DRUGS & SUPPLEMENTS
WARNING: ASTHMA-RELATED DEATH
Long-acting beta2-adrenergic agonists (LABA), such as formoterol, one of the active ingredients in Momeplus, increase the risk of asthma-related death. Data from a large placebo-controlled U.S. study that compared the safety of another long-acting beta2-adrenergic agonist (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol is considered a class effect of the LABA, including formoterol. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients. Therefore, when treating patients with asthma, Momeplus should only be used for patients not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue Momeplus) if possible without loss of asthma control, and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use Momeplus for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids.
WARNING: ASTHMA-RELATED DEATH
See full prescribing information for complete boxed warning.
1 INDICATIONS AND USAGE
Momeplus is a combination product containing a corticosteroid and a long-acting beta2-adrenergic agonist indicated for:
1.1 Treatment of Asthma
Momeplus is indicated for the treatment of asthma in patients 12 years of age and older.
Long-acting beta2-adrenergic agonists, such as formoterol, one of the active ingredients in Momeplus, increase the risk of asthma-related death. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients . Therefore, when treating patients with asthma, Momeplus should only be used for patients not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue Momeplus) if possible without loss of asthma control, and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use Momeplus for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids.
Important Limitation of Use
2 DOSAGE AND ADMINISTRATION
For oral inhalation only.
Treatment of asthma in patients ≥12 years: 2 inhalations twice daily of Momeplus 100 mcg/5 mcg or 200 mcg/5 mcg. Starting dosage is based on prior asthma therapy and disease severity. (2.2)
2.1 Administration Information
Momeplus should be administered as two inhalations twice daily every day (morning and evening) by the orally inhaled route. Shake well prior to each inhalation. After each dose, the patient should be advised to rinse his/her mouth with water without swallowing.
The cap from the mouthpiece of the actuator should be removed before using Momeplus.
Momeplus should be primed before using for the first time by releasing 4 test sprays into the air, away from the face, shaking well before each spray. In cases where the inhaler has not been used for more than 5 days, prime the inhaler again by releasing 4 test sprays into the air, away from the face, shaking well before each spray.
The Momeplus canister should only be used with the Momeplus actuator. The Momeplus actuator should not be used with any other inhalation drug product. Actuators from other products should not be used with the Momeplus canister.
2.2 Recommended Dosage
The dosage is either 2 inhalations twice daily of Momeplus 100 mcg/5 mcg or Momeplus 200 mcg/5 mcg. The maximum recommended dosage is two inhalations of Momeplus 200 mcg/5 mcg twice daily (maximum daily dosage 800 mcg/20 mcg).
When choosing the starting dosage strength of Momeplus, consider the patients' disease severity, based on their previous asthma therapy, including the inhaled corticosteroid dosage, as well as the patients' current control of asthma symptoms and risk of future exacerbation.
The maximum benefit may not be achieved for 1 week or longer after beginning treatment. Individual patients may experience a variable time to onset and degree of symptom relief. For patients who do not respond adequately after 2 weeks of therapy with two inhalations of Momeplus 100 mcg/5 mcg twice daily (morning and evening), increasing the dosage to two inhalations of Momeplus 200 mcg/5 mcg twice daily (morning and evening) may provide additional asthma control.
Do not use more than two inhalations twice daily of the prescribed strength of Momeplus as some patients are more likely to experience adverse effects with higher doses of formoterol. If symptoms arise between doses, an inhaled short-acting beta2-agonist should be taken for immediate relief.
If a previously effective dosage regimen of Momeplus fails to provide adequate control of asthma, the therapeutic regimen should be re-evaluated and additional therapeutic options, e.g., replacing the current strength of Momeplus with a higher strength, adding additional inhaled corticosteroid, or initiating oral corticosteroids, should be considered.
3 DOSAGE FORMS AND STRENGTHS
Momeplus is a pressurized metered dose inhaler that is available in 2 strengths.
Momeplus 100 mcg/5 mcg delivers 100 mcg of Momeplus furoate and 5 mcg of formoterol fumarate dihydrate per actuation.
Momeplus 200 mcg/5 mcg delivers 200 mcg of Momeplus furoate and 5 mcg of formoterol fumarate dihydrate per actuation.
