Full Prescribing Info
Contents
Drospirenone, ethinyl estradiol.
Description
Each tablet contains: Drospirenone 3.00 mg, Ethinyl Estradiol 0.03 mg.
Excipients/Inactive Ingredients: Lactose monohydrate, Maize starch, Pregelatinized starch, Crosspovidone (Plasdone XL-10), Crosspovidone (Plasdone XL), Povidone K-30, Polysorbate 80, Magnesium stearate, Methylene chloride, Methanol, Opadry II yellow, Purified water.
Action
Pharmacology: Pharmacodynamics: Estrogen-prosgestin combinations produce a contraceptive effect mainly by suppressing the hypothalamic-pituitary system resulting in prevention of ovulation. The estrogen acts mainly by suppressing secretion of follicle-stimulating hormone (FSH), resulting in prevention of follicular development and the rise of plasma estradiol concentration which is thought to be the stimulus for release of luteinizing hormone (LH). In combination products, the progestin appears to act mainly by inhibiting the preovulatory rise of LH. Long-term administration of these combination products results inhibition of both FSH and LH secretion. It has been suggested that oral contraceptives may also produce a direct effect on ovarian steroidogenesis or the response of the ovary to gonadotropins. In addition, changes in the cervical mucus may prevent sperm penetration; however, further studies are required to determine the precise effects of estrogen-progestin combinations on sperm activity.
Endometrial changes depend on the type of oral contraceptive administered. Conventional-cycle combination products are usually associated with a shortened period of endometrial proliferation followed by an early but brief and limited secretory activity in the epithelium of endometrial glands. After several oral contraceptive cycles, thinning or regression of the endometrium may occur, resulting in reduced menstrual flow or possible amenorrhea.
Pharmacokinetics: Estrogens: Ethinyl estradiol is rapidly absorbed with peak concentrations attained within 2 hours. It undergoes considerable first-pass elimination. Mestranol is demethylated to ethinyl estradiol. Ethinyl estradiol is 97% to 98% bound to plasma albumin. Half-life varies from 6 to 20 hours. It is excreted in bile and urine as conjugates and undergoes some enterohepatic recirculation. Estradiol valerate peak concentrations are attained within approximately 6 hours with 60% bound to plasma albumin. Estradiol undergoes extensive first-pass effect and metabolites are mainly excreted in the urine. The terminal half-life is approximately 14 hours.
Drospirenone: Absorption: Oral contraceptive steroids are generally well absorbed from GI tract.
Absolute bioavailability: 76%.
Mean peak serum concentration: 36.9 ng/mL at about 1.7 hours.
Peak serum concentrations: 1 to 3 hours after administration.
Steady state: mean peak drospirenone concentration of 78.7-87.5 ng/mL in about 1.6-1.8 hours after a dose.
Distribution: Contraceptive steroids are widely distributed into body tissue and fluids. The apparent volume of distribution for contraceptive steroid reportly ranges from 1.5-4.3 L/kg.
Protein bound: 97% with albumin. It does not appear to bind to sex hormone binding globulin (SHBG).
Metabolism: Drospirenone is metabolized to 2 major inactive metabolites, which according to one study are formed independently of the cytochrome P-450 enzyme system. The manufacturers state that drospirenone is metabolized only to a minor extent in vitro, mainly by CYP3A4. At least 20 metabolites have been detected in urine or feces.
Elimination: Terminal half-life: 30 hours.
Toxicology: Preclinical safety data: Mutagenicity and carcinogenicity: Chromosomal abnormalities determined in peripheral lymphocytes have been increased in woman receiving oral contraceptives compared with non users.
Prolonged continuous administration of natural or synthetic estrogen in certain animal species increases the frequency of certain benign or malignant tumors including those of the breast, cervix, uterus, vagina, ovary, pituitary and liver. Drospirenone has increased the frequency of benign and total (benign plus malignant) adrenal gland pheochromocytomas in rats and the frequency of carcinoma of the harderian gland in mice.
