Smoking was thought to be a very lucrative phenomenon once. Formerly regarded solely as a “lifestyle choice,” smoking is now recognized as a chronic, relapsing disorder caused because of addiction. Large number of diseases has been associated with chronic smoking, causing a great amount of mortality and morbidity. By stopping as early as possible, there can be a reduction in the risk of cancer, lung and heart disease. There is also a reduction in the damage caused to the lungs. The introduction of nicotine replacement therapy (NRT) to cut down addiction, has successfully led to a decrease in the mortality and morbidity and to better quality of life in tobacco users.

Nicotex contains nicotine polacrilex and is available in two strengths as 2mg and 4mg chewing gums. The principal mechanism of action of Nicotex is to partially replace the nicotine formally obtained from tobacco. It provides small and sustained quantities of nicotine without the harmful gases of smoking, to reduce the severity of withdrawal symptoms and cravings. Second possible mechanism of benefit has been suggested to be the potential for nicotine medications to desensitize nicotinic anticholinergic receptors (nAchRs). Such desensitization would result in a reduced effect of nicotine from cigarettes, such that if a person relapses to smoking while taking NRT, the cigarette would be less satisfying and the person less likely to resume. Hence NRT also provide a coping mechanism, making cigarettes less rewarding to smoke.

Overall, NRT offers low abuse potential and adherence advantages because of the ease of usage. NRT can be used and is considered relatively safe during pregnancy or in patients with unstable cardiac disease, if the alternative is smoking. Medicinal nicotine is unlikely to be more harmful in this context than continued intake of nicotine (and the associated tar, carbon monoxide, and other harmful products) from cigarettes.

INDICATIONS
Nicotex chewing gum is indicated for smoking cessation therapy.

DOSAGE AND ADMINISTRATION

If 25 or more cigarettes a day; use 4 mg nicotine gum.
Less than 25 cigarettes a day; use 2 mg nicotine gum.

Use according to the following 12 week schedule:  

Weeks 1-6	Weeks 7-9	Weeks 10-12
1 gum every 1 to 2 hours	1 gum every 2 to 4 hours	1 gum every 4 to 8 hours

Do not exceed more than 24 gums a day.

Over a 12-week period, NICOTEX allows the body to gradually adjust to have less nicotine. Fewer and fewer gums of NICOTEX will be required until no longer needed. This means that it will leave the smoker, smoke-free in 12 weeks.

Chronic Obstructive Pulmonary Disease (COPD) deserves special attention due to its high prevalence and significant associated mortality. The road from diagnosis to death from COPD is not an easy one and it makes life miserable for the patient as well as for the family members.

The understanding of COPD has increased tremendously in past few years and contrary to the nomenclature which actually is a misnomer; it is not just limited to the lungs. There are significant associated systemic co morbidities. Also, COPD is not only about airflow limitation but also about other significant changes occurring in the lungs like mucociliary dysfunction, structural damage and abnormal airway inflammation, making it a truly a multi component disease. All these things act in synergy with each other to set in what we can truly call as the Vicious cycle of COPD.

As the understanding of the disease enhanced so did the drug therapy. Previously anticholinergics were considered the only treatment for COPD. They continue to remain the backbone for bronchodilation in COPD; however the role of beta2 bronchodilators and inhaled corticosteroids has been well established. All these drugs take care of the different aspects of the pathophysiology of COPD thereby giving comprehensive control than what the individual drugs could achieve. Infact, researches in the UK in their news letter PULSE dated January 2008, have published their interesting findings on the INSPIRE study and urged for the development for a triple drug inhaler for severe COPD.

Keeping all these things in mind Cipla is proud to launch the world's first triple drug combination inhaler TRIOHALE for the treatment of severe COPD. By doing so we are achieving good control and also enhancing the patient compliance.

INDICATIONS
TRIOHALE Inhaler is indicated as third line treatment of severe cases of COPD when monotherapy and second line therapy with two drugs do not respond adequately.

DOSAGE & ADMINISTRATION

TRIOHALE Inhaler

Adults
The recommended dosage is the inhalation of two puffs, once daily. It is recommended to use TRIOHALE inhaler with the Zerostat /Zerostat-V spacer.

Foracort forte is a combination product containing higher dose of formoterol (12 mcg) and budesonide (400 mcg) for management of COPD and also severe asthma. The higher dose of formoterol in Foracort forte is keeping in mind the recommendation that bronchodilators are the first line management of COPD.

Treatment of COPD depends on the severity of the disease, with short acting bronchodilators being recommended for as required use in mild COPD and long acting bronchodilators for regular therapy in patients with moderate COPD. The GOLD guidelines recommend the use of inhaled corticosteroids in addition to bronchodilators especially in patients with severe to very severe COPD (FEV 1< 50%) and repeated exacerbations.

Exacerbations have a significant impact on the disease as well as the patient, resulting in hospitalizations, reduced quality of life and even mortality. Each exacerbation of COPD results in as much muscle mass damage in the chest as 3 years of ageing and also reportedly a loss in lung function of around 8 ml. Thus exacerbations have adverse effects on the patient's health and also on the severity of the underlying disease, subsequently worsening the patient's condition, which takes a long time to recover.

Inhaled corticosteroids exert anti inflammatory effects in airways by a ttenuating neutrophil activation & recruitment, reducing CD8/CD4 lymphocyte ratio and inflammatory mediators interleukin-8 (IL 8), tumor necrosis factor-alpha (TNF-a). Thus helping to reduce the frequency and severity of exacerbations and helping to improve symptoms and quality of life in patients with COPD.

The combination of formoterol/budesonide in patients with COPD (FEV 1 <50%), has shown number of clinical benefits – reduction in severe exacerbations and oral steroid courses, improvement in FEV 1, reduction in symptoms and improvement in quality of life (SGRQ score).

Indications

Asthma
Foracort Forte is indicated in the regular treatment of asthma where use of a combination (inhaled corticosteroid and long-acting beta 2 -agonist) is appropriate:

- patients not adequately controlled with inhaled corticosteroids and “as needed” inhaled short-acting beta 2 -agonists.

or

- patients already adequately controlled on both inhaled corticosteroids and long-acting beta 2 -agonists.

COPD
Symptomatic treatment of patients with severe COPD (FEV 1 < 50% predicted normal) and a history of repeated exacerbations, who have significant symptoms despite regular therapy with long-acting bronchodilators.

Dosage & Administration

Asthma
Foracort Forte is not intended for the initial management of asthma

Recommended doses:

Adults (18 years and older): 1 inhalation/Rotacap twice daily. Some patients may require up to a maximum of 2 inhalations/Rotacaps twice daily.

Adolescents (12-17 years): 1 inhalation/Rotacap twice daily.

Children under 12 years: Efficacy and safety have not been fully studied in children. Foracort Forte is not recommended for children under 12 years of age.

Foracort Forte should be used as Formoterol/Budesonide maintenance therapy only. Lower strengths are available for the Formoterol/Budesonide maintenance and reliever therapy regimen.

COPD

Recommended doses:

Adults: 1 inhalation/Rotacap twice daily.

ZorDox (Doxofylline) is a novel methylxanthine bronchodilator characterized by the presence of a dioxolane group in position 7, which differentiates it from theophylline.

The mechanism of action of Doxofylline is similar to theophylline which results in inhibition of phosphodiesterase enzymes followed by the increase of intracellular concentrations of cyclic AMP that causes smooth muscle relaxation. But, in contrast to theophylline, doxofylline has much lower affinities towards adenosine A1 and A2 receptors, which accounts for its better safety profile.

Bronchodilator activities of doxofylline have been demonstrated in clinical trials involving patients with either asthma or COPD. Data from clinical trials have confirmed that doxofylline is associated with less GI, cardiac and central nervous system untoward effects. Doxofylline has been confirmed to be a safe alternative to the classical xanthine derivatives. Due to its favorable safety profile, the therapeutic range of doxofylline is significantly wider with respect to that of theophylline.

Indications
ZorDox is indicated for the treatment of bronchial asthma and chronic obstructive pulmonary disease (COPD) in adults.

Dosage and Administration
Adults
ZorDox tablet should be taken as one tablet (400 mg) two times a day. The dosage may be increased to thrice daily according to the prescribing physician.

