QVAR

Physicians Total Care, Inc.

FULL PRESCRIBING INFORMATION: CONTENTS*

• QVAR DESCRIPTION
• CLINICAL PHARMACOLOGY
• CLINICAL TRIALS
• QVAR INDICATIONS AND USAGE
• QVAR CONTRAINDICATIONS
• WARNINGS
• PRECAUTIONS
• QVAR ADVERSE REACTIONS
• OVERDOSAGE
• QVAR DOSAGE AND ADMINISTRATION
• HOW SUPPLIED
• PATIENT'S INSTRUCTIONS
• PRINCIPAL DISPLAY PANEL

FULL PRESCRIBING INFORMATION

QVAR DESCRIPTION

The active component of QVAR 40 mcg Inhalation Aerosol and QVAR 80 mcg Inhalation Aerosol is beclomethasone dipropionate, USP, an anti-inflammatory corticosteroid having the chemical name 9-chloro-11β,17,21-trihydroxy-16β-methylpregna-1,4-diene-3,20-dione 17,21-dipropionate. Beclomethasone dipropionate (BDP) is a diester of beclomethasone, a synthetic corticosteroid chemically related to dexamethasone. Beclomethasone differs from dexamethasone in having a chlorine at the 9-alpha carbon in place of a fluorine, and in having a 16 beta-methyl group instead of a 16 alpha-methyl group. Beclomethasone dipropionate is a white to creamy white, odorless powder with a molecular formula of C₂₈H₃₇ClO₇ and a molecular weight of 521.1. Its chemical structure is:

QVAR is a pressurized, metered-dose aerosol intended for oral inhalation only. Each unit contains a solution of beclomethasone dipropionate in propellant HFA-134a (1,1,1,2 tetrafluoroethane) and ethanol. QVAR 40 mcg delivers 40 mcg of beclomethasone dipropionate from the actuator and 50 mcg from the valve. QVAR 80 mcg delivers 80 mcg of beclomethasone dipropionate from the actuator and 100 mcg from the valve. Both products deliver 50 microliters (59 milligrams) of solution formulation from the valve with each actuation. Each canister provides 100 inhalations. QVAR should be "primed" or actuated twice prior to taking the first dose from a new canister, or when the inhaler has not been used for more than ten days. Avoid spraying in the eyes or face while priming QVAR. This product does not contain chlorofluorocarbons (CFCs).

CLINICAL PHARMACOLOGY

Airway inflammation is known to be an important component in the pathogenesis of asthma. Inflammation occurs in both large and small airways. Corticosteroids have multiple anti-inflammatory effects, inhibiting both inflammatory cells (e.g., mast cells, eosinophils, basophils, lymphocytes, macrophages, and neutrophils) and release of inflammatory mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines). These anti-inflammatory actions of corticosteroids such as beclomethasone dipropionate contribute to their efficacy in asthma.

Beclomethasone dipropionate is a prodrug that is rapidly activated by hydrolysis to the active monoester, 17 monopropionate (17-BMP). Beclomethasone 17 monopropionate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor which is approximately 13 times that of dexamethasone, 6 times that of triamcinolone acetonide, 1.5 times that of budesonide and 25 times that of beclomethasone dipropionate. The clinical significance of these findings is unknown.

Studies in patients with asthma have shown a favorable ratio between topical anti-inflammatory activity and systemic corticosteroid effects with recommended doses of QVAR.

Beclomethasone dipropionate (BDP) undergoes rapid and extensive conversion to beclomethasone-17-monopropionate (17-BMP) during absorption. The pharmacokinetics of 17-BMP has been studied in asthmatics given single doses.

The mean peak plasma concentration (C_max) of BDP was 88 pg/ml at 0.5 hour after inhalation of 320 mcg using QVAR (four actuations of the 80 mcg/actuation strength). The mean peak plasma concentration of the major and most active metabolite, 17-BMP, was 1419 pg/ml at 0.7 hour after inhalation of 320 mcg of QVAR. When the same nominal dose is provided by the two QVAR strengths (40 and 80 mcg/actuation), equivalent systemic pharmacokinetics can be expected. The C_max of 17-BMP increased dose proportionally in the dose range of 80 and 320 mcg.

Three major metabolites are formed via cytochrome P450 3A catalyzed biotransformation - beclomethasone-17-monopropionate (17-BMP), beclomethasone-21-monopropionate (21-BMP) and beclomethasone (BOH). Lung slices metabolize BDP rapidly to 17-BMP and more slowly to BOH. 17-BMP is the most active metabolite.

