glutethimide in pre-menopausal women with inducible porphyria and metastatic breast carcinoma.

Precautions

  • A mother that is breastfeeding should refrain from doing so as the medication is likely to get into the milk and affect a baby.
  • Both men and women that are on this medication should refrain from conceiving a child. Barrier methods such as condoms or contraception are recommended. Ask the doctor when it would be safe to conceive a child.
  • Any person that has an allergic reaction to any ingredient of this medication should not take it.
  • Before the start of aminoglutethimide treatment, the patient should inform the doctor of any other medication they are taking, including but not limited to: vitamins, herbal and over-the-counter drugs.
  • It is figured that one-half of the patients that are put under aminoglutethimide treatment must be put on replacement steroid medication owed to the little production of required steroids formed by the adrenal glands.
  • The doctor should be informed if a woman is pregnant before receiving this treatment as the drug may be dangerous to the fetus.

Storage

  • The drug should be protected from light.
  • Aminoglutethimide should not be stored above 30ÂșC.
  • A tight, light-resistant container should be used to dispense the drug.

Warnings

Aminoglutethimide may lead to adrenocortical hypofunction, particularly under conditions of stress, such as trauma, surgery or acute illness. Patients ought to be vigilantly monitored and administered with mineralocorticoid and hydrocortisone supplements.

Aminoglutethimide may also contain aldosterone production by the adrenal cortex causing persistent hypertension or orthostatic. The blood pressure should, therefore, be observed in all patients at suitable intervals. Advice should be given to patients on the possible episode of dizziness and weakness as symptoms of hypotension, and of actions to be taken in case of an occurrence.

The effects of aminoglutethimide may be affected severely when taken with alcohol.

Aminoglutethimide causes fetal damage if given to a pregnant woman. Women who have been on treatment, however, go on to have healthy pregnancies.

When the drug was administered to rats at the maximum daily human dose, Aminoglutethimide led to a reduction in fetal implantation, a list of teratogenic effects as well as a rise in fetal deaths. The medication also leads to pseudohermaphroditism in rats and hamsters treated with around three times the maximum daily human dosage. If the medication must be used during pregnancy, or the patient gets pregnant while taking the drug, they should be informed of the probable danger to the fetus.

Overdose

Notably, no deaths have so far been reported due to an overdose of aminoglutethimide.

Signs and Symptoms

A severe overdose with aminoglutethimide is likely to decrease the production of steroids in the adrenal cortex to the extent that is relevant clinically. The following signs may be expected:

  • Respiratory depression (also known as hypoventilation)
  • Hypotension or hypovolemic shock resulting from dehydration
  • Drowsiness, coma, lethargy, ataxia, fatigue, dizziness. Extreme weakness is likely to manifest with separated doses of 3g daily).
  • Nausea as well as vomiting
  • Loss of water and sodium

The signs and symptoms of severe overdose with aminoglutethimide are often aggravated if hypnotics, alcohol, tricyclic antidepressants or tranquilizers have been taken at the same time.

Summary

Aminoglutethimide is a hormone therapy that is used to treat cancer since cancer of the adrenal glands is associated with surplus steroid production in the human body, which may eventually cause Cushing's syndrome. Aminoglutethimide stems the creation of the steroids, resulting in a reduction in the symptoms.

Furthermore, androgens and estrogens are likely to play a role in the increase of some varieties of cancer cells. Inhibiting the production, this hormone may decrease the rise in cancers such as prostate cancers or hormone responsive advanced breast cancer.

The medication is given orally, and some patients may be given steroids so that they can replace the ones produced by the body and should only be administered by the doctor.

A patient should disclose to the doctor any medication they are using such as herbal or over-the-counter drugs since failure to disclose this information may cause fatal reactions to aminoglutethimide.

In case of an overdose, a patient should visit a medical practitioner as soon as possible so that treatment of the overdose can commence immediately.

Patients are typically monitored by having planned meetings with their doctors while receiving treatment. Patients usually have blood tests to monitor steroid level and hormones in their body. Patients are always being watched for particular signs that indicate a steroid or hormone deficiency, such as vomiting, nausea, poor appetite, weight loss, diarrhea, dizziness, and weakness. Patients are advised to contact their doctor or healthcare provider if they experience these symptoms.

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Last Reviewed:
December 10, 2017
Last Updated:
April 04, 2018