Hyaluronidase / Nivolumab Dosage

Medically reviewed by Drugs.com. Last updated on Feb 24, 2025.

Applies to the following strengths: nvhy 10,000 units-600 mg/5 mL

Usual Adult Dose for:

Renal Cell Carcinoma
Melanoma - Metastatic
Non-Small Cell Lung Cancer
Head and Neck Cancer
Urothelial Carcinoma
Colorectal Cancer
Hepatocellular Carcinoma
Esophageal Carcinoma
Gastric Cancer

Usual Adult Dose for Renal Cell Carcinoma

ADVANCED RENAL CELL CARCINOMA:
Monotherapy or Following IV Nivolumab and Ipilimumab Combination Therapy:

Nivolumab 600 mg-hyaluronidase 10,000 units subcutaneously every 2 weeks

Nivolumab 1200 mg-hyaluronidase 20,000 units subcutaneously every 4 weeks
Duration of therapy: Until disease progression or unacceptable toxicity

Combination Therapy:

Nivolumab 600 mg-hyaluronidase 10,000 units subcutaneously every 2 weeks

Nivolumab 1200 mg-hyaluronidase 20,000 units subcutaneously every 4 weeks
Administer in combination with cabozantinib 40 mg orally once a day without food
Duration of therapy:
Nivolumab-hyaluronidase: Until disease progression, unacceptable toxicity, or up to 2 years
Cabozantinib: Until disease progression or unacceptable toxicity

Comments:

Administer subcutaneously into the abdomen or thigh over 3 to 5 minutes.
Consult the manufacturer product information of therapeutic agents given in combination with this drug for complete dosing recommendations.
Limitation of use: This drug is not indicated in combination with ipilimumab for the treatment of renal cell carcinoma (RCC).

Uses:

As monotherapy, for the first-line treatment of patients with intermediate or poor risk advanced RCC following treatment with IV nivolumab and ipilimumab combination therapy
As monotherapy, for the treatment of advanced RCC in patients who have received prior anti-angiogenic therapy
In combination with cabozantinib, for the first-line treatment of advanced RCC

Usual Adult Dose for Melanoma - Metastatic

UNRESECTABLE OR METASTATIC MELANOMA:
Monotherapy or Following IV Nivolumab and Ipilimumab Combination Therapy:

Nivolumab 600 mg-hyaluronidase 10,000 units subcutaneously every 2 weeks

Nivolumab 1200 mg-hyaluronidase 20,000 units subcutaneously every 4 weeks
Duration of therapy: Until disease progression or unacceptable toxicity

ADJUVANT TREATMENT OF MELANOMA:

Nivolumab 600 mg-hyaluronidase 10,000 units subcutaneously every 2 weeks

Nivolumab 1200 mg-hyaluronidase 20,000 units subcutaneously every 4 weeks
Duration of therapy: Until disease recurrence or unacceptable toxicity for up to 1 year

Comments:

Administer subcutaneously into the abdomen or thigh over 3 to 5 minutes.
Limitations of Use: This drug is not indicated in combination with ipilimumab for the treatment of unresectable or metastatic melanoma

Uses:

As monotherapy, for the treatment of unresectable or metastatic melanoma
As monotherapy, for the treatment of unresectable or metastatic melanoma following treatment with IV nivolumab and ipilimumab combination therapy
As monotherapy, for the adjuvant treatment of completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma

Usual Adult Dose for Non-Small Cell Lung Cancer

MONOTHERAPY FOR METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC):

Nivolumab 600 mg-hyaluronidase 10,000 units subcutaneously every 2 weeks

Nivolumab 1200 mg-hyaluronidase 20,000 units subcutaneously every 4 weeks
Duration of therapy: Until disease progression or unacceptable toxicity

NEOADJUVANT TREATMENT OF RESECTABLE NSCLC:

Nivolumab 900 mg-hyaluronidase 15,000 units with platinum-doublet chemotherapy on the same day every 3 weeks
Duration of therapy: In combination with platinum-doublet chemotherapy for 3 cycles

NEOADJUVANT AND ADJUVANT TREATMENT OF RESECTABLE NSCLC:
Neoadjuvant Treatment:

Nivolumab 900 mg-hyaluronidase 15,000 units with platinum-doublet chemotherapy on the same day every 3 weeks
Duration of therapy: In combination with platinum-doublet chemotherapy until disease progression or unacceptable toxicity, for up to 4 cycles

Adjuvant Treatment as a Single Agent Following Neoadjuvant Therapy and Surgery:

Nivolumab 1200 mg-hyaluronidase 20,000 units every 4 weeks
Duration of therapy: Until disease progression, recurrence, or unacceptable toxicity, for up to 13 cycles

(up to 1 year)

Comments:

Administer subcutaneously into the abdomen or thigh over 3 to 5 minutes.
Consult the manufacturer product information of therapeutic agents given in combination with this drug for dosing recommendations.
Limitations of Use: This drug is not indicated in combination with ipilimumab for the treatment of metastatic NSCLC.