The in vitro protein binding for 17-BMP was reported to be 94-96% over the concentration range of 1000 to 5000 pg/mL. Protein binding was constant over the concentration range evaluated. There is no evidence of tissue storage of BDP or its metabolites.

The major route of elimination of inhaled BDP appears to be via hydrolysis. More than 90% of inhaled BDP is found as 17-BMP in the systemic circulation. The mean elimination half-life of 17-BMP is 2.8 hours. Irrespective of the route of administration (injection, oral or inhalation), BDP and its metabolites are mainly excreted in the feces. Less than 10% of the drug and its metabolites are excreted in the urine.

Formal pharmacokinetic studies using QVAR were not conducted in any special populations.

The pharmacokinetics of 17-BMP, including dose and strength proportionalities, is similar in children and adults, although the exposure is highly variable. In 17 children (mean age 10 years), the C_max of 17-BMP was 787 pg/ml at 0.6 hour after inhalation of 160 mcg (four actuations of the 40 mcg/actuation strength of HFA beclomethasone dipropionate). The systemic exposure to 17-BMP from 160 mcg of HFA-BDP administered without a spacer was comparable to the systemic exposure to 17-BMP from 336 mcg CFC-BDP administered with a large volume spacer in 14 children (mean age 12 years). This implies that approximately twice the systemic exposure to 17-BMP would be expected for comparable mg doses of HFA-BDP without a spacer and CFC-BDP with a large volume spacer.

Improvement in asthma control following inhalation can occur within 24 hours of beginning treatment in some patients, although maximum benefit may not be achieved for 1 to 2 weeks, or longer. The effects of QVAR on the hypothalamic-pituitary-adrenal (HPA) axis were studied in 40 corticosteroid naive patients. QVAR, at doses of 80, 160 or 320 mcg twice daily was compared with placebo and 336 mcg twice daily of beclomethasone dipropionate in a CFC propellant based formulation (CFC-BDP). Active treatment groups showed an expected dose-related reduction in 24-hour urinary free cortisol (a sensitive marker of adrenal production of cortisol). Patients treated with the highest recommended dose of QVAR (320 mcg twice daily) had a 37.3% reduction in 24-hour urinary free cortisol compared to a reduction of 47.3% produced by treatment with 336 mcg twice daily of CFC-BDP. There was a 12.2% reduction in 24 hour urinary free cortisol seen in the group of patients that received 80 mcg twice daily of QVAR and a 24.6% reduction in the group of patients that received 160 mcg twice daily. An open label study of 354 asthma patients given QVAR at recommended doses for one year assessed the effect of QVAR treatment on the HPA axis (as measured by both morning and stimulated plasma cortisol). Less than 1% of patients treated for one year with QVAR had an abnormal response (peak less than 18 mcg/dL) to short-cosyntropin test.

CLINICAL TRIALS

Blinded, randomized, parallel, placebo-controlled and active-controlled clinical studies were conducted in 940 adult asthma patients to assess the efficacy and safety of QVAR in the treatment of asthma. Fixed doses ranging from 40 mcg to 160 mcg twice daily were compared to placebo, and doses ranging from 40 mcg to 320 mcg twice daily were compared with doses of 42 mcg to 336 mcg twice daily of an active CFC-BDP comparator. These studies provided information about appropriate dosing through a range of asthma severity. A blinded, randomized, parallel, placebo-controlled study was conducted in 353 pediatric patients (age 5-12 years) to assess the efficacy and safety of HFA beclomethasone dipropionate in the treatment of asthma. Fixed doses of 40 mcg and 80 mcg twice daily were compared with placebo in this study. In these adult and pediatric efficacy trials, at the doses studied, measures of pulmonary function [forced expiratory volume in 1 second (FEV₁) and morning peak expiratory flow (AM PEF)] and asthma symptoms were significantly improved with QVAR treatment when compared to placebo.

In controlled clinical trials with adult patients not adequately controlled with beta-agonist alone, QVAR was effective at improving asthma control at doses as low as 40 mcg twice daily (80 mcg/day). Comparable asthma control was achieved at lower daily doses of QVAR than with CFC-BDP. Treatment with increasing doses of both QVAR and CFC-BDP generally resulted in increased improvement in FEV₁. In this trial the improvement in FEV₁ across doses was greater for QVAR than for CFC-BDP, indicating a shift in the dose response curve for QVAR.

In a 6 week clinical trial, 270 steroid naive patients with symptomatic asