Aleena is a progestin indicated for females as an oral contraceptive.

Drospirenone is a progestin and is indicated for use by females of reproductive potential to prevent pregnancy. It is an oral contraceptive that lowers the risk of becoming pregnant primarily by suppressing ovulation. Drospirenone is a spironolactone analogue with anti-mineralocorticoid activity.

Absorption: The pharmacokinetics of oral Drospirenone is dose-proportional following single doses ranging from 1-10 mg. Maximum concentrations (Cmax) of Drospirenone in plasma of about 27 ng/ml are reached at about 2-6 hours after single ingestion of During a treatment cycle, maximum steady-state concentrations of Drospirenone in serum of about 41 ng/ml are reached after about 10 days of treatment. Concomitant ingestion of food has no influence on the extent of absorption of Drospirenone.

Distribution: Drospirenone is 95% to 97% bound to serum albumin & does not bind to sex hormone binding globulin (SHBG) or corticosteroid-binding globulin (CBG). The apparent volume of distribution of Drospirenone is approximately 4 L/kg.

Metabolism: Drospirenone is extensively metabolized after oral administration. The two main metabolites of found in human plasma were identified to be the acid form of generated by opening of the lactone ring and the 4,5-dihydro Drospirenone-3-sulfate, formed by reduction and subsequent sulfation. These metabolites were shown not to be pharmacologically active. Drospirenone is also subject to oxidative metabolism catalyzed by CYP3A4.

Excretion: Drospirenone serum concentrations are characterized by a terminal disposition phase half-life of approximately 30 hours after both single and multiple dose regimens. Excretion of Drospirenone was nearly complete after ten days and amounts excreted were slightly higher in feces compared to urine. Drospirenone was extensively metabolized and only trace amounts of unchanged Drospirenone were excreted in urine and feces.

Drospirenone (white active and light pink inert tablets) is swallowed whole once a day. Take one tablet daily for 28 consecutive days; one white active tablet daily during the first 24 days and one light pink inert tablet daily during the 4 following days. Tablets must be taken every day at about the same time of the day so that the interval between two tablets is always 24 hours.

Instructions for starting of Drospirenone: Starting in females with no current use of hormonal contraception (Day 1 Start) Important: Consider the possibility of ovulation and conception prior to initiation of this product. Tablet Color: Drospirenone active tablets are white (Day 1 to Day 24). Drospirenone inert tablets are light pink (Day 25 to Day 28).

Day 1 Start :

Take the first white active tablet on the first day of menses.

Take subsequent white active tablets once daily at the same time each day for a total of 24 days.

Take one light pink inert tablet daily for 4 days and at time of day that active tablets were taken.

Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the day after taking the last inactive tablet).

Instructions for switching of Drospirenone:

Switching from another contraceptive method to Drospirenone: Start Drospirenone.

A Combined Oral Contraceptive (COC): On the day when the new pack of the previous COC would have started.

Transdermal Patch: On the day when next application would have been scheduled.

Vaginal ring: On the day when next insertion would have been scheduled.

Injection: On the day when next injection would have been scheduled.

Intrauterine contraceptive: On the day of removal.

Implant: On the day of removal.

Refer to the Patient Information and Instructions for Use for additional instructions for counseling patient concerning proper use.

Effects of Other Drugs on Hormonal Contraceptives: Substances Decreasing the Systemic Concentrations of Hormonal Contraceptives (HCs) and Potentially Diminishing the Efficacy of HCs. Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the systemic concentrations of HCs and potentially diminish the effectiveness of HCs or increase breakthrough bleeding. Some drugs

or herbal products that may decrease the effectiveness of HCs include efavirenz, phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, rifabutin, rufinamide, aprepitant, and products containing St. John's wort. Interactions between HCs and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel females to use an alternative non-hormonal method of contraception or a back-up method when enzyme inducers are used with HCs, and to continue back-up non-hormonal contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability.

Substances Increasing the Systemic Concentrations of Hormonal Contraceptives (HCs): In a clinical drug-drug interaction study conducted in premenopausal females, once daily co-administration of Aleena 3 mg/ethinyl estradiol (EE) 0.02 mg containing tablets with strong CYP3A4 inhibitor, ketoconazole 200 mg twice daily for 10 days resulted in a moderate increase of Aleena systemic exposure. Influence of Aleena on Other Medicinal Products Based on in vitro studies and in vivo interaction studies in female volunteers using omeprazole, simvastatin and midazolam as marker substrate, an interaction of Aleena with the metabolism of other active substances is unlikely.

Potential to Increase Serum Potassium Concentration: There is a potential for an increase in serum potassium concentration in females taking Aleena with other drugs that may increase serum potassium concentration (for example, ACE inhibitors, angiotensin-II receptor antagonists, potassium-sparing diuretics, potassium supplementation, heparin, aldosterone antagonists, and NSAIDS.

