Guselkumab is a subcutaneously administered interleukin 23 (IL-23) blocker approved for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy and is also approved for treating psoriatic arthritis (PsA). Compared to placebo, biologic drugs like guselkumab are able to achieve at least a 90% reduction from baseline in the PASI composite score (PASI 90) for induction therapy in patients with moderate to severe plaque psoriasis, and are more effective than traditional standard treatments. The ideal therapy for individual patients with plaque psoriasis is determined by treat to target strategies and severity of disease, including the presence or absence of psoriatic arthritis; guselkumab was not specifically evaluated regarding its place in PsA treatment due to ongoing investigation of this agent at the time of publication. As with other biologics that target interleukins, the drug may increase the risk for infections; all potential drug recipients should be evaluated for active or latent tuberculosis infection prior to initiating therapy.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable 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.
Subcutaneous Administration
-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.
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.
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.
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.
The possibility exists for guselkumab to affect host defenses against infection. During two 16-week, psoriasis clinical trials, infections were noted in 23% of guselkumab recipients and 21% of subjects in the placebo control group. Specific infections occurring in guselkumab treated patients included upper respiratory tract infections and pharyngitis (14.3%), viral gastroenteritis (1.3%), tinea infections (1.1%), herpes infections (1.1%), and Candida infections (candidiasis, less than 1%). All of the listed infections were mild to moderate and did not require treatment discontinuation. Serious infections occurred in up to 0.2% of subjects for both the guselkumab and placebo treatment groups. The safety profile of guselkumab was similar in patients enrolled in psoriatic arthritis trials with the exception of bronchitis and decreased neutrophil counts. Bronchitis was reported in 1.6%, 2.9%, and 1.1% of patients who received guselkumab every 8 weeks, guselkumab every 4 weeks, and placebo, respectively. Decreased neutrophil count was reported in 1.6% of patients on guselkumab every 4 weeks compared to 0.3% in patients on guselkumab every 8 weeks and in no patients on placebo. The majority of events of reduced neutrophil count were mild, transient, not associated with infection and did not lead to discontinuation. Instruct patients to seek medical advice if signs or symptoms of infection develop. Closely monitor patients who develop an infection while receiving treatment; drug discontinuation is recommended for patients who develop a serious infection. In addition, testing for latent tuberculosis (TB) is needed before treatment initiation. Start treatment for tuberculosis in patients with a positive test result for latent tuberculosis. Monitor all guselkumab recipients, regardless of latent TB test result, for signs and symptoms of active TB during and after treatment.
Diarrhea and gastroenteritis developed in 1.6% and 1.3%, respectively, of patients treated with guselkumab during clinical trials.
Adverse events reported by guselkumab recipients during clinical trials included headache (4.6%), arthralgia (2.7%), and migraine (less than 1%).
During clinical trials, urticaria occurred in more than 0.1% but less than 1% of patients treated with guselkumab in the psoriasis clinical studies and at a higher rate than with placebo. An injection site reaction (defined as localized erythema, bruising, hematoma, bleeding, swelling, edema, induration, inflammation, pain, skin discoloration, pruritus, and urticaria) developed in 4.5% of guselkumab recipients during clinical trials.
During clinical trials, elevated hepatic enzymes were observed in more patients receiving treatment with guselkumab (2.6%) than in patients receiving placebo (1.9%). Of the 21 guselkumab-treated patients who developed elevated hepatic enzymes, all events except 1 were mild to moderate in severity. None of the laboratory abnormalities required treatment discontinuation.
During a 52-week, psoriasis clinical trial, approximately 6% of drug recipients (n = 46) experienced antibody formation to guselkumab. Of the patients who developed antibodies, 7% were classified as neutralizing antibodies. Twenty-one of the 46 patients exhibited lower guselkumab trough concentrations, including 1 patient who experienced a loss of efficacy after developing high antibody titers. When the trial was extended to 156 weeks, approximately 9% of patients treated with guselkumab developed antibodies to the drug, with 6% being classified as neutralizing antibodies. However, these antidrug antibodies were generally not associated with changes in clinical response or development of injection site reactions. In a 24-week, psoriatic arthritis clinical study, 2% of drug recipients (n = 15) experienced antibody formation to guselkumab. Only 1 of these patients was classified as having neutralizing antibodies. Due to the small number of patients, definitive conclusions on the impact of antibody formation on guselkumab pharmacokinetics, efficacy, and safety can not be made.
Rash and other serious hypersensitivity reactions or anaphylaxis have been reported during postmarketing use of guselkumab. In some cases drug recipients required hospitalization. Due to the voluntary nature of postmarketing reports, neither a frequency nor definitive causal relationship can be established.
Guselkumab is contraindicated for use in patients with a history of serious hypersensitivity reaction to guselkumab or to any of the product excipients. Guselkumab has been associated with a risk of serious hypersensitivity reactions or anaphylaxis during postmarketing use. Some cases resulted in hospitalization. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and immediately discontinue use of the drug.
