Gadoquatrane

There are no available data on gadoquatrane use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. GBCAs cross the placenta and result in fetal exposure. In human placental imaging studies, contrast was visualized in the placenta and fetal tissues after maternal GBCA administration. Based on animal studies, use of GBCAs during pregnancy may result in fetal gadolinium retention. Published epidemiological studies on the association between GBCAs and adverse fetal outcomes have reported inconsistent findings and have important methodological limitations.

In animal reproduction studies, there were no adverse developmental effects observed in rats or rabbits with intravenous administration of gadoquatrane during organogenesis. Because of the potential risks of gadolinium to the fetus, use gadoquatrane only if imaging is essential during pregnancy and cannot be delayed.

There are no data on the presence of gadoquatrane in human milk, the effects on the breastfed infant, or the effects on milk production. However, published lactation data on other GBCAs indicate that 0.01% to 0.04% of the maternal gadolinium dose is present in breast milk, and there is limited GBCA gastrointestinal absorption in the breast-fed infant. Gadoquatrane is present in rat milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for gadoquatrane and any potential adverse effects on the breastfed infant from gadoquatrane or from the underlying maternal condition.

Carcinogenicity

Carcinogenicity studies in animals have not been conducted with gadoquatrane.

Mutagenesis

Gadoquatrane was not mutagenic or clastogenic with or without metabolic activation in five strains of the Ames bacterial mutagenicity assay (TA100, TA98, TA1535, TA1537, and TA102), or in vitro and in vivo micronucleus assays.

Impairment of Fertility

No adverse effects on reproductive performance or pregnancy outcome were observed in parental rats following daily intravenous administration of gadoquatrane before and during gestation at up to 0.54 mmol Gd/kg/day (corresponding to 4 times the human exposure). At 1.54 mmol Gd/kg/day (12 times the human exposure), a slight increase in the number of dead embryos and the percentage of post-implantation loss (4 of the 20 females in the treatment group each having at least 3 dead embryos) was observed and considered potentially related to gadoquatrane.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety of gadoquatrane was evaluated in four clinical studies in a total of 842 patients who received a single 0.01 mmol/kg dose. This safety population included 697 adult patients from two active comparator, cross-over studies, 52 adult patients from a dose-finding study, and 93 pediatric patients.

Adult Patients

Among the 749 adult patients (who were exposed to gadoquatrane), the mean age was 56 years (range: 18 years to 89 years). Of these patients, 67% were White, 29% Asian, 1% Black or African American, and 3% of other or unspecified race, and 10% were Hispanic or Latino, 76% not Hispanic or Latino, and 14% of unspecified ethnicity.

The following table lists adverse reactions that occurred in ≥0.2% of adult patients who received 0.01 mmol/kg gadoquatrane.

Adverse Reactions Reported in ≥0.2% of Adult Patients Who Received Gadoquatrane:

^* Injection site reactions include injection site pain, catheter site pain, injection site coldness, and injection site erythema.

Adverse reactions that occurred in <0.2% of adult patients who received 0.01 mmol/kg gadoquatrane included erythema, abdominal discomfort, toothache, feeling cold, decreased glomerular filtration rate, urinary sediment, urinary white blood cells, urticaria, dyspnea, rhinalgia, arthralgia, limb discomfort, hematuria, vertigo, and hyperbilirubinemia.

Pediatric Patients

Among the 93 pediatric patients, the mean age was 7 years (range: 28 days to less than 18 years). Of these patients, 57% were White, 38% Asian, 1% Black or African American, and 4% of unspecified race, and 14% were Hispanic or Latino, 80% not Hispanic or Latino, and 6% of unspecified ethnicity.

Adverse reactions in pediatric patients who received 0.01 mmol/kg gadoquatrane included (each occurring in 1% of patients): apnea, pyrexia, decreased platelet count, erythema, and rash.