Dosing and uses of Triferic (ferric pyrophosphate)
Adult dosage forms and strengths
iron (III)
solution to add to bicarbonate concentrate of the hemodialysate
- 27.2mg/5mL ampule (5.44mg/mL)
- 272mg/50mL ampule (5.44mg/mL)
powder packet to add to bicarbonate concentrate of the hemodialysate
- 272mg/packet
Iron Replacement for HDD-CKD
Indicated for the replacement of iron to maintain hemoglobin in adult patients with hemodialysis-dependent chronic kidney disease (HDD-CKD)
Add 1 ampule (27.2mg FE [III]) to 2.5 gallons of bicarbonate concentrate
Administer at each dialysis procedure for as long as patients are receiving maintenance hemodialysis therapy for chronic kidney disease
Dosing Considerations
Limitations of use
- Not intended for use in patients receiving peritoneal dialysis
- Has not been studied in patients receiving home hemodialysis
Pediatric dosage forms and strengths
Safety and efficacy not established
Triferic (ferric pyrophosphate) adverse (side) effects
>10%
Procedural hypotension (21.6%)
1-10%
Muscle spasms (9.6%)
Headache (9.2%)
Pain in extremity (6.8%)
Peripheral edema (6.8%)
Dyspnea (5.8%)
Back pain (4.5%)
Pyrexia (4.5%)
Urinary tract infection (4.5%)
Asthenia (4.1%)
Fatigue (3.8%)
Arteriovenous fistula thrombosis (3.4%)
Arteriovenous fistula site hemorrhage (3.4%)
<1%
Hypersensitivity reactions (0.3%)
Frequency not defined
Asthenia
Dizziness
Constipation
Nausea
Pruritus
Warnings
Contraindications
None
Cautions
Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving parenteral iron products; monitor during and after hemodialysis
Iron status should be determined on predialysis blood samples; postdialysis serum iron parameters may overestimate serum iron and transferrin saturation
Pregnancy and lactation
Human Data
Pregnancy category: C
There are no adequate and well-controlled studies in pregnant women
However, all pregnancies, regardless of exposure to any drug, have a background rate of 2-4% for major malformations and 15-20% for pregnancy loss
Use during pregnancy only if the potential benefit justifies the potential risk to the fetus
Animal Data
In a fertility and early embryonic development study in female rats, the maternally toxic ferric pyrophosphate citrate dose of 40 mg/kg administered 3x/week by IV infusion was not toxic to the developing embryo
In embryo-fetal developmental toxicity studies, ferric pyrophosphate citrate was administered during the period of organogenesis as a 1-hr IV infusion to pregnant rats and rabbits; no maternal or developmental toxicity was observed at doses up to 30 mg/kg/day in rats and 20 mg/kg/day in rabbits
Maternally toxic doses affected embryo-fetal development, resulting in postimplantation loss due to early resorptions, abnormal placentae, decreased fetal body weight, and fetal head and vertebral malformations at 90 mg/kg/day in rats and vertebral malformations at 40 mg/kg/day in rabbits
A prenatal and postnatal development study was conducted in pregnant rats with IV doses of up to 90 mg/kg/day; the maternally toxic dose of 90 mg/kg/day resulted in reductions in the number of live offspring and lower offspring body weights
There were no adverse effects on survival of offspring at doses up to 30 mg/kg/day, or on behavior, sexual maturation, or reproductive parameters of offspring at any dose leveL
Lactation
Unknown if distributed in human breast milk
A decision should be made whether to discontinue nursing or to avoid therapy, taking into account risks versus benefits
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Triferic (ferric pyrophosphate)
Mechanism of action
Contains iron in the form of ferric pyrophosphate citrate and is added to hemodialysate solution to be administered to patients by transfer across the dialyzer membrane
Iron delivered into the circulation binds to transferrin for transport to erythroid precursor cells to be incorporated into hemoglobin
Pharmacokinetics
Vd: 0.765-0.859 L (4 hr infusion); 2.08 L (12 hr infusion)
Half-life: 1.48 hr
Clearance: 0.406-0.556 L/hr (4 hr infusion); 0.661 L/hr (12 hr infusion)
Administration
Preparation
Inspect ampules for signs of precipitation prior to mixing with the bicarbonate concentrate Ampules appear slightly yellow-green in color
Should only be added to the bicarbonate concentrate and should NOT be added to acid concentrate mixtures
Add ferric pyrophosphate to bicarbonate concentrate used for generation of the hemodialysate
The final concentration in the final hemodialysate is 2 μM (110 mcg/L)
Add 27.2 mg (1 ferric pyrophosphate ampule) to 2.5 gallons (9.46 L) of bicarbonate concentrate for preparation of the hemodialysate
Multiple ampules can be added to the master bicarbonate mix at each center at a ratio of 1 ampule to each 2.5 gallons of bicarbonate concentrate
Dialysate Administration
Administer at each dialysis procedure for as long as patients are receiving maintenance hemodialysis therapy for CKd
The dosage is expressed as mg of iron (III); contains 5.44 mg/mL (27.2 mg per 5 mL ampule)
Storage
Unopened ampules: Protect from light in the aluminum pouch at controlled room temperature (20-25°C [68-77°F]; excursions permitted as low as 15°C or as high as 30°C (59°F or 86°F)
Admixture: Hemodialysis solutions should be used within 24 hr of the preparation of the ferric pyrophosphate/bicarbonate concentrate mixture
