Durvalumab

Durvalumab is a prescription medicine used as a single agent or in combination with chemotherapy to treat the following conditions in adults:

• Non-Small Cell Lung Cancer (NSCLC)
• Small Cell Lung Cancer (SCLC)
• Biliary Tract Cancers (BTC)
• Hepatocellular Carcinoma (HCC)
• Endometrial Cancer
• Muscle-invasive Bladder Cancer (MIBC)
• Gastric or Gastroesophageal Junction Adenocarcinoma (GC/GEJC)

Durvalumab is available under the following different brand names: Imfinzi

Common side effects of Durvalumab include:

• nausea
• constipation
• diarrhea
• abdominal pain
• vomiting
• decreased appetite
• stomatitis
• cough
• dyspnea
• pneumonitis/radiation pneumonitis
• upper respiratory tract infections
• rash
• alopecia
• pruritus
• fatigue
• asthenia
• musculoskeletal pain
• peripheral neuropathy
• headache
• anemia
• pyrexia
• decreased hemoglobin
• decreased neutrophils
• decreased lymphocytes
• decreased platelets
• decreased magnesium
• decreased calcium
• decreased or increased potassium
• decreased sodium
• Increased alanine aminotransferase
• Increased aspartate aminotransferase
• increased alkaline phosphatase
• increased blood creatinine

Serious side effects of Durvalumab include:

• immune-mediated adverse reactions, such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis, dermatological reactions and pancreatitis
• serious or life-threatening infusion-related reaction
• complications of allogeneic hematopoietic stem cell transplant (HSCT)

Rare side effects of Durvalumab 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 dosage

Injectable solution

• 50mg/mL (2.4 mL, 10 mL single-dose vials)

Non-Small Cell Lung Cancer (NSCLC)

Single-agent therapy

• Weighing 30 kg and more: 10 mg/kg intravenously every 2 weeks or 1500 mg intravenously every 4 weeks
• Weighing less than 30 kg: 10 mg/kg intravenously every 2 weeks
• Continue until disease progression or unacceptable toxicity, or a maximum of 12 months
• Combination with platinum-containing chemotherapy

Neoadjuvant therapy

• Weighing 30 kg and more: 1500 mg intravenously every 3 weeks
• Weighing less than 30 kg: 20 mg/kg intravenously every 3 weeks
• Administer in combination with chemotherapy for up to 4 cycles before surgery

Adjuvant therapy

• Weighing 30 kg and more: 1500 mg intravenously every 4 weeks
• Weighing less than 30 kg: 20 mg/kg intravenously every 4 weeks
• Administer as a single agent and continue until disease progression, unacceptable toxicity, or a maximum of 12 cycles after surgery
• Combination with tremelimumab and platinum-based chemotherapy
• Weighing 30 kg and more: 1500 mg intravenously plus tremelimumab 75 mg intravenously
• Weighing less than 30 kg: 20 mg/kg intravenously plus tremelimumab 1 mg/kg intravenously
• Cycles 1-4
  • Dose interval every 3 weeks
  • Administer tremelimumab, durvalumab and chemotherapy
• Cycle 5 (week 12)
  • Starting at cycle 5, the dose interval changes from every 3 weeks to every 4 weeks
  • Administer durvalumab and chemotherapy
  • Note: If <4 cycles of platinum-based chemotherapy were received, the remaining cycles of tremelimumab (up to a total of 5) should be given after the platinum-based chemotherapy phase, in combination with durvalumab, every 4 weeks
  • Optional pemetrexed therapy from week 12 until disease progression or intolerable toxicity for patients with non-squamous disease who received treatment with pemetrexed and carboplatin/cisplatin
• Cycle 6 (week 16)
  • Administer tremelimumab, durvalumab and chemotherapy
• Cycle 7 (week 20) and thereafter
• Administer durvalumab and chemotherapy
• Continue durvalumab until disease progression or intolerable toxicity
• Platinum-based chemotherapy regimens (non-squamous NSCLC)
• Carboplatin plus nab-paclitaxel, OR
  • Carboplatin or cisplatin plus pemetrexed
  • Platinum-based chemotherapy regimens (squamous NSCLC)
• Carboplatin plus nab-paclitaxel, OR
  • Carboplatin or cisplatin plus gemcitabine

