ALTAVERA- levonorgestrel and ethinyl estradiol kit

ALTAVERA by

Drug Labeling and Warnings

ALTAVERA by is a Prescription medication manufactured, distributed, or labeled by Xiromed, LLC., XIROMED PHARMA ESPANA, S.L. , Aspen Oss B.V.. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

BOXED WARNING

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WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs, including Altavera, are contraindicated in women who are over 35 years of age and smoke [see CONTRAINDICATIONS and WARNINGS (1)].

DESCRIPTION

Altavera (levonorgestrel and ethinyl estradiol tablets) is a combination oral contraceptive (COC) consisting of 21 peach active tablets, each containing 0.15 mg of levonorgestrel, a synthetic progestin and 30 mcg of ethinyl estradiol, an estrogen, and 7 white inert tablets (without hormones).

The structural formulas for the active components are:

LevonorgestrelC21H28O2 MW: 312.4

Ethinyl EstradiolC20H24O2 MW: 296.4

Ethinyl Estradiol is 19-nor-17α-pregna-1,3,5(10)-trien-20-yne-3, 17-diol.

Each peach active tablet contains the following inactive ingredients: lactose anhydrous, iron oxide black, iron oxide red, iron oxide yellow, magnesium stearate, polyethylene glycol, polyvinyl alcohol-part hydrolyzed, povidone, talc, titanium dioxide.

Each white inert tablet contains the following inactive ingredients: lactose anhydrous, magnesium stearate, polyethylene glycol, polyvinyl alcohol-part hydrolyzed, povidone, talc, titanium dioxide.

CLINICAL PHARMACOLOGY

Combination oral contraceptives prevent pregnancy primarily by suppressing ovulation.

INDICATIONS AND USAGE

Altavera is indicated for use by females of reproductive potential to prevent pregnancy.

CONTRAINDICATIONS

Altavera is contraindicated in females who are known to have the following conditions:

• A high risk of arterial or venous thrombotic diseases. Examples include women who are known to:
  • Smoke, if over age 35 [see BOXED WARNING and WARNINGS (1)].
  • Have current or history of deep vein thrombosis or pulmonary embolism [see WARNINGS (1)].
  • Have cerebrovascular disease [see WARNINGS (1)].
  • Have coronary artery disease [see WARNINGS (1)].
  • Have thrombogenic valvular or thrombogenic rhythm diseases of the heart (for example, subacute bacterial endocarditis with valvular disease, or atrial fibrillation) [see WARNINGS (1)].
  • Have inherited or acquired hypercoagulopathies [see (1)].
  • Have uncontrolled hypertension or hypertension with vascular disease [see WARNINGS (3)].
  • Have diabetes mellitus and are over age 35, diabetes mellitus with hypertension or vascular disease or other end-organ damage, or diabetes mellitus of >20 years duration [see WARNINGS (7)].
  • Have headaches with focal neurological symptoms, migraine headaches with aura, or over age 35 with any migraine headaches [see WARNINGS (8)].

• Current or history of breast cancer or other estrogen- or progestin-sensitive cancer.
• Liver tumors, acute viral hepatitis, or severe (decompensated) cirrhosis [see WARNINGS (2)].
• Use of Hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, due to the potential for ALT elevations [see WARNINGS (5)].
• Undiagnosed abnormal uterine bleeding [see WARNINGS (9)].
• Pregnancy, because there is no reason to use COCs during pregnancy [see PRECAUTIONS (6)].

WARNINGS

1. Thromboembolic Disorders and Other Vascular Conditions

• Stop Altavera if an arterial or venous thrombotic/thromboembolic event occurs.
• Stop Altavera if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions and evaluate for retinal vein thrombosis immediately.
• Discontinue Altavera during prolonged immobilization. If feasible, stop Altavera at least four weeks before and through two weeks after major surgery, or other surgeries known to have an elevated risk of thromboembolism.
• Start Altavera no earlier than four weeks after delivery in females who are not breast-feeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the likelihood of ovulation increases after the third postpartum week.
• Before starting Altavera evaluate any past medical history or family history of thrombotic or thromboembolic disorders and consider whether the history suggests an inherited or acquired hypercoagulopathy. Altavera is contraindicated in females with a high risk of arterial or venous thrombotic/thromboembolic diseases (see CONTRAINDICATIONS).

Arterial Events
COCs increase the risk of cardiovascular events and cerebrovascular events, such as myocardial infarction and stroke. The risk is greater among older women (> 35 years of age), smokers, and females with hypertension, dyslipidemia, diabetes, or obesity.

Altavera is contraindicated in women over 35 years of age who smoke (see CONTRAINDICATIONS). Cigarette smoking increases the risk of serious cardiovascular events from COC use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked.

Venous Events
Use of COCs increases the risk of venous thromboembolic events (VTEs), such as deep vein thrombosis and pulmonary embolism. Risk factors for VTEs include smoking, obesity, and family history of VTE, in addition to other factors that contraindicate use of COCs (see CONTRAINDICATIONS). While the increased risk of VTE associated with use of COCs is well-established, the rates of VTE are even greater during pregnancy, and especially during the postpartum period (see Figure 1). The rate of VTE in females using COCs has been estimated to be 3 to 9 cases per 10,000 woman-years.

The risk of VTE is highest during the first year of use of a COC and when restarting hormonal contraception after a break of four weeks or longer. Based on results from a few studies, there is some evidence that this is true for non-oral products as well. The risk of thromboembolic disease due to COCs gradually disappears after COC use is discontinued.