Uses:

As monotherapy, for the treatment of metastatic NSCLC with progression on or after platinum-based chemotherapy. Patients with epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving treatment with this drug.
In combination with platinum-doublet chemotherapy, as a neoadjuvant treatment of resectable (tumors at least 4 cm or node positive) NSCLC
In combination with platinum-doublet chemotherapy, for the neoadjuvant treatment of resectable (tumors at least 4 cm or node positive) NSCLC and no known EGFR mutations or ALK rearrangements, followed by use of this combination drug as monotherapy in the adjuvant setting after surgical resection

Usual Adult Dose for Head and Neck Cancer

MONOTHERAPY:

Nivolumab 600 mg-hyaluronidase 10,000 units subcutaneously every 2 weeks

Nivolumab 1200 mg-hyaluronidase 20,000 units subcutaneously every 4 weeks

Comments:

Administer subcutaneously into the abdomen or thigh over 3 to 5 minutes.
Duration of therapy: Until disease progression or unacceptable toxicity.

Use: As monotherapy, for the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after platinum-based therapy

Usual Adult Dose for Urothelial Carcinoma

MONOTHERAPY FOR LOCALLY ADVANCED OR METASTATIC UROTHELIAL CARCINOMA:

Nivolumab 600 mg-hyaluronidase 10,000 units subcutaneously every 2 weeks

Nivolumab 1200 mg-hyaluronidase 20,000 units subcutaneously every 4 weeks
Duration of therapy: Until disease progression or unacceptable toxicity.

ADJUVANT TREATMENT OF UROTHELIAL CARCINOMA:

Nivolumab 600 mg-hyaluronidase 10,000 units subcutaneously every 2 weeks

Nivolumab 1200 mg-hyaluronidase 20,000 units subcutaneously every 4 weeks
Duration of therapy: Until disease recurrence or unacceptable toxicity for up to 1 year

FIRST-LINE UNRESECTABLE OR METASTATIC UROTHELIAL CARCINOMA:
Combination Therapy:

Nivolumab 900 mg-hyaluronidase 15,000 units subcutaneously every 3 weeks
Administer this drug in combination with cisplatin and gemcitabine on the same day every 3 weeks
Duration of therapy: In combination with cisplatin and gemcitabine for up to 6 cycles

As a Single Agent After Completing Combination Therapy:

Nivolumab 600 mg-hyaluronidase 10,000 units subcutaneously every 2 weeks

Nivolumab 1200 mg-hyaluronidase 20,000 units subcutaneously every 4 weeks
Duration of therapy: After completing up to 6 cycles of combination therapy, administer as single agent until disease progression, unacceptable toxicity, or up to 2 years from first dose

Comments:

Administer subcutaneously into the abdomen or thigh over 3 to 5 minutes.
Consult the manufacturer product information of therapeutic agents given in combination with this drug for dosing recommendations.

Uses:

As monotherapy, for the adjuvant treatment of urothelial carcinoma (UC) in patients at high risk of recurrence after undergoing radical resection of UC
As monotherapy, for the treatment of locally advanced or metastatic UC with disease progression during or following platinum-containing chemotherapy, OR disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
In combination with cisplatin and gemcitabine, for the first-line treatment of unresectable or metastatic UC

Usual Adult Dose for Colorectal Cancer

MONOTHERAPY OR FOLLOWING IV NIVOLUMAB AND IPILIMUMAB COMBINATION THERAPY:

Nivolumab 600 mg-hyaluronidase 10,000 units subcutaneously every 2 weeks

Nivolumab 1200 mg-hyaluronidase 20,000 units subcutaneously every 4 weeks
Duration of therapy: Until disease progression or unacceptable toxicity.

Comments:

Administer subcutaneously into the abdomen or thigh over 3 to 5 minutes.
Limitations of Use: This drug is not indicated in combination with ipilimumab for the treatment of microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC).

