MAXIFLO Rotacaps (Formoterol fumarate + Fluticasone propionate)

Table of Content

Composition

MAXIFLO-100 Rotacaps

Each capsule contains

Formoterol fumarate Dihydrate IP……………………6 mcg

Fluticasone propionate IP…. ………..100 mcg

Excipient………………………………..q.s.

MAXIFLO – 250 Rotacaps

Each capsule contains

Formoterol fumarate Dihydrate IP…………………..6 mcg

Fluticasone propionate IP……………250 mcg

Excipient……………………………....q.s.

Dosage Form

Dry Powder for inhalation

Description

MAXIFLO Rotacaps is a combination of fluticasone propionate, a synthetic corticosteroid and formoterol; a selective long acting beta2-agonist.

Fluticasone propionate is a synthetic, trifluorinated glucocorticoid with potent anti-inflammatory activity. Formoterol is a very potent long-acting adrenoceptor beta2-agonist with a high intrinsic activity and a rapid onset of action. As with other combinations of inhaled corticosteroids and long-acting beta2-adrenergic agonists, the additive effect produces a reduction in the exacerbation of asthma.

Pharmacology

Pharmacodynamics

MAXIFLO Rotacaps contain both fluticasone and formoterol; therefore, the mechanisms of action described below for the individual components apply to MAXIFLO Rotacaps. These drugs represent two classes of medications (a synthetic corticosteroid and a long-acting, selective beta2-adrenoceptor agonist) that have different effects on the clinical, physiological, and inflammatory indices of asthma.

Fluticasone Propionate

Fluticasone propionate is a synthetic, trifluorinated corticosteroid with potent anti-inflammatory activity. Fluticasone propionate reduces the symptoms, improves lung function and prevents exacerbations of asthma, with fewer adverse effects than when corticosteroids are administered systemically. The use of an inhaled steroid improves symptomatic control of asthma, should reduce the need for short-acting bronchodilators and may limit the reduction in lung function over time.

Formoterol Fumarate

Formoterol fumarate is a potent long-acting, selective beta2-adrenergic agonist with a rapid onset of action. Inhaled formoterol fumarate acts locally in the lungs as a bronchodilator, which provides symptomatic relief. After a single dose, onset of bronchodilation occurs rapidly within 1-3 minutes, with duration of effect of at least 12 hours. In vitro studies have shown that formoterol has over 200-fold greater agonist activity at beta2-receptors than at beta1-receptors. The in vitro binding selectivity to beta2-adrenoceptors over beta1-adrenoceptors is higher for formoterol than for salbutamol (5 times), whereas salmeterol has a higher (3 times) beta2-selectivity ratio than formoterol.  Formoterol has been studied in the treatment of conditions associated with COPD, and has been shown to improve symptoms and pulmonary function and quality of life. Formoterol acts on the reversible component of the disease.

Although beta2-receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta1-receptors are the predominant receptors in the heart, there are also beta2-receptors in the human heart, which comprise 10–50% of the total beta-adrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective beta2-agonists may have cardiac effects.

The pharmacological effects of beta2-adrenoceptor agonist drugs, including formoterol, are, at least in part, attributable to the stimulation of intracellular adenyl cyclase, the enzyme that catalyses the conversion of adenosine triphosphate (ATP) to cyclic-3′, 5′-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibit the release of mediators of immediate hypersensitivity from the cells, especially from mast cells.

Pharmacokinetics

Fluticasone Propionate

Absorption:  Fluticasone propionate acts locally in the lung; therefore, plasma levels do not predict therapeutic effect. Absorption is initially rapid then prolonged. 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.

Distribution:  Following intravenous administration, fluticasone propionate is extensively distributed in the body. 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.

Metabolism:  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 17 beta-carboxylic acid derivative of fluticasone propionate, which is formed through the cytochrome P450 3A4 isoform subfamily (CYP 3A4) pathway. This metabolite has only very weak affinity for the glucocorticoid receptor of human lung cytosol in vitro.

Elimination:  87-100% of an oral dose is excreted in the faeces, up to 75% as parent compound. There is also a non-active major metabolite. 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.

Formoterol Fumarate

Absorption: Following inhalation of a single 120 mcg dose of formoterol fumarate by healthy subjects, formoterol was rapidly absorbed into plasma, reaching a maximum drug concentration of 91.6 pg/mL within 5 minutes of inhalation. In COPD patients treated for 12 weeks with formoterol fumarate 12 or 24 mcg b.i.d., the mean plasma concentrations of formoterol ranged between 4.0 and 8.9 pg/mL and 8.0 and 17.3 pg/mL, respectively, at 10 min, 2 h and 6 h post inhalation.

