Dupixent (dupilumab)

No dosing information is available for this tab.

Administer dupilumab by subcutaneous injection using the pre-filled syringe or pre-filled pen. The pre-filled pen formulation is indicated for use only in adults and pediatric patients >=2 years of age. The pre-filled syringe formulation is indicated for use in adults and pediatric patients >=6 months of age. Although dupilumab is intended for use under the guidance of a clinician, a caregiver or patient >=12 years of age may administer dupilumab using the prefilled syringe or pen after appropriate training on subcutaneous injection technique is provided. In pediatric patients >=12 years of age, dupilumab should be administered under adult supervision. Self-administration in pediatric patients ages 6 months to <12 years of age is not recommended and dupilumab pre-filled syringe should be administered by a caregiver in this population.

Administer subcutaneous injections of dupilumab into the thigh or abdomen (except within 2 inches of the navel). The upper arm may also be an appropriate site if a caregiver administers the injection. Rotate injection sites for all subsequent doses. Do not inject into areas where the skin is tender, damaged, bruised, or scarred.

Dupilumab is supplied in single-dose pre-filled syringes and single-dose pre-filled pens containing either 300 mg/2 mL or 200 mg/1.14 mL of the drug. Refrigerate the pre-filled syringes and pens at 2-8degreesC in their original carton to protect from light; do not freeze or shake the injection. If necessary, the pre-filled syringes and pens may be kept at room temperature up to 25degreesC for a maximum of 14 days; after removal from the refrigerator, use the pre-filled syringes and pens within 14 days or discard them.

Remove the appropriate number of pre-filled syringes or pre-filled pens from refrigeration and allow the drug to reach room temperature for 30 minutes (for the 200 mg/1.14 mL syringes or pens) or 45 minutes (for the 300 mg/2 mL syringes or pens) prior to injection. Do not remove the needle cap while warming to room temperature and do not expose the drug to heat or direct sunlight. Prior to administration, inspect the solution and do not use if particulates, discoloration, or cloudiness is observed. After administration, discard any unused product remaining in the pre-filled syringe or pen.

If a weekly dose of dupilumab is missed, administer the dose as soon as possible, and initiate a new weekly schedule from the date of the last administered dose. If an every 2 week dose is missed, administer the dose within 7 days of the missed dose and then resume the original schedule. If the missed dose is not administered within 7 days, administer the dose, initiating a new schedule based on this date. If an every 4 week dose is missed, administer the dose within 7 days from the missed dose and then resume the original schedule. If the missed dose is not administered within 7 days, administer the dose, initiating a new schedule based on this date.

Consult the manufacturer's prescribing information for additional information on preparation and administration requirements.

No dosing information is available for this tab.

An effect of dupilumab on pharmacokinetic properties of co-administered medications is not expected. Common co-administered medications had no effect on dupilumab pharmacokinetics in patients with moderate to severe asthma when population analyses were conducted.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Selected Immunosuppressive Agents/Live Vaccines; Live Bcg

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: A variety of disease modifying agents suppress the immune system. Immunocompromised patients may be at increased risk for uninhibited replication after administration of live, attenuated vaccines or intravesicular BCG. Immune response to vaccines may be decreased during periods of immunocompromise.(1)

CLINICAL EFFECTS: The expected serum antibody response may not be obtained and/or the vaccine may result in illness.(1) After instillation of intravesicular BCG, immunosuppression may interfere with local immune response, or increase the severity of mycobacterial infection following inadvertent systemic exposure.(2)

PREDISPOSING FACTORS: Immunosuppressive diseases (e.g. hematologic malignancies, HIV disease), treatments (e.g. radiation) and drugs may all increase the magnitude of immunodeficiency.

PATIENT MANAGEMENT: The Centers for Disease Control(CDC) Advisory Committee on Immunization Practices (ACIP) states that live-virus and live, attenuated vaccines should not be administered to patients who are immunocompromised. The magnitude of immunocompromise and associated risks should be determined by a physician.(1) For patients scheduled to receive chemotherapy, vaccination should ideally precede the initiation of chemotherapy by 14 days. Patients vaccinated while on immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated at least 3 months after discontinuation of therapy.(1) Patients who receive anti-B cell therapies should not receive live vaccines for at least 6 months after such therapies due to a prolonged duration of immunosuppression. An exception is the Zoster vaccine, which can be given at least 1 month after receipt of anti-B cell therapies.(1) The US manufacturer of abatacept states live vaccines should not be given during or for up to 3 months after discontinuation of abatacept.(2) The US manufacturer of live BCG for intravesicular treatment of bladder cancer states use is contraindicated in immunosuppressed patients.(3) The US manufacturer of daclizumab states live vaccines are not recommended during and for up to 4 months after discontinuation of treatment.(4) The US manufacturer of guselkumab states that live vaccines should be avoided during treatment with guselkumab.(5) The US manufacturer of inebilizumab-cdon states that live vaccines are not recommended during treatment and after discontinuation until B-cell repletion. Administer all live vaccinations at least 4 weeks prior to initiation of inebilizumab-cdon.(6) The US manufacturer of ocrelizumab states that live vaccines are not recommended during treatment and until B-cell repletion occurs after discontinuation of therapy. Administer all live vaccines at least 4 weeks prior to initiation of ocrelizumab.(7) The US manufacturer of ozanimod states that live vaccines should be avoided during and for up to 3 months after discontinuation of ozanimod.(8) The US manufacturer of siponimod states that live vaccines are not recommended during treatment and for up to 4 weeks after discontinuation of treatment.(9) The US manufacturer of ustekinumab states BCG vaccines should not be given in the year prior to, during, or the year after ustekinumab therapy.(10) The US manufacturer of satralizumab-mwge states that live vaccines are not recommended during treatment and should be administered at least four weeks prior to initiation of satralizumab-mwge.(11) The US manufacturer of ublituximab-xiiy states that live vaccines are not recommended during treatment and until B-cell recovery. Live vaccines should be administered at least 4 weeks prior to initiation of ublituximab-xiiy.(12) The US manufacturer of etrasimod states that live vaccines should be avoided during and for 5 weeks after treatment. Live vaccines should be administered at least 4 weeks prior to initiation of etrasimod.(13) The US manufacturer of emapalumab-lzsg states that live vaccines should not be administered to patients receiving emapalumab-lzsg and for at least 4 weeks after the last dose of emapalumab-lzsg. The safety of immunization with live vaccines during or following emapalumab-lzsg therapy has not been studied.(14) The US manufacturer of sibeprenlimab-szsi states live vaccines should not be given within 30 days prior to initiation or during treatment with sibeprenlimab-szsi.(15)

DISCUSSION: Killed or inactivated vaccines do not pose a danger to immunocompromised patients.(1) Patients with a history of leukemia who are in remission and have not received chemotherapy for at least 3 months are not considered to be immunocompromised.(1)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Igg Antibodies And Derivatives/Efgartigimod-Alfa

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod-alfa may decrease concentrations of compounds that bind to the human FcRn.(3)

Igg Antibodies And Derivatives/Nipocalimab-Aahu

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Nipocalimab-aahu binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of nipocalimab-aahu states that nipocalimab-aahu should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, nipocalimab-aahu should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with nipocalimab-aahu have not been performed. Nipocalimab-aahu may decrease concentrations of compounds that bind to the human FcRn.(3)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Igg Antibodies And Derivatives/Rozanolixizumab-Noli

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3)

DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3)

Selected Weak Cyp2d6 Inhibitors/Tamoxifen

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Inhibitors of CYP2D6 may inhibit the conversion of tamoxifen to endoxifen (an active metabolite of tamoxifen).(1-2) The role of endoxifen in tamoxifen's efficacy has been debated and may involve a minimum concentration level.(3-5)

CLINICAL EFFECTS: Concurrent use of inhibitors of CYP2D6 may decrease the effectiveness of tamoxifen in preventing breast cancer recurrence.

PREDISPOSING FACTORS: Concurrent use of weak CYP2D6 inhibitors in patients who are CYP2D6 intermediate metabolizers should be avoided. Patients who are CYP2D6 poor metabolizers lack CYP2D6 function and are not affected by CYP2D6 inhibition.

