Usual Adult Dose for Endometriosis

Mild Disease:

• Initial dose: 200 to 400 mg orally per day, given in 2 divided doses
• Maintenance dose: Gradual downward titrations should be performed to maintain amenorrhea.
• Duration of therapy: Up to 9 months

Moderate to Severe Disease or Patients Infertile due to Endometriosis:

• Initial dose: 800 mg orally per day, given in 2 divided doses
• Maintenance dose: Gradual downward titrations should be performed to maintain amenorrhea.
• Duration of therapy: Up to 9 months

Comments:

• Treatment should begin during menstruation, OR appropriate pregnancy tests should be performed prior to starting treatment ensure that the patient is not pregnant while on treatment.
• Treatment should continue uninterrupted 3 to 6 months, but may continue for up to 9 months.
• Treatment may be reinstituted if symptoms recur.

Use: Treatment of endometriosis amenable to hormonal management

Usual Adult Dose for Fibrocystic Breast Disease

100 to 400 mg orally per day, given in 2 divided doses

Comments:

• Most patients may be treated with simple measures (e.g., padded brassieres, analgesics). Patients requiring treatment with this drug may have symptoms of severe pain and tenderness.
• Patients should be advised that treatment is not innocuous; hormone level alterations and symptom recurrence are very common after discontinuation of treatment.
• This drug is usually effective in decreasing symptoms of fibrocystic breast disease (e.g., nodularity, pain, tenderness); pain and tenderness are typically eliminated in 2 to 3 months, and nodularity is usually eliminated after 4 to 6 months of uninterrupted treatment.
• Approximately 50% of patients will have symptom recurrence within 1 year; treatment may be reinstated in this patient population if necessary.

Use: Treatment of symptomatic fibrocystic breast disease by suppression of ovarian function

Usual Adult Dose for Angioedema

Initial dose: 200 mg orally 2 to 3 times a day

• After a favorable initial response, continuing doses should be determined by decreasing the dose by 50% or less at intervals of 1 to 3 months (or longer).
• If an attack occurs, the daily dose may be increased by 200 mg.

Comment: Patients should be monitored closely during dose adjustments, especially in patients with airway involvement.

Use: Prevention of all types of angioedema (e.g., cutaneous, abdominal, laryngeal) in male and female patients

Renal Dose Adjustments

Renal dysfunction: Data not available
Marked renal dysfunction: Contraindicated

Liver Dose Adjustments

Liver dysfunction: Frequent monitoring recommended.
Marked liver dysfunction: Contraindicated

Precautions

US BOXED WARNINGS:
PREGNANCY:

• Use of this drug in pregnancy is contraindicated.
• A sensitive test (e.g., beta subunit test if available) capable of determining early pregnancy is recommended immediately prior to start of therapy.
• Additionally, a non-hormonal method of contraception should be used during therapy.
• If a patient becomes pregnant while taking this drug, administration of the drug should be discontinued and the patient should be apprised of the potential risk to the fetus.
• Exposure to this drug in utero may result in androgenic effects of the female fetus; reports of clitoral hypertrophy, labial fusion, urogenital sinus defect, vaginal atresia, and ambiguous genitalia have been received.

STROKE RISK:

• Thromboembolism, thrombotic and thrombophlebitic events including sagittal sinus thrombosis and life-threatening or fatal strokes have been reported.

HEPATIC EFFECTS:

• Experience with long-term therapy with this drug is limited. Peliosis hepatitis and benign hepatic adenoma have been observed with long-term use. Peliosis hepatitis and hepatic adenoma may be silent until complicated by acute, potentially life-threatening intraabdominal hemorrhage.
• The physician therefore should be alert to this possibility.
• Attempts should be made to determine the lowest dose that will prove adequate protection.
• If the drug was begun at a time of exacerbation of hereditary angioneurotic edema due to trauma, stress or other cause, periodic attempts to decrease or withdraw therapy should be considered.

PSEUDOTUMOR CEREBRI:

• This drug has been associated with several cases of benign intracranial hypertension, also known as pseudotumor cerebri.
• Early signs and symptoms of benign intracranial hypertension include papilledema, headache, nausea and vomiting, and visual disturbances.
• Patients with these symptoms should be screened for papilledema and, if present, the patients should be advised to discontinue this drug immediately and be referred to a neurologist for further diagnosis and care.

Safety and efficacy have not been established in patients younger than 18 years; this drug is not recommended for use in these patients.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Non-hormonal contraceptive devices should be used during treatment.

Storage requirements:

• Protect from light.

General:

• Ovulation and cyclic bleeding usually resume within 60 to 90 days after discontinuation of treatment.
• This drug may be used in conjunction with surgery or in patients not responding to other treatments (as sole therapy) for the treatment of endometriosis.

Monitoring:

• Hematologic: Periodic hematologic tests
• Hepatic: Periodic liver function tests; hepatic ultrasonography (for patients receiving repeated treatment courses or on long-term treatment)
• Respiratory: Change in voice

Patient advice:

• Patients, especially professional singers, should be told to immediately report any change in voice during or after treatment.
• Patients should be told to use non-hormonal methods of contraception during treatment.
• Patients of childbearing potential should be apprised of the potential harm to the fetus.
• Female patients should discontinue treatment and should speak to a healthcare provider immediately if pregnancy occurs.