These Highlights Do Not Include All The Information Needed To Use Zycubo Safely And Effectively. See Full Prescribing Information For Zycubo.

These Highlights Do Not Include All The Information Needed To Use Zycubo Safely And Effectively. See Full Prescribing Information For Zycubo.
SPL v2
SPL
SPL Set ID e3aeefc2-f44d-4337-9c2e-3dba44a89e48
Route
SUBCUTANEOUS
Published
Effective Date 2025-09-10
Document Type 34391-3 HUMAN PRESCRIPTION DRUG LABEL

Drug Facts

Composition & Product

Active Ingredients
Copper Histidinate (2.9 mg)

Identifiers & Packaging

Marketing Status
NDA Active Since 2026-01-12
Description

ZYCUBO is indicated for the treatment of Menkes disease in pediatric patients.

Indications and Usage

ZYCUBO is indicated for the treatment of Menkes disease in pediatric patients.

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.

Warnings and Precautions

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 )

Contraindications

None.

Adverse Reactions

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 )]

Medication Information

Warnings and Precautions

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 )

Indications and Usage

ZYCUBO is indicated for the treatment of Menkes disease in pediatric patients.

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.

Contraindications

None.

Adverse Reactions

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 )]

Description

ZYCUBO is indicated for the treatment of Menkes disease in pediatric patients.

Section 42229-5

Limitations of Use

ZYCUBO is not indicated for the treatment of Occipital Horn Syndrome.

Section 51945-4

Principal Display Panel - 2.9 mg Carton Label

NDC 42358-329-01

Zycubo ®

(copper histidinate) for injection

2.9 mg/vial

For subcutaneous injection

One Single-Dose vial

Discard unused portion after each single use.

Do not administer more than one dose from the vial.

Rx only

Section 59845-8

INSTRUCTIONS FOR USE

ZYCUBO ® [zye kyoo boe]

(copper histidinate)

for injection, for subcutaneous use

This Instructions for Use contains information on how to prepare and inject ZYCUBO. Read this Instructions for Use before you prepare and inject a dose of ZYCUBO for the first time and each time you get a ZYCUBO refill. There may be new information. This information does not take the place of talking to your healthcare provider about your child's medical condition or their treatment.

ZYCUBO is for subcutaneous injection only (inject directly under the skin). Always follow the specific instructions given by your healthcare provider.

  • If you have questions about preparing or injecting ZYCUBO, call SentynlCares | ZYCUBO Patient Support Services at 1-888-251-2800.

Important information you need to know before preparing and injecting ZYCUBO:

  • Your healthcare provider should show you the right way to prepare and inject your child's prescribed dose of ZYCUBO before you do this for the first time.
  • Your healthcare provider will prescribe the amount of ZYCUBO needed for each dose for your child. Confirm the amount of ZYCUBO needed at each visit with your child's healthcare provider.
  • ZYCUBO comes as a powder or cake in a vial. Each vial of ZYCUBO must be mixed with 0.9% sodium chloride to mix (dissolve) the powder or cake before use.
  • Do not mix ZYCUBO with anything other than 0.9% sodium chloride.
  • Vials of ZYCUBO are for 1 time use only. Throw the vial away after use, even if there is medicine left in the vial. Do not save for later use. Throw away used vials in your household trash.
  • If your child misses a dose of ZYCUBO, inject the dose as soon as possible. Inject the next scheduled dose at least 6 hours after you finish injecting the missed dose.
  • Do not expose ZYCUBO to any heat source, such as a microwave or hot water.
  • Do not share needles and syringes. See Step 13: “Throw away (dispose of) used needles and syringes.”

Storing ZYCUBO and other supplies:

Vials of ZYCUBO before mixing:

  • Store ZYCUBO in the refrigerator between 36°F to 46°F (2°C to 8°C).
  • Keep ZYCUBO vials in the original carton until you are ready to use it.

Vials of ZYCUBO after mixing:

  • If you do not use the ZYCUBO solution right away after mixing, store the mixed ZYCUBO vial:
    • in the refrigerator between 36°F to 46°F (2°C to 8°C) and use within 24 hours. Throw away (discard) the mixed ZYCUBO vial if not used within 24 hours.
    • at room temperature between 68°F to 77°F (20°C to 25°C) and use within 4 hours. Throw away (discard) the mixed ZYCUBO vial if not used within 4 hours.
  • Write the date and time you mixed ZYCUBO with 0.9% sodium chloride on the carton.
  • Do not shake ZYCUBO after it has been mixed.

Other supplies:

  • Store other supplies according to the manufacturer instructions (see Step 2: “Gather and check other supplies” for a list of supplies needed).

Keep ZYCUBO and all medicines out of the reach of children.

Preparing and injecting ZYCUBO

Step 1: Gather and check ZYCUBO vial for damage and expiration date

  • a)
    Remove the ZYCUBO carton from the refrigerator. Remove the ZYCUBO vial from the carton.

  • b)
    Check the ZYCUBO vial for damage and the expiration date.
    • Do not use the vial and contact the healthcare provider if the vial is damaged, expired or the flip-off cap on the vial is broken or missing.

  • c)
    Allow the ZYCUBO vial to sit at room temperature for about 30 minutes.