Following inhalation of 12 to 96 mcg of formoterol fumarate by 10 healthy males, urinary excretion of both (R,R)- and (S,S)-enantiomers of formoterol increased proportionally to the dose. Thus, absorption of formoterol following inhalation appeared linear over the dose range studied.

In studies investigating the cumulative urinary excretion of formoterol and/or its (RR) and (SS)-enantiomers, absorption increased linearly with the dose after inhalation of 12-96 micrograms of dry powder or aerosol formulations. After 12 weeks’ administration of 12 or 24 micrograms formoterol powder twice daily, the urinary excretion of unchanged formoterol increased by 63-73% in adult patients with asthma, by 19-38% in adult patients with COPD and by 18-84% in children. These results suggested a modest and self-limiting accumulation of formoterol in plasma after repeated dosing.

Distribution: The binding of formoterol to human plasma proteins in vitro was 61%-64% (34% primarily to albumin). There is no saturation of binding sites in the concentration range reached with therapeutic doses. The concentrations of formoterol used to assess the plasma protein binding were higher than those achieved in plasma following inhalation of a single 120 micrograms dose.

Metabolism: Formoterol is metabolized primarily by direct glucuronidation with O-demethylation followed by further glucuronidation being another pathway. Minor pathways involve sulfate conjugation of formoterol and deformylation followed by sulfate conjugation. Multiple isozymes catalyse the glucuronidation (UGT1A1, 1A3, 1A6, 1A7, 1A8, 1A9, 1A10, 2B7 and 2B15) and O-demethylation (CYP 2D6, 2C19, 2C9 and 2A6) of formoterol, and consequently the potential for metabolic drug-drug interaction is low. Formoterol did not inhibit cytochrome P450 isozymes at therapeutically relevant concentrations. The kinetics of formoterol is similar after single and repeated administration, indicating no auto-induction or inhibition of metabolism.

Excretion: In asthmatic and COPD patients treated for 12 weeks with 12 or 24 micrograms formoterol fumarate twice daily, approximately 10% and 7% of the dose, respectively, were recovered in the urine as unchanged formoterol. In asthmatic children, approximately 6% of the dose was recovered in the urine as unchanged formoterol after multiple dosing of 12 and 24 micrograms. The (R, R) and (S, S)-enantiomers accounted for 40% and 60% respectively of urinary recovery of unchanged formoterol, after single doses (12 to 120 micrograms) in healthy volunteers, and after single and repeated doses in asthma patients. After a single oral dose of 3H-formoterol, 59-62% of the dose was recovered in the urine and 32-34% in the faeces. Renal clearance of formoterol is 150 mL/min. From urinary excretion rates measured in these subjects, the mean terminal elimination half-lives for the (R,R)- and (S,S)-enantiomers were determined to be 13.9 and 12.3 hours, respectively. Peak excretion occurs within 1.5 hours. Approximately 6.4-8% of the dose was recovered in the urine as unchanged formoterol, with the (R, R) and (S, S)-enantiomers contributing 40% and 60%, respectively.  

Indications

MAXIFLO Rotacaps are indicated in the regular maintenance 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 severe COPD.

Dosage and Administration

Asthma

Adults and Adolescents (12 years and older)

MAXIFLO-100: 1-2 Rotacaps twice daily

MAXIFLO-250: 1-2 Rotacaps twice daily

Children (5 years and older)

MAXIFLO-100: One Rotacap twice daily

Not recommended for children below 5 years of age.

COPD

MAXIFLO – 250: Two Rotacaps twice daily

Contraindications

MAXIFLO Rotacaps are contraindicated in patients with a history of hypersensitivity to formoterol or any other component of the drug product.

Warnings and Precautions

Patients should be made aware that MAXIFLO Rotacaps must be used daily for optimum benefit, even when asymptomatic.

MAXIFLO Rotacaps should not be used to treat acute asthma symptoms for which a fast and short-acting bronchodilator is required. Patients should be advised to have their relief medication available at all times.

Patients should not be initiated on MAXIFLO 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 fluticasone propionate/formoterol fumarate combination. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation on Maxiflo Rotacaps.

Increasing use of short-acting bronchodilators to relieve asthma symptoms indicates a deterioration of asthma control, and these patients should be reviewed by a physician. Sudden and progressive deterioration in the control of asthma is potentially life-threatening and these patients require urgent medical assessment. Patients should be medically reviewed when their current dosage of MAXIFLO Rotacaps fails to give adequate control of asthma. Consideration should be given to either increasing, or to additional corticosteroid therapies. The lowest effective dose of MAXIFLO Rotacaps should be used. Treatment with MAXIFLO Rotacaps should not be stopped abruptly in patients with asthma, due to risk of exacerbation. Therapy should be down-titrated under the supervision of a physician.

To Avoid Overtreatment and Unnecessary Adverse Effects

Initiate therapy with sufficient medication to achieve best lung function promptly after about 3 months of good control (which is characterised by few symptoms, minimal use of short-acting beta2 agonists, and no exercise limitation), reduce inhaled corticosteroids to the minimum dose needed to maintain adequate asthma control (‘stepping down’).

Consider seasonal adjustment of doses as the minimum required dose may vary. As with all inhaled medication containing corticosteroids, MAXIFLO Rotacaps should be administered with caution in patients with pulmonary tuberculosis, untreated systemic infections, ocular herpes simplex or patients with fungal, viral or other infections of the airway. Any such infections must always be adequately treated if MAXIFLO Rotacaps is being used.

An exacerbation of the clinical symptoms of asthma may be due to acute respiratory tract bacterial infection and treatment may require appropriate antibiotics, increased inhaled corticosteroids and a short course of oral corticosteroids. A rapid-acting inhaled bronchodilator should be used as rescue medication.

The prophylactic use of fluticasone propionate/formoterol fumarate combination in exercise-induced asthma has not been studied. For such use, a separate rapid-acting bronchodilator should be considered.

Cardiovascular Effects

Cardiovascular effects such as increases in systolic blood pressure and heart rate, may occasionally be seen with all sympathomimetic drugs, especially at higher than therapeutic doses. For this reason, MAXIFLO Rotacaps should be administered with caution in patients with pre-existing cardiovascular disorders, including prolongation of the QTc interval. Formoterol itself may induce prolongation of the QTc interval.

A transient decrease in serum potassium may occur with all sympathomimetic drugs at higher therapeutic doses.

MAXIFLO Rotacaps should be used with caution in patients with a history of thyrotoxicosis, phaeochromocytoma, diabetes mellitus, uncorrected hypokalaemia or patients predisposed to low levels of serum potassium, hypertrophic obstructive cardiomyopathy, idiopathic sub-valvular aortic stenosis, severe hypertension, aneurysm or other severe cardiovascular disorders, such as ischaemic heart disease, cardiac arrhythmias or severe heart failure.

As for all beta2-agonists, additional blood sugar controls should be considered for diabetic patients.

Potentially serious hypokalaemia may result from systemic beta2-agonist therapy.

Concomitant treatment of beta2-agonists with drugs which can induce or potentiate a hypokalaemic effect. e.g. xanthine derivatives, steroids and diuretics, may add to a possible hypokalaemic effect of the of beta2-agonist. Particular caution is recommended in unstable asthma with variable use of rescue bronchodilators, in acute severe asthma as the associated risk may be augmented by hypoxia and in other conditions when the likelihood for hypokalaemia adverse effects is increased. It is recommended that serum potassium levels are monitored during these circumstances. Care should be taken when transferring patients to MAXIFLO Rotacaps therapy, particularly if there is any reason to suppose that adrenal function is impaired from previous systemic steroid therapy.

As with other inhalation therapy paradoxical bronchospasm may occur, with an immediate increase in wheezing after dosing. In such a case, MAXIFLO Rotacaps should be discontinued immediately, the patient assessed and alternative therapy instituted, if necessary.

Possible Systemic Effects, Including Adrenocortical Function, Bone Density and Growth

Inhaled steroids are designed to direct glucocorticoid delivery to the lungs in order to reduce overall systemic glucocorticoid exposure and side effects. With sufficient doses however, all inhaled steroids can have adverse effects; possible systemic effects include Cushing’s syndrome, Cushingoid features, depression of the hypothalamic-pituitary adrenal (HPA) axis, reduction of bone mineral density, cataract, glaucoma and retardation of growth rate in children and adolescents. More rarely, psychological or behavioural effects have included psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression, particularly in children.

The lowest dose of inhaled fluticasone that causes suppression of the HPA axis (as indicated by the 24-hour urinary cortisol concentrations), effects on bone mineral density or growth retardation in children has not yet been established. Some depression of plasma cortisol may occur in a small number of adult patients on higher doses (e.g. >1 mg/day). In situations of possible impaired adrenal function, HPA axis function should be monitored regularly. Adrenal function and adrenal reserve usually remain within normal range on inhaled fluticasone propionate therapy. However, prolonged treatment with high doses of inhaled corticosteroids may result in adrenal suppression and acute adrenal crisis.

Data regarding the effect of long term use of inhaled fluticasone on bone mineral density in elderly patients are limited.

Patients in a medical or surgical emergency, who in the past have required high doses of inhaled steroids and/or intermittent treatment with oral steroids, remain at risk of impaired adrenal reserve for a considerable time. The extent of the adrenal impairment may require specialist advice before elective procedures. The possibility of residual impaired adrenal response should always be borne in mind in emergency and elective situations likely to produce stress and appropriate corticosteroid treatment must be considered.

In rare cases, inhaled therapy may unmask underlying eosinophilic conditions (e.g. Churg Strauss syndrome). These cases have usually been associated with reduction or withdrawal of oral corticosteroid therapy. A direct causal relationship has not been established.

Additional systemic corticosteroid treatment should be considered during periods of stress or elective surgery.

Visual Disturbance

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

Effects on Laboratory Tests

A transient decrease in serum potassium may occur with all sympathomimetic drugs (formoterol component of Maxiflo Rotacaps) at higher therapeutic doses.

Drug Interactions

No formal drug interaction studies have been performed with fluticasone propionate/formoterol fumarate combination.

CYP34A Inhibitors

There is an increased risk of systemic side-effects when combining fluticasone propionate with potent CYP3A4 inhibitors. Fluticasone propionate, an individual component of Maxiflo Rotacaps, is a substrate of CYP 3A4. Caution needs to be taken in long-term treatment of co-medication of strong CYP3A4 inhibitors (e.g. ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nelfinavir, saquinavir, ketoconazole, telithromycin) together with MAXIFLO Rotacaps and co-administration with such drugs should be avoided if possible. Particularly co-medication of ritonavir should be avoided unless the benefit outweighs the increased risks. Information about this interaction is lacking for inhaled fluticasone propionate, but a marked increase in fluticasone propionate plasma levels is expected. Cases of Cushing's syndrome and adrenal suppression have been reported.

Non-Potassium Sparing Diuretics

The ECG changes and/or hypokalaemia that may result from the administration of non-potassium sparing diuretics (such as loop or thiazide 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 co-administration of a beta-agonist with non-potassium sparing diuretics.

Xanthine Derivatives and Glucocorticosteroids

Xanthine derivatives and glucocorticosteroids may add to the possible hypokalaemic effect of beta-agonists discussed above.

Digitalis Glycosides

Hypokalaemia may increase the risk of arrhythmias in patients who are treated with digitalis glycosides.

Halogenated Hydrocarbon Anaesthetics

There is an elevated risk of arrhythmias in patients receiving concomitant anaesthesia with halogenated hydrocarbons.

Monoamine Oxidase Inhibitors

Concomitant treatment with monoamine oxidase inhibitors (MAOIs), including agents with similar properties such as furazolidone and procarbazine, may precipitate hypertensive reactions.

Drugs known to Prolong QTc interval

Formoterol fumarate, as with other beta2-agonists, should be administered with extreme caution to patients being treated with MAOIs or tricyclic antidepressants (or within two weeks of their discontinuation), or drugs known to prolong the electrocardiographic QTc interval such as quinidine, disopyramide, procainamide, phenothiazines and antihistamines. Drugs that are known to prolong the QTc interval increase the risk of ventricular arrhythmias.

Adrenergic Drugs

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 may be potentiated. Concomitant use of beta-adrenergic drugs can have a potentially additive effect.

Beta-Blockers

Beta-adrenergic receptor antagonists (beta-blockers) and formoterol fumarate may inhibit the effect of each other when administered concurrently. Beta-blockers may also produce severe bronchospasm in asthmatic patients. Therefore, patients with asthma should not normally be treated with beta-blockers and this includes beta-blockers used as eye drops for treatment of glaucoma. 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.

L-Dopa, L-Thyroxine, Oxytocin and Alcohol

L-dopa, L-thyroxine, oxytocin and alcohol can impair cardiac tolerance towards beta2 sympathomimetics.

Sodium Cromoglycate

MAXIFLO Rotacaps contain sodium cromoglycate at non-pharmacological levels. Patients should not discontinue any cromoglycate-containing medication.

Renal Impairment

Pharmacokinetic studies using formoterol/fluticasone have not been conducted to examine differences in patients with renal impairment.

Hepatic Impairment

Pharmacokinetic studies using formoterol/fluticasone have not been conducted to examine differences in patients with hepatic impairment. The pharmacokinetics of formoterol have not been studied in subjects with hepatic impairment. However, since fluticasone propionate is predominantly cleared by hepatic metabolism, an increased exposure can be expected in patients with severe hepatic impairment.

Pregnancy

There are no adequate and well-controlled studies with fluticasone propionate/formoterol fumarate combination in pregnant women. Studies in animals have shown reproductive toxicity.  Administration of MAXIFLO Rotacaps is not recommended during pregnancy and should only be considered if the expected benefit to the mother is greater than any possible risk to the fetus.

Labour

Because of the potential for beta-agonist interference with uterine contractility, use of MAXIFLO Rotacaps for the management of asthma during labour should be restricted to those patients in whom the benefit outweighs the risks, and the lowest effective dose to maintain adequate asthma control should be used.

Lactation

It is not known whether fluticasone propionate or formoterol fumarate, or their metabolites, are excreted in human breast milk. Such excretion has been demonstrated for both drugs in lactating rats. In addition, growth and survival of pups were found to be decreased when lactating rats were given formoterol fumarate at oral doses greater than 1 mg/kg/day. A risk to the suckling child cannot be excluded. Use of MAXIFLO Rotacaps in women who are breastfeeding should only be considered if the expected benefit to the nursing mother is greater than any possible risk to the infant.

Paediatric Use

The safety and efficacy of fluticasone propionate/formoterol fumarate have not been assessed in children under 12 years of age. Therefore, MAXIFLO Rotacaps are not recommended for children under 12 years.

Geriatric Use

There is no need to adjust the dose in elderly patients

Undesirable Effects

Adverse effects of fluticasone propionate/formoterol fumarate combination are listed by system organ class (SOC), in order of decreasing seriousness within each SOC in Table 1.

Table 1: Adverse Effects Associated with Fluticasone Propionate/Formoterol Fumarate Combination

System Organ Class

 

 

 

Adverse Effect

Frequency

Infections and infestations

 

Oral candidiasis

Oral fungal infection

Sinusitis

Rare

Metabolism and nutrition disorders

Hyperglycaemia

Uncommon

Psychiatric disorders

 

Sleep disorders including insomnia

 

Uncommon

 

Abnormal dreams

Agitation

Rare

 

Psychomotor hyperactivity, anxiety,

depression, aggression, behavioural changes (predominantly in children)

Not known

 

Nervous system disorders

 

Headache

Tremor

Dizziness

Dysgeusia

Uncommon

 

Ear and labyrinth disorders

Vertigo

Rare

Cardiac disorders

 

Palpitations

Ventricular extrasystoles

Uncommon

 

Angina pectoris

Tachycardia

Angina pectoris

Tachycardia

Vascular disorders

Hypertension

Rare

Respiratory, thoracic and mediastinal disorders

 

Exacerbation of asthma

Dysphonia

Throat irritation

Uncommon

 

Dyspnoea

Cough

Rare

 

Gastrointestinal disorders

 

Dry mouth

 

Uncommon

 

Diarrhoea

Dyspepsia

Rare

Skin and subcutaneous tissue disorders

Rash

Uncommon

Pruritus

Rare

Musculoskeletal connective tissue disorders

Muscle spasms

 

Rare

 

General and administration site disorders

 

Peripheral oedema

Uncommon

Asthenia

Rare

Frequency: very common (≥ 1/10); common (≥ 1/100 and <1/10); uncommon (≥ 1/1,000 and <1/100); rare (≥ 1/10,000 and < 1/1,000); very rare (<1/10,000 including isolated reports); not known (cannot be estimated from the available data).

As with other inhalation therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing and shortness of breath after dosing. Paradoxical bronchospasm responds to a rapid-acting inhaled bronchodilator and should be treated immediately. Inhalation therapy should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary.

