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guselkumab
Classes
Antipsoriatic Monoclonal Antibodies and Others
Interleukin-23 (IL-23) Inhibitors
Administration
For subcutaneous use only. Do not inject intravenously or intramuscularly.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The solution should be colorless to slightly yellow and may contain a few small translucent particles. Do not use if discolored, cloudy, or if foreign particulate matter is present.
Only an individual trained in subcutaneous drug delivery should administer the injection. A patient who is appropriately trained in injection technique may self-inject if the prescriber deems the action appropriate. However, the first injection needs to be under the supervision of a qualified health care professional.
Refer to the manufacturer provided "Instructions for Use" for the specific injection product to be used.[62120]
Prior to injection:
Remove the prefilled syringe or One-Press patient-controlled injector from the refrigerator. Keep in the carton on a flat surface at room temperature for at least 30 minutes before use. Do not warm the syringe or injector any other way.
Check the expiration date on the carton. Do not use if the expiration date has passed or if the seal on the carton is broken.[62120]
Use of the pre-filled syringe:
Each single-use prefilled syringe contains 100 mg/mL of guselkumab.
Choose an injection site. Subcutaneous injection sites include the front part of the middle thigh (recommended), the abdominal region (except 2-inch area around the navel), or the outer area of the upper arm (if healthcare provider or another person will administer into the arm).
Rotate injection sites with each injection.
Do not administer where the skin is tender, bruised, red, hard, thick, scaly, or affected by psoriasis.
Clean the injection site.
Inspect the syringe. Do not use a damaged or dropped syringe.
Injection:
Pull off the needle cap. After the cap is off, the pre-filled syringe should be used within 5 minutes.
Use your hand to pinch the skin at the injection site. Position syringe at about a 45-degree angle to the skin.
Insert needle with a quick, dart-like motion. Release the pinched skin and place the free hand on the body of the prefilled syringe.
Press the plunger all the way down until it stops to inject the entire 1 mL contents of the pre-filled syringe.
Release the plunger. The safety guard will cover the needle and lock it into place, removing the needle from your skin.
Do not rub the injection site; slight bleeding may occur. If needed, cover with a bandage.
Disposal: Dispose of the used syringe properly in an FDA-cleared sharps disposal container right away after use. Do not re-use the syringe. No preservatives are present; discard any unused portion.[62120]
Use of the One-Press patient-controlled injector:
Each single-use One-Press injector contains 100 mg/mL of guselkumab.
Choose an injection site. Subcutaneous injection sites include the front part of the middle thigh (recommended), the abdominal region (except 2-inch area around the navel), or the outer area of the upper arm (if healthcare provider or another person will administer into the arm).
Rotate injection sites with each injection.
Do not administer where the skin is tender, bruised, red, hard, thick, scaly, or affected by psoriasis.
Clean the injection site with alcohol swab and allow it to dry.
Check the liquid in the viewing window of the One-Press injector. It should be clear to slightly yellow and may contain tiny white or clear particles. You may also see 1 or more air bubbles; this is normal.
Injection:
Pull off the bottom cap. A few drops of liquid may be visible; this is normal. The injection must be administered within 5 minutes of removing the cap.
Position the injector straight onto the skin (about a 90-degree angle to the injection site).
Push the handle all the way down until the teal body is not visible.
You may hear a 'click' when the injection begins. Keep pushing. If you feel resistance, keep pushing; this is normal. The medication injects as you push. Do this at a speed that is comfortable. Inject the entire contents of the One-Press injector. DO NOT lift the device during the injection, as this will lock the needle guard (showing a yellow band) and the full dose will not be delivered.
The injection is complete when the teal body is not visible, and you cannot press the handle anymore. You may hear a 'click'.
Lift the injector straight up off the skin. The yellow band will indicate that the needle guard is locked.
Do not rub the injection site; slight bleeding may occur. If needed, cover with a bandage.