Inhalation aerosol containing a combination of Momeplus furoate (100 or 200 mcg) and formoterol fumarate dihydrate (5 mcg) per actuation. (3)
4.1 Status Asthmaticus
Momeplus is contraindicated in the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required.
Momeplus is contraindicated in patients with known hypersensitivity to Momeplus furoate, formoterol fumarate, or any of the ingredients in Momeplus .
5 WARNINGS AND PRECAUTIONS
5.1 Asthma-Related Death
Long-acting beta2-adrenergic agonists, such as formoterol, one of the active ingredients in Momeplus, increase the risk of asthma-related death. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients. Therefore, when treating patients with asthma, physicians should only prescribe Momeplus for patients with asthma not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue Momeplus) if possible without loss of asthma control, and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use Momeplus for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids.
A 28-week, placebo-controlled US study comparing the safety of salmeterol with placebo, each added to usual asthma therapy, showed an increase in asthma-related deaths in patients receiving salmeterol (13/13,176 in patients treated with salmeterol vs. 3/13,179 in patients treated with placebo; RR 4.37, 95% CI 1.25, 15.34). This finding with salmeterol is considered a class effect of the LABAs, including formoterol, one of the active ingredients in Momeplus. No study adequate to determine whether the rate of asthma-related death is increased with Momeplus has been conducted.
Clinical studies with formoterol suggested a higher incidence of serious asthma exacerbations in patients who received formoterol fumarate than in those who received placebo. The sizes of these studies were not adequate to precisely quantify the differences in serious asthma exacerbation rates between treatment groups.
5.2 Deterioration of Disease and Acute Episodes
Momeplus should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of asthma. Momeplus has not been studied in patients with acutely deteriorating asthma. The initiation of Momeplus in this setting is not appropriate.
Increasing use of inhaled, short-acting beta2-agonists is a marker of deteriorating asthma. In this situation, the patient requires immediate re-evaluation with reassessment of the treatment regimen, giving special consideration to the possible need for replacing the current strength of Momeplus with a higher strength, adding additional inhaled corticosteroid, or initiating systemic corticosteroids. Patients should not use more than 2 inhalations twice daily of Momeplus.
Momeplus is not indicated for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. An inhaled, short-acting beta2-agonist, not Momeplus, should be used to relieve acute symptoms such as shortness of breath.
When beginning treatment with Momeplus, patients who have been taking oral or inhaled, short-acting beta2-agonists on a regular basis (e.g., 4 times a day) should be instructed to discontinue the regular use of these drugs.
5.3 Excessive Use of Momeplus and Use with Other Long-Acting Beta2-Agonists
As with other inhaled drugs containing beta2-adrenergic agents, Momeplus should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medications containing long-acting beta2-agonists, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Patients using Momeplus should not use an additional long-acting beta2-agonist (e.g., salmeterol, formoterol fumarate, arformoterol tartrate) for any reason, including prevention of exercise-induced bronchospasm (EIB) or the treatment of asthma.
5.4 Local Effects
In clinical trials, the development of localized infections of the mouth and pharynx with Candida albicans have occurred in patients treated with Momeplus. If oropharyngeal candidiasis develops, it should be treated with appropriate local or systemic antifungal therapy while remaining on treatment with Momeplus therapy, but at times therapy with Momeplus may need to be interrupted. Advise patients to rinse the mouth after inhalation of Momeplus.
Persons who are using drugs that suppress the immune system are more susceptible to infections than healthy individuals.
Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In such children or adults who have not had these diseases or who are not properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.
Momeplus should be used with caution, if at all, in patients with active or quiescent tuberculosis infection of the respiratory tract, untreated systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.
5.6 Transferring Patients from Systemic Corticosteroid Therapy
Particular care is needed for patients who are transferred from systemically active corticosteroids to Momeplus because deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids. After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal function.
Patients who have been previously maintained on 20 mg or more per day of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infection (particularly gastroenteritis) or other conditions associated with severe electrolyte loss. Although Momeplus may improve control of asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of corticosteroid systemically and does NOT provide the mineralocorticoid activity necessary for coping with these emergencies.
