Safety Update: New Sorbitol-Containing IV Remsima Formulation

Key Points: A new liquid infusion formulation of Remsima (infliximab) has been introduced in Europe as a 100 mg and 350 mg concentrate for infusion. Unlike the original powder form, the new concentrate contains sorbitol (45 mg/mL)ema.europa.eu. Because patients with hereditary fructose intolerance (HFI) cannot safely metabolize sorbitol, this formulation must not be given to HFI patientsema.europa.eu. Even very small intravenous doses of sorbitol in HFI can trigger life-threatening reactions (severe hypoglycemia, acute liver failure, bleeding, kidney failure and death)ema.europa.eu. Health professionals should confirm that patients have no history of HFI before using the new IV Remsima and should counsel and document this in the patient’s recordfamhp.beema.europa.eu. The original Remsima powder for infusion (which contains no sorbitol) remains available and should be used for any patient with HFIema.europa.euema.europa.eu.

What is Remsima (Infliximab)?

Remsima is a biosimilar of infliximab (the reference product Remicade) and acts as an anti-inflammatory (anti-TNF) monoclonal antibodyema.europa.euema.europa.eu. It was first authorized in the EU in 2013 and is used when other treatments have failed. Indications include the treatment of:

• Rheumatoid arthritis (with methotrexate)
• Ankylosing spondylitis
• Psoriatic arthritis
• Psoriasis
• Crohn’s disease (moderate to severe or fistulizing)
• Ulcerative colitis (moderate to severe)ema.europa.eu.

In children (≥6 years), it is approved for severe active Crohn’s disease or ulcerative colitis unresponsive to other therapyema.europa.eu. Infliximab works by binding tumor necrosis factor-alpha (TNF-α) – a key molecule in driving inflammation – thereby reducing inflammation in the joints, gut, skin and other tissuesema.europa.eu.

Historically, IV infliximab (Remsima) has been supplied as a lyophilized powder to be reconstituted (made into solution) before infusion. In late 2025, a new liquid concentrate formulation was introduced to streamline preparation. The new product is a 40 mg/mL concentrate available in 100 mg (2.5 mL) and 350 mg (8.75 mL) vialsema.europa.eu. It requires no reconstitution (only dilution before infusion) and cuts preparation time and potential for errorcelltrion.com.

What’s Different About the New IV Formulation?

The new Remsima IV concentrate is chemically identical to old Remsima (same infliximab), but differs in formulation. Its vial contains 45 mg of sorbitol per mLema.europa.eu. Sorbitol was included as a stabilizing excipient in the liquid formulation. By contrast, the original Remsima powder vials contain no sorbitol at all. As the EMA CHMP noted, “the new formulation is associated with the following new contraindication: Patients with hereditary fructose intolerance (HFI)”ema.europa.eu. In other words, the presence of sorbitol means the new infusion form cannot be used in HFI.

Importantly, Remsima’s subcutaneous (SC) formulation (a separate injectable form) also contains sorbitol, but it has been judged safe for HFI patients due to the much slower absorption via skin. The warning applies specifically to intravenous sorbitol exposureema.europa.eu.

Regulatory status (late 2025): In September 2025 the EMA’s Committee (CHMP) gave a positive opinion for this variationema.europa.eu. In November 2025, the European Commission authorized the IV liquid formulation (100 mg and 350 mg vials) for the same indications as the original productcelltrion.com. A Direct Healthcare Professional Communication (DHPC) was issued (EMA publication date 8 Dec 2025) to raise awareness of the sorbitol/HFI issueema.europa.eu.

Hereditary Fructose Intolerance (HFI): What Is It?

Hereditary fructose intolerance is a rare genetic metabolic disorder (estimated 1 in 20,000–30,000 peoplemedlineplus.gov). It is inherited in an autosomal recessive pattern: patients have two faulty copies of the ALDOB gene, encoding the enzyme aldolase Bncbi.nlm.nih.govmedlineplus.gov. Aldolase B is needed to break down fructose-1-phosphate, an intermediate in fructose metabolism.

Affected infants are typically normal at birth and only become ill when fruit or other sources of fructose/sucrose are introduced into the diet (often around weaning)ncbi.nlm.nih.govmedlineplus.gov. After ingesting fructose (or sucrose, which contains fructose), HFI patients develop gastrointestinal symptoms (nausea, bloating, vomiting) and hypoglycemia (low blood sugar)ncbi.nlm.nih.govmedlineplus.gov. Chronic exposure leads to liver and kidney injury: jaundice, hepatomegaly, and eventually hepatic cirrhosis; failure to thrive; and if unchecked, seizures, coma and deathmedlineplus.gov. In essence, without the aldolase B enzyme, fructose-1-phosphate builds up in liver cells and poisons the metabolismncbi.nlm.nih.govmedlineplus.gov.

