Dulera (mometasone furoate/formoterol fumarate)

Each 2-mL single-dose vial of formoterol fumarate oral inhalation solution contains 20 mcg of formoterol fumarate. The oral inhalation solution does not require dilution prior to administration by nebulization. The actual amount of drug delivered to the lungs will depend on patient factors and the type of nebulization system used and its performance.

Each actuation of the oral aerosol inhaler containing the fixed combination of formoterol fumarate dihydrate and budesonide delivers 5.1 mcg of formoterol fumarate dihydrate and 91 or 181 mcg of budesonide from the valve and delivers 4.5 mcg of formoterol fumarate dihydrate and 80 or 160 mcg of budesonide from the actuator per metered spray, depending on the preparation used. The strength of formoterol/budesonide preparations and dosage of the fixed combination are expressed in terms of drug delivered from the mouthpiece of the actuator. The actual amount of drug delivered to the lungs depends on factors such as the patient's coordination between the actuation of the inhaler and inspiration through the delivery system. The commercially available formoterol/budesonide aerosol inhaler delivers 60 metered sprays per 6- or 6.9-g canister and 120 metered sprays per 10.2-g canister.

After priming of the oral aerosol inhaler containing the fixed combination of formoterol fumarate and glycopyrrolate, each actuation of the oral aerosol inhaler (Bevespi(R) Aerosphere(R)) delivers 5.5 mcg of formoterol fumarate and 10.4 mcg of glycopyrrolate (equivalent to 8.3 mcg of glycopyrronium) from the valve. Dosage is expressed in terms of drug delivered from the mouthpiece; each actuation of the inhaler delivers 4.8 mcg of formoterol fumarate and 9 mcg of glycopyrrolate (equivalent to 7.2 mcg of glycopyrronium) from the actuator. The actual amount of drug delivered to the lungs depends on factors such as the patient's coordination between actuation of the device and inspiration through the delivery system. Commercially available formoterol/glycopyrrolate aerosol inhaler delivers 28 or 120 metered sprays per 5.9- or 10.7-g canister, respectively.

Each actuation of the oral aerosol inhaler containing the fixed combination of formoterol fumarate dihydrate and mometasone furoate delivers 5.5 mcg of formoterol fumarate dihydrate and 115 or 225 mcg of mometasone furoate from the valve and delivers 5 mcg of formoterol fumarate dihydrate and 100 or 200 mcg of mometasone furoate from the actuator per metered spray, depending on the preparation used. The strength of formoterol/mometasone preparations and dosage of the fixed combination are expressed in terms of drug delivered from the mouthpiece of the actuator. The actual amount of drug delivered to the lungs may depend on factors such as the patient's coordination between actuation of the device and inspiration through the delivery system. Commercially available formoterol/mometasone aerosol inhaler delivers 60 or 120 metered sprays per 8.8- or 13-g canister, respectively.

Dosage of mometasone furoate is expressed in terms of the salt.

Mometasone/formoterol is a fixed combination of mometasone furoate and formoterol fumarate dihydrate; dosage of the mometasone component is expressed in terms of the salt and dosage of the formoterol component is expressed in terms of the hydrated salt.

The strength and dosage of mometasone furoate administered as an oral inhalation powder (Asmanex(R) Twisthaler(R)) is expressed as the nominal (labeled) dose contained in the Twisthaler(R) device. The actual amount of drug delivered to the lungs depends on factors such as the patient's inspiratory flow. Based on standardized in vitro testing at a flow rate of 30 and 60 L/minute at a constant volume of 2 L, each actuation of the Twisthaler(R) inhaler labeled as containing 220 or 110 mcg of mometasone furoate delivers 200 or 100 mcg of mometasone furoate, respectively, from the mouthpiece. In adults and adolescents 12 years of age or older with asthma of varying severity, mean peak inspiratory flow through the Twisthaler(R) device was 69 L/minute. Mean peak inspiratory flow through the Twisthaler(R) device in pediatric patients 5-8 or 9-12 years of age exceeded 50 or 60 L/minute, respectively.

Each actuation of the mometasone furoate oral aerosol metered-dose inhaler (Asmanex(R) HFA) delivers 115 or 225 mcg of mometasone furoate from the valve and 100 or 200 mcg of mometasone furoate from the actuator, depending on the preparation used. The strength and dosage of these mometasone preparations are expressed in terms of drug delivered from the mouthpiece of the actuator. The actual amount of drug delivered to the lungs may depend on factors such as the patient's coordination between actuation of the device and inspiration through the delivery system. Commercially available Asmanex(R) HFA aerosol inhaler delivers 120 actuations per 13-g canister.

