Truqap

Capivasertib

In combination w/ fulvestrant for the treatment of adult patients w/ oestrogen receptor +ve, HER2 -ve locally advanced or metastatic breast cancer w/ ≥1 PIK3CA/AKT1/PTEN-alterations following recurrence or progression on or after an endocrine-based regimen.

400 mg bd, approx 12 hr apart, for 4 days followed by 3 days off treatment. Co-administer w/ fulvestrant 500 mg administered on days 1, 15, & 29, & once mthly thereafter. Co-administration w/ strong & moderate CYP3A4 inhibitor Reduce to 320 mg bd.

May be taken with or without food: Swallow whole w/ water. Do not chew, crush, dissolve, or divide. Do not ingest if broken, cracked, or otherwise not intact.

Hypersensitivity.

Risk of severe hyperglycaemia associated w/ ketoacidosis; diarrhoea; skin drug reactions, including erythema multiforme & dermatitis exfoliative generalised. Closely monitor patients w/ history of DM. Test for fasting blood glucose levels & HbA1c prior to treatment & at regular intervals during treatment. Clinical consequences of diarrhoea may include dehydration, hypokalaemia & acute kidney injury which have all, together w/ cardiac arrhythmias (w/ hypokalaemia as risk factor), been reported during treatment. Monitor for signs & symptoms of rash or dermatitis. Dosing may be interrupted, reduced, or permanently discontinued based on severity of diarrhoea & skin drug reactions. Efficacy & safety have not been studied in patients w/ symptomatic visceral disease; history of clinically significant cardiac disease (including QTcF >470 msec, any factors that increased risk of QTc prolongation/arrhythmic events/cardiac function impairment); pre-existing type 1 diabetes or type 2 diabetes requiring insulin, & those w/ HbA1c >8% (63.9 mmol/mol). Avoid co-administration w/ strong CYP3A4 inhibitors; strong & moderate CYP3A4 inducers. May have minor influence on ability to drive & use machines. Administer to patients w/ moderate hepatic impairment only if benefit outweighs risk, & closely monitor for signs of toxicity. Not recommended for patients w/ severe renal impairment & severe hepatic impairment, during pregnancy, & in women of childbearing potential not using contraception. Discontinue breast-feeding during treatment. Female patients should use effective contraception during treatment & for at least 4 wk after completion of treatment. Male patients should use effective contraception during treatment & for at least 16 wk after completion of treatment. May impair fertility in males of reproductive potential. Safety & efficacy in childn 0-18 yr have not been established. Limited data in elderly ≥75 yr. Combine Truqap plus fulvestrant w/ LH releasing hormone (LHRH) agonist in pre- or perimenopausal women. Consider administration of LHRH agonist in men according to current clinical practice standards.

UTI; anaemia; hyperglycaemia, decreased appetite; headache; diarrhoea, nausea, vomiting, stomatitis; rash, pruritus; fatigue. Hypersensitivity; hypokalaemia; dysgeusia, dizziness, syncope; acute kidney injury; dry mouth, abdominal pain, dyspepsia; dry skin, erythema multiforme; mucosal inflammation, pyrexia; increased blood creatinine, increased HbA1c.

Increased plasma conc w/ strong CYP3A4 inhibitors (eg, boceprevir, ceritinib, clarithromycin, cobicistat, conivaptan, ensitrelvir, idelalisib, indinavir, itraconazole, josamycin, ketoconazole, lonafarnib, mibefradil, mifepristone, nefazodone, nelfinavir, posaconazole, ribociclib, ritonavir, saquinavir, telaprevir, telithromycin, troleandomycin, tucatinib, voriconazole, grapefruit or grapefruit juice); moderate CYP3A4 inhibitors (eg, aprepitant, ciprofloxacin, cyclosporine, diltiazem, erythromycin, fluconazole, fluvoxamine, tofisopam, verapamil). Decreased plasma conc w/ strong CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampicin, St. John's wort). Decreased AUC w/ enzalutamide. Potential decrease in conc w/ moderate CYP3A4 inducers (eg, bosentan, cenobamate, dabrafenib, elagolix, etravirine, lersivirine, lesinurad, lopinavir, lorlatinib, metamizole, mitapivat, modafinil, nafcillin, pexidartinib, phenobarb, rifabutin, semagacestat, sotorasib, talviraline, telotristat ethyl, thioridazine). Increased AUC of midazolam. May increase conc of CYP3A substrates w/ narrow therapeutic window (eg, carbamazepine, cyclosporine, fentanyl, pimozide, simvastatin, tacrolimus). May increase systemic exposure of sensitive CYP2D6 substrates w/ narrow therapeutic index; sensitive UGT1A1 substrates w/ narrow therapeutic index (eg, irinotecan). May decrease systemic exposure of sensitive CYP2B6 substrates w/ narrow therapeutic index (eg, bupropion). May increase exposure of medicinal products that are sensitive to inhibition of BCRP, OATP1B1 &/or OATP1B3 if they are metabolised by CYP3A4 (eg, simvastatin); medicinal products that are sensitive to inhibition of MATE1, MATE2K & OCT2 (eg, dofetilide, procainamide). Transient serum creatinine increases may be observed during treatment w/ Truqap due to inhibition of OCT2, MATE1 & MATE2K by capivasertib.

Targeted Cancer Therapy

L01EX27 - capivasertib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.

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