PATIENT MANAGEMENT: Although data on this interaction are conflicting, it may be prudent to use alternatives to CYP2D6 inhibitors when possible in patients taking tamoxifen. The US manufacturer of tamoxifen states that the impact on the efficacy of tamoxifen by strong CYP2D6 inhibitors is uncertain and makes no recommendation regarding coadministration with inhibitors of CYP2D6.(12) The manufacturer of paroxetine (a strong CYP2D6 inhibitor) states that alternative agents with little or no CYP2D6 inhibition should be considered.(13) The National Comprehensive Cancer Network's breast cancer guidelines advises caution when coadministering strong CYP2D6 inhibitors with tamoxifen.(14) NCCN states when prescribing a selective serotonin reuptake inhibitor (SSRI), it is reasonable to avoid SSRIs that are strong and moderate CYP2D6 inhibitors, particularly fluoxetine and paroxetine, if an appropriate alternative exists.(14) Cancer Care Ontario breast cancer guidelines state concurrent use of weak CYP2D6 inhibitors should be closely monitored.(15) The European Society of Medical Oncology (ESMO) clinical practice guidelines for early breast cancer states patients on tamoxifen should be advised to avoid concurrent use of strong and moderate CYP2D6 inhibitors. Consider alternatives to tamoxifen if CYP2D6 inhibitors cannot be replaced with alternative agents.(16) If concurrent therapy is warranted, the risks versus benefits should be discussed with the patient.

DISCUSSION: Some studies have suggested that administration of fluoxetine, paroxetine, and quinidine with tamoxifen or a CYP2D6 poor metabolizer phenotype may result in a decrease in the formation of endoxifen (an active metabolite of tamoxifen) and a shorter time to breast cancer recurrence.(1-2,9) A retrospective study of 630 breast cancer patients found an increasing risk of breast cancer mortality with increasing durations of coadministration of tamoxifen and paroxetine. In the adjusted analysis, absolute increases of 25%, 50%, and 75% in the proportion of time of overlapping use of tamoxifen with paroxetine was associated with 24%, 54%, and 91% increase in the risk of death from breast cancer, respectively.(18) The CYP2D6 genotype of the patient may have a role in the effects of this interaction. Patients with wild-type CYP2D6 genotype may be affected to a greater extent by this interaction. Patients with a variant CYP2D6 genotype may have lower baseline levels of endoxifen and may be affected to a lesser extent by this interaction.(6-10) In a retrospective review, 1,325 patients treated with tamoxifen for breast cancer were classified as being poor 2D6 metabolizers (lacking functional CYP2D6 enzymes), intermediate metabolizers (heterozygous alleles), or extensive metabolizers (possessing 2 functional alleles). After a mean follow-up period of 6.3 years, the recurrence rates were 14.9%, 20.9%, and 29.0%, in extensive metabolizers, intermediate metabolizers, and poor metabolizers, respectively.(11) In October of 2006, the Advisory Committee Pharmaceutical Science, Clinical Pharmacology Subcommittee of the US Food and Drug Administration recommended that the US tamoxifen labeling be updated to include information about the increased risk of breast cancer recurrence in poor CYP2D6 metabolizers (either by genotype or drug interaction).(19-20) The labeling changes were never made due to ongoing uncertainty about the effects of CYP2D6 genotypes on tamoxifen efficacy. In contrast to the above information, two studies have shown no relationship between CYP2D6 genotype and breast cancer outcome.(21-23) As well, a number of studies found no association between use of CYP2D6 inhibitors and/or antidepressants in patients on tamoxifen and breast cancer recurrence,(24-28) though the studies were limited by problematic selection of CYP2D6 inhibitors and short follow-up. Weak inhibitors of CYP2D6 include: alogliptin, artesunate, celecoxib, chloroquine, cimetidine, clobazam, clomipramine, cobicistat, delavirdine, diltiazem, dimenhydrinate, diphenhydramine, dronabinol, dupilumab, echinacea, enasidenib, fedratinib, felodipine, fluvoxamine, gefitinib, hydralazine, imatinib, labetalol, lorcaserin, nicardipine, osilodrostat, ranitidine, ritonavir, sarpogrelate, sertraline, verapamil and viloxazine.(29)

Weak Cyp2d6 Inhibitors/Eliglustat

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Weak inhibitors of CYP2D6 may inhibit the metabolism of eliglustat. If the patient is also taking an inhibitor of CYP3A4, eliglustat metabolism can be further inhibited.(1)

CLINICAL EFFECTS: Concurrent use of an agent that is a weak inhibitor of CYP2D6 may result in elevated levels of and clinical effects of eliglustat, including prolongation of the PR, QTc, and/or QRS intervals, which may result in life-threatening cardiac arrhythmias.(1)

PREDISPOSING FACTORS: If the patient is also taking an inhibitor of CYP3A4 and/or has hepatic impairment, eliglustat metabolism can be further inhibited.(1) The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2)

PATIENT MANAGEMENT: The dosage of eliglustat with weak inhibitors of CYP2D6 in poor CYP2D6 metabolizers should be limited to 84 mg daily.(1) The dosage of eliglustat with weak inhibitors of CYP2D6 in extensive CYP2D6 metabolizers with mild (Child-Pugh Class A) hepatic impairment should be limited to 84 mg daily.(1) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting.