Disposal: Dispose of the used One-Press injector properly in an FDA-cleared sharps disposal container right away after use. Do not re-use the One-Press injector. No preservatives are present; discard any unused portion.[62120]
Adverse Reactions
serious hypersensitivity reactions or anaphylaxis / Rapid / Incidence not known
antibody formation / Delayed / 2.0-9.0
elevated hepatic enzymes / Delayed / 2.6-2.6
candidiasis / Delayed / 0-1.0
migraine / Early / 0.1-1.0
hematoma / Early / Incidence not known
edema / Delayed / Incidence not known
bleeding / Early / Incidence not known
erythema / Early / Incidence not known
infection / Delayed / 23.0-23.0
pharyngitis / Delayed / 14.3-14.3
headache / Early / 4.6-4.6
injection site reaction / Rapid / 4.5-4.5
arthralgia / Delayed / 2.7-2.7
diarrhea / Early / 1.6-1.6
urticaria / Rapid / 0.1-1.0
pruritus / Rapid / Incidence not known
skin discoloration / Delayed / Incidence not known
rash / Early / Incidence not known
Common Brand Names
Tremfya
Dea Class
Rx
Description
Subcutaneous interleukin-23 (IL-23) blocker
Used to treat moderate-to-severe plaque psoriasis and psoriatic arthritis in adults
May increase the risk for infections; evaluate patients for tuberculosis before use
Dosage And Indications
100 mg subcutaneously at weeks 0 and 4, and then 100 mg subcutaneously every 8 weeks.
100 mg via subcutaneous injection at week 0, week 4, and then every 8 weeks after that. May give as monotherapy or concomitantly with conventional disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate.
Dosing Considerations
Specific data for patients with hepatic impairment are not available; it appears that no dosage adjustments are needed.
Specific data for patients with renal impairment are not available; it appears that no dosage adjustments are needed.
Drug Interactions
Abatacept: (Major) Concomitant use of abatacept with other biologic agents, such as guselkumab, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. There is insufficient experience to assess the safety and efficacy of abatacept administered concurrently with guselkumab.
Acetaminophen; Codeine: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as codeine. Monitor for altered patient response to codeine; codeine dosage adjustments may be needed. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Amitriptyline: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as tricyclic antidepressants (TCA). Monitor TCA concentrations if guselkumab is initiated or discontinued; the TCA dose may need to be adjusted. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Amoxapine: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as amoxapine. Monitor amoxapine concentrations if guselkumab is initiated or discontinued; the amoxapine dose may need to be adjusted. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as codeine. Monitor for altered patient response to codeine; codeine dosage adjustments may be needed. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Bacillus Calmette-Guerin Vaccine, BCG: (Major) Avoid use of live vaccines in patients being treated with guselkumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving guselkumab. In addition, guselkumab may decrease the vaccine-induced immune response. Before initiation of guselkumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as codeine. Monitor for altered patient response to codeine; codeine dosage adjustments may be needed. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as codeine. Monitor for altered patient response to codeine; codeine dosage adjustments may be needed. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Canakinumab: (Major) Avoid the concomitant use of canakinumab with other interleukin inhibitors, such as guselkumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Chlordiazepoxide; Amitriptyline: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as tricyclic antidepressants (TCA). Monitor TCA concentrations if guselkumab is initiated or discontinued; the TCA dose may need to be adjusted. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Chlorpheniramine; Codeine: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as codeine. Monitor for altered patient response to codeine; codeine dosage adjustments may be needed. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Clomipramine: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as tricyclic antidepressants (TCA). Monitor TCA concentrations if guselkumab is initiated or discontinued; the TCA dose may need to be adjusted. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Codeine: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as codeine. Monitor for altered patient response to codeine; codeine dosage adjustments may be needed. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Codeine; Guaifenesin: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as codeine. Monitor for altered patient response to codeine; codeine dosage adjustments may be needed. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as codeine. Monitor for altered patient response to codeine; codeine dosage adjustments may be needed. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Codeine; Phenylephrine; Promethazine: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as codeine. Monitor for altered patient response to codeine; codeine dosage adjustments may be needed. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Codeine; Promethazine: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as codeine. Monitor for altered patient response to codeine; codeine dosage adjustments may be needed. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Desipramine: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as tricyclic antidepressants (TCA). Monitor TCA concentrations if guselkumab is initiated or discontinued; the TCA dose may need to be adjusted. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Doxepin: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as tricyclic antidepressants (TCA). Monitor TCA concentrations if guselkumab is initiated or discontinued; the TCA dose may need to be adjusted. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Imipramine: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as tricyclic antidepressants (TCA). Monitor TCA concentrations if guselkumab is initiated or discontinued; the TCA dose may need to be adjusted. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Intranasal Influenza Vaccine: (Major) Avoid use of live vaccines in patients being treated with guselkumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving guselkumab. In addition, guselkumab may decrease the vaccine-induced immune response. Before initiation of guselkumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Live Vaccines: (Major) Avoid use of live vaccines in patients being treated with guselkumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving guselkumab. In addition, guselkumab may decrease the vaccine-induced immune response. Before initiation of guselkumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Maprotiline: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as maprotiline. Monitor maprotiline concentrations if guselkumab is initiated or discontinued; the maprotiline dose may need to be adjusted. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Avoid use of live vaccines in patients being treated with guselkumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving guselkumab. In addition, guselkumab may decrease the vaccine-induced immune response. Before initiation of guselkumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Measles/Mumps/Rubella Vaccines, MMR: (Major) Avoid use of live vaccines in patients being treated with guselkumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving guselkumab. In addition, guselkumab may decrease the vaccine-induced immune response. Before initiation of guselkumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Methadone: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as methadone. Monitor methadone concentrations if guselkumab is initiated or discontinued; the methadone dose may need to be adjusted. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Nortriptyline: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as tricyclic antidepressants (TCA). Monitor TCA concentrations if guselkumab is initiated or discontinued; the TCA dose may need to be adjusted. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and guselkumab is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and guselkumab may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If guselkumab is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and guselkumab is a moderate CYP2D6 inhibitor.
