medroxyprogesterone acetate and estradiol cypionate
Lunelle

Available forms
Available by prescription only
Injection: 25 mg medroxyprogesterone acetate and 5 mg estradiol cypionate per 0.5 ml

Indications and dosages
 Prevention of pregnancy. Women older than age 16 who have achieved menarche: 0.5 ml I.M. into deltoid, gluteus maximus, or anterior thigh. Give first injection within first 5 days of onset of a normal menstrual period, within 5 days of a complete first trimester abortion, or at least 4 weeks postpartum if not breast-feeding (at least 6 weeks postpartum if breast-feeding). Give second and subsequent injections monthly (28 to 30 days, not to exceed 33 days) after previous injection.

Pharmacodynamics
Contraceptive action: Medroxyprogesterone acetate and estradiol cypionate inhibit secretion of gonadotropins, which prevents follicular maturation and ovulation. Other possible actions include thickening of cervical mucus, reduction of the volume of cervical mucus, and thinning of the endometrium.

Pharmacokinetics
Absorption: Maximum plasma level typically occurs within 1 to 10 days postinjection for medroxyprogesterone and 1 to 7 days postinjection for estradiol cypionate.
Distribution: Medroxyprogesterone acetate binds primarily to serum albumin. Estradiol is primarily bound to sex hormone-binding globulin and albumin. About 3% of estradiol remains unbound. Unbound estrogens are known to modulate pharmacologic response.
Metabolism: Medroxyprogesterone acetate is metabolized to numerous derivatives. Estradiol cypionate is metabolized to a parent active compound.
Excretion: Most medroxyprogesterone is excreted in the urine as glucoronide conjugates with only small amounts as sulfates. Estrogen metabolites are primarily excreted in the urine as glucorunides and sulfates.

Contraindications and precautions
Contraindicated in patients with known or suspected pregnancy, thrombophlebitis or thromboembolic disorders, a history of deep vein thrombophlebitis or thromboembolic disorders, and cerebral vascular or coronary artery disease. Also contraindicated in patients with undiagnosed abnormal genital bleeding and in patients with liver dysfunction or disease (such as history of hepatic adenoma or carcinoma), or history of cholestatic jaundice of pregnancy or jaundice with prior hormonal contraceptive use, including severe pruritus of pregnancy. Contraindicated in patients with carcinoma of the endometrium, breast, or other known or suspected estrogen-dependent neoplasia. Also contraindicated in patients hypersensitive to any of drug’s ingredients, patients who smoke heavily (15 or more cigarettes per day) and are older than age 35, and patients with severe hypertension, diabetes with vascular involvement, headaches with focal neurologic symptoms, and valvular heart disease with complications.
  Use cautiously in patients with hypertension, hyperlipidemias, obesity, diabetes, and liver dysfunction. Also use cautiously in patients who smoke and in patients with a history of depression.

Interactions
Drug-drug. Acetaminophen: Decreases plasma levels. Monitor patient.
Aminoglutethimide: May decrease medroxyprogesterone acetate levels. Recommend additional method of contraception.
Antibiotics (ampicillin, griseofulvin, tetracycline): Decreases contraceptive effectiveness. Recommend additional method of contraception.
Anticonvulsants (carbamazepine, phenobarbital, phenytoin): Increases metabolism of some synthetic estrogens and progestins, which could result in reduced contraceptive effectiveness. Recommend additional method of contraception.
Cyclosporine, prednisolone, theophylline: Increases levels of these drugs. Monitor serum levels and adjust as needed.
Phenylbutazone: May decrease contraceptive effectiveness and increase menstrual irregularities. Recommend additional method of contraception.
Rifampin: Increases metabolism of some synthetic estrogens and progestins, resulting in decreased contraceptive effectiveness and more irregular bleeding. Recommend additional method of contraception.
Drug-herb. St John’s wort: May induce hepatic enzymes (cytochrome P-450) and transporter proteins, reduce the effectiveness of contraceptives, and result in breakthrough bleeding. Discourage use or advise use of a second method of contraception.
Drug-lifestyle. Smoking: Increases risk of thromboembolic disorders. Discourage smoking.