Each actuation of the oral aerosol inhaler containing the fixed combination of mometasone furoate and formoterol fumarate (Dulera(R)) delivers 115 or 225 mcg of mometasone furoate and 5.5 mcg of formoterol fumarate dihydrate from the valve and delivers 100 or 200 mcg of mometasone furoate and 5 mcg of formoterol fumarate dihydrate from the actuator per metered spray, depending on the preparation used. The strength and dosage of mometasone/formoterol preparations are expressed in terms of drug delivered from the mouthpiece of the actuator. The actual amount of drug delivered to the lungs may depend on factors such as the patient's coordination between actuation of the device and inspiration through the delivery system. Commercially available mometasone/formoterol aerosol inhaler delivers 60 or 120 metered sprays per 8.8- or 13-g canister, respectively.

No dosing information is available for this tab.

No dosing information is available for this tab.

The following information addresses potential interactions with formoterol fumarate. When formoterol fumarate is used in fixed combination with budesonide, glycopyrrolate, or mometasone furoate, interactions associated with budesonide, glycopyrrolate, and mometasone also should be considered. No formal drug interaction studies have been performed to date with the fixed-combination preparations containing formoterol fumarate and budesonide, glycopyrrolate, or mometasone.

The following information addresses potential interactions with mometasone furoate. When mometasone furoate is used in fixed combination with formoterol fumarate (mometasone/formoterol), interactions associated with formoterol also should be considered. No formal drug interaction studies have been performed to date with the mometasone/formoterol fixed combination.

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

Agents Affecting Plasma Cortisol Levels/Cosyntropin

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: Agents affecting plasma cortisol levels may impact the accuracy of the cosyntropin diagnostic test.(1)

CLINICAL EFFECTS: Concurrent use of agents affecting plasma cortisol levels may impact the accuracy of the cosyntropin diagnostic test.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of cosyntropin states accuracy of diagnosis using the cosyntropin diagnostic test may be complicated by concomitant medications affecting plasma cortisol levels.(1) Agents affecting plasma cortisol levels and recommendation to stop prior to cosyntropin diagnostic test include: - Glucocorticoids: May elevate plasma cortisol levels. Stop these drugs on the day of testing. Long-acting glucocorticoids may need to be stopped for a longer period before testing. - Spironolactone: May elevate plasma cortisol levels. Stop spironolactone on the day of testing. - Estrogen: May elevate plasma total cortisol levels. Discontinue estrogen containing drugs 4 to 6 weeks prior to testing to allow cortisol binding globulin levels to return to levels within the reference range. Alternatively, concomitant measurement of cortisol binding globulin at the time of testing can be done; if cortisol binding globulin levels are elevated, plasma total cortisol levels are considered inaccurate.(1)

DISCUSSION: Concurrent use of agents affecting plasma cortisol levels may impact the accuracy of the cosyntropin diagnostic test.(1)

Glucocorticoids/Desmopressin

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: Glucocorticoids increase the risk of hyponatremia.(1-4)

CLINICAL EFFECTS: Concurrent use of glucocorticoids may increase the risk of hyponatremia with desmopressin.(1-4)

PREDISPOSING FACTORS: Predisposing factors for hyponatremia include: polydipsia, renal impairment (eGFR < 50 ml/min/1.73m2), illnesses that can cause fluid/electrolyte imbalances, age >=65, medications that cause water retention and/or increase the risk of hyponatremia (carbamazepine, chlorpromazine, lamotrigine, loop diuretics, NSAIDs, opioids, SSRIs, thiazide diuretics, and/or tricyclic antidepressants).

PATIENT MANAGEMENT: The concurrent use of systemic or inhaled glucocorticoids with desmopressin is contraindicated.(1-4) Desmopressin may be initiated 3 days or 5 half-lives after glucocorticoid discontinuation, whichever is longer. If concurrent use is deemed medically necessary, make sure serum sodium levels are normal before beginning therapy and consider using the desmopressin nasal 0.83 mcg dose. Consider measuring serum sodium levels more frequently than the recommended intervals of: within 7 days of concurrent therapy initiation, one month after concurrent therapy initiation and periodically during treatment. Counsel patients to report symptoms of hyponatremia, which may include: headache, nausea/vomiting, feeling restless, fatigue, drowsiness, dizziness, muscle cramps, changes in mental state (confusion, decreased awareness/alertness), seizures, coma, and trouble breathing. Counsel patients to limit the amount of fluids they drink in the evening and night-time and to stop taking desmopressin if they develop a stomach/intestinal virus with nausea/vomiting or any nose problems (blockage, stuffy/runny nose, drainage).(1)

DISCUSSION: In clinical trials of desmopressin for the treatment of nocturia, 4 of 5 patients who developed severe hyponatremia (serum sodium <= 125 mmol/L) were taking systemic or inhaled glucocorticoids. Three of these patients were also taking NSAIDs and one was receiving a thiazide diuretic.(2) Drugs associated with hyponatremia may increase the risk, including loop diuretics, carbamazepine, chlorpromazine, glucocorticoids, lamotrigine, NSAIDs, opioids, SSRIs, thiazide diuretics, and/or tricyclic antidepressants.(1,3-4)

Sympathomimetics/Dihydroergotamine

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: Concurrent use of dihydroergotamine and sympathomimetics may result in additive or synergistic effect on peripheral blood vessels.(1)

CLINICAL EFFECTS: Concurrent use of dihydroergotamine and sympathomimetics may result in increased blood pressure due to peripheral vasoconstriction.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Dihydroergotamine is contraindicated with sympathomimetics because the combination may result in additive or synergistic elevation of blood pressure.(1)

DISCUSSION: Significant elevation in blood pressure has been reported in patients treated with dihydroergotamine.(1) Sympathomimetics can be expected to have additional effects on blood pressure.

