Anastrozole
Indications
Anastrozole is used for:
Breast cancer, Ovulation induction
Adult Dose
Oral
Advanced or locally advanced breast cancer, Adjuvant treatment in early breast cancer
Adult: In postmenopausal women: 1 mg daily. Adjuvant treatment may be continued for up to 5 yr.
Hepatic Impairment
Mild-to-moderate impairment or stable hepatic cirrhosis: Dose adjustment not necessary
Severe hepatic impairment: Not studied
Child Dose
Renal Dose
Administration
May be taken with or without food.
Contra Indications
Pregnancy. Hypersensitivity, premenopausal women.
Precautions
Moderate or severe hepatic impairment, hyperlipidaemias. Laboratory test for menopause if status is doubtful. Bone mass density test should be conducted at the start of the therapy and at regular intervals thereafter.
Lactation: Unknown whether drug is excreted in milk; not recommended given potential for serious adverse reactions in nursing infants
Pregnancy-Lactation
Pregnancy
Based on findings from animal studies and mechanism of action, therapy may cause fetal harm when administered to pregnant woman; there are no studies on use in pregnant women
Advise pregnant women and females of reproductive potential of potential risk to a fetus
Verify pregnancy status of females of reproductive potential prior to initiation of therapy
Based on animal studies, therapy can cause fetal harm when administered to a pregnant woman
Advise females of reproductive potential to use effective contraception during treatment and for at least 3 weeks after last dose
Based on studies in female animals, treatment may impair fertility in females of reproductive potential
Animal data
Anastrozole caused embryo-fetal toxicities in rats at maternal exposure that were 9 times the human clinical exposure, based on area under the curve (AUC); in rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 16 times the recommended human dose on a mg/m2 basis
Lactation
There are no data on presence of drug or metabolites in human milk, or effects on breast-fed child or on milk production; because many drugs are excreted in human milk and because of tumorigenicity shown for anastrozole in animal studies, or potential for serious adverse reactions in breast-fed child from treatment, advise lactating women not to breastfeed during treatment and for 2 weeks after last dose
Interactions
Efficacy decreased by oestrogens. Plasma concentrations decreased by tamoxifen.
Adverse Effects
Side effects of Anastrozole :
>10%
Hot flashes (12-36%), Vasodilation (25-36%), Fatigue (19%), Mood disturbances (19%), Nausea and vomiting (19%), Weakness (16-19%), Arthritis (17%), Pain (17%), Arthralgia (2-15%), Pharyngitis (14%), Depression (13%), Hypertension (2-13%), Bone pain (11%), Increased cough (11%), Osteoporosis (11%), Rash (8-11%)
1-10%
Accidental injury (10%), Back pain (10%), Fracture (10%), Headache (10%), Insomnia (10%), Peripheral edema (10%), Dyspnea (8-10%), Abdominal pain (9%), Infection (9%), Lymphedema (9%), Diarrhea (8-9%), Constipation (7-9%), Breast pain (8%), Dizziness (8%), Urinary tract infection (8%), Chest pain (7%), Dyspepsia (7%), Paresthesia (5-7%), Anxiety (6%), Cataracts (6%), Flu syndrome (6%), Sinusitis (6%), Vulvovaginitis (6%), Xerostomia (6%), Breast neoplasm (5%), Bronchitis (5%), Cyst (5%), Diaphoresis (5%), Neoplasm (5%), Vaginal bleeding (5%), Fractures of spine, hip, or wrist (4%), Ischemic cardiovascular disease (4%), Vaginal hemorrhage (4%), Vaginitis (4%), Leukorrhea (3-4%), Deep vein thrombosis (2%), Endometrial cancer (intact uterus at baseline) (2%), Ischemic cerebrovascular event (2%), Weight gain (2%), Lethargy (1%)
Mechanism of Action
Anastrozole prevents conversion of androstenedione to estrone and testosterone to oestradiol by inhibiting aromatase, thus leading to significantly reduced serum oestradiol concentrations.