Activella

• Overview
• Consumer Information
• Professional Information

 

Activella Side Effects Center

What Is Activella?

Activella (estradiol, norethindrone acetate) is a combination of the female hormones estrogen and progesterone used to treat the symptoms of menopause such as feelings of warmth in the face, neck and chest, or sudden intense spells of heat and sweating ("hot flashes" or "hot flushes"); to treat vulvar and vaginal changes (itching, burning, dryness in or around the vagina, difficulty or burning with urination) caused by menopause; and to replace estrogen in conditions such as hypogonadism, removal of the ovaries, or primary ovarian failure that result in a lack of estrogen. Activella is also used to prevent thinning of the bones (osteoporosis). Activella is available in generic form.

What Are Side Effects of Activella?

Common side effects of Activella include:

• stomach upset,
• nausea,
• vomiting,
• bloating,
• breast tenderness or enlargement,
• headache,
• weight changes,
• weakness,
• swelling of the hands or feet,
• spotty darkening of the skin (particularly on the face),
• difficulty in wearing contact lenses,
• vaginal irritation or discomfort,
• changes in menstrual cycle,
• painful menstruation, or
• break-through bleeding.

Tell your doctor if you have serious side effects of Activella including:

• mental/mood changes (such as depression, memory loss),
• breast lumps,
• increased or new vaginal irritation/itching/odor/discharge,
• severe stomach or abdominal pain,
• persistent nausea or vomiting,
• yellowing eyes or skin,
• dark urine,
• swelling hands/ankles/feet, or
• increased thirst or urination.

Dosage for Activella

Dosing of Activella is either 1.0 mg/0.5 mg (estradiol, norethindrone acetate) or 0.5 mg/0.1 mg (estradiol, norethindrone acetate). The lowest effective dose and the shortest treatment duration should be used.

What Drugs, Substances, or Supplements Interact with Activella?

Activella may interact with anticoagulants (blood thinners). Other drugs may also interact with Activella. Tell your doctor all prescription or over-the-counter medicines and supplements you use.

Activella During Pregnancy and Breastfeeding

Activella must not be used during pregnancy. If you become pregnant or think you may be pregnant, tell your doctor. This medication passes into breast milk. It may reduce the quality and amount of breast milk produced. Consult your doctor before breastfeeding.

Additional Information

Our Activella (estradiol, norethindrone acetate) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

 

Activella Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• heart attack symptoms--chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating;
• signs of a stroke--sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, problems with vision or balance;
• signs of a blood clot--sudden vision loss, stabbing chest pain, feeling short of breath, coughing up blood, pain or warmth in one or both legs;
• swelling or tenderness in your stomach;
• jaundice (yellowing of the skin or eyes);
• memory problems, confusion, unusual behavior;
• unusual vaginal bleeding, pelvic pain;
• a lump in your breast; or
• high levels of calcium in your blood--nausea, vomiting, constipation, increased thirst or urination, muscle weakness, bone pain, lack of energy.

Common side effects may include:

• nausea, vomiting, bloating, stomach cramps;
• fluid retention (swelling, rapid weight gain);
• headache;
• breast pain;
• thinning scalp hair; or
• vaginal itching or discharge, changes in your menstrual periods, breakthrough bleeding.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Activella (Estradiol, Norethindrone Acetate)

 

Activella Professional Information

SIDE EFFECTS

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

• Cardiovascular Disorders [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
• Malignant Neoplasms [see BOXED WARNING, WARNINGS AND PRECAUTIONS]

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.

Adverse reactions reported with Activella 1 mg/0.5 mg by investigators during clinical trials regardless of causality assessment are shown in Table 1.

TABLE 1 : ALL TREATMENT-EMERGENT ADVERSE REACTIONS REGARDLESS OF RELATIONSHIP REPORTED AT A FREQUENCY OF ≥ 5 PERCENT WITH ACTIVELLA 1 MG/0.5 MG