Figure 1 shows the risk of developing a VTE for females who are not pregnant and do not use oral contraceptives, for females who use oral contraceptives, for pregnant females, and for females in the postpartum period. To put the risk of developing a VTE into perspective: If 10,000 females who are not pregnant and do not use oral contraceptives are followed for one year, between 1 and 5 of these females will develop a VTE.

Figure 1. Likelihood of Developing a VTE

2. Liver Disease

Elevated Liver Enzymes
Altavera is contraindicated in females with acute viral hepatitis or severe (decompensated) cirrhosis of liver (see CONTRAINDICATIONS). Discontinue Altavera if jaundice develops. Acute liver test abnormalities may necessitate the discontinuation of COC use until the liver tests return to normal and COC causation has been excluded.

Liver Tumors
Altavera is contraindicated in females with benign or malignant liver tumors (see CONTRAINDICATIONS). COCs increase the risk of hepatic adenomas. An estimate of the attributable risk is 3.3 cases/100,000 COC users. Rupture of hepatic adenomas may cause death from abdominal hemorrhage.

Studies have shown an increased risk of developing hepatocellular carcinoma in long-term (> 8 years) COC users. The attributable risk of liver cancers in COC users is less than one case per million users.

3. Hypertension

Altavera is contraindicated in females with uncontrolled hypertension or hypertension with vascular disease (see CONTRAINDICATIONS). For all females, including those with well- controlled hypertension, monitor blood pressure at routine visits and stop Altavera if blood pressure rises significantly.

An increase in blood pressure has been reported in females using COCs, and this increase is more likely in older women with extended duration of use. The effect of COCs on blood pressure may vary according to the progestin in the COC.

4. Age-related Considerations

The risk for cardiovascular disease and prevalence of risk factors for cardiovascular disease increase with age. Certain conditions, such as smoking and migraine headache without aura, that do not contraindicate COC use in younger females, are contraindications to use in women over 35 years of age [see CONTRAINDICATIONS and WARNINGS (1) ]. Consider the presence of underlying risk factors that may increase the risk of cardiovascular disease or VTE, particularly before initiating a COC for women over 35 years, such as:

• Hypertension
• Diabetes
• Dyslipidemia
• Obesity

5. Risk of Liver Enzyme Elevations with Concomitant Hepatitis C Treatment

During clinical trials with the Hepatitis C combination drug regimen that contains ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, ALT elevations greater than 5 times the upper limit of normal (ULN), including some cases greater than 20 times the ULN, were significantly more frequent in women using ethinyl estradiol-containing medications such as COCs. Discontinue Altavera prior to starting therapy with the combination drug regimen ombitasvir/paritaprevir/ritonavir, with or without dasabuvir (see CONTRAINDICATIONS). Altavera can be restarted approximately 2 weeks following completion of treatment with the combination drug regimen.

6. Gallbladder Disease

Studies suggest an increased risk of developing gallbladder disease among COC users. Use of COCs may also worsen existing gallbladder disease.

A past history of COC-related cholestasis predicts an increased risk with subsequent COC use. Females with a history of pregnancy-related cholestasis may be at an increased risk for COC- related cholestasis.

7. Adverse Carbohydrate and Lipid Metabolic Effects
Hyperglycemia
Altavera is contraindicated in diabetic women over age 35, or females who have diabetes with hypertension, nephropathy, retinopathy, neuropathy, other vascular disease, or females with diabetes of > 20 years duration (see CONTRAINDICATIONS). Altavera may decrease glucose tolerance. Carefully monitor prediabetic and diabetic females who are using Altavera.

Dyslipidemia
Consider alternative contraception for females with uncontrolled dyslipidemia. Altavera may cause adverse lipid changes.

Females with hypertriglyceridemia, or a family history thereof, may have an increase in serum triglyceride concentrations when using Altavera, which may increase the risk of pancreatitis.

8. Headache
Altavera is contraindicated in females who have headaches with focal neurological symptoms or have migraine headaches with aura, and in women over age 35 years who have migraine headaches with or without aura (see CONTRAINDICATIONS).

If a woman using Altavera develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue Altavera if indicated. Consider discontinuation of Altavera if there is an increased frequency or severity of migraines during COC use (which may be prodromal of a cerebrovascular event).

9. Bleeding Irregularities and Amenorrhea
Unscheduled Bleeding and Spotting
Females using Altavera 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.

In two clinical trials of Altavera (1084 subjects reporting for a total of 8186 treatment cycles and 238 subjects reporting for a total of 1102 treatment cycles), breakthrough bleeding occurred in 6.9% and 8.1% of reported cycles, and spotting occurred in 8.6% and 7.9% of reported cycles over the total study duration, respectively. In the two trials, intermenstrual bleeding (i.e., breakthrough bleeding and/or spotting) occurred in 13.1% and 12.9% of reported cycles over the total study duration, respectively. In one trial, 33 subjects out of 1084 (3.0%) discontinued due to bleeding irregularities (i.e., breakthrough bleeding and spotting); in the other trial, 6 subjects out of 238 (2.5%) discontinued due to bleeding irregularities.

Amenorrhea and Oligomenorrhea
Females who use Altavera may experience absence of scheduled (withdrawal) bleeding, even if they are not pregnant. In two clinical trials of Altavera, one including 8186 reported treatment cycles, and the other including 1102 reported treatment cycles, amenorrhea occurred in 1.5% of treatment cycles in each trial.

