PROHANCE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROHANCE (PROHANCE).
Gadolinium-based paramagnetic contrast agent that enhances T1-weighted MRI signal by shortening the longitudinal relaxation time of water protons.
| Metabolism | Not metabolized; excreted unchanged via renal glomerular filtration. |
| Excretion | Primarily renal (glomerular filtration), with >95% of the administered dose excreted unchanged in urine within 24 hours; less than 1% fecal or biliary. |
| Half-life | Terminal elimination half-life is approximately 1.5–2 hours in patients with normal renal function; increases to 4–12 hours in moderate to severe renal impairment; correlates with creatinine clearance. |
| Protein binding | <1% bound to plasma proteins (no significant binding to albumin or others). |
| Volume of Distribution | 0.26–0.34 L/kg (distribution primarily in extracellular fluid; low tissue uptake, consistent with a hydrophilic contrast agent). |
| Bioavailability | Not applicable (IV administration only); bioavailability is 100% when given intravenously. |
| Onset of Action | Immediately upon intravenous injection; contrast enhancement observed within minutes on MRI. |
| Duration of Action | Clinical imaging enhancement lasts for approximately 60–90 minutes post-injection, allowing for routine MRI acquisition. |
0.1 mmol/kg (0.2 mL/kg) intravenous bolus; not to exceed 0.1 mmol/kg for single dose; may repeat once within 30 minutes for certain indications.
| Dosage form | INJECTABLE |
| Renal impairment | GFR 30-59 mL/min/1.73 m²: reduce dose to 0.07 mmol/kg (0.14 mL/kg); GFR <30 mL/min/1.73 m²: contraindicated (increased risk of nephrogenic systemic fibrosis). |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment; severe impairment (Child-Pugh C): use with caution, monitor for gadolinium retention. |
| Pediatric use | Age <2 years: 0.1 mmol/kg (0.2 mL/kg) IV; maximum 0.1 mmol/kg per dose; may repeat once if necessary. Age ≥2 years: same as adult. |
| Geriatric use | No specific dose adjustment; use lowest effective dose, monitor renal function closely to avoid gadolinium accumulation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROHANCE (PROHANCE).
| Breastfeeding | Gadoteridol is excreted into breast milk in very small amounts; the milk-to-plasma (M/P) ratio is approximately 0.038. In lactating rats, peak milk concentrations were 4.5% of maternal dose. For humans, the infant dose is estimated at 0.01–0.04% of maternal intravenous dose, considered negligible. Because of minimal absorption from infant gastrointestinal tract (non-lipophilic) and low excretion, breastfeeding can be continued without interruption for this agent, but some guidelines suggest discarding milk for 24 hours post-administration. |
| Teratogenic Risk | Gadoteridol (PROHANCE) is a gadolinium-based contrast agent. In animal studies, no teratogenic effects were observed at doses up to 2.5 times the human dose, but fetal growth retardation occurred. In humans, gadolinium agents cross the placenta and are associated with risk of nephrogenic systemic fibrosis (NSF) in the fetus if used during pregnancy. The FDA categorizes as pregnancy category C; use only if clearly needed. First trimester: avoid due to organogenesis sensitivity; second/third trimester: limited data, potential accumulation in amniotic fluid; unknown risk of NSF. |
■ FDA Black Box Warning
Nephrogenic systemic fibrosis (NSF) risk in patients with acute or chronic severe renal insufficiency (eGFR < 30 mL/min/1.73m2) or hepatorenal syndrome.
| Serious Effects |
["History of allergic reaction to gadolinium-based contrast agents","Severe renal impairment (eGFR < 30 mL/min/1.73m2)","Acute kidney injury","Hepatorenal syndrome"]
| Precautions | ["Risk of nephrogenic systemic fibrosis in patients with renal impairment","Hypersensitivity reactions including anaphylaxis","Injection site reactions","Extravasation risk","Interference with serum calcium measurements"] |
Loading safety data…
| Fetal Monitoring | Maternal: Monitor for allergic reactions, nephrotoxicity in renal impairment (risk of NSF). Fetal: No specific monitoring; avoid use in pregnancy unless benefit outweighs risk. In neonates exposed in utero, no specific follow-up required except if maternal NSF or severe renal impairment present. |
| Fertility Effects | No specific studies on human fertility; animal studies show no impairment of fertility at clinically relevant doses. No known effect on spermatogenesis or oogenesis. |