Step 2: Gather and check other supplies

  • 1 vial of 0.9% sodium chloride
    • Check the expiration date on the vial.
    • Do not use the vial if the expiration date has passed.
    • Do not use the vial if the flip-off cap on the vial is broken or missing.
  • One (1) sterile, 3 mL syringe with 1 inch needle (16 to 22 gauge) for preparing ZYCUBO
  • One (1) sterile, 1 mL syringe with 1/2 inch needle (23 to 27 gauge) for injecting ZYCUBO.
    • Check the expiration dates of both sterile syringes with sterile needles.
    • Do not use if the expiration date has passed.
    • Do not use if the packaging is damaged.
  • Alcohol wipes
  • Gauze pads or Cotton ball
  • 1 sharps disposal container (see Step 13: “Throw away (dispose of) used needles and syringes”)
  • Gloves (if instructed by your healthcare provider)






Step 3: Wash your hands

If you have been told to wear gloves to prepare and inject ZYCUBO, put them on now.

Step 4: Prepare the vials

  • a)
    Remove the flip-off cap from the sodium chloride vial and ZYCUBO vial.
  • b)
    Throw away (discard) the vial caps in the trash.









  • c)
    Clean the rubber stopper of each vial with an alcohol wipe and allow to air dry.
    • Do not blow on the stopper to dry it faster.

Note: If you touch the rubber stopper, clean it again with a new alcohol wipe.







Step 5: Prepare the syringe used for withdrawing sodium chloride

  • a)
    Remove a 3 mL syringe with needle from the plastic packaging.







  • b)
    Pull the needle cover straight off and throw it away in the trash.
    • Do not touch the needle or let the needle touch any surface.






Step 6: Withdraw 1 mL of sodium chloride into syringe

  • a)
    Hold the syringe barrel with one hand. With your other hand, draw air into the syringe by pulling back on the plunger rod until the top of the plunger lines up with the 1 mL mark on the syringe.





  • b)
    Hold the sodium chloride vial on a clean, flat work surface and insert the needle into the center of the sodium chloride vial stopper.

    Note: If you remove the needle at any point, clean the rubber stopper with a new alcohol wipe before reinserting the needle.







  • c)
    Turn the vial upside down.













  • d)
    Slowly push up on the plunger rod to push all the air from the syringe into the vial.











  • e)
    Make sure the tip of the needle is in the sodium chloride solution. Slowly pull down on the plunger rod of the syringe until the top of the plunger reaches the 1 mL mark on the syringe.



  • f)
    Gently tap the syringe barrel to remove as many air bubbles as possible. It is acceptable if some air bubbles remain in the syringe after you tap the syringe.









    • Push the plunger rod up to remove as many large air bubbles as you can.













  • g)
    Check to make sure that 1 mL of sodium chloride has been withdrawn into the syringe. If the amount is less than 1 mL, repeat Steps 6e and 6f until you have 1 mL of sodium chloride.











  • h)
    Remove the needle and syringe from the sodium chloride vial. Be careful not to move the plunger.



































Step 7: Mix ZYCUBO until dissolved

  • a)
    Hold the ZYCUBO vial on a clean, flat work surface.
  • b)
    Insert the syringe with 1 mL of sodium chloride into the center of the ZYCUBO vial stopper.

  • c)
    Tilt the vial so that the tip of the needle is pointing toward the inside wall of the vial.









    • With your thumb, slowly push the plunger rod down all the way. The liquid should go down the inside wall of the vial.











  • d)
    Carefully remove the needle from the vial. Throw away (dispose of) the used needle and syringe in your sharps disposal container right away.
    • Do not try to recap the needle.See Step 13: “Throw away (dispose of) used needles and syringes.”









  • e)
    Gently swirl the vial continuously until the powder is completely dissolved. Do not shake the vial.



















Step 8: Check solution

Check that the ZYCUBO solution is a blue color.

  • Do not use if the mixed solution is not a blue color, is cloudy, or contains particles. Ask your pharmacist for a replacement vial.
Step 9: Determine the injection time

After mixing, inject the ZYCUBO solution right away or inject the ZYCUBO solution:

  • within 24 hours if stored in the refrigerator. Throw away (discard) the mixed ZYCUBO vial if not used within 24 hours.
    • If you store the mixed ZYCUBO vial in the refrigerator, remove the vial from the refrigerator and allow it to sit at room temperature for about 30 minutes.
  • within 4 hours if stored at room temperature. Throw away (discard) the mixed ZYCUBO vial if not used within 4 hours.

  • If you do not inject the ZYCUBO solution right away:
    • Wash your hands well with soap and water.











    • Wipe the rubber stopper of the mixed ZYCUBO vial with a new alcohol wipe and allow to air dry.
      • Do not blow on the rubber stopper to dry faster.















Step 10: Prepare a syringe with the prescribed dose of ZYCUBO

  • a)
    Remove a 1 mL syringe with needle from the plastic packaging.











  • b)
    Pull the needle cover straight off and throw it away in the trash.
    • Do not touch the needle or let the needle touch any surface.







  • c)
    Hold the mixed ZYCUBO vial on a clean, flat work surface and insert the needle into the center of the ZYCUBO vial stopper.

    Note: If you remove the needle at any point, clean the rubber stopper with a new alcohol wipe before reinserting the needle.

  • d)
    Turn the vial upside down.













  • e)
    Move the needle so that the tip is in the ZYCUBO solution.









  • f)
    Slowly pull back on the plunger rod to fill the syringe with 0.5 mL of ZYCUBO solution. The top of the plunger should line up with the 0.5 mL mark on the syringe.















  • g)
    Gently tap the syringe barrel to remove as many air bubbles as possible. It is acceptable if some air bubbles remain in the syringe after you tap the syringe.
    • Push the plunger rod up to remove as many large air bubbles as you can.



  • h)
    Check to make sure that 0.5 mL of ZYCUBO solution has been withdrawn into the syringe. If the amount is less than 0.5 mL, repeat Steps 10f and 10g until you have 0.5 mL of ZYCUBO solution.









  • i)
    Remove the needle and syringe from the ZYCUBO vial.













  • j)
    Throw away the used ZYCUBO vial in your household trash after use, even if there is medicine left in the vial.






























Step 11: Prepare the injection site

ZYCUBO is injected under the skin (subcutaneously).

  • a)
    Choose one (1) of the following injection sites:
    • stomach area (abdominal area), 2 inches from belly button,
    • buttocks, or
    • outer area of the upper arm or thigh.

  • Change (rotate) the injection site with each injection to reduce your risk of skin problems.
  • Do not give injections into areas where the skin is scarred, tender, bruised, red or hard.
  • b)
    Clean the injection site with a new alcohol wipe.

  • c)
    Let the injection site air dry.
    • Do not touch, wipe, fan, or blow on it.












Step 12: Inject ZYCUBO

  • a)
    Pinch the skin around the clean injection site with one hand. With the other hand, hold the syringe and fully insert the needle into the skin at a 45-degree angle. Do not press the plunger rod until you are ready to inject.
  • b)
    Push the plunger rod all the way down to inject all of the ZYCUBO solution.
  • c)
    Remove the needle from the injection site at the same 45-degree angle it was inserted.
    • If you see any blood, lightly press a cotton ball or gauze at the injection site. Apply an adhesive bandage if necessary. Do not rub the injection site.
    • If the injection site becomes red or sore, call your healthcare provider right away.


Step 13: Throw away (dispose of) used needles and syringes

  • Put your used needles and syringes in an FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) needles and syringes in your household trash.
  • If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:
    • made of heavy-duty plastic,
    • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
    • upright and stable during use,
    • leak-resistant, and
    • properly labeled to warn of hazardous waste inside the container.
  • When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: https://www.fda.gov/safesharpsdisposal.
  • Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.
  • Keep the sharps disposal container out of the reach of children.


If you have questions about preparing or injecting ZYCUBO, call SentynlCares | ZYCUBO Patient Support Services at 1-888-251-2800.

Manufactured by: Zydus Lifesciences Ltd., Vadodara – 391510, India

Manufactured for: Sentynl Therapeutics, Inc., Solana Beach, CA 92075

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Issued: 1/2026
11 Description

ZYCUBO (copper histidinate) for injection is a copper replacement product. The chemical name is copper, (L-histidinato-ϰN,ϰN3,ϰO)(L-histidinato-ϰN,ϰO)-, (SP-5-14-C)-. The molecular formula is C12H16CuN6O4, and the molecular weight is 371.84 g/mol. Copper histidinate is soluble in water.

The chemical structure is:

ZYCUBO is a sterile, preservative-free, blue lyophilized powder or cake for subcutaneous injection after reconstitution with 1 mL sterile 0.9% Sodium Chloride Injection, USP. Each single-dose vial contains 2.9 mg of copper histidinate (equivalent to 0.5 mg elemental copper). The resultant solution has a concentration of 2.9 mg/mL and a pH of 7.4.

2.7 Missed Dose

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

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.

8.5 Geriatric Use

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

14 Clinical Studies

The efficacy of ZYCUBO was evaluated in pediatric patients with Menkes disease (age at treatment initiation ranges 0.1 to 31.4 months) receiving 3 years of copper histidinate treatment in two open-label, single-arm clinical trials (Trial 1, NCT00001262 and Trial 2, NCT00811785). Data from ZYCUBO-treated patients in these two trials were compared to data from an untreated contemporaneous external control cohort as collected under a protocol amendment of Trial 2. In both trials, pediatric patients:

  • Less than 1 year of age received 1.45 mg of ZYCUBO administered subcutaneously twice daily until 1 year of age.
  • Equal to or greater than 1 year of age received 1.45 mg of ZYCUBO subcutaneously once daily for up to 3 years.

Overall survival was evaluated in a subset of the pooled population from Trial 1 and Trial 2, referred to as the pooled efficacy population. This efficacy population included only patients with Menkes disease who carried a severe pathogenic variant of the ATP7A gene (duplication/deletion, nonsense, or a canonical splice junction variant) and were born after 1999. There were 83 pediatric patients (66 ZYCUBO; 17 external control) in this pooled efficacy population: 21 patients (21 ZYCUBO) from Trial 1 and 62 patients (45 ZYCUBO; 17 external control) from Trial 2.