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.

After discontinuation of a COC, amenorrhea or oligomenorrhea may occur, especially if these conditions were pre-existent.

10. Depression
Carefully observe females with a history of depression and discontinue Altavera if depression recurs to a serious degree. Data on the association of COCs with onset of depression or exacerbation of existing depression are limited.

11. Cervical Cancer
Some studies suggest that COCs are associated with an increase in the risk of cervical cancer or intraepithelial neoplasia. There is controversy about the extent to which these findings are due to differences in sexual behavior and other factors.

12. Effect on Binding Globulins
The estrogen component of Altavera may raise the serum concentrations of thyroxine- binding globulin, sex hormone-binding globulin, and cortisol-binding globulin. The dose of replacement thyroid hormone or cortisol therapy may need to be increased.

13. Hereditary Angioedema
In females with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema.

14. Chloasma
Chloasma may occur with Altavera use, especially in females with a history of chloasma gravidarum. Advise females with a history of chloasma to avoid exposure to the sun or ultraviolet radiation while using Altavera.

PRECAUTIONS

1. Lipid Disorders
Women who are being treated for hyperlipidemias should be followed closely if they elect to use oral contraceptives. Some progestogens may elevate LDL levels and may render the control of hyperlipidemias more difficult [see WARNINGS (7)].

In patients with familial defects of lipoprotein metabolism receiving estrogen-containing preparations, there have been case reports of significant elevations of plasma triglycerides leading to pancreatitis.

2. Fluid Retention
Oral contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention.

3. Gastrointestinal Motility
Diarrhea and/or vomiting may reduce hormone absorption (see DOSAGE AND ADMINISTRATION).

4. Drug Interactions
The sections below provide information on substances for which data on drug interactions with COCs are available. There is little information available about the clinical effect of most drug interactions that may affect COCs. However, based on the known pharmacokinetic effects of these drugs, clinical strategies to minimize any potential adverse effect on contraceptive effectiveness or safety are suggested.

Consult the approved product labeling of all concurrently used drugs to obtain further information about interactions with COCs or the potential for metabolic enzyme or transporter system alterations.

No drug-drug interaction studies were conducted with Altavera.

4.1 Effects of Other Drugs on Combined Oral Contraceptives

Substances Decreasing the Plasma Concentrations of COCs and Potentially Diminishing the Efficacy of COCs:

Table 1 includes substances that demonstrated an important drug interaction with Altavera.

Table 1: Significant Drug Interactions Involving Substances That Affect COCs

Metabolic Enzyme Inducers
Clinical effect	Concomitant use of COCs with metabolic enzyme inducers may decrease the plasma concentrations of the estrogen and/or progestin component of COCs. Decreased exposure of the estrogen and/or progestin component of COCs may potentially diminish the effectiveness of COCs and may lead to contraceptive failure or an increase in breakthrough bleeding.
Prevention or management	Counsel females to use an alternative method of contraception or a backup method when enzyme inducers are used with COCs. Continue backup contraception for 28 days after discontinuing the enzyme inducer to maintain contraceptive reliability.
Examples	Aprepitant, barbiturates, bosentan, carbamazepine, efavirenz, felbamate, griseofulvin, oxcarbazepine, phenytoin, rifampin, rifabutin, rufinamide, topiramate, products containing St. John’s worta, and certain protease inhibitors (see separate section on protease inhibitors below).
Colesevelam
Clinical effect	Concomitant use of COCs with colesevelam significantly decreases systemic exposure of ethinylestradiol. Decreased exposure of the estrogen component of COCs may potentially reduce contraceptive efficacy or result in an increase in breakthrough bleeding, depending on the strength of ethinyl estradiol in the COC.
Prevention or management	Administer 4 or more hours apart to attenuate this drug interaction.

aInduction potency of St. John’s wort may vary widely based on preparation.

Substances increasing the systemic exposure of COCs:
Co-administration of atorvastatin or rosuvastatin and COCs containing ethinyl estradiol increase systemic exposure of ethinyl estradiol by approximately 20 to 25 percent. Ascorbic acid and acetaminophen may increase systemic exposure of ethinyl estradiol, possibly by inhibition of conjugation. CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of COCs.

Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) protease inhibitors and non­ nucleoside reverse transcriptase inhibitors:
Significant decreases in systemic exposure of the estrogen and/or progestin have been noted when COCs are co-administered with some HIV protease inhibitors (e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir), some HCV protease inhibitors (e.g., boceprevir and telaprevir), and some non-nucleoside reverse transcriptase inhibitors (e.g., nevirapine). In contrast, significant increases in systemic exposure of the estrogen and/or progestin have been noted when COCs are co-administered with certain other HIV protease inhibitors (e.g., indinavir and atazanavir/ritonavir) and with other non-nucleoside reverse transcriptase inhibitors (e.g., etravirine).

4.2 Effects of Combined Oral Contraceptives on Other Drugs

Table 2 provides significant drug interaction information for drugs co-administered with Altavera.