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

Agents That Affect Catecholamines/Iobenguane I 123

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

MECHANISM OF ACTION: Many compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells.(1)

CLINICAL EFFECTS: Compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with imaging completed with iobenguane.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Discuss the use of agents that affect catecholamines. Discontinue drugs that reduce catecholamine uptake or deplete catecholamine stores prior to imaging with iobenguane. Before imaging with iobenguane, discontinue agents that affect catecholamines for at least 5 biological half-lives, as clinically tolerated.(1)

DISCUSSION: Many agents may reduce catecholamine uptake or deplete catecholamine stores.(1) Examples include: - CNS stimulants or amphetamines (e.g. cocaine, methylphenidate, dextroamphetamine) - norepinephrine and dopamine reuptake inhibitors (e.g. phentermine) - norepinephrine and serotonin reuptake inhibitors (e.g. tramadol) - monoamine oxidase inhibitors (e.g. phenelzine, linezolid) - central monoamine depleting drugs (e.g. reserpine) - non-select beta adrenergic blocking drugs (e.g. labetalol) - alpha agonists or alpha/beta agonists (e.g. pseudoephedrine, phenylephrine, ephedrine, phenylpropanolamine, naphazoline) - tricyclic antidepressants or norepinephrine reuptake inhibitors (e.g. amitriptyline, bupropion, duloxetine, mirtazapine, venlafaxine) - botanicals that may inhibit reuptake of norepinephrine, serotonin or dopamine (e.g. ephedra, ma huang, St. John's Wort, yohimbine)

Agents That Affect Catecholamines/Iobenguane I 131

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

MECHANISM OF ACTION: Many compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells.(1)

CLINICAL EFFECTS: Compounds that reduce catecholamine uptake or that deplete catecholamine stores may impact the dosimetry calculations or effectiveness of iobenguane.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Discuss the use of agents that affect catecholamines. Discontinue drugs that reduce catecholamine uptake or deplete catecholamine stores for at least 5 half-lives before administration of either the dosimetry or a therapeutic dose of iobenguane. Do not administer these drugs until at least 7 days after each iobenguane dose.(1)

DISCUSSION: Many agents may reduce catecholamine uptake or deplete catecholamine stores.(1) Examples include: - CNS stimulants or amphetamines (e.g. cocaine, methylphenidate, dextroamphetamine) - norepinephrine and dopamine reuptake inhibitors (e.g. phentermine) - norepinephrine and serotonin reuptake inhibitors (e.g. tramadol) - monoamine oxidase inhibitors (e.g. phenelzine, linezolid) - central monoamine depleting drugs (e.g. reserpine) - non-select beta adrenergic blocking drugs (e.g. labetalol) - alpha agonists or alpha/beta agonists (e.g. pseudoephedrine, phenylephrine, ephedrine, phenylpropanolamine, naphazoline) - tricyclic antidepressants or norepinephrine reuptake inhibitors (e.g. amitriptyline, bupropion, duloxetine, mirtazapine, venlafaxine) - botanicals that may inhibit reuptake of norepinephrine, serotonin or dopamine (e.g. ephedra, ma huang, St. John's Wort, yohimbine) - calcium channel blockers

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)

Beta-2 Agonists/Non-Cardioselective Beta-Blockers

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

MECHANISM OF ACTION: Non-cardioselective beta-blockers and beta-2 agonists may antagonize the effects of each other.

CLINICAL EFFECTS: Diminished response to either the beta-agonist, beta-blocker, or both may occur. Beta-blockers may also induce bronchospasm.

PREDISPOSING FACTORS: Patients receiving beta-2 agonists for the treatment of asthma may be more at risk for bronchospasm.

PATIENT MANAGEMENT: If possible, avoid beta-blocker therapy in asthmatic patients requiring beta-2 agonist therapy. If beta-blocker therapy is required, use a cardio-selective beta-blocker. For timolol ophthalmic drops, counsel patients to apply pressure to the inner corner of the eye after administration to prevent systemic absorption. Monitor patients for decreased effects of either agent, such as increased need for/use of beta-2 agonists or increased heart rate or blood pressure.

