Anastrozole 1 mg

Anastrozole 1 mg (Anastrozole) · ATC L02BG03

Aromatase inhibitor · non-steroidal (triazole)

Each film-coated tablet contains Anastrozole 1 mg.

For the full list of excipients, see section 6.1.

Tablet for oral administration.

Therapeutic indications

Management of estrogen-dependent conditions and control of estrogenic effects during androgen therapy, as determined by a physician.

Posology and method of administration

Take orally as directed by a physician. Swallow whole with water. Do not exceed the prescribed dose.

Contraindications

Known hypersensitivity to the active substance or excipients. Pregnancy and breastfeeding. Not for use in premenopausal women. Use under specialist supervision only.

Special warnings and precautions for use

Keep out of the reach and sight of children. Contains a substance prohibited in sport (WADA).

Interaction with other medicinal products

Oestrogens and oestrogen-containing preparations

Directly antagonise the pharmacological action of anastrozole by restoring oestrogen receptor stimulation; concurrent use negates the therapeutic effect and is not recommended.

Tamoxifen

Co-administration reduces anastrozole plasma concentrations by approximately 27%; combined use has shown no efficacy benefit over tamoxifen alone and is not recommended.

Bisphosphonates and other bone-active agents

A pharmacodynamic interaction of clinical benefit: used to offset the accelerated bone loss associated with profound oestrogen deprivation; bone mineral density monitoring guides use.

Coumarin anticoagulants (warfarin, acenocoumarol)

Although anastrozole itself shows no clinically relevant inhibition of the major cytochrome P450 isoenzymes at therapeutic doses, alterations in oestrogen status and hepatic protein synthesis may shift INR; anticoagulation should be monitored more closely.

LHRH analogues and other agents inducing oestrogen deficiency

Additive suppression of the hypothalamic–pituitary–gonadal axis, increasing the risk of vasomotor symptoms and bone demineralisation.

Potent CYP inducers or inhibitors (e.g. rifampicin, azole antifungals)

Anastrozole is cleared mainly by hepatic dealkylation and glucuronidation; marked hepatic enzyme induction may theoretically reduce exposure, though no clinically significant interaction has been established at therapeutic doses.

Use in special populations

Pregnancy and breastfeeding

Contraindicated. Anastrozole is embryotoxic and foetotoxic in animals and profound oestrogen suppression is incompatible with the maintenance of pregnancy. Women of childbearing potential must use effective non-hormonal contraception during treatment and for a period after discontinuation as directed by the prescriber. It is unknown whether anastrozole passes into human milk; breastfeeding must be discontinued.

Paediatric population

Not recommended. Safety and efficacy have not been established in children and adolescents, and oestrogen is essential to epiphyseal maturation and the pubertal accrual of bone mass; aromatase inhibition in this group risks impaired bone mineralisation and disturbed growth.

Elderly

No dose adjustment is required on the grounds of age alone; pharmacokinetics are not meaningfully altered. Baseline and periodic bone mineral density assessment is advisable, as age-related bone loss compounds treatment-induced demineralisation.

Renal impairment

Renal clearance accounts for a minor share of elimination and no dose adjustment is needed in mild to moderate impairment. In severe impairment (creatinine clearance below 30 ml/min) administration should be undertaken with caution and under supervision, as clinical data are limited.

Hepatic impairment

Clearance is reduced by approximately 30% in stable hepatic cirrhosis; no dose adjustment has been recommended in mild to moderate impairment, but the product has not been studied in severe hepatic impairment and use in that setting is not recommended. Liver function should be monitored where impairment is present.

Athletes

Anastrozole is prohibited at all times, in and out of competition, under Section S4 (Hormone and Metabolic Modulators) of the WADA Prohibited List. Its presence in a sample constitutes an anti-doping rule violation irrespective of therapeutic intent; use in an athlete subject to the WADA Code requires a granted Therapeutic Use Exemption.

