ESTRAMUSTINE :
Alkylating agent :
Special pediatric considerations are noted when applicable, otherwise adult provisions apply.
[1] :
Estramustine phosphate is a combination of estradiol with nornitrogen mustard. The precise mechanism of action of estramustine is unknown. Unlike other alkylating agents, estramustine does not directly damage DNA.
[2,3,4,5] :
| Oral Absorption | 75% absorbed, rate and extent of absorption decreased when taken with milk, food or calcium-rich drugs | |
| Distribution | appears to concentrate in prostatic tissue | |
| cross blood brain barrier? | no information found | |
| Vd | no information found | |
| PPB | no information found | |
| Metabolism | dephosphorylated in intestines and plasma, then oxidized in liver | |
| active metabolite(s) | estramustine, estromustine | |
| inactive metabolite(s) | yes | |
| Excretion | urine and feces | |
| feces | 14-21% in 7 days | |
| urine | 22-36% in 2-8 days | |
| t1/2 | 20 hours | |
| Cl | no information found | |
[6] :
Prostate cancer
No pediatric indications.
Health Protection Branch approved indication.
[6,7] :
Contraindicated
in patients with severe hepatic or cardiac disease, or active thrombophlebitis or thromboembolic disorders.
Low-dose breast radiation
prior to treatment may prevent gynecomastia in male patients.
Estramustine is potentially mutagenic and carcinogenic. Patients should be advised to use birth control if their partner is of child-bearing age. Breast feeding is not recommended due to the potential secretion into breast milk and because it interferes with milk volume and content.
[6,8] :
| ORGAN SITE | SIDE EFFECT | ONSET | |||
| cardiovascular | congestive heart failure (rare) | D | |||
| thromboembolism | D | ||||
| sodium retention, edema | D | ||||
| dermatologic | skin rash (rare) | E | |||
| endocrine | impotence and decreased libido (20-50%) | E | |||
| gynecomastia | L | ||||
| gastrointestinal | nausea (transient) | I | |||
| vomiting (occasional) | I | ||||
| diarrhea (rare) | E | ||||
| hematologic | myelosuppression (uncommon) | E | |||
| hepatic | elevated liver function tests | E | |||
| renal/metabolic | decreased glucose tolerance | D | |||
Dose-limiting side effects are underlined.
I = immediate (onset in hours to days); E = early (days to weeks); D = delayed (weeks to months); L = late (months to years)
[6] :
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
| milk, milk products or calcium-containing drugs (eg, calcium supplements, some antacids) | decreased effect of estramustine | impaired absorption of estramustine | do not take simultaneously with estramustine |
[6,9]
Capsules: Estramustine sodium phosphate 140 mg; store in the refrigerator (2-8o C); keep bottle tightly closed. Bisulfite-, gluten-, lactose- and tartrazine-free.
[2,3,4] :
Refer to protocol by which patient is being treated.
Oral:
daily: 14 mg/kg/day (ie, one 140 mg capsule for each 10 kg) in 3-4 divided doses
range: 10-16 mg/kg/day
Capsules should be taken on an empty stomach (1 hour before or 2 hours after a meal).
Adequate trial:
30 days
Dosage in myelosuppression: administer with caution, no details found Dosage in renal failure: no adjustment required Dosage in hepatic failure: administer with caution, no details found
ESTRAMUSTINE FACT SHEET
FOR THE HEALTH CARE PROFESSIONAL
| OTHER NAMES | estramustine sodium phosphate, EMCYT(r), ESTRACYT(r) |
| USES * HPB approved | prostate cancer * |
| DOSAGE FORMS | oral capsule: 140 mg (refrigerate) |
| USUAL DOSE RANGE | oral: 10-16 mg/kg/day po in 3-4 divided doses on an empty stomach |
| DOSE REDUCTIONS | severe uncontrolled nausea and vomiting |
| ONSET | SIDE EFFECT * may be life-threatening side effects in bold, italic type are common |
| IMMEDIATE (hours to days) | nausea and vomiting (20-50%) |
| EARLY (days to weeks) | impotence or decreased sex drive (decreased libido) diarrhea (20-50%) elevated liver function tests low WBC (myelosuppression) skin rash (rare) |
| DELAYED/LATE (weeks to years) | breast swelling or tenderness (gynecomastia, 20-50%) fluid retention (edema) congestive heart failure (secondary to edema) stroke loss of diabetic control (decreased glucose tolerance) |
| CONTRAINDICATIONS | severe liver (hepatic) or heart (cardiac) disease blood clots (thromboembolic disorders) known hypersensitivity to either estradiol or mechlorethamine |
| SIGNIFICANT INTERACTIONS | calcium (milk and milk products, calcium supplements, calcium-containing antacids, etc.) |
| LABORATORY MONITORING | monthly: CBC, liver function tests, kidney function tests. |
TEACHING AIDS * For the Patient: Estramustine
For the Patient: Nausea
Chemotherapy and You: a Guide to Self-help During Treatment
NOTES:
* Give estramustine with a glass of water on an empty stomach, either 1 hour before or 2 hours after eating.
Avoid calcium products such as milk or milk products, calcium supplements and calcium containing antacids (eg, TUMS(r)) for at least 1 hour before or 2 hours after each dose.
Do not open estramustine capsules. Avoid skin contact with estramustine.
FOR THE PATIENT
Estramustine : Other names: estramustine sodium phosphate, EMCYT(r), ESTRACYT(r)
Estramustine (ess-tra-MUSS-teen) is a drug which is used to treat prostate cancer. It is a white capsule to take by mouth.
