copper histidinate

Action and Spectrum

Actions and Spectrum:  

Action:  

Menkes disease is a rare pediatric disorder of copper deficiency inherited in an X-linked recessive pattern and results from mutations in the ATP7A copper transporter gene, leading to markedly reduced intestinal copper uptake. Affected patients exhibit defective dietary copper absorption, limited transport of copper across the blood–brain barrier, and abnormal function of multiple copper-dependent enzymes.  

Drug Interaction

Adverse Reaction

Frequency defined   

>10% 

Fracture (12%)
Volume depletion (12%)
Pyrexia (12%)
Tachycardia (12%)
Vomiting (15%)
Hypotension (16%)
Hemorrhage (18%)
Bacterial infection (20%)
Seizure (23%)
Respiratory failure (23%)
Viral infection (27%)
Pneumonia (30%) 

1-10% 

Local administration reaction (7%)
Renal and urinary tract infection (9%)
Cardiopulmonary failure (9%)
Anemia (9%)
Fungal infection (9%)
Diarrhea (10%)
Transaminases elevation (10%) 

Black Box Warning

Black Box Warning

None

Contraindication / Caution

Contraindication/Caution

Contraindication 

None 

Caution 

Hematological abnormalities 

Liver dysfunction 

Drug-induced kidney injury 

Pregnancy / Lactation

Pregnancy warnings:      

Pregnancy category: N/A  

Lactation: Excreted into human milk is unknown  

Pregnancy Categories:          

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester.  

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.    

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.     

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.     

Category N: There is no data available for the drug under this category.

Pharmacology

Pharmacology:  

Pharmacodynamics:   

Menkes disease is a rare pediatric disorder of copper deficiency inherited in an X-linked recessive pattern and results from mutations in the ATP7A copper transporter gene, leading to markedly reduced intestinal copper uptake. Affected patients exhibit defective dietary copper absorption, limited transport of copper across the blood–brain barrier, and abnormal function of multiple copper-dependent enzymes. To overcome the gastrointestinal absorption defect, copper histidinate is administered subcutaneously. 

Pharmacokinetics:  

Absorption  

Following administration, peak plasma concentrations are reached approximately 45 minutes. 

Distribution  

The drug is not protein bound and has a large volume of distribution of about 1,034 L. 

Metabolism  

Its metabolism has not been well characterized. 

Excretion and Elimination  

Elimination occurs with a terminal half-life of approximately 75 hours and a serum clearance of 10.3 L/hour, with elemental copper primarily excreted via the biliary route. 

Adminstartion

Administration:   

For subcutaneous preparation, aseptic technique should be used throughout the process. The lyophilized powder should be reconstituted using a sterile, disposable 3-mL syringe fitted with a 1-inch needle of 16-22 gauge. 

Patient Information Leaflet

Patient information leaflet  

Generic Name: copper histidinate  

Why do we use copper histidinate?   

Copper histidinate is used primarily as copper replacement therapy for the treatment of Menkes disease in pediatric patients. It is administered to correct systemic copper deficiency, improve copper-dependent enzyme activity, and support neurologic and connective tissue development by bypassing the defective intestinal copper absorption seen in this condition.