ferric pyrophosphate DIALYSATE (Rx)

>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

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

There are no available data on pregnant women to inform a drug-associated risk of major birth defects and miscarriage; use drug during pregnancy only if potential benefit justifies potential risk to 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

Contraception

Advise females of reproductive potential to use effective contraception measures to prevent pregnancy during treatment and for at least 2 weeks following completion of therapy

Lactation

There is no information regarding presence in human milk, effects on breastfed child, or on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition

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.

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)

Dialysate 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 5-mL ampule) to 2.5 gallons (9.46 L) of bicarbonate concentrate for preparation of the hemodialysate OR 272 mg (1 25-mL ampule or 1 powder packet) to 25 gallons of bicarbonate concentrate

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