Paroxetine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with guselkumab is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and guselkumab is a moderate CYP2D6 inhibitor.
Perphenazine; Amitriptyline: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as tricyclic antidepressants (TCA). Monitor TCA concentrations if guselkumab is initiated or discontinued; the TCA dose may need to be adjusted. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Pimozide: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with CYP2D6 substrates that have a narrow therapeutic index, such as pimozide. Monitor pimozide concentrations if guselkumab is initiated or discontinued; pimozide dose adjustments may be needed. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Protriptyline: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as tricyclic antidepressants (TCA). Monitor TCA concentrations if guselkumab is initiated or discontinued; the TCA dose may need to be adjusted. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Rotavirus Vaccine: (Major) Avoid use of live vaccines in patients being treated with guselkumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving guselkumab. In addition, guselkumab may decrease the vaccine-induced immune response. Before initiation of guselkumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Major) Avoid use of live vaccines in patients being treated with guselkumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving guselkumab. In addition, guselkumab may decrease the vaccine-induced immune response. Before initiation of guselkumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Smallpox Vaccine, Vaccinia Vaccine: (Major) Avoid use of live vaccines in patients being treated with guselkumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving guselkumab. In addition, guselkumab may decrease the vaccine-induced immune response. Before initiation of guselkumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Thioridazine: (Moderate) Monitor for an altered patient response to thioridazine if coadministration with guselkumab is necessary. Guselkumab therapy may restore CYP450 activities to higher levels than pretreatment, leading to increased metabolism of CYP450 substrates as compared to metabolism prior to treatment. While some drug interaction studies determined guselkumab was not likely to promote such interactions, the effect on CYP2D6 was less certain and variable due to the low numbers of subjects studied. Therefore, CYP2D6 substrates with a narrow therapeutic index may have fluctuations in drug levels and therapeutic effect. Thioridazine is a CYP2D6 substrate and narrow therapeutic index drug.
Tricyclic antidepressants: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as tricyclic antidepressants (TCA). Monitor TCA concentrations if guselkumab is initiated or discontinued; the TCA dose may need to be adjusted. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Trimipramine: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as tricyclic antidepressants (TCA). Monitor TCA concentrations if guselkumab is initiated or discontinued; the TCA dose may need to be adjusted. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Typhoid Vaccine: (Major) Avoid use of live vaccines in patients being treated with guselkumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving guselkumab. In addition, guselkumab may decrease the vaccine-induced immune response. Before initiation of guselkumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Upadacitinib: (Major) Do not use upadacitinib in combination with biologic immunosuppressives, such as guselkumab, because of the possibility of increased immunosuppression and increased infection risk. Upadacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs. Most patients taking upadacitinib who developed serious infections were taking concomitant immunosuppressives such as methotrexate or corticosteroids.
Varicella-Zoster Virus Vaccine, Live: (Major) Avoid use of live vaccines in patients being treated with guselkumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving guselkumab. In addition, guselkumab may decrease the vaccine-induced immune response. Before initiation of guselkumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
Yellow Fever Vaccine, Live: (Major) Avoid use of live vaccines in patients being treated with guselkumab; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving guselkumab. In addition, guselkumab may decrease the vaccine-induced immune response. Before initiation of guselkumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines.
How Supplied
Tremfya Subcutaneous Inj Sol: 1mL, 100mg
Maximum Dosage
100 mg/dose subcutaneously.
