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Ferric derisomaltose (Iron isomaltoside): Drug information

Ferric derisomaltose (Iron isomaltoside): Drug information
(For additional information see "Ferric derisomaltose (Iron isomaltoside): Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Monoferric
Brand Names: Canada
  • Monoferric
Pharmacologic Category
  • Iron Preparations
Dosing: Adult

Note: Route of administration: IV iron replacement is preferred over oral replacement in several clinical situations (eg, poor GI absorption, lack of response to or poor tolerability of oral iron, need for rapid repletion, chronic kidney disease, active inflammatory bowel disease, cancer, chronic or extensive blood loss) (Ref). Dosage expression: Dose is expressed in mg of elemental iron. Test dose: A test dose is not required.

Iron-deficiency anemia, treatment

Iron-deficiency anemia, treatment: IV:

≥50 kg: 1 g as a single dose (Ref) or up to 3 doses of 500 mg administered over 7 days (Ref).

<50 kg: 20 mg/kg as a single dose.

Canadian labeling: Cumulative dose may be determined using the Ganzoni formula or Simplified Dosing Table, or by using a fixed dose based on weight (see dosing above). In clinical studies described in the Canadian labeling, the Ganzoni formula was used in patients with chronic kidney disease (Ref) and the Simplified Dosing Table was used in patients with iron-deficiency anemia from other causes (Ref).

Ganzoni formula:

Iron need (mg) = BW (kg) × (target Hb [g/dL] – actual Hb [g/dL]) × 2.4 + iron stores (mg)a

BW= weight in kg; for individuals with obesity, use ideal body weight

aFor patients >35 kg, the iron stores are 500 mg or above. Some guidelines suggest using 10 to 15 mg iron/kg body weight and others suggest 1 g iron as stores.

Simplified Dosing Table:

Hb (g/dL)

Weight <50 kg

Weight 50 to <70 kg

Weight ≥70 kg

≥10 g/dL

500 mg

1 g

1.5 g

<10 g/dL

500 mg

1.5 g

2 g

Note: For administration by IV infusion, maximum single dose is 1.5 g or 20 mg/kg (whichever is less). Administer doses ≤1 g over at least 20 minutes and doses >1 g over at least 30 minutes. For administration by IV bolus, maximum single dose is 500 mg; maximum rate of administration is 250 mg/minute. For either method of administration, if total dose exceeds what can be given in a single administration, administer in divided doses separated by ≥7 days.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment: Adult

US labeling:

There are no dosage adjustments provided in the manufacturer's labeling.

Canadian labeling:

Avoid use in patients with hepatic dysfunction (ALT and/or AST elevations >3 x ULN) where iron overload is the precipitating factor. Use is contraindicated in patients with decompensated liver cirrhosis or active hepatitis.

Dosing: Older Adult

Refer to adult dosing, use with caution.

Dosing: Obesity: Adult

It is recommended to use ideal body weight in patients with obesity when calculating cumulative doses with the Ganzoni formula (Ref).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Monoferric: 1000 mg/10 mL (10 mL)

Generic Equivalent Available: US

No

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Monoferric: 100 mg/mL (1 mL, 5 mL, 10 mL)

Administration: Adult

IV:

Infusion: Administer doses up to 1 g over ≥20 minutes. Administer doses >1 g over ≥30 minutes (Ref). Monitor for signs and symptoms of hypersensitivity reactions during and for ≥30 minutes and until clinically stable following infusion.

IV bolus injection: Single doses up to 500 mg may be administered as a slow IV bolus injection (undiluted or diluted) at a maximum rate of 250 mg/minute (Ref).

Use: Labeled Indications

Iron-deficiency anemia: Treatment of iron-deficiency anemia in adults who have intolerance to oral iron or unsatisfactory response to oral iron, or those with nonhemodialysis-dependent chronic kidney disease.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%:

Dermatologic: Skin rash (1%)

Endocrine & metabolic: Hypophosphatemia (4%)

Gastrointestinal: Nausea (1%)

<1%: Asthma, infusion related reaction, severe hypersensitivity reaction

Postmarketing: Abdominal pain, anaphylaxis, anxiety, arthralgia, back pain, chest pain, chills, constipation, cough, diaphoresis, diarrhea, dizziness, dysgeusia, dyspnea, erythema of skin, fatigue, fever, flu-like symptoms, flushing, headache, hypersensitivity reaction, hypertension, hypotension, increased liver enzymes, loss of consciousness, muscle spasm, myalgia, nausea and vomiting, nonimmune anaphylaxis, paresthesia, phlebitis, pruritus, seizure, shock, skin discoloration, syncope, tachycardia, urticaria

Contraindications

Serious hypersensitivity to ferric derisomaltose or any component of the formulation.