Adverse reactions
CNS: emotional lability, depression, headache, nervousness, dizziness, asthenia.
CV: thromboembolism, edema.
EENT: intolerance to contact lenses.
GI: abdominal pain, nausea, enlarged abdomen.
GU: amenorrhea, dysmenorrhea, menorrhagia, metrorrhagia, vaginal candidiasis, vulvovaginal disorder.
Hepatic: tumors, cholestatic jaundice.
Metabolic: weight gain.
Skin: acne, alopecia.
Other: breast tenderness or pain, decreased libido, hypersensitivty reactions, gall bladder disease.

Effects on lab test results
• May increase total circulating sex steroid, corticoid, triglyceride, plasma and urinary steroid, gonadotropin, sulfobromophthalein, folate, prothrombin, and factor VII, VIII, IX, and X levels. May decrease antithrombin III level.
• May increase liver function test values, norepinephrine-induced platelet aggregability, thyroid-binding globulin, and total thyroid hormone. May decrease free T₃ resin uptake, glucose tolerance, and sex hormone-binding globulin concentration.

Overdose and treatment
Overdose may cause nausea, vomiting, vaginal bleeding, or other menstrual irregularities.
 Supportive measures are recommended.

Special considerations
• The use of hormonal contraceptives is linked to increased risk of MI, CVA, hepatic neoplasia, and gallbladder disease.
• Monthly injection is effective for contraception during the first cycle of use when administered as recommended.
• If more than 33 days have elapsed since last injection, pregnancy should be considered and another injection shouldn’t be given until pregnancy is ruled out.
• Shortening the injection interval could lead to a change in menstrual pattern.
• Don’t use bleeding episodes to guide the injection schedule.
• Shake the aqueous suspension vigorously just before use to ensure a uniform suspension.
• Provide yearly physical examinations. Monitor breast examination closely in women with breast nodules or family history of breast cancer.
• When switching patients from other methods of birth control, give drug in a manner that ensures continuous contraceptive coverage based on the mechanism of action from both methods. For example, patients switching from hormonal contraceptives should have their first injection within 7 days after taking their last active pill.
• Discontinue use at least 4 weeks before and for 2 weeks after elective surgery that may be linked to increased risk of thromboembolism.
• Don’t use during periods of prolonged immobilization or within 4 weeks after childbirth.
• Store injection at 59° to 86° F (15° to 30° C).
Breast-feeding patients
• Effects of drug in breast-feeding women haven’t been evaluated and are unknown. However, estrogen administration to breast-feeding women has resulted in a decrease in the quantity and quality of breast milk.
• Small amounts of combined hormonal contraceptives have appeared in breast milk with no deleterious effects to the child. However, breast-feeding women shouldn’t begin a combined hormonal contraceptive until 6 weeks postpartum.
Pediatric patients
• Use of this product before menarche isn’t indicated.
• Safety and efficacy are expected to be the same in adolescents younger than age 16.
Geriatric patients
• Not indicated in postmenopausal women.

Patient education
 ALERT Teach patient that this product is intended to prevent pregnancy and won’t protect against sexually transmitted diseases, such as HIV (AIDS), genital warts, genital herpes, chlamydia, gonorrhea, hepatitis B, and syphillis.
• Advise patient that injection must be given every 28 to 30 days. If more than 33 days have passed since an injection, pregnancy must be ruled out before another injection can be given.
• Tell patient that menstrual bleeding patterns may be disrupted while receiving drug. Advise patient to report excessive or prolonged bleeding.
• Tell patient that weight gain may occur while taking drug.
• Advise patient who wears contact lenses to have an eye examination if visual changes or changes in lens tolerance develop while taking drug.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use