Table 2: Significant Drug Interaction Information for Drugs Co-Administered With COCs

Lamotrigine
Clinical effect	Concomitant use of COCs with lamotrigine may significantly decrease systemic exposure of lamotrigine due to induction of lamotrigine glucuronidation. Decreased systemic exposure of lamotrigine may reduce seizure control.
Prevention or management	Dose adjustment may be necessary. Consult the approved product labeling for lamotrigine.
Thyroid Hormone Replacement Therapy or Corticosteroid Replacement Therapy
Clinical effect	Concomitant use of COCs with thyroid hormone replacement therapy or corticosteroid replacement therapy may increase systemic exposure of thyroid- binding and cortisol-binding globulin (see Warnings, EFFECT ON BINDING GLOBULINS).
Prevention or management	The dose of replacement thyroid hormone or cortisol therapy may need to be increased. Consult the approved product labeling for the therapy in use (see Warnings, EFFECT ON BINDING GLOBULINS).
Other Drugs
Clinical effect	Concomitant use of COCs may decrease systemic exposure of acetaminophen, morphine, salicylic acid, and temazepam. Concomitant use with ethinyl estradiol­ containing COCs may increase systemic exposure of other drugs (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole).
Prevention or management	The dosage of drugs that can be affected by this interaction may need to be increased. Consult the approved product labeling for the concomitantly used drug.

4.3 Effect on Laboratory Tests
The use of COCs may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins.

5. Carcinogenesis
See WARNINGS (11).

6. Pregnancy
Risk Summary
Altavera is contraindicated in pregnancy because there is no reason to use COCs in pregnancy. Discontinue Altavera if pregnancy occurs. Epidemiologic studies and meta- analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to COCs before conception or during early pregnancy. Animal studies to evaluate embryo/fetal toxicity were not conducted.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4 percent and 15 to 20 percent, respectively.

7. Lactation
Risk Summary
Contraceptive hormones and/or metabolites are present in human milk. COCs can reduce milk production in breast-feeding females. This reduction can occur at any time but is less likely to occur once breast-feeding is well-established. When possible, advise the nursing female to use other methods of contraception until she discontinues breast-feeding. (see DOSAGE AND ADMINISTRATION). The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for Altavera and any potential adverse effects on the breast-fed child from Altavera or from the underlying maternal condition.

8. Pediatric Use
Safety and efficacy of Altavera have been established in females of reproductive potential. Use of Altavera before menarche is not indicated.

9. Geriatric Use
Altavera has not been studied in postmenopausal women and is not indicated in this population.

10. PATIENT COUNSELING INFORMATION

• Counsel patients that cigarette smoking increases the risk of serious cardiovascular events from COC use, and that women who are over 35 years old and smoke should not use COCs.
• Counsel patients that this product does not protect against HIV-infection (AIDS) and other sexually transmitted infections.
• Counsel patients to take one tablet daily by mouth at the same time every day. Instruct patients what to do in the event pills are missed.
• Counsel patients to use a back-up or alternative method of contraception when enzyme inducers are used with COCs.
• Counsel patients who are breastfeeding or who desire to breastfeed that COCs may reduce breast milk production. This is less likely to occur if breastfeeding is well established.
• Counsel any patient who starts Altavera postpartum, and who has not yet had a period, to use an additional method of contraception until she has taken a light-orange tablet for 7 consecutive days.
• Counsel patients that amenorrhea may occur. Pregnancy should be considered in the event of amenorrhea, and should be ruled out if amenorrhea is associated with symptoms of pregnancy, such as morning sickness or unusual breast tenderness.

ADVERSE REACTIONS

The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling:

• Serious cardiovascular adverse events [see BOXED WARNING and WARNINGS (1)]
• Vascular events [see WARNINGS (1)]
• Liver disease [see WARNINGS(2)]
• Hypertension [see WARNINGS(3)]
• Gallbladder disease [see WARNINGS (6)]
• Carbohydrate and lipid effects [see WARNINGS (7)]
• Headache [see WARNINGS (8)]
• Carcinoma of the cervix [see WARNINGS (11)]

Adverse reactions reported by COC users and described elsewhere in the labeling are:

• Bleeding irregularities and amenorrhea [see WARNINGS (9)]
• Mood changes, including depression [see WARNINGS (10)]
• Melasma/chloasma which may persist [see WARNINGS (14)]
• Edema/fluid retention [see PRECAUTIONS (2)]
• Diminution in lactation when given immediately postpartum [see PRECAUTIONS (7)]

The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug-related: Breast tenderness, pain, enlargement, secretion; Nausea, vomiting and gastrointestinal symptoms (such as abdominal pain, cramps and bloating); Change in menstrual flow; Temporary infertility after discontinuation of treatment; Change in weight or appetite (increase or decrease); Change in cervical erosion and secretion; Cholestatic jaundice; Rash (allergic); Vaginitis, including candidiasis; Change in corneal curvature (steepening); Intolerance to contact lenses; Mesenteric thrombosis; Decrease in serum folate levels; Exacerbation of systemic lupus erythematosus; Exacerbation of porphyria; Exacerbation of chorea; Aggravation of varicose veins; Anaphylactic/anaphylactoid reactions, including urticaria, angioedema, and severe reactions with respiratory and circulatory symptoms.

The following adverse reactions have been reported in users of oral contraceptives, and the association has been neither confirmed nor refuted: Congenital anomalies; Premenstrual syndrome; Cataracts; Optic neuritis, which may lead to partial or complete loss of vision; Cystitis-like syndrome; Nervousness; Dizziness; Hirsutism; Loss of scalp hair; Erythema multiforme; Erythema nodosum; Hemorrhagic eruption; Impaired renal function; Hemolytic uremic syndrome; Budd-Chiari syndrome; Acne; Changes in libido; Colitis; Sickle-cell disease; Cerebral-vascular disease with mitral valve prolapse; Lupus-like syndromes; Pancreatitis; Dysmenorrhea.