Patients in the pooled efficacy population were assigned to 1 of 4 cohorts as described in Table 2.

Table 2. Patient Cohorts in the Pooled Efficacy Population

All values are in median (range)

1 Within 4 weeks of birth or within 4 weeks of birth corrected for prematurity (i.e., < 40 weeks' gestation)

2 After 4 weeks of birth or after 4 weeks of birth corrected for prematurity (i.e., < 40 weeks' gestation)

Treated Cohorts Untreated Cohorts
ZYCUBO- Early Treatment

(ZYCUBO-ET)

n=31 		ZYCUBO- Late Treatment

(ZYCUBO-LT)

n=35 		External Control-Early Treatment

(EC-ET)

n=17 		External Control-Late Treatment

(EC-LT)

n=16
Eligibility Started ZYCUBO treatment within 4 weeks of birth [1] Started ZYCUBO treatment after 4 weeks of birth [2]
  • No prior ZYCUBO or copper treatment
  • Asymptomatic for significant neurological signs and symptoms approximately 4 weeks after birth
  • Survived at least 4 weeks after diagnosis
  • Subset of the EC-ET cohort
  • Diagnosed with Menkes disease after 4 weeks of birth
  • Survived at least 2 weeks after diagnosis
Age at diagnosis (months) 0.1 (-4.5 – 1.9) 4.8 (0.4 – 29.4) 4.7 (2.1 – 22.2) 5.6 (2.1 – 22.2)
Age at treatment initiation (months) 0.4 (0.1 – 1.9) 7.1 (1.3 – 31.4) NA NA
Treatment duration (months) 34.1 (1.1 – 36) 20 (1.3 – 36) NA NA

In the 4 cohorts, 81 patients were male (98%) except for 2 female (2%) patients in ZYCUBO-LT. The pooled efficacy population included patients with the following race and ethnicity: 52 White (63%), 11 Hispanic (13%), 8 Black or African American (10%), 6 Unknown (7%), 4 Other (5%), and 2 Asian or Pacific Islander (2%). The majority of patients in all 4 cohorts were born prematurely: ZYCUBO-ET = 77%, ZYCUBO-LT = 66%, EC-ET = 82%, and EC-LT = 81%.

4 Contraindications

None.

6 Adverse Reactions

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)]
12.2 Pharmacodynamics

Patients with Menkes disease have low serum concentrations of copper and ceruloplasmin. Treatment with ZYCUBO increases serum copper and ceruloplasmin concentrations in patients with Menkes disease.

The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of ZYCUBO have not been fully characterized.

12.3 Pharmacokinetics

The geometric mean (CV%) maximum serum concentration (Cmax) of copper histidinate was 67 (36%) ng/mL, the geometric mean (CV%) area under the concentration-time curve from time 0 to 24 hours (AUC0-24hr) was 186 (21%) ng•hr/mL, and the geometric mean (CV%) area under the concentration-time curve from time 0 to infinity (AUC0-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.

At the recommended dosage, the mean (SD) serum copper concentration increased from a baseline concentration of 30 (25) mcg/dL to 114 (38) mcg/dL at 12 months, and gradually decreased over the 36-month treatment period, with a mean (SD) serum copper concentration of 63 (31) mcg/dL at 36 months. The mean (SD) serum ceruloplasmin concentration was 12 (12) mg/dL at baseline, 33 (11) mg/dL at 12 months, and 20 (8) mg/dL at 36 months [see Clinical Studies (14)].

1 Indications and Usage

ZYCUBO is indicated for the treatment of Menkes disease in pediatric patients.

12.1 Mechanism of Action

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 a bioavailable copper replacement therapy that is administered as a subcutaneous injection to bypass the impaired gastrointestinal absorption observed in patients with Menkes disease.

5 Warnings and Precautions

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)

2 Dosage and Administration
  • 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)
3 Dosage Forms and Strengths

For Injection: 2.9 mg of copper histidinate (equivalent to 0.5 mg elemental copper) as a blue lyophilized powder or cake in a single-dose vial for reconstitution.

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)].

2.6 Administration Instructions

A caregiver may administer ZYCUBO to patients after proper training in subcutaneous injection technique if a healthcare provider determines that it is appropriate (see Instructions for Use ). Administer ZYCUBO using a sterile disposable 1 mL syringe and 1/2 inch injection needle (between 23 to 27 gauge).

Slowly withdraw 0.5 mL of reconstituted ZYCUBO solution from the vial and inject subcutaneously.

Administer ZYCUBO by subcutaneous injection at separate sites in the abdominal area (2 inches from the navel), buttocks, and the outer lateral aspect of the upper arm or thigh. Rotate injection sites with each injection to reduce the risk of lipodystrophy. Do not give injections into areas where the skin is scarred, tender, bruised, red, or hard.

Discard unused portion after each single use. Do not administer more than one dose from the vial.

17 Patient Counseling Information

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Instructions for Use).

2.5 Storage of Reconstituted Solution

If the reconstituted ZYCUBO vial is not used immediately, store the vial refrigerated at 2°C to 8°C (36° to 46°F) for up to 24 hours or at controlled room temperature at 20°C to 25°C (68°F to 77°F) for up to 4 hours.

Discard the reconstituted ZYCUBO vial if not used within 24 hours of refrigeration or within 4 hours at room temperature.

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.
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.

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)].

2.3 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. 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 evaluation when resuming a dosage as clinically indicated [see Warnings and Precautions (5.1)].

Structured Label Content

Section 42229-5 (42229-5)

Limitations of Use

ZYCUBO is not indicated for the treatment of Occipital Horn Syndrome.

Section 51945-4 (51945-4)

Principal Display Panel - 2.9 mg Carton Label

NDC 42358-329-01

Zycubo ®

(copper histidinate) for injection

2.9 mg/vial

For subcutaneous injection

One Single-Dose vial

Discard unused portion after each single use.

Do not administer more than one dose from the vial.

Rx only

Section 59845-8 (59845-8)

INSTRUCTIONS FOR USE

ZYCUBO ® [zye kyoo boe]

(copper histidinate)

for injection, for subcutaneous use

This Instructions for Use contains information on how to prepare and inject ZYCUBO. Read this Instructions for Use before you prepare and inject a dose of ZYCUBO for the first time and each time you get a ZYCUBO refill. There may be new information. This information does not take the place of talking to your healthcare provider about your child's medical condition or their treatment.

ZYCUBO is for subcutaneous injection only (inject directly under the skin). Always follow the specific instructions given by your healthcare provider.

  • If you have questions about preparing or injecting ZYCUBO, call SentynlCares | ZYCUBO Patient Support Services at 1-888-251-2800.

Important information you need to know before preparing and injecting ZYCUBO:

  • Your healthcare provider should show you the right way to prepare and inject your child's prescribed dose of ZYCUBO before you do this for the first time.
  • Your healthcare provider will prescribe the amount of ZYCUBO needed for each dose for your child. Confirm the amount of ZYCUBO needed at each visit with your child's healthcare provider.
  • ZYCUBO comes as a powder or cake in a vial. Each vial of ZYCUBO must be mixed with 0.9% sodium chloride to mix (dissolve) the powder or cake before use.
  • Do not mix ZYCUBO with anything other than 0.9% sodium chloride.
  • Vials of ZYCUBO are for 1 time use only. Throw the vial away after use, even if there is medicine left in the vial. Do not save for later use. Throw away used vials in your household trash.
  • If your child misses a dose of ZYCUBO, inject the dose as soon as possible. Inject the next scheduled dose at least 6 hours after you finish injecting the missed dose.
  • Do not expose ZYCUBO to any heat source, such as a microwave or hot water.
  • Do not share needles and syringes. See Step 13: “Throw away (dispose of) used needles and syringes.”

Storing ZYCUBO and other supplies:

Vials of ZYCUBO before mixing:

  • Store ZYCUBO in the refrigerator between 36°F to 46°F (2°C to 8°C).
  • Keep ZYCUBO vials in the original carton until you are ready to use it.

Vials of ZYCUBO after mixing:

  • If you do not use the ZYCUBO solution right away after mixing, store the mixed ZYCUBO vial:
    • in the refrigerator between 36°F to 46°F (2°C to 8°C) and use within 24 hours. Throw away (discard) the mixed ZYCUBO vial if not used within 24 hours.
    • at room temperature between 68°F to 77°F (20°C to 25°C) and use within 4 hours. Throw away (discard) the mixed ZYCUBO vial if not used within 4 hours.
  • Write the date and time you mixed ZYCUBO with 0.9% sodium chloride on the carton.
  • Do not shake ZYCUBO after it has been mixed.

Other supplies:

  • Store other supplies according to the manufacturer instructions (see Step 2: “Gather and check other supplies” for a list of supplies needed).

Keep ZYCUBO and all medicines out of the reach of children.

Preparing and injecting ZYCUBO

Step 1: Gather and check ZYCUBO vial for damage and expiration date

  • a)
    Remove the ZYCUBO carton from the refrigerator. Remove the ZYCUBO vial from the carton.

  • b)
    Check the ZYCUBO vial for damage and the expiration date.
    • Do not use the vial and contact the healthcare provider if the vial is damaged, expired or the flip-off cap on the vial is broken or missing.

  • c)
    Allow the ZYCUBO vial to sit at room temperature for about 30 minutes.



Step 2: Gather and check other supplies

  • 1 vial of 0.9% sodium chloride
    • Check the expiration date on the vial.
    • Do not use the vial if the expiration date has passed.
    • Do not use the vial if the flip-off cap on the vial is broken or missing.
  • One (1) sterile, 3 mL syringe with 1 inch needle (16 to 22 gauge) for preparing ZYCUBO
  • One (1) sterile, 1 mL syringe with 1/2 inch needle (23 to 27 gauge) for injecting ZYCUBO.
    • Check the expiration dates of both sterile syringes with sterile needles.
    • Do not use if the expiration date has passed.
    • Do not use if the packaging is damaged.
  • Alcohol wipes
  • Gauze pads or Cotton ball
  • 1 sharps disposal container (see Step 13: “Throw away (dispose of) used needles and syringes”)
  • Gloves (if instructed by your healthcare provider)






Step 3: Wash your hands

If you have been told to wear gloves to prepare and inject ZYCUBO, put them on now.

