Pembrolizumab Berahyaluronidase

Pembrolizumab-Berahyaluronidase is a prescription medication indicated for the treatment of:

• Unresectable or metastatic melanoma
• Non-Small Cell Lung Cancer (NSCLC)
• Malignant Pleural Mesothelioma (MPM)
• Head and Neck Squamous Cell Cancer (HNSCC)
• Urothelial Cancer
• Microsatellite Instability-High or Mismatch Repair Deficient Cancer
• Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer (CRC)
• Gastric Cancer
• Esophageal Cancer
• Cervical Cancer
• Hepatocellular Carcinoma (HCC)
• Biliary Tract Cancer (BTC)
• Merkel Cell Carcinoma (MCC)
• Renal Cell Carcinoma (RCC)
• Endometrial Carcinoma
• Tumor Mutational Burden-High (TMB-H) Cancer
• Cutaneous Squamous Cell Carcinoma (cSCC)
• Triple-Negative Breast Cancer (TNBC)

Pembrolizumab-Berahyaluronidase is available under the following different brand names: Keytruda Qlex, Pembrolizumab-Berahyaluronidase alfa-pmph

Common side effects of Pembrolizumab-Berahyaluronidase include:

• nausea
• tiredness 
• muscle, bone and joint pain
• rash
• diarrhea
• fever
• cough
• decreased appetite
• itching
• shortness of breath/difficulty breathing
• constipation
• abdominal pain
• nausea
• vomiting
• hair loss
• mouth sores
• trouble sleeping
• high blood pressure
• urinary tract infection
• hoarseness
• blisters or rash on the palms and soles
• swelling of the lining of the mouth, nose, eyes, throat, intestines, or vagina
• tingling or numbness of the arms or legs
• dry eye
• changes in sense of taste
• neuritis
• decreased thyroid hormone levels
• decreased white blood cell count
• decreased platelet count

Serious side effects of Pembrolizumab-Berahyaluronidase include:

• symptoms of lung problems may include cough, shortness of breath, or chest pain
• symptoms of intestinal problems may include diarrhea, black or tarry stools, or severe abdominal pain
• symptoms of liver problems may include yellowing of the skin or whites of the eyes, dark urine, severe nausea or vomiting, bleeding or bruising more than normal, or pain on the right side of the abdomen
• symptoms of hormone gland problems may include unusual headaches, eye problems, eye sensitivity to light, rapid heartbeat, increased sweating, extreme tiredness, weight gain or weight loss, feeling more hungry or thirsty than usual, urinating more often than usual, hair loss, feeling cold, constipation, voice getting deeper, dizziness or fainting, and changes in mood or behavior such as decreased sex drive, irritability, or forgetfulness
• symptoms of kidney problems may include decreased urine output, blood in the urine, swelling of the ankles, or loss of appetite
• symptoms of skin problems may include rash, itching, skin blistering or peeling, swollen lymph nodes, fever, or painful sores or ulcers in the mouth, nose, throat, or genital area
• symptoms of allergic and injection-related reactions may include chills, itching or rash, flushing, shortness of breath or wheezing, dizziness, fainting, fever, and/or back pain
• risk of organ or tissue transplant rejection
• complications of a donor stem-cell (allogeneic) transplant, including serious problems such as graft-versus-host disease (GVHD)

Rare side effects of Pembrolizumab-Berahyaluronidase include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Injection, solution for SC

• (395 mg/4,800 units)/2.4 mL single-dose vial
• (790 mg/9,600 units)/4.8 mL single-dose vial

Melanoma

Adult dosage

Unresectable or metastatic melanoma

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Continue until disease progression or unacceptable toxicity

Adjuvant treatment

• 395 mg/4,800 units SC every 3 weeks
• Continue until disease recurrences, unacceptable toxicity, or for up to 12 months

Pediatric dosage

• 395 mg/4,800 units SC every 3 weeks
• Continue until disease recurrences, unacceptable toxicity, or for up to 12 months

Non-small Cell Lung Cancer

Adult dosage

Single-agent for localized disease

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Continue until disease progression or unacceptable toxicity, or up to 24 months

Single-agent for unresectable or advanced disease

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Continue until disease progression or unacceptable toxicity, or up to 24 months

Combination therapy for resectable NSCLC

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Give before chemotherapy when given on the same day
• Give neoadjuvant treatment in combination with chemotherapy for 12 weeks or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by adjuvant therapy with Pembrolizumab-Berahyaluronidase as a single agent after surgery for 39 weeks or until disease recurrence or unacceptable toxicity

Combination therapy for metastatic NSCLC

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Give before chemotherapy when given on the same day
• Give neoadjuvant treatment in combination with chemotherapy for 12 weeks or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by adjuvant therapy with Pembrolizumab-Berahyaluronidase as a single agent after surgery for 39 weeks or until disease recurrence or unacceptable toxicity