OVERDOSAGE

There have been no reports of serious adverse outcomes from overdose of COCs, including ingestion by children. Overdose may cause uterine bleeding in females and nausea.

DOSAGE AND ADMINISTRATION

1. How to Start and Take Altavera
Altavera is dispensed in a compact dispenser containing 28 tablets (see HOW SUPPLIED). Altavera may be started using either a Day 1 start or a Sunday start (see Table 3). For the first cycle of a Sunday start regimen, an additional method of contraception should be used until after the first 7 consecutive days of administration.

Table 3: Instructions for Administration of Altavera

Starting Altavera in females with no current use of hormonal contraception	Day 1 start Take first tablet without regard to meals on the first day of menses Take subsequent tablets once daily at the same time each day 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 tablet)
	Sunday start; Take first tablet without regard to meals on the first Sunday after the onset of menstrual period Take subsequent tablets once daily at the same time each day Use additional nonhormonal contraception for the first seven days of product use 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 tablet)
Switching from another contraceptive method A COC	Start Altavera: On the day when the new pack of the previous COC would have been 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

Starting Altavera after Abortion or Miscarriage

First-trimester

• After a first-trimester abortion or miscarriage, Altavera may be started immediately. An additional method of contraception is not needed if Altavera is started immediately.
• If Altavera is not started within 5 days after termination of the pregnancy, the patient should use additional non-hormonal contraception (such as condoms or spermicide) for the first seven days of her first cycle of Altavera.

Second-trimester

• Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start Altavera following the instructions in Table 3 for Day 1 or Sunday start. Use additional non-hormonal contraception (such as condoms or spermicide) for the first seven days of the patient’s first cycle of Altavera (see CONTRAINDICATIONS, WARNINGS (1), PRECAUTIONS (10) and FDA-APPROVED PATIENT LABELING). Starting Altavera after ChildbirthDo not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with Altavera following the instructions in Table 3 for women not currently using hormonal contraception.Altavera is not recommended for use in lactating women (see PRECAUTIONS (7) and FDA-APPROVED PATIENT LABELING).If the woman has not yet had a period postpartum, consider the possibility of ovulation and conception occurring prior to use of Altavera (see CONTRAINDICATIONS, WARNINGS (9), PRECAUTIONS (6) and FDA­ APPROVED PATIENT LABELING).

2. Dosing Altavera
Instruct patients to take one tablet by mouth at the same time every day. To achieve maximum contraceptive effectiveness, patients must take Altavera as directed, in the order directed on the blister pack. The failure rate may increase when pills are missed or taken incorrectly.

3. Missed doses
Instruct patients about the handling of missed doses (e.g., to take single missed pills as soon as possible) and to follow the dosing instructions provided in the FDA-approved patient labeling.

Table 4: Instructions for Missed Altavera Tablets

• If one active tablet is missed in Weeks 1, 2, or 3: Take the tablet as soon as possible. Continue taking one tablet a day until the pack is finished.
• If two active tablets are missed in Week 1 or Week 2: Take the two missed tablets as soon as possible and the next two active tablets the next day. Continue taking one tablet a day until the pack is finished. Additional nonhormonal contraception (such as condoms or spermicide) should be used as back-up if the patient has sex within 7 days after missing tablets.
• If two active tablets are missed in the third week or three or more active tablets are missed in a row in Weeks 1, 2, or 3: Day 1 start: Throw out the rest of the pack and start a new pack that same day.; Sunday start: Continue taking one tablet a day until Sunday, then throw out the rest of the pack and start a new pack that same day. ; Additional nonhormonal contraception (such as condoms or spermicide) should be used as back-up if the patient has sex within 7 days after missing tablets.

4. Advice in Case of Gastrointestinal Disturbances
If vomiting occurs within 3 to 4 hours after taking Altavera, the patient should proceed as if she missed a tablet. In case of prolonged vomiting or diarrhea, absorption may not be complete and additional contraceptive measures should be taken.

HOW SUPPLIED

Altavera tablets (levonorgestrel and ethinyl estradiol, 0.15 mg/30 mcg) are available in packages of 3 compact dispensers, each containing 28 tablets:

• 21 Active Tablets: Peach, round, unscored, debossed with SZon one side and J4on the other side.
• 7 Inert Tablets: White, round, unscored, debossed with SZon one side and J1on the other side.
• 1 individual blister: NDC: 70700-116-84
• 3 individual blisters: NDC: 70700-116-85

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

XIROMED, LLC.
Florham Park, NJ 07932

PI-116-02
Rev. 04/2020

Patient Information

ALTAVERA [all-tuh-VAIR-uh]
(levonorgestrel 0.15 mg and ethinyl estradiol 30 mcg tablets)

What is the most important information I should know about Altavera?

Do not use Altavera if you smoke cigarettes and are over 35 years old. Smoking increases your risk of serious cardiovascular side effects from hormonal birth control pills, including death from heart attack, blood clots or stroke. This risk increases with age and the number of cigarettes you smoke.

What is Altavera?
Altavera is a birth control pill (oral contraceptive) used by women to prevent pregnancy.

How does Altavera work for contraception?
Your chance of getting pregnant depends on how well you follow the directions for taking your birth control pills. The better you follow the directions, the less chance you have of getting pregnant.

Based on the results of clinical studies, about 1 to 5 out of 100 women may get pregnant during the first year they use Altavera.

The following chart shows the chance of getting pregnant for women who use different methods of birth control. Each box on the chart contains a list of birth control methods that are similar in effectiveness. The most effective methods are at the top of the chart. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant.