Step 4: Prepare the vials

  • a)
    Remove the flip-off cap from the sodium chloride vial and ZYCUBO vial.
  • b)
    Throw away (discard) the vial caps in the trash.









  • c)
    Clean the rubber stopper of each vial with an alcohol wipe and allow to air dry.
    • Do not blow on the stopper to dry it faster.

Note: If you touch the rubber stopper, clean it again with a new alcohol wipe.







Step 5: Prepare the syringe used for withdrawing sodium chloride

  • a)
    Remove a 3 mL syringe with needle from the plastic packaging.







  • b)
    Pull the needle cover straight off and throw it away in the trash.
    • Do not touch the needle or let the needle touch any surface.






Step 6: Withdraw 1 mL of sodium chloride into syringe

  • a)
    Hold the syringe barrel with one hand. With your other hand, draw air into the syringe by pulling back on the plunger rod until the top of the plunger lines up with the 1 mL mark on the syringe.





  • b)
    Hold the sodium chloride vial on a clean, flat work surface and insert the needle into the center of the sodium chloride vial stopper.

    Note: If you remove the needle at any point, clean the rubber stopper with a new alcohol wipe before reinserting the needle.







  • c)
    Turn the vial upside down.













  • d)
    Slowly push up on the plunger rod to push all the air from the syringe into the vial.











  • e)
    Make sure the tip of the needle is in the sodium chloride solution. Slowly pull down on the plunger rod of the syringe until the top of the plunger reaches the 1 mL mark on the syringe.



  • f)
    Gently tap the syringe barrel to remove as many air bubbles as possible. It is acceptable if some air bubbles remain in the syringe after you tap the syringe.









    • Push the plunger rod up to remove as many large air bubbles as you can.













  • g)
    Check to make sure that 1 mL of sodium chloride has been withdrawn into the syringe. If the amount is less than 1 mL, repeat Steps 6e and 6f until you have 1 mL of sodium chloride.











  • h)
    Remove the needle and syringe from the sodium chloride vial. Be careful not to move the plunger.



































Step 7: Mix ZYCUBO until dissolved

  • a)
    Hold the ZYCUBO vial on a clean, flat work surface.
  • b)
    Insert the syringe with 1 mL of sodium chloride into the center of the ZYCUBO vial stopper.

  • c)
    Tilt the vial so that the tip of the needle is pointing toward the inside wall of the vial.









    • With your thumb, slowly push the plunger rod down all the way. The liquid should go down the inside wall of the vial.











  • d)
    Carefully remove the needle from the vial. Throw away (dispose of) the used needle and syringe in your sharps disposal container right away.
    • Do not try to recap the needle.See Step 13: “Throw away (dispose of) used needles and syringes.”









  • e)
    Gently swirl the vial continuously until the powder is completely dissolved. Do not shake the vial.



















Step 8: Check solution

Check that the ZYCUBO solution is a blue color.

  • Do not use if the mixed solution is not a blue color, is cloudy, or contains particles. Ask your pharmacist for a replacement vial.
Step 9: Determine the injection time

After mixing, inject the ZYCUBO solution right away or inject the ZYCUBO solution:

  • within 24 hours if stored in the refrigerator. Throw away (discard) the mixed ZYCUBO vial if not used within 24 hours.
    • If you store the mixed ZYCUBO vial in the refrigerator, remove the vial from the refrigerator and allow it to sit at room temperature for about 30 minutes.
  • within 4 hours if stored at room temperature. Throw away (discard) the mixed ZYCUBO vial if not used within 4 hours.

  • If you do not inject the ZYCUBO solution right away:
    • Wash your hands well with soap and water.











    • Wipe the rubber stopper of the mixed ZYCUBO vial with a new alcohol wipe and allow to air dry.
      • Do not blow on the rubber stopper to dry faster.















Step 10: Prepare a syringe with the prescribed dose of ZYCUBO

  • a)
    Remove a 1 mL syringe with needle from the plastic packaging.











  • b)
    Pull the needle cover straight off and throw it away in the trash.
    • Do not touch the needle or let the needle touch any surface.







  • c)
    Hold the mixed ZYCUBO vial on a clean, flat work surface and insert the needle into the center of the ZYCUBO vial stopper.

    Note: If you remove the needle at any point, clean the rubber stopper with a new alcohol wipe before reinserting the needle.

  • d)
    Turn the vial upside down.













  • e)
    Move the needle so that the tip is in the ZYCUBO solution.









  • f)
    Slowly pull back on the plunger rod to fill the syringe with 0.5 mL of ZYCUBO solution. The top of the plunger should line up with the 0.5 mL mark on the syringe.















  • g)
    Gently tap the syringe barrel to remove as many air bubbles as possible. It is acceptable if some air bubbles remain in the syringe after you tap the syringe.
    • Push the plunger rod up to remove as many large air bubbles as you can.



  • h)
    Check to make sure that 0.5 mL of ZYCUBO solution has been withdrawn into the syringe. If the amount is less than 0.5 mL, repeat Steps 10f and 10g until you have 0.5 mL of ZYCUBO solution.