Canadian labeling: Additional contraindications (not in US labeling): Serious hypersensitivity to other parenteral iron products, decompensated liver cirrhosis or active hepatitis; non-iron-deficiency anemia (eg, hemolytic anemia); iron overload (eg, hemochromatosis; hemosiderosis).

Warnings/Precautions

Concerns related to adverse effects:

• Extravasation: Avoid extravasation (extravasation may cause local skin irritation or skin discoloration).

• Hypersensitivity/anaphylactoid reactions: Serious hypersensitivity reactions, including anaphylactic-type reactions (some life threatening and fatal) have been reported. Monitor during and for ≥30 minutes after each administration and until clinically stable. Equipment for resuscitation, medication, and trained personnel experienced in handling emergencies should be immediately available during infusion. Discontinue use immediately with signs of hypersensitivity and administer appropriate therapy.

Other warnings/precautions:

• Iron overload: Excessive iron therapy may lead to excess iron storage and possibly iatrogenic hemosiderosis or hemochromatosis. Do not administer iron in the presence of iron overload. Periodic monitoring of hemoglobin, hematocrit, serum ferritin, and transferrin saturation during therapy is recommended.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Dimercaprol: May enhance the nephrotoxic effect of Iron Preparations. Risk X: Avoid combination

Pregnancy Considerations

Iron transfer to the fetus is regulated by the placenta (BSH [Pavord 2020]; NAS 2020).

There is a risk of adverse maternal reactions (eg, anaphylaxis, hypotension, shock) following use of parenteral iron which may result in fetal bradycardia, especially during the second and third trimesters. Although the risk is rare, immediate treatment for anaphylactoid and/or hypersensitivity reactions should be available (BSH [Pavord 2020]). Fetal bradycardia has been observed following maternal administration of ferric derisomaltose (Woodward 2015).

Maternal iron requirements increase during pregnancy. Untreated iron deficiency and iron-deficiency anemia (IDA) in pregnant patients are associated with adverse pregnancy outcomes, including low birth weight, preterm birth, and increased perinatal mortality (ACOG 2021; BSH [Pavord 2020]). Maternal iron deficiency is also associated with fatigue, increased risk of postpartum depression, and possibly postpartum hemorrhage (BSH [Pavord 2020]).

Oral and parenteral iron are effective at replacing iron stores in pregnant patients (ACOG 2021), Most studies note iron therapy improves maternal hematologic parameters, however, data related to clinical outcomes in the mother and neonate are limited (FIGO 2019; NAS 2020; USPSTF [Siu 2015]). Parenteral iron therapy may be used in pregnant patients who cannot tolerate or respond to oral iron, when iron deficiency occurs later in pregnancy, or when malabsorption is present (ACOG 2021; BSH [Pavord 2020]).

Ferric derisomaltose has been evaluated for the treatment anemia during pregnancy, including IDA following postpartum hemorrhage (Holm 2017a; Holm 2017b; Holms 2019; Wesström 2020). However, due to limited safety data in early pregnancy, use of intravenous iron is generally not started until the second or third trimester (ACOG 2021; BSH [Pavord 2020]; FIGO 2019).

Breastfeeding Considerations

Ferric derisomaltose is present in breast milk.

Endogenous iron concentrations in breast milk vary by postpartum age and are lower than concentrations in the maternal plasma (Dorea 2000; Emmett 1997). Breast milk concentrations of iron are maintained in lactating patients with mild to moderate iron-deficiency anemia (IDA), but concentrations decrease if IDA is moderate to severe (El-Farrash 2012) or severe (Kumar 2008).

Following maternal administration of a single dose of ferric derisomaltose immediately postpartum, breast milk concentrations of iron transiently increased but the mean breast milk concentrations of iron remained within normal limits (Holm 2017c).

Iron deficiency and IDA are associated with adverse effects in postpartum patients (eg, altered cognition, depression, fatigue) that may influence interactions with the infant. Iron supplementation in the postpartum patient should be initiated as soon as possible following delivery when gestational anemia is a concern (WHO 2016). Parenteral iron therapy may be used in postpartum patients with uncorrected anemia at delivery who cannot tolerate, do not respond to, or are noncompliant with oral iron therapy, or the severity of anemia requires prompt management (BSH [Pavord 2020]).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother; monitor breastfed infants for constipation and diarrhea.