	Endometrial Hyperplasia Study (12-Months)		Vasomotor Symptoms Study (3-Months)		Osteoporosis Study (2-Years)
	Activella 1 mg/0.5 mg (n=295)	1 mg E2 (n=296)	Activella1 mg/0.5 mg (n=29)	Placebo (n=34)	Activella1 mg/0.5 mg (n=47)	Placebo (n=48)
Body as a Whole
Back Pain	6%	5%	3%	3%	6%	4%
Headache	16%	16%	17%	18%	11%	6%
Digestive System
Nausea	3%	5%	10%	0%	11%	0%
Gastroenteritis	2%	2%	0%	0%	6%	4%
Nervous System
Insomnia	6%	4%	3%	3%	0%	8%
Emotional Lability	1%	1%	0%	0%	6%	0%
Respiratory System
Upper Respiratory	18%	15%	10%	6%	15%	19%
Tract Infection
Sinusitis	7%	11%	7%	0%	15%	10%
Metabolic and Nutritional
Weight Increase	0%	0%	0%	0%	9%	6%
Urogenital System
Breast Pain	24%	10%	21%	0%	17%	8%
Post-Menopausal Bleeding	5%	15%	10%	3%	11%	0%
Uterine Fibroid	5%	4%	0%	0%	4%	8%
Ovarian Cyst	3%	2%	7%	0%	0%	8%
Resistance Mechanism
Infection Viral	4%	6%	0%	3%	6%	6%
Moniliasis Genital	4%	7%	0%	0%	6%	0%
Secondary Terms
Injury Accidental	4%	3%	3%	0%	17%*	4%*
Other Events	2%	3%	3%	0%	6%	4%
* including one upper extremity fracture in each group

Adverse reactions reported with Activella 0.5 mg/0.1 mg by investigators during clinical trials regardless of causality assessment are shown in Table 2.

TABLE 2 : ALL TREATMENT-EMERGENT ADVERSE REACTIONS REGARDLESS OF RELATIONSHIP REPORTED AT A FREQUENCY OF ≥ 5 PERCENT WITH ACTIVELLA 0.5 MG/0.1 MG<

	Activella 0.5 mg/0.1 mg (n=194)	Placebo (n=200)
Body as a Whole
Back Pain	10%	4%
Headache	22%	19%
Pain in extremity	5%	4%
Digestive System
Nausea	5%	4%
Diarrhea	6%	6%
Respiratory System
Nasopharyngitis	21%	18%
Urogenital System
Endometrial thickening	10%	4%
Vaginal hemorrhage	26%	12%

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Activella. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Genitourinary System

Changes in vaginal bleeding pattern and abnormal withdrawal bleeding or flow; breakthrough bleeding; spotting; dysmenorrhea, increase in size of uterine leiomyomata; vaginitis, including vaginal candidiasis; change in amount of cervical secretion; changes in cervical ectropion; pre-menstrual-like syndrome; cystitis-like syndrome; ovarian cancer; endometrial hyperplasia; endometrial cancer.

Breast

Tenderness, enlargement, pain, nipple discharge, galactorrhea; fibrocystic breast changes; breast cancer.

Cardiovascular

Deep and superficial venous thrombosis; pulmonary embolism; thrombophlebitis; myocardial infarction, stroke; increase in blood pressure.

Gastrointestinal

Nausea, vomiting; changes in appetite; cholestatic jaundice; abdominal pain/cramps, flatulence, bloating; increased incidence of gallbladder disease and pancreatitis.

Skin

Chloasma or melasma that may persist when drug is discontinued; erythema multiforme; erythema nodosum; hemorrhagic eruption; loss of scalp hair; seborrhea; hirsutism; itching; skin rash; pruritus.

Eyes

Retinal vascular thrombosis, intolerance to contact lenses.

Central Nervous System

Headache; migraine; dizziness; mental depression; chorea; insomnia; nervousness; mood disturbances; irritability; exacerbation of epilepsy; dementia.

Miscellaneous

Increase or decrease in weight; edema; leg cramps; changes in libido; fatigue; exacerbation of asthma; increased triglycerides; hypersensitivity; anaphylactoid/anaphylactic reactions.

DRUG INTERACTIONS

Co-administration of estradiol with norethindrone acetate did not elicit any apparent influence on the pharmacokinetics of norethindrone acetate. Similarly, no relevant interaction of norethindrone acetate on the pharmacokinetics of estradiol was found within the NETA dose range investigated in a single dose study.

Estradiol

In-vitro and in-vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism. Inducers of CYP3A4 such as St. John's wort (Hypericum perforatum) preparations, phenobarbital, carbamazepine, and rifampin may reduce plasma concentrations of estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile. Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and result in adverse reactions.

Norethindrone Acetate

Drugs or herbal products that induce or inhibit cytochrome P-450 enzymes, including CYP3A4, may decrease or increase the serum concentrations of norethindrone.

Read the entire FDA prescribing information for Activella (Estradiol, Norethindrone Acetate)

&Copy; Activella Patient Information is supplied by Cerner Multum, Inc. and Activella Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.