guselkumab (Rx)

>10%

Infections (23%)

Upper respiratory tract infections (14.3%)

1-10%

Headache (4.6%)

Injection site reactions (4.5%)

Arthralgia (2.7%)

Elevated liver enzymes (2.6%)

Diarrhea (1.6%)

Gastroenteritis (1.3%)

Tinea infections (1.1%)

Herpes simplex infections (1.1%)

Postmarketing Reports

Immune system disorders: Hypersensitivity, including anaphylaxis

Skin and subcutaneous tissue disorders: Rash

Contraindications

History of serious hypersensitivity reaction to guselkumab or to any of the excipients

Cautions

May increase infection risk; consider risks and benefits in patients with a chronic infection or history of recurrent infection; discontinue drug if patient develops serious infection or is not responding to therapy; treatment should not be initiated in patients with any clinically important active infection until infection resolves or is adequately treated

Serious hypersensitivity reactions, including anaphylaxis, reported with postmarket use; some cases required hospitalization; if a serious hypersensitivity reaction occurs, discontinue drug and initiate appropriate therapy

Do not initiate in patients with clinically important active infection until infection resolves or is adequately treated

Screen for tuberculosis (TB) before initiating treatment; initiate treatment for latent TB prior to administering guselkumab; monitor patients for signs and symptoms of active TB during and after treatment

Consider completion of all age-appropriate immunizations before initiating guselkumab; avoid live vaccines

Drug interaction overview

• Avoid use of live vaccines

• CYP450 substrates

  • The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (eg, interleukin [IL]-1, IL-6, IL-10, tumor necrosis factor-alpha, interferon) during chronic inflammation
  • Guselkumab may modulate serum levels of some cytokines
  • Therefore, upon initiating or discontinuing guselkumab in patients who are receiving concomitant drugs that are CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for effect (eg, for warfarin) or drug concentration (eg, for cyclosporine) and consider dosage modification of the CYP450 substrate

Pregnancy

There is a pregnancy registry that monitors pregnancy outcomes in women exposed to drug during pregnancy; encourage patients to enroll by calling 1-877-311- 8972

No available data on use in pregnant women to inform a drug-associated risk of adverse developmental outcomes

Human IgG antibodies are known to cross the placental barrier; therefore, guselkumab may be transmitted from the mother to the developing fetus

Animal studies

• In a combined embryofetal development and prenatal and postnatal development study, no adverse developmental effects were observed in infants born to pregnant monkeys after SC administration during organogenesis through parturition at doses up to 30 times the maximum recommended human dose (MRHD)
• Neonatal deaths were observed at 6-to 30-times the MRHD

Lactation

Unknown if distributed in human breast milk; maternal IgG is known to be present in human milk

Guselkumab was not detected in the milk of lactating cynomolgus monkeys

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Monoclonal antibody (IgG1-lambda) that inhibits IL-23 by selectively binding to p19 subunit of IL-23; IL-23 is a natural cytokine associated with inflammatory and immune responses; guselkumab inhibits the proinflammatory actions of IL-23, thereby decreasing cytokine and chemokine release

Absorption

Bioavailability: 49%

Peak plasma time (100-mg dose): 5.5 days

Peak plasma concentration: 8.09 mcg/mL

Distribution

Vd: 13.5 L

Metabolism

Exact pathway not characterized; expected to degrade into small peptides and amino acids via catabolic pathways similarly to endogenous IgG

Elimination

Half-life: 15-18 days

Total body clearance: 0.516 L/day

SC Preparation

Remove from refrigerator; allow syringe to reach room temperature (~30 min) before removing syringe cap

Preservative free; visually inspect syringe for any particulates or discoloration prior to administration

SC Administration

For SC use only; inject full amount (1 mL)

Do not inject areas where skin is tender, bruised, red, hard, thick, scaly, or affected by psoriasis

Discard unused drug and syringes in a puncture resistant container

Intended for use under physician supervision and guidance; administer SC by a healthcare professional or patient may self-inject after proper training

If dose was missed, inject as soon as possible, then adjust dosing schedule accordingly

Storage

Store refrigerated at 2-8°C (36-46°F)

Protect from light until use

Do not freeze