Version July 2025
(For additional information see "Remestemcel-L: Pediatric drug information")
Dosage guidance:
Dosing: Dose should be based on actual body weight.
Clinical considerations: Premedications: Premedicate with corticosteroids (eg, hydrocortisone) and antihistamines (eg, diphenhydramine) ~30 to 60 minutes prior to remestemcel-L infusion (Ref).
Graft-versus-host disease (GVHD), acute, steroid refractory, treatment:
Infants ≥2 months, Children, and Adolescents:
Initial: IV: 2 × 106 mesenchymal stromal cells (MSC)/kg/dose twice weekly for 4 consecutive weeks (total of 8 infusions). Doses should be separated by at least 3 days. Assess clinical response after 28 ± 2 days.
Retreatment: May consider retreatment after 28 days if: Partial or mixed response or GVHD recurs after complete response; dose varies based on indication for retreatment.
Partial or mixed response: IV: 2 × 106 mesenchymal stromal cells (MSC)/kg/dose once weekly for 4 additional weeks (total of 4 infusion).
Recurrence of GVHD after complete remission: IV: 2 × 106 mesenchymal stromal cells (MSC)/kg/dose twice weekly for 4 consecutive weeks (total of 8 infusions). Doses should be separated by at least 3 days.
No response: Consider alternative therapy.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for infants, children, and adolescents.
>10%:
Cardiovascular: Cardiac arrythmia, edema, hypertension, hypotension
Dermatologic: Skin rash
Gastrointestinal: Abdominal pain, diarrhea, vomiting
Hematologic & oncologic: Hemorrhage, thrombocytopenia (grades ≥3)
Hepatic: Increased gamma-glutamyl transferase (grades ≥3), increased serum bilirubin (grades ≥3)
Infection: Infection (including bacterial infection [including staphylococcal bacteremia], fungal infection, viral infection)
Neuromuscular & skeletal: Arthralgia
Respiratory: Cough, respiratory failure
Miscellaneous: Fever
Frequency not defined:
Gastrointestinal: Gastroenteritis
Hypersensitivity: Hypersensitivity (including infusion-related reaction)
Respiratory: Interstitial pneumonitis
Hypersensitivity to dimethyl sulfoxide or porcine and bovine proteins.
Concerns related to adverse effects:
• Ectopic tissue formation: Due to the ability of human mesenchymal stromal cells to differentiate into mesenchymal lineage cells such as bone, cartilage, and fat cells, ectopic tissue may be formed.
• Hypersensitivity/infusion reactions: Infusion reactions may occur with remestemcel-L, including dyspnea, fever, and hypotension. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO) and/or porcine and bovine material in remestemcel-L. Premedication (with antihistamines and corticosteroids) may reduce the potential for infusion reactions. Interrupt therapy if reactions occur; do not readminister in patients with severe of life-threatening reactions.
• Infection: Remestemcel-L is derived from human cells and human, porcine, and bovine reagents and has a risk of transmitting infectious diseases caused by known or unknown agents. Donors are screened for increased infection risk (infection with HIV, human T-cell lymphotropic virus, hepatitis B virus, hepatitis C virus, West Nile virus, Cytomegalovirus, Epstein-Barr virus, and Syphilis [Treponema pallidum]). Donors are also screened Creutzfeldt-Jakob disease, as well as communicable disease risks associated with xenotransplantation. Remestemcel-L cell banks are tested for human and animal viruses, retroviruses, bacteria, fungi, yeast, and mycoplasma. Although human and animal-derived reagents are tested for animal viruses, bacteria, fungi, and mycoplasma prior to use, these measures may not eliminate the risk of transmission of these or other infectious diseases/agents.
Other warnings/precautions:
• Excipients: Remestemcel-L contains excipients (DMSO, human serum albumin, and/or bovine and porcine material), which are associated with hypersensitivity reactions; some excipients are associated with severe reactions, including anaphylaxis.
• Universal precautions: Remestemcel-L contains human cells; follow universal precautions and facility biosafety guidelines for handling and disposal to avoid potential transmission of infectious diseases.
