dac-KLYE-zue-mab

Therapeutic Classification: Immunosuppressant agents

Pharmacologic Classification: interleukin antagonists, monoclonal antibodies

• Patients with relapsing forms of multiple sclerosis who have had an inadequate response to 2 drugs.

• Binds specifically to the CD25 subunit of the interleukin-2 (IL-2) receptor on activated lymphocytes, preventing further activation of lymphocytes.

• Fewer exacerbations of relapsing multiple sclerosis and fewer lesions.

Absorption: 90% absorbed following subcut administration.

Distribution: Minimally distributed to tissues.

Metabolism/Excretion: Degraded by proteolytic enzymes located throughout the body.

Half-life: 21 days.

(blood levels)

Contraindicated in:

• Hypersensitivity
• Hepatic impairment (including ALT or AST 2x ULN)
• Autoimmune hepatitis or other autoimmune condition involving the liver
• Pedi: Children <17 yr (due to risks of hepatic injury and immune-mediated disorders).

Use Cautiously in:

• Current or a history of depression
• OB: Safety not established
• Lactation: Weigh benefits of breastfeeding against possible adverse effects.

CNS: SUICIDAL IDEATION/BEHAVIORS, depression.

Derm: rash, acne, dermatitis, eczema, psoriasis.

EENT: nasopharyngitis, rhinitis.

GI: AUTOIMMUNE HEPATITIS, HEPATOTOXICITY, colitis, hyperbilirubinemia, ↑ liver enzymes, oropharyngeal pain.

Hemat: anemia, lymphadenopathy.

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS, ANGIOEDEMA, AND URTICARIA), INFECTIONS (INCLUDING URINARY TRACT INFECTIONS, UPPER RESPIRATORY TRACT INFECTIONS, VIRAL INFECTIONS, AND TUBERCULOSIS), fever.

Drug-Drug:

• Concurrent use of hepatotoxic drugs can ↑ risk of hepatotoxicity.
• May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions.

Drug-Natural Products:

• Concurrent use with hepatotoxic herbal products can ↑ risk of hepatotoxicity.

• SC (Adults): 150 mg once monthly.

• Solution for subcutaneous injection (in prefilled syringe or prefilled autoinjector): 150 mg/mL;

• Obtain tuberculosis (TB) test prior to starting therapy. If positive, treat TB before starting therapy; do not administer to patients with TB or other active infections (upper respiratory tract, urinary tract, viral). If serious infection develops, consider withholding daclizumab until infection resolves.
• Monitor for signs and symptoms of hepatic dysfunction (unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, jaundice, dark urine) periodically during therapy. If signs and symptoms occur, monitor hepatic function tests and interrupt or discontinue therapy as needed.
• Assess mental status (orientation, mood, behavior) before and periodically during therapy. Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
• Monitor for signs of anaphylactic or hypersensitivity reactions (hypotension, bronchospasm, wheezing, swelling of face, tongue, or throat, laryngeal edema, fever, rash, urticaria,) at each dose. If a severe hypersensitivity reaction occurs, discontinue daclizumab permanently.

• Monitor AST, ALT, and total bilirubin prior to starting, monthly before each dose, and monthly for up to 6 mo after last dose of daclizumab therapy. Do not administer if AST or ALT 2 x upper limit of normal. If AST or ALT >5 x upper limit of normal OR total bilirubin >2 x upper limit of normal OR AST or ALT 3 but <5 x upper limit of normal and total bilirubin >1.5 but <2 x upper limit of normal, interrupt daclizumab therapy and investigate other causes of ↑. If no other causes identified, discontinue daclizumab. If other causes found, re-assess risk-benefit of daclizumab and consider whether to resume therapy when both AST or ALT <2 x upper limit of normal and total bilirubin upper limit of normal.
  • Screen patient for Hepatitis B and C prior to therapy; do not administer to patients with pre-existing hepatic disease.

• Only available through a restricted program, Zinbryta REMS program, due to risks of hepatic and immune-mediated disorders. Prescribers must be trained and certified, patients must enroll and comply with on-going monitoring, and pharmacies must be certified and only dispense to authorized patients. List of qualified pharmacies is available by calling 1-800-456-2255.
• SC: Remove from refrigerator 30 min prior to injection to allow to warm to room temperature. Solution is colorless to slightly yellow and clear to slightly opalescent; do not administer solutions that are discolored or contain particulate matter. Administer once monthly in thigh, abdomen, or back of arm. Pinch skin and inject needle at 90° angle, do not aspirate, then release skin and inject solution. Store in refrigerator, if unavailable may be stored at room temperature and protected from light for up to 30 days, then discard. Do not place back in refrigerator after reaching room temperature; do not freeze.

• Instruct patient on proper technique, storage and disposal of equipment. Administer missed doses as soon as possible but no >2 wks late. After 2 wks, omit missed dose and take next dose at scheduled time; do not double doses. Advise patient to read Medication Guide and Instructions for Use before starting therapy and with each Rx refill in case of changes.
• Advise patient to notify health care professional immediately if signs and symptoms of hepatotoxicity (nausea, vomiting, stomach pain, unusual tiredness, loss of appetite, yellowing of skin or whites of eyes, dark urine), hypersensitivity reactions, infections, skin reactions (rash, skin irritation), lymphadenopathy (tender, swollen, painful lymph nodes), or colitis (fever, stomach pain, blood in stools, persistent diarrhea) occur.
• Advise patient and family to notify health care professional if behavioral changes, thoughts about suicide or dying, attempts to commit suicide; new or worse depression; feeling sad or crying spells, sleeping a lot more or a lot less than usual, feeling hopeless or helpless, irritability, anger, aggressive, trouble paying attention, frequently tired or sleepy, or other unusual changes in behavior or mood occur.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Instruct patient not to receive any vaccinations and to avoid contact with persons receiving oral polio vaccine during and for up to 4 mo after discontinuation of therapy without advice of health care professional.
• Advise female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
• Emphasize the importance of monthly lab tests during and for 6 mo following therapy.
• Advise patient to carry Zinbryta Patient Wallet Card at all times and show care to other treating health care professionals.

• Fewer exacerbations of relapsing multiple sclerosis and fewer lesions.

Zinbryta

• Risk for infection (Side Effects).
• Risk for suicide (Adverse Reactions).
• Deficient knowledge, Relate med (Patient/Family Teaching).