Who should not take Altavera?

Do not take Altavera if you:
smoke and are over 35 years of age
had blood clots in your arms, legs, lungs, or eyes
had a problem with your blood that makes it clot more than normal
have certain heart valve problems or irregular heart beat
had a stroke
had a heart attack
have high blood pressure that cannot be controlled by medicine
have diabetes with kidney, eye, nerve, or blood vessel damage
have certain kinds of severe migraine headaches with aura, numbness, weakness or changes in vision, or any migraine headaches if you are over 35 years of age
had breast cancer or any cancer that is sensitive to female hormones
have liver problems, including liver tumors
have any unexplained vaginal bleeding
are pregnant
take any Hepatitis C drug combination containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir. This may increase levels of the liver enzyme “alanine aminotransferase” (ALT) in the blood.

If any of these conditions happen while you are taking Altavera, stop taking Altavera right away and talk to your healthcare provider. Use non-hormonal contraception when you stop taking Altavera.

What should I tell my healthcare provider before taking Altavera?

Tell your healthcare provider if you:
are pregnant or think you may be pregnant
are depressed now or have been depressed in the past
had yellowing of your skin or eyes (jaundice) caused by pregnancy (cholestasis of pregnancy)
are breastfeeding or plan to breastfeed. Altavera may decrease the amount of breast milk you make. A small amount of the hormones in Altavera may pass into your breast milk. Talk to your healthcare provider about the best birth control method for you while breastfeeding.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.

Altavera may affect the way other medicines work, and other medicines may affect how well Altavera works.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I take Altavera?

Read the Instructions for Use at the end of this Patient Information.

What are the possible serious side effects of Altavera?
Like pregnancy, Altavera may cause serious side effects, including blood clots in your lungs, heart attack, or a stroke that may lead to death. Some other examples of serious blood clots include blood clots in the legs or eyes.

Serious blood clots can happen especially if you smoke, are obese, or are older than 35 years of age. Serious blood clots are more likely to happen when you:
○ first start taking birth control pills
○ restart the same or different birth control pills after not using them for a month or more

Call your healthcare provider or go to a hospital emergency room right away if you have:

• leg pain that will not go away: sudden change in vision or blindness
• sudden shortness of breath: chest pain
• a sudden, severe headache unlike your usual headaches: weakness of numbness in your arm or leg

Other serious side effects include:

liver problems, including:
○ rare liver tumors
○ jaundice (cholestasis), especially if you previously had cholestasis of pregnancy. Call your healthcare provider if you have yellowing of your skin or eyes.
high blood pressure. You should see your healthcare provider for a yearly check of your blood pressure.
 gallbladder problems
 changes in the sugar and fat (cholesterol and triglycerides) levels in your bloodchanges in the sugar and fat (cholesterol and triglycerides) levels in your blood
new or worsening headaches, including migraine headachesnew or worsening headaches, including migraine headaches
irregular or unusual vaginal bleeding and spotting between your menstrual periods, especially during the first 3 months of taking Altavera.
 depression
possible cancer in your breast and cervix
 swelling of your skin especially around your mouth, eyes, and in your throat (angioedema). Call your healthcare provider if you have a swollen face, lips, mouth tongue or throat, which may lead to difficulty swallowing or breathing. Your chance of having angioedema is higher if you have a history of angioedema.
 dark patches of skin around your forehead, nose, cheeks and around your mouth, especially during pregnancy (chloasma).Women who tend to get chloasma should avoid spending a long time in sunlight, tanning booths, and under sun lamps while taking Altavera. Use sunscreen if you have to be in the sunlight.

What are the most common side effects of oral contraceptives?

• nausea: weight gain
• vomiting: breast tenderness
• bleeding between menstrual periods: difficulty wearing contact lenses

These are not all the possible side effects of Altavera. For more information, ask your healthcare provider or pharmacist.

You may report side effects to the FDA at 1-800-FDA-1088.

What else should I know about taking Altavera?
If you are scheduled for any lab tests, tell your healthcare provider you are taking Altavera. Certain blood tests may be affected by Altavera.
Altavera does not protect against HIV-infection (AIDS) and other sexually transmitted infections.

How should I store Altavera?
 Store Altavera at room temperature between 68°F to 77°F (20°C to 25°C).
Protect from light.

General information about the safe and effective use of Altavera.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Altavera for a condition for which it was not prescribed. Do not give Altavera to other people, even if they have the same symptoms that you have.

This Patient Information Leaflet summarizes the most important information about Altavera. You can ask your pharmacist or healthcare provider for information about Altavera that is written for health professionals.

For more information, call 1-844-XIROMED (844-947-6633).

Do birth control pills cause cancer?
Birth control pills do not seem to cause breast cancer. However, if you have breast cancer now, or have had it in the past, do not use birth control pills because some breast cancers are sensitive to hormones.

Women who use birth control pills may have a slightly higher chance of getting cervical cancer. However, this may be due to other reasons such as having more sexual partners.

What if I want to become pregnant?
You may stop taking the pill whenever you wish. Consider a visit with your healthcare provider for a pre-pregnancy checkup before you stop taking the pill.

What should I know about my period when taking Altavera?
Your periods may be lighter and shorter than usual. Some women may miss a period. Irregular vaginal bleeding or spotting may happen while you are taking Altavera, especially during the first few months of use. This usually is not a serious problem. It is important to continue taking your pills on a regular schedule to prevent a pregnancy.

