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Pregnancy Category: C
Pharmacologic: monoclonal antibodies
Pharmacologic: monoclonal antibodies
Treatment of unresectable/metastatic melanoma.
Binds to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activation; binding results in augmented T-cell activation and proliferation.
↓ spread of melanoma.
Absorption: IV administration results in complete bioavailability.
Distribution: Crosses the placenta.
Metabolism and Excretion: Unknown.
Half-life: 14.7 days.
Contraindicated in: Lactation: Avoid breast feeding.
Use Cautiously in: Obstetric: Use only if potential maternal benefit justifies potential risk to the fetus; may cause fetal harm; Pediatric: Safety and effectiveness not established.
Adverse Reactions/Side Effects
Central nervous system
- encephalitis (life-threatening)
- fatigue (most frequent)
Ear, Eye, Nose, Throat
- hearing loss
- immune-mediated ocular disease
- immune-mediated colitis (life-threatening)
- immune-mediated hepatitis (life-threatening)
- colitis (most frequent)
- diarrhea (most frequent)
- immune-mediated dermatitis including toxic epidermal necrolysis (life-threatening)
- pruritus (most frequent)
- rash (most frequent)
- immune-mediated endrocrinopathies including hypopituitarism, hypothyroidism, hyperthyroidism, adrenal insufficiency, Cushing's syndrome, and hypogonadism (life-threatening)
- immune-mediated neuropathy (life-threatening)
- sarcoidosis (life-threatening)
Drug-Drug interactionNone noted.
Intravenous (Adults) 3 mg/kg every 3 wk for a total of 4 doses.
Solution for IV infusion (requires further dilution): 5 mg/mL
- Monitor for signs and symptoms of entercolitis (diarrhea, abdominal pain, mucus or blood in stool, with or without fever) and bowel perforation (peritoneal signs, ileus). Rule out infection and consider endoscopic evaluation. If severe enterocolitis occurs, discontinue ilipimumab and start systemic corticosteroids at doses of 1–2 mg/kg/day of prednisone or equivalents. At improvement to Grade 1 or less, taper corticosteroid over at least 1 mo. Withhold dose for moderate enterocolitis; administer anti-diarrheal treatment and if persists for >1 wk, start corticosteroids at a dose of 0.5 mg/kg/day of prednisone or equivalent.
- Assess for signs and symptoms of hepatotoxicity (yellowing of skin or whites of eyes, unusual darkening of urine, unusual tiredness, pain in right upper stomach) before each dose. If hepatotoxicity occurs, rule out infectious or malignant causes. Permanently discontinue ipilimumab if Grade 3–5 hepatotoxicity occurs and start systemic corticosteroids at a dose of 1–2 mg/kg/day of prednisone or equivalent. When liver function tests show sustained improvement or return to baseline, start corticosteroid taper over 1 mo. May administer mycophenolate in patients with persistent severe hepatitis despite high-dose corticosteroids. Withhold ipilimumab in patients with Grade 2 hepatotoxicity.
- Monitor for signs and symptoms of dermatitis (rash, pruritus). Unless other causes are identified, assume immune-mediated dermatitis. Permanently discontinue ipilimumab in patients with Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations. Administer corticosteroids at a dose of 1–2 mg/kg/day of prednisone or equivalent. When dermatitis is controlled, taper corticosteroids over at least 1 mo. Withhold ipilimumab in patients with moderate to severe signs and symptoms. Treat mild to moderate dermatitis symptomatically. Administer topical or systemic corticosteroids if there is no improvement of symptoms within 1 wk.
- Monitor for symptoms of motor or sensory neuropathy (unilateral or bilateral weakness, sensory alterations, paresthesia). Permanently discontinue ipilimumab in patients with severe neuropathy (interfering with daily activities). Institute treatment as needed. Consider systemic corticosteroids of 1–2 mg/kg/day of prednisone or equivalent for severe neuropathy. Withhold dose of ipilimumab in patients with moderate neuropathy (not interfering with daily activities).