Treatment for HFI is strict avoidance of fructose, sucrose and sorbitol in the dietncbi.nlm.nih.govncbi.nlm.nih.gov. Foods and drugs containing these must be avoided to prevent severe metabolic crisesncbi.nlm.nih.govncbi.nlm.nih.gov. Infants often develop a strong aversion to sweets. With proper diet, patients can have normal growth and life expectancyncbi.nlm.nih.govncbi.nlm.nih.gov.

Why Is Sorbitol Dangerous in HFI?

Although sorbitol is a sugar alcohol (often used as a sweetener or excipient), the body converts sorbitol into fructose. In HFI patients, any sorbitol ingestion effectively delivers fructose internally. In those lacking aldolase B, even a small IV dose of sorbitol triggers the same toxic cascade as fructose. As one EMA communication explains: “in patients with HFI, even small amounts of intravenously administered sorbitol can result in severe adverse reactions, including hypoglycaemia, acute hepatic failure, haemorrhagic syndrome, renal failure, and death”ema.europa.eu.

Put simply, sorbitol (via sorbitol dehydrogenase) is oxidized to fructose, then phosphorylated to fructose-1-phosphate. Without functional aldolase B, fructose-1-phosphate accumulates, depleting cellular phosphate and ATPncbi.nlm.nih.gov. This leads to severe hypoglycemia (since glucose release is blocked), liver and kidney damage, and coagulopathy. In fact, medical reports have documented fatal outcomes in HFI patients after IV sorbitol infusion. The DHPC emphasizes that intravenous sorbitol is absolutely contraindicated in HFIema.europa.eu.

(As a side note, the subcutaneous Remsima syringe also has sorbitol, but because absorption is slower and partial metabolism in skin, it is not listed as contraindicated. The warning applies only to the IV infusion formema.europa.eu.)

Clinical and Prescribing Implications

• Screen for HFI: Before using the new Remsima concentrate, healthcare professionals must confirm the patient does not have hereditary fructose intolerancefamhp.be. This means reviewing medical history for any HFI diagnosis or symptoms, and considering family history.
• Use alternate formulation if HFI: For any patient known or suspected to have HFI, do not use the new sorbitol-containing infusion. Instead, the original Remsima powder (no sorbitol) or another TNF inhibitor should be used. The old IV powder formulation will remain available for this purposeema.europa.euema.europa.eu. The DHPC explicitly notes that the existing infusion (powder) form will continue to be supplied alongside the new concentrateema.europa.eu.
• Patient education: Patients should be informed that a rare sugar intolerance (HFI) could make this medicine dangerous for them. If a patient with HFI is prescribed Remsima, a special patient reminder card and updated leaflet will note the new contraindicationdrugoffice.gov.hkfamhp.be.
• Documentation and labeling: Treatment records and infusion orders should specify which formulation is used. Pharmacies should flag HFI contraindication when dispensing the IV concentrate. The product label (SmPC and package leaflet) for Remsima has been updated to list HFI as a contraindication for the concentrate for infusionema.europa.eu.
• Adverse event reporting: Any suspected reactions linked to sorbitol (e.g. unexplained hypoglycemia or hepatic injury) should be reported via pharmacovigilance channels, especially if in a patient not known to have HFI.

In practice, the key is vigilance. The chance of encountering HFI is low (estimated 1/20,000), but the consequences are severe. Rheumatologists, gastroenterologists and infusion nurses should brief their teams about asking patients about fructose intolerance or advising specialists (e.g. pediatric metabolic clinics) about this new safety issue. Note that dietary fructose malabsorption (common bloating) is different and not the concern here – the alert is specifically for genetic HFI.

Regulatory Guidance and References

The European Medicines Agency (EMA) has coordinated this safety update. A Direct Healthcare Professional Communication (DHPC) was published by EMA on 8 December 2025, jointly by the MAH (Celltrion) and regulatory authorities, to summarize the issueema.europa.euema.europa.eu. The DHPC, as well as updates to the EMA-approved product information, make it clear that the new concentrate “contains sorbitol and is therefore contraindicated in patients with hereditary fructose intolerance”ema.europa.euema.europa.eu.

This information has also been flagged by EMA’s Pharmacovigilance Risk Assessment Committee (PRAC). Meeting highlights (Sept 2025) note that PRAC discussed the DHPC and clarified that the existing powder form will remain availableema.europa.eufamhp.be. National regulatory bodies (e.g. Belgium’s FAMHP and Hong Kong’s Drug Office) have echoed the EMA guidancefamhp.bedrugoffice.gov.hk.

Healthcare professionals should follow the updated Summary of Product Characteristics (SmPC) and patient leaflet for Remsima once published. The SmPC now lists HFI as a contraindication for the IV concentrate (in section 4.3) and details the sorbitol content in section 6.1. For further details, see the EMA DHPC and product data pages.

In summary: The new Remsima IV liquid formulation makes infusion preparation faster, but contains sorbitol. Because sorbitol can trigger severe toxicity in hereditary fructose intolerance, this update imposes a new contra­indication. Clinicians should exclude HFI before using the concentrate, keep the old formulation available for such patients, and inform patients of this issue. Proper vigilance will help maintain the safety of infliximab therapy in all eligible patients.