Product Index

For the use of Registered Medical Practitioner or a Hospital or a Laboratory only

 

Qualitative and Quantitative Composition

SEROFLO 100 Rotacaps

Each rotacap contains:

Salmeterol (As Salmeterol Xinafoate IP)………50 mcg

Fluticasone Propionate IP ..................................100 mcg

Excipient…………………….................................q.s.

SEROFLO 250 Rotacaps

Each rotacap contains:

Salmeterol (As Salmeterol Xinafoate IP)………50 mcg

Fluticasone Propionate IP................................. 250 mcg

Excipient…………………….................................q.s.

SEROFLO 500 Rotacaps

Each rotacap contains:

Salmeterol (As Salmeterol Xinafoate IP)...……50 mcg

Fluticasone Propionate IP..................................500 mcg

Excipient……………………................................q.s.

Dosage Form and Strength

Dry powder for inhalation

Salmeterol xinafoate/ fluticasone propionate

(50/ 100 mcg, 50/ 250 mcg, 50/ 500 mcg)

Clinical Particulars

Therapeutic Indication

SEROFLO Rotacaps are indicated in the regular treatment of asthma, where use of a combination (long-acting beta₂-agonist and inhaled corticosteroid) has been found to be appropriate, and in patients with COPD.

Posology and Method of Administration

Asthma

Adults and Adolescents (12 years and older)

SEROFLO-100 Rotacaps: One rotacap twice daily

SEROFLO-250 Rotacaps: One rotacap twice daily

SEROFLO-500 Rotacaps: One rotacap twice daily

Children (4 years and older)

SEROFLO-100 Rotacaps: One rotacap twice daily

COPD

SEROFLO-250 Rotacaps: One rotacap twice daily

SEROFLO-500 Rotacaps: One rotacap twice daily

SEROFLO Rotacaps should only be inhaled with the Cipla Rotahaler/Revolizer device. SEROFLO Rotacaps must not be swallowed.

Contraindications

SEROFLO Rotacaps are contraindicated in patients with a history of hypersensitivity to any of the component of the product.

SEROFLO Rotacaps are contraindicated in the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required.

Special Warnings and Precautions for Use

General

Patients should be made aware that SEROFLO Rotacaps must be used daily for optimum benefit, even when asymptomatic. SEROFLO Rotacaps should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of asthma. As with all inhaled medication containing corticosteroids, SEROFLO Rotacaps should be administered with caution in patients with pulmonary tuberculosis. Patients should not be initiated on SEROFLO Rotacaps during an exacerbation, or if they have significantly worsening or acutely deteriorating asthma. Serious asthma-related adverse events and exacerbations may occur during treatment with SEROFLO Rotacaps. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation on SEROLFO Rotacaps. Treatment with SEROFLO Rotacaps should not be stopped abruptly in patients with asthma due to risk of exacerbation. Therapy should be down-titrated under physician supervision. For patients with COPD cessation of therapy may also be associated with symptomatic decompensation and should be supervised by a physician.

Serious Asthma-Related Events – Hospitalizations, Intubations, Death

Use of LABA as monotherapy (without ICS) for asthma is associated with an increased risk of asthma-related death. Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA monotherapy. When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone.

Deterioration of Disease and Acute Episodes

Salmeterol/ Fluticasone Propionate combination should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of asthma. It has not been studied in subjects with acutely deteriorating asthma. The initiation of this combination in this setting is not appropriate.

Serious acute respiratory events, including fatalities, have been reported when salmeterol, a component of this combination, has been initiated in patients with significantly worsening or acutely deteriorating asthma. In most cases, these have occurred in patients with severe asthma (e.g., patients with a history of corticosteroid dependence, low pulmonary function, intubation, mechanical ventilation, frequent hospitalizations, previous life-threatening acute asthma exacerbations) and in some patients with acutely deteriorating asthma (e.g., patients with significantly increasing symptoms; increasing need for inhaled, short-acting beta2-agonists; decreasing response to usual medications; increasing need for systemic corticosteroids; recent emergency room visits; deteriorating lung function). However, these events have occurred in a few patients with less severe asthma as well. It was not possible from these reports to determine whether salmeterol contributed to these events.

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 SEROFLO Rotacaps with a higher strength, adding additional ICS, or initiating systemic corticosteroids. Patients should not use more than 2 inhalations twice daily of salmeterol/fluticasone combination.

Salmeterol/fluticasone combination should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. It has not been studied in the relief of acute symptoms and extra doses should not be used for that purpose. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist.

When beginning treatment with salmeterol/fluticasone combination, 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.

Excessive Use of salmeterol/fluticasone combination and Use with Other Long-acting Beta2-agonists

Salmeterol/fluticasone combination should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medicines containing LABA, 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 fluticasone/salmeterol combination should not use another medicine containing a LABA (e.g., salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason.

Local Effects of Inhaled Corticosteroids

In clinical trials, the development of localized infections of the mouth and pharynx with Candida albicans has occurred in subjects treated with salmeterol/fluticasone combination. When such an infection develops, it should be treated with appropriate local or systemic (i.e., oral) antifungal therapy while treatment with SEROFLO Rotacaps continues, but at times therapy with SEROFLO Rotacaps may need to be interrupted. Advise the patient to rinse his/her mouth with water without swallowing following inhalation to help reduce the risk of oropharyngeal candidiasis.

Pneumonia

Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of pneumonia and exacerbations frequently overlap.

Lower respiratory tract infections, including pneumonia, have been reported in patients with chronic obstructive pulmonary disease (COPD) following the inhaled administration of corticosteroids, including fluticasone propionate and salmeterol/fluticasone combination.

Immunosuppression

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 been 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 a patient is exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If a patient is exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.

ICS should be used with caution, if at all, in patients with active or quiescent tuberculosis infections of the respiratory tract; systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.

Transferring Patients from Systemic Corticosteroid Therapy

Particular care is needed for patients who have been transferred from systemically active corticosteroids to ICS because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available ICS. After withdrawal from systemic corticosteroids, a number of months are required for recovery of hypothalamic-pituitary-adrenal (HPA) function.

Patients who have been previously maintained on 20 mg or more 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 SEROFLO Rotacaps may control asthma symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of glucocorticoid systemically and does NOT provide the mineralocorticoid activity that is necessary for coping with these emergencies.

During periods of stress or a 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 warning card indicating that they may need supplementary systemic corticosteroids during periods of stress or a severe asthma attack.

Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to SEROFLO Rotacaps. Prednisone reduction can be accomplished by reducing the daily prednisone dose by 2.5 mg on a weekly basis during therapy with SEROFLO Rotacaps. Lung 8 function (mean forced expiratory volume in 1 second or morning peak expiratory flow ), beta-agonist use, and asthma symptoms should be carefully monitored during withdrawal of oral corticosteroids. In addition, 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 SEROFLO Rotacaps  may unmask allergic conditions previously suppressed by the systemic corticosteroid therapy (e.g., rhinitis, conjunctivitis, eczema, arthritis, 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, depression) despite maintenance or even improvement of respiratory function.

Hypercorticism and Adrenal Suppression

Fluticasone propionate, a component of SEROFLO Rotacaps, will often help control asthma symptoms with less suppression of HPA function than therapeutically equivalent oral doses of prednisone. Since fluticasone propionate is absorbed into the circulation and can be systemically active at higher doses, the beneficial effects of SEROFLO Rotacaps in minimizing HPA dysfunction may be expected only when recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose. A relationship between plasma levels of fluticasone propionate and inhibitory effects on stimulated cortisol production has been shown after 4 weeks of treatment with fluticasone propionate inhalation aerosol. Since individual sensitivity to effects on cortisol production exists, physicians should consider this information when prescribing SEROFLO Rotacaps.

Because of the possibility of significant systemic absorption of ICS in sensitive patients, patients treated with SEROFLO Rotacaps 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 who are sensitive to these effects. If such effects occur, SEROFLO Rotacaps should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids, and other treatments for management of asthma symptoms should be considered.

Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors

The use of strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with SEROFLO Rotacaps is not recommended because increased systemic corticosteroid and increased cardiovascular adverse effects may occur (see Drug interactions).

Paradoxical Bronchospasm and Upper Airway Symptoms

As with other inhaled medicines, SEROFLO Rotacaps can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with SEROFLO Rotacaps, it should be treated immediately with an inhaled, short-acting bronchodilator; SEROFLO Rotacaps  should be discontinued immediately; and alternative therapy should be instituted. Upper airway symptoms of laryngeal spasm, irritation, or swelling, such as stridor and choking, have been reported in patients receiving salmeterol/fluticasone combination.

Immediate Hypersensitivity Reactions

Immediate hypersensitivity reactions (e.g., urticaria, angioedema, rash, bronchospasm, hypotension), including anaphylaxis, may occur after administration of SEROFLO Rotacaps.

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 (see Overdosage). Therefore, SEROFLO Rotacaps, like all products containing sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Salmeterol, a component of SEROFLO Rotacaps, 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 salmeterol at recommended doses, if they occur, the drug may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiogram (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. Large doses of inhaled or oral salmeterol (12 to 20 times the recommended dose) have been associated with clinically significant prolongation of the QTc interval, which has the potential for producing ventricular arrhythmias. Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs.

Reduction in Bone Mineral Density

Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing ICS. The clinical significance of small changes in BMD with regard to long-term consequences such as fracture is unknown. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids), should be monitored and treated with established standards of care. Since patients with COPD often have multiple risk factors for reduced BMD, assessment of BMD is recommended prior to initiating fluticasone/salmeterol combination and periodically thereafter. If significant reductions in BMD are seen and fluticasone/salmeterol combination is still considered medically important for that patient’s COPD therapy, use of medicine to treat or prevent osteoporosis should be strongly considered.

Effect on Growth

Orally inhaled corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. Monitor the growth of pediatric patients receiving SEROFLO Rotacaps routinely (e.g., via stadiometry). To minimize the systemic effects of orally inhaled corticosteroids, including SEROFLO Rotacaps  titrate each patient’s dosage to the lowest dosage that effectively controls his/her symptoms (see Dosage and administration, use in specific populations).

Glaucoma and Cataracts

Glaucoma, increased intraocular pressure, and cataracts have been reported in patients with asthma following the long-term administration of ICS, including fluticasone propionate, a component of SEROFLO Rotacaps . Consider referral to an ophthalmologist in patients who develop ocular symptoms or use SEROFLO Rotacaps long term.

Eosinophilic Conditions and Churg-Strauss Syndrome

In rare cases, patients on inhaled fluticasone propionate, a component of SEROFLO Rotacaps, may present with systemic eosinophilic conditions. Some of these patients have clinical features of vasculitis consistent with Churg-Strauss syndrome, a condition that is often treated with systemic corticosteroid therapy. These events usually, but not always, have been associated with the reduction and/or withdrawal of oral corticosteroid therapy following the introduction of fluticasone propionate. Cases of serious eosinophilic conditions have also been reported with other ICS in this clinical setting. Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients. A causal relationship between fluticasone propionate and these underlying conditions has not been established.

Coexisting Conditions

SEROFLO Rotacaps, like all medicines containing sympathomimetic amines, should be used with caution in patients with convulsive disorders or thyrotoxicosis and in those who are unusually responsive to sympathomimetic amines. Large doses of the related beta2-adrenoceptor agonist albuterol, when administered intravenously, have been reported to aggravate preexisting diabetes mellitus and ketoacidosis.

Hypokalemia and Hyperglycemia

Beta-adrenergic agonist medicines may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects (see Pharmacology). 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 trials with salmeterol/fluticasone combination at recommended doses.

Drugs Interactions

SEROFLO Rotacaps has been used concomitantly with other drugs, including short-acting beta2-agonists, methylxanthines, and intranasal corticosteroids, commonly used in patients with asthma without adverse drug reactions. No formal drug interaction trials have been performed with SEROFLO Rotacaps.

Inhibitors of Cytochrome P450 3A4

Fluticasone propionate and salmeterol, the individual components of SEROFLO Rotacaps, are substrates of CYP3A4. The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with SEROFLO Rotacaps is not recommended because increased systemic corticosteroid and increased cardiovascular adverse effects may occur.

Monoamine Oxidase Inhibitors and Tricyclic Antidepressants

SEROFLO Rotacaps should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents, because the action of salmeterol, a component of SEROFLO Rotacaps, on the vascular system may be potentiated by these agents.

Beta-adrenergic Receptor Blocking Agents

Beta-blockers not only block the pulmonary effect of beta-agonists, such as salmeterol, a component of SEROFLO Rotacaps, but may also produce severe bronchospasm in patients with asthma. Therefore, patients with asthma should not normally be treated with beta-blockers. However, under certain circumstances, there may be no acceptable alternatives to the use of beta-adrenergic blocking agents for these patients; cardioselective beta-blockers could be considered, although they should be administered with caution.

Non–Potassium-Sparing Diuretics

The ECG changes and/or hypokalemia that may result from the administration of non–potassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, such as salmeterol, a component of SEROFLO Rotacaps, 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 SEROFLO Rotacaps with non–potassium-sparing diuretics.

Use in Special Population

Patients with Renal Impairment

Formal pharmacokinetic studies using SEROFLO Rotacaps have not been conducted in patients with renal impairment.

Patients with Hepatic Impairment

Formal pharmacokinetic studies using SEROFLO Rotacaps have not been conducted in patients with hepatic impairment. However, since both fluticasone propionate and salmeterol are predominantly cleared by hepatic metabolism, impairment of liver function may lead to accumulation of fluticasone propionate and salmeterol in plasma. Therefore, patients with hepatic disease should be closely monitored.

Pregnant Women

Administration of SEROFLO Rotacaps to pregnant women should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus. The lowest effective dose of fluticasone propionate needed to maintain adequate asthma control should be used in the treatment of pregnant women.

Lactating Women

There are no available data on the presence of fluticasone propionate or salmeterol in human milk, the effects on the breastfed child, or the effects on milk production. Other corticosteroids have been detected in human milk. However, fluticasone propionate and salmeterol concentrations in plasma after inhaled therapeutic doses are low and therefore concentrations in human breast milk are likely to be correspondingly low. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SEROFLO Rotacaps and any potential adverse effects on the breastfed child.

Pediatric Patients

The safety and effectiveness of salmeterol/fluticasone combination in children with asthma younger than 4 years have not been established.

ICS, including fluticasone propionate, a component of the formulation, may cause a reduction in growth velocity in children and adolescents. The growth of pediatric patients receiving orally inhaled corticosteroids, including fluticasone/salmeterol combination, should be monitored.

If a child or adolescent on any corticosteroid appears to have growth suppression, the possibility that he/she is particularly sensitive to this effect of corticosteroids should be considered. The potential growth effects of prolonged treatment should be weighed against the clinical benefits obtained. To minimize the systemic effects of orally inhaled corticosteroids, including fluticasone/salmeterol combination, each patient should be titrated to the lowest strength that effectively controls his/her asthma.

Geriatric Patients

Clinical trials of salmeterol/fluticasone combination did not include sufficient numbers of subjects aged 65 years and older to determine whether older subjects respond differently than younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. In addition, as with other products containing beta2-agonists, special caution should be observed when using SEROFLO Rotacaps in geriatric patients who have concomitant cardiovascular disease that could be adversely affected by beta2-agonists.

Effects on Ability to Drive & Use Machines

SEROFLO Rotacaps has no or negligible influence on the ability to drive and use medicines.

Undesirable Effects

As SEROFLO Rotacaps contains salmeterol and fluticasone propionate, the type and severity of side effects associated with each of the compounds may be expected. There is no incidence of additional side effects following concurrent administration of the two compounds.

Use of long-acting beta agonist may result into:

Serious asthma-related events including hospitalizations, intubations and death, cardiovascular and central nervous system effects

Systemic and local corticosteroid use may result in the following: Candida albicans infection, pneumonia in patients with COPD, immunosuppression, hypercorticism and adrenal suppression, reduction in bone mineral density, growth retardation, glaucoma and cataracts.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse events that occurred in the groups receiving salmeterol/fluticasone in trials, with an incidence of 3% or more and at a greater incidence than with placebo were:

Ear, nose, and throat: Upper respiratory tract infection, pharyngitis, upper respiratory inflammation, sinusitis, hoarseness/dysphonia, candidiasis of mouth/throat, throat irritation

Lower respiratory: Viral respiratory infections, bronchitis, cough

Neurology: Headache, dizziness

Gastrointestinal: Nausea and vomiting, gastrointestinal discomfort and pain, diarrhea, viral gastrointestinal infections

Non-site specific: Candidiasis unspecified site, fever, malaise, and fatigue

Musculoskeletal:  Musculoskeletal pain, muscle cramps and spasms, traumatic fractures, arthralgia, myalgia

Other adverse reactions not previously listed, whether considered drug-related or not by the investigators, that were reported more frequently by subjects with asthma treated or COPD treated with fluticasone/salmeterol combination compared with subjects treated with placebo include the following: palpitations, tachycardia, cardiac arrhythmias (including supraventricular tachycardia and extrasystoles), atrial fibrillation, angina pectoris lymphatic signs and symptoms; muscle injuries; fractures; wounds and lacerations; contusions and hematomas; ear signs and symptoms; nasal signs and symptoms; nasal sinus disorders; nasopharyngitis; nasal congestion; paradoxical bronchospasm; keratitis and conjunctivitis; dental discomfort and pain; gastrointestinal signs and symptoms; oral ulcerations; oral discomfort and pain; lower respiratory signs and symptoms; pneumonia; back pain; muscle stiffness, tightness, and rigidity; bone and cartilage disorders; sleep disorders; compressed nerve syndromes; viral infections; pain; chest symptoms; fluid retention; bacterial infections; unusual taste; viral skin infections; skin flakiness and acquired ichthyosis; disorders of sweat and sebum, hypothyroidism, dry eyes, edema and swelling, hypersensitivity reactions including; dyspnea, bronchospasm, anaphylactic reactions including anaphylactic shock, angioedema,  Cushing's syndrome, Cushingoid features, adrenal suppression, hypokalemia, hypoglycemia, anxiety, sleep disorders, behavioral changes including psychomotor hyperactivity and irritability (predominantly in children), growth retardation in chidren, decreased bone mineral density, depression, aggression (predominantly in children), tremor, cataract, glaucoma, vision blurred.

Common adverse reactions (≥3% and greater than placebo) seen in the pediatric subjects but not reported in the adult and adolescent clinical trials include: throat irritation and ear, nose, and throat infections.

Laboratory Test Abnormalities:

Elevation of hepatic enzymes was reported in ≥1% of subjects in clinical trials. The elevations were transient and did not lead to discontinuation from the trials. In addition, there were no clinically relevant changes noted in glucose or potassium. 

Postmarketing Experience:

In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during post-approval use of any formulation of fluticasone propionate, and/or salmeterol regardless of indication. 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. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to fluticasone propionate, and/or salmeterol or a combination of these factors.

Cardiac Disorders: Arrhythmias (including atrial fibrillation, extrasystoles, supraventricular tachycardia), ventricular tachycardia

Endocrine Disorders: Cushing’s syndrome, Cushingoid features, growth velocity reduction in children/adolescents, hypercorticism

Eye Disorders: Glaucoma

Gastrointestinal Disorders: Abdominal pain, dyspepsia, xerostomia

Immune System Disorders: Immediate and delayed hypersensitivity reaction (including very rare anaphylactic reaction). Very rare anaphylactic reaction in patients with severe milk protein allergy

Infections and Infestations: Esophageal candidiasis

Metabolic and Nutrition Disorders: Hyperglycemia, weight gain

Musculoskeletal, Connective Tissue, and Bone Disorders: Arthralgia, cramps, myositis, osteoporosis

Nervous System Disorders: Paresthesia, restlessness

Psychiatric Disorders: Agitation, aggression, depression, behavioral changes, including hyperactivity and irritability have been reported very rarely and primarily in children.

Reproductive System and Breast Disorders: Dysmenorrhea

Respiratory, Thoracic, and Mediastinal Disorders: Chest congestion; chest tightness; dyspnea; facial and oropharyngeal edema, immediate bronchospasm; paradoxical bronchospasm; tracheitis; wheezing; reports of upper respiratory symptoms of laryngeal spasm, irritation, or swelling such as stridor or choking

Skin and Subcutaneous Tissue Disorders: Ecchymoses, photodermatitis.

Vascular Disorders: Pallor

If you experience any side-effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the national pharmacovigilance program of India by calling on 1800 180 3024 or you can report to Cipla Ltd on 18002677779. By reporting side-effects, you can help provide more information on the safety of this product.

Overdose

There are no data available from clinical trials on overdose with salmeterol/fluticasone; however data on overdose with both drugs are given below:

The signs and symptoms of salmeterol overdose are tremor, headache and tachycardia. The preferred antidotes are cardioselective beta-blocking agents, which should be used with caution in patients with a history of bronchospasm. If SEROFLO ROTACAPS therapy has to be withdrawn due to overdose of the beta agonist component of the drug, provision of appropriate replacement steroid therapy should be considered. Additionally, hypokalaemia can occur and potassium replacement should be considered.

Acute: Acute inhalation of fluticasone propionate doses in excess of those recommended may lead to temporary suppression of adrenal function. This does not need emergency action as adrenal function is recovered in a few days, as verified by plasma cortisol measurements.

Chronic Overdose of Inhaled Fluticasone Propionate:

Adrenal reserve should be monitored and treatment with a systemic corticosteroid may be necessary. When stabilised, treatment should be continued with an inhaled corticosteroid at the recommended dose. In cases of both acute and chronic fluticasone propionate overdose SEROFLO Rotacaps therapy may still be continued at a suitable dosage for symptom control.

Pharmacological Properties

Mechanism of Action

SEROFLO ROTACAPS contains salmeterol and fluticasone propionate which have differing modes of action. The respective mechanisms of action of both drugs are discussed below.

Salmeterol:

Salmeterol is a selective long-acting (12 hour) β2 adrenoceptor agonist with a long side chain which binds to the exo-site of the receptor.

Salmeterol produces a longer duration of bronchodilation, lasting for at least 12 hours, than recommended doses of conventional short-acting β2 agonists.

Fluticasone propionate:

Fluticasone propionate given by inhalation at recommended doses has a glucocorticoid anti-inflammatory action within the lungs, resulting in reduced symptoms and exacerbations of asthma, with less adverse effects than when corticosteroids are administered systemically.

Pharmacodynamic Properties

Asthma clinical trials

A twelve month study (Gaining Optimal Asthma ControL, GOAL), in 3416 adult and adolescent patients with persistent asthma, compared the safety and efficacy of salmeterol/fluticasone combination versus inhaled corticosteroid (Fluticasone Propionate) alone to determine whether the goals of asthma management were achievable. Treatment was stepped up every 12 weeks until **total control was achieved or the highest dose of study drug was reached. GOAL showed more patients treated with salmeterol/fluticasone combination achieved asthma control than patients treated with ICS alone and this control was attained at a lower corticosteroid dose.

Well controlled asthma was achieved more rapidly with salmeterol/fluticasone combination than with ICS alone. The time on treatment for 50% of subjects to achieve a first individual well-controlled week was 16 days for salmeterol/fluticasone combination compared to 37 days for the ICS group. In the subset of steroid naive asthmatics the time to an individual well controlled week was 16 days in the salmeterol/fluticasone combination treatment compared to 23 days following treatment with ICS.

The results of this study suggest that salmeterol/fluticasone combination 50/100 micrograms bd may be considered as initial maintenance therapy in patients with moderate persistent asthma for whom rapid control of asthma is deemed essential.

A double blind, randomised, parallel group study in 318 patients with persistent asthma aged ≥18 years evaluated the safety and tolerability of administering two inhalations twice daily (double dose) of salmeterol/fluticasone combination for two weeks. The study showed that doubling the inhalations of each strength of salmeterol/fluticasone combination for up to 14 days resulted in a small increase in beta agonist-related adverse events (tremor; 1 patient vs 0, palpitations; 6 vs 1 , muscle cramps; 6 vs 1 ) and a similar incidence of inhaled corticosteroid related adverse events (e.g. oral candidiasis; 6 vs 16 , hoarseness; 2 vs 4 ) compared to one inhalation twice daily. The small increase in β agonist-related adverse events should be taken into account if doubling the dose of SFC is considered by the physician in adult patients requiring additional short-term (up to 14 days) inhaled corticosteroid therapy.

Paediatric population:

In a trial conducted in 158 children aged 6 to 16 years with symptomatic asthma, the combination of salmeterol/fluticasone combination is equally efficacious to doubling the dose of fluticasone propionate regarding symptom control and lung function. This study was not designed to investigate the effect on exacerbations.

In a 12 week trial of children aged 4 to 11 years treated with either salmeterol/fluticasone combination 50/100 or salmeterol 50 micrograms + fluticasone propionate 100 micrograms both twice daily, both treatment arms experienced a 14% increase in peak expiratory flow rate as well as improvements in symptom score and rescue salbutamol use. There were no differences between the 2 treatment arms. There were no differences in safety parameters between the 2 treatment arms.

In a 12 week trial of children 4 to 11 years of age randomized in a parallel-group study with persistent asthma and who were symptomatic on inhaled corticosteroid, safety was the primary objective. Children received either salmeterol/fluticasone combination (50/100 micrograms) or fluticasone propionate (100 micrograms) alone twice daily. Two children on salmeterol/fluticasone combination and 5 children on fluticasone propionate withdrew because of worsening asthma. After 12 weeks no children in either treatment arm had abnormally low 24 hour urinary cortisol excretion. There were no other differences in safety profile between the treatment arms.

COPD clinical trials

TORCH was a 3-year study to assess the effect of treatment with salmeterol/fluticasone combination 50/500 micrograms bd, salmeterol 50 micrograms bd, fluticasone propionate (FP) 500 micrograms bd or placebo on all-cause mortality in patients with COPD. COPD patients with a baseline (pre-bronchodilator) FEV1 <60% of predicted normal were randomised to double-blind medication. During the study, patients were permitted usual COPD therapy with the exception of other inhaled corticosteroids, long-acting bronchodilators and long-term systemic corticosteroids. Survival status at 3 years was determined for all patients regardless of withdrawal from study medication. The primary endpoint was reduction in all cause mortality at 3 years for salmeterol/fluticasone combination vs Placebo.

There was a trend towards improved survival in subjects treated with salmeterol/fluticasone combination compared with placebo over 3 years however this did not achieve the statistical significance level p≤0.05.

The percentage of patients who died within 3 years due to COPD-related causes was 6.0% for placebo, 6.1% for salmeterol, 6.9% for FP and 4.7% for salmeterol/fluticasone combination.

The mean number of moderate to severe exacerbations per year was significantly reduced with salmeterol/fluticasone combination as compared with treatment with salmeterol, FP and placebo (mean rate in the salmeterol/fluticasone combination group 0.85 compared with 0.97 in the salmeterol group, 0.93 in the FP group and 1.13 in the placebo). This translates to a reduction in the rate of moderate to severe exacerbations of 25% (95% CI: 19% to 31%; p<0.001) compared with placebo, 12% compared with salmeterol (95% CI: 5% to 19%, p=0.002) and 9% compared with FP (95% CI: 1% to 16%, p=0.024). Salmeterol and FP significantly reduced exacerbation rates compared with placebo by 15% (95% CI: 7% to 22%; p<0.001) and 18% (95% CI: 11% to 24%; p<0.001) respectively.

Health Related Quality of Life, as measured by the St George's Respiratory Questionnaire (SGRQ) was improved by all active treatments in comparison with placebo. The average improvement over three years for salmeterol/fluticasone combination compared with placebo was -3.1 units (95% CI: -4.1 to -2.1; p<0.001), compared with salmeterol was -2.2 units (p<0.001) and compared with FP was -1.2 units (p=0.017). A 4-unit decrease is considered clinically relevant.

The estimated 3-year probability of having pneumonia reported as an adverse event was 12.3% for placebo, 13.3% for salmeterol, 18.3% for FP and 19.6% for salmeterol/fluticasone combination (Hazard ratio for SFC vs placebo: 1.64, 95% CI: 1.33 to 2.01, p<0.001). There was no increase in pneumonia related deaths; deaths while on treatment that were adjudicated as primarily due to pneumonia were 7 for placebo, 9 for salmeterol, 13 for FP and 8 for SFC. There was no significant difference in probability of bone fracture (5.1% placebo, 5.1% salmeterol, 5.4% FP and 6.3% salmeterol/fluticasone combination; Hazard ratio for salmeterol/fluticasone combination vs placebo: 1.22, 95% CI: 0.87 to 1.72, p=0.248.

Pharmacokinetic Properties

Absorption:

Fluticasone Propionate: Healthy Subjects: Fluticasone propionate acts locally in the lung; therefore, plasma levels do not predict therapeutic effect. Studies using oral dosing of labeled and unlabeled drug have demonstrated that the oral systemic bioavailability of fluticasone propionate is negligible (<1%), primarily due to incomplete absorption and presystemic metabolism in the gut and liver. In contrast, the majority of the fluticasone propionate delivered to the lung is systemically absorbed.

Following administration of salmeterol/fluticasone combination to healthy adult subjects, peak plasma concentrations of fluticasone propionate were achieved in 1 to 2 hours. In a single-dose crossover study, a higher-than-recommended dose of salmeterol/fluticasone combination was administered to 14 healthy adult subjects. Two (2) inhalations of the following treatments were administered: salmeterol/fluticasone combination 500/50, fluticasone propionate powder 500 mcg and salmeterol powder 50 mcg given concurrently, and fluticasone propionate powder 500 mcg alone. Mean peak plasma concentrations of fluticasone propionate averaged 107, 94, and 120 pg/mL, respectively, indicating no significant changes in systemic exposures of fluticasone propionate.

In 15 healthy subjects, systemic exposure to fluticasone propionate from 4 inhalations of salmeterol/fluticasone pMDI 230/21 (fluticasone propionate 230 mcg and salmeterol 21 mcg) (920/84 mcg) and 2 inhalations of salmeterol/fluticasone DPI 500/50 (1,000/100 mcg) were similar between the 2 inhalers (i.e., 799 vs. 832 pg•hr/mL, respectively), but approximately half the systemic exposure from 4 inhalations of fluticasone propionate pMDI 220 mcg (880 mcg, AUC = 1,543 pg•hr/mL). Similar results were observed for peak fluticasone propionate plasma concentrations (186 and 182 pg/mL from salmeterol/fluticasone pMDI and DPI respectively, and 307 pg/mL from the fluticasone propionatepMDI). Absolute bioavailability of fluticasone propionate was 5.3% and 5.5% following administration of  salmeterol/fluticasone pMDI and DPI respectively.

Asthma and COPD Patients: Peak steady-state fluticasone propionate plasma concentrations in adult patients with asthma (N = 11) ranged from undetectable to 266 pg/mL after a 500-mcg twice-daily dose of fluticasone propionate inhalation powder using the salmeterol/fluticasone DPI. The mean fluticasone propionate plasma concentration was 110 pg/mL. Full pharmacokinetic profiles were obtained from 9 female and 16 male patients with asthma given fluticasone propionate inhalation powder 500 mcg twice daily from 14 female and 43 male patients with COPD given 250 or 500 mcg twice daily. No overall differences in fluticasone propionate pharmacokinetics were observed.

Peak steady-state fluticasone propionate plasma concentrations in patients with COPD averaged 53 pg/mL (range, 19.3 to 159.3 pg/mL) after treatment with 250 mcg twice daily (N = 30) and 84 pg/mL (range, 24.3 to 197.1 pg/mL) after treatment with 500 mcg twice daily (N = 27) via the fluticasone propionate DPI. In another study in patients with COPD, peak steady-state fluticasone propionate plasma concentrations averaged 115 pg/mL (range, 52.6 to 366.0 pg/mL) after treatment with 500 mcg twice daily via the fluticasone propionate DPI (N = 15) and 105 pg/mL (range, 22.5 to 299.0 pg/mL) via DPI (N = 24).

Salmeterol Xinafoate: Healthy Subjects: Salmeterol xinafoate, an ionic salt, dissociates in solution so that the salmeterol and 1-hydroxy-2-naphthoic acid (xinafoate) moieties are absorbed, distributed, metabolized, and eliminated independently. Salmeterol acts locally in the lung; therefore, plasma levels do not predict therapeutic effect.

Following administration of salmeterol/fluticasone combination in DPI to healthy adult subjects, peak plasma concentrations of salmeterol were achieved in about 5 minutes.

In 15 healthy subjects receiving salmeterol/fluticasone pMDI 230/21 (920/84 mcg) and DPI 500/50 (1,000/100 mcg), systemic exposure to salmeterol was higher (317 vs. 169 pg•hr/mL) and peak salmeterol concentrations were lower (196 vs. 223 pg/mL) following pMDI compared with DPI, although pharmacodynamic results were comparable.

Asthma Patients: Because of the small therapeutic dose, systemic levels of salmeterol are low or undetectable after inhalation of recommended doses (50 mcg of salmeterol inhalation powder twice daily). Following chronic administration of an inhaled dose of 50 mcg of salmeterol inhalation powder twice daily, salmeterol was detected in plasma within 5 to 45 minutes in 7 patients with asthma; plasma concentrations were very low, with mean peak concentrations of 167 pg/mL at 20 minutes and no accumulation with repeated doses.

Distribution:

Fluticasone Propionate: Following intravenous administration, the initial disposition phase for fluticasone propionate was rapid and consistent with its high lipid solubility and tissue binding. The volume of distribution averaged 4.2 L/kg. The percentage of fluticasone propionate bound to human plasma proteins averages 91%. Fluticasone propionate is weakly and reversibly bound to erythrocytes and is not significantly bound to human transcortin.

Salmeterol: The percentage of salmeterol bound to human plasma proteins averages 96% in vitro over the concentration range of 8 to 7,722 ng of salmeterol base per milliliter, much higher concentrations than those achieved following therapeutic doses of salmeterol.

Metabolism:

Fluticasone Propionate: The total clearance of fluticasone propionate is high (average, 1,093 mL/min), with renal clearance accounting for less than 0.02% of the total. The only circulating metabolite detected in man is the 17β-carboxylic acid derivative of fluticasone propionate, which is formed through the CYP 3A4 pathway. This metabolite had less affinity (approximately 1/2,000) than the parent drug for the glucocorticoid receptor of human lung cytosol in vitro and negligible pharmacological activity in animal studies. Other metabolites detected in vitro using cultured human hepatoma cells have not been detected in man.

Salmeterol: Salmeterol base is extensively metabolized by hydroxylation, with subsequent elimination predominantly in the feces. No significant amount of unchanged salmeterol base was detected in either urine or feces.

An in vitro study using human liver microsomes showed that salmeterol is extensively metabolized to α-hydroxysalmeterol (aliphatic oxidation) by CYP 3A4. Ketoconazole, a strong inhibitor of CYP 3A4, essentially completely inhibited the formation of α-hydroxysalmeterol in vitro.

Elimination:

Fluticasone Propionate: Following intravenous dosing, fluticasone propionate showed polyexponential kinetics and had a terminal elimination half-life of approximately 7.8 hours. Less than 5% of a radiolabeled oral dose was excreted in the urine as metabolites, with the remainder excreted in the feces as parent drug and metabolites. Terminal half-life estimates of fluticasone propionate for pMDI, DPI, and fluticasone propionate CFC inhalation aerosol were similar and averaged 5.6 hours.

Salmeterol: In 2 healthy adult subjects who received 1 mg of radiolabeled salmeterol (as salmeterol xinafoate) orally, approximately 25% and 60% of the radiolabeled salmeterol was eliminated in urine and feces, respectively, over a period of 7 days. The terminal elimination half-life was about 5.5 hours (1 volunteer only).

The xinafoate moiety has no apparent pharmacologic activity. The xinafoate moiety is highly protein bound (>99%) and has a long elimination half-life of 11 days. No terminal half-life estimates were calculated for salmeterol following administration of DPI.

Non-Clinical Properties

Animal Toxicology or Pharmacology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Fluticasone Propionate:

Fluticasone propionate demonstrated no tumorigenic potential in mice at oral doses up to 1,000 mcg/kg (approximately 5 times the MRHDID on a mcg/m2 basis) for 78 weeks or in rats at inhalation doses up to 57 mcg/kg (approximately 0.5 times the MRHDID on a mcg/m2 basis) for 104 weeks.

