siltuximab

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: Used up in the binding process.

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

Time/Action Profile ⬆ ⬇

(blood levels)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	end of infusion	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Severe infections
OB: Pregnancy (↑ risk of infection in infants);
Lactation: Lactation.

Use Cautiously in:

End stage renal disease or severe hepatic impairment;
Pedi: Safety and effectiveness not established in children;
Geri: Older adults may be more sensitive to drug effects.

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema, hypotension

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

F and E: dehydration

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

GU: renal impairment

Hemat: thrombocytopenia

Metab: hyperuricemia, weight gain, ↑lipids

MS: musculoskeletal pain

Neuro: fatigue, headache

Misc: ↑risk of infection, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), infusion reactions

Interactions ⬆ ⬇

Drug-drug:

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

Route/Dosage ⬆ ⬇

IV (Adults ): 11 mg/kg every 3 wks.

Availability ⬆ ⬇

Lyophilized powder for injection : 100 mg/vial; 400 mg/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.

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: 20 mg/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
Rep: Caution females of reproductive potential to use effective contraception and to avoid breastfeeding during and for at least 3 mo following therapy.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