Angeliq film-coated tablets

Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause

Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause

Angeliq film-coated tablets and Estradiol (Angeliq film-coated tablets) combination is used to treat moderate to severe hot flashes and other symptoms of menopause or low amounts of estrogen in women who still have a uterus (womb). It is also used to treat changes in and around the vagina (such as vaginal dryness, itching, and burning) caused by menopause in women who still have a uterus.

Angeliq film-coated tablets and Estradiol (Angeliq film-coated tablets) are female hormones called progestins and estrogens that make up this combination medicine. Angeliq film-coated tablets and Estradiol (Angeliq film-coated tablets) works by preventing symptoms, such as feeling of warmth in the face, neck, and chest, or sudden strong feelings of heat and sweating (hot flashes) in women during menopause..

Angeliq film-coated tablets and Estradiol (Angeliq film-coated tablets) is available only with your doctor's prescription.

Each pack of Angeliq film-coated tablets covers 28 days of treatment. Treatment is continuous, which means that the next pack follows immediately without a break. The tablets are to be swallowed whole with some liquid irrespective of food intake and should preferably be taken at the same time every day. In case a tablet is forgotten, it should be taken as soon as possible. If more than 24 hours have elapsed, the missed tablet should not be taken. If several tablets are forgotten, bleeding may occur.

Women who do not take estrogens or women who change from a continuous combination product may start treatment at any time. Women changing from a continuous sequential or cyclic hormone therapy (HT) should complete the current cycle of therapy before initiating Angeliq film-coated tablets therapy.

Use of estrogen, alone or in combination with a progestin, should be limited to the lowest effective dose available and for the shortest duration consistent with treatment goals and risks for the individual woman. Patients should be reevaluated periodically as clinically appropriate to determine if treatment is still necessary.

Treatment Of Moderate To Severe Vasomotor Symptoms Due To Menopause

The dosage is one Angeliq film-coated tablets 0.25 mg DRSP/0.5 mg E2 tablet or one Angeliq film-coated tablets 0.5 mg DRSP/1 mg E2 tablet taken by mouth once daily.

Treatment Of Moderate To Severe Symptoms Of Vulvar And Vaginal Atrophy Due To Menopause

The dosage is one Angeliq film-coated tablets 0.5 mg DRSP/1 mg E2 tablet taken by mouth once daily.

When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.

How supplied

Dosage Forms And Strengths

Angeliq film-coated tablets 0.25 mg DRSP/0.5 mg E2 Tablets: round, biconvex, yellow, film-coated, embossed with a “EL” inside a hexagon

Angeliq film-coated tablets 0.5 mg DRSP/1 mg E2 Tablets: round, biconvex, pink, film-coated, embossed with a “CK” inside a hexagon

Angeliq film-coated tablets is supplied in packages of three blisterpacks:

Angeliq film-coated tablets 0.25 mg DRSP/0.5 mg E2

Angeliq film-coated tablets 0.25 mg DRSP/0.5 mg E2 tablets are available as round, biconvex yellow film-coated tablets embossed with “EL” inside a hexagon.

3 blisters of 28 tablets NDC 50419-482-03

Angeliq film-coated tablets 0.5 mg DRSP/1 mg E2

Angeliq film-coated tablets 0.5 mg DRSP/1 mg E2 tablets are available as round, biconvex pink film-coated tablets embossed with “CK” inside a hexagon.

3 blisters of 28 tablets NDC 50419-483-03

Storage And Handling

Store at 25° C (77° F); excursions permitted to 15–30° C (59–86° F).

Manufactured for: Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ 07981. Revised: June 2015

See also:
What is the most important information I should know about Angeliq film-coated tablets?

Do not prescribe Angeliq film-coated tablets to women with any of the following conditions:

Use Angeliq film-coated tablets as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Angeliq film-coated tablets. Talk to your pharmacist if you have questions about this information.
• Take Angeliq film-coated tablets by mouth with or without food.
• Swallow Angeliq film-coated tablets whole with some liquid. Do not break, crush, dissolve, or chew before swallowing. If you cannot swallow Angeliq film-coated tablets whole, tell your doctor. You may need a different medicine.
• Grapefruit and grapefruit juice may increase the risk of side effects from Angeliq film-coated tablets. Talk to your doctor before including grapefruit or grapefruit juice in your diet while taking Angeliq film-coated tablets.
• Take Angeliq film-coated tablets on a regular schedule to get the most benefit from it.
• Taking Angeliq film-coated tablets at the same time each day will help you remember to take it.
• Continue to take Angeliq film-coated tablets even if you feel well. Do not miss any doses.
• If you miss a dose of Angeliq film-coated tablets, take it as soon as possible. If more than 24 hours have passed since you missed a dose of Angeliq film-coated tablets, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Angeliq film-coated tablets.