Fluticasone propionate did not induce gene mutation in prokaryotic or eukaryotic cells in vitro. No significant clastogenic effect was seen in cultured human peripheral lymphocytes in vitro or in the in vivo mouse micronucleus test.

Fertility and reproductive performance were unaffected in male and female rats at subcutaneous doses up to 50 mcg/kg (approximately 0.5 times the MRHDID for adults on a mcg/m² basis).

Salmeterol:

In an 18-month carcinogenicity study in CD-mice, salmeterol at oral doses of 1,400 mcg/kg and above (approximately 10 times the MRHDID based on comparison of the plasma AUCs) caused a dose-related increase in the incidence of smooth muscle hyperplasia, cystic glandular hyperplasia, leiomyomas of the uterus, and ovarian cysts. No tumors were seen at 200 mcg/kg (approximately 2 times the MRHDID for adults based on comparison of the AUCs).

In a 24-month oral and inhalation carcinogenicity study in Sprague Dawley rats, salmeterol caused a dose-related increase in the incidence of mesovarian leiomyomas and ovarian cysts at doses of 680 mcg/kg and above (approximately 80 times the MRHDID on a mcg/m2 basis). No tumors were seen at 210 mcg/kg (approximately 25 times the MRHDID on a mcg/m² basis). These findings in rodents are similar to those reported previously for other beta-adrenergic agonist drugs. The relevance of these findings to human use is unknown.

Salmeterol produced no detectable or reproducible increases in microbial and mammalian gene mutation in vitro. No clastogenic activity occurred in vitro in human lymphocytes or in vivo in a rat micronucleus test.

Fertility and reproductive performance were unaffected in male and female rats at oral doses up to 2,000 mcg/kg (approximately 230 times the MRHDID for adults on a mcg/m² basis).

Preclinical

Studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated the occurrence of cardiac arrhythmias and sudden death (with histologic evidence of myocardial necrosis) when beta-agonists and methylxanthines are administered concurrently. The clinical relevance of these findings is unknown.

Description

SEROFLO ROTACAPS is a combination of fluticasone propionate and salmeterol xinafoate.

One active component of SEROFLO ROTACAPS is fluticasone propionate, a corticosteroid having the chemical name S-(fluoromethyl) 6alpha,9-difluoro-11beta,17-dihydroxy-16alpha-methyl-3-oxoandrosta-1,4-diene-17beta carbothioate, 17-propionate and the following chemical structure:

Fluticasone propionate is a white powder with a molecular weight of 500.6, and the empirical formula is C₂₅H₃₁F₃O₅S. It is practically insoluble in water, freely soluble in dimethyl sulfoxide and dimethylformamide, and slightly soluble in methanol and 95% ethanol.

The other active component of SEROFLO ROTACAPS is salmeterol xinafoate, a beta2-adrenergic bronchodilator. Salmeterol xinafoate is the racemic form of the 1-hydroxy-2-naphthoic acid salt of salmeterol. It has the chemical name 4-hydroxy-alpha¹- amino] methyl]-1,3-benzenedimethanol, 1-hydroxy-2-naphthalenecarboxylate and the following chemical structure:

Salmeterol xinafoate is a white powder with a molecular weight of 603.8, and the empirical formula is C₂₅H₃₇NO₄•C₁₁H₈O₃. It is freely soluble in methanol; slightly soluble in ethanol, chloroform, and isopropanol; and sparingly soluble in water.

SEROFLO ROTACAPS contains fluticasone propionate and salmeterol xinafoate along with the excipient lactose.

Pharmaceutical Particulars

Incompatibilities

Not applicable

Shelf-life

As on pack.

Packaging Information

SEROFLO 100 ROTACAPS

SEROFLO 250 ROTACAPS

SEROFLO 500 ROTACAPS

Each sales pack contains 30 Rotacaps.

Storage & Handling Instruction

Store below 30°C.

Protect from moisture.

Keep away from children.

Patient Counselling Information

What is SEROFLO ROTACAPS?

• SEROFLO ROTACAPS combines the inhaled corticosteroid (ICS) medicine fluticasone propionate and the long-acting beta2-adrenergic agonist (LABA) medicine salmeterol.

• ICS medicines such as fluticasone propionate help to decrease inflammation in the lungs. Inflammation in the lungs can lead to breathing problems.
• LABA medicines such as salmeterol help the muscles around the airways in your lungs stay relaxed to prevent symptoms, such as wheezing, cough, chest tightness, and shortness of breath. These symptoms can happen when the muscles around the airways tighten. This makes it hard to breathe.

• SEROFLO ROTACAPS is not used to relieve sudden breathing problems and will not replace a rescue Rotacaps.

• SEROFLO ROTACAPS is for asthmatic patients who need both an ICS and LABA medicine.

Do not use SEROFLO ROTACAPS:

• to relieve sudden breathing problems.
• as a rescue Rotacaps.
• if you are allergic to fluticasone propionate, salmeterol, or any of the ingredients in SEROFLO ROTACAPS.

Before using SEROFLO ROTACAPS, tell your healthcare provider if you:

• have heart problems
• have high blood pressure.
• have seizures.
• have thyroid problems.
• have diabetes.
• have liver problems.
• have weak bones (osteoporosis).
• have an immune system problem.
• have or have had eye problems such as glaucoma, increased pressure in your eye, cataracts, or other changes in vision.
• have any type of viral, bacterial, or fungal infection.
• are exposed to chickenpox or measles.
• are pregnant or plan to become pregnant. It is not known if SEROFLO ROTACAPS may harm your unborn baby.
• are breastfeeding. It is not known if the medicines in SEROFLO ROTACAPS pass into your milk and if they can harm your baby.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. SEROFLO ROTACAPS and certain other medicines may interact with each other. This may cause serious side effects. Especially tell your healthcare provider if you take antifungal or anti-HIV medicines. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

SEROFLO Rotacaps contains lactose, which is a type of sugar. If you have been told by your doctor that you have an intolerance to some sugars, talk to your doctor before using this medicine. The amount of lactose in this medicine does not normally cause problems in people who are lactose intolerant. The excipient lactose contains small amounts of milk proteins, which may cause an allergic reaction.

How should I use SEROFLO ROTACAPS?