What are the ingredients in Altavera?

Active ingredients: Each peach pill contains levonorgestrel and ethinyl estradiol.

Inactive ingredients:
Peach pills: lactose anhydrous, iron oxide black, iron oxide red, iron oxide yellow, magnesium stearate, polyethylene glycol, polyvinyl alcohol-part hydrolyzed, povidone, talc, and titanium dioxide.

White pills: lactose anhydrous, magnesium stearate, polyethylene glycol, polyvinyl alcohol-part hydrolyzed, povidone, talc, and titanium dioxide.

XIROMED, LLC.
Florham Park, NJ 07932

Rev. 02/2020

Instructions For Use

ALTAVERA [all-tuh-VAIR-uh]
(levonorgestrel 0.15 mg and ethinyl estradiol tablets 30 mcg)

Important Information about taking Altavera
Take 1 pill every day at the same time. Take the pills in the order directed on your pill pack.
Do not skip your pills, even if you do not have sex often. If you miss pills (including starting the pack late) you could get pregnant. The more pills you miss, the more likely you are to get pregnant.
If you have trouble remembering to take Altavera, talk to your healthcare provider.
When you first start taking Altavera, spotting or light bleeding in between your periods may occur. Contact your healthcare provider if this does not go away after a few months.
You may feel sick to your stomach (nauseous), especially during the first few months of taking Altavera. If you feel sick to your stomach, do not stop taking the pill. The problem will usually go away. If your nausea does not go away, call your healthcare provider.
Missing pills can also cause spotting or light bleeding, even when you take the missed pills later. On the days you take 2 pills to make up for missed pills (see What should I do if I miss any Altavera pills? below), you could also feel a little sick to your stomach.
It is not uncommon to miss a period. However, if you miss a period and have not taken Altavera according to directions, or feel like you may be pregnant, call your healthcare provider. If you have a positive pregnancy test, you should stop taking Altavera.
If you have vomiting or diarrhea within 3-4hours of taking a light-orange pill, take another light-orange pill as soon as possible. Continue taking all your remaining pills in order. Start the first pill of your next pill pack the day after finishing your current pill pack. This will be 1 day earlier than originally scheduled. Continue on your new schedule.
If you have vomiting or diarrhea for more than 1 day, your birth control pills may not work as well. Use an additional birth control method, like condoms or spermicide, until you check with your healthcare provider.
Stop taking Altavera at least4 weeks before you have major surgery and do not restart after the surgery without asking your healthcare provider. Be sure to use other forms of contraception (like condoms or spermicide) during this time period.

Before you start taking Altavera:
 Decide what time of day you want to take your pill. It is important to take it at the same time every day and in the order as directed on your pill pack.
 Look at your pill pack. Your pill pack consists of 1 card that holds 28 individually sealed pills. The 28 pills consist of 21 light-orange pills (3 rows of 7 pills) and 7 pink pills (1 row of 7 pills). See Figure A.

Figure A

Also find:
o Where on the card to start taking pills (upper left corner) and
o In what order to take the pills (follow the weeks)
Be sure you have ready at all times another kind of birth control (such as condoms or spermicide), to use as a back-up in case you miss pills.

When should I start taking Altavera?

If you start taking Altavera and you have not used a hormonal birth control method before:
There are 2 ways to start taking your birth control pills. You can either start on a Sunday (Sunday Start) or on the first day (Day 1) of your natural menstrual period (Day 1 Start). Your healthcare provider should tell you when to start taking your birth control pill.
 If you use the Sunday Start, use non-hormonal back-up contraception such as condoms or spermicide for the first 7 days that you take Altavera. You do not need back-up contraception if you use the Day 1 Start.

If you start taking Altavera and you are switching from another birth control pill:
Start your new Altavera pack on the same day that you would start the next pack of your previous birth control method.
Do not continue taking the pills from your previous birth control pill pack.

If you start taking Altavera and previously used a vaginal ring:
Start using Altavera on the day you would have started the next ring.

If you start taking Altavera and previously used a transdermal patch:
Start using Altavera on the day you would have started a new cycle (first patch application).

If you start taking Altavera and you are switching from a progestin-only method such as an implant or injection:
Start taking Altavera on the day of removal of your implant, or on the day when you would have had your next injection.

If you start taking Altavera and you are switching from an intrauterine device or system (IUD or IUS):
Start taking Altavera on the day of removal of your IUD or IUS.
You do not need back-up contraception if your IUD or IUS is removed on the first day (Day 1) of your period. If your IUD or IUS is removed on any other day, use non-hormonal back-up contraception such as condoms or spermicide for the first 7 days that you take Altavera.

Keep a calendar to track your period: If this is the first time you are taking birth control pills, read, “When should I start taking Altavera?” above. Follow these instructions for either a Sunday Start or a Day 1 Start.

Instructions for using your Altavera Pill Dispenser: 

Sunday Start:
You will use a Sunday Start if your healthcare provider told you to take your first pill on a Sunday.
Take pill 1 on the Sunday after your period starts. To remove your pill from the dispenser, press the pill through the hole in the bottom of the dispenser.
If your period starts on a Sunday, take pill "1" that day and refer to Day 1 Start instructions below.
Take 1pill every day in the order on the pill dispenser at the same time each day for28 days.
After taking the last pill on Day 28 from the pill dispenser, start taking the first pill from a new pack, on the same day of the week as the first pack (Sunday). Take the first pill in the new pack whether or not you are having your period.
Use non-hormonal back-up contraception such as condoms or spermicide for the first 7 days of the first cycle that you take Altavera.