Fertility: Studies have found a slight delay in return to fertility but no absolute impairment of fertility following discontinuance of fixed-combination conventional-cycle oral contraceptives. A survey of pregnant women attending antenatal clinics in England reported that the time to conception following discontinuance of long-term (i.e., longer than 2 years) use of fixed-combination oral contraceptives (8.2 months) was two fold longer than time to conception following condom use (4.2 months).
Indications/Uses
Prevention of pregnancy. The patient may also experience the following additional benefits: improvement in symptoms such as bloating, swelling or weight gain, due to fluid retention. Improvement in acne, and reduction in greasiness of the skin and hair.
Dosage/Direction for Use
Take the tablet at about the same time each day, with some liquid if necessary. Follow the direction of the arrows until all 21 tablets have been taken. During the next 7 days take no tablets. A period should begin during these 7 days (the withdrawal bleed). Usually it will start on day 2-3 after the last tablet. Start taking the next pack on the 8th day (the day after the 7-day tablet-free break) even if the period continues. This means that new packs will always start on the same day of the week, and withdrawal bleed will occur on about the same days, each month.
Start with the first pack: Start taking Gveza on the first day of the cycle (that is, the first day of period). Take a tablet marked with that day of the week. For example, if period starts on a Friday, take a tablet marked Friday. Then follow the days in order. Gveza will work immediately, it is not necessary to use an additional contraceptive method.
Missed dose: Depending on the day of the cycle on which one tablet has been missed, patient may need to take additional contraceptive precautions, for example a barrier method such as a condom. Take the tablets according to the following principles: If less than 12 hours late when taking a tablet, the protection against pregnancy is not reduced. Take the tablet as soon as remembered and then continue taking the tablets again at the usual time.
If more than 12 hours late in taking a tablet, protection against pregnancy may be reduced. The more tablets forgotten, the greater the risk that the protection from pregnancy is reduced. There is a particularly high risk of becoming pregnant if tablets are missed at the beginning of the pack or at the end (the last of the 21 tablets). Therefore, follow the rules given as follows.
More than one tablet forgotten in a pack: Contact a doctor.
Do not take more than 2 tablets on a given day, to make up for missed pills.
If tablets are forgotten in a pack, and there is no expected bleeding that should start in the normal tablet free break, pregnancy is a possibility. Contact a doctor before starting the next pack.
1 tablet missed during week 1: If patient has forgotten to start a new pack, or have missed tablet(s) during the first 7 days of the pack, there is a risk of being pregnant (if they had sex in the 7 days before forgetting the tablet). In that case contact a doctor before starting the next pack. See also the "missed pill chart" for details.
If patient has had no sex in the 7 days before the oversight, take the missed tablet as soon as remembered (even if this means taking two tablets at the same time) and take the next tablets at the usual time. Use extra contraceptive precautions (barrier method) for the next 7 days.
1 tablet missed during week 2: Take the missed tablet as soon as remembered (even if this means taking two tablets at the same time) and take the next tablets at the usual time. The reliability of the pill is maintained. There is no need to use extra contraceptive precautions.
1 tablet missed during week 3: Choose either of the following options, without the need for extra contraceptive precautions.
1. Take the missed tablet as soon as remembered (even if this means taking two tablets at the same time) and take the next tablets at the usual time. Start the next pack as soon as the current pack is finished so that no gap is left between packs. A withdrawal bleed may not occur until the end of the second pack but may have spotting or breakthrough bleeding while taking the tablets. Or
2. Stop taking tablets from the current pack, have a tablet-free break of 7 days or less (also count the day a tablet is missed) and continue with the next pack. (See Figure.)

Click on icon to see table/diagram/image

Dosage adjustment in hepatic impairment: Contraindicated in patients with hepatic dysfunction.
Dosage adjustment in renal impairment: I.V.: Note: Contraindicated in patients with renal dysfunction.
Overdosage
Serious ill effects have not been reported following acute overdosage of OCs in young children. Overdosage may cause nausea and vomiting. Withdrawal bleeding may occur in females.
Because drospirenone has antimineralocorticoid properties, serum potassium and sodium concentrations and indicators of metabolic acidosis should be monitored in the event of overdosage with a drospirenone-containing oral contraceptive.
