Rajani

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:

• Feeling more or less hungry.
• Weight gain.
• Headache.
• Upset stomach or throwing up.
• Cramps.
• Bloating.
• Period (menstrual) changes. These include spotting or bleeding between cycles.
• Enlarged breasts.
• Breast soreness.
• Lowered interest in sex.
• This medicine may cause dark patches of skin on your face. Avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun.

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.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Rajani (ethinyl estradiol, drospirenone, and levomefolate) or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Rajani. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Oral Contraceptive

Rajani is indicated for use by women to prevent pregnancy.

Premenstrual Dysphoric Disorder (PMDD)

Rajani is also indicated for the treatment of symptoms of premenstrual dysphoric disorder (PMDD) in women who choose to use an oral contraceptive as their method of contraception. The effectiveness of Rajani for PMDD when used for more than three menstrual cycles has not been evaluated.

The essential features of PMDD according to the Diagnostic and Statistical Manual-4th edition (DSM-IV) include markedly depressed mood, anxiety or tension, affective lability, and persistent anger or irritability. Other features include decreased interest in usual activities, difficulty concentrating, lack of energy, change in appetite or sleep, and feeling out of control. Physical symptoms associated with PMDD include breast tenderness, headache, joint and muscle pain, bloating and weight gain. In this disorder, these symptoms occur regularly during the luteal phase and remit within a few days following onset of menses; the disturbance markedly interferes with work or school, or with usual social activities and relationships with others. Diagnosis is made by healthcare providers according to DSM-IV criteria, with symptomatology assessed prospectively over at least two menstrual cycles. In making the diagnosis, care should be taken to rule out other cyclical mood disorders.

Rajani has not been evaluated for the treatment of premenstrual syndrome (PMS).

Acne

Rajani is indicated for the treatment of moderate acne vulgaris in women at least 14 years of age, who have no known contraindications to oral contraceptive therapy and have achieved menarche. Rajani should be used for the treatment of acne only if the patient desires an oral contraceptive for birth control.

Folate Supplementation

Rajani is indicated in women who choose to use an oral contraceptive as their method of contraception, to raise folate levels for the purpose of reducing the risk of a neural tube defect in a pregnancy conceived while taking the product or shortly after discontinuing the product.

Pregnancy

There is little or no increased risk of birth defects in women who inadvertently use COCs during early pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to low dose COCs prior to conception or during early pregnancy.

The administration of COCs to induce withdrawal bleeding should not be used as a test for pregnancy. COCs should not be used during pregnancy to treat threatened or habitual abortion.

Women who do not breastfeed may start COCs no earlier than four weeks postpartum.

Nursing Mothers

When possible, advise the nursing mother to use other forms of contraception until she has weaned her child. Estrogen-containing COCs can reduce milk production in breastfeeding mothers. This is less likely to occur once breastfeeding is well-established; however, it can occur at any time in some women. Small amounts of oral contraceptive steroids and/or metabolites are present in breast milk.

After oral administration of 3 mg DRSP/0.03 mg EE tablets (Yasmin**), about 0.02% of the DRSP dose was excreted into the breast milk of postpartum women within 24 hours. This results in a maximal daily dose of about 0.003 mg DRSP in an infant.

Studies to date indicate there is no adverse effect of folate on nursing infants.

Pediatric Use

Safety and efficacy of Rajani has been established in women of reproductive age. Efficacy is expected to be the same for postpubertal adolescents under the age of 18 and for users 18 years and older. Use of this product before menarche is not indicated.

Geriatric Use

Rajani has not been studied in postmenopausal women and is not indicated in this population.

Patients with Renal Impairment

Rajani is contraindicated in patients with renal impairment [see Contraindications (4) and Warnings and Precautions (5.2)].

In subjects with creatinine clearance (CLcr) of 50 to 79 mL/min, serum DRSP concentrations were comparable to those in a control group with CLcr greater than or equal to 80 mL/min. In subjects with CLcr of 30 to 49 mL/min, serum DRSP concentrations were on average 37% higher than those in the control group. In addition, there is a potential to develop hyperkalemia in subjects with renal impairment whose serum potassium is in the upper reference range, and who are concomitantly using potassium-sparing drugs [see Clinical Pharmacology (12.3)].

Patients with Hepatic Impairment

Rajani is contraindicated in patients with hepatic disease [see Contraindications (4) and Warnings and Precautions (5.4)]. The mean exposure to DRSP in women with moderate liver impairment is approximately three times higher than the exposure in women with normal liver function. Rajani has not been studied in women with severe hepatic impairment.

Race

No clinically significant difference was observed between the pharmacokinetics of DRSP or EE in Japanese versus Caucasian women [see Clinical Pharmacology (12.3)].

There have been no reports of serious ill effects from overdose, including ingestion by children. Overdosage may cause withdrawal bleeding in females and nausea.

DRSP is a spironolactone analogue which has antimineralocorticoid properties. Serum concentration of potassium and sodium, and evidence of metabolic acidosis, should be monitored in cases of overdose.

Levomefolate calcium doses of 17 mg/day (37-fold higher than the levomefolate calcium dose of Rajani) were well tolerated after long-term treatment up to 12 weeks.

How Supplied

Rajani (drospirenone, ethinyl estradiol and levomefolate calcium tablets and levomefolate calcium tablets) is available in packages of three blister packs (NDC 52544-298-31).

The film-coated tablets are rounded with biconvex faces, one side is debossed with “W” on one side and “296” or “297” on the other side.

Each blister pack (28 film-coated tablets) contains in the following order:

• 24 round, biconvex, white, film-coated tablets with “W” debossed on one side and “296” on the other side, each containing 3 mg drospirenone, 0.02 mg ethinyl estradiol, and 0.451 mg levomefolate calcium

• 4 round, biconvex, light orange, film-coated tablets with “W” debossed on one side and “297” on the other side, each containing 0.451 mg levomefolate calcium

Storage

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Common side effects of Rajani include: headache and spotting. Other side effects include: irregular menses and migraine. See below for a comprehensive list of adverse effects.

Applies to drospirenone / ethinyl estradiol / levomefolate calcium: oral tablet

Cardiovascular

Cardiovascular side effects have included hypertension, arterial or deep venous thrombotic events, strokes, and myocardial infarctions.[Ref]

Genitourinary

Genitourinary side effects have included breast tenderness, decreased libido, unscheduled (breakthrough or intracyclic) bleeding and spotting.

Gastrointestinal

Gastrointestinal side effects have included nausea, vomiting, and inflammatory bowel disease.[Ref]

Hepatic

Hepatic side effects have included jaundice, cholestasis and hepatic adenomas.[Ref]

Metabolic

Metabolic side effects have included gallbladder disease, liver function disturbances, liver tumors, hyperkalemia, hypertriglyceridemia, changes in glucose tolerance, and effect on peripheral insulin resistance (including diabetes mellitus).[Ref]

Nervous system

Nervous system side effects have included an increase in frequency or severity of migraine headaches.[Ref]

Ocular

Ocular side effects have included loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions.[Ref]

Psychiatric

Psychiatric side effects have included irritability, depression and affect lability.[Ref]

Oncologic

Oncologic side effects have included carcinoma of the breasts and reproductive organs.[Ref]

Musculoskeletal

Musculoskeletal side effects have included systemic lupus erythematosus.[Ref]

Dermatologic

Dermatologic side effects have included chloasma, angioedema, erythema nodosum, and erythema multiforme.[Ref]

Hypersensitivity

Hypersensitivity side effects have included anaphylactic reaction.[Ref]

Some side effects of Rajani may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.