DISCUSSION: Paroxetine (30 mg daily), a strong inhibitor of CYP2D6, increased eliglustat (84 mg BID) maximum concentration (Cmax) and area-under-curve (AUC) by 7-fold and 8.4-fold, respectively, in extensive metabolizers. Physiologically-based pharmacokinetic (PKPB) models suggested paroxetine would increase eliglustat Cmax and AUC by 2.1-fold and 2.3-fold, respectively, in intermediate metabolizers. PKPB models suggested ketoconazole may increase the Cmax and AUC of eliglustat (84 mg daily) by 4.3-fold and 6.2-fold, respectively, in poor metabolizers.(1) PKPB models suggested terbinafine, a moderate inhibitor of CYP2D6, would increase eliglustat Cmax and AUC by 3.8-fold and 4.5-fold, respectively, in extensive metabolizers and by 1.6-fold and 1.6-fold, respectively in intermediate metabolizers. PKPB models suggest that concurrent eliglustat (84 mg BID), paroxetine (a strong inhibitor of CYP2D6), and ketoconazole would increase eliglustat Cmax and AUC by 16.7-fold and 24.2-fold, respectively, in extensive metabolizers. In intermediate metabolizers, eliglustat Cmax and AUC would be expected to increase 7.5-fold and 9.8-fold, respectively.(1) PKPB models suggest that concurrent eliglustat (84 mg BID), terbinafine (a moderate inhibitor of CYP2D6), and ketoconazole would increase eliglustat Cmax and AUC by 10.2-fold and 13.6-fold, respectively, in extensive metabolizers. In intermediate metabolizers, eliglustat Cmax and AUC would be expected to increase 4.2-fold and 5-fold, respectively.(1) A single dose of rolapitant increased dextromethorphan, a CYP2D6 substrate, about 3-fold on days 8 and day 22 following administration. Dextromethorphan levels remained elevated by 2.3-fold on day 28 after single dose rolapitant. The inhibitory effects of rolapitant on CYP2D6 are expected to persist beyond 28 days.(5) Weak inhibitors of CYP2D6 include: alogliptin, artesunate, celecoxib, chloroquine, chlorpromazine, clobazam, clomipramine, desvenlafaxine, dimenhydrinate, diphenhydramine, dronabinol, dupilumab, echinacea, enasidenib, felodipine, gefitinib, hydralazine, hydroxychloroquine, lorcaserin, methadone, panobinostat, propafenone, sarpogrelate, sertraline, vemurafenib, and venlafaxine.(3,4)

*Known hypersensitivity to the drug or any ingredient in the formulation.

There are no contraindication contraindications for this drug.

• Parasitic infection

• Arthralgia
• Blepharitis
• Blepharoptosis
• Conjunctivitis
• Dry eye
• Keratitis
• Nasolacrimal duct stenosis

Adverse effects reported in >=1% of patients receiving dupilumab in clinical studies for atopic dermatitis include injection site reactions, ocular effects (conjunctivitis, blepharitis, keratitis, pruritus, dry eye), eosinophilia, and herpes simplex virus infection.

Adverse effects reported in >=1% of patients receiving dupilumab in clinical studies for asthma include injection site reactions, oropharyngeal pain, and eosinophilia.

Adverse effects reported in >=1% of patients receiving dupilumab in clinical studies for CRSwNP include injection site reactions, eosinophilia, insomnia, toothache, gastritis, arthralgia, and conjunctivitis.

Adverse effects reported in >=2% of patients receiving dupilumab in clinical studies for eosinophilic esophagitis include injection site reactions, upper respiratory tract infections, arthralgia, and herpes viral infections.

Adverse effects reported in >=2% of patients receiving dupilumab in clinical studies for prurigo nodularis include nasopharyngitis, conjunctivitis, herpes infection, dizziness, myalgia, and diarrhea.

Adverse effects reported in >=2% of patients receiving dupilumab in clinical studies for COPD include viral infection, headache, nasopharyngitis, back pain, diarrhea, arthralgia, urinary tract infection, local administration reactions, rhinitis, eosinophilia, toothache, and gastritis.