Use: As monotherapy, or as monotherapy following treatment with IV nivolumab and ipilimumab combination therapy, for the treatment of MSI-H or dMMR metastatic CRC that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

Usual Adult Dose for Hepatocellular Carcinoma

MONOTHERAPY OR FOLLOWING IV NIVOLUMAB AND IPILIMUMAB COMBINATION THERAPY:

Nivolumab 600 mg-hyaluronidase 10,000 units subcutaneously every 2 weeks

Nivolumab 1200 mg-hyaluronidase 20,000 units subcutaneously every 4 weeks
Duration of therapy: Until disease progression or unacceptable toxicity.

Comments:

Administer subcutaneously into the abdomen or thigh over 3 to 5 minutes.
Limitations of Use: This drug is not indicated in combination with ipilimumab for the treatment of hepatocellular carcinoma (HCC).

Use: As monotherapy, for the treatment of HCC previously treated with sorafenib and following treatment with IV nivolumab and ipilimumab

Usual Adult Dose for Esophageal Carcinoma

ESOPHAGEAL SQUAMOUS CELL CARCINOMA:
Monotherapy:

Nivolumab 600 mg-hyaluronidase 10,000 units subcutaneously every 2 weeks

Nivolumab 1200 mg-hyaluronidase 20,000 units subcutaneously every 4 weeks
Duration of therapy: Until disease progression or unacceptable toxicity

Combination therapy:

Nivolumab 600 mg-hyaluronidase 10,000 units subcutaneously every 2 weeks

Nivolumab 1200 mg-hyaluronidase 20,000 units subcutaneously every 4 weeks
Administer in combination with fluoropyrimidine- and platinum-containing chemotherapy.
Duration of therapy:
Nivolumab-hyaluronidase: Until disease progression, unacceptable toxicity, or up to 2 years
Chemotherapy: Until disease progression or unacceptable toxicity

RESECTED ESOPHAGEAL OR GASTROESOPHAGEAL JUNCTION CANCER:
Adjuvant Treatment:

Nivolumab 600 mg-hyaluronidase 10,000 units subcutaneously every 2 weeks

Nivolumab 1200 mg-hyaluronidase 20,000 units subcutaneously every 4 weeks
Duration of therapy: Until disease recurrence or unacceptable toxicity for up to 1 year

ESOPHAGEAL ADENOCARCINOMA, GASTROESOPHAGEAL JUNCTION CANCER, AND GASTRIC CANCER:
Combination Therapy:

Nivolumab 600 mg-hyaluronidase 10,000 units subcutaneously with fluoropyrimidine- and platinum-containing chemotherapy every 2 weeks

Nivolumab 900 mg-hyaluronidase 15,000 units subcutaneously with fluoropyrimidine- and platinum-containing chemotherapy every 3 weeks
Duration of therapy:
Nivolumab-hyaluronidase: Until disease progression, unacceptable toxicity, or up to 2 years
Chemotherapy: Until disease progression or unacceptable toxicity

Comments:

Administer subcutaneously into the abdomen or thigh over 3 to 5 minutes.
Consult the manufacturer product information of therapeutic agents given in combination with this drug for dosing recommendations.
Limitations of Use: This drug is not indicated in combination with ipilimumab for the treatment of unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).

Uses:

As monotherapy, for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in patients who have received neoadjuvant chemoradiotherapy
As monotherapy, for the treatment of unresectable advanced, recurrent, or metastatic ESCC after prior fluoropyrimidine- and platinum-based chemotherapy
In combination with fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of unresectable advanced or metastatic ESCC
In combination with fluoropyrimidine- and platinum-containing chemotherapy, for the treatment of advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma

Usual Adult Dose for Gastric Cancer

ESOPHAGEAL SQUAMOUS CELL CARCINOMA:
Monotherapy:

Nivolumab 600 mg-hyaluronidase 10,000 units subcutaneously every 2 weeks

Nivolumab 1200 mg-hyaluronidase 20,000 units subcutaneously every 4 weeks
Duration of therapy: Until disease progression or unacceptable toxicity

Combination therapy:

Nivolumab 600 mg-hyaluronidase 10,000 units subcutaneously every 2 weeks

Nivolumab 1200 mg-hyaluronidase 20,000 units subcutaneously every 4 weeks
Administer in combination with fluoropyrimidine- and platinum-containing chemotherapy.
Duration of therapy:
Nivolumab-hyaluronidase: Until disease progression, unacceptable toxicity, or up to 2 years
Chemotherapy: Until disease progression or unacceptable toxicity

RESECTED ESOPHAGEAL OR GASTROESOPHAGEAL JUNCTION CANCER:
Adjuvant Treatment:

Nivolumab 600 mg-hyaluronidase 10,000 units subcutaneously every 2 weeks

Nivolumab 1200 mg-hyaluronidase 20,000 units subcutaneously every 4 weeks
Duration of therapy: Until disease recurrence or unacceptable toxicity for up to 1 year

ESOPHAGEAL ADENOCARCINOMA, GASTROESOPHAGEAL JUNCTION CANCER, AND GASTRIC CANCER:
Combination Therapy:

Nivolumab 600 mg-hyaluronidase 10,000 units subcutaneously with fluoropyrimidine- and platinum-containing chemotherapy every 2 weeks

Nivolumab 900 mg-hyaluronidase 15,000 units subcutaneously with fluoropyrimidine- and platinum-containing chemotherapy every 3 weeks
Duration of therapy:
Nivolumab-hyaluronidase: Until disease progression, unacceptable toxicity, or up to 2 years
Chemotherapy: Until disease progression or unacceptable toxicity

Comments:

Administer subcutaneously into the abdomen or thigh over 3 to 5 minutes.
Consult the manufacturer product information of therapeutic agents given in combination with this drug for dosing recommendations.
Limitations of Use: This drug is not indicated in combination with ipilimumab for the treatment of unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).

Uses:

As monotherapy, for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in patients who have received neoadjuvant chemoradiotherapy
As monotherapy, for the treatment of unresectable advanced, recurrent, or metastatic ESCC after prior fluoropyrimidine- and platinum-based chemotherapy
In combination with fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of unresectable advanced or metastatic ESCC
In combination with fluoropyrimidine- and platinum-containing chemotherapy, for the treatment of advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma

Renal Dose Adjustments

IMMUNE-MEDIATED NEPHRITIS WITH RENAL DYSFUNCTION:

Grades 2 or 3 increased blood creatinine: Withhold treatment. May resume therapy after complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue therapy if complete or partial resolution is not achieved within 12 weeks of last treatment dose OR unable to reduce prednisone to 10 mg per day or less [or equivalent] within 12 weeks of initiating steroids.
Grade 4 increased blood creatinine: Permanently discontinue therapy

Liver Dose Adjustments

IMMUNE-MEDIATED HEPATITIS WITH TUMOR INVOLVEMENT OF LIVER:

If baseline AST or ALT is above 1 and up to 3 times the upper limit of normal (3 x ULN) and increases greater than 5 and up to 10 x ULN, OR if baseline AST or ALT is above 3 and up to 5 x ULN and increases above 8 and up to 10 x ULN: Withhold treatment. May resume therapy after complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue therapy if complete or partial resolution is not achieved within 12 weeks of last treatment dose OR unable to reduce prednisone to 10 mg per day or less [or equivalent] within 12 weeks of initiating steroids.
If AST or ALT increases above 10 x ULN, OR total bilirubin increases above 3 x ULN: Permanently discontinue therapy

IMMUNE-MEDIATED HEPATITIS AND NO TUMOR INVOLVEMENT OF LIVER:

If AST or ALT increases above 3 and up to 8 x ULN, OR total bilirubin increases above 1.5 and up to 3 x ULN: Withhold treatment. May resume therapy after complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue therapy if complete or partial resolution is not achieved within 12 weeks of last treatment dose OR unable to reduce prednisone to 10 mg per day or less [or equivalent] within 12 weeks of initiating steroids.
If AST or ALT increases above 8 x ULN, OR total bilirubin increases above 3 x ULN: Permanently discontinue therapy

ELEVATED LIVER ENZYMES DURING COMBINATION THERAPY WITH CABOZANTINIB:

If AST or ALT increases above 3 x ULN and up to 10 x ULN with concurrent total bilirubin less than 2 x ULN: Withhold combination therapy until adverse reactions recover to Grade 0 or 1.
Consider corticosteroid therapy for hepatic adverse reactions if therapy is withheld or discontinued when administered in combination with cabozantinib.
After recovery, rechallenge may be considered with either nivolumab-hyaluronidase, cabozantinib, or both. If rechallenging with cabozantinib (with or without use of this drug) refer to the manufacturer product information for cabozantinib.
If AST or ALT increases above 10 x ULN, or increases above 3 x ULN with concurrent total bilirubin 2 x ULN or greater: Permanently discontinue treatment with both this drug and cabozantinib.

Dose Adjustments

GENERAL CONSIDERATIONS:

No dose reductions are recommended.
In general, withhold therapy for severe (Grade 3) immune-mediated adverse reactions.
Permanently discontinue treatment for:
Life-threatening (Grade 4) immune-mediated adverse reactions
Recurrent severe (Grade 3) immune-mediated adverse reactions requiring systemic immunosuppression
Inability to reduce the daily corticosteroid dosage to 10 mg or less of prednisone (or equivalent) within 12 weeks of initiating corticosteroids

IMMUNE MEDIATED ADVERSE REACTIONS:
Colitis:

Grade 2 or 3: Withhold treatment. May resume therapy after complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue therapy if complete or partial resolution is not achieved within 12 weeks of last treatment dose OR unable to reduce prednisone to 10 mg per day or less [or equivalent] within 12 weeks of initiating steroids.
Grade 4: Permanently discontinue therapy

Endocrinopathies:

Grade 2: Depending on clinical severity, consider withholding for Grade 2 endocrinopathy until symptom improvement with hormone replacement. Resume once acute symptoms have resolved.
Grades 3 or 4: Withhold therapy until clinically stable, or permanently discontinue depending on severity

Exfoliative Dermatologic Conditions:

Suspected Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), or toxic epidermal necrolysis (TEN): Withhold treatment
Confirmed SJS, DRESS, or TEN: Permanently discontinue therapy

Myocarditis:

Grades 2, 3, or 4: Permanently discontinue therapy

Neurological Toxicities:

Grade 2: Withhold therapy. May resume therapy after complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue therapy if complete or partial resolution is not achieved within 12 weeks of last treatment dose OR unable to reduce prednisone to 10 mg per day or less [or equivalent] within 12 weeks of initiating steroids.
Grade 3 or 4: Permanently discontinue therapy

Pneumonitis:

Grade 2: Withhold treatment. May resume therapy after complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue therapy if complete or partial resolution is not achieved within 12 weeks of last treatment dose OR unable to reduce prednisone to 10 mg per day or less [or equivalent] within 12 weeks of initiating steroids.
Grade 3 or 4: Permanently discontinue therapy

Precautions

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

For subcutaneous use only in the abdomen or thigh; DO NOT administer IV.
This drug is intended for administration by a health care provider only.
Administer the full contents of the syringe into the subcutaneous tissue of 1 of the 4 quadrants of the abdomen, or thigh, over a period of 3 to 5 minutes; alternate injections sites for subsequent doses.
Do not inject into areas where the skin is tender, red, or bruised, or in areas with scars or moles.
If administration is interrupted, continue administering at the same site, or at an alternate site.
Do not administer other subcutaneous medications at the same site used for this drug.
Consult the manufacturer product information prior to product for complete administration instructions.

Switching from IV nivolumab to this product:

Patients currently receiving IV nivolumab as a single agent, or in combination with chemotherapy or cabozantinib, may switch to this subcutaneous product at their next scheduled dose.

Storage requirements:

Store vials under refrigeration (2C to 8C [36F to 46F]) in the original carton to protect from light.
Do not freeze or shake this product.
Once withdrawn into the syringe, this drug should be used immediately. If not used immediately, store prepared syringe as follows:
Under refrigeration for up to 48 hours protected from light
At room temperature (20C to 25C [68F to 77F]) for up to 8 hours; protection from light is not required

Reconstitution/preparation techniques:

This drug is contained in a ready-to-use solution for one-time use; do not dilute or shake.
Avoid medication errors by ensuring prepared product is for subcutaneous use only.
Consult the manufacturer product information prior to preparing this drug for administration.

Compatibility information:

No incompatibilities were observed between this drug and most subcutaneous administration sets.

General:

Providers should be aware that this combination product differs in its dosage and administration than IV nivolumab products.

Monitoring:

Hepatic: Liver enzymes, especially during combination therapy with cabozantinib (before initiation and periodically during therapy)
Immunologic: For signs/symptoms of immune-mediated adverse reactions (during therapy); monitor liver

enzymes, creatinine, and thyroid function for early identification of immune reactions (at baseline and periodically during therapy)

Metabolic: For hyperglycemia or other signs/symptoms of diabetes (during therapy)
Other: For complications in patients who received allogenic hematopoietic stem cell transplant (HSCT) before or after treatment with this drug (during therapy)

Patient advice:

Read the US FDA-approved patient labeling (Medication Guide).
Understand the risk of immune-mediated adverse reactions associated with use of this drug.
Contact your health care provider immediately if signs/symptoms of immune-mediate reactions occur.
Recognize the risk associated with therapy if this drug is used prior to or after an allogeneic HSCT.
Females of childbearing potential: This drug may cause fetal harm. Use effective contraception during therapy and for 5 months after the last dose.
Breastfeeding is not recommended during therapy and for 5 months after the last dose.