Head & Neck Squamous Cell Carcinoma (HNSCC)

Adult dosage

Single-agent therapy

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Continue until disease progression or unacceptable toxicity, or up to 24 months

Combination therapy

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Give before chemotherapy when given on the same day
• Continue until disease progression or unacceptable toxicity, or up to 24 months

Neoadjuvant/neoadjuvant therapy

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Give before chemotherapy when given on the same day
• Continue until disease progression or unacceptable toxicity, or up to 24 months

Urothelial Carcinoma

Adult dosage

Combination with enfortumab vedotin

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Administer after enfortumab vedotin when given on the same day
• Continue until disease progression or unacceptable toxicity, or up to 24 months

Single-agent therapy

Locally advanced or metastatic urothelial carcinoma

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Continue until disease progression or unacceptable toxicity, or up to 24 months

Bacillus Calmette-Guerin (BCG)-unresponsive bladder cancer

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Continue until persistent or recurrent high-risk nonmuscle invasive bladder cancer (NMIBC), disease progression, unacceptable toxicity, or up to 24 months

Microsatellite Instability-High Cancer

Adult and pediatric dosage

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Continue until persistent or recurrent high-risk NMIBC, disease progression, unacceptable toxicity, or up to 24 months

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

Adult dosage

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Continue until persistent or recurrent high-risk NMIBC, disease progression, unacceptable toxicity, or up to 24 months

Gastric Cancer

Adult dosage

HER2-positive

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Administer before trastuzumab and chemotherapy when given on the same day
• Continue until persistent or recurrent high-risk NMIBC, disease progression, unacceptable toxicity, or up to 24 months

HER2-negative

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Administer before chemotherapy when given on the same day
• Continue until persistent or recurrent high-risk NMIBC, disease progression, unacceptable toxicity, or up to 24 months

Esophageal Cancer

Adult dosage

Single-agent therapy

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Continue until persistent or recurrent high-risk NMIBC, disease progression, unacceptable toxicity, or up to 24 months

Combination therapy

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Administer before chemotherapy when given on the same day
• Continue until persistent or recurrent high-risk NMIBC, disease progression, unacceptable toxicity, or up to 24 months

Cervical Cancer

Adult dosage

Single-agent therapy

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Continue until persistent or recurrent high-risk NMIBC, disease progression, unacceptable toxicity, or up to 24 months

Combination chemotherapy

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Administer before chemotherapy when given on the same day
• Continue until persistent or recurrent high-risk NMIBC, disease progression, unacceptable toxicity, or up to 24 months

Combination chemoradiotherapy (CRT)

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Administer before CRT when given on the same day
• Continue until disease progression, unacceptable toxicity, or up to 24 months

Hepatocellular Carcinoma

Adult dosage

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Continue until disease progression, unacceptable toxicity, or up to 24 months

Merkel Cell Carcinoma

Adult and pediatric dosage

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Continue until persistent or recurrent high-risk NMIBC, disease progression, unacceptable toxicity, or up to 24 months

Renal Cell Carcinoma (RCC)

Adult dosage

First-line treatment

In combination with axitinib

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Plus, axitinib 5 mg orally two times a day
• Continue until persistent or recurrent high-risk NMIBC, disease progression, unacceptable toxicity, or up to 24 months

In combination with lenvatinib

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Plus, lenvatinib 20 mg orally daily
• Continue until persistent or recurrent high-risk NMIBC, disease progression, unacceptable toxicity, or up to 24 months

Adjuvant treatment

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Continue until persistent or recurrent high-risk NMIBC, disease progression, unacceptable toxicity, or up to 24 months

Endometrial Cancer

Adult dosage

Combination therapy with lenvatinib

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Plus lenvatinib 20 mg orally daily
• Continue until persistent or recurrent high-risk NMIBC, disease progression, unacceptable toxicity, or up to 24 months

Combination with carboplatin and paclitaxel chemotherapy

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Administer before carboplatin and paclitaxel when given on the same day

Single-agent therapy

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Continue until disease progression, unacceptable toxicity, or up to 24 months

Tumor Mutational Burden-High Cancer

Adult and pediatric dosage

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Continue until disease progression, unacceptable toxicity, or up to 24 months

Cutaneous Squamous Cell Carcinoma

Adult dosage

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Continue until disease progression, unacceptable toxicity, or up to 24 months

Breast Cancer

Adult dosage

High-risk early-stage triple-negative breast cancer (TNBC)

Neoadjuvant treatment

• 395 mg/4,800 units SC every 3 weeks x 8 doses, or
• 790 mg/9,600 units SC every 6 weeks x 3 doses
• Administer before chemotherapy when given on the same day
• Duration: 24 weeks or until disease progression or unacceptable toxicity
• Follow with adjuvant treatment

