Romurtide

Summary

Romurtide is a synthetic muramyl‑dipeptide (MDP) analogue classified as an immunomodulatory peptide. It is approved for prescription use and administered intravenously or subcutaneously. The drug is used to stimulate immune cells, particularly to restore leukocyte and platelet counts in patients whose blood cells have been depleted by chemotherapy or radiotherapy, and has been explored for local immunotherapy of malignant pleural effusion.

Mechanism of Action

Romurtide mimics the minimal immunostimulatory motif of bacterial cell‑wall peptidoglycan (N‑acetyl‑muramyl‑L‑alanine‑D‑isoglutamine). By binding to pattern‑recognition receptors on monocytes and macrophages, it triggers intracellular signaling that leads to the production of pro‑inflammatory cytokines such as TNF‑α, IL‑1β, IL‑6, IL‑8 and MCP‑1. The cytokine surge promotes proliferation and activation of neutrophils, monocytes and, indirectly, platelet precursors, enhancing host defence against infections.

What the Research Shows

Pre‑clinical work in mice showed that romurtide increased resistance to bacterial, fungal and viral challenges and raised leukocyte and platelet numbers. Clinical observations in cancer patients receiving chemotherapy or radiotherapy reported restoration of leukocyte counts and, in some studies, platelet recovery. A Japanese study of 30 radiotherapy patients receiving 200 µg subcutaneously twice weekly for two weeks demonstrated a rise in neutrophils from the first week, though platelet counts did not improve and four patients experienced fever. In a small intrapleural trial (six lung‑cancer patients), a single 200 µg dose prevented pleural‑effusion re‑accumulation in four cases and induced a rapid neutrophil influx and local cytokine elevation. Overall, evidence consists of animal data, case series and uncontrolled clinical reports, without large randomised trials.

Reported Benefits

Available data suggest romurtide can accelerate recovery of neutrophil counts after myelosuppressive therapy, potentially lowering infection risk in chemotherapy or radiotherapy patients. Local intrapleural administration has shown promise in controlling malignant pleural effusion, with observed reductions in fluid re‑accumulation and heightened immune cell activity at the site. Animal studies further support broad enhancement of host defence mechanisms.

Limitations of the Evidence

Clinical evidence is limited to small, uncontrolled studies, primarily from Japan, with no randomized controlled trials confirming efficacy for infection prevention or cancer outcomes. The effect on platelet recovery is inconsistent, and optimal timing relative to radiotherapy remains uncertain. Long‑term safety and comparative effectiveness versus standard growth‑factor therapies have not been established.

Safety Considerations

Romurtide has been generally well tolerated in the reported studies. Mild fever occurred in a minority of radiotherapy patients, and no serious adverse events were noted in the intrapleural trial. No major systemic toxicities were reported, but the limited sample size means rare adverse effects could be undetected. Caution is advised when administering immediately after radiation due to transient leukocyte fluctuations.

How It Is Administered

Romurtide is supplied as a sterile peptide solution for intravenous or subcutaneous injection. Clinical protocols have used 200 µg subcutaneously, five times per week for two weeks, or a single 200 µg intrapleural instillation for malignant pleurisy. The drug is administered by healthcare professionals in a clinical setting.

Routes of Administration

Goals & Uses

• ImmunostimulationImmunomodulationModerate
• Platelet recoveryHematopoietic SupportModerate
• Hematopoietic recovery after radiotherapyHematopoietic SupportModerate
• Neutropenia recoveryHematologyModerate
• Treatment of chemotherapy-induced leukopeniaHematopoietic SupportHigh

Contraindications

• Known hypersensitivity to Romurtide or excipientsAllergyHigh
• Severe hepatic or renal impairmentOrgan ImpairmentModerate
• Hypersensitivity to romurtide or MDP analoguesAllergyHigh
• Autoimmune disordersImmuneModerate

Adverse Effects

• Fever / PyrexiaSystemicCommon
• Hypersensitivity reactionsImmunologicRare
• Injection site reactionsLocalCommon
• Malaise / fatigueSystemicUncommon
• Chills / rigorsSystemicCommon
• FeverSystemicUncommonElevated body temperature
• Elevated liver enzymesHepaticUncommonIncrease in AST/ALT or other hepatic markers
• Injection site erythemaLocalCommonRedness at the injection site

Drug Interactions

• Cytotoxic chemotherapy agentsLow
• Immunosuppressants (e.g., corticosteroids)Moderate
• Concurrent myelosuppressive chemotherapyModerate

Population Constraints

• PregnancyReproductive SafetyRelative
• Pediatric patientsAgeRelative
• Pediatric patients (<12 y)AgeRelative
• Elderly patientsAgeRelative
• Pregnant womenReproductiveRelative

Regulatory Status

• European UnionUnapprovedNo marketing authorization in the European Union.
• United StatesUnapprovedInvestigational; not FDA‑approved.
• United KingdomUnapprovedNot authorized for clinical use.

Approved in Japan for clinical use to treat leukopenia induced by chemotherapy or radiotherapy. Not approved by the US FDA or EMA. Limited regulatory recognition outside Japan.

Evidence & Sources

• Development of the cytokine inducer romurtide: experimental studies and clinical application
  Journal ArticleModerateAzuma I1992-01-01T00:00:00.000000Z
• [Study on the most appropriate time for Romurtide administration (Nopia) in radiotherapy patients]
  Journal ArticleModerateYokouchi J, et al.1997-01-01T00:00:00.000000Z
• Review: inducer of cytokines in vivo: overview of field and romurtide experience
  Journal ArticleModerateAzuma I1992-01-01T00:00:00.000000Z
• Intrapleural therapy with MDP-Lys (L18), a synthetic derivative of muramyl dipeptide, against malignant pleurisy associated with lung cancer
  Journal ArticleModerateYanagawa H, et al.2000-01-01T00:00:00.000000Z
• Potentiation of host defense mechanism against infection by a cytokine inducer, an acyl-MDP derivative, MDP-Lys(L18) (romurtide) in mice and humans
  Journal ArticleModerateAzuma I, Otani T1994-01-01T00:00:00.000000Z
• [Biochemical and immunological properties of the fractions of tubercle bacilli]
  Journal ArticleModerateAzuma I1998-01-01T00:00:00.000000Z

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