The common adverse events that occur with ≥1%incidence in any treatment group in the pooled analysis were as follows:

Infections and Infestations

Bronchitis, ear infection, gastroenteritis viral, influenza, laryngitis, nasopharyngitis, pharyngitis, pneumonia pneuomococcal, respiratory infection, rhinitis, sinusitis, tonsillitis, upper respiratory tract infection, urinary tract infection, viral infection, 

Respiratory thoracic and mediastinal disorders: Asthma, cough, dyspnea, dysphonia, rhinitis allergic, rhinitis seasonal

Nervous system disorders: Headache

Psychiatric disorders: Depression

Renal and urinary disorders: Dysuria

Reproductive and breast disorders: Adenomyosis

Gastrointestinal disorders: Abdominal pain upper, diarrhea, vomiting

Musculoskeletal and connective tissue disorder: Arthralgia, back pain, myalgia, pain in extremity

Injury, poisoning and procedural complications: Fall, neck injury

Metabolism and nutrition disorders: Hypercholesterolaemia, hyperlipidaemia

Vascular disorders: Hypertension

Neoplasms benign, malignant and unspecified (including cysts and polyps): Melanocytic naevus, prostatic adenoma, skin papilloma

Surgical and medical procedures: Dental prosthesis placement   

As MAXIFLO Rotacaps contains formoterol and fluticasone propionate, the type and severity of side effects associated with each of the compounds may be expected.

Formoterol Fumarate

Hypersensitivity reactions (including hypotension, angioneurotic oedema, pruritus, exanthema), QTc interval prolongation, hypokalaemia, nausea, myalgia, increased blood lactate levels. Treatment with beta2-agonists such as formoterol may result in an increase in blood levels of insulin, free fatty acids, glycerol and ketone bodies.

Fluticasone Propionate

Hypersensitivity reactions including urticaria, pruritus, angioedema (mainly facial and oropharyngeal), anaphylactic reactions. Systemic effects of inhaled corticosteroids may occur, particularly at high dosages prescribed for prolonged periods. These may include Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma, sleep disorders, contusion, skin atrophy and susceptibility to infections. The ability to adapt to stress may be impaired. The systemic effects described, however, are much less likely to occur with inhaled corticosteroids than with oral corticosteroids. Prolonged treatment with high doses of inhaled corticosteroids may result in clinically significant adrenal suppression and acute adrenal crisis. Additional systemic corticosteroid cover may be required during periods of stress (trauma, surgery, infection).

Post marketing Experience

Eye disorders: vision blurred.

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

Overdosage

There are no data available from clinical trials on overdose with fluticasone propionate/formoterol fumarate combination. Information on overdose by the single active components is provided below:

Fluticasone Propionate

Symptoms: Acute inhalation of fluticasone propionate doses in excess of those recommended may lead to temporary suppression of hypothalamic pituitary adrenocortical (HPA) axis function. HPA axis function usually recovers in a few days, as verified by plasma cortisol measurements. Treatment with the inhaled corticosteroid should be continued at the recommended dose to control asthma.

There are reports on rare cases of acute adrenal crisis. Children and adolescents <16 years taking high doses of fluticasone propionate: (typically ≥ 1000 microgram/day) may be at particular risk. Presenting symptoms are typically vague and may include anorexia, abdominal pain, weight loss, tiredness, headache, nausea, vomiting and hypotension. Typical symptoms of an adrenal crisis are decreased level of consciousness, hypoglycaemia and/or seizures.

Following chronic use of very high doses, a degree of atrophy of the adrenal cortex and HPA axis suppression may occur. Monitoring of adrenal reserve may be necessary. Possible systemic effects include Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma.

Treatment: In cases of fluticasone propionate overdose the dose of MAXIFLO Rotacaps should be tapered. In the management of chronic overdose, oral or systemic corticosteroids may be required in situations of stress. All patients deemed to be chronically overdosed should be treated as if steroid dependent with a suitable maintenance dose of a systemic corticosteroid. Therapy with MAXIFLO Rotacaps inhaler may still be continued at a suitable dosage for symptom control.

Formoterol Fumarate

Symptoms: An overdose of formoterol would likely lead to an exaggeration of effects that are typical for beta2-agonists, in which case the following adverse experiences may occur: angina, hypertension or hypotension, palpitations, tachycardia, arrhythmia, prolonged QTc-interval, headache, tremor, nervousness, muscle cramps, dry mouth, insomnia, fatigue, malaise, seizures, metabolic acidosis, hypokalaemia, hyperglycaemia, nausea and vomiting.

Treatment: Treatment of formoterol over-dosage consists of discontinuation of the medication 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 in cases of formoterol overdose. Cardiac monitoring is recommended in cases of overdosage.

Storage and Handling Instructions

Store below 30ºC.

Do not freeze.

Packaging Information

MAXIFLO - 100 Rotacaps

MAXIFLO – 250 Rotacaps

Sales pack contains 30 Rotacaps

Last Updated: February 2019

Last Reviewed: February 2019