  • i)
    Remove the needle and syringe from the ZYCUBO vial.













  • j)
    Throw away the used ZYCUBO vial in your household trash after use, even if there is medicine left in the vial.






























Step 11: Prepare the injection site

ZYCUBO is injected under the skin (subcutaneously).

  • a)
    Choose one (1) of the following injection sites:
    • stomach area (abdominal area), 2 inches from belly button,
    • buttocks, or
    • outer area of the upper arm or thigh.

  • Change (rotate) the injection site with each injection to reduce your risk of skin problems.
  • Do not give injections into areas where the skin is scarred, tender, bruised, red or hard.
  • b)
    Clean the injection site with a new alcohol wipe.

  • c)
    Let the injection site air dry.
    • Do not touch, wipe, fan, or blow on it.












Step 12: Inject ZYCUBO

  • a)
    Pinch the skin around the clean injection site with one hand. With the other hand, hold the syringe and fully insert the needle into the skin at a 45-degree angle. Do not press the plunger rod until you are ready to inject.
  • b)
    Push the plunger rod all the way down to inject all of the ZYCUBO solution.
  • c)
    Remove the needle from the injection site at the same 45-degree angle it was inserted.
    • If you see any blood, lightly press a cotton ball or gauze at the injection site. Apply an adhesive bandage if necessary. Do not rub the injection site.
    • If the injection site becomes red or sore, call your healthcare provider right away.


Step 13: Throw away (dispose of) used needles and syringes

  • Put your used needles and syringes in an FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) needles and syringes in your household trash.
  • If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:
    • made of heavy-duty plastic,
    • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
    • upright and stable during use,
    • leak-resistant, and
    • properly labeled to warn of hazardous waste inside the container.
  • When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: https://www.fda.gov/safesharpsdisposal.
  • Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.
  • Keep the sharps disposal container out of the reach of children.


If you have questions about preparing or injecting ZYCUBO, call SentynlCares | ZYCUBO Patient Support Services at 1-888-251-2800.

Manufactured by: Zydus Lifesciences Ltd., Vadodara – 391510, India

Manufactured for: Sentynl Therapeutics, Inc., Solana Beach, CA 92075

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Issued: 1/2026
11 Description (11 DESCRIPTION)

ZYCUBO (copper histidinate) for injection is a copper replacement product. The chemical name is copper, (L-histidinato-ϰN,ϰN3,ϰO)(L-histidinato-ϰN,ϰO)-, (SP-5-14-C)-. The molecular formula is C12H16CuN6O4, and the molecular weight is 371.84 g/mol. Copper histidinate is soluble in water.

The chemical structure is:

ZYCUBO is a sterile, preservative-free, blue lyophilized powder or cake for subcutaneous injection after reconstitution with 1 mL sterile 0.9% Sodium Chloride Injection, USP. Each single-dose vial contains 2.9 mg of copper histidinate (equivalent to 0.5 mg elemental copper). The resultant solution has a concentration of 2.9 mg/mL and a pH of 7.4.

2.7 Missed Dose

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

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.

8.5 Geriatric Use

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

14 Clinical Studies (14 CLINICAL STUDIES)

The efficacy of ZYCUBO was evaluated in pediatric patients with Menkes disease (age at treatment initiation ranges 0.1 to 31.4 months) receiving 3 years of copper histidinate treatment in two open-label, single-arm clinical trials (Trial 1, NCT00001262 and Trial 2, NCT00811785). Data from ZYCUBO-treated patients in these two trials were compared to data from an untreated contemporaneous external control cohort as collected under a protocol amendment of Trial 2. In both trials, pediatric patients:

  • Less than 1 year of age received 1.45 mg of ZYCUBO administered subcutaneously twice daily until 1 year of age.
  • Equal to or greater than 1 year of age received 1.45 mg of ZYCUBO subcutaneously once daily for up to 3 years.

Overall survival was evaluated in a subset of the pooled population from Trial 1 and Trial 2, referred to as the pooled efficacy population. This efficacy population included only patients with Menkes disease who carried a severe pathogenic variant of the ATP7A gene (duplication/deletion, nonsense, or a canonical splice junction variant) and were born after 1999. There were 83 pediatric patients (66 ZYCUBO; 17 external control) in this pooled efficacy population: 21 patients (21 ZYCUBO) from Trial 1 and 62 patients (45 ZYCUBO; 17 external control) from Trial 2.

Patients in the pooled efficacy population were assigned to 1 of 4 cohorts as described in Table 2.