Guselkumab therapy may increase the risk of infection. In clinical trials, a higher rate of infections was reported with guselkumab when compared to placebo. Do not initiate guselkumab therapy in patients with any clinically significant active infection until the infection resolves or is adequately treated. Likewise, carefully consider the risks and benefits of administering the drug to patients with a chronic infection or a history of a recurrent infectious disease. Instruct patients to seek medical advice if signs or symptoms of an infection develop. If a severe infection develops or if an infection is not responding to standard therapy, discontinue guselkumab until the infection resolves. Upper respiratory tract infection, gastroenteritis, tinea fungal infection, and herpes simplex viral infection occurred more frequently in the guselkumab group than in the placebo group during clinical trials. The rate of serious infections for both groups was 0.2% or less.
Evaluate all potential recipients of guselkumab for tuberculosis infection before initiating treatment. Do not administer guselkumab to patients with active tuberculosis infection. For patients with latent tuberculosis, antituberculosis therapy should be administered before initiating guselkumab. Consider antituberculosis treatment for patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed. Monitor patients closely for signs and symptoms of active tuberculosis infection during and after treatment.
Avoid the use of live vaccines in patients treated with guselkumab. No data are available on the response to live or inactive vaccines. Consider completing all age appropriate immunizations before initiating treatment with guselkumab.
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; patients are encouraged to enroll in the registry by visiting www.mothertobaby.org/ongoing-study/tremfya-guselkumab, by calling 1-877-311-8972, or by emailing [email protected].
Use guselkumab with caution during breast-feeding until specific data or guideline recommendations are available. There are no data on the presence of guselkumab in human milk, the effects on the breast-fed infant, or the effects on milk production. Guselkumab was not detected in the milk of lactating cynomolgus monkeys. Due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk. Maternal IgG is known to be present in human milk. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for guselkumab and any potential adverse effects on the nursing infant from the drug or the underlying maternal condition.
The safety and efficacy of guselkumab have not been established in infants, children, or adolescents less than 18 years of age.
Before starting guselkumab therapy, test potential drug recipients for hepatitis B (surface antigen and core antibody), hepatitis C (IgG), and HIV serum status (HIV-1 and HIV-2 antibodies and HIV-1 antigen). Consider ongoing screening (e.g., annually) in people who are at increased risk for HIV, hepatitis B, or hepatitis C infection. Retest for HIV infection in any person who displays symptoms or other conditions that may suggest HIV seroconversion or infection. In patients found to be infected with HIV, consider involving relevant specialists to ensure HIV viral load is suppressed on antiretroviral therapy. Similarily, retest for viral hepatitis in any person who develops unexplained elevations in hepatic enzymes. It is recommended to consult a hepatologist when using a biological therapy in patients who are infected with hepatitis B or C, whether newly diagnosed or chronically infected.
Patients who undergo surgery while taking a biologic therapy, such as guselkumab, may be at higher risk for postoperative infections. In patients undergoing elective surgery, balance the risk of postoperative infection against the risk of developing a severe or unstable disease by stopping the biologic therapy. When possible, it is advised to stop the biologic therapy 3- to 5-times the half-live or the length of the treatment cycle (whichever is longer) between the last dose and the planned surgery. Restart the biologic therapy postoperatively if there is no evidence of infection and wound healing is satisfactory.
For the treatment of moderate to severe plaque psoriasis in persons who are candidates for systemic therapy or phototherapy:
Subcutaneous dosage:
Adults: 100 mg subcutaneously at weeks 0 and 4, and then 100 mg subcutaneously every 8 weeks.
For the treatment of active psoriatic arthritis:
Subcutaneous dosage:
Adults: 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.
Maximum Dosage Limits:
-Adults
100 mg/dose subcutaneously.
-Geriatric
100 mg/dose subcutaneously.
-Adolescents
Safety and efficacy not established.
-Children
Safety and efficacy not established.
-Infants
Safety and efficacy not established.
-Neonates
Safety and efficacy not established.
Patients with Hepatic Impairment Dosing
Specific data for patients with hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific data for patients with renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
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.
Chikungunya 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.
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.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
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.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (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.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (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.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (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.
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.
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.
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.
-Route-Specific Pharmacokinetics
Subcutaneous Route
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.
-Special Populations
Hepatic Impairment
No specific studies have been conducted to determine the effect of hepatic impairment on the pharmacokinetics of guselkumab.
Renal Impairment
No specific studies have been conducted to determine the effect of renal impairment on the pharmacokinetics of guselkumab.
Geriatric
No apparent differences in clearance were observed in geriatric subjects 65 years or older compared to younger adults, suggesting no dose adjustment is needed for elderly patients.
Obesity
Clearance and volume of distribution of guselkumab increases as body weight increases, however, observed clinical trial data indicate that dose adjustment for body weight is not needed.