siltuximab

General

Pronunciation:
sil-tux-i-mab


Trade Name(s)

  • Sylvant

Ther. Class.
orphan drugs

Pharm. Class.
interleukin antagonists

Indications

Treatment of multicentric Castleman's disease (MCD) patients who are negative for HIV and human herpesvirus-8 (HHV-8).

Action

Binds to interleukin-6 (IL-6) preventing binding to IL-6 receptors. MCD is associated with overproducton of IL-6.

Therapeutic Effect(s):

Decreased tumor load and manifesations of MCD including infections, fevers, weight loss, fatigue and night sweats.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Unk

Metabolism and Excretion: Used up in the binding process.

Half-life: 20.6 days (range 14.2–29.7 days)

TIME/ACTION PROFILE (blood levels)

ROUTEONSETPEAKDURATION
IVunkend of infusionunk

Contraindication/Precautions

Contraindicated in:

  • Hypersensitvity
  • Severe infections
  • OB: Pregnancy should be avoided (contraception required during and for three mos following siltuximab)
  • Lactation: Discontinue siltuximab or discontinue breastfeeding.

Use Cautiously in:

  • End stage renal disease or severe hepatic impairment
  • Geri: Elderly patients may be more sensitive to drug effects;
  • Pedi: Safe and effective use in children has not been established.

Adverse Reactions/Side Effects

CNS: fatigue, headache

CV: edema, hypotension

GI: GI PERFORATION, abdominal pain/distention, diarrhea, ↓ appetite, constipation, oropharyngeal pain

GU: renal impairment

Derm: pruritus, rash, dry skin, eczema, psoriasis, skin hyperpigmentation

F and E: dehydration

Hemat: thrombocytopenia

Metabolic: hyperuricemia, ↑ lipids, weight gain

MS: musculoskeletal pain

Misc: infusion-related reactions including anaphylaxis, severe allergic reactions and cytokine release syndromes, ↑ risk of infection

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  • May ↓ immune response to live vaccines (avoid administration)
  • May restore function of CYP450 enzyme and ↑ metabolism of drugs that are substrates of CYP450s (including CYP3A4) especially those with narrow therapeutic indeces including atorvastatin, cyclosprorine, hormonal contraceptives, lovastatin, theophylline and warfarin; careful monitoring is recommended during and for several wk after treament with siltuximab.

Route/Dosage

IV:(Adults)11 mg/kg every three wks.

Availability

Lyophilized powder for intravenous infusion (requires reconstitution/dilution: 100 mg single-use vial, 400 mg single-use vial

Assessment

  • Assess for signs of infection (fever, dyspnea, flu-like symptoms, frequent or painful urination, redness or swelling at the site of a wound), prior to injection. Siltuximab is contraindicated in patients with active infection. New infections should be monitored closely. Signs and symptoms of inflammation (fever) may be lessened due to suppression from siltuximab. Infections may be fatal, especially in patients taking immunosuppressive therapy. If patient develops a serious infection, discontinue siltuximab until infection is controlled
  • Monitor patient for signs of anaphylaxis (urticaria, dyspnea, facial edema) during and following infusion. Medications (antihistamines, corticosteroids, epinephrine) and equipment should be readily available in the event of a severe reaction. Discontinue siltuximab immediately if anaphylaxis or other severe allergic reaction occurs.
  • Monitor for signs and symptoms of infusion reactions (back pain, chest pain or discomfort, nausea, vomiting, flushing, erythema, palpitations) during infusion. May premedicate with antihistamine, acetaminophen, and corticosteroids. Discontinue siltuximab permanently if infusion is not tolerated after premedication.

Lab Test Considerations:

Monitor absolute neutrophil count (ANC), platelet count, and hemoglobin prior to each dose for first 12 doses and every 3 dosing cycles thereafter. Do not administer unless ANC ≥1.0 x 109/L, platelet count ≥75 x 109/L, and <17 g/dL. If criteria are not met, delay dose until ANC ≥1.0 x 109/L, platelet count 50 x 109/L, and <17 g/dL. Do not reduce dose.

Potential Diagnoses

Implementation

IV Administration

  • Intermittent Infusion: Allow vial to come to room temperature for 30 min before preparing infusion and remain at room temperature during preparation. For 100 mg vial reconstitute with 5.2 mL and 400 mg vial with 20 mL Sterile Water for Injection. Concentration: 20mg/mL.Gently swirl until all powder dissolved; do not shake. Particles should dissolve within 60 min. Do not administer solutions that are discolored or contain particulate matter. Reconstituted solution must be diluted within 2 hrs. Diluent:Using a 21–gauge 1 1/2 inch needle, inject reconstituted solution slowly into 250 mL bag of D5W. Bag must be made of Polyvinyl chloride (PVC) with Di-{2-ethylhexyl}phthalate (DEHP), or Polyolefin (PO). Invert gently to mix. Discard unused portion.
  • Rate:Infuse over 1 hr using administration set lined with polyvinyl chloride (PVC) with di-{2-ethylhexyl}phthalate (DEHP) or polyurethane (PU), containing a 0.2­ micron inline polyethersulfone (PES) filter. Infusion must be completed within 4 hrs.
  • Y-Site Incompatibility: Do not administer in same line with other solutions or medications.

Patient/Family Teaching

  • Explain purpose of siltuximab to patient. Advise patient to read Patient Information prior to starting therapy and before each infusion in case of changes.
  • Advise patient to notify health care professional at risk for GI perforation (have or have had any stomach or bowel (intestine) problems, such as diverticulitis or ulcers) or if pain in stomach area occurs.
  • Advise patient to notify health care professional if signs and symptoms of infection or allergic reactions (difficulty breathing, chest tightness, wheezing, severe dizziness or light-headedness, swelling of the lips or skin rash) occur.
  • Advise patient to avoid receiving live vaccines during therapy.
  • Advise patient to consult health care professional before taking other Rx or OTC medications, vitamins, or herbal products
  • Caution female patients to use effective contraception during and for at least 3 mo following therapy. Advise patient to avoid breastfeeding during therapy.

Evaluation/Desired Outcomes

Decreased tumor load and manifestations of MCD including infections, fevers, weight loss, fatigue and night sweats.

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