First Time In India

COPD medication in pack of ten rotacaps

Duoset is the combination of widely used anticholinergic (Ipratropium) and short acting beta 2 -agonist Levosalbutamol, which is pure isomer of salbutamol, for Chronic Obstructive Pulmonary Disease (COPD) management. The guidelines state that “Bronchodilators are central to the symptomatic management of COPD”.

Duoset being available in a pack of ten rotacaps, helps to cater to the need of the primary care practitioner in providing a cost effective therapy. This would help the primary care practitioner to initiate the ideal therapy – inhaled bronchodilators which are the first line of treatment for COPD patients.

Indication
Duoset is indicated for use in patients with COPD and on a regular inhaled bronchodilator, who continue to have evidence of bronchospasm and require a second bronchodilator.

Dosage & Administration
The dosage of Duoset is one rotacap four times a day. Patients may take additional inhalations as required; however the total number of rotacaps should not exceed 6 in 24 hours. Duoset Rotacaps should be used only with the Cipla Rotahaler.

First Time In India

Asthma medication in pack of ten rotacaps

 Bekform is the rationale, guideline recommended, cost-effective combination of Inhaled corticosteroid + Long acting beta 2 agonist (ICS+LABA), preferably catering to the need of primary care practitioner.

Bekform combines the time tested ICS Beclomethasone dipropionate (BDP) and rapid acting bronchodilator formoterol fumarate.

The major concern of primary care is about the high cost of asthma medication which may act as a barrier for initiating and adhering with asthma therapy leading to uncontrolled asthma, disability and absenteeism.

Bekform is the first brand in respiratory market, available in pack of ten Rotacaps, making asthma treatment accessible to all asthmatic patients. Bekform provides a cost effective therapy, which reduces the initial outlay for the patient & thus prevents the patient from discontinuing the medication due to high cost.

BDP the first inhaled corticosteroid introduced in 1972, represented a significant therapeutic advance as its low oral bioavailability, high systemic clearance and inhalation formulation imparted a much wider therapeutic ratio than any oral corticosteroid. Over the past 30-35 years a number of clinical trials published on beclomethasone have well established this molecule. BDP gets metabolised by esterase enzymes to beclomethasone-17-monopropionate, which is the active metabolite and has potent anti inflammatory activity. BDP administered by inhaled route acts exclusively in the airways and at usual doses, has no systemic effects and does not suppress the hypothalamic-pituitary-adrenal axis (HPA). One of the characteristics of beclomethasone, is its hepatic metabolization into inactive metabolite; thus reducing the systemic availability of the drug.

Formoterol, a selective beta2- agonist, produces effective dose proportional bronchodilation in patients with reversible obstructive airway disease. Formoterol is a highly potent, long-acting beta2- agonist, combining the clinical advantages of rapid onset of action which is similar to salbutamol with the advantage of longer duration of action around 12 hr. Formoterol is approximately 107 times more potent than salmeterol and 323 times more potent than salbutamol in relaxing isolated human bronchi.

INDICATIONS
Bekform is 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.

DOSAGE AND ADMINISTRATION
Asthma
Adults:
Bekform 200/400 Rotacaps
1-2 Rotacaps twice daily

Children above 6 years:
Bekform 200 Rotacaps
1 Rotacap twice daily

Allergic rhinitis (AR) deserves attention due to its high prevalence in the general population along with significant associated morbidity. Intranasal corticosteroids are the most effective agents available for nasal symptoms and are more potent than antihistamines. However the long term safety of steroids has always been the main concern of clinicians.

Ciclesonide has an edge over the other steroids as far as safety is concerned due to its unique pharmacological properties.

Ciclesonide is a site activated pro drug, which is converted to its active component des-ciclesonide in the nose by the respiratory esterases. It forms reversible fatty acid esters inside the cell. It has a very high receptor binding affinity, higher lipophilicity which makes it very potent as well as long acting. It has less than 1% bioavailability, with 99% protein binding and very rapid clearance, making it one of the safest steroids. Ciclesonide is present in a unique hypotonic suspension (it is the 1 st time that a steroid nasal spray is available in a hypotonic suspension).

Clinical studies have shown its efficacy in both seasonal and perennial allergic rhinitis. Studies have shown it be to be very safe even on long term use. Infact, ciclesonide should be the intranasal steroid of choice for AR in patients with concomitant asthma taking inhaled steroids for the same, as studies have shown that there is no further inhibition of the HPA axis in these patients.

