b'26single published case report of intravenous decitabine use throughout thePregnancy Testing first trimester during pregnancy describes adverse developmental outcomes,Verify the pregnancy status in females of reproductive potential prior to including major birth defects (structural abnormalities). In animal reproductioninitiating INQOVI. studies, intravenous administration of decitabine to pregnant mice and ratsContraception during organogenesis at doses approximately 7% of the recommendedFemales human dose on a body surface area (mg/m2) basis caused adverseAdvise females of reproductive potential to use effective contraception developmental outcomes, including increased embryo-fetal mortality,during treatment with INQOVI and for 6 months after the last dose. alterations to growth, and structural abnormalities (see Data). AdviseMales pregnant women of the potential risk to a fetus.Based on genotoxicity findings, advise males with female partners of The estimated background risk of major birth defects and miscarriage forreproductive potential to use effective contraception during treatment with the indicated population is unknown. All pregnancies have a backgroundINQOVI and for 3 months after the last dose [see Nonclinical Toxicology risk of birth defect, loss, or other adverse outcomes. In the U.S. general(13.1) in the full Prescribing Information]. population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% toInfertility 20%, respectively.Based on findings of decitabine and cedazuridine in animals, INQOVIDatamay impair male fertility [see Nonclinical Toxicology (13.1) in the full Human DataPrescribing Information]. The reversibility of the effect on fertility is There are no available data on INQOVI use in pregnant women.unknown. A single published case report of intravenous decitabine pregnancy exposure8.4 Pediatric Use in a 39-year-old woman with a hematologic malignancy described multipleThe safety and effectiveness of INQOVI have not been established in thstructural abnormalities after 6 cycles of therapy in the 18week of gestation.pediatric patients. These abnormalities included holoprosencephaly, absence of nasal bone,8.5 Geriatric Use mid-facial deformity, cleft lip and palate, polydactyly, and rocker-bottomOf the 208 patients in clinical studies who received INQOVI, 75% werefeet. The pregnancy was terminated.age 65 years and older, while 36% were age 75 years and older. No overall Animal Datadifferences in safety or effectiveness were observed between patientsNo reproductive or developmental toxicity studies have been conductedage 65 years and older, 75 years and older, and younger patients. with INQOVI or cedazuridine.8.6 Renal Impairment In utero exposure to decitabine causes temporal-related defects in the ratNo dosage modification of INQOVI is recommended for patients withand/or mouse, which include growth suppression, exencephaly, defectivemild or moderate renal impairment (creatinine clearance [CLcr] of 30 toskull bones, rib/sternabrae defects, phocomelia, digit defects, micrognathia,89 mL/min based on Cockcroft-Gault). Due to the potential for increased gastroschisis, and micromelia. Decitabine inhibits proliferation and increasesadverse reactions, monitor patients with moderate renal impairment (CLcr apoptosis of neural progenitor cells of the fetal central nervous system30 to 59 mL/min) frequently for adverse reactions. INQOVI has not been (CNS) and induces palatal clefting in the developing murine fetus. studied in patients with severe renal impairment (CLcr 15 to 29 mL/min)Studies in mice have also shown that decitabine administration duringor end-stage renal disease (ESRD: CLcr 15 mL/min) [see Clinical osteoblastogenesis (Day 10 of gestation) induces bone loss in offspring.Pharmacology (12.3) in the full Prescribing Information]. In mice exposed to single intraperitoneal decitabine injections (0, 0.9 and 3.0 mg/m2, approximately 2% and 7% of the recommended daily clinical17 PATIENT COUNSELING INFORMATION dose, respectively) over gestation Days 8, 9, 10 or 11, no maternal toxicityAdvise the patient to read the FDA-approved patient labeling (Patient was observed, but reduced fetal survival was observed after treatment at Information). 3 mg/m2 and decreased fetal weight was observed at both dose levels. TheMyelosuppression 3 mg/m2 dose elicited characteristic fetal defects for each treatment day,Advise patients of the risk of myelosuppression and to report any symptoms including supernumerary ribs (both dose levels), fused vertebrae and ribs,of fever, infection, anemia, or bleeding to their healthcare provider as soon cleft palate, vertebral defects, hind-limb defects, and digital defects of as possible. Advise patients for the need for laboratory monitoring [see fore- and hind-limbs.Warnings and Precautions (5.1) in the full Prescribing Information]. In rats given a single intraperitoneal injection of 2.4, 3.6 or 6 mg/m2Embryo-Fetal Toxicity decitabine (approximately 5, 8, or 13% the daily recommended clinical dose,Advise pregnant women of the potential risk to a fetus. Advise females of respectively) on gestation Days 9-12, no maternal toxicity was observed.reproductive potential to inform their healthcare provider of a known or No live fetuses were seen at any dose when decitabine was injected onsuspected pregnancy [see Warnings and Precautions (5.2), Use in Specific gestation Day 9. A significant decrease in fetal survival and reduced fetalPopulations (8.1) in the full Prescribing Information]. weight at doses greater than 3.6 mg/m2 was seen when decitabine wasAdvise females of reproductive potential to use effective contraception given on gestation Day 10. Increased incidences of vertebral and ribduring treatment with INQOVI and for 6 months after the last dose [see anomalies were seen at all dose levels, and induction of exophthalmia,Use in Specific Populations (8.3) in the full Prescribing Information]. exencephaly, and cleft palate were observed at 6.0 mg/m 2 . IncreasedAdvise males with female partners of reproductive potential to use effective incidence of foredigit defects was seen in fetuses at doses greater than contraception during treatment with INQOVI and for 3 months after the last 3.6 mg/m2. Reduced size and ossification of long bones of the fore-limbdose [see Use in Specific Populations (8.3), Nonclinical Toxicology (13.1) and hind-limb were noted at 6 mg/m2.in the full Prescribing Information]. The effect of decitabine on postnatal development and reproductive capacityLactation 2was evaluated in mice administered a single 3 mg/m intraperitoneal injectionAdvise women not to breastfeed during treatment with INQOVI and for(approximately 7% the recommended daily clinical dose) on Day 10 of2 weeks after the last dose [see Use in Specific Populations (8.2) in the full gestation. Body weights of males and females exposed in utero to decitabinePrescribing Information]. were significantly reduced relative to controls at all postnatal time points.Administration No consistent effect on fertility was seen when female mice exposed inAdvise patients to take INQOVI at approximately the same time each dayutero were mated to untreated males. Untreated females mated to maleson an empty stomach. Instruct patients to avoid eating for at least 2 hours exposed in utero showed decreased fertility at 3 and 5 months of age (36%before and 2 hours after taking INQOVI. Advise patients on what to do when and 0% pregnancy rate, respectively). Follow up studies indicated thata dose is missed or vomited [see Dosage and Administration (2.2) in the treatment of pregnant mice with decitabine on gestation Day 10 wasfull Prescribing Information]. associated with a reduced pregnancy rate resulting from effects on sperm production in the F1-generation.Full Prescribing Information is available at www.inqovi.com/pi or by calling 8.2 Lactation1-844-824-4648. Risk Summary There are no data on the presence of cedazuridine, decitabine, or their metabolites in human milk or on their effects on the breastfed child or milk production. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with TAIHO ONCOLOGY, INC. 3/2022 INQOVI and for 2 weeks after the last dose. 8.3 Females and Males of Reproductive Potential INQOVI can cause fetal harm when administered to a pregnant woman[see Use in Specific Populations (8.1) in the full Prescribing Information].'