During periods of stress or severe asthma attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for further instruction. These patients should also be instructed to carry a medical identification card indicating that they may need supplementary systemic corticosteroids during periods of stress or severe asthma attack.
Patients requiring systemic corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to Momeplus. Lung function (FEV1 or PEF), beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of systemic corticosteroids. In addition to monitoring asthma signs and symptoms, patients should be observed for signs and symptoms of adrenal insufficiency such as fatigue, lassitude, weakness, nausea and vomiting, and hypotension.
Transfer of patients from systemic corticosteroid therapy to Momeplus may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy, e.g., rhinitis, conjunctivitis, eczema, arthritis, and eosinophilic conditions.
During withdrawal from oral corticosteroids, some patients may experience symptoms of systemically active corticosteroid withdrawal, e.g., joint and/or muscular pain, lassitude, and depression, despite maintenance or even improvement of respiratory function.
5.7 Hypercorticism and Adrenal Suppression
Momeplus furoate, a component of Momeplus, will often help control asthma symptoms with less suppression of HPA function than therapeutically equivalent oral doses of prednisone. Since Momeplus furoate is absorbed into the circulation and can be systemically active at higher doses, the beneficial effects of Momeplus in minimizing HPA dysfunction may be expected only when recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose.
Because of the possibility of systemic absorption of inhaled corticosteroids, patients treated with Momeplus should be observed carefully for any evidence of systemic corticosteroid effects. Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response.
It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis) may appear in a small number of patients, particularly when Momeplus furoate is administered at higher than recommended doses over prolonged periods of time. If such effects occur, the dosage of Momeplus should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids and for management of asthma symptoms.
5.8 Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors
Caution should be exercised when considering the coadministration of Momeplus with ketoconazole, and other known strong CYP3A4 inhibitors because adverse effects related to increased systemic exposure to Momeplus furoate may occur .
5.9 Paradoxical Bronchospasm and Upper Airway Symptoms
Momeplus may produce inhalation induced bronchospasm with an immediate increase in wheezing after dosing that may be life-threatening. If inhalation induced bronchospasm occurs, it should be treated immediately with an inhaled, short-acting bronchodilator. Momeplus should be discontinued immediately and alternative therapy instituted.
5.10 Immediate Hypersensitivity Reactions
Immediate hypersensitivity reactions may occur after administration of Momeplus, as demonstrated by cases of urticaria, flushing, allergic dermatitis, and bronchospasm.
5.11 Cardiovascular and Central Nervous System Effects
Excessive beta-adrenergic stimulation has been associated with seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats/min, arrhythmias, nervousness, headache, tremor, palpitation, nausea, dizziness, fatigue, malaise, and insomnia. Therefore, Momeplus should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
Formoterol fumarate, a component of Momeplus, can produce a clinically significant cardiovascular effect in some patients as measured by pulse rate, blood pressure, and/or symptoms. Although such effects are uncommon after administration of Momeplus at recommended doses, if they occur, the drug may need to be discontinued. In addition, beta-agonists have been reported to produce ECG changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression. The clinical significance of these findings is unknown. Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs.
5.12 Reduction in Bone Mineral Density
Decreases in bone mineral density have been observed with long-term administration of products containing inhaled corticosteroids, including Momeplus furoate, one of the components of Momeplus. The clinical significance of small changes in BMD with regard to long-term outcomes, such as fracture, is unknown. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants and corticosteroids) should be monitored and treated with established standards of care.
In a 2-year double-blind study in 103 male and female asthma patients 18 to 50 years of age previously maintained on bronchodilator therapy (Baseline FEV1 85%–88% predicted), treatment with Momeplus furoate dry powder inhaler 200 mcg twice daily resulted in significant reductions in lumbar spine (LS) BMD at the end of the treatment period compared to placebo. The mean change from Baseline to Endpoint in the lumbar spine BMD was -0.015 (-1.43%) for the Momeplus furoate group compared to 0.002 (0.25%) for the placebo group. In another 2-year double-blind study in 87 male and female asthma patients 18 to 50 years of age previously maintained on bronchodilator therapy (Baseline FEV1 82%–83% predicted), treatment with Momeplus furoate 400 mcg twice daily demonstrated no statistically significant changes in lumbar spine BMD at the end of the treatment period compared to placebo. The mean change from Baseline to Endpoint in the lumbar spine BMD was -0.018 (-1.57%) for the Momeplus furoate group compared to -0.006 (-0.43%) for the placebo group.