100 mg/dose subcutaneously.
Safety and efficacy not established.
Safety and efficacy not established.
Safety and efficacy not established.
Safety and efficacy not established.
Mechanism Of Action
Guselkumab is a human IgG1 lambda monoclonal antibody that selectively binds to the p19 subunit of interleukin 23 (IL-23) cytokine, inhibiting its interaction with the IL-23 receptor. A naturally occurring cytokine, IL-23 is involved in normal inflammatory and immune responses. By inhibiting the interaction of IL-23 with its receptor, guselkumab blocks the release of proinflammatory cytokines and chemokines. In addition, guselkumab reduces serum concentrations of IL-17A, IL-17F, and IL-22 relative to pretreatment concentrations in patients with psoriasis. Serum concentrations of acute phase proteins C-reactive protein, serum amyloid A, and IL-6, and Th17 effector cytokines IL-17A, IL-17F, and IL-22 were reduced in psoriatic arthritis patients treated with guselkumab. The relationship between these pharmacodynamic markers and the mechanism by which guselkumab exerts its clinical effect is not fully understood.
Pharmacokinetics
Guselkumab is administered subcutaneously. The drug exhibits linear pharmacokinetics in both healthy subjects and patients with psoriasis. The apparent volume of distribution in patients with psoriasis is 13.5 L. Although the exact mechanism by which guselkumab is metabolized has not been studied, the drug is expected to be degraded into small peptides and amino acids by catabolic pathways in a similar manner as endogenous IgG. In patients with psoriasis, the rate of drug elimination is 0.516 L per day, resulting in a mean half-life of 15 to 18 days. The pharmacokinetics of guselkumab in patients with psoriatic arthritis are reported to be similar to those patients with plaque psoriasis.[62120]
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP2D6
The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNFalpha, interferon) during chronic inflammation. The administration of guselkumab may, in theory, normalize the formation of CYP450 enzymes, resulting in drug interactions. Data from drug-drug interaction studies involving patients with moderate-to-severe plaque psoriasis suggest guselkumab has a low potential for clinically relevant interactions with substrates of CYP3A4, CYP2C9, CYP2C19, and CYP1A2. However, the results were highly variable because of the limited number of subjects in the study. The potential for guselkumab interaction with substrates of drugs metabolized by CYP2D6 cannot be ruled out. Changes in exposure (AUC) of midazolam, S-warfarin, omeprazole, and caffeine after a single dose of guselkumab were not clinically relevant. For dextromethorphan (a CYP2D6 substrate), changes in exposure after guselkumab were not clinically relevant in 9 out of 10 subjects; however, a 2.9-fold change in dextromethorphan exposure (AUC) was observed in one individual. Upon initiation of guselkumab in patients who are receiving concomitant CYP450 substrates with a narrow therapeutic index, consider monitoring for changes in drug concentrations and therapeutic effect; consider dosage adjustment as needed.[62120]
The absolute bioavailability of guselkumab in healthy subjects following a single 100 mg subcutaneous injection is approximately 49%. In healthy subjects, a single 100 mg dose produces a mean maximum serum concentration of 8.09 +/- 3.68 mcg/mL approximately 5.5 days post dose. Approximate steady-state trough concentrations of 1.2 mcg/mL are observed in patients with plaque psoriasis or psoriatic arthritis following 100 mg doses at weeks 0, 4, and every 8 weeks thereafter.
Pregnancy And Lactation
Only administer guselkumab during pregnancy if the benefit justifies the potential risk to the fetus. There are no available data regarding guselkumab use during human pregnancy to inform a drug-associated risk of adverse developmental outcomes for the exposed infant. Human IgG antibodies are known to cross the placental barrier; therefore, guselkumab may be transmitted from the mother to the developing fetus. In a combined embryofetal development and pre-and postnatal development study, no adverse developmental effects were observed in infants born to pregnant cynomolgus monkeys after subcutaneous administration of guselkumab 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. No guselkumab-related effects on functional or immunological development were observed in the monkey infants from birth through 6 months of age. The applicability of these findings in relation to guselkumab exposure in human neonates and infants is not known, and no specific recommendations regarding vaccination timing for exposed neonates or infants are available at this time. Guidelines generally recommend avoidance of biologic use during pregnancy when possible until more data are available from the manufacturer for the specific drug, the pregnancy registry, or from updated guidelines. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to guselkumab; information about the registry can be obtained at mothertobaby.org/ongoing-study/tremfya or by calling 1-877-311-8972.