Renal impairment
Adrenal insufficiency
Presence or history of progestin sensitive cancers
Liver tumors, benign or malignant, or hepatic impairment

Undiagnosed abnormal uterine bleeding

The following clinically significant Side Effects are described elsewhere in other sections of the labeling:

Hyperkalemia
Bleeding Irregularities and Amenorrhea

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Acne
Metrorrhagia
Headache
Breast pain
Weight increased
Dysmenorrhea
Nausea
Vaginal hemorrhage
Libido decreased
Breast tenderness
Menstruation irregularity

Based on epidemiologic studies and meta-analyses, there is little or no increased risk of birth defects in the children of females who inadvertently use oral progestin during early pregnancy. Discontinue it if pregnancy occurs, because there is no reason to use hormonal contraceptives during pregnancy. Negligible amounts of Drospirenone are excreted in breast milk. Thus, at therapeutic doses of it, no effects on breastfed newborns/infants are anticipated. General, no adverse effects have been found on milk production or on the health growth, or development of the infant with use of POPs.

Hyperkalemia: Aleena, a progestin, which has anti-mineralocorticoid activity, including the potential for hyperkalemia in high-risk females, comparable to a 25 mg dose of spironolactone. Aleena is contraindicated in females with conditions that predispose to hyperkalemia (e.g. renal impairment, hepatic impairment, and adrenal insufficiency). Females receiving daily, long-term treatment for chronic conditions or diseases with medications that may increase serum potassium concentration should have their serum potassium concentration checked prior to starting treatment and during the first treatment cycle. Consider monitoring serum potassium concentration in females at increased risk for hyperkalemia i.e., those females who take a strong CYP3A4 inhibitor long-term and concomitantly with Aleena. Strong CYP3A4 inhibitors include azole antifungals (e.g. ketoconazole, itraconazole, voriconazole), HIV/HCV protease inhibitors (e.g., indinavir, boceprevir), and clarithromycin. Monitor females taking Aleena who later develop medical conditions  and/or begin medication that put them at an increased risk for hyperkalemia.

Thromboembolic Disorders: Epidemiological studies have not indicated an association between progestin-only preparations and an increased risk of myocardial infarction, cerebral thromboembolism, or venous  thromboembolism. It is unknown whether the risk of VTE is increased with Aleena alone; however, if there is a risk, it is expected to be lower than that of Aleena in combination with ethinyl estradiol. When prescribing Drosperinone, consider the increased risk of thromboembolism inherent in the postpartum period and in females with a history of thromboembolism. Discontinue Drosperinone if arterial or venous thromboembolic events occur. Consider discontinuing Aleena, if feasible, in case of Aleena prolonged immobilization due to surgery or illness.

Bone Loss: Treatment with Aleena leads to decreased estradiol serum levels. It is unknown if this may cause a clinically relevant loss of bone mineral density.

Liver Disease: Discontinue Aleena if jaundice or acute or chronic disturbances of liver function develop. Do not resume use until markers of liver function return to normal and Aleena causation has been excluded. Aleena is contraindicated in females with liver tumors, benign or malignant, or hepatic impairment.

Ectopic Pregnancy: Be alert to the possibility of ectopic pregnancy in females who become pregnant or complain of lower abdominal pain while on Aleena.

Risk of Hyperglycemia in Patients with Diabetes: Some patients receiving progestins, including Aleena, may exhibit a decrease in insulin sensitivity. Therefore, patients with diabetes may be at greater risk of hyperglycemia and may require additional medication adjustments or monitoring.

Bleeding Irregularities and Amenorrhea: Females using Aleena may experience unscheduled (breakthrough or intracyclic) bleeding and spotting, especially during the first three months of use. Bleeding irregularities may resolve over time or by changing to a different contraceptive product. If bleeding persists or occurs after previously regular cycles, evaluate for causes such as pregnancy or malignancy. If scheduled bleeding does not occur, consider the possibility of pregnancy. If the patient has not adhered to the prescribed dosing schedule (missed one or two active tablets or started taking them on a day later than she should have, consider the possibility of pregnancy at the time of the first missed period and perform appropriate diagnostic measures. If the patient has adhered to the prescribed dosing schedule and misses two consecutive periods, rule out pregnancy.

Depression: Carefully observe females for a history of depression and discontinue Aleena if depression recurs to a serious degree. Data on the association of progestin-oacontraceptive products with onset of depression and exacerbation of depression are limited.

There have been no reports of serious deleterious effects from overdosage of Aleena. Symptoms that may occur include are nausea, vomiting, and vaginal bleeding. There are no antidotes and treatment should be to provide symptomatic support. Aleena is a spironolactone analogue which has antimineralocorticoid properties. Therefore, serum potassium and sodium, and evidence of metabolic acidosis, should be monitored in cases of overdose.

Store below 30°C and dry place. Keep away from light. Keep out of the reach of children.