5.13 Effect on Growth
Orally inhaled corticosteroids, including Momeplus, may cause a reduction in growth velocity when administered to pediatric patients. Monitor the growth of pediatric patients receiving Momeplus routinely (e.g., via stadiometry). To minimize the systemic effects of orally inhaled corticosteroids, including Momeplus, titrate each patient's dose to the lowest dosage that effectively controls his/her symptoms .
5.14 Glaucoma and Cataracts
Glaucoma, increased intraocular pressure, and cataracts have been reported following the use of long-term administration of inhaled corticosteroids, including Momeplus furoate, a component of Momeplus. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts .
5.15 Coexisting Conditions
Momeplus, like other medications containing sympathomimetic amines, should be used with caution in patients with aneurysm, pheochromocytoma, convulsive disorders, or thyrotoxicosis; and in patients who are unusually responsive to sympathomimetic amines. Doses of the related beta2-agonist albuterol, when administered intravenously, have been reported to aggravate preexisting diabetes mellitus and ketoacidosis.
5.16 Hypokalemia and Hyperglycemia
Beta2-agonist medications may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease in serum potassium is usually transient, not requiring supplementation. Clinically significant changes in blood glucose and/or serum potassium were seen infrequently during clinical studies with Momeplus at recommended doses.
6 ADVERSE REACTIONS
Long-acting beta2-adrenergic agonists, such as formoterol, one of the active ingredients in Momeplus, increase the risk of asthma-related death. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients. Data from a large placebo-controlled US trial that compared the safety of another long-acting beta2-adrenergic agonist or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol .
Systemic and local corticosteroid use may result in the following:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Most common adverse reactions (reported in ≥3% of patients) included:
To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience
The safety data described below is based on 3 clinical trials which randomized 1913 patients 12 years of age and older with asthma, including 679 patients exposed to Momeplus for 12 to 26 weeks and 271 patients exposed for 1 year. Momeplus was studied in two placebo- and active-controlled trials (n=781 and n=728, respectively) and in a long-term 52-week safety trial (n=404). In the 12 to 26-week clinical trials, the population was 12 to 84 years of age, 41% male and 59% female, 73% Caucasians, 27% non-Caucasians. Patients received two inhalations twice daily of Momeplus (100 mcg/5 mcg or 200 mcg/5 mcg), Momeplus furoate MDI (100 mcg or 200 mcg), formoterol MDI (5 mcg) or placebo. In the long-term 52-week active-comparator safety trial, the population was 12 years to 75 years of age with asthma, 37% male and 63% female, 47% Caucasians, 53% non-Caucasians and received two inhalations twice daily of Momeplus 100 mcg/5 mcg or 200 mcg/5 mcg, or an active comparator.
The incidence of treatment emergent adverse reactions associated with Momeplus in Table 1 below is based upon pooled data from 2 clinical trials 12 to 26 weeks in duration in patients 12 years and older treated with two inhalations twice daily of Momeplus (100 mcg/5 mcg or 200 mcg/5 mcg), Momeplus furoate MDI (100 mcg or 200 mcg), formoterol MDI (5mcg) or placebo.
Oral candidiasis has been reported in clinical trials at an incidence of 0.7% in patients using Momeplus 100 mcg/5 mcg, 0.8% in patients using Momeplus 200 mcg/5 mcg and 0.5% in the placebo group.
Long-Term Clinical Trial Experience
In a long-term safety trial in patients 12 years and older treated for 52 weeks with Momeplus 100 mcg/5 mcg (n=141), Momeplus 200 mcg/5 mcg (n=130) or an active comparator (n=133), safety outcomes in general were similar to those observed in the shorter 12 to 26 week controlled trials. No asthma-related deaths were observed. Dysphonia was observed at a higher frequency in the longer term treatment trial at a reported incidence of 7/141 (5%) patients receiving Momeplus 100 mcg/5 mcg and 5/130 (3.8%) patients receiving Momeplus 200 mcg/5 mcg. No clinically significant changes in blood chemistry, hematology, or ECG were observed.
