TRUQAP
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRUQAP (TRUQAP).
TRUQAP (capivasertib) is an orally available, selective inhibitor of AKT (protein kinase B) isoforms 1, 2, and 3. AKT is a key component of the PI3K/AKT/mTOR signaling pathway, which is frequently dysregulated in cancer. By inhibiting AKT, TRUQAP reduces downstream signaling, leading to decreased cell proliferation, survival, and angiogenesis.
| Metabolism | TRUQAP is primarily metabolized by CYP3A4 and CYP2C8. It is also a substrate of P-glycoprotein (P-gp). |
| Excretion | Primarily metabolized via CYP3A4; 22.5% of dose excreted unchanged in feces, <1% unchanged in urine. Biliary excretion of metabolites accounts for ~77% of total clearance. |
| Half-life | Terminal elimination half-life is approximately 30 hours (range 24-38 h) in healthy subjects; supports once-daily dosing; prolonged in hepatic impairment. |
| Protein binding | 99.6% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent Vd is 975 L (approximately 14 L/kg for a 70 kg individual), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is 45% under fasted conditions; increased to 60% with a high-fat meal. |
| Onset of Action | Oral: Peak plasma concentration achieved 4-6 hours post-dose; clinical effect (antitumor activity) observed after 2-4 weeks of continuous dosing. |
| Duration of Action | Continuous pharmacodynamic effect due to sustained target inhibition; dosing is once daily without interruption; duration of response varies by tumor type. |
400 mg orally twice daily with food until disease progression or unacceptable toxicity.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended for severe renal impairment (CrCl <30 mL/min) due to lack of data. |
| Liver impairment | For Child-Pugh A (mild): no adjustment. For Child-Pugh B (moderate): reduce dose to 300 mg twice daily. Not recommended for Child-Pugh C (severe). |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended for elderly; however, monitor renal function and volume status, as elderly patients may be more susceptible to gastrointestinal toxicities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRUQAP (TRUQAP).
| Breastfeeding | There are no data on the presence of capivasertib in human milk, its effects on the breastfed infant, or effects on milk production. Because of the potential for serious adverse reactions in breastfed infants from TRUQAP, advise women not to breastfeed during treatment and for 1 week after the last dose. M/P ratio: not determined. |
| Teratogenic Risk | TRUQAP (capivasertib) is an AKT inhibitor. Based on its mechanism of action and animal studies, it is expected to cause fetal harm when administered to a pregnant woman. In animal reproduction studies, capivasertib was embryo-fetal lethal and caused malformations at exposures below the human exposure at the recommended dose. There are no adequate and well-controlled studies in pregnant women. First trimester: High risk of teratogenicity; contraindicated. Second and third trimesters: Potential for fetal harm; use only if benefit outweighs risk and consider fetal monitoring. |
■ FDA Black Box Warning
No black box warnings.
| Serious Effects |
["No absolute contraindications identified.","Relative: Patients with severe hepatic impairment (Child-Pugh Class C) are not recommended for treatment."]
| Precautions | ["Hyperglycemia: Monitor glucose levels; withhold or discontinue if severe.","Rash: Management may require dose interruption, reduction, or discontinuation.","Diarrhea: Provide supportive care; adjust dose if severe.","Fetal harm: Can cause fetal harm; advise contraceptive use in women of reproductive potential and men with female partners."] |
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| Fetal Monitoring | Monitor complete blood count (CBC) for neutropenia, thrombocytopenia, and anemia. Monitor serum glucose and HbA1c for hyperglycemia. Monitor serum creatinine, liver function tests (ALT, AST, bilirubin), and electrolytes. Monitor for signs of diarrhea, rash, and other adverse reactions. In pregnant women, fetal ultrasound to monitor for growth restriction and other abnormalities. Consider pregnancy testing before initiation. |
| Fertility Effects | Based on animal studies, TRUQAP may impair fertility in females and males. In female rats, capivasertib caused disruption of estrous cycles and reduced fertility indices at exposures similar to human exposure. In male rats, adverse effects on sperm parameters were observed. The effects on human fertility are unknown, but caution is advised. |