Day 1 Start:
You will use a Day 1 Start if your doctor told you to take your first pill (Day 1) on the first day of your period.
Take1 pill every day in the order of the pill dispenser, at the same time each day, for 28 days. To remove your pill from the dispenser, press the pill through the hole in the bottom of the dispenser.
After taking the last pill on Day 28 from the pill dispenser, start taking the first pill from a new pack, on the same day of the week as the first pack. Take the first pill in the new pack whether or not you are having your period.

What should I do if I miss any Altavera pills?

If you miss 1 pill in Weeks 1, 2, or 3, follow these steps:
Take it as soon as you remember. Take the next pill at your regular time. This means you may take 2 pills in 1 day.
Then continue taking 1 pill every day until you finish the pack.
You do not need to use a back-up birth control method if you have sex.

If you miss 2 pills in Week 1 or Week 2 of your pack, follow these steps:
Take the 2 missed pills as soon as possible and the next 2 pills the next day.
Then continue to take 1 pill every day until you finish the pack.
Use a non-hormonal birth control method (such as a condom or spermicide) as a back-up if you have sex during the first 7 days after missing your pills.

If you miss 2 pills in a row in Week 3, or you miss 3 or more pills in a row during Weeks 1, 2, or 3 of the pack, follow these steps:
If you are a Day 1 Starter:
o Throw out the rest of the pill pack and start a new pack that same day.
o You may not have your period this month, but this is expected. However, if you miss your period 2 months in a row, call your healthcare provider because you might be pregnant.
o You could become pregnant if you have sex during the first 7 days after you restart your pills. You MUST use a non-hormonal birth control method (such as a condom or spermicide) as a back-up if you have sex during the first 7 days after you restart your pills.

 If you are a Sunday Starter:
o Keep taking 1 pill every day until Sunday. On Sunday, throw out the rest of the pack and start a new pack of pills that same day.
o Use a non-hormonal birth control method (such as a condom or spermicide) as a back-up if you have sex during the first 7 days after you restart your pills.

If you have any questions or are unsure about the information in this leaflet, call your healthcare provider.

This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration.

XIROMED, LLC.
Florham Park, NJ 07932

PIL-116-02

Rev. 04/2020

Principal Display Panel

NDC 70700-116-85

ALTAVERATM
(Levonorgestrel and Ethinyl Estradiol Tablets, USP) 0.15 mg/0.03 mg

28 Day Regimen

1 unit

Rx Only

INGREDIENTS AND APPEARANCE

ALTAVERA 
levonorgestrel and ethinyl estradiol kit

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 70700-116

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 70700-116-85	3 in 1 CARTON	01/01/2018
1	NDC: 70700-116-84	1 in 1 CARTON
1		1 in 1 BLISTER PACK; Type 0: Not a Combination Product

Quantity of Parts
Part #	Package Quantity	Total Product Quantity
Part 1		21
Part 2		7

Part 1 of 2

ALTAVERA 
levonorgestrel and ethinyl estradiol tablet

Product Information
Route of Administration	ORAL

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
LEVONORGESTREL (UNII: 5W7SIA7YZW) (LEVONORGESTREL - UNII:5W7SIA7YZW)	LEVONORGESTREL	0.15 mg
ETHINYL ESTRADIOL (UNII: 423D2T571U) (ETHINYL ESTRADIOL - UNII:423D2T571U)	ETHINYL ESTRADIOL	0.03 mg

Inactive Ingredients
Ingredient Name	Strength
ANHYDROUS LACTOSE (UNII: 3SY5LH9PMK)
FERROSOFERRIC OXIDE (UNII: XM0M87F357)
FERRIC OXIDE RED (UNII: 1K09F3G675)
FERRIC OXIDE YELLOW (UNII: EX438O2MRT)
MAGNESIUM STEARATE (UNII: 70097M6I30)
POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)
POLYVINYL ALCOHOL (UNII: 532B59J990)
POVIDONE, UNSPECIFIED (UNII: FZ989GH94E)
TALC (UNII: 7SEV7J4R1U)
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)

Product Characteristics
Color	BROWN (peach)	Score	no score
Shape	ROUND	Size	6mm
Flavor		Imprint Code	SZ;J4
Contains

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA079102	01/01/2018

Part 2 of 2

INERT 
inert tablet

Product Information
Route of Administration	ORAL

Inactive Ingredients
Ingredient Name	Strength
ANHYDROUS LACTOSE (UNII: 3SY5LH9PMK)
MAGNESIUM STEARATE (UNII: 70097M6I30)
POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)
POLYVINYL ALCOHOL (UNII: 532B59J990)
POVIDONE, UNSPECIFIED (UNII: FZ989GH94E)
TALC (UNII: 7SEV7J4R1U)
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)

Product Characteristics
Color	WHITE	Score	no score
Shape	ROUND	Size	6mm
Flavor		Imprint Code	SZ;J1
Contains

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA079102	01/01/2018

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA079102	01/01/2018

Labeler - Xiromed, LLC. (080228637)

Registrant - XIROMED PHARMA ESPANA, S.L. (468835741)

Establishment
Name	Address	ID/FEI	Business Operations
Aspen Oss B.V.		491013870	api manufacture(70700-116)

Establishment
Name	Address	ID/FEI	Business Operations
Aspen Oss B.V.		491017488	api manufacture(70700-116)