Read the step-by-step instructions for using SEROFLO ROTACAPS

• Do not use SEROFLO ROTACAPS unless your healthcare provider has taught you how to use the Rotacaps and you understand how to use it correctly.
• Read the Instructions for Use provided with Revolizer and Rotahaler for details on how to use the device.
• SEROFLO ROTACAPS comes in 3 different strengths. Your healthcare provider has prescribed the strength that is best for you.
• Use SEROFLO ROTACAPS exactly as your healthcare provider tells you to use it.
• Do not use SEROFLO ROTACAPS more often than prescribed.
• Use 1Rotacap (capsule) of SEROFLO ROTACAPS 2 times each day. Use SEROFLO ROTACAPS at the same time each day, about 12 hours apart.
• Rinse your mouth with water after breathing in the medicine. Spit out the water. Do not swallow it.
• If you miss a dose of SEROFLO ROTACAPS, just skip that dose. Take your next dose at your usual time. Do not take 2 doses at 1 time.
• If you take too much SEROFLO ROTACAPS, call your healthcare provider or go to the nearest hospital emergency room right away if you have any unusual symptoms, such as worsening shortness of breath, chest pain, increased heart rate, or shakiness.
• Do not use other medicines that contain a LABA for any reason. Ask your healthcare provider or pharmacist if any of your other medicines are LABA medicines.
• Do not stop using SEROFLO ROTACAPS, even if you are feeling better, unless your healthcare provider tells you to.
• SEROFLO ROTACAPS does not relieve sudden breathing problems. Always have a rescue Rotacaps with you to treat sudden symptoms. If you do not have a rescue Rotacaps, call your healthcare provider to have one prescribed for you.
• Rinse your mouth with water without swallowing after each dose of SEROFLO ROTACAPS. This will help lessen the chance of getting a yeast infection (thrush) in your mouth and throat.
• Call your healthcare provider or get medical care right away if:

• your breathing problems get worse.
• you need to use your rescue medicine more often than usual.
• your rescue medicine does not work as well to relieve your symptoms.
• you need to use 4 or more inhalations of your rescue medicine in 24 hours for 2 or more days in a row.
• you use 1 whole canister of your rescue inhaler in 8 weeks.
• your peak flow meter results decrease. Your healthcare provider will tell you the numbers that are right for you.
• you have asthma and your symptoms do not improve after using SEROFLO ROTACAPS regularly for 1 week.

What are the possible side effects of SEROFLO ROTACAPS?

SEROFLO ROTACAPS can cause serious side effects, including:

• fungal infection in your mouth or throat (thrush). Rinse your mouth with water without swallowing after using SEROFLO ROTACAPS to help reduce your chance of getting thrush.
• pneumonia. SEROFLO ROTACAPS contains fluticasone propionate and salmeterol inhalation powder. SEROFLO ROTACAPS is used to treat people with asthma and people with chronic obstructive pulmonary disease (COPD). People with COPD have a higher chance of getting pneumonia. SEROFLO ROTACAPS may increase the chance of you getting pneumonia. It is not known if SEROFLO ROTACAPS is safe and effective in people with COPD. Call your healthcare provider right away if you have any of the following symptoms:

• increase in mucus (sputum) production
• chills
• change in mucus color
• increased cough
• fever
• increased breathing problems

• weakened immune system and increased chance of getting infections (immunosuppression).
• reduced adrenal function (adrenal insufficiency). Adrenal insufficiency is a condition where the adrenal glands do not make enough steroid hormones. This can happen when you stop taking oral corticosteroid medicines (such as prednisone) and start taking a medicine containing an inhaled steroid (such as SEROFLO ROTACAPS). During this transition period, when your body is under stress such as from fever, trauma (such as a car accident), infection, surgery, or worse COPD symptoms, adrenal insufficiency can get worse and may cause death.

Symptoms of adrenal insufficiency include:

• feeling tired
• nausea and vomiting
• lack of energy
• low blood pressure (hypotension)
• weakness

• sudden breathing problems immediately after inhaling your medicine. If you have sudden breathing problems immediately after inhaling your medicine, stop using SEROFLO ROTACAPS and call your healthcare provider right away.
• serious allergic reactions. Call your healthcare provider or get emergency medical care if you get any of the following symptoms of a serious allergic reaction:

• rash
• swelling of your face, mouth, and tongue
• hives
• breathing problems

• effects on heart.

• increased blood pressure
• chest pain
• a fast or irregular heartbeat

• effects on nervous system.

• tremor
• nervousness

• bone thinning or weakness (osteoporosis).
• slowed growth in children. Your child’s growth should be checked regularly by the healthcare provider while using SEROFLO ROTACAPS.
• eye problems including glaucoma, increased pressure in your eye, cataracts, or other changes in vision. You should have regular eye exams while using SEROFLO ROTACAPS.
• changes in laboratory blood levels (sugar, potassium, certain types of white blood cells).

Common side effects of SEROFLO ROTACAPS include:

• upper respiratory tract infection
• headache
• throat irritation
• dizziness
• hoarseness and voice changes
• nausea and vomiting

These are not all the possible side effects of SEROFLO ROTACAPS. If you experience any side-effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the national pharmacovigilance program of India by calling on 1800 180 3024 or you can report to Cipla Ltd on 18002677779. By reporting side-effects, you can help provide more information on the safety of this product.

How should I store SEROFLO ROTACAPS?

• Store SEROFLO ROTACAPS below 30°C.
• Protect from moisture
• Keep SEROFLO ROTACAPS and all medicines away from children.

General information about the safe and effective use of SEROFLO ROTACAPS.

Medicines are sometimes prescribed for purposes other than those listed in a prescribing information. Do not use SEROFLO ROTACAPS for a condition for which it was not prescribed. Do not give SEROFLO ROTACAPS to other people, even if they have the same symptoms that you have. It may harm them.

Details of Manufacturers

Cipla Ltd.

Peninsula Business Park, Ganapatrao Kadam Marg,

Lower Parel (West), Mumbai,

Maharashtra 400013.

Details of Permission or License Number with Date

MNB/05/109 Dated 24/04/2020

Mfg Lic. No 536 Dated 19/10/2016

M.L NO.M/447/2007 Dated 23/12/2016

Date of Revision

31/08/2020