Use: Labeled Indications

Vasomotor symptoms associated with menopause: Treatment of moderate to severe vasomotor symptoms associated with menopause in women with a uterus.

Vulvar and vaginal atrophy associated with menopause: Treatment of moderate to severe vulvar and vaginal atrophy due to menopause in women with a uterus.

Limitations of use: When used solely for the treatment of vulvar and vaginal atrophy, topical vaginal products should be considered.

Note: The International Society for the Study of Women

See also:
What other drugs will affect Angeliq film-coated tablets?

No formal drug-drug interaction studies have been conducted for Angeliq film-coated tablets.

Metabolic Interactions

Effect of Angeliq film-coated tablets on Other Drugs

The potential effect of DRSP on CYP2C19 activity was investigated in a clinical pharmacokinetic study using omeprazole as a marker substrate. No significant effect of DRSP on the systemic clearance of the CYP3A4 product omeprazole sulfone was found. These results demonstrated that DRSP did not inhibit CYP2C19 and CYP3A4 in vivo. Two further clinical drug-drug interaction studies using simvastatin and midazolam as marker substrates for CYP3A4, respectively, were performed and the results of these studies demonstrated that pharmacokinetics of the CYP3A4 substrates were not influenced by steady-state DRSP concentrations.

Co-administration of DRSP and drugs that may increase serum potassium: There is a potential for an increase in serum potassium in women taking DRSP with other drugs that may affect electrolytes, such as ACE inhibitors, angiotensin receptor blockers, or NSAIDs, more pronounced in diabetic women.

Electrolytes were studied in postmenopausal women with hypertension and/or diabetes mellitus requiring an ACE inhibitor or angiotensin receptor blocker. After 28 days of exposure to 1 mg E2 and 3 mg DRSP (n=112) or placebo (n=118). The mean change from baseline in serum potassium was 0.11 mEq/L for the E2/DRSP group and 0.08 mEq/L for the placebo group. None of the subjects with serum potassium concentrations ≥ 5.5 mEq/L had cardiovascular adverse events.

A drug-drug interaction study of DRSP 3 mg/E2 1 mg versus placebo was performed in mildly hypertensive postmenopausal women taking enalapril maleate 10 mg twice daily. Potassium concentrations were obtained every other day for a total of 2 weeks in all subjects. Mean serum potassium concentrations in the DRSP/E2 treatment group relative to baseline were 0.22 mEq/L higher than those in the placebo group. On Day 14, the ratios for serum potassium Cmax and AUC in the DRSP/E2 group to those in the placebo group were 0.955 (90% CI: 0.914, 0.999) and 1.01 (90% CI: 0.944, 1.08), respectively. No patient in either treatment group developed hyperkalemia (serum potassium concentrations > 5.5 mEq/L).

Of note, occasional or chronic use of NSAID medication was not restricted in any of the Angeliq film-coated tablets clinical trials.

Effect of Other Drugs on Estrogens and Progestins

In vitro and in vivo studies have shown that estrogens and progestins are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen and progestin drug metabolism. In a clinical drug-drug interaction study conducted in premenopausal women, once daily co-administration of DRSP 3 mg/E2 1.5 mg containing tablets with strong CYP3A4 inhibitor, ketoconazole 200 mg twice daily for 10 days resulted in a moderate increase of exposure and a mild increase of peak concentration for DRSP. The E2 exposure and peak concentration were unaffected by ketoconazole, although the exposure and peak concentration of estrone (E1) increased. Although no clinically relevant effects on any safety or laboratory parameters including serum potassium were observed, this study only assessed subjects for 10 days. The clinical impact for a woman taking a DRSP-containing combination hormone and chronic use of a CYP3A4/5 inhibitor is unknown.

Substances Decreasing The Exposure And Possibly Diminishing The Efficacy Of Estrogens And Progestins (Enzyme Inducers)

Inducers of CYP3A4 such as St. John's wort (Hypericum perforatum), phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens and progestins, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile.

Substances Increasing The Exposure Of Estrogens And Progestins (Enzyme Inhibitors)

Concomitant administration of moderate or strong CYP3A4 inhibitors such as azole antifungals (for example, ketoconazole, itraconazole, voriconazole, fluconazole), verapamil, macrolides (for example, clarithromycin, erythromycin), diltiazem, and grapefruit juice did increase the plasma concentrations of the estrogen or the progestin or both.

HIV/HCV Protease Inhibitors And Non-Nucleoside Reverse Transcriptase Inhibitors

Significant changes (increase or decrease) in the plasma concentrations of estrogen and progestin have been noted in some cases of co-administration with HIV/HCV protease inhibitors or with non-nucleoside reverse transcriptase inhibitors.

Interaction With Alcohol

Acute alcohol ingestion during use of hormone therapy may lead to elevations of circulating E2 concentrations.

See also:
What are the possible side effects of Angeliq film-coated tablets?

The following serious adverse reactions are discussed elsewhere in the labeling:

Cardiovascular Disorders

Malignant Neoplasms

Clinical Trials Experience

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.

From clinical trials with different dose formulations of Angeliq film-coated tablets containing E2 dose ranging from 0.5 mg to 1.0 mg combined with DRSP dose ranging from 0.25 mg to 3 mg:

• The most common adverse reactions were gastrointestinal and abdominal pain, female genital bleeding, breast pain and headache. The frequencies of common adverse reactions, in general, were higher for the Angeliq film-coated tablets dose formulation containing E2 1 mg compared to Angeliq film-coated tablets containing E2 0.5 mg.
• The most common adverse reactions leading to drug discontinuation in controlled clinical trials were abdominal pain, headache, postmenopausal bleeding, breast tenderness, and weight increased.

Placebo-Controlled Trial

In a placebo-controlled trial evaluating Angeliq film-coated tablets 0.25 mg DRSP/0.5 mg E2, 183 postmenopausal women received at least one dose of DRSP 0.25 mg/0.5 mg E2 and 180 received placebo. Study subjects were treated for 3 cycles of 28 days each for a total of 12 weeks of treatment. The median age was 53 years (range: 40-77 years) and over 50% of subjects had a hysterectomy, 68% were Caucasian and 24% were Black. Table 1 summarizes adverse reactions reported in at least 2% of subjects receiving Angeliq film-coated tablets 0.25 mg DRS/0.5 mg E2 and at a higher incidence than subjects receiving placebo.

Table 1: Adverse Reactions that Occurred at a Frequency of ≥ 2% with Angeliq film-coated tablets 0.25 mg DRSP/0.5 mg E2 and at a higher incidence than placebo

Pooled Data Of Clinical Trials With Different Dose Formulations Of Angeliq film-coated tablets

Data from 13 clinical trials in postmenopausal subjects treated with different dose formulations of Angeliq film-coated tablets containing 1 mg E2 (1 mg E2 + 0.5 mg – 3.0 mg DRSP; N=2842) were pooled to provide an overall estimate of adverse reactions. Similarly, data from 2 clinical trials with Angeliq film-coated tablets containing 0.5 mg E2 (0.5 mg E2 + DRSP 0.25 mg – 0.5 mg; N=853) were pooled for the same purpose. Table 2 shows adverse reactions reported in at least 1% of subjects treated with Angeliq film-coated tablets.

Table 2: Adverse Reactions that Occurred at a Frequency of ≥ 1% in Clinical Trials

Adverse Reactions in clinical studies were coded using the MedDRA dictionary (version 13.0). Different MedDRA terms representing the same medical phenomenon have been grouped together as single adverse reactions to avoid diluting or obscuring the true effect.

Postmarketing Experience

The following additional adverse reactions have been reported during post approval use of Angeliq film-coated tablets. Because these reactions are reported voluntarily from a population of uncertain size, reliably estimating their frequency or establishing a causal relationship to drug exposure is not always possible.

Immune System Disorders: Hypersensitivity reactions, including rash, pruritis, and urticaria

Reproductive system and breast disorders: Breast cancer

Vascular disorders: venous and arterial thromboembolic events (peripheral deep venous occlusion, thrombosis and embolism/pulmonary vascular occlusion, thrombosis, embolism and infarction/myocardial infarction/cerebral infarction and stroke not specified as hemorrhagic)