6.2 Postmarketing Experience
The following adverse reactions have been reported during post-approval use of Momeplus or post-approval use with inhaled Momeplus furoate or inhaled formoterol fumarate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Cardiac disorders: angina pectoris, cardiac arrhythmias, e.g., atrial fibrillation, ventricular extrasystoles, tachyarrhythmia
Immune system disorders: immediate and delayed hypersensitivity reactions including anaphylactic reaction, angioedema, severe hypotension, rash, pruritus
Investigations: electrocardiogram QT prolonged, blood pressure increased (including hypertension)
Metabolism and nutrition disorders: hypokalemia, hyperglycemia
Respiratory, thoracic and mediastinal disorders: asthma aggravation, which may include cough, dyspnea, wheezing and bronchospasm
7 DRUG INTERACTIONS
In clinical trials, concurrent administration of Momeplus and other drugs, such as short-acting beta2-agonist and intranasal corticosteroids have not resulted in an increased frequency of adverse drug reactions. No formal drug interaction studies have been performed with Momeplus. The drug interactions of the combination are expected to reflect those of the individual components.
7.1 Inhibitors of Cytochrome P450 3A4
The main route of metabolism of corticosteroids, including Momeplus furoate, a component of Momeplus, is via cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4). After oral administration of ketoconazole, a strong inhibitor of CYP3A4, the mean plasma concentration of orally inhaled Momeplus furoate increased. Concomitant administration of CYP3A4 inhibitors may inhibit the metabolism of, and increase the systemic exposure to, Momeplus furoate. Caution should be exercised when considering the coadministration of Momeplus with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) .
7.2 Adrenergic Agents
If additional adrenergic drugs are to be administered by any route, they should be used with caution because the pharmacologically predictable sympathetic effects of formoterol, a component of Momeplus, may be potentiated.
7.3 Xanthine Derivatives
Concomitant treatment with xanthine derivatives may potentiate any hypokalemic effect of formoterol, a component of Momeplus.
Concomitant treatment with diuretics may potentiate the possible hypokalemic effect of adrenergic agonists. The ECG changes and/or hypokalemia that may result from the administration of non-potassium-sparing diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is not known, caution is advised in the coadministration of Momeplus with non-potassium-sparing diuretics.
7.5 Monoamine Oxidase Inhibitors, Tricyclic Antidepressants, and Drugs Known to Prolong the QTc Interval
Momeplus should be administered with caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, macrolides, or drugs known to prolong the QTc interval or within 2 weeks of discontinuation of such agents, because the action of formoterol, a component of Momeplus, on the cardiovascular system may be potentiated by these agents. Drugs that are known to prolong the QTc interval have an increased risk of ventricular arrhythmias.
7.6 Beta-Adrenergic Receptor Antagonists
Beta-adrenergic receptor antagonists and formoterol may inhibit the effect of each other when administered concurrently. Beta-blockers not only block the therapeutic effects of beta2-agonists, such as formoterol, a component of Momeplus, but may produce severe bronchospasm in patients with asthma. Therefore, patients with asthma should not normally be treated with beta-blockers. However, under certain circumstances, e.g., as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-blockers in patients with asthma. In this setting, cardioselective beta-blockers could be considered, although they should be administered with caution.
7.7 Halogenated Hydrocarbons
There is an elevated risk of arrhythmias in patients receiving concomitant anesthesia with halogenated hydrocarbons.