Monitoring Parameters

CKD patients: Hematocrit, hemoglobin, serum ferritin, serum iron, transferrin, percent transferrin saturation (TSAT), TIBC (takes ~4 weeks of treatment to see increased serum iron and ferritin, and decreased TIBC); iron status should be assessed ≥48 hours after last dose (due to rapid increase in values following administration); signs/symptoms of hypersensitivity reactions (during and ≥30 minutes following infusion); hypotension (during and following infusion). Evaluate iron status (TSAT and ferritin) when deciding to start or continue iron therapy, and at least every 3 months in patients also receiving ESA therapy. Monitor ferritin and TSAT more frequently when monitoring response to IV iron therapy, when initiating or increasing ESA dose, when there is blood loss, and in any other situations where iron stores may become depleted (KDIGO 2012).

Reference Range

Anemia, adults (KDIGO 2012): Hemoglobin: <13 g/dL (males) or <12 g/dL (females). Iron deficiency, adults (KDIGO 2012): Most CKD patients with ferritin >100 ng/mL have normal bone marrow iron stores. However, many CKD patients with ferritin levels higher than 100 ng/mL or transferrin saturation >20% will respond to iron supplementation.

Mechanism of Action

Ferric derisomaltose contains iron and a carbohydrate moiety where the iron is tightly bound in a matrix structure (iron [III] atoms and derisomaltose). The particle is metabolized through the reticuloendothelial system in the liver and spleen which divide the complex into iron and derisomaltose. Iron is immediately bound and stored as ferritin, and derisomaltose moiety is either metabolized or excreted (Kalra 2016).

Pharmacokinetics

Onset: Therapeutic response: A few days

Distribution: 3 to 3.5 L (Nordfjeld 2012)

Metabolism: Reticuloendothelial system (RES) in liver and spleen to iron and isomaltoside (Kalra 2016)

Half-life elimination: 1 to 4 days (dose dependent)

Time to peak, serum: 0.57 to 1.53 hours (dose dependent)

Excretion: Urine and feces (negligible)

Pricing: US

Solution (Monoferric Intravenous)

1000 mg/10 mL (per mL): $313.72

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Diafer (CZ, DK, GB, IE, NL, RU, SE);
  • Monofar (BG, DE, EE, HR, IS, LT, LV, PT, RO);
  • Monofer (AT, AU, DK, FI, GB, GR, HK, KP, NL, NO, RU, SE);
  • Monoferro (ES);
  • Monover (IE, PL)


