Zycubo (copper histidinate)

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Administer copper histidinate subcutaneously.

Reconstitute the commercially available lyophilized powder using a sterile disposable 3 mL syringe and 1 inch needle (between 16-22 gauge). To prepare the drug, remove one vial from the refrigerator and set aside for approximately 30 minutes to allow it to reach room temperature (20-25degrees). Tilt the vial and slowly inject 1 mL of 0.9% sodium chloride injection down the inside wall. Gently swirl the vial continuously until the powder is completely dissolved; do not shake. Once reconstituted, each vial will yield a concentration of 2.9 mg/mL. Visually inspect the reconstituted solution for particulate matter and discoloration. The solution should be blue; discard the drug if particles are present or if the solution is discolored (not blue) or cloudy. Do not mix with other medications.

Administer copper histidinate using a sterile disposable 1 mL syringe and 1/2 inch injection needle (between 23-27 gauge). Slowly withdraw 0.5 mL of the reconstituted solution from the vial and administer the subcutaneous injection into separate sites in the abdominal area (2 inches from the navel), buttocks, and outer lateral aspect of the upper arm or thigh. Rotate injection sites to reduce the risk of lipodystrophy. Do not administer injections into skin that is scarred, tender, bruised, red, or hard. Discard any unused portion after each single use. Do not administer more than one dose from the vial.

If a dose is missed, administer the missed dose as soon as possible. Administer the next scheduled dose at least 6 hours after the missed dose is administered.

Store copper histidinate vials in the refrigerator at 2-8degrees in the original carton. If the reconstituted solution is not used immediately, store the vial in the refrigerator at 2-8degrees for up to 24 hours or at controlled room temperature (20-25degrees) for up to 4 hours. Discard the reconstituted solution if not used within 24 hours of refrigeration or within 4 hours at room temperature.

No dosing information is available for this tab.

No dosing information is available for this tab.

No drug interaction studies have been conducted with copper histidinate. Copper histidinate is a weak inhibitor of cytochrome P-450 (CYP) 1A2, CYP2B6, CYP2C9, CYP2C19, and CYP2D6. The drug is not an inducer of CYP1A2, CYP2B6, or CYP3A. Copper histidinate is not a substrate of breast cancer resistance protein (BCRP), P-glycoprotein (P-gp), multidrug and toxin compound extrusion (MATE) 1, MATE2-K, organic anion transporter (OAT)1, OAT3, organic anion transporting polypeptide (OATP)1B1, OAT1B3, or organic cation transporter (OCT)2. The drug is an inhibitor of bile salt export pump (BSEP) and MATE1. Copper histidinate is a slight inducer of CYP1A2. Copper histidinate is a weak inhibitor of BCRP, MATE2K, OCT1, and OCT2, but not an inhibitor of P-gp, OAT1, OAT3, OATP1B1, or OATP1B3.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*None.

• Wilson's disease

There are no severe contraindications for this drug.

• Biliary tract disorder
• Hepatic cirrhosis

The most common adverse reactions occurring in >=7% of patients treated with copper histidinate 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.

More Frequent

• Acute respiratory failure
• Bacterial infection
• Dyspnea
• Fracture
• Hemorrhage
• Hypovolemia
• Pneumonia
• Seizure disorder
• Tachycardia

Less Frequent

• Abnormal hepatic function tests
• Copper toxicity
• Dehydration
• Respiratory syncytial virus infection
• Upper respiratory infection
• Viral infection

More Frequent

• Fever
• Hypotension
• Vomiting

Less Frequent

• Anemia
• Diarrhea
• Fungal infection
• Injection site sequelae
• Urinary tract infection

No enhanced messaging available.

The safety and effectiveness of copper histidinate for the treatment of Menkes disease have been established in pediatric patients.

In juvenile rats with normal baseline copper levels, subcutaneous administration of copper histidinate twice daily for 13 weeks at 1, 2, and 5 mg/kg from postnatal day (PND) 10 (the equivalent of a human newborn) to PND 100 (the equivalent of a human adult) resulted in histopathological findings in the kidney (tubular necrosis, eosinophilic globules), liver (single cell necrosis, inflammation, fibrosis), and spleen (increased cellularity and pigmented macrophages). In addition, increased liver transaminases (ALT, AST) and bilirubin, and decreased red blood cells, hemoglobin, and hematocrit were observed at the 5-mg/kg dose. Changes in liver (necrosis, inflammation, ALT, AST) and kidney (eosinophilic globules) were also noted with the 1-mg/kg dose.

There are no available data on copper histidinate 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 copper histidinate.

There are no data on the presence of copper histidinate and its metabolites in human or animal milk, the effects on the breastfed infant, or the effects on milk production. Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for copper histidinate and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.

Menkes disease is a disease of pediatric patients. Clinical trials of copper histidinate did not include patients 65 years of age and older.