Undesirable effects

Musculoskeletal and connective tissue

Arthralgia, joint stiffness, myalgia, bone pain, reduced bone mineral density with osteopenia or osteoporosis on prolonged use, increased fracture risk, trigger finger and carpal tunnel syndrome

Vascular and general

Hot flushes, asthenia, fatigue, peripheral oedema

Nervous system

Headache, somnolence, paraesthesia, dysgeusia, carpal-tunnel-type sensory symptoms

Reproductive system and breast

Vaginal dryness, vaginal bleeding (particularly in the first weeks of treatment or on switching from hormonal therapy), reduced libido

Metabolism and nutrition

Anorexia, hypercholesterolaemia and adverse shifts in the lipid profile, weight change

Hepatobiliary

Elevated alanine and aspartate aminotransferases, raised alkaline phosphatase and gamma-glutamyltransferase, hepatitis (rare)

Gastrointestinal

Nausea, vomiting, diarrhoea, dyspepsia

Skin and subcutaneous tissue

Rash, alopecia or hair thinning, urticaria; erythema multiforme, Stevens–Johnson syndrome and cutaneous vasculitis have been reported very rarely

Overdose

Clinical experience of deliberate overdose is limited; anastrozole has been tolerated in single doses of up to 60 mg and daily doses of up to 10 mg without dose-limiting toxicity, and no dose has been established at which anastrozole is life-threatening. Expected features are exaggerated pharmacological effects — nausea, vomiting, dizziness, asthenia and vasomotor symptoms. There is no specific antidote; management is symptomatic and supportive, with the patient closely observed. Dialysis may be considered since anastrozole is not highly protein bound, and vomiting should not be induced in an obtunded patient.

Pharmacodynamic properties

Anastrozole is a non-steroidal, selective aromatase inhibitor of the triazole class (ATC L02BG03). It binds reversibly and competitively to the haem group of the cytochrome P450 aromatase enzyme complex (CYP19), thereby blocking the peripheral conversion of androstenedione and testosterone into oestrone and oestradiol respectively. In postmenopausal women, in whom oestrogen derives almost exclusively from peripheral aromatisation in adipose tissue, muscle and liver, daily administration of 1 mg produces suppression of circulating oestradiol of approximately 97% relative to baseline, with maximal suppression attained within 3 to 4 days of continuous dosing. Anastrozole possesses no intrinsic progestogenic, androgenic or oestrogenic activity and, at clinically relevant exposures, does not interfere with adrenal corticosteroid or aldosterone synthesis, so glucocorticoid or mineralocorticoid replacement is not required.

Pharmacokinetic properties

Absorption after oral administration is rapid and essentially complete, with peak plasma concentrations typically reached within 2 hours under fasting conditions; food slows the rate but not the overall extent of absorption, and exposure is unaffected clinically. Plasma protein binding is low, at approximately 40%, and steady state is reached after some 7 days of once-daily dosing with an accumulation ratio of roughly three- to four-fold. Anastrozole is extensively metabolised in the liver — accounting for over 85% of elimination — by N-dealkylation, hydroxylation and glucuronidation, the principal circulating metabolite triazole being pharmacologically inactive against aromatase; less than 10% of the dose is excreted unchanged in urine. The terminal elimination half-life is approximately 40 to 50 hours, which supports once-daily administration as determined by the prescriber.

List of excipients

Tablet core: lactose monohydrate, povidone K30, sodium starch glycolate (Type A), colloidal anhydrous silica, magnesium stearate. Film-coat: hypromellose 6 cP, macrogol 300, titanium dioxide (E171). The 1 mg dose is presented on a fine-particle lactose carrier and blended by geometric dilution so that content uniformity is met to Ph. Eur. 2.9.40 / USP <905> on every batch.

Excipient warnings

Contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Incompatibilities

Not applicable to this dosage form.

Shelf life

36 months from the date of manufacture in the unopened container.

After first opening

No special in-use storage requirements. Tablets should be left in the intact blister until immediately before administration; a tablet removed from its blister must not be returned to it and should be taken at once or discarded.

Storage

Store below 25 °C in a dry place. Keep tablets in the outer carton until use.

Container

50 film-coated tablets in PVC/PVdC–aluminium push-through blisters (10 tablets per blister, 5 blisters per carton), enclosed in a tamper-evident, GS1-serialised outer carton with the patient leaflet. Blister-forming film and lidding foil are qualified to ISO 15378. Not all pack sizes may be marketed.

Disposal

No special requirements for handling. Any unused medicinal product or waste material, including partially used blisters and the outer carton, should be disposed of in accordance with local requirements; do not dispose of via wastewater or household waste.

Pack

50 Tablets

GTIN

05012345678914

Serial

6630 0271 9945 12

LOT

AN2614N

MFG

02 / 2027

EXP

02 / 2030

Every carton carries a GS1 DataMatrix and a verification code; a pack can be checked at ergopharm.net/verify.

Ergopharm Advanced Research Centre, Tandalja, Vadodara, Gujarat 390012, India. For Export Only.

Report a suspected adverse reaction or quality defect to pv@ergopharm.net.