Copper Histidinate

Menkes disease is an X-linked recessive disorder caused by pathogenic variants in the copper transport ATPase encoded by ATP7A . Patients with Menkes disease have impaired absorption of copper from their diet, impaired transport of copper across the blood-brain barrier, and dysregulation of many copper-dependent enzymes.

• ZYCUBO is indicated for the treatment of Menkes disease in pediatric patients. ZYCUBO is a copper replacement product indicated for the treatment of Menkes disease in pediatric patients.

• None.contraindicated

Before initiating ZYCUBO, obtain baseline serum copper and ceruloplasmin levels, serum electrolytes, kidney and liver function, and complete blood count. ( 2.1 ) The recommended dosage of ZYCUBO in pediatric patients: Less than 1 year of age is 1.45 mg twice daily (8-12 hours between injections). ( 2.2 ) 1 year of age to less than 17 years of age is 1.45 mg once daily. ( 2.2 ) Monitor serum copper and ceruloplasmin levels, serum electrolytes, kidney and liver function, and complete blood count (CBC). ( 2.3 ) Reconstitute ZYCUBO and administer subcutaneously. ( 2.4 , 2.6 ) See Full Prescribing Information for additional preparation, storage, and administration instructions. ( 2.4 , 2.5 , 2.6 ) 2.1 Recommended Testing Before Initiating ZYCUBO Before initiating ZYCUBO, obtain baseline serum copper and ceruloplasmin levels, serum electrolytes, kidney and liver function, and complete blood count (CBC) [see Warnings and Precautions ( 5.1 )] . 2.2 Recommended Dosage and Administration The recommended dosage of ZYCUBO in pediatric patients: Less than 1 year of age is 1.45 mg administered subcutaneously twice daily (8-12 hours between injections). 1 year of age to less than 17 years of age is 1.45 mg administered subcutaneously once daily. 2.3 Dosage and Administration Modifications and Monitoring Monitor serum copper and ceruloplasmin levels, serum electrolytes, kidney and liver function, and complete blood count (CBC) every 6 weeks for the first 6 months, then every 3 months for 18 months, and then every 6 months thereafter during ZYCUBO treatment.

Copper Accumulation and Risk of Toxicity : Exogenous administration of copper with ZYCUBO may lead to further copper accumulation and has the potential to result in drug-induced kidney injury, liver dysfunction, and hematological abnormalities. Monitor patients during ZYCUBO treatment. Adjust dosage if necessary. ( 2.2 , 5.1 , 6.1 ) 5.1 Copper Accumulation and Risk of Toxicity Impaired copper transport in patients with Menkes disease can lead to copper accumulation and organ impairment in the kidneys, liver, and hematopoietic system. Treatment with ZYCUBO may lead to further copper accumulation and related toxicity, especially in the first two years of life given renal and hepatic immaturity. Obtain baseline serum copper and ceruloplasmin levels, serum electrolytes, kidney and liver function, and complete blood count (CBC). After initiating ZYCUBO, monitor laboratory values every 6 weeks for the first 6 months, then every 3 months for 18 months, and then every 6 months thereafter during ZYCUBO treatment. If laboratory abnormalities are detected, consider reducing the frequency of ZYCUBO administration or temporarily withholding or permanently discontinuing ZYCUBO. Return to increased frequency of laboratory monitoring when resuming a dosage as clinically indicated. Drug-Induced Kidney Injury Copper accumulation with ZYCUBO use has the potential to result in renal tubular toxicity in patients with Menkes disease. Routinely monitor patients starting or re-starting ZYCUBO for signs and symptoms of renal tubular toxicity.

The following clinically significant adverse reactions are described elsewhere in the labeling: Copper Accumulation and Risk of Toxicity: Drug-Induced Kidney Injury, Liver Dysfunction, Hematological Abnormalities [see Warnings and Precautions ( 5.1 )] Most common adverse reactions (incidence ≥7%) were pneumonia, viral infection, respiratory failure, seizure, bacterial infection, hemorrhage, hypotension, vomiting, tachycardia, pyrexia, volume depletion, fracture, dyspnea, transaminases elevation, diarrhea, fungal infection, anemia, and local administration reaction. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sentynl Therapeutics, Inc. at 1-888-507-5206 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety analysis from 2 open-label, single-arm clinical trials included a total of 129 ZYCUBO-treated patients with an age range from 0 to 48 months. Patients less than 1 year of age received ZYCUBO 1.45 mg twice daily, and patients 1 year of age and older received ZYCUBO 1.45 mg once daily. The median exposure duration was 24 months (range: 1 to 39 months) [see Clinical Studies ( 14 )] .

8.1 Pregnancy Risk Summary There are no available data on ZYCUBO use during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with ZYCUBO. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. 8.2 Lactation Risk Summary There are no data on the presence of copper histidinate and its metabolites in either human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for ZYCUBO and any potential adverse effects on the breastfed infant from ZYCUBO or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of ZYCUBO for the treatment of Menkes disease have been established in pediatric patients, and the information on this use is discussed throughout the labeling.

Metabolism

The geometric mean (CV%) maximum serum concentration (C max ) of copper histidinate was 67 (36%) ng/mL, the geometric mean (CV%) area under the concentration-time curve from time 0 to 24 hours (AUC 0-24hr ) was 186 (21%) ng•hr/mL, and the geometric mean (CV%) area under the concentration-time curve from time 0 to infinity (AUC 0-inf ) was 296 (15%) ng•hr/mL following a single subcutaneous dose of 3 mg copper histidinate (approximately twice the approved recommended dose for Menkes disease patients 1 year old or older) in healthy adult subjects.

• Jan 12, 2026NDANDA211241Sentynl Theraps Inc

1. 1Urosepsis1100%

The 2 most recently updated of 2 ClinicalTrials.gov registrations naming Copper Histidinate as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Long Term Follow-up on Menkes Disease Patients
  Active not recruiting · Observational · 50 enrolled · Sentynl Therapeutics, Inc.
  NCT04337684updated 2026-03-02
• Copper Histidinate Treatment for Menkes Disease
  Approved for marketing · Expanded access · Sentynl Therapeutics, Inc.
  NCT04074512updated 2026-03-02

Frequently asked questions

How does Copper Histidinate work?

Menkes disease is an X-linked recessive disorder caused by pathogenic variants in the copper transport ATPase encoded by ATP7A . Patients with Menkes disease have impaired absorption of copper from their diet, impaired transport of copper across the blood-brain barrier, and dysregulation of many copper-dependent enzymes.

What is Copper Histidinate used for?

According to FDA labeling, Copper Histidinate carries indications including: ZYCUBO is indicated for the treatment of Menkes disease in pediatric patients. ZYCUBO is a copper replacement product indicated for the treatment of Menkes disease in pediatric patients.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Copper Histidinate?

Copper Histidinate is classified as Ion Transporter Interactions, Inorganic Ion Absorption Alteration.

What are the brand names for Copper Histidinate?

Copper Histidinate is marketed under brand names including Zycubo.

What are the contraindications for Copper Histidinate?

Copper Histidinate labeling lists contraindications including: None.. Always consult the full prescribing information and a clinician.