Ryoncil: FDA approved December 2024; anticipated availability unknown.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Kit, Intravenous:
Ryoncil <12.5kg: Remestemcel-L-rknd 1 x 3.8 mL [contains albumin human, beef extract (bovine), dimethyl sulfoxide, pork (porcine) protein]
Ryoncil 62.5kg to <75kg: Remestemcel-L-rknd 6 x 3.8 mL [contains albumin human, beef extract (bovine), dimethyl sulfoxide, pork (porcine) protein]
Kit, Intravenous [preservative free]:
Ryoncil 12.5kg to <25kg: Remestemcel-L-rknd 2 x 3.8 mL [contains albumin human, beef extract (bovine), dimethyl sulfoxide, pork (porcine) protein]
Ryoncil 25kg to <37.5kg: Remestemcel-L-rknd 3 x 3.8 mL [contains albumin human, beef extract (bovine), dimethyl sulfoxide, pork (porcine) protein]
Ryoncil 37.5kg to <50kg: Remestemcel-L-rknd 4 x 3.8 mL [contains albumin human, beef extract (bovine), dimethyl sulfoxide, pork (porcine) protein]
Ryoncil 50kg to <62.5kg: Remestemcel-L-rknd 5 x 3.8 mL [contains albumin human, beef extract (bovine), dimethyl sulfoxide, pork (porcine) protein]
Ryoncil 75kg to <87.5kg: Remestemcel-L-rknd 7 x 3.8 mL [contains albumin human, beef extract (bovine), dimethyl sulfoxide, pork (porcine) protein]
Ryoncil 87.5kg to <100kg: Remestemcel-L-rknd 8 x 3.8 mL [contains albumin human, beef extract (bovine), dimethyl sulfoxide, pork (porcine) protein]
No
Kit (Ryoncil 12.5kg to <25kg Intravenous)
2 x 3.8 mL (per each): $0.00
Kit (Ryoncil 25kg to <37.5kg Intravenous)
3 x 3.8 mL (per each): $0.00
Kit (Ryoncil 37.5kg to <50kg Intravenous)
4 x 3.8 mL (per each): $0.00
Kit (Ryoncil 50kg to <62.5kg Intravenous)
5 x 3.8 mL (per each): $0.00
Kit (Ryoncil 62.5kg to <75kg Intravenous)
6 x 3.8 mL (per each): $0.00
Kit (Ryoncil 75kg to <87.5kg Intravenous)
7 x 3.8 mL (per each): $0.00
Kit (Ryoncil 87.5kg to <100kg Intravenous)
8 x 3.8 mL (per each): $0.00
Kit (Ryoncil <12.5kg Intravenous)
1 x 3.8 mL (per each): $0.00
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.
Note: Premedicate with corticosteroids (eg, hydrocortisone) and antihistamines (eg, diphenhydramine) ~30 to 60 minutes prior to remestemcel-L infusion.
Parenteral: IV infusion: Infusion must occur within 5 hours of the thaw start time of the first set of vials. Administer via blood filter (pore size 40 to 260 microns) and an infusion pump. After infusion, flush line according to institutional protocol. Refer to manufacturer's labeling for additional details.
Infusion rate is based on patient weight:
<35 kg: Administer over 60 minutes.
≥35 kg: Administer at a rate of ≤6 mL/minute.
Rate adjustment for infusion-related reactions or hypersensitivity: Interrupt infusion and initiate appropriate medical treatment. If reaction severe or life-threatening, do not readminister.
Acute graft versus host disease: Treatment of steroid refractory acute graft versus host disease in pediatric patients ≥2 months of age.
None known.
There are no known significant interactions.
Animal reproduction studies have not been conducted.
It is not known if remestemcel-L is present in breast milk.
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.
Signs and symptoms of hypersensitivity or acute infusion reactions.
The active ingredient in remestemcel-L is comprised of culture-expanded mesenchymal stromal cells isolated from the bone marrow of healthy human adult donors. In vitro studies show that mesenchymal stromal cells inhibit T cell activation as measured by proliferation and secretion of proinflammatory cytokines. Alloreactive donor-derived T-cells are involved in mediating the systemic inflammation, cytotoxicity, and potential end organ damage associated with graft versus host disease. The exact mechanism of action of remestemcel-L is unclear but may be related to immunomodulatory effects.