- Monitor for clinical signs and symptoms of hypophysitis, adrenal insufficiency (including adrenal crisis), and hyper or hypothyroidism (fatigue, headache, mental status changes, abdominal pain, unusual bowel habits, hypotension). Unless other causes are determined, consider signs and symptoms as immune-mediated endocrinopathies. Withhold ipilimumab in symptomatic patients and initiate corticosteroids at 1–2 mg/kg/day of prednisone or equivalents. Initiate hormone replacement therapy as needed.
- Assess eyes for signs and symptoms of uveitis, iritis, or episcleritis. Administer corticosteroid eyedrops if these occur. Permanently discontinue ipilimumab for immune-mediated occular disease unresponsive to local immunosuppressive therapy.
- Lab Test Considerations: Monitor liver function tests (AST, ALT, bilirubin) prior to each dose of ipilimumab; ↑ frequency of monitoring if levels ↑. Withhold ipilimumab in patients with Grade 2 hepatotoxicity. With complete or partial resolution (Grade 0–1), and patient receiving <7.5 mg prednisone, resume at a dose of 3 mg/kg every 3 weeks until administration of all 4 planned doses or 16 weeks from first dose, whichever occurs earlier. Discontinue ipilimumab permanently with Grade 3–5 hepatotoxicity and administer systemic corticosteroids at a dose of 1 to 2 mg/kg/day of prednisone or equivalent. Initiate corticosteroid taper when liver function tests show sustained improvement or return to baseline; continue to taper over 1 mo.
- Monitor thyroid function tests and serum chemistries at start of therapy, before each dose, and as clinically indicated.
Potential Nursing DiagnosesImpaired skin integrity (Indications)
- Withhold dose for any moderate immune-mediated adverse reactions or for symptomatic endocrinopathy. For patients with complete or partial resolution of adverse reactions (Grade 0–1), who are receiving equivalents of <7.5 mg prednisone/day, resume isilimumab at a dose of 3 mg/kg every 3 wks until administration of all 4 planned doses or 16 wks from 1st dose, whichever occurs earlier.
- Permanently discontinue if persistent moderate adverse reactions or inability to reduce corticosteroid dose to equivalent of prednisone 7.5 mg/day, failure to complete full treatment course within 16 wks from infusion of 1st dose, or severe or life threatening adverse reactions occur including: Colitis with abdominal pain, fever, or peritoneal signs; ↑ in stool frequency of 7 or more over baseline, stool incontinence. Need for IV hydration for >24 hrs, GI hemorrhage and GI perforation; AST or ALT >5 times the upper limits of normal or total bilirubin >3 times the upper limit of normal; Stevens-Johnson syndome, toxic epidermal necrolysis, or rash complicated by full-thickness dermal ulceration, or necrotic, bullous, or hemorrhagic manifestations; Severe motor or sensory neuropathy, Guillian-Barre syndrome, or myasthenia gravis; Severe immune-mediated reactions involving any organ system (nephritis, pneumonitis, pancreatitis, non-infectious myocarditis); and Immune-mediated ocular disease that is unresponsive to topical immunosuppressive therapy.
- Allow vial to stand at room temperature for 5 min prior to preparation of infusion. Withdraw amount of ipilimumab required and transfer to IV bag. Diluent: Dilute with 0.9% NaCL or D5W.Concentration: 1 mg/mL to 2 mg/mL. Mix slowly by gentle inversion; do not shake. Solution is clear, pale yellow, and may contain translucent-to-white amorphous particles; do not administer if cloudy, discolored, or contains particulate matter. Store for up to 24 hr at room temperature or refrigerated; do not freeze, protect from light. Discard partially used vials.
- Rate: Infuse over 90 min through a sterile, non-pyrogenic, low-protein-binding in-line filter. Flush the IV line with 0.9% NaCl or D5W after each dose.
- Y-Site Incompatibility: Do not mix with or infuse with other solutions or products.
- Inform patient of the risk of immune-mediated reactions due to T-cell activation and proliferation. Advise patients these may be severe and fatal. Instruct patient to notify health care professional immediately if signs and symptoms occur.
- Instruct patient to read the Medication Guide before starting therapy and before each dose of ipilimumab.
- Advise female patients to notify health care professional if pregnancy is planned or suspected or if breast feeding. Contraception should be used throughout therapy. Women must choose to discontinue breast feeding or ipilimumab.
- ↓ spread of melanoma.