Delgocitinib (Monograph)

Brand name: Anzupgo
Drug class: Janus Kinase Inhibitors

Introduction

Delgocitinib is a Janus kinase (JAK) inhibitor.

Uses for Delgocitinib

Delgocitinib has the following uses:

Delgocitinib is indicated for the topical treatment of moderate to severe chronic hand eczema in adults who have had an inadequate response to, or for whom topical corticosteroids are not advisable.

Use of delgocitinib in combination with other JAK inhibitors or potent immunosuppressants is not recommended.

Delgocitinib Dosage and Administration

General

Delgocitinib is available in the following dosage form(s) and strength(s):

Cream: Each g of delgocitinib cream contains 20 mg of delgocitinib.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• See the full prescribing information for recommended immunizations prior to treatment.

• Do not use more than 30 g per 2 weeks or 60 g per month.

• Apply twice daily to skin of the affected areas only on the hands and wrists.

• For topical use only. Not for oral, ophthalmic, or intravaginal use.

Cautions for Delgocitinib

Contraindications

None.

Warnings/Precautions

Serious Infections

Delgocitinib may increase the risk of infections. Eczema herpeticum was observed in a subject treated with delgocitinib. Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other opportunistic pathogens have been reported in patients receiving oral or topical JAK inhibitors.

Avoid use of delgocitinib in patients with an active or serious infection.

Consider the risks and benefits of treatment prior to initiating delgocitinib in patients with chronic or recurrent infection; patients who have been exposed to tuberculosis; patients with a history of a serious or an opportunistic infection; and patients with underlying conditions that may predispose them to infection.

Closely monitor patients for the development of signs and symptoms of infection during and after treatment with delgocitinib. A patient who develops a new infection during treatment with delgocitinib should undergo prompt and complete diagnostic testing; appropriate antimicrobial therapy should be initiated and the patient should be closely monitored. Interrupt treatment with delgocitinib if a patient develops a serious infection. Do not resume delgocitinib until the infection resolves or is adequately treated.

Viral Reactivation

Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical trials with delgocitinib. If a patient develops herpes zoster, consider interrupting delgocitinib treatment until the episode resolves.

The impact of delgocitinib on chronic viral hepatitis reactivation is unknown. Patients with active hepatitis B or C infection were excluded from clinical trials with delgocitinib. Consider viral hepatitis screening and monitoring for reactivation in accordance with clinical guidelines before starting therapy and during therapy with delgocitinib. If signs of reactivation occur, consult a hepatitis specialist. Delgocitinib is not recommended for use in patients with active hepatitis B or hepatitis C.

Non-melanoma Skin Cancers

Non-melanoma skin cancers including basal cell carcinoma have been reported in subjects treated with delgocitinib. Periodic skin examinations of the application sites are recommended for all patients, particularly those with risk factors for skin cancer. Advise patients to avoid sunlamps and minimize exposure to sunlight by wearing sun-protective clothing or using broad-spectrum sunscreen.

Immunizations

Prior to delgocitinib treatment, complete all age-appropriate vaccinations as recommended by current immunization guidelines, including herpes zoster vaccinations. Avoid vaccination with live vaccines immediately prior to, during, and immediately after delgocitinib treatment.

Potential Risks Related to JAK Inhibition

It is not known whether delgocitinib may be associated with the observed or potential adverse reactions of JAK inhibition.

In a large, randomized, postmarketing safety trial of an oral JAK inhibitor in combination with methotrexate in rheumatoid arthritis patients 50 years of age and older with at least one cardiovascular risk factor, higher rates of all-cause mortality, including sudden cardiovascular death, major adverse cardiovascular events (MACE), overall thrombosis, deep venous thrombosis (DVT), pulmonary embolism (PE), and malignancies (excluding non-melanoma skin cancer) were observed in patients treated with the JAK inhibitor compared to those treated with TNF blockers. Delgocitinib is not indicated for use in rheumatoid arthritis.

Treatment with oral and topical JAK inhibitors has been associated with increases in lipid parameters including total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides.

Specific Populations

Pregnancy

The available data on the use of topical delgocitinib during pregnancy is insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

In animal reproduction studies, oral administration of delgocitinib to pregnant rats and rabbits during the period of organogenesis did not result in adverse developmental effects at doses 120 or 193 times, respectively, the maximum recommended human dose (MRHD) based on AUC comparison.

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, and other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.

Lactation

There are no data on the presence of delgocitinib in human milk, the effects on the breastfed infant, or the effects on milk production. After oral administration, delgocitinib was present in the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for delgocitinib and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.

To minimize potential infant exposure, advise breastfeeding women to avoid direct contact with the nipple and surrounding area immediately after applying delgocitinib to the hands and/or wrists.

Pediatric Use

The safety and efficacy of delgocitinib have not been established in pediatric patients.

Geriatric Use

Of the 691 subjects exposed to delgocitinib in clinical trials, 59 subjects (8.5%) were 65 years of age and older and 10 subjects (1.4%) were 75 years of age and older. No overall differences in safety or effectiveness were observed between subjects 65 years of age and older and younger adult subjects.

Common Adverse Effects

Adverse reactions that were reported in ≤ 1% of subjects were application site pain, paresthesia, pruritus, erythema, and bacterial skin infections including finger cellulitis, paronychia, other skin infections, leukopenia, and neutropenia.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Delgocitinib, a Janus kinase (JAK) inhibitor, inhibits the activity of JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2). JAK signaling involves recruitment of signal transducers and activators of transcription (STATs) to cytokine receptors, and activation and subsequent localization of STATs to the nucleus, leading to the expression of cytokine-responsive genes to induce specific biological responses in target cells. The exact mechanism of action of delgocitinib in the treatment of moderate to severe chronic hand eczema is currently not known.

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Patient Information).

• Advise patients that delgocitinib is for topical use only and is not for ophthalmic, oral, or intravaginal use.

• Advise patients to limit treatment to 30 g per 2 weeks or 60 g per month.

• Instruct patients to clean and dry affected areas prior to applying delgocitinib. Instruct patients to apply delgocitinib, twice daily, to affected areas only on the hands and wrists, and avoid contact with eyes, mouth, or other mucous membranes.

• Inform patients that delgocitinib may lower the ability of their immune system to fight infections and to contact their healthcare provider immediately if they develop any signs or symptoms of infection.

• Inform patients that delgocitinib may increase the risk of developing non-melanoma skin cancers. Inform patients that periodic skin examinations should be performed while using delgocitinib. Instruct patients to inform their healthcare provider if they have ever had any type of cancer. Advise patients to avoid sunlamps and minimize exposure to sunlight by wearing sun-protective clothing or using broad-spectrum sunscreen.

• Advise patients treated with delgocitinib to avoid use of live vaccines immediately prior to, during, and immediately after treatment.

• Advise breastfeeding women to avoid direct contact with the nipple and surrounding area immediately after applying delgocitinib to the hands and/or wrists to minimize infant exposure.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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