Adverse effects reported in >=2% of patients receiving dupilumab in clinical studies for chronic spontaneous urticaria include injection site reactions.

Adverse effects reported in >=2% of patients receiving dupilumab in clinical studies for bullous pemphigoid include arthralgia, conjunctivitis, blurred vision, herpes viral infections, and keratitis.

Adverse effects reported in patients receiving dupilumab in clinical studies for allergic fungal rhinosinusitis were similar to those seen in patients with chronic rhinosinusitis with nasal polyps.

Rare or Very Rare

• Acquired symblepharon
• Acute myocardial infarction
• Anaphylaxis
• Angioedema
• Ascariasis
• Cerebrovascular accident
• Corneal ulcer
• Enterobiasis
• Eosinophilic granulomatosis with polyangiitis
• Eosinophilic pneumonia
• Erythema nodosum
• Psoriasis
• Psoriatic arthritis
• Serum sickness
• Urticaria
• Vasculitis
• Vision impairment

More Frequent

• Conjunctivitis
• Eosinophilia
• Herpes simplex infection
• Injection site sequelae
• Pain in oropharynx

Less Frequent

• Arthralgia
• Blepharitis
• Diarrhea
• Dizziness
• Dry eye
• Gastritis
• Insomnia
• Keratitis
• Myalgia
• Ocular itching
• Pharyngitis
• Toothache
• Upper respiratory infection

Rare or Very Rare

• Allergic conjunctivitis
• Ectropion
• Edema
• Erythema
• Facial edema
• Flushing
• Gait abnormality
• Nasolacrimal duct stenosis
• Pruritus of skin
• Skin rash
• Skin scaling
• Stinging of skin

No enhanced messaging available.

Atopic Dermatitis: Safety and efficacy of dupilumab have been established in pediatric patients >=6 months of age with moderate to severe atopic dermatitis. Use of dupilumab in this age group is supported by various clinical trials; one included 251 adolescents 12-17 years of age with moderate to severe atopic dermatitis, another included 367 children 6-11 years of age with severe atopic dermatitis, and another included 162 children 6 months to 5 years of age with moderate-to-severe atopic dermatitis. Safety and effectiveness were comparable between pediatric and adult patients in these studies. An open-label extension study included 275 adolescents 12-17 years of age, 368 children 6-11 years of age, and 180 children 6 months to 5 years of age with atopic dermatitis; no new safety signals were identified. Safety and efficacy in pediatric patients younger than 6 months of age with atopic dermatitis have not been established.

Asthma: Safety and efficacy of dupilumab as an add-on maintenance therapy in patients with moderate to severe asthma characterized by an eosinophilic phenotype or with oral corticosteroid dependent asthma have been established in pediatric patients >=6 years of age. A total of 107 adolescents ages 12-17 years old with moderate to severe asthma were included in asthma clinical trials and received either 200 mg or 300 mg dupilumab every 2 weeks. For both doses tested, improvements in FEV1 were observed. With the 200 mg biweekly dose, patients had a reduction in the rate of severe exacerbations similar to adults. Dupilumab exposure was higher in adolescent patients than adults at respective dose levels, mainly accounted for by differences in body weight. The adverse profile in adolescents was comparable to adults. A total of 408 pediatric patients ages 6-11 years old with moderate to severe asthma were included in asthma clinical trials and received either 100 mg or 200 mg dupilumab every 2 weeks. Improvements in lung function and asthma exacerbations were demonstrated. Effectiveness of dupilumab 300 mg every 4 weeks in this patient population with a body weight 15 to <30 kg was extrapolated from the efficacy of 100 mg dupilumab biweekly in clinical trials, with support from population pharmacokinetic analyses demonstrating higher drug exposure levels with a dosage of 300 mg every 4 weeks. Eighteen patients (15 to <30 kg) out of 365 pediatric patients were exposed to dupilumab 300 mg every 4 weeks in the open-label extension study, and the safety profile in these 18 patients was consistent with what was seen in previous clinical trials. Safety and efficacy in pediatric patients <6 years of age with asthma have not been established.

CRSwNP: Safety and efficacy have been established in pediatric patients >=12 years of age. Use of dupilumab in this age group is supported by evidence from well-controlled studies in adults, pharmacokinetic data from adult and pediatric patients >=12 years of age with moderate-to-severe asthma and adults with inadequately controlled CRSwNP, and safety data in pediatric patients >=12 years of age with moderate-to-severe asthma. Safety and efficacy in pediatric patients <12 years of age have not been established.