For country code abbreviations (show table)
  1. American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 233: Anemia in pregnancy. Obstet Gynecol. 2021;138(2):e55-e64. doi:10.1097/AOG.0000000000004477 [PubMed 34293770]
  2. Auerbach M, Henry D, Derman RJ, Achebe MM, Thomsen LL, Glaspy J. A prospective, multi-center, randomized comparison of iron isomaltoside 1000 versus iron sucrose in patients with iron deficiency anemia; the FERWON-IDA trial. Am J Hematol. 2019;94(9):1007-1014. doi:10.1002/ajh.25564 [PubMed 31243803]
  3. Auerbach M. Treatment of iron deficiency anemia in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 13, 2021.
  4. Bhandari S, Kalra PA, Berkowitz M, Belo D, Thomsen LL, Wolf M. Safety and efficacy of iron isomaltoside 1000/ferric derisomaltose versus iron sucrose in patients with chronic kidney disease: the FERWON-NEPHRO randomized, open-label, comparative trial. Nephrol Dial Transplant. 2021;36(1):111-120. doi:10.1093/ndt/gfaa011 [PubMed 32049331]
  5. Derman R, Roman E, Modiano MR, Achebe MM, Thomsen LL, Auerbach M. A randomized trial of iron isomaltoside versus iron sucrose in patients with iron deficiency anemia. Am J Hematol. 2017;92(3):286-291. doi:10.1002/ajh.24633 [PubMed 28052413]
  6. Dorea JG. Iron and copper in human milk. Nutrition. 2000;16(3):209-220. doi:10.1016/s0899-9007(99)00287-7 [PubMed 10705077]
  7. El-Farrash RA, Ismail EA, Nada AS. Cord blood iron profile and breast milk micronutrients in maternal iron deficiency anemia. Pediatr Blood Cancer. 2012;58(2):233-238. doi: 10.1002/pbc.23184. [PubMed 21548016]
  8. Emmett PM, Rogers IS. Properties of human milk and their relationship with maternal nutrition. Early Hum Dev. 1997;49(suppl):S7-S28. doi:10.1016/s0378-3782(97)00051-0 [PubMed 9363415]
  9. FIGO Working Group on Good Clinical Practice in Maternal-Fetal Medicine. Good clinical practice advice: Iron deficiency anemia in pregnancy. Int J Gynaecol Obstet. 2019;144(3):322-324. doi:10.1002/ijgo.12740 [PubMed 30710364]
  10. Holm C, Thomsen LL, Norgaard A, Langhoff-Roos J. Single-dose intravenous iron infusion or oral iron for treatment of fatigue after postpartum haemorrhage: a randomized controlled trial. Vox Sang. 2017a;112(3):219-228. [PubMed 28198084]
  11. Holm C, Thomsen LL, Norgaard A, Langhoff-Roos J. Single-dose intravenous iron infusion versus red blood cell transfusion for the treatment of severe postpartum anaemia: a randomized controlled pilot study. Vox Sang. 2017b;112(2):122-131. [PubMed 28010050]
  12. Holm C, Thomsen LL, Norgaard A, Markova V, Michaelsen KF, Langhoff-Roos J. Iron concentration in breast milk normalised within one week of a single high-dose infusion of iron isomaltoside in randomised controlled trial. Acta Paediatr. 2017c;106(2):256-260. doi:10.1111/apa.13681 [PubMed 27883237]
  13. Holm C, Thomsen LL, Langhoff-Roos J. Intravenous iron isomaltoside treatment of women suffering from severe fatigue after postpartum hemorrhage. J Matern Fetal Neonatal Med. 2019;32(17):2797-2804. doi:10.1080/14767058.2018.1449205 [PubMed 29558233]
  14. Kalra P, Bhandari S. Efficacy and safety of iron isomaltoside (Monofer®) in the management of patients with iron deficiency anemia. Int J Nephrol Renovasc Dis. 2016;9:53-64. [PubMed 27022297]
  15. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guidelines for Anemia in Chronic Kidney Disease (2012). https://kdigo.org/wp-content/uploads/2016/10/KDIGO-2012-Anemia-Guideline-English.pdf. Accessed June 17, 2019.
  16. Kumar A, Rai AK, Basu S, et al. Cord blood and breast milk iron status in maternal anemia. Pediatrics. 2008;121(3):e673-677. doi:10.1542/peds.2007-1986 [PubMed 18310187]
  17. Monoferric (ferric derisomaltose) [prescribing information]. Morristown, NJ: Pharmacosmos Therapeutics Inc; August 2022.
  18. Monoferric (ferric derisomaltose) [product information]. Kirkland, Quebec, Canada: Pfizer Canada Inc; September 2021.
  19. National Academies of Sciences, Engineering, and Medicine. Nutrition During Pregnancy and Lactation: Exploring New Evidence: Proceedings of a Workshop. The National Academies Press; 2020. https://doi.org/10.17226/25841
  20. Nordfjeld K, Andreasen K, Thomsen L. Pharmacokinetics of iron isomaltoside 1000 in patients with inflammatory bowel disease. Drug Des Devel Ther. 2012;6:43-51. [PubMed 22419860]
  21. Pavord S, Daru J, Prasannan N, Robinson S, Stanworth S, Girling J; BSH Committee. UK guidelines on the management of iron deficiency in pregnancy. Br J Haematol. 2020;188(6):819-830. doi:10.1111/bjh.16221 [PubMed 31578718]
  22. Refer to manufacturer's labeling.
  23. Siu AL; U.S. Preventive Services Task Force. Screening for iron deficiency anemia and iron supplementation in pregnant women to improve maternal health and birth outcomes: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2015;163(7):529-536. doi:10.7326/M15-1707 [PubMed 26344176]
  24. Wesström J. Safety of intravenous iron isomaltoside for iron deficiency and iron deficiency anemia in pregnancy. Arch Gynecol Obstet. 2020;301(5):1127-1131. doi:10.1007/s00404-020-05509-2 [PubMed 32270330]
  25. World Health Organization (WHO). Guideline: iron supplementation in postpartum women. Geneva: World Health Organization; 2016. [PubMed 27583315]
  26. Woodward T, Kay T, Rucklidge M. Fetal bradycardia following maternal administration of low-molecular-weight intravenous iron. Int J Obstet Anesth. 2015;24(2):196-197. [PubMed 25794420]
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