Iron isomaltoside (Monoferric, Monofer) is an intravenous formulation of iron. It is indicated for the treatment of adults with iron deficiency who are intolerant to oral iron.

Iron isomaltoside (Monoferric, Monofer) Uses:

Note: It is not approved in the US.

• Iron-deficiency anemia:

  • It is used to treat iron-deficiency anemia in adults who have an inadequate response to oral iron or are intolerant to oral iron replacement therapy.

Iron sucrose (Venofer) is another commonly used parenteral iron formulation. Venofer is usually administered as a slow intravenous infusion with doses per day not exceeding 300 mg. Iron Isomaltoside has the advantage of fewer hospital/ clinic visits and less number of doses per course as the maximum dose per infusion is 1500 mg of iron.

Iron isomaltoside (Monoferric, Monofer) Dosing in Adults:

Note: Dose expressed here are as elemental iron.

Iron isomaltoside (Monoferric, Monofer) Dose in the treatment of Iron-deficiency anemia: IV:

Note:

• The cumulative dose should be calculated before initiating the treatment.
• The Ganzoni formula was used to calculate the cumulative dose of iron required in patients with kidney disease while the simplified table was used to calculate the total iron required in patients without kidney disease.

• Ganzoni formula:

  • Iron required in mg = weight in kgs x (target Hgb – actual Hgb) x 2.4 + depot iron in mg
  • Generally, the depot iron stores in patients weighing more than 35 kgs are taken as 500 mg or above.
  • A depot iron dose of 10 to 15 mg of iron/kg body weight has been suggested by some guidelines.
  • The depot iron in pregnancy and lactation is taken as 1000 mg.

Simplified Table for the total cumulative dose of iron:

Iron isomaltoside (Monoferric, Monofer) Use in Children:

Iron isomaltoside has not been studied in children.

Iron isomaltoside (Monoferric, Monofer) Pregnancy Risk Category: C

• Fetal bradycardia has been caused by maternal iron isomaltoside administration.
• In pregnancy, maternal iron requirements increase. Except for very severe anemia, the iron requirements of the foetus are not affected by maternal iron deficiency.
• If left untreated, maternal iron deficiency can lead to adverse outcomes for fetuses, including preterm birth, low birth weight and increased risk of perinatal death.
• Iron deficiency is the same treatment for pregnant women as for non-pregnant ladies. 
• Except for women with an insufficient response to oral iron or who are allergic to iron (women suffering from malabsorption or other inflammatory bowel disorders), oral iron therapy is not recommended.
• Postpartum women have been tested for the drug. When iron isomaltoside is used, the manufacturer recommends contraceptives for females with reproductive potential.

Use of iron isomaltoside during breastfeeding

• Breast milk contains iron isomaltoside, which is excreted from breast milk.
• During breastfeeding, iron needs for mothers increase. Except for mothers with severe iron deficiency, the iron content in breastmilk is fairly stable.
• One intravenous injection of the drug causes a temporary increase in iron content in breastmilk. After that, the levels return to normal.

Iron isomaltoside (Monoferric, Monofer) Dose in Kidney Disease:

In the manufacturer's labeling, an adjustment in the dose has not been provided in patients with kidney disease.

Iron isomaltoside (Monoferric, Monofer) Dose in Liver Disease:

• No dosage adjustments have been provided in the manufacturer's labeling.
• It should be avoided in patients with hepatic dysfunction manifesting as raised liver enzymes (thrice the upper limits of normal).
• The drug is contraindicated in patients with active hepatitis or decompensated liver disease.

Iron isomaltoside (Monoferric, Monofer) Side Effects:

• Cardiovascular:

  • Hypertension
  • Procedural Hypotension
  • Peripheral Edema
  • Transient Hypertension
  • Hypotension

• Central Nervous System:

  • Headache
  • Dizziness
  • Falling
  • Fatigue
  • Paresthesia

• Dermatologic:

  • Skin Rash
  • Exfoliation Of Skin
  • Pruritus

• Endocrine & Metabolic:

  • Hyperkalemia
  • Hypophosphatemia
  • Hyperphosphatemia
  • Decreased Serum Calcium

• Gastrointestinal:

  • Nausea
  • Constipation
  • Diarrhea
  • Vomiting
  • Abdominal Pain

• Genitourinary:

  • Urinary Tract Infection

• Hematologic & Oncologic:

  • C-Reactive Protein Increased

• Hepatic:

  • Increased Serum Alanine Aminotransferase
  • Increased Serum Aspartate Aminotransferase

• Hypersensitivity:

  • Severe Hypersensitivity Reaction

• Neuromuscular & Skeletal:

  • Arthralgia
  • Back Pain
  • Myalgia
  • Limb Pain
  • Muscle Spasm

• Respiratory:

  • Nasopharyngitis
  • Oropharyngeal Pain
  • Cough
  • Dyspnea
  • Lower Respiratory Tract Infection
  • Upper Respiratory Tract Infection

• Miscellaneous:

  • Fever

Contraindications to Iron isomaltoside (Monoferric, Monofer):

• Allergy reactions to iron isomaltoside or iron parenteral products or any component of this formulation
• Patients suffering from active hepatitis, or decompensated liver disease;
• Hemolytic anemia
• Iron overload conditions such as hemochromatosis or hemosiderosis can occur.
• Multiple allergies.

Warnings and precautions

• Extravasation:

  • Extravasation can cause skin irritation and skin discoloration.

• Hypersensitivity and anaphylactoid reactions are: [Canadian-Boxed Warning]

  • There have been severe allergic reactions to the drug, including anaphylaxis and hypotension.
  • The patient must be closely monitored throughout the infusion, and for at least 30 minutes after each infusion, until they are stable.
  • Atopic conditions such as asthma or atopic dermatitis can lead to serious allergic reactions. Patients suffering from inflammatory conditions such as rheumatoidarthritis or systemic lupus-erythematosus are at increased risk for allergic reactions.
  • It is important that the drug be administered only in areas where qualified personnel and equipment are available for resuscitation.
  • Treatment must be stopped immediately if hypersensitivity is detected.

• Hypophosphatemia

  • Although hypophosphatemia was observed in some patients, the majority of them remain symptomatic.
  • Reports indicate that hypophosphatemia was observed in 20% and 2% respectively of patients with and without kidney disease.
  • Most patients see a normalization in serum phosphate levels within four weeks after the last dose.

• Hypotension

  • Hypotension can occur especially when intravenous injections are given quickly.
  • Patients should not receive intravenous injections too quickly and should be monitored for at least 30 minutes after infusion.

• Hepatic impairment

  • Patients with active hepatitis and decompensated liver disease should not receive parenteral iron.
  • Patients with severe hepatic impairment, such as elevated liver enzymes three times the normal limit, should avoid it.

• Infections

  • Avoid parenteral iron for patients with bacteria or those suffering from severe, acute, or chronic, anemia.

• Porphyria Cutanea Tarda (PCT):

  • Patients with porphyria Cutanea Tarta should avoid the drug. Patients with iron overload should be monitored.

Iron isomaltoside: Drug Interaction

Monitoring Parameters:

• Hemoglobin, hematocrit, and iron studied (serum ferritin, serum iron, TIBC) should be monitored;
• Patients should be monitored for hypotension and anaphylactic reactions during and for at least 30 minutes following the infusion.
• KDOQI guidelines recommend monitoring iron status every one to three months. Patients may need frequent monitoring after a course of intravenous iron.

How to administer Iron isomaltoside (Monoferric, Monofer)?

Note:

• Patients should be monitored for allergic reactions and hypotension during the treatment and for thirty minutes following the infusion. The injection can also be administered via the dialysis line.

How to administer iron isomaltoside 500 mg?

• Iron isomaltoside is administered as a slow intravenous injection.
• It may be administered at a rate not exceeding 250 mg/minute.
• A single dose of up to 500 mg may be administered diluted or undiluted as a slow intravenous injection.

How to administer a dose of 1000 mg or more?

• It can also be administered as an intravenous infusion.
• Doses up to 1000 mg may be administered as slow intravenous infusions over at least 20 minutes.
• Doses exceeding 1000 mg should be administered over 30 minutes or more.
• Doses up to 20 mg of iron/kg (not exceeding 1500 mg) may be administered as a single infusion.
• Doses exceeding 20 mg/kg should be administered as two infusions at least one week apart.

Mechanism of action of Iron isomaltoside (Monoferric, Monofer):

• Iron isomaltoside is iron bound to a carbohydrate moiety within a matrix-like structure that contains iron (III) and isomaltoside pentamers.
• Iron-isomaltoside (in the liver, spleen) is converted to iron and isomaltoside by the reticuloendothelial systems.
• While the iron is stored in ferritin, the isomaltoside moiety of the isomaltoside is metabolized and excreted.

Onset: Therapeutic response:

• A few days

Metabolism:

• Reticuloendothelial system (RES) in the liver and spleen to iron and isomaltoside.

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)

International Brand Names of Iron isomaltoside:

• MONOFERRIC
• Diafer
• Monofar
• Monofer
• Monoferro
• Monover

Iron isomaltoside Brand Names In Pakistan: