Interacting drugs- summary

 Aminoglutethmide +

Anticoagulants

anticoagulant effects be decreased

Dexamethasone

 loss of dexamethasone-induced adrenal suppression. If a corticosteroid is needed substitute hydrocortisone

Digitoxin

 digitoxin clearance increased

 Medroxyprogesterone

 medroxyprogesterone serum levels decreased

Theophylline

 action of theophyllline reduced

Cushnings syndrome

 Suppression of adrenal function

Most frquent effects are-

Drowsiness ( 33% ) , Morbiliform skin rash ( 17% ) Nausea and anorexia ( 12.5% ),

These are reversible and often disappear spontaneously within 1 to 2 weeks of continued therapy

Hepatic- isolated liver function tests, suspected hepatotoxicity (< 0.1%), cholestatic jaundice

Hematologic- (rare) neutropenia, leukopenia, and pancytopenia

Endocrine- adrenal insufficiency, hypothyroidism, masculainization and hisutism in females and precocious sex development in males have occassionally occurred.

CNS- headache, dizziness, possibly caused by decreased vascular resistence or orthostatasis

Dermatologic- rash, often reversible on continued therapy, pruritus. These may be allergic or hypersentivity reactions. Urticaria has occure rarely.

Miscellaneous- vomiting, myalgia, fever, possibly related to therapy, occured in several patients on aminoglutethimide for < 4 weeks when given with other drugs

Hypersentivity to glutethimide or aminoglutethimide

Special precautions-

Monitoring- hypothyroidism may occur. Make appropiate clinical observations and perform thyroid function studies. Supplematary thyroid hormone may be required.

Hematologic abnormalities have been reported.

Elevations in AST,alkaline phosphatase and bilirubin have been reported.

Perform clinical observations and regular laboratory studies before and during therapy.

Determine serum electrolytes periodically.

Warnings

Duration of therapy- because aminoglutethimide does not affect the underlying disease process it has been used primarily until more definitive therapy ie surgery can be undertaken. or in such cases where such therapy is not appropiate. Only a small number of patients have been treated for > 3 months.

Cortical hypofunction- may cause cortical hypofunction, especially under conditions of stress such as surgery, trauma, or acute illness. Monitor patients carefully and give hydrocortisone and mineralocorticoid supplements. Do not use dexamethasone.

Hypotension- aminoglutethimide- may suppress aldosterone production by the adrenal cortex and may cause ortostatic or persistent hypotension. Monitor blood pressure in all patients at appropiate intervals.

Pregnancy- if the drug must be used during pregnancy or if the patient becomes pregnant while taking the drug, appraise her of the potential hazard to the fetus.

Lactation- decide whether to discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother.

Children- safety and efficacy have not been established. 

Indication-

Cushnings syndrome

 Suppression of adrenal function

Dosage-

Give 250mg 4 times daily, preferably at 6 hour intervals.Follow adrenal cortical response by careful monitoring of plasma corticol until the desired level of suppression is reached.

If corticol  suppression is inadequate, dosage may be increased in increments of 250mg daily at an intreval of 1 to 2 weeks to a total daily dose of 2g

Dose reduction or discontinuation may be required in the event of adverse reactions

1. May produce drowsiness or dizziness, patients should observe caution while driving or performing other tasks requiring alertness, coordinatin or physical dexterity.

2. May cause rash, fainting, weakness or headache, notify physician if pronounced

3. Nausea and loss of appetite may occur during the first 2 weeks of therapy, notify physician if these persist or become pronounced.

4 Allergies- Tell your doctor if you ever had allergic reactions to glutethimide or aminoglutethime

5. Pregnancy- Aminoglutethimide has been shown to cause birth defects in humans and animals. However this medicine may be needed in serious diseases or in other situations that threaten the mothers life. Tell your doctor if you are pregnant.

6. Breast feeding- This medicine has been reported to cause problems in nursing babies.

7. Children- There is no specific information comparing use of aminoglutethimde in children. However, there is a chance that aminoglutethimde could cause premature growth and sexual development in males or development of male features in females

8. Elderly- lack of energy is more likely to occur in the elderly, who are more sensitive to the effects of aminoglutethimide.

9. Other medicines- When you ate taking aminoglutethemide it is especially important that your doctor know if you are taking any of the following- Dexamthasone- eg Decadron- aminogluthemide increases the rate at which dexamethasone is removed from the body.

10. Other medical problems- Presence of other medical problems may affect the use of aminogluthemide- Make sure that you tell your doctor if you have any of the medical problems-

Chicken pox- or recent exposure to Hepes Zoster (shingles) risk of severe disease afecting other parts of the body

Infection- may affect the adrenal cortex. If a steroid supplement is used a change in dosage may be needed.

Underactive thyroid- aminogluthemide can cause underactive thyroid.

11. Missed dose- if you miss a dose of this medicine and remember within 2 to 4 hours of the missed dose take it as soon as possible. Then go back to your dosing schedule. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

12. Storage- Keep out of reach of children- Store away from heat and and direct light. Do not store in bathroom , near kitchen sink or in any damp places. Heat or damp may cause the medicine to break down. Do not keep outdated medicine or medicnesno longer required. Make sure that discared medicines are kept out of reach of children.

Pharmacology

Aminoglutthimide inhibits the enzyme conversion of cholesterol to delta 5 pregenolone thereby reducing the synthesis of adrenal glucocorticoids ,mineralocorticoids, estrogens, and androgens Aminogluthemide blocks several other steps insteroid synthesis including the hydroxylations required for the aromatization ofandrogens to estrogens.

Pharmacokinetics

Aminogluthemide is efectively absorbed orally and is minimally bound to plasma protein. Its half-lfe is 11 to 16 hours initially, but decreases after 1 to 2 weeks to 5 to 9 hours.Approximately 24% to 54% is excreted unchanged in the urine and 20% to 50% is excreted as acetylated metabolite (less than one-fifth as active as the parent compound.

Pregnancy

If the drug must be used during pregnancy or if the patient becomes pregnant while taking the drug, appraise her of the potential hazard to the fetus.

Lactation

Decide whether to discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother.

Children-

Safety and efficacy have not been established.