Jascayd (nerandomilast)

Reduce nerandomilast dosage to 9 mg twice daily when given with strong CYP3A inhibitors.

No dosage adjustment is required for coadministration with moderate or weak CYP3A inhibitors.

Administer nerandomilast orally twice daily, approximately 12 hours apart, with or without food.

Swallow tablets whole or dispersed in water.

For patients unable to swallow tablets whole, disperse the tablet without crushing in approximately 100 mL non-carbonated, room-temperature water. Stir regularly for 15-20 minutes until the tablet is dispersed into small pieces (it will not fully dissolve). Drink the dispersion within 2 hours; if not taken immediately, stir again before drinking. Rinse the glass with an additional 100 mL of water and drink to ensure the full dose is administered.

Store the tablets in the original container to protect from light. Store at 20-25degreesC; excursions permitted to 15-30degreesC.

No dosing information is available for this tab.

Nerandomilast is a cytochrome P-450 (CYP) 3A substrate.

Nerandomilast does not inhibit CYP3A4, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP2D6.

Nerandomilast is a substrate of P-glycoprotein (P-gp) but not of breast cancer resistance protein (BCRP), organic anion transporting polypeptide 1B1 (OATP1B1), organic anion transporting polypeptide 1B3 (OATP1B3), organic anion transporter 1 (OAT1), organic anion transporter 3 (OAT3), or organic cation transporter 2 (OCT2).

Nerandomilast inhibits P-gp, multidrug and toxin extrusion protein 1 (MATE1), and multidrug and toxin extrusion protein 2-K (MATE2-K); this is not expected to cause clinically significant drug interactions.

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

Nerandomilast (9 Mg)/Moderate Cyp3a4 Inducers

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: Moderate CYP3A4 inducers may induce the metabolism of nerandomilast by CYP3A4.

CLINICAL EFFECTS: Concurrent or recent use of moderate CYP3A4 inducers may reduce the clinical effectiveness of nerandomilast.(1)

PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.

PATIENT MANAGEMENT: The recommended dose of nerandomilast with moderate CYP3A4 inducers is 18 mg twice daily. For patients who are unable to tolerate 18 mg twice daily, do not reduce the dosage to 9 mg twice daily in patients taking moderate CYP3A4 inducers.(1)

DISCUSSION: Nerandomilast is primarily metabolized by CYP3A4.(1) Moderate CYP3A4 inducers linked to this monograph include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, fexinidazole, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat, thioridazine, and tovorafenib.(2,3)

Nerandomilast/Strong Cyp3a4 Inducers

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: Strong CYP3A4 inducers may induce the metabolism of nerandomilast by CYP3A4.

CLINICAL EFFECTS: Concurrent or recent use of strong CYP3A4 inducers may reduce the clinical effectiveness of nerandomilast.(1)

PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.

PATIENT MANAGEMENT: Concurrent use of nerandomilast and strong CYP3A4 inducers should be avoided.(1)

DISCUSSION: Nerandomilast is primarily metabolized by CYP3A4.(1) Strong CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine and St. John's wort.(2,3)

There are no severe interactions for this drug.

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

Nerandomilast/Strong Cyp3a4 Inhibitors

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

MECHANISM OF ACTION: Agents that are strong CYP3A4 inhibitors may inhibit the metabolism of nerandomilast.(1)

CLINICAL EFFECTS: The coadministration of nerandomilast with strong CYP3A4 inhibitors may increase nerandomilast systemic exposure and may result in increased adverse reactions.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of nerandomilast states the dose of nerandomilast should be reduced to 9 mg twice daily with concurrent use of strong CYP3A4 inhibitors.(1)

DISCUSSION: In healthy subjects, concurrent use of nerandomilast with itraconazole, a strong CYP3A4 inhibitor, (200 mg once daily for 4 days) increased the area-under-curve (AUC) and concentration maximum (Cmax) of nerandomilast by 2.2-fold and 1.3-fold, respectively.(1) Strong CYP3A4 inhibitors linked to this monograph include: adagrasib, boceprevir, ceritinib, clarithromycin, cobicistat, ensitrelvir, grapefruit, idelalisib, indinavir, itraconazole, josamycin, ketoconazole, levoketoconazole, lonafarnib, lopinavir, mibefradil, mifepristone, nefazodone, nelfinavir, nirmatrelvir, paritaprevir, posaconazole, relacorilant, ribociclib, saquinavir, telaprevir, telithromycin, tipranavir, troleandomycin, tucatinib, and voriconazole.(2,3)

*None.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

• No disease contraindications

The most common adverse reactions (incidence >=5%) reported with nerandomilast in clinical studies were diarrhea, COVID-19, upper respiratory tract infection, depression, decreased weight, decreased appetite, nausea, fatigue, headache, vomiting, back pain, and dizziness.

Less Frequent

• Atrial fibrillation
• Malignant neoplasm of lung
• Malignant neoplasm of skin

More Frequent

• COVId-19
• Depression
• Diarrhea
• Upper respiratory infection
• Weight loss

Less Frequent

• Anorexia
• Back pain
• Dizziness
• Fatigue
• General weakness
• Headache disorder
• Nausea
• Vomiting

Rare or Very Rare

• Elevated serum amylase
• Vasculitis

No enhanced messaging available.

The safety and effectiveness of nerandomilast for the treatment of IPF or PPF have not been established in pediatric patients.

There are no adequate data on nerandomilast use in pregnant women to assess the risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Based on animal studies, nerandomilast may increase the risk of fetal loss; embryo-fetal losses occurred in pregnant rats at exposures approximately 5 times the maximum recommended human dose. Inform female patients of this risk.

Untreated idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) can cause maternal respiratory failure and death, as well as intrauterine growth restriction, preterm birth, fetal hypoxia, and neonatal death.

There are no data on the presence of nerandomilast or its metabolite in human milk, effects on the breastfed infant, or on milk production. Nerandomilast is present in animal milk and may therefore be present in human milk. The benefits of breastfeeding should be weighed against the mother's clinical need for nerandomilast and the potential risks to the breastfed infant from the drug or the underlying maternal condition.

No dosage adjustment is needed for geriatric patients.

In the FIBRONEER-IPF study, 79% of nerandomilast-treated patients with IPF were >=65 years of age and 32% of patients were >=75 years of age. In the FIBRONEER-ILD study, 63% of nerandomilast-treated patients were >=65 years of age and 19% of patients were >=75 years of age. No overall differences in safety or effectiveness were observed between older and younger adult patients.