Eosinophilic esophagitis: Safety and efficacy have been established in pediatric patients >=1 year of age, weighing at least 15 kg, for the treatment of eosinophilic esophagitis. Support for use of dupilumab in this age group include results from a well-controlled study involving adults and 72 pediatric patients (12 to 17 years of age), a study involving 61 pediatric patients (1 to 11 years of age), and pharmacokinetic data. Safety and efficacy in pediatric patients <1 year of age or weighing <15 kg have not been established.

Prurigo nodularis: Safety and efficacy in pediatric patients have not been established.

COPD: Safety and efficacy in pediatric patients have not been established.

Chronic spontaneous urticaria: Safety and efficacy have been established in pediatric patients >=2 years of age. Support for use of dupilumab in this age group include results from 2 well-controlled studies in adults and pediatric patients >=12 years of age, pharmacokinetic data involving 6 pediatric patients (12-17 years of age), pharmacokinetic data in 18 pediatric patients (2-11 years of age), and safety data from pediatric patients with other indications. Safety and efficacy in pediatric patients <2 years of age and/or weighing <15 kg have not been established.

Bullous pemphigoid: Safety and efficacy in pediatric patients have not been established.

Allergic Fungal Rhinosinusitis: Safety and efficacy have been established in pediatric patients >=6 years of age. Support for use of dupilumab in this age group include results from a well-controlled study in adults and pediatric patients >=12 years of age, pharmacokinetic data involving 3 pediatric patients (>=12 years of age) with allergic fungal rhinosinusitis, pharmacokinetic and safety data in pediatric patients 6-11 years of age in other indications. Safety and efficacy in pediatric patients <6 years of age have not been established.

A pregnancy exposure registry that monitors outcomes in women exposed to dupilumab during pregnancy has been established.

Data from case reports and case series have not identified any drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Because human immunoglobulin G (IgG) is known to cross the placenta, the potential exists for fetal exposure to dupilumab. There are known adverse effects on maternal and fetal outcomes associated with untreated or poorly controlled asthma during pregnancy, including increased risk of preeclampsia, low birth weight, and small for gestational age in the neonate.

There was no evidence of embryofetal toxicity or malformations and no adverse effects on morphologic, functional, or immunologic development of offspring in a study in cynomolgus monkeys given a homologous antibody against the IL-4 receptor alpha subunit (IL-4Ralpha) subcutaneously once weekly during organogenesis through parturition at doses up to 10 times the maximum recommended human dose of subcutaneous dupilumab.

It is not known whether dupilumab is distributed into human milk, affects milk production, or affects breast-fed infants.

Human IgG is known to be distributed into human milk.

The benefits of breast-feeding and the importance of dupilumab to the woman should be considered along with potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

The manufacturer makes no specific dosage recommendations for geriatric patients.

Of the 1539 patients with atopic dermatitis who received dupilumab in clinical trials, 70 were 65 years of age or older. Although no overall differences in safety or efficacy were observed between geriatric patients and younger adults, the number of individuals 65 years of age and older in these clinical trials is insufficient to determine whether geriatric patients respond differently than younger adults.

Of the 1977 patients with asthma who received dupilumab in clinical trials, 240 were >=65 years of age. Of the 440 patients with CRSwNP who received dupilumab in clinical trials, 79 patients were >=65 years of age. Efficacy and safety in this age group were similar in both trials for asthma and CRSwNP compared to the overall study population.

Clinical studies of dupilumab in patients with eosinophilic esophagitis, prurigo nodularis, or allergic fungal rhinosinusitis did not include sufficient numbers of individuals >=65 years of age to assess whether these patients respond differently from younger adults.

Of the 1874 patients with COPD randomized in clinical trials of dupilumab, 1072 were >=65 years of age and 244 were >=75 years of age. No overall differences in safety or efficacy were observed between patients >=65 years of age and younger adults.

Of the 198 patients with chronic spontaneous urticaria who received dupilumab in clinical trials, 30 were >=65 years of age and 7 were >=75 years of age; efficacy and safety in patients >=65 years of age were similar to the overall study population.

Of the 53 patients with bullous pemphigoid who received dupilumab in clinical trials, 40 were >=65 years of age and 22 were >=75 years of age. Blurred vision occurred more frequently in patients >=65 years of age as compared to younger patients (10 versus 0%).