Adjuvant treatment

• 395 mg/4,800 units SC every 3 weeks x 9 doses, or
• 790 mg/9,600 units SC every 6 weeks x 4 doses
• Duration: 27 weeks or until disease progression or unacceptable toxicity
• Locally recurrent unresectable or metastatic TNBC
• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Administer before chemotherapy when given on the same day
• Continue until disease progression, unacceptable toxicity, or up to 24 months

Biliary Tract Cancer

Adult dosage

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Administer before chemotherapy when given on the same day
• Continue until disease progression, unacceptable toxicity, or up to 24 months

Malignant Pleural Mesothelioma

Adult dosage

• 395 mg/4,800 units SC every 3 weeks, or
• 790 mg/9,600 units SC every 6 weeks
• Administer before chemotherapy when given on the same day
• Continue until disease progression, unacceptable toxicity, or up to 24 months

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Visit the RxList Drug Interaction Checker for any drug interactions. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Known hypersensitivity to berahyaluronidase alfa, hyaluronidase, or to any of its excipients

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Pembrolizumab-Berahyaluronidase?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Pembrolizumab-Berahyaluronidase?”

Cautions

• Immune-mediated adverse reactions
  • Severe and fatal immune-mediated reactions reported
  • May occur in any organ system or tissue and at any time after starting therapy, including after discontinuation
  • For suspected reactions, initiate appropriate workup to exclude alternative etiologies (e.g., infection)
  • Institute medical management promptly; consult specialists as appropriate
  • Hold or permanently discontinue based on severity
  • Administer systemic corticosteroids (e.g., 1-2 mg/kg/day prednisone or equivalent) until improvement to grade 1 or less, then taper corticosteroids over at least 1 month
  • Other systemic immunosuppressants may be required if reactions are not controlled with corticosteroids
• Immune-mediated pneumonitis
  • Fatal cases reported
  • Incidence of pneumonitis is higher following prior thoracic radiation
• Immune-mediated colitis
  • Frequently associated with diarrhea
  • Cytomegalovirus (CMV) infection/reactivation reported with corticosteroid-refractory immune-mediated colitis
  • For corticosteroid-refractory colitis, consider repeating infectious workups to exclude alternative etiologies
  • Immune-mediated hepatitis
  • Rare cases reported with single-agent therapy
  • Evaluate liver enzymes before initiating and periodically during therapy
• Immune-mediated endocrinopathies
  • Immune-mediated adrenal insufficiency, hypophysitis, thyroiditis, hyperthyroidism, hypothyroidism, and type 1 diabetes mellitus (may present with diabetic ketoacidosis) have been reported
  • Initiate symptomatic treatment (.eg, hormone replacement, insulin) as clinically indicated
  • Evaluate thyroid function before initiation and periodically during therapy
  • For patients with triple-negative breast cancer treated in the neoadjuvant setting: monitor blood cortisol before initiation, before surgery, and as clinically indicated
• Immune-mediated nephritis
  • May occur with renal dysfunction
  • Evaluate renal function before initiation and periodically during therapy
• Immune-mediated dermatologic reactions
  • Exfoliative dermatitis may occur (e.g., Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis)
  • Treat mild to moderate nonexfoliative rashes with topical emollients and/or topical corticosteroids
  • Hold or permanently discontinue, depending on severity
• Hypersensitivity and administration-related reactions
  • Can cause severe or life-threatening administration-related reactions, including hypersensitivity and anaphylaxis
  • Monitor for signs and symptoms of administration-related systemic reactions, including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever
  • Interrupt injection (if not already fully administered) and resume if symptoms resolve for mild or moderate hypersensitivity and administration-related systemic reactions
  • Stop injection and permanently discontinue for severe or life-threatening hypersensitivity and administration-related systemic reactions
• Complications of allogeneic HSCT
  • Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody
  • Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause)
  • These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT
  • Follow patients closely for evidence of transplant-related complications and intervene promptly; consider the benefits versus risks of treatment with a PD-1/PD-L1 blocking antibody before or after an allogeneic HSCT
  • Combination therapy with a thalidomide analogue and dexamethasone
  • Use not recommended
  • Increased mortality reported in patients with multiple myeloma who received pembrolizumab in combination with a thalidomide analogue and dexamethasone
• Embryo-fetal toxicity
  • Fetal harm may occur if used during pregnancy
  • Advise pregnant patients of the potential risk to the fetus
  • Effective contraception is recommended during and after therapy in females of reproductive potential

Pregnancy and Lactation

• Based on its mechanism of action, fetal harm may occur when administered during pregnancy
• No human data is available regarding the risk of embryo-fetal toxicity

Contraception

• Advise females of reproductive potential to use effective contraception during treatment and for at least 4 months following the final dose

Lactation

• Maternal IgG is known to be present in human milk; effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to this drug are unknown
• No studies have been conducted to assess the impact of pembrolizumab on milk production or its presence in breast milk
• Instruct women to discontinue nursing during treatment and for 4 months after the final dose