INQOVI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INQOVI (INQOVI).
INQOVI is a combination of decitabine, a hypomethylating agent that inhibits DNA methyltransferase, and cedazuridine, a cytidine deaminase inhibitor that prevents degradation of decitabine, increasing its systemic exposure.
| Metabolism | Decitabine is primarily metabolized by deamination via cytidine deaminase; cedazuridine inhibits cytidine deaminase, reducing decitabine metabolism. |
| Excretion | Decitabine and cedazuridine are primarily excreted renally. Following oral administration, 58-64% of the decitabine dose and 93% of the cedazuridine dose are recovered in urine, with <2% in feces. Renal excretion is the main elimination pathway for both components. |
| Half-life | The terminal elimination half-life of decitabine is approximately 2.5 hours (range 1.5-3.5 hours) following oral INQOVI administration. Cedazuridine has a similar half-life of about 2 hours. The half-lives are short, necessitating daily dosing for 5 days per cycle. |
| Protein binding | Decitabine is less than 1% bound to plasma proteins. Cedazuridine is approximately 30% bound to plasma proteins, mainly to albumin. |
| Volume of Distribution | The apparent volume of distribution of decitabine is approximately 63 L (about 0.9 L/kg for a 70 kg individual), indicating extensive distribution into total body water. Cedazuridine has a Vd of about 27 L (0.39 L/kg). |
| Bioavailability | The absolute oral bioavailability of decitabine in INQOVI is approximately 100% when co-administered with cedazuridine, compared to intravenous decitabine. Cedazuridine bioavailability is about 80%. |
| Onset of Action | Clinical response (e.g., hematologic improvement) is typically assessed after 2-4 cycles (each cycle is 28 days). Onset of action for decitabine is delayed due to its mechanism of DNA hypomethylation requiring multiple cell divisions. |
| Duration of Action | The pharmacodynamic effect (DNA hypomethylation) persists for the duration of treatment and declines after cessation. Clinical duration of response varies; median response duration in clinical studies was approximately 8-10 months for complete remission. |
INQOVI (decitabine and cedazuridine) is administered orally once daily on days 1 through 5 of a 28-day cycle. The recommended dose is 1 tablet (35 mg decitabine and 100 mg cedazuridine) taken on an empty stomach.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment is recommended for mild to moderate renal impairment (CrCl ≥30 mL/min). The safety and efficacy in severe renal impairment (CrCl <30 mL/min) have not been established. |
| Liver impairment | No dose adjustment is recommended for mild to moderate hepatic impairment (Child-Pugh A or B). The safety and efficacy in severe hepatic impairment (Child-Pugh C) have not been studied. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established. |
| Geriatric use | No specific dose adjustment is required for elderly patients; clinical studies included patients aged 65 years and older, and no overall differences in safety or efficacy were observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for INQOVI (INQOVI).
| Breastfeeding | No data on excretion into human breast milk. Due to potential for serious adverse reactions (myelosuppression, carcinogenesis), breastfeeding is contraindicated during INQOVI therapy and for at least 3 months after last dose. M/P ratio unknown. |
| Teratogenic Risk | INQOVI (decitabine and cedazuridine) is embryotoxic and teratogenic in animal studies. First trimester exposure carries highest risk of fetal malformations (neural tube, skeletal, cardiac defects). Second and third trimester exposure may cause fetal growth restriction and myelosuppression. Contraindicated in pregnancy unless no safer alternative. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to decitabine, cedazuridine, or any component of the formulation"]
| Precautions | ["Myelosuppression (neutropenia, thrombocytopenia, anemia)","Increased risk of infections","Hemorrhage","Hepatotoxicity","Embryo-fetal toxicity"] |
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| Fetal Monitoring | Monitor complete blood counts (CBC) weekly, hepatic function, renal function, and signs of infection. Perform pregnancy test prior to initiation. Fetal ultrasound for growth and anatomy if exposure occurs. Monitor for fetal myelosuppression via cord blood sampling if clinically indicated. |
| Fertility Effects | INQOVI may impair fertility in both males and females. Decitabine causes testicular degeneration and reduced spermatogenesis in animals. Ovarian toxicity (follicular depletion) reported. Advise fertility preservation options prior to treatment. |