Ryaltris (olopatadine HCl/mometasone furoate)

Dosage of olopatadine hydrochloride is expressed in terms of olopatadine.

Dosage adjustment for olopatadine nasal spray is not necessary in patients with hepatic or renal impairment.

No dosing information is available for this tab.

No dosing information is available for this tab.

Specific drug interaction studies involving olopatadine ophthalmic solution or nasal spray and other drugs have not been conducted to date.

Olopatadine does not inhibit the in vitro metabolism of substrates of cytochrome P-450 (CYP) isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, or 3A4.

There are no contraindication interactions for this drug.

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

Agents That Affect Iodide/Radioactive Iodide

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

MECHANISM OF ACTION: Many compounds can affect iodide protein binding and alter iodide pharmacokinetics and pharmacodynamics.(1)

CLINICAL EFFECTS: Compounds that affect iodide pharmacokinetics and pharmacodynamics may impact the effectiveness of radioactive iodide.(1)

PREDISPOSING FACTORS: Compounds that affect iodide pharmacokinetics and pharmacodynamics are expected to have the most impact during therapy using radioactive iodide. Diagnostic procedures would be expected to be impacted less.

PATIENT MANAGEMENT: Discuss the use of agents that affect iodide pharmacokinetics and pharmacodynamics with the patient's oncologist.(1) Because indocyanine green contains sodium iodide, the iodine-binding capacity of thyroid tissue may be reduced for at least one week following administration. Do not perform radioactive iodine uptake studies for at least one week following administration of indocyanine green.(2) The manufacturer of iopamidol states administration may interfere with thyroid uptake of radioactive iodine and decrease therapeutic and diagnostic efficacy. Avoid thyroid therapy or testing for up to 6 weeks post administration of iopamidol.(3)

DISCUSSION: Many agents interact with radioactive iodine. The average duration of effect is: anticoagulants - 1 week antihistamines - 1 week anti-thyroid drugs, e.g: carbimazole, methimazole, propylthiouracil - 3-5 days corticosteroids - 1 week iodide-containing medications, e.g: amiodarone - 1-6 months expectorants - 2 weeks Lugol solution - 3 weeks saturated solution of potassium iodine - 3 weeks vitamins - 10-14 days iodide-containing X-ray contrast agents - up to 1 year lithium - 4 weeks phenylbutazone - 1-2 weeks sulfonamides - 1 week thyroid hormones (natural or synthetic), e.g.: thyroxine - 4 weeks tri-iodothyronine - 2 weeks tolbutamide - 1 week topical iodide - 1-9 months (1)

Agents That Affect Iodide/Sodium Iodide I 131

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

MECHANISM OF ACTION: Many compounds can affect iodide protein binding and alter iodide pharmacokinetics and pharmacodynamics.(1,2)

CLINICAL EFFECTS: Compounds that affect iodide pharmacokinetics and pharmacodynamics may impact the effectiveness of radioactive iodide.(1,2)

PREDISPOSING FACTORS: Compounds that affect iodide pharmacokinetics and pharmacodynamics are expected to have the most impact during therapy using radioactive iodide. Diagnostic procedures would be expected to be impacted less.

PATIENT MANAGEMENT: Discuss the use of agents that affect iodide pharmacokinetics and pharmacodynamics with the patient's oncologist.(1,2) Because indocyanine green contains sodium iodide, the iodine-binding capacity of thyroid tissue may be reduced for at least one week following administration. Do not perform radioactive iodine uptake studies for at least one week following administration of indocyanine green.(3) The manufacturer of iopamidol states administration may interfere with thyroid uptake of radioactive iodine and decrease therapeutic and diagnostic efficacy. Avoid thyroid therapy or testing for up to 6 weeks post administration of iopamidol.(4)

DISCUSSION: Many agents interact with radioactive iodine. The average duration of effect is: anticoagulants - 1 week antihistamines - 1 week anti-thyroid drugs, e.g: carbimazole, methimazole, propylthiouracil - 3-5 days corticosteroids - 1 week iodide-containing medications, e.g: amiodarone - 1-6 months expectorants - 2 weeks Lugol solution - 3 weeks saturated solution of potassium iodine - 3 weeks vitamins - 10-14 days iodide-containing X-ray contrast agents - up to 1 year lithium - 4 weeks phenylbutazone - 1-2 weeks sulfonamides - 1 week thyroid hormones (natural or synthetic), e.g.: thyroxine - 4 weeks tri-iodothyronine - 2 weeks tolbutamide - 1 week topical iodide - 1-9 months (1,2)

Selected Glucocorticoids/Relacorilant

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

MECHANISM OF ACTION: Relacorilant is a reversible antagonist of the glucocorticoid receptor (GR) and a strong CYP3A4 inhibitor.(1) Strong CYP3A4 inhibitors may inhibit the metabolism of corticosteroids metabolized by CYP3A4.(1)

CLINICAL EFFECTS: Relacorilant may antagonize the effect of glucocorticoids, and glucocorticoids may decrease the effect of relacorilant. Conditions requiring glucocorticoids may be exacerbated and adrenal insufficiency may occur.(1) Relacorilant may also increase systemic exposure to and effects from corticosteroids metabolized by CYP3A4, including Cushing's syndrome and adrenal suppression.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Relacorilant is contraindicated in patients who require glucocorticoids for life-saving purposes (e.g., immunosuppression after organ transplant). In patients taking glucocorticoids for other purposes, avoid relacorilant if possible. If coadministration cannot be avoided, consider alternative corticosteroids that are less affected by CYP3A4 inhibitors, like beclomethasone, prednisone, and prednisolone, and monitor relacorilant and glucocorticoid responses. If adrenal insufficiency occurs, withhold relacorilant and administer glucocorticoid therapy. High doses of glucocorticoids may be required to overcome glucocorticoid receptor antagonism, which may continue for up to 6 days after the last dose of relacorilant. After adrenal insufficiency resolves, resume the previous dose, reduce dose, or permanently discontinue relacorilant based on the severity, as recommended in the manufacturer prescribing information.(1)

DISCUSSION: Relacorilant antagonizes the glucocorticoid receptor. Relacorilant is contraindicated in patients receiving glucocorticoids for life-saving conditions and should be avoided in patients taking glucocorticoids for other conditions.(1) In a study, boceprevir (800 mg TID for 7 days) increased the area-under-curve (AUC) of a single dose of prednisone (40 mg) by 22%. The maximum concentration (Cmax) and AUC of prednisolone increased by 16% and 37%, respectively.(4) A study of 14 healthy adults found that concurrent use of ketoconazole with ciclesonide increased the AUC of ciclesonide's active metabolite, des-ciclesonide, by approximately 3.6-fold at steady state, while levels of ciclesonide remained unchanged. However, the study concluded that no dosage adjustments were required because ciclesonide has a very low potential to cause side effects.(5) A study in 18 healthy subjects examined the effects of ritonavir (100 mg twice daily) on fluticasone nasal spray (200 mcg daily). In most subjects, fluticasone was undetectable (<10 pg/ml) when administered alone. In subjects in whom fluticasone was detectable when given alone, Cmax and area-under-curve AUC averaged 11.9 pg/ml and 8.43 pg x hr/ml, respectively. With concurrent ritonavir, fluticasone Cmax and AUC increased to 318 pg/ml and 3102.6 pg x hr/ml, respectively.(7-9) This reflects increases in Cmax and AUC by 25-fold and 350-fold, respectively.(7) The cortisol AUC decreased by 86%.(11-14) In a study in 10 healthy subjects, ritonavir (200 mg twice daily for 4 and 14 days) increased the AUC of a single dose of prednisolone by 1.41-fold and 1.30-fold, respectively, after 4 days and 14 days of ritonavir.(15) There have been several case reports of Cushing's syndrome in patients treated concurrently with ritonavir and inhaled budesonide,(16-17) dexamethasone,(18) injectable triamcinolone,(19-22) nasal fluticasone.(24-42) Hepatitis has also been reported with concurrent budesonide and ritonavir.(43) In a study in 9 healthy subjects, mibefradil (50 mg once daily for 3 days) increased the AUC, Cmax, and elimination half-life of methylprednisolone by 3.8-fold, 1.8-fold, and 2.7-fold, respectively.(44) In a study in 8 healthy subjects, following nefazodone administration the following changes were seen with methylprednisolone: mean (+/-SD) area under the concentration-time curve was significantly higher (1393 +/- 343 vs. 2966 +/- 928 ug*h/L; P < 0.005), apparent clearance was lower (28.7 +/- 7.2 vs. 14.6 +/- 7.8 L/h; P < 0.02) and the terminal elimination half-life was longer (2.28 +/- 0.49 vs. 3.32 +/- 0.95 hours; P < 0.02).(45) Selected steroids metabolized by CYP3A4 are linked to this monograph.(46)

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

Mometasone/Selected Cyp3a4 Inhibitors

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

MECHANISM OF ACTION: CYP3A4 inhibitors may inhibit the metabolism of mometasone.(1-14,17)

CLINICAL EFFECTS: Concurrent use of CYP3A4 inhibitors may result in increased systemic exposure to and effects from mometasone, including Cushing's syndrome and adrenal suppression.(1-14,17)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Use caution when using concurrent therapy with mometasone and CYP3A4 inhibitors. Alternative corticosteroids that are less affected by CYP3A4 inhibitors should be considered, like beclomethasone and prednisolone.(14) If concurrent therapy is warranted, patients should be closely monitored for systemic effects. The corticosteroid may need to be discontinued.