Take estramustine with a glass of water on an empty stomach either 1 hour before eating or 2 hours after eating. Do not open capsules.
It is important to take estramustine exactly as directed by your doctor. Make sure you understand the directions.
If you miss a dose of estramustine, take it as soon as you can if it is within 4 hours of the missed dose. If it is over 4 hours since your missed dose, skip the missed dose and go back to your usual dosing times.
Store estramustine capsules in the refrigerator, tightly closed and out of the reach of children. Do not freeze.
Calcium can interact with estramustine. Calcium is found in dairy products such as milk and cheese, calcium supplements and some antacids. Avoid these products for at least 1 hour before and 2 hours after taking your dose of estramustine.
Other drugs may interact with estramustine. Tell your doctor if you are taking any other drugs as your dose may need to be changed. Check with your doctor or pharmacist before you start taking any new drugs.
The drinking of alcohol (in small amounts) will not affect the safety or usefulness of estramustine.
Estramustine may damage sperm and cause sterility which may be permanent. It is best to use birth control if your partner is of childbearing age. If you plan to have children, discuss this with your doctor before taking estramustine.
Tell doctors or dentists that you are taking estramustine before you receive any treatment from them.
| SIDE EFFECTS | MANAGEMENT |
| Nausea and vomiting may occur. | *Drink plenty of fluids. *Eat often in small amounts. *Try the ideas in For the Patient: Nausea . |
| Breast swelling or soreness often occurs. | This may return to normal when you stop taking estramustine. |
| SIDE EFFECTS | MANAGEMENT |
| Diarrhea may occur. | *Drink plenty of fluids. *Eat often in small amounts. *Eat low fibre foods such as rice, white bread and cooked vegetables. *Avoid high fibre foods such as bran, whole grain breads and cereals, nuts, raw fruits and raw vegetables. |
| Loss of libido (sex drive) often occurs. | This may return to normal when you stop taking estramustine. |
| Swelling of hands, feet or lower legs may occur if your body retains extra fluid. | *Elevate your feet when sitting. *Avoid tight clothing. |
| Sugar control may be affected in diabetics. | *Check your blood or urine sugar regularly if you are diabetic. |
STOP TAKING YOUR ESTRAMUSTINE AND SEE YOUR DOCTOR OR GET EMERGENCY HELP IMMEDIATELY IF YOU HAVE:
Signs of a blood clot such as sudden tenderness or hardness over a vein; calf tenderness; sudden onset of cough, chest pain or shortness of breath.
Signs of a stroke such as sudden onset of: severe headache, eyesight changes, slurred speech, loss of coordination, weakness or numbness in arm or leg.
Signs of an infection such as fever (over 100degF or 38degC); chills; cough; sore throat; pain or burning when you pass urine; redness, pain or swelling of any area of your body; sores forming anywhere on your body.
Signs of bleeding problems such as black, tarry stools; blood in urine; pinpoint red spots on skin.
SEE YOUR DOCTOR AS SOON AS POSSIBLE (DURING OFFICE HOURS) IF YOU HAVE:
Skin rash. Signs of anemia such as unusual tiredness or weakness.
CHECK WITH YOUR DOCTOR IF ANY OF THE FOLLOWING CONTINUE OR BOTHER YOU:
Uncontrolled nausea, vomiting, or diarrhea. For diabetics; uncontrolled blood sugars. Excessive breast swelling or soreness. Swelling of hands, feet or lower legs.
REPORT ADDITIONAL PROBLEMS TO YOUR DOCTOR.
See Chemotherapy and You: a Guide to Self-help During Treatment available free from the Canadian Cancer Society for more information on managing side effects.
Haskell CM, ed. Cancer treatment, 3rd ed. Philadelphia: WB Saunders Co, 1990:101-2.
Dorr RT, Fritz WL eds. Cancer chemotherapy handbook. New York: Elsevier Science Publishing Co Inc, 1980:407-9.
Reynolds JEF, ed. Martindale: The extra pharmacopoeia, 28th ed. London: Pharmaceutical Press, 1982:208.
Knoben JE, Anderson PO, eds. Handbook of clinical drug data, 6th ed. Hamilton: Drug Intelligence Publications Inc, 1988:408.
Gunnarsson PO, Davidsson T, Andersson SB, et al. Impairment of estramustine phosphate by concurrent intake of milk and food. European J Clin Pharmacol 1990; 38:189-93.
Krogh CME, ed. Compendium of pharmaceuticals and specialties, 27th ed. Ottawa: Canadian Pharmaceutical Association, 1992:378.
BCCA GUEMCYT protocol: Estramustine phosphate for androgen independent prostate cancer, 17 Jul 93.
USP DI Volume I: Drug information for the health care professional, 13th ed. Rockville: United States Pharmacopeial Convention Inc, 1993:1330-2.
Pharmacia (Canada) Inc. Emcyt bottle label. Baie D'Urfe, Quebec.
USP DI Volume II: Advice for the patient: drug information in lay language, 13th ed. Rockville: United States Pharmacopeial Convention Inc, 1993:578-80.
Benson RC, Hartley-Asp. Mechanism of action and clinical uses of estramustine. Cancer Invest 1990; 8:375-80.
Benson RC, Gill GM. Estramustine phosphate compared with diethylstilbestrol. Am J Clin Oncol 1986; 9:341-51.
Benson RC, Wear JB, Gill GM. Treatment of Stage D hormone resistant cancer of the prostate with estramustine phosphate. J Urol 1979; 121:452-4.