Small Cell Lung Cancer (SCLC)

Single-agent therapy

• weighing 30 kg and more: 1500 mg intravenously every 4 weeks
• weighing less than 30 kg: 20 mg/kg intravenously every 4 weeks
• Continue until disease progression, unacceptable toxicity, or a maximum of 24 months
• Combination with chemotherapy

Cycles 1-4

• Each cycle is 21 days
• Durvalumab 1500 mg (for adults weighing less than 30 kg, dose at 20 mg/kg) intravenously on Day 1 PLUS
• Etoposide 80-100 mg/m2 intravenously daily on Days 1-3 PLUS
• Carboplatin AUC 5 or 6 on Day 1 OR
• Cisplatin 75-80 mg/m2 on Day 1 intravenously
• Subsequent cycles as a single agent
  • weighing 30 kg and more: 1500 mg intravenously every 4 weeks
  • weighing less than 30 kg: 10 mg/kg intravenously every 2 weeks
• Continue until disease progression or unacceptable toxicity

Biliary Tract Cancers (BTC)

• Cycles 1-8 in combination with chemotherapy
• Each cycle is 21 days
• Day 1
  • Durvalumab 1500 mg (for adults weighing less than 30 kg, dose at 20 mg/kg) intravenously plus
  • Gemcitabine 1000 mg/m2 intravenously plus
  • Cisplatin 25 mg/m2 intravenously
• Day 8
  • Gemcitabine 1000 mg/m2 intravenously plus
  • Cisplatin 25 mg/m2 intravenously
  • Subsequent cycles as a single agent
  • Durvalumab 1500 mg intravenously every 4 weeks (for adults weighing less than 30 kg, dose at 10 mg/kg intravenously every 2 weeks)
  • Continue until disease progression or unacceptable toxicity

Hepatocellular Carcinoma (HCC)

• Each cycle is 28 days
  • Cycle 1 in combination with tremelimumab
    • Weighing 30 kg and more: Tremelimumab 300 mg intravenously x 1 dose, then durvalumab 1500 mg intravenously
    • Weighing less than 30 kg: Tremelimumab 4 mg/kg intravenously x 1 dose, then durvalumab 20 mg/kg intravenously
  • Cycle 2 and thereafter as a single agent
    • Weighing 30 kg and more: Durvalumab 1500 mg intravenously every 4 weeks
    • Weighing less than 30 kg: Durvalumab 20 mg/kg intravenously every 4 weeks
    • Continue until disease progression or unacceptable toxicity

Endometrial Cancer

• Cycles 1-6 in combination with chemotherapy
• Administer on Day 1 of each 21-day cycle
• Adults weighing 30 kg and more 
• Durvalumab 1120 mg intravenously
  • Carboplatin AUC of 5 or 6 mg/mL/min intravenously over 1 hr, and
  • Paclitaxel 175 mg/m2 intravenously over 3 hr
  • Adults weighing less than 30 kg 
• Durvalumab 15 mg/kg intravenously
  • Carboplatin AUC of 5 or 6 mg/mL/min intravenously over 1 hr, and
  • Paclitaxel 175 mg/m2 intravenously over 3 hr
• Cycle 7 and thereafter as a single agent
  • Weighing 30 kg: Durvalumab 1500 mg intravenously every 4 weeks
  • Weighing less than 30 kg: Durvalumab 20 mg/kg intravenously every 4 weeks
  • Continue until disease progression or unacceptable toxicity

Bladder Cancer

• Neoadjuvant therapy (with chemotherapy)
  • Administer every 3 weeks for 4 cycles before surgery
  • Adults weighing 30 kg and more: 1500 mg intravenously
  • Adults weighing less than 30 kg: 20 mg/kg intravenously
  • Administer in combination with gemcitabine (1000 mg/m2) and cisplatin (70 mg/m2)
• Adjuvant therapy (single agent)
  • Administer every 4 weeks for up to 8 cycles after surgery
  • Adults weighing 30 kg and more: 1500 mg intravenously
  • Adults weighing less than 30 kg: 20 mg/kg intravenously
  • Continue until disease progression that precludes definitive surgery, recurrence, or unacceptable toxicity or a maximum of 8 cycles after surgery