Table 2. Patient Cohorts in the Pooled Efficacy Population

All values are in median (range)

1 Within 4 weeks of birth or within 4 weeks of birth corrected for prematurity (i.e., < 40 weeks' gestation)

2 After 4 weeks of birth or after 4 weeks of birth corrected for prematurity (i.e., < 40 weeks' gestation)

Treated Cohorts Untreated Cohorts
ZYCUBO- Early Treatment

(ZYCUBO-ET)

n=31 		ZYCUBO- Late Treatment

(ZYCUBO-LT)

n=35 		External Control-Early Treatment

(EC-ET)

n=17 		External Control-Late Treatment

(EC-LT)

n=16
Eligibility Started ZYCUBO treatment within 4 weeks of birth [1] Started ZYCUBO treatment after 4 weeks of birth [2]
  • No prior ZYCUBO or copper treatment
  • Asymptomatic for significant neurological signs and symptoms approximately 4 weeks after birth
  • Survived at least 4 weeks after diagnosis
  • Subset of the EC-ET cohort
  • Diagnosed with Menkes disease after 4 weeks of birth
  • Survived at least 2 weeks after diagnosis
Age at diagnosis (months) 0.1 (-4.5 – 1.9) 4.8 (0.4 – 29.4) 4.7 (2.1 – 22.2) 5.6 (2.1 – 22.2)
Age at treatment initiation (months) 0.4 (0.1 – 1.9) 7.1 (1.3 – 31.4) NA NA
Treatment duration (months) 34.1 (1.1 – 36) 20 (1.3 – 36) NA NA

In the 4 cohorts, 81 patients were male (98%) except for 2 female (2%) patients in ZYCUBO-LT. The pooled efficacy population included patients with the following race and ethnicity: 52 White (63%), 11 Hispanic (13%), 8 Black or African American (10%), 6 Unknown (7%), 4 Other (5%), and 2 Asian or Pacific Islander (2%). The majority of patients in all 4 cohorts were born prematurely: ZYCUBO-ET = 77%, ZYCUBO-LT = 66%, EC-ET = 82%, and EC-LT = 81%.

4 Contraindications (4 CONTRAINDICATIONS)

None.

6 Adverse Reactions (6 ADVERSE REACTIONS)

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)]
12.2 Pharmacodynamics

Patients with Menkes disease have low serum concentrations of copper and ceruloplasmin. Treatment with ZYCUBO increases serum copper and ceruloplasmin concentrations in patients with Menkes disease.

The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of ZYCUBO have not been fully characterized.

12.3 Pharmacokinetics

The geometric mean (CV%) maximum serum concentration (Cmax) of copper histidinate was 67 (36%) ng/mL, the geometric mean (CV%) area under the concentration-time curve from time 0 to 24 hours (AUC0-24hr) was 186 (21%) ng•hr/mL, and the geometric mean (CV%) area under the concentration-time curve from time 0 to infinity (AUC0-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.

At the recommended dosage, the mean (SD) serum copper concentration increased from a baseline concentration of 30 (25) mcg/dL to 114 (38) mcg/dL at 12 months, and gradually decreased over the 36-month treatment period, with a mean (SD) serum copper concentration of 63 (31) mcg/dL at 36 months. The mean (SD) serum ceruloplasmin concentration was 12 (12) mg/dL at baseline, 33 (11) mg/dL at 12 months, and 20 (8) mg/dL at 36 months [see Clinical Studies (14)].

1 Indications and Usage (1 INDICATIONS AND USAGE)

ZYCUBO is indicated for the treatment of Menkes disease in pediatric patients.

12.1 Mechanism of Action

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 a bioavailable copper replacement therapy that is administered as a subcutaneous injection to bypass the impaired gastrointestinal absorption observed in patients with Menkes disease.

5 Warnings and Precautions (5 WARNINGS AND PRECAUTIONS)

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)

2 Dosage and Administration (2 DOSAGE AND ADMINISTRATION)
  • 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)
3 Dosage Forms and Strengths (3 DOSAGE FORMS AND STRENGTHS)

For Injection: 2.9 mg of copper histidinate (equivalent to 0.5 mg elemental copper) as a blue lyophilized powder or cake in a single-dose vial for reconstitution.

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)].

2.6 Administration Instructions

A caregiver may administer ZYCUBO to patients after proper training in subcutaneous injection technique if a healthcare provider determines that it is appropriate (see Instructions for Use ). Administer ZYCUBO using a sterile disposable 1 mL syringe and 1/2 inch injection needle (between 23 to 27 gauge).

Slowly withdraw 0.5 mL of reconstituted ZYCUBO solution from the vial and inject subcutaneously.

Administer ZYCUBO by subcutaneous injection at separate sites in the abdominal area (2 inches from the navel), buttocks, and the outer lateral aspect of the upper arm or thigh. Rotate injection sites with each injection to reduce the risk of lipodystrophy. Do not give injections into areas where the skin is scarred, tender, bruised, red, or hard.

Discard unused portion after each single use. Do not administer more than one dose from the vial.

17 Patient Counseling Information (17 PATIENT COUNSELING INFORMATION)

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Instructions for Use).

2.5 Storage of Reconstituted Solution

If the reconstituted ZYCUBO vial is not used immediately, store the vial refrigerated at 2°C to 8°C (36° to 46°F) for up to 24 hours or at controlled room temperature at 20°C to 25°C (68°F to 77°F) for up to 4 hours.

Discard the reconstituted ZYCUBO vial if not used within 24 hours of refrigeration or within 4 hours at room temperature.

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.
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.

2.1 Recommended Testing Before Initiating Zycubo (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)].

2.3 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. 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 evaluation when resuming a dosage as clinically indicated [see Warnings and Precautions (5.1)].

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Source: dailymed · Ingested: 2026-02-15T11:52:36.959402 · Updated: 2026-03-14T22:44:06.575433