DISCUSSION: In a study in 24 healthy subjects, inhaled mometasone furoate (400 mcg delivered by a dry powder inhaler twice daily for 9 days) with ketoconazole (200 mg on Days 4 to 9) increased systemic mometasone furoate concentrations from <150 pg/mL on Day 3 prior to coadministration of ketoconazole to a peak plasma concentrations of mometasone furoate >200 pg/mL on Day 9 (211-324 pg/mL).(14) There have been several case reports of Cushing's syndrome in patients treated concurrently with ritonavir and nasal fluticasone and mometasone.(15) A review of corticosteroid use patients on protease inhibitors detailed the interactions that can result in accumulation of corticosteroids, leading to adrenal suppression and Cushing's syndrome.(16) Selected CYP3A4 inhibitors linked to this monograph include: atazanavir, boceprevir, ceritinib, cobicistat, darunavir, ensitrelvir, fosamprenavir, idelalisib, indinavir, lenacapavir, lonafarnib, lopinavir, mibefradil, nelfinavir, nirmatrelvir, paritaprevir, saquinavir, telaprevir, tipranavir, and tucatinib.(17)

Known hypersensitivity to mometasone furoate or any ingredient in the formulation.

There are no contraindication contraindications for this drug.

• Nasal septal perforation
• Nasal septal ulcers
• Nasal trauma
• Ocular herpes simplex
• Ocular hypertension
• Open angle glaucoma
• Operation on nose
• Severe infection

• Adrenocortical insufficiency
• Cataracts
• Epistaxis
• Inactive tuberculosis
• Nasal septal ulcers
• Parasitic infection

Adverse effects occurring in 5% or more of patients receiving mometasone furoate for the treatment of allergic rhinitis include headache, viral infection, pharyngitis, epistaxis/blood-tinged mucus, coughing, and upper respiratory tract infection; in addition, dysmenorrhea, musculoskeletal pain, and sinusitis (in patients 12 years of age or older) and vomiting (in patients 3-11 years of age).

Adverse effects occurring in 5% or more of patients receiving mometasone furoate for the treatment of nasal polyposis and more frequently than with placebo include epistaxis.

More Frequent

• Viral infection

Less Frequent

• Asthma
• Bronchitis
• Chest pain
• Dysmenorrhea
• Earache
• Nasal septal perforation
• Nasal septal ulcers
• Sinusitis
• Upper respiratory infection

Rare or Very Rare

• Anaphylaxis
• Angioedema
• Cataracts
• Dysgeusia
• Glaucoma
• Impaired wound healing
• Increased creatine kinase level
• Lesion of nasal mucosa
• Migration of implant
• Nasal candidiasis
• Nasal septal perforation
• Oral candidiasis
• Parosmia

More Frequent

• Conjunctivitis
• Cough
• Dysgeusia
• Epistaxis
• Epistaxis
• Headache disorder
• Otitis
• Pharyngitis
• Upper respiratory infection

Less Frequent

• Arthralgia
• Cough
• Diarrhea
• Dyspepsia
• Headache disorder
• Myalgia
• Nausea
• Presyncope
• Rhinitis
• Sneezing
• Urinary tract infection

Rare or Very Rare

• Depression
• Dizziness
• Drowsy
• Fatigue
• Flu-like symptoms
• Influenza
• Loss of sense of smell
• Nasal pain
• Nasal passage irritation
• Parosmia
• Pharyngitis
• Sore throat
• Vomiting
• Xerostomia

No enhanced messaging available.

Safety and efficacy of intranasal mometasone furoate not established in children younger than 2 years of age for the treatment of allergic rhinitis or younger than 18 years of age for the treatment of nasal polyposis, respectively. Intranasal corticosteroids, including mometasone furoate, may cause a reduction in growth velocity in pediatric patients. (See General Precautions: Systemic Corticosteroid Effects, in Cautions.)

Category C. (See Users Guide.) Administration of corticosteroids during pregnancy may result in hypoadrenalism in the infant.

Reproduction studies in rats and rabbits receiving oral olopatadine dosages of 600 or 400 mg/kg daily, respectively (i.e., 93,750 or 62,500 times the maximum recommended human ocular dosage, respectively, based on a drop size of 40 mcL, and approximately 1000 or 1400 times the maximum recommended human dose, respectively, for adults on a mg/m2 basis), have not revealed evidence of teratogenicity. However, a decrease in the number of live fetuses was observed in rabbits and rats receiving oral olopatadine dosages of 25 and 60 mg/kg (approximately 88 and 100 times the maximum recommended human dose, respectively, for adults on a mg/m2 basis) or higher. In rats receiving an oral olopatadine dose of 60 mg/kg (approximately 100 times the maximum recommended human dose for adults on a mg/m2 basis), viability and body weights of pups were reduced on day 4 postpartum; however, no effect on viability was observed at a dose of 20 mg/kg (approximately 35 times the maximum recommended human dose for adults on a mg/m2 basis). There are no adequate and well-controlled studies to date using olopatadine in pregnant women, and the drug should be used during pregnancy only if the potential benefits justify the possible risks to the embryo or fetus.

Not known whether mometasone furoate is distributed in milk. Caution is advised if the drug is administered in nursing women.

Olopatadine is distributed into milk in rats following oral administration. It is not known whether topical ophthalmic administration of olopatadine could result in sufficient systemic absorption to produce detectable quantities in milk; therefore, olopatadine ophthalmic solutions should be used with caution in nursing women. Olopatadine nasal spray should be used in nursing women only if the potential benefits to the woman outweigh the potential risks to the infant.

No substantial differences in safety and efficacy relative to younger adults.