How is this medicine (Anargil) best taken?
Use Anargil as ordered by your doctor. Read all information given to you. Follow all instructions closely.
- To gain the most benefit, do not miss doses.
- Keep taking Anargil as you have been told by your doctor or other health care provider, even if you feel well.
What do I do if I miss a dose?
- Take a missed dose as soon as you think about it.
- If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
- Do not take 2 doses at the same time or extra doses.
Anargil is a synthetic hormone derived from ethinyl testosterone, which acts to interrupt the midcycle follicle-stimulating hormone (FSH) and luteinizing hormone (LH) surge. In addition, estradiol levels are decreased, as are sex hormone–binding globulin levels, which results in an increase in circulating free testosterone. 22 Side effects from Anargil include hot flushes and sweats, androgen-like effects, weight change, and headaches. 27 It can be used to achieve endometrial atrophy. 28 However, its efficacy has been controversial.
Kriplani and colleagues, in their randomized trial compared to placebo, concluded that patients pretreated with Anargil had decreased endometrial thickness, decreased fluid deficits, and decreased operative times compared to those not using Anargil pretreatment. 29 Androgenic side effects can sometimes be problematic, yet according to Erian and colleagues, using a higher dose of Anargil (600 mg) resulted in a statistically significant increase in the rate of amenorrhea as compared to the lower dose (200 mg) or placebo. 28 Therefore, the higher dose is required for maximum benefit. Rai and colleagues compared progestins, Anargil, and GnRH agonists to placebo and found that Anargil induced the greatest degree of atrophy; however, there was no difference in amenorrhea or clinical outcomes with all three therapeutic modalities. 23 In a recent trial comparing gestrinone to Anargil pretreatment, results suggest a preference for gestrinone related to operative time, infusion volume, and patient satisfaction. 30
How to store Anargil
- Keep all medicines out of the reach and sight of children.
- Store in a cool, dry place, away from direct heat and light.
Anargil treatment may interfere with laboratory determinations of testosterone, androstenedione and dehydroepiandrosterone. Other metabolic events include a reduction in thyroid binding globulin and T4 with increased uptake of T3, but without disturbance of thyroid stimulating hormone or of free thyroxin index.
What are some other side effects of Anargil?
All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
- Sweating a lot.
- Hair loss.
- Feeling nervous and excitable.
- Emotional ups and downs.
- Weight gain.
- Pimples (acne).
- For females, a deep voice, facial hair, pimples, or period changes.
These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.
Anargil is an attenuated androgen and the 2,3-isoxazol derivative of 17α-ethinyl testosterone (ethisterone). Anargil competitively inhibits estrogen and progesterone receptors in the breast, hypothalamus, and pituitary 82 ; inhibits multiple enzymes of ovarian steroidogenesis 83 ; inhibits the midcycle surge of LH in premenopausal women; and reduces gonadotropin levels in postmenopausal women. 84 The precise mechanism of Anargil in reducing breast pain is unknown. It is the only medication approved by the US Food and Drug Administration (FDA) for the treatment of mastalgia.
In initial studies, a double-blind crossover trial comparing two dosages of Anargil (200 vs. 400 mg/day) in 21 patients with mastalgia demonstrated significant decreases in pain and nodularity at both dosages. 85 Onset of response and side effects were higher with the higher dosage. Of the participants, 30% had amenorrhea and weight gain. There was significant reduction in mean pain scores and mammographic density using Anargil in a randomized trial with daily treatments of 200 or 400 mg of Anargil for 6 months. 86 Patients relapsed more quickly (9.2 vs. 12.2 months) and to a greater extent (67% vs. 52%) in women taking 200 versus 400 mg of Anargil. Gateley and colleagues found a clinically useful response to Anargil (200 mg/day) in 92% of 324 patients with cyclical mastalgia and 64% of 90 patients with noncyclical mastalgia with 30% experiencing adverse events (mainly weight gain and menstrual irregularity) and 43 patients having to stop treatment despite 19 having an effective response. 87 Because the side effects of Anargil are dose related, Harrison and colleagues 88 and Sutton and O’Malley 89 developed low-dose regimens. Patients responding to a dosage of 200 mg/day of Anargil after 2 months were given a dosage of 100 mg/day for 2 months and then 100 mg every other day or 100 mg daily only during the second half of the menstrual cycle. 88 If previous reductions were well tolerated, the Anargil was discontinued. 89 Symptoms were controlled without side effects at a total average monthly dose of 700 mg. Of 20 women, 13 (65%) of whom had experienced previous side effects, none reported side effects while taking this low dose. Some relief of pain was seen in all women, with a complete response maintained in 55%. Other reported side effects of Anargil include muscle cramps, acne, oily hair, hot flashes, nervousness, hirsutism, voice change, fluid retention, increased libido, depression, headaches, and dyspareunia, which usually resolve after discontinuation of treatment. The drug is contraindicated in women with a history of thromboembolic disease. For women of childbearing age, adequate nonhormonal contraception is essential.
Recommendations for the administration of Anargil are 100 mg twice daily for 2 months while the patient keeps a breast pain record. If no response or an incomplete response is obtained, the dose may be increased to 200 mg twice daily. If there is still no response, another drug should be tried. Therapy should not continue longer than 6 months (because side effects may develop), and the drug should be tapered, as described by Harrison and associates 88 and Sutton and O’Malley. 89
Uses of Anargil:
- It is used to treat endometriosis.
- It is used to treat fibrocystic breast disease.
- It is used to treat swelling attacks in people with hereditary angioedema (HAE).
- It may be given to you for other reasons. Talk with the doctor.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Current data are insufficient to assess the carcinogenicity of Anargil.