Contraindications
In women who are hypersensitive to the drug or any ingredient in the formulation and in those with known or suspected pregnancy, undiagnosed abnormal genital bleeding, diplopia or any ocular lesion arising from ophthalmic vascular disease, classical migraine, active liver disease, or history of cholestatic jaundice with pregnancy or with prior use of oral contraceptives.
The drug also are contraindicated during breast-feeding and in women who have or have had thrombophlebitis or thromboembolic disorders, cerebrovascular or coronary artery disease (including myocardial infraction), severe hypertension, diabetes with vascular involvement, known or suspected carcinoma of the breast, known or suspected estrogen-dependent neoplasia (eg, carcinoma of the endometrium), or benign or malignant liver tumor that developed during oral contraceptive or other estrogen use. Oral contraceptives containing the progestin drospirenone are contraindicated in women with renal impairment, hepatic tumors (benign or malignant) or hepatic disease, adrenal insufficiency, high risk of arterial or venous thrombotic diseases, undiagnosed abnormal uterine bleeding, history of breast cancer or other estrogen- or progestin-sensitive cancer, and in pregnancy.
Special Precautions
Use of estrogen-progestin oral contraceptives is associated with an increased risk of several serious conditions including thromboembolism, arterial thrombosis (e.g., stroke, myocardial infarction), liver tumor, gallbladder disease, visual disturbances, fetal abnormalities, and hypertension. The risk of thrombotic events is even higher in women with other risk factors for these events. Cigarette smoking increases the risk of serious adverse cardiovascular effects during oral contraceptive use. The risk increases with age and with heavy smoking (15 or more cigarettes daily) and is markedly greater in women older than 35 years of age. Women who are receiving estrogen-progestin contraceptives should be strongly advised not to smoke. Women older than 35 years of age who smoke, and women with ischemic heart disease or a history of this disease, should not use estrogen-progestin contraceptives. Estrogen-progestin contraceptives should be used with caution in women with cardiovascular disease risk factors. In addition, potential noncontraceptive benefits associated with use of estrogen-progestin contraceptives can be considered.
Women receiving estrogen-progestin contraceptives should be advised to notify their clinician if signs or symptoms of thromboembolic or thrombotic disorders (e.g., thrombophlebitis, pulmonary embolism, cerebrovascular insufficiency, coronary occlusion, retinal thrombosis, mesenteric thrombosis) occur, including sudden severe headache or vomiting, disturbance of vision or speech, sudden partial or complete loss of vision, dizziness or faintness, weakness or numbness in an extremity, sharp or crushing chest pain, unexplained cough, hemoptysis, sudden shortness of breath, calf pain, or heaviness in the chest. Oral contraceptive combinations containing drospirenone should be discontinued if an arterial or venous thrombotic event occurs during therapy. Women currently receiving an oral contraceptive combination containing drospirenone should be informed of the potential risk of thromboembolic events. Patients also should be advised about the current information available regarding the risk of VTE with oral contraceptives containing drospirenone. Known risk factors for development of VTE include smoking, obesity family history, and other factors that contraindicate the use of oral contraceptive combinations. Patients should discuss their risk of VTE with their clinician before deciding which contraceptive method to use. The risk of thromboembolic disease associated with oral contraceptive use gradually disappears after such therapy is discontinued. However, the FDA states that patients should not discontinue oral contraceptives containing drospirenone without consulting a clinician.
Effects on ability to drive and use machine: No information.
Use in Children: Safety and efficacy of estrogen-progestin contraceptives have been established in women of reproductive age. Safety and efficacy are expected to be identical for postpubertal adolescents under 16 years of age and user 16 years of age or older. Estrogen-progestin contraceptive are not indicated before menarche.
Use in Elderly: Oral contraceptives have not been evaluated in women 65 years of age and older and are not indicated in this population.
Use In Pregnancy & Lactation
Pregnancy: (Pregnancy category X).
Rule out pregnancy before initiating or continuing OCs and always consider it if withdrawal bleeding does not occur. Rule out pregnancy before continuing OCs for any patient who has missed 2 consecutive periods. If the patient has not adhered to the prescribed schedule, consider the possibility of pregnancy at the time of the first missed period and withhold further use until pregnancy has been ruled out. If pregnancy is confirmed, apprise the patient of the potential risks to the fetus. The majority of recent studies do not indicate a teratogenic effect, particularly cardiac anomalies and limb reduction defects, when OCs are taken inadvertently during early pregnancy.