DISCUSSION: Many patients with asymptomatic or mild reactive airways disease tolerate beta-blockers well. Most patients with COPD do not have bronchospastic component to their illness and may be given beta-blockers. Heart failure treatment guidelines recommend beta-blockers in the presence of COPD. Non-selective beta-blockers have been shown to have a negative effect on lung function (FEV1) and airway hyperresponsiveness (AHR) in patients with asthma and COPD.(1) An open-label study using the nonselective beta blocker nadolol showed no effect on salbutamol in 10 patients with mild asthma not on controller therapy.(2) A study in 8 healthy men showed that long acting propranolol (160 mg) only effected airway dilation at the 200 mcg salbutamol dose. The 800 mcg and 1600 mcg dose were unaffected. However, penbutolol prevented any significant airway dilation with all doses of salbutamol.(3) In a double blind, three-way, crossover study, 44% (7/16 patients) of patients taking metoprolol showed a greater than 20% decrease in FEV1 compared to 19% (3 patients) after dilevalol and 6% (1 patient) after placebo. Dilevalol and metoprolol significantly inhibited isoproterenol response compared to placebo.(4) A double-blind, randomized, crossover study in 10 asthmatic patients showed that intravenous propranolol produced marked symptomatic bronchoconstriction. Only a slight but significant inhibition of bronchomotor sensitivity to isoproterenol was noted during esmolol infusion.(5) In 18 patients with reversible bronchial asthma, labetalol caused a significant increase in FEV1 and metoprolol caused a significant decrease in FEV1. Concurrent administration of isoproterenol and labetalol caused a further increase in FEV1. The effect of isoproterenol was decreased by metoprolol (100, 200mg).(6) In one study propranolol (0.06mg/kg IV) was shown to almost completely block the effects of isoproterenol in asthmatics. Metoprolol (0.12mg/kg IV) did not affect isoproterenol.(7) Studies have shown that cardioselective beta-blockers are safe for patients with asthma and COPD.(8,9,10) Nebivolol and celiprolol significantly decreased FEV1. Inhalation of albuterol (up to 800mcg) significantly improved FEV1, but the values after nebivolol and celiprolol administration were lower than the initial values.(11) Administration of metoprolol did not cause any respiratory problems in 9 asthmatic patients. There was no significant difference between the metoprolol and placebo groups in the respiratory response to an isoproterenol aerosol in 24 asthmatic patients.(12) Eight male asthmatic patients were given 10 mg bisoprolol, 20 mg bisoprolol, and 100 mg metoprolol. Both bisoprolol and metoprolol caused bronchoconstriction measured by a significant fall in PEFR (peak expiratory flow rate). Terbutaline was able to reverse bronchoconstriction in all patients.(13) A double blind, placebo-controlled study analyzed the use of atenolol 100mg, metoprolol 100mg, or acebutolol 400 mg in 8 asthmatic patients before and after exercise. All three drugs reduced significantly FEV1 and PEFR. Administration of terbutaline improved all respiratory indices.(14) A double-blind crossover trial in 10 asthmatic patients showed that a single IV dose of atenolol 3mg caused slight impairment of ventilatory function. A dose of salbutamol by inhalation was able to reverse the bronchial effect of atenolol.(15) Propranolol (80mg/day), oxprenolol (80mg/day), atenolol (100mg/day), and celiprolol 200mg/day were given to 10 asthmatic patients in a randomized, crossover design with a two week washout period between each drug. The non-beta 1 selective beta blockers (propranolol, oxprenolol) caused a significant reduction in FEV1 and inhibited the bronchodilator response to inhaled salbutamol. Atenolol and celiprolol (beta1 selective beta blockers) did not significantly affect respiratory function or antagonize salbutamol effects.(16) A double blind, randomized, within patient, placebo-controlled study compared the cardioselective beta-blocker atenolol to the non-selective propranolol. Atenolol caused a significantly less drop in FEV1 compared to propranolol. The effect of isoprenaline plus the beta blockers were also studied. Both atenolol and propranolol effected isoprenaline FEV1 dose response curves but the greatest displacement was seen with propranolol.(17) The pulmonary effects of celiprolol 200 mg, celiprolol 400mg, propranolol 40mg, atenolol 100 mg were evaluated in 34 asthmatic patients. Propranolol and atenolol caused significant reductions in pulmonary function. Propranolol pretreatment caused a significant reduction in the effect of the bronchodilator. Celiprolol did not antagonize the bronchodilators.(18) A double-blind, placebo controlled, randomized, crossover design study studied the effects of propranolol 80mg or celiprolol 200 or 400mg on pulmonary function. Propranolol produced a significant decrease in FEV1 and FVC. Celiprolol and placebo had similar results. The effect of aerosolized terbutaline was also measured. Even at supratherapeutic doses, terbutaline was unable to restore pulmonary function parameters to baseline levels after treatment with propranolol. Terbutaline caused further bronchodilation after administration of celiprolol.(19) Eleven asthmatic patients showed significant bronchoconstriction in small airways after propranolol 40mg and pindolol 2.5mg in a double blind, randomized trial. Large airways only showed bronchoconstriction with propranolol. Terbutaline 0.5mg subcutaneous was given after pretreatment with propranolol and pindolol. The bronchodilator effect of terbutaline on large airways was diminished after both propranolol and timolol.(20)

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)

Sympathomimetics/Ergot Alkaloids

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

MECHANISM OF ACTION: Concurrent use of ergot alkaloids and sympathomimetics may result in additive or synergistic effect on peripheral blood vessels.

CLINICAL EFFECTS: Concurrent use of ergot alkaloids and sympathomimetics may result in increased blood pressure due to peripheral vasoconstriction.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: When possible, avoid the concurrent use of ergot alkaloids and sympathomimetics. If concurrent use is warranted, monitor blood pressure and for signs of vasoconstriction. Decreasing the dose of one or both drugs may be necessary.

DISCUSSION: There have been reports of severe vasoconstriction resulting in gangrene in patients receiving intravenous ergonovine with dopamine or norepinephrine.

Sympathomimetics/Selected Inhalation Anesthetic Agents

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

MECHANISM OF ACTION: The exact mechanism is unknown. The anesthetics produce conduction changes that increase impulse re-entry into the myocardial tissue.(1) The anesthetics' ability to precipitate arrhythmias is enhanced by elevated arterial blood pressure, tachycardia, hypercapnia, and/or hypoxia, events that stimulate the release of endogenous catecholamines.(1)

CLINICAL EFFECTS: Concurrent use of inhalation anesthetic agents and sympathomimetics may result in ventricular arrhythmias or sudden blood pressure and heart rate increase during surgery.(2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Monitor blood pressure and avoid use of sympathomimetics in patients being treated with anesthetics on the day of surgery.(2) Intravenous use of epinephrine during surgery with halothane and related halogenated general anesthetics should be strongly discouraged. When intravenous epinephrine is necessary, nitrous oxide anesthesia supplemented with ether, muscle relaxants, or opioids should be used instead of halothane.(3,4) Epinephrine may safely be used subcutaneously with the following precautions: the patient is adequately ventilated to prevent hypoxia or respiratory acidosis; the total dose of epinephrine is limited to 100 mcg/10 minute period or 300 mcg/hour in adults, 3.5 mcg/Kg in infants, 2.5 mcg/Kg in children up to two years of age, and 1.45 mcg/Kg in children over two years of age; a minimum effective concentration of anesthetic is maintained; the drugs are not co-administered in patients with hypertension or other cardiovascular disorders; and the cardiac rhythm is continuously monitored during and after injection.(3-10) If arrhythmias occur after the administration of the epinephrine, the drugs of choice are lidocaine or propranolol, depending on the type of arrhythmia.(1)

DISCUSSION: Administration of epinephrine during halothane anesthesia may may lead to serious ventricular arrhythmias.(3-6,11-18) This has occurred when epinephrine was administered intravenously,(6) when it was administered with lidocaine as a dental block,(11,14) or when it was administered supraperiosteally.(5) Norepinephrine has been shown to interact with halothane in a manner similar to epinephrine.(1) In two case reports, patients were given terbutaline (0.25 to 0.35 mg) for wheezing following induction of anesthesia with halothane. One patient's heart rate increased from 68 to 100 beats/minute, and the ECG showed premature ventricular contractions and bigeminy, while the other patient developed multiple unifocal premature ventricular contractions and bigeminy. The arrhythmias resolved in both patients following lidocaine administration.(19) Although not documented, isoproterenol causes effects on the heart similar to terbutaline(20) and would probably interact with halothane in a similar manner. Other inhalation anesthetics that increase the incidence of arrhythmias with epinephrine include chloroform,(20) methoxyflurane,(20) and enflurane.(12) A similar interaction may be expected between the other inhalation anesthetics and sympathomimetics.

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

Beta-Agonists; Anticholinergics; Theophylline/Methacholine

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

MECHANISM OF ACTION: Beta-agonists, anticholinergics, and theophylline may inhibit the action of methacholine on the airway.(1)

CLINICAL EFFECTS: The result of the methacholine challenge test may not be accurate.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The following drugs should be held before a methacholine challenge for the the duration indicated:(1) - short-acting beta-agonists: 6 hours - long-acting beta-agonists: 36 hours - short-acting anti-cholinergics: 12 hours - long-acting anti-cholinergics: at least 168 hours (7 days) - oral theophylline: 12-48 hours

DISCUSSION: Beta-agonists, anticholinergics, and theophylline may inhibit the action of methacholine on the airway and cause inaccurate test results.

Corticosteroids/Quinolones

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

MECHANISM OF ACTION: Quinolone-induced arthropathy is a class effect of the quinolones.(1) Exactly how corticosteroid use increases the risk of tendon rupture is unknown.