8 USE IN SPECIFIC POPULATIONS
There are no randomized clinical studies of Momeplus, Momeplus furoate, or formoterol fumarate in pregnant women. There are clinical considerations with the use of Momeplus in pregnant women . Animal reproduction studies with Momeplus are not available; however, studies are available with its individual components, Momeplus furoate and formoterol fumarate. In animal reproduction studies, subcutaneous administration of Momeplus furoate to pregnant mice, rats, or rabbits caused increased fetal malformations and decreased fetal survival and growth following administration of doses that produced exposures approximately 1/3 to 8 times the maximum recommended human dose (MRHD) on a mcg/m2 or AUC basis . However, experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than humans. In animal reproduction studies, oral administration of formoterol fumarate to pregnant rats and rabbits caused increased fetal malformations (rats and rabbits), decreased fetal weight (rats), and increased neonatal mortality (rats) following administration of doses that produced exposures approximately 1200 to 49,000 times the MRHD on a mg/m2 or AUC basis . These adverse effects generally occurred at large multiples of the MRHD when formoterol fumarate was administered by the oral route to achieve high systemic exposures. No effects were observed in a study with rats that received formoterol fumarate by the inhalation route at an exposure approximately 500 times the MRHD.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Disease-associated maternal and/or embryo/fetal risk
In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes such as preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control.
Labor or delivery
There are no adequate and well-controlled human studies that have studied the effects of Momeplus during labor and delivery. Because of the potential for beta-agonist interference with uterine contractility, use of Momeplus during labor should be restricted to those patients in whom the benefits clearly outweigh the risk.
In an embryofetal development study with pregnant mice dosed throughout the period of organogenesis, Momeplus furoate produced cleft palate at an exposure approximately one-third of the MRHD (on a mcg/m2 basis with maternal subcutaneous doses of 60 mcg/kg and above) and decreased fetal survival at an exposure approximately equivalent to the MRHD (on a mcg/m2 basis with a maternal subcutaneous dose of 180 mcg/kg). No toxicity was observed with a dose that produced an exposure approximately one-tenth of the MRHD (on a mcg/m2 basis with maternal topical dermal doses of 20 mcg/kg and above).
In an embryofetal development study with pregnant rats dosed throughout the period of organogenesis, Momeplus furoate produced fetal umbilical hernia at exposures approximately 6 times the MRHD (on a mcg/m2 basis with maternal topical dermal doses of 600 mcg/kg and above) and delays in fetal ossification at exposures approximately 3 times the MRHD (on a mcg/m2 basis with maternal topical dermal doses of 300 mcg/kg and above).
In another reproductive toxicity study, pregnant rats were dosed with Momeplus furoate throughout pregnancy or late in gestation. Treated animals had prolonged and difficult labor, fewer live births, lower birth weight, and reduced early pup survival at an exposure that was approximately 8 times the MRHD (on an area under the curve (AUC) basis with a maternal subcutaneous dose of 15 mcg/kg). There were no findings with an exposure approximately 4 times the MRHD (on an AUC basis with a maternal subcutaneous dose of 7.5 mcg/kg).
Embryofetal development studies were conducted with pregnant rabbits dosed with Momeplus furoate by either the topical dermal route or oral route throughout the period of organogenesis. In the study using the topical dermal route, Momeplus furoate caused multiple malformations in fetuses (e.g., flexed front paws, gallbladder agenesis, umbilical hernia, hydrocephaly) at an exposure approximately 3 times the MRHD (on a mcg/m2 basis with maternal topical dermal doses of 150 mcg/kg and above). In the study using the oral route, Momeplus furoate caused increased fetal resorptions and cleft palate and/or head malformations (hydrocephaly and domed head) at an exposure approximately 1/2 of the MRHD (on AUC basis with a maternal oral dose of 700 mcg/kg). At an exposure approximately 2 times the MRHD (on an AUC basis with a maternal oral dose of 2800 mcg/kg), most litters were aborted or resorbed. No effects were observed at an exposure approximately 1/10 of the MRHD (on an AUC basis with a maternal oral dose of 140 mcg/kg).
In embryofetal development studies with pregnant rats and rabbits dosed throughout the period of organogenesis, formoterol fumarate did not cause malformations in either species. However, for pregnant rats dosed throughout organogenesis, formoterol fumarate caused delayed fetal ossification at an exposure approximately 80 times the MRHD (on a mcg/m2 basis with maternal oral doses of 200 mcg/kg and higher) and decreased fetal weight at an exposure approximately 2400 times the MRHD (on a mcg/m2 basis with maternal oral doses of 6000 mcg/kg and above). In a pre- and post-natal development study with rats dosed during the late stage of pregnancy, formoterol fumarate caused stillbirth and neonatal mortality at an exposure approximately 2400 times the MRHD (on a mcg/m2 basis with maternal oral doses of 6000 mcg/kg and above). However, no effects were observed in this study at an exposure approximately 80 times the MRHD (on a mcg/m2 basis with a maternal oral dose of 200 mcg/kg).
