VIJOICE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VIJOICE (VIJOICE).
Phosphoinositide 3-kinase (PI3K) inhibitor that selectively inhibits PI3Kδ (delta isoform) with less activity against PI3Kγ. It blocks the PI3K/AKT/mTOR signaling pathway, reducing proliferation and survival of malignant B cells.
| Metabolism | Primarily metabolized by cytochrome P450 (CYP) 3A4. Minor contributions from CYP2C8 and CYP2D6. Major metabolite is the N-desmethyl derivative (M1), which is inactive. |
| Excretion | Primarily biliary excretion (≈89% of dose recovered in feces as parent drug and metabolites). Renal excretion accounts for <2% of the dose as unchanged drug. |
| Half-life | Terminal elimination half-life is approximately 50–100 hours. Due to this long half-life, steady-state is reached after about 2–3 weeks of daily dosing, allowing for once-daily administration. |
| Protein binding | >99% bound to plasma proteins, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 2.5 L/kg, indicating extensive tissue distribution. This large Vd reflects high tissue binding and partitioning into fatty tissues. |
| Bioavailability | Oral bioavailability is approximately 30% under fasting conditions. When administered with a low-fat meal, exposure increases; with a high-fat meal, Cmax and AUC are significantly increased (≈1.5- to 2-fold). |
| Onset of Action | Time to clinical effect (reduction in tumor size or symptom improvement) varies; generally, first assessments are performed at 8 weeks of continuous therapy. |
| Duration of Action | Duration of action is prolonged due to long half-life; dosing is continuous once daily. Clinical benefit may be maintained for months to years depending on disease response. |
Adult: 200 mg orally twice daily, with or without food.
| Dosage form | TABLET |
| Renal impairment | eGFR >60 mL/min/1.73m²: No adjustment; eGFR 30-60: Reduce to 200 mg once daily; eGFR 15-29: Reduce to 200 mg every other day; eGFR <15 or dialysis: Not recommended. |
| Liver impairment | Child-Pugh A: No adjustment; Child-Pugh B: Reduce to 200 mg once daily; Child-Pugh C: Not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended based on age alone; monitor for increased adverse effects, especially renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VIJOICE (VIJOICE).
| Breastfeeding | No human data on alpelisib in breast milk. Animal studies indicate alpelisib and its metabolites are excreted in rat milk. Due to potential for serious adverse reactions in breastfed infants (e.g., severe diarrhea, hyperglycemia, rash), breastfeeding is not recommended during treatment and for at least 1 week after the last dose. M/P ratio is unknown. |
| Teratogenic Risk | VIJOICE (alpelisib) is contraindicated in pregnancy. Based on its mechanism of action (PI3Kα inhibition) and animal studies, it can cause fetal harm. There are no adequate human data; however, in animal reproduction studies, alpelisib was embryotoxic, fetotoxic, and teratogenic at maternal exposures below the clinical dose. First trimester exposure carries the highest risk of major congenital malformations. Second and third trimester exposure may cause fetal growth restriction, oligohydramnios, and fetal renal impairment due to PI3K signaling involvement in placental and fetal development. |
■ FDA Black Box Warning
Fatal and serious toxicities: infections, diarrhea/colitis, cutaneous reactions, pneumonitis. Risk of hepatotoxicity. Use only in patients who have received at least two prior systemic therapies and for whom no other therapy is available. Not recommended for use with other PI3K inhibitors.
| Serious Effects |
None known.
| Precautions | Infections (fatal and serious, including Pneumocystis jirovecii pneumonia and cytomegalovirus), diarrhea/colitis (severe, including fatal), cutaneous reactions (Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms), pneumonitis (non-infectious, including fatal), hepatotoxicity (elevated transaminases/bilirubin), neutropenia, embryo-fetal toxicity. Monitor blood counts, liver function, and for signs of infection. |
Loading safety data…
| Fetal Monitoring | If unintentional exposure occurs during pregnancy, immediate maternal-fetal monitoring is required: serial fetal ultrasound to assess growth, amniotic fluid volume, and renal anatomy; maternal monitoring for hyperglycemia, diarrhea, and rash. Pregnancy testing should be performed prior to initiation and monthly during treatment. Effective contraception must be used for at least 1 week after the last dose. |
| Fertility Effects | Based on animal studies, alpelisib may impair male and female fertility. In female rats, ovarian follicular degeneration and altered estrous cycles were observed. In male rats, testicular degeneration and decreased sperm motility occurred at clinically relevant exposures. Reversibility not established. Human fertility effects unknown; advise patients of potential risk. |