The over riding clinical aim of promoting this steroid is to enhance the safety of intranasal steroids without compromising on the efficacy.

INDICATIONS
CICLOPSPRAY is indicated in patients with seasonal or perennial allergic rhinitis above 12 years of age.

DOSAGE AND ADMINISTRATION
Each spray of CICLOSPRAY contains 50 mcg. Dosage is 200 mcg per day. Hence, 2 sprays each nostril, once daily.

Pulmonary Arterial Hypertension (PAH) is a rare, but devastating and life-threatening disease, with poor prognosis and high mortality. It is characterized by progressive elevation of pulmonary vascular resistance and pulmonary artery pressure.

The current therapeutic options available for PAH include anticoagulants, calcium channel blockers, prostacyclin analogues and endothelin receptor antagonists. Calcium channel blockers are effective in only a minority of patients. Endothelin receptor antagonists and prostacyclin analogues have proven benefits but are not available in our country, thereby limiting the therapeutic options for patients with PAH. All the above mentioned choices are limited by drug tolerability, drug cost and inconvenience associated with administration techniques and dosing schedules.

Sildenafil citrate was the first licensed oral phosphodiesterase inhibitor type 5 (PDE 5) to become available and has revolutionized the treatment of erectile dysfunction. Due to its vasodilating properties, sildenafil has recently been approved by the European Union and US - FDA for use in PAH (WHO Class I). It has shown to improve pulmonary hemodynamics, six minute walk distance and the functional class in PAH. These benefits are maintained over a period of 1 year. It is therefore widely used as a first line agent for the treatment of PAH, particularly in patients with WHO/NYHA Functional Class II & III. Sildenafil (ASSURANS), with its ease of administration and apparently mild adverse effect profile make it an attractive option both as a sole agent and in combination with other agents for the treatment of PAH. Sildenafil (ASSURANS) has also demonstrated efficacy in various types of PAH due to known and unknown etiologies and also in other types of PH including PH due to lung fibrosis, CHF, hypoxia.

Indications

ASSURANS i s indicated for the treatment of pulmonary arterial hypertension (WHO Group I) to improve exercise ability.

The efficacy of sildenafil has not been evaluated in patients currently on bosentan therapy.

Dosage and Administration

The recommended dose of ASSURANS i s 20 mg three times a day (t.i.d.). ASSURANS tablets should be taken approximately 4-6 hours apart, with or without food. Treatment with doses higher than 20 mg t.i.d. is not recommended.

Consistent with its known effects on the nitric oxide/cGMP pathway, sildenafil was shown to potentiate the hypotensive effects of nitrates, and its administration to patients who are using organic nitrates, either regularly and/or intermittently, in any form is therefore contraindicated.

Sildenafil is contraindicated in patients with known hypersensitivity to any component of the tablet

Montair LC is the unique combination of an antileukotriene montelukast with a newer second generation antihistamine levocetirizine. It gives extensive relief from the symptoms of seasonal allergic rhinitis (SAR). It is made available in oral tablet form and is to taken only once daily. This increases the acceptance and thereby the compliance of this combination.

Montair LC - Combination of the two best
Levocetirizine is a newer 2 nd generation antihistamine which is very potent, minimally sedating, has no anti cholinergic property, can be used once daily, safe, well tolerated and also posses some anti inflammatory properties. It is currently the most preferred antihistamine. It controls the early symptoms of AR like sneezing, itching and rhinorrhoea.

Montelukast belongs to that category of drugs which specifically blocks leukotrienes which are the underlying cause of inflammation. Montelukast selectively blocks the action of leukotrienes. Hence it controls the late symptoms of AR like congestion and stuffiness. It is a well tolerated and safe drug and can be given only once daily.

By combining the two best mediator blockades, we ensure that all the symptoms of AR are taken care of that to with an oral medication with only once daily dosing.

INDICATIONS
Montair LC is indicated for the patients of seasonal allergic rhinitis above 15 years of age.

DOSAGE AND ADMINISTRATION
Each tablet of Montair LC contains montelukast 10 mg and levocetirizine 5 mg.
In adults, one tablet once daily.

Fullform combines a time tested inhaled corticosteroid beclomethasone dipropionate (BDP) and rapid acting bronchodilator formoterol fumarate.

It has been reported that majority of patients with asthma are in the developing world and the financial burden due to asthma for them as well as their families is very high. Inadequate treatment and the high cost of medications may act as a barrier for initiating and adhering with asthma therapy leading to uncontrolled asthma, disability and absenteeism. Fullform will help in making rationale and guideline recommended asthma treatment accessible FOR ONE AND ALL .

Beclomethasone dipropionate (BDP) the first inhaled corticosteroid introduced in 1972, represented a significant therapeutic advance as its low oral bioavailability, high systemic clearance and inhalation formulation imparted a much wider therapeutic ratio than any oral corticosteroid. Over the past 30-35 years a number of clinical trials published on beclomethasone have well established this molecule. BDP is a synthetic halogenated corticosteroid, which gets metabolised by esterase enzymes to beclomethasone-17-monopropionate, which is the active metabolite and has potent anti inflammatory activity. BDP administered by inhaled route acts exclusively in the airways and at usual doses, has no systemic effects and does not suppress the hypothalamic-pituitary-adrenal axis (HPA). One of the characteristics of beclomethasone, is its hepatic metabolization into inactive metabolite; thus reducing the systemic availability of the drug.

Formoterol, a selective beta2-adrenoceptor agonist, produces effective dose proportional bronchodilation in patients with reversible obstructive airway disease. Formoterol is a highly potent, long-acting beta2-adrenoceptor-selective agonist, combining the clinical advantages of rapid onset of action with duration of action in excess of 12 hours. Formoterol is approximately 107 times more potent than salmeterol and 323 times more potent than salbutamol in relaxing isolated human bronchi. Like other selective beta2-adrenoceptor agonists, formoterol has minimal stimulating effects on beta1-adrenoceptors and virtually no effect on beta1-adrenoceptors. In vitro studies have shown that formoterol has more than 200-fold greater agonist activity at beta2-adrenoceptors than at beta1-adrenoceptors .

INDICATIONS
FULLFORM is 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.

DOSAGE AND ADMINISTRATION
Asthma
Adults:
FULLFORM 200/400 Rotacaps
1-2 Rotacaps twice daily

Children above 6 years:
FULLFORM 200 Rotacaps
1 Rotacap twice daily

Adults and children above 6 years
FULLFORM 100 Inhaler
1-2 inhalations twice daily

simplyOne combining a novel inhaled corticosteroid (ICS)  - ‘Ciclesonide' and best long-acing beta2-agonist (LABA) – ‘Formoterol' represents a significant advancement for management of patients with asthma. Simplyone combines the safety and efficacy of ciclesonide with the unique bronchodilatory properties of formoterol.

simplyOne - Highlights

• Rapid onset of action providing quick relief due to formoterol.
• Enhanced Safety Profile - High margin of safety for ciclesonide- the ideal corticosteroid with substantially reduced risk for both oropharyngeal and systemic side effects.
•  Safest (ICS+LABA) combination especially in patients requiring higher doses of inhaled steroids to control their asthma, without the associated concerns regarding side-effects.
• Longer Duration of Action - The dosage can be tapered to once daily therapy after control is achieved with initial twice daily treatment.
• The benefits obtained with formoterol/budesonide combination when used as maintenance as well as reliever therapy, approved by GINA 2006, may even be extended to this new combination – simplyOne .
• Simplified asthma therapy – Thus improving adherence and better disease control.

simplyOne is 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.

Dosage And Administration
Asthma
Adults and Adolescents (12 years and older)

simplyOne 80/160 Inhaler
1 to 2 inhalations twice daily

simplyOne 100 Rotacaps
1 to 2 Rotacaps twice daily

simplyOne 200 Rotacaps
1 to 2 Rotacaps twice daily

simplyOne 400 Rotacaps
1 Rotacap twice daily

The maximum recommended dose for ciclesonide is 640 mcg (MDI) and 800 mcg (DPI). The dose of simplyOne is individual and adjusted according to disease severity. When control has been achieved, the dose should be titrated to the lowest effective dose, which could include simplyOne given once daily.