In embryofetal development studies, conducted by another testing laboratory, with pregnant rats and rabbits dosed throughout the period of organogenesis, formoterol fumarate was teratogenic in both species. Umbilical hernia, a malformation, was observed in rat fetuses at exposures approximately 1200 times the MRHD (on a mcg/m2 basis with maternal oral doses of 3000 mcg/kg/day and above). Brachygnathia, a skeletal malformation, was observed in rat fetuses at an exposure approximately 6100 times the MRHD (on a mcg/m2 basis with a maternal oral dose of 15,000 mcg/kg/day). In another study with rats, no teratogenic effects were observed with exposures up to approximately 500 times the MRHD (on a mcg/m2 basis with a maternal inhalation dose of 1200 mcg/kg/day). Subcapsular cysts on the liver were observed in rabbit fetuses at an exposure approximately 49,000 times the MRHD (on a mcg/m2 basis with a maternal oral dose of 60,000 mcg/kg/day). No teratogenic effects were observed with exposures up to approximately 3000 times the MRHD (on a mcg/m2 basis with a maternal oral dose of 3500 mcg/kg).
There are no available data on the presence of Momeplus, Momeplus furoate, or formoterol fumarate in human milk, the effects on the breastfed child, or the effects on milk production. Other inhaled corticosteroids, similar to Momeplus furoate, are present in human milk. Formoterol fumarate is present in rat milk; however, due to species specific differences in lactation physiology, animal lactation data may not reliably predict levels in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Momeplus and any potential adverse effects on the breastfed infant from Momeplus or from the underlying maternal condition.
8.4 Pediatric Use
The safety and effectiveness of Momeplus have been established in patients 12 years of age and older in 3 clinical trials up to 52 weeks in duration. In the 3 clinical trials, 101 patients 12 to 17 years of age were treated with Momeplus. Patients in this age-group demonstrated efficacy results similar to those observed in patients 18 years of age and older. There were no obvious differences in the type or frequency of adverse drug reactions reported in this age group compared to patients 18 years of age and older. Similar efficacy and safety results were observed in an additional 22 patients 12 to 17 years of age who were treated with Momeplus in another clinical trial. The safety and efficacy of Momeplus have not been established in children less than 12 years of age.
Controlled clinical studies have shown that inhaled corticosteroids may cause a reduction in growth velocity in pediatric patients. In these studies, the mean reduction in growth velocity was approximately 1 cm per year and appears to depend upon dose and duration of exposure. This effect was observed in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients than some commonly used tests of HPA axis function. The long-term effects of this reduction in growth velocity associated with orally inhaled corticosteroids, including the impact on final adult height, are unknown. The potential for "catch up" growth following discontinuation of treatment with orally inhaled corticosteroids has not been adequately studied.
The growth of children and adolescents receiving orally inhaled corticosteroids, including Momeplus, should be monitored routinely (e.g., via stadiometry). If a child or adolescent on any corticosteroid appears to have growth suppression, the possibility that he/she is particularly sensitive to this effect should be considered. The potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the risks associated with alternative therapies. To minimize the systemic effects of orally inhaled corticosteroids, including Momeplus, each patient should be titrated to his/her lowest effective dose .
8.5 Geriatric Use
A total of 77 patients 65 years of age and older (11 of whom were 75 years and older) have been treated with Momeplus in 3 clinical trials up to 52 weeks in duration. Similar efficacy and safety results were observed in an additional 28 patients 65 years of age and older who were treated with Momeplus in another clinical trial. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. As with other products containing beta2-agonists, special caution should be observed when using Momeplus in geriatric patients who have concomitant cardiovascular disease that could be adversely affected by beta2-agonists. Based on available data for Momeplus or its active components, no adjustment of dosage of Momeplus in geriatric patients is warranted.
8.6 Hepatic Impairment
Concentrations of Momeplus furoate appear to increase with severity of hepatic impairment .
