Adova

Adova is a drug indicated in the treatment of breast cancer in post-menopausal women. It is used both in adjuvant therapy (i.e. following surgery) and in metastatic breast cancer. It decreases the amount of estrogens that the body makes. Adova belongs in the class of drugs known as aromatase inhibitors. It inhibits the enzyme aromatase, which is responsible for converting androgens (produced by women in the adrenal glands) to estrogens.

Adjuvant Treatment

Adova tablets are indicated for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer.

First-Line Treatment

Adova tablets are indicated for the first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer.

Second-Line Treatment

Adova tablets are indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. Patients with ER-negative disease and patients who did not respond to previous tamoxifen therapy rarely responded to Adova tablets.

Adova is used to treat certain types of breast cancer in women who have already stopped menstruating (postmenopausal). It is also used for women who have already had other cancer treatments (e.g., tamoxifen).

Many breast cancer tumors grow in response to estrogen. Adova interferes with the production of estrogen in the body. As a result, the amount of estrogen that the tumor is exposed to is reduced, limiting the growth of the tumor.

Adova is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, Adova is used in certain patients with the following medical conditions:

• Breast cancer, neoadjuvant treatment for hormone receptor-positive, operable or potentially operable, locally advanced disease in postmenopausal women (treatment for advanced breast cancer that may respond to surgery in women who have already stopped menstruating).

The recommended dose of Adova for adults including the elderly is one 1 mg tablet once a day.

For postmenopausal women with hormone receptor-positive early invasive breast cancer, the recommended duration of adjuvant endocrine treatment is 5 years.

Special Populations: Paediatric Population: Adova is not recommended for use in children and adolescents due to insufficient data on safety and efficacy.

Renal Impairment: No dose change is recommended in patients with mild or moderate renal impairment. In patients with severe renal impairment, administration of Adova should be performed with caution.

Hepatic Impairment: No dose change is recommended in patients with mild hepatic disease. Caution is advised in patients with moderate to severe hepatic impairment.

Administration: Adova should be taken orally.

See also:
What is the most important information I should know about Adova?

Do not use Adova if you are pregnant. It could harm the unborn baby.

You may need to take a pregnancy test before using Adova, to make sure you are not pregnant.

You should not use this medication if you are allergic to Adova, if you are breast-feeding a baby, or if you have not yet completed menopause. Adova is not for use in men or children.

Before using Adova, tell your doctor if you have heart disease, circulation problems, a history of stroke or blood clot, severe liver disease, high cholesterol, osteoporosis, or low bone mineral density.

Adova may not work as well if you take it together with tamoxifen or an estrogen medication (such as hormone replacement therapy, estrogen creams, or birth control pills, injections, implants, skin patches, and vaginal rings). Before you start taking Adova, tell your doctor if you also take tamoxifen or estrogen.

You may need to keep taking Adova for up to 5 years. Follow your doctor's instructions.

Use Adova as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient information leaflet is available with Adova. Talk to your pharmacist if you have questions about this information.
• Take Adova by mouth with or without food.
• Continue to take Adova even if you feel well. Do not miss any doses.
• If you miss a dose of Adova, take it as soon as possible. If it is almost time for your next dose, 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 Adova.

Use: Labeled Indications

Breast cancer:

First-line treatment of locally-advanced or metastatic breast cancer (hormone receptor-positive or unknown) in postmenopausal women

Adjuvant treatment of early hormone receptor-positive breast cancer in postmenopausal women

Treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy

Off Label Uses

Endometrial or uterine cancers (recurrent or metastatic)

Hormonal agents such as progestational agents or tamoxifen may be used in the management of recurrent or metastatic endometrial cancer; in select patients, aromatase inhibitors, including Adova, may be considered. A small phase II trial evaluated Adova in a group of unselected patients with advanced recurrent or persistent endometrial cancer; the results showed minimal activity of Adova.

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What other drugs will affect Adova?

Adova inhibited in vitro metabolic reactions catalyzed by cytochromes P450 1A2, 2C8/9, and 3A4 but only at relatively high concentrations. Adova did not inhibit P450 2A6 or the polymorphic P450 2D6 in human liver microsomes. Adova did not alter the pharmacokinetics of antipyrine. Although there have been no formal interaction studies other than with antipyrine, based on these in vivo and in vitro studies, it is unlikely that co-administration of a 1 mg dose of Adova with other drugs will result in clinically significant drug inhibition of cytochrome P450-mediated metabolism of the other drugs.

An interaction study with warfarin showed no clinically significant effect of Adova on warfarin pharmacokinetics or anticoagulant activity.

At a median follow-up of 33 months, the combination of Adova and tamoxifen did not demonstrate any efficacy benefit when compared with tamoxifen in all patients as well as in the hormone receptor-positive subpopulation. This treatment arm was discontinued from the trial. Based on clinical and pharmacokinetic results from the ATAC trial, tamoxifen should not be administered with Adova (see CLINICAL PHARMACOLOGY ñ Drug Interactions and CLINICAL PHARMACOLOGY - Clinical Studies - Adjuvant Treatment of Breast Cancer in Postmenopausal Women subsections). Co-administration of Adova and tamoxifen resulted in a reduction of Adova plasma levels by 27% compared with those achieved with Adova alone.

Estrogen-containing therapies should not be used with Adova as they may diminish its pharmacologic action.

Drug/Laboratory Test Interactions

No clinically significant changes in the results of clinical laboratory tests have been observed.

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What are the possible side effects of Adova?

Unless specified, the following frequency categories were calculated from the number of adverse events reported in a large phase III study conducted in 9,366 postmenopausal women with operable breast cancer treated for 5 years (ATAC Study).

The table below presents the frequency of pre-specified adverse events in the ATAC study, irrespective of causality, reported in patients receiving trial therapy and up to 14 days after cessation of trial therapy.

The ATAC trial data showed that patients receiving Adova had an increase in joint disorders (including arthritis, arthrosis, and arthralgia) compared with patients receiving tamoxifen. Patients receiving Adova had an increase in the incidence of fractures (including fractures of spine, hip and wrist) compared with patients receiving tamoxifen. These differences were statistically significant. Fracture rates of 22 per 1,000 patient-years and 15 per 1000 patient-years were observed for the Adova and tamoxifen groups, respectively, after a median follow up of 68 months. The observed fracture rate for Adova is similar to the range reported in age-matched postmenopausal populations. It has not been determined whether the rates of fracture and osteoporosis seen in ATAC in patients on Adova treatment reflect a protective effect of tamoxifen, a specific effect of Adova, or both.

The incidence of osteoporosis was 10.5% in patients treated with Adova and 7.3% in patients treated with tamoxifen.

Patients receiving Adova had a decrease in hot flushes, vaginal bleeding, vaginal discharge, endometrial cancer, venous thromboembolic events (including deep venous thrombosis) and ischaemic cerebrovascular events compared with patients receiving tamoxifen. These differences were statistically significant.

Results from the ATAC trial bone substudy, at 12 and 24 months demonstrated that patients receiving Adova had a mean decrease in both lumbar spine and total hip bone mineral density (BMD) compared to baseline. Patients receiving tamoxifen had a mean increase in both lumbar spine and total hip BMD compared to baseline.

Slight increases in total cholesterol have also been observed in clinical trials with Adova, although the clinical significance has not been determined.