The use of female sex hormones (eg, estrogens) during early pregnancy may seriously damage the offspring. However, there is no conclusive evidence that OC use is associated with an increase in birth defects when taken inadvertently during early pregnancy. Previously, a few studies reported that OCs might be associated with birth defects, but these findings have not been seen in more recent studies. Nevertheless, do not use during pregnancy unless clearly necessary.
Do not administer OCs to induce withdrawal bleeding as a test for pregnancy.
Do not use OCs during pregnancy to treat threatened or habitual abortion.
Lactation: Estrogen-progestin contraceptives may decrease the quantity and quality of milk if given in the immediate postpartum period. Small amounts of the hormonal agents in estrogen-progestin contraceptives are distributed into milk and adverse effects such as jaundice and breast enlargement have been reported in nursing infants of woman receiving cyclic regimens; therefore, because of the theoretical risk, some clinicians recommend that lactating women receiving high-dose postcoital contraceptive regimens use alternative milk sources for their infants for at least 24 hours after completion of the regimen. When possible, the use of cyclic estrogen-progestin contraceptives should be deferred until the infant has been weaned. Long-term follow-up after oral contraceptive use showed no apparent clinical effect on breast-feeding mothers or children whose mothers were breast-feeding and using oral contraceptives.
Adverse Reactions
Serious: Arterial thromboembolism; cerebral hemorrhage; cerebral thrombosis; coronary thrombosis; focal nodular hyperplasia of the liver; gall bladder disease; hepatic adenomas or benign liver tumors; hypertension; mesenteric thrombosis; MI; pulmonary embolism; ruptured cyst; thrombophlebitis and venous thrombosis with or without embolism; uterine leiomyoma.
CNS: Dizziness, headache; mental depression; migraine.
Dermatologic: Melasma (may persist); rash (allergic).
Endocrine: Breast pain, tenderness, enlargement, secretion, diminution in lactation when given immediately postpartum.
GI: Abdominal cramps, bloating; cholestatic jaundice; nausea and vomiting (occurring in approximately 10% to 30% of patients during the first cycle, less common with low doses, and the majority resolve in 3 months).
GU: Amenorrhea during and after treatment; BTB (the majority, more than 80%, resolve in 3 months), spotting, change in menstrual flow; change in cervical erosion and secretions; invasive cervical cancer; temporary infertility after discontinuation; vaginal candidiasis.
Ophthalmic: Change in corneal curvature (steepening); contact lens intolerance; neuro-ocular lesions (eg, retinal thrombosis, optic neuritis).
Miscellaneous: Edema; reduced carbohydrate tolerance; weight change (increase or decrease); prevalence of cervical chlamydia trachomatis may be increased; hirsutism (rare).
The following associations have been neither confirmed nor refuted: acne; acute hepatitis; anemia; Budd-Chiarri syndrome; cataracts; cerebrovascular disease with mitral valve prolapse; changes in appetite; change in libido; colitis; colonic Crohn disease; cystitis-like syndrome; dizziness; EEG abnormalities; endometrial, cervical, and breast carcinoma; erythema multiforme; erythema nodosum; fatigue; gingivitis; headache; hemolytic uremic syndrome; hemorrhagic eruption; herpes gestationis; hirsutism; itching; loss of scalp hair; lupus erythematosus or lupus-like syndromes; malignant hypertension; malignant melanoma; nervousness; pancreatitis; porphyria; photosensitivity; pituitary tumors; premenstrual syndrome; pulmonary embolism; renal function impairment; rhinitis; sickle cell disease; vaginitis.
Drug Interactions
See Table.

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Caution For Usage
Incompatibilities: No information.
Storage
Do not store above 30 °C.
MIMS Class
ATC Classification
G03AA12 - drospirenone and ethinylestradiol ; Belongs to the class of progestogens and estrogens in fixed combinations. Used as systemic contraceptives.
Presentation/Packing
FC tab (round, yellow) x 21's.
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