10.1 Signs and Symptoms
Momeplus: Momeplus contains both Momeplus furoate and formoterol fumarate; therefore, the risks associated with overdosage for the individual components described below apply to Momeplus.
Momeplus Furoate: Chronic overdosage may result in signs/symptoms of hypercorticism . Single oral doses up to 8000 mcg of Momeplus furoate have been studied on human volunteers with no adverse reactions reported.
Formoterol Fumarate: The expected signs and symptoms with overdosage of formoterol are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of any of the following signs and symptoms: angina, hypertension or hypotension, tachycardia, with rates up to 200 beats/min., arrhythmias, nervousness, headache, tremor, seizures, muscle cramps, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, hypokalemia, hyperglycemia, and insomnia. Metabolic acidosis may also occur. Cardiac arrest and even death may be associated with an overdose of formoterol.
The minimum acute lethal inhalation dose of formoterol fumarate in rats is 156 mg/kg (approximately 63,000 times the MRHD on a mcg/m2 basis). The median lethal oral doses in Chinese hamsters, rats, and mice provide even higher multiples of the MRHD.
Momeplus: Treatment of overdosage consists of discontinuation of Momeplus together with institution of appropriate symptomatic and/or supportive therapy. The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of Momeplus. Cardiac monitoring is recommended in cases of overdosage.
Momeplus 100 mcg/5 mcg and Momeplus 200 mcg/5 mcg are combinations of Momeplus furoate and formoterol fumarate dihydrate for oral inhalation only.
One active component of Momeplus is Momeplus furoate, a corticosteroid having the chemical name 9,21-dichloro-11(Beta),17-dihydroxy-16 (alpha)-methylpregna-1,4-diene-3,20-dione 17-(2-furoate) with the following chemical structure:
Reading the counter
When to replace your Momeplus:
How do I store Momeplus?
How to clean your Momeplus:
The mouthpiece should be cleaned using a dry wipe after every 7 days of use.
Routine cleaning instructions:
Manufactured for: Merck Sharp & Dohme Corp., a subsidiary of
MERCK & CO., INC., Whitehouse Station, NJ 08889, USA
Manufactured by: 3M Health Care Ltd., Loughborough, United Kingdom.
This Medication Guide has been approved by the U.S. Food and Drug Administration.
For patent information: www.merck.com/product/patent/home.html
The trademarks depicted herein are owned by their respective companies.
Copyright © 2010 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
All rights reserved.
PRINCIPAL DISPLAY PANEL - 100 mcg/5 mcg Inhaler Carton
(mometasone furoate and
formoterol fumarate dihydrate)
100 mcg/5 mcg
For oral inhalation only
Attention Health Care Professional:
Dispense the enclosed Medication Guide to each patient.
SHAKE WELL BEFORE USING.
Momeplus canister to be used with Momeplus actuator only.
120 Metered Actuations
Net Wt. 13g
PRINCIPAL DISPLAY PANEL - 100 mcg/5 mcg Inhaler Carton
PRINCIPAL DISPLAY PANEL - 200 mcg/5 mcg Inhaler Carton
(mometasone furoate and
formoterol fumarate dihydrate)
200 mcg/5 mcg
For oral inhalation only
Attention Health Care Professional:
Dispense the enclosed Medication Guide to each patient.
SHAKE WELL BEFORE USING.
Momeplus canister to be used with Momeplus actuator only.
120 Metered Actuations
Net Wt. 13g
PRINCIPAL DISPLAY PANEL - 200 mcg/5 mcg Inhaler Carton
Momeplus pharmaceutical active ingredients containing related brand and generic drugs:
Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.
Momeplus available forms, composition, doses:
Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.
Momeplus destination | category:
Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.
Momeplus Anatomical Therapeutic Chemical codes:
A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.
Momeplus pharmaceutical companies:
Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.
Frequently asked QuestionsCan i drive or operate heavy machine after consuming Momeplus?
Depending on the reaction of the Momeplus after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Momeplus not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is Momeplus addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
ReviewsDrugs.com conducted a study on Momeplus, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Momeplus consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.
The information was verified by Dr. Arunabha Ray, MD Pharmacology