Glenza

Instructions for enzalutamide

Common name: enzalutamide

Trade name: Xtandi

All names: enzalutamide, enzalutamide, Xtandi, MDV 3100,

Usage and dosage:

160 mg, administered orally, once a day. Swallow capsule whole. Do not chew, dissolve, or open capsules. Can be taken with or without food.

Adverse reactions:

(1) The most common adverse reactions (5%): weakness/fatigue, back pain, diarrhea, joint pain, hot flashes, topical edema, muscle bone pain, headache, upper respiratory tract infection, muscle weakness, dizziness, insomnia, lower respiratory tract infection, spinal cord compression and cauda equina syndrome, hematuria, sensory abnormalities, anxiety and hypertension.

(2) Seizures: the most common adverse reaction leading to treatment discontinuation (0.9%)

(3) Laboratory abnormalities: neutropenia, elevated ALT, elevated bilirubin.

(4) Infection or sepsis.

(5) Falls and fall-related injuries.

(6) Hallucinations: Most of the patients with hallucinations were taking opioid-containing drugs at the time of the incident. Hallucinations include visual, tactile, and undefined.

Contraindications:

Pregnancy. Depending on its mechanism of action, XTANDI may cause fetal lethality. XTANDI is contraindicated in female patients who are pregnant or planning to become pregnant.

Notes:

Special groups: children: The safety and effectiveness of this product in pediatric patients have not been determined. Elderly: No definite differences, but greater susceptibility in certain age groups cannot be ruled out. Patients with Renal Impairment: No initial dose adjustment is required in patients with mild to moderate renal impairment. Patients with severe renal impairment (Ccr<30m]/min ) and end-stage renal disease have not been evaluated. Patients with hepatic impairment: No initial dose adjustment is required in patients with mild or moderate hepatic impairment. Patients with severe hepatic impairment (Child-Pugh category C) have not been evaluated.

Lactation: XTANDI is not suitable for nursing women because it is not known whether enzalutamide is excreted in breast milk. However, many drugs are secreted into breast milk, and XTANDI can cause harm to the fetus. Women taking this drug therefore need to choose between stopping breastfeeding or stopping the drug.
Pediatric Use: There is no data on the safety and effectiveness of XTANDI in pediatric use.
Usage in the elderly: In a randomized clinical trial of 800 people, 71% of the patients were over 65 years old and 25% were over 75 years old. The experimental results did not observe age-related differences in overall efficacy and safety.
Patients with Kidney Impairment: There are no trials specifically targeting XTANDI in patients with kidney impairment. Population-based pharmacokinetic analysis using data from clinical trials in patients with metastatically refractory prostate cancer and healthy volunteers. The trial results showed that there was no significant difference between patients with mild to moderate renal impairment (30 ml/min creatinine clearance 89 ml/min) and patients with normal renal function.
Patients with Liver Impairment: A trial specifically targeting the use of XTANDI in patients with liver impairment showed no significant difference between patients with mild to moderate liver impairment (creatinine clearance 30 ml/min and 89 ml/min) compared with patients with normal liver function.

Interactions:

(1) Drugs that inhibit or induce CYP2C8: Strong CYP2C8 inhibitors increase the AU C of this product and should be avoided in combination. If it is unavoidable, reduce the dose of this product. The in vivo effects of combining CYP2C8 inducers with this product have not been evaluated and should be avoided if possible.

(2) Drugs that inhibit or induce CYP3A4: Combination with strong CYP3A4 inhibitors may increase the AUC of this product. The in vivo effects of CYP3A4 inducers combined with this product have not been evaluated. The concomitant use of strong CYP3A4 inducers (such as carbamazepine, phenobarbital, phenytoin, non-IJ kabutin, non-IJ fampicin, rifapentine) with this product may reduce the plasma exposure of this product, so combined use should be avoided. It is recommended to select a CYP3A4 inducer with no or minimal induction potential when used together. Moderate CYP3A4 inducers (such as bosartan, efavirenz, etJvirine, modafinil, teafcillin and St. John's wort) may also reduce the plasma exposure of this product and therefore their coadministration should also be avoided.

(3) The effect of this product on drug metabolism peak: enzalutamide is a strong CYP3A4 inducer and a moderate CYP2C9 and CYP2Cl9 inducer. At steady state, this product reduces plasma exposure to midazolam (CYP3A4 substrate), warfarin (CYP2C9 substrate), and some (CYP2C19). Avoid coadministration of this product with drugs metabolized by CYP3A4 (such as alfentanil, cyclotoxin, dihydroergot gum, ergot gum, fentanyl, pimozide, quinidine, sirolimus, tacroins), CYP2C9 (such as phenytoin, warfarin) and CYP2Cl9 (such as s-mephenytoin) with narrow therapeutic windows, because enzalulamide may reduce their exposure. If coadministration with warfarin cannot be avoided, additional INR monitoring should be performed.

Overdose:

In the event of overdose, discontinue medication and initiate general supportive medical measures. Overdose can increase the risk of epilepsy.

Storage:

Store at 8°F to 77°F (20°C to 25°C) in a dry, airtight container.

Mechanism of action:

Enzalutamide is an androgen receptor inhibitor that competitively inhibits the binding of androgens to the receptor, and inhibits the nuclear transport of the androgen receptor and the interaction between the receptor and DNA. In vitro experimental studies have shown that enzalutamide can inhibit the proliferation of prostate cancer cells and induce their death. In mouse prostate cancer xenograft model experiments, enzalutamide can reduce tumor volume. The main metabolite of enzalutamide is N-desmethylenzalutamide, which exhibits similar inhibitory activity to enzalutamide in vitro.