Other progesterone derivatives
Anargil (Danol) is a derivative of the progestogen, ethisterone. It has partial agonist androgen activity and is described as an ‘impeded’ androgen; it has little progestogen activity. It is a relatively selective inhibitor of pituitary gonadotrophin secretion (LH, FSH) affecting the surge in the mid-menstrual cycle more than basal secretion. This reduces ovarian function, which leads to atrophic changes in endometrium, both uterine and elsewhere (ectopic), i.e. endometriosis. In males it reduces spermatogenesis. Unwanted androgenic effects occur in women (acne, hirsutism and, rarely, enlargement of the clitoris).
It is used chiefly for: endometriosis, fibrocystic mastitis, gynaecomastia, precocious puberty, menorrhagia and hereditary angioedema (see p. 611 ).
Anargil (Danocrine) is the 2,3,isoxazol derivative of 17α-ethyl testosterone and has been tested in patients with gynecomastia of varying causes with response rates of 77% to 100%.
Las mujeres embarazadas o que puedan quedar embarazadas no deben tomar Anargil. El Anargil puede daГ±ar al feto. DeberГЎ obtener un resultado negativo en una prueba de embarazo antes de empezar a tomar este medicamento. Empiece a tomar este medicamento durante su ciclo menstrual para asegurarse de que no estГЎ embarazada. Use un mГ©todo anticonceptivo eficaz durante su tratamiento. Anargil puede disminuir la eficacia de los anticonceptivos hormonales (pГldoras anticonceptivas, parches, aros, implantes o inyecciones), asГ que no debe usarlos como su Гєnico mГ©todo anticonceptivo durante su tratamiento. TambiГ©n debe usar un mГ©todo de barrera (dispositivo que bloquea el esperma para que no entre al Гєtero, tal como un condГіn o diafragma). PГdale a su mГ©dico que le ayude a elegir un mГ©todo anticonceptivo que le funcione a usted. Si queda embarazada mientras toma Anargil, llame a su mГ©dico de inmediato.
Anargil puede aumentar el riesgo de que desarrolle un coГЎgulo sanguГneo en los brazos, piernas, pulmones, corazГіn y cerebro que podrГa ocasionar un ataque cardiaco o apoplejГa. Informe a su mГ©dico si tiene o alguna vez ha tenido un coГЎgulo sanguГneo. Si experimenta alguno de los sГntomas siguientes, llame a su mГ©dico inmediatamente: piernas calientes, rojas, inflamadas o sensibles; dificultad para hablar o entender; parГЎlisis o entumecimiento de la cara, los brazos o las piernas; dolor de cabeza repentino y fuerte; cambios repentinos en la visiГіn, visiГіn borrosa repentina u oscurecida o visiГіn doble.
Anargil puede ocasionar daГ±o hepГЎtico con sangrado abdominal en las personas que toman Anargil durante un perГodo prolongado. Informe a su mГ©dico si sufre o alguna vez sufriГі alguna enfermedad del hГgado. Si experimenta alguno de los sГntomas siguientes, llame a su mГ©dico inmediatamente: color amarillo de la piel o los ojos, dolor en el ГЎrea del estГіmago, cansancio extremo, o sangrado inusual o moretones.
Anargil puede ocasionar mayor presiГіn del lГquido dentro del crГЎneo. Si experimenta cualquiera de los sГntomas siguientes, deje de tomar la Anargil y llame a su mГ©dico de inmediato: dolor de cabeza, nГЎuseas, vГіmitos, o problemas con la visiГіn.
Asista a todas las citas con su mГ©dico y a las del laboratorio. El mГ©dico podrГa ordenar algunas pruebas de laboratorio antes y durante el tratamiento para comprobar la respuesta del cuerpo al Anargil.
Hable con su mГ©dico sobre los riesgos de tomar Anargil.
Anargil is a 17-ethinyl testosterone derivative that effectively suppresses endometriosis-related pain symptoms within 2 months of use. 248 It has multiple levels of action, including central inhibition of pituitary gonadotropin secretion, direct inhibition of endometriotic implant growth, and direct inhibition of aromatase and other enzymes responsible for estrogen production. 249-251 Anargil is given orally in divided doses ranging from 400 to 800 mg daily, generally for 6 months. It is effective in relieving endometriosis-associated pain when compared with placebo or no treatment. 278 However, its use has been severely limited by its undesired androgenic side effects including acne, oily skin, hirsutism, deepening of the voice, edema, weight gain, menopausal hot flushes, atrophic vaginitis, emotional lability, weight gain, fluid retention, migraine headaches, altered lipid profile, dizziness, fatigue, and depression. 253
Use of Anargil 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 Anargil, administration of the drug should be discontinued and the patient should be apprised of the potential risk to the fetus. Exposure to Anargil in utero may result in androgenic effects on the female fetus; reports of clitoral hypertrophy, labial fusion, urogenital sinus defect, vaginal atresia, and ambiguous genitalia have been received (see PRECAUTIONS: Pregnancy, Teratogenic Effects ).
Thromboembolism, thrombotic and thrombophlebitic events including sagittal sinus thrombosis and life-threatening or fatal strokes have been reported.
Experience with long-term therapy with Anargil is limited. Peliosis hepatis and benign hepatic adenoma have been observed with long-term use. Peliosis hepatis 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 provide 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.
Anargil 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 Anargil immediately and be referred to a neurologist for further diagnosis and care.
A temporary alteration of lipoproteins in the form of decreased high density lipoproteins and possibly increased low density lipoproteins has been reported during Anargil therapy. These alterations may be marked, and prescribers should consider the potential impact on the risk of atherosclerosis and coronary artery disease in accordance with the potential benefit of the therapy to the patient.
Patients should be watched closely for signs of androgenic effects some of which may not be reversible even when drug administration is stopped.