CLINICAL EFFECTS: Concurrent use of quinolones and corticosteroids may increase the risk of tendonitis and/or tendon rupture. This affect is most common in the Achilles tendon, but has been reported in the rotator cuff (shoulder), hand, biceps, thumb, and other tendons.(2-9)

PREDISPOSING FACTORS: Risk factors for tendinitis and tendon rupture include age greater than 60; a history of kidney, heart, or lung transplantation, strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis.

PATIENT MANAGEMENT: Quinolone use should be discontinued if the patient experiences pain, inflammation, or rupture of a tendon. Patients experiencing discomfort or pain should be instructed to rest and refrain from exercise until the diagnosis of tendonitis tendon rupture has been excluded.(2-9)

DISCUSSION: Ruptures of the shoulder, hand, Achilles tendon, or other tendons that required surgical repair or resulted in prolonged disability have been reported in patients receiving ciprofloxacin,(2) gatifloxacin,(3) levofloxacin,(4) lomefloxacin,(5) moxifloxacin,(6) nalidixic acid,(7) norfloxacin,(8) and ofloxacin.(9) A retrospective review of the IMS Health database examined quinolone use use from July 1, 1992 to June 30, 1998. The adjusted relative risk of tendon disorder with concurrent quinolone use was 1.9. Relative risk increased to 3.2 in patients aged 60 or older compared to 0.9 in patients aged less than 60. In patients aged 60 or older who used corticosteroids and quinolones concurrently, relative risk increased to 6.2.(10) In contrast, another retrospective review examined patients from a health insurance claims database and found no apparent effect from concurrent quinolone and corticosteroid use.(11) In a review of the follow-up to 42 spontaneously reported case of quinolone-associated tendon disorders in the Netherlands between January, 1988 and January, 1998, risk factors for tendon disorders included age older than 60, oral corticosteroid use, and existing joint problems.(12) In a review of the Swiss Drug Monitoring system, four of seven cases of levofloxacin-associated tendon problems also involved concurrent oral or inhaled corticosteroids.(13) In a review of the Medline database from 1966-2001, 98 case reports of tendinopathy associated with quinolones were located. Thirty-two (32.7%) of the patients had received systemic or inhaled corticosteroids before and during quinolone therapy. Of the 40 patients who suffered a tendon rupture, 21 (52.5%) were receiving corticosteroids.(14) Other authors have reported cases of tendon disorders in patients receiving concurrent corticosteroids and ciprofloxacin,(15) levofloxacin, (16-20) and ofloxacin.(21)

Inhaled Direct-Acting Sympathomimetics/Tricyclic Compounds

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

MECHANISM OF ACTION: Unknown. However, it is speculated that direct-acting sympathomimetic amines have an enhanced effect due to tricyclic blockage of norepinephrine reuptake.

CLINICAL EFFECTS: Increased effect of direct acting sympathomimetics.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The concurrent use of inhaled sympathomimetics and tricyclic compounds or the use of these agents within 14 days of each other should be approached with extreme caution.

DISCUSSION: Epinephrine and other direct-acting sympathomimetic amines exert enhanced cardiovascular effects (e.g., arrhythmias, hypertension, and tachycardia) in individuals concurrently receiving or previously treated with tricyclic antidepressants. Protriptyline, amitriptyline, and desipramine have also been reported to interact with direct-acting sympathomimetics. Similarity between cyclobenzaprine and the tricyclic antidepressants consideration of tricyclic antidepressant interactions for cyclobenzaprine.

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)

Formoterol fumarate and fixed combinations containing formoterol fumarate are contraindicated in patients hypersensitive to the drug or any ingredient in the formulation.

Because of the risk of asthma-related death and hospitalization, use of formoterol for the treatment of asthma without concomitant use of long-term asthma controller therapy, such as inhaled corticosteroids, is contraindicated. (See Asthma-related Death and Serious Asthma-related Events under Warnings/Precautions: Warnings, in Cautions and also see Uses: Bronchospasm.)

Formoterol fumarate in fixed combination with budesonide (formoterol/budesonide; Symbicort(R)) and formoterol fumarate in fixed combination with mometasone furoate (formoterol/mometasone; Dulera(R)) are contraindicated as primary treatment of status asthmaticus or other acute episodes of asthma or chronic obstructive pulmonary disease (COPD) when intensive measures are required.

Formoterol fumarate in fixed combination with glycopyrrolate (formoterol/glycopyrrolate; Bevespi(R) Aerosphere(R)) is not indicated for the treatment of asthma.

Mometasone furoate and the fixed combination containing mometasone furoate and formoterol fumarate (mometasone/formoterol) are contraindicated for primary treatment of severe acute asthmatic attacks or status asthmaticus when intensive measures (e.g., oxygen, parenteral bronchodilators, IV corticosteroids ) are required.

Mometasone furoate is contraindicated in patients hypersensitive to the drug or any ingredient (e.g., milk proteins) in the formulation. Mometasone oral inhalation powder contains small amounts of lactose, which has trace amounts of milk proteins. Anaphylactic reactions in patients with milk protein allergy have been reported; therefore, patients with known milk protein allergy should not receive mometasone oral inhalation powder.

Mometasone/formoterol fixed combination is contraindicated in patients hypersensitive to mometasone, formoterol, or any ingredient in the formulation.

There are no contraindication contraindications for this drug.

• Fungal infection
• Ocular hypertension
• Osteoporosis
• Parasitic infection

• Active tuberculosis
• Cardiac arrhythmia
• Cataracts
• Chickenpox
• Chronic myocardial ischemia
• Diabetes mellitus
• Disease of liver
• Glaucoma
• Hypertension
• Hypokalemia
• Hypothalamic-pituitary insufficiency
• Immunosuppression
• Measles
• Osteopenia
• Pheochromocytoma
• Seizure disorder
• Thyrotoxicosis

Adverse effects occurring in 2% or more of adults in clinical trials receiving formoterol fumarate oral inhalation solution for the treatment of COPD include diarrhea, nausea, vomiting, nasopharyngitis, dry mouth, dizziness, and insomnia.

Adverse effects occurring in 3% or more of patients receiving formoterol fumarate in fixed combination with budesonide for the treatment of asthma include nasopharyngitis, headache, upper respiratory tract infection, pharyngolaryngeal pain, sinusitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis.

Adverse effects occurring in 3% or more of patients receiving formoterol fumarate in fixed combination with budesonide for the treatment of COPD include nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection.

Adverse effects occurring in 2% or more of patients receiving formoterol fumarate in fixed combination with glycopyrrolate for the treatment of COPD and more frequently than in those receiving placebo include urinary tract infection and cough.

Adverse effects occurring in 3% or more of patients receiving formoterol fumarate in fixed combination with mometasone furoate for the treatment of asthma and more frequently than in those receiving placebo include nasopharyngitis, sinusitis, and headache.

Adverse effects occurring in 5% or more of patients receiving mometasone furoate oral inhalation powder for the treatment of asthma include headache, allergic rhinitis, pharyngitis, upper respiratory tract infection, sinusitis, oral candidiasis, dysmenorrhea, musculoskeletal pain, back pain, and dyspepsia.

Adverse effects occurring in 3% or more of patients receiving mometasone furoate oral inhalation aerosol for the treatment of asthma include nasopharyngitis, headache, sinusitis, bronchitis, and influenza.

Adverse effects occurring in 3% or more of patients receiving the mometasone/formoterol fixed combination for the treatment of asthma and more frequently than in those receiving placebo include nasopharyngitis, sinusitis, and headache.

Less Frequent

• Chest pain
• Tremor

Rare or Very Rare

• Anaphylaxis
• Anaphylaxis
• Angina
• Angioedema
• Angioedema
• Asthma exacerbation
• Asthma exacerbation
• Atrial fibrillation
• Cardiac arrhythmia
• Cataracts
• Glaucoma
• Hyperglycemia
• Hypersensitivity drug reaction
• Hypertension
• Hypokalemia
• Hypotension
• Hypothalamic-pituitary insufficiency
• Immunosuppression
• Infection
• Malaise
• Metabolic acidosis
• Ocular hypertension
• Osteopenia
• Paradoxical bronchospasm
• Paradoxical bronchospasm
• Tachycardia
• Ventricular premature beats

More Frequent

• Allergic rhinitis
• Back pain
• Diarrhea
• Dizziness
• Dysmenorrhea
• Dyspepsia
• Headache disorder
• Headache disorder
• Insomnia
• Musculoskeletal pain
• Nausea
• Oral candidiasis
• Pharyngitis
• Pharyngitis
• Sinusitis
• Upper respiratory infection
• Vomiting
• Xerostomia

Less Frequent

• Acute abdominal pain
• Cough
• Cramps
• Dyspnea
• Muscle spasm
• Myalgia
• Nausea
• Oropharyngeal candidiasis
• Urinary tract infection

Rare or Very Rare

• Anorexia
• Arthralgia
• Blurred vision
• Cough
• Dry throat
• Earache
• Epistaxis
• Fatigue
• Fatigue
• Flu-like symptoms
• Gastroenteritis
• Nasal passage irritation
• Nervousness
• Pain
• Palpitations
• Pruritus of skin
• Pruritus of skin
• Skin rash
• Skin rash
• Symptoms of anxiety
• Urticaria
• Voice change
• Vomiting

No enhanced messaging available.

Formoterol fumarate oral inhalation solution (Perforomist(R)) and formoterol fumarate in fixed combination with glycopyrrolate (Bevespi(R) Aerosphere(R)) are not indicated for use in children. Safety and efficacy of these preparations in children have not been established.

Safety and efficacy of formoterol fumarate in fixed combination with budesonide (Symbicort(R)) in pediatric patients 12 years of age or older with asthma have been established in studies of up to 12 months' duration. Safety and efficacy of formoterol/budesonide in pediatric patients 6 to less than 12 years of age with asthma have been established in studies of up to 12 weeks' duration; however, the manufacturer states that safety and efficacy of the fixed-combination preparation in children younger than 6 years of age with asthma have not been established.

Safety and efficacy of formoterol fumarate in fixed combination with mometasone furoate (Dulera(R)) in pediatric patients 12 years of age or older with asthma have been established in studies of up to 12 months' duration.

Available data from controlled clinical trials suggest that monotherapy with long-acting beta2-adrenergic agonists increases the risk of asthma-related hospitalization in pediatric and adolescent patients. (See Asthma-related Death and Serious Asthma-related Events under Warnings/Precautions: Warnings, in Cautions.)

Safety and efficacy of mometasone furoate oral inhalation powder have not been established in children younger than 4 years of age.

Safety and efficacy of mometasone furoate oral inhalation aerosol have not been established in children younger than 12 years of age.

Safety and efficacy of the mometasone/formoterol fixed combination have not been established in children younger than 12 years of age.

Use of corticosteroids may lead to suppression of growth in children and adolescents. Therefore, pediatric patients receiving prolonged therapy with orally inhaled mometasone should be monitored periodically (e.g., via stadiometry) for possible adverse effects on growth and development. The benefits of corticosteroid therapy should be weighed against the possibility of growth suppression and the availability of safe and effective alternative therapies. Pediatric patients should be maintained on the lowest possible dosage of mometasone that controls asthma symptoms.

Category C. (See Users Guide.) Formoterol may interfere with uterine contractility; carefully weigh benefit versus risk in labor.

There is an increased risk of adverse perinatal outcomes (e.g., preeclampsia, premature birth, low birth weight, and neonates small for gestational age) in women with poorly or moderately controlled asthma. Pregnant women with asthma should be closely monitored and therapy adjusted as necessary to maintain optimal asthma control.

The effects of formoterol fumarate in fixed combination with budesonide, glycopyrrolate, or mometasone furoate during labor and delivery are not known. Because of the potential for beta-agonist interference with uterine contractility, use of formoterol in fixed combination with budesonide, glycopyrrolate, or mometasone during labor should be restricted to those patients in whom the benefits clearly outweigh the risk.

Category C.

There are no adequate and well-controlled studies with mometasone furoate in pregnant women. The drug should be used during pregnancy only if potential benefits justify potential risks to the fetus.

There is an increased risk of adverse perinatal outcomes (e.g., preeclampsia, premature birth, low birth weight, neonates small for gestational age) in women with poorly or moderately controlled asthma. Pregnant women with asthma should be closely monitored and therapy adjusted as necessary to maintain optimal asthma control.

The effects of mometasone furoate in fixed combination with formoterol fumarate during labor and delivery are not known. Because of the potential for beta-agonist interference with uterine contractility, use of the mometasone/formoterol fixed combination during labor should be restricted to those patients in whom the benefits clearly outweigh the risks.

Hypoadrenalism may occur in infants of women who have received substantial oral corticosteroid dosages during pregnancy. These infants should be carefully monitored.

Formoterol is distributed into milk in rats; it is not known whether formoterol is distributed into human milk. Effects of formoterol fumarate on breast-fed infants or milk production also are not known.

The benefits of breast-feeding and the woman's clinical need for formoterol fumarate alone or in fixed combination with budesonide or mometasone should be considered along with any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

Because many drugs are distributed into human milk, caution should be exercised when formoterol fumarate in fixed combination with glycopyrrolate is administered to nursing women. Since there are no data from controlled clinical studies, the manufacturer of formoterol/glycopyrrolate states that a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

It is not known whether mometasone furoate is distributed into milk; however, other corticosteroids are distributed into milk. Data are not available on the effects of the drug on the breast-fed child or milk production. The benefits of breast-feeding and the importance of mometasone to the woman should be considered along with any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition. The manufacturer of mometasone oral inhalation powder (Asmanex(R) Twisthaler(R)) states that caution is advised if mometasone furoate is administered in nursing women.

The manufacturer of the mometasone/formoterol fixed combination states that a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

The manufacturers of formoterol fumarate and formoterol fumarate in fixed combination with budesonide, glycopyrrolate, or mometasone furoate state that dosage adjustment is not required in geriatric patients.

No substantial differences in safety and efficacy of formoterol alone or in fixed combination with budesonide, glycopyrrolate, or mometasone furoate have been observed in geriatric patients relative to younger adults. However, the manufacturers state that the possibility that some geriatric patients may exhibit increased sensitivity to formoterol or fixed combinations containing formoterol cannot be ruled out. (See Dosage and Administration: Special Populations.)

Although no overall differences in safety and efficacy of orally inhaled mometasone furoate were observed in geriatric patients relative to younger adults, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.