Gastric or Gastroesophageal Junction Adenocarcinoma

Neoadjuvant therapy

• Weighing 30 kg and more: 1500 mg intravenously every 4 weeks with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for up to 2 cycles before surgery
• Weighing less than 30 kg: 20 mg/kg intravenously every 4 weeks with FLOT for up to 2 cycles before surgery
• Administer until disease progression that precludes definitive surgery or unacceptable toxicity.
• Administer FLOT on Days 1 and 15 of cycles 1 and 2
• Administer durvalumab before chemotherapy when given on the same day

Adjuvant therapy

• Weighing 30 kg and more: 1500 mg intravenously every 4 weeks with FLOT for up to 2 cycles, followed by durvalumab 1500 mg (as a single agent) every 4 weeks for up to 10 cycles
• Weighing less than 30 kg: 20 mg/kg intravenously every 4 weeks with FLOT for up to 2 cycles, followed by durvalumab 20 mg/kg (as a single agent) every 4 weeks for up to 10 cycles
• Administer until progression or recurrence, unacceptable toxicity, or a maximum of 12 cycles after surgery
• Administer FLOT on Days 1 and 15 of cycles 1 and 2
• Administer durvalumab before chemotherapy when given on the same day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Durvalumab has no known severe interactions with other drugs.
• Serious interactions of durvalumab include:
  • corticosteroids
• Moderate interactions of durvalumab include:
  • acetaminophen
  • antibiotics
  • desmopressin
  • efgartigimod alfa
  • proton pump inhibitors
  • ketoconazole
• Durvalumab has no known mild interactions with other drugs.

Warnings

This medication contains durvalumab. Do not take Imfinzi if you are allergic to durvalumab or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• None

Effects of Drug Abuse

• No information available.

Short-Term Effects

• See "What Are Side Effects Associated with Using Durvalumab?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Durvalumab?"

Cautions

• Immune-mediated pneumonitis or interstitial lung disease reported; monitor for signs and symptoms; evaluate patients with suspected pneumonitis with radiographic imaging
• Administer corticosteroids, prednisone 1 to 2 mg per kg per day or equivalent for moderate (Grade 2) pneumonitis or prednisone 1 to 4 mg per kg per day or equivalent for more severe (Grade 3-4) pneumonitis, followed by taper; interrupt or permanently discontinue therapy based on the severity
• Immune-mediated hepatitis reported; monitor for abnormal liver tests each cycle during treatment
• Immune-mediated colitis or diarrhea reported; monitor for signs and symptoms
• Immune-mediated endocrinopathies (e.g., hypothyroidism, hyperthyroidism, adrenal insufficiency, type 1 diabetes mellitus, hypophysitis, hypopituitarism) have occurred; monitor for symptoms of these conditions
• Rare reports of other immune-mediated adverse effects (e.g., aseptic meningitis, hemolytic anemia, rash, ITP, myocarditis, myositis, nephritis, uveitis, keratitis) have occurred
• Severe infusion-related reactions reported; monitor for signs and symptoms and slow infusion rate or interrupt infusion if needed; if severe, withhold or permanently discontinue
• Can cause fetal harm

Pregnancy and Lactation

Based on its mechanism of action, durvalumab can cause fetal harm if administered to a pregnant woman. Human immunoglobulin G1 (IgG1) is known to cross the placental barrier; therefore, durvalumab has the potential to be transmitted from the mother to the developing fetus. In animal reproduction studies, administration of durvalumab to pregnant cynomolgus monkeys from the confirmation of pregnancy through delivery resulted in increased in premature delivery, fetal loss, and premature neonatal death.

Females of reproductive potential are advised to use effective contraception during treatment and for 3 months following the last dose of durvalumab.

It is unknown if durvalumab is distributed in human breast milk; human IgG1 is excreted in human milk. Durvalumab was present in the milk of lactating cynomolgus monkeys and was associated with premature neonatal death. Because of the potential for adverse reactions in breastfed infants, breastfeeding women are advised not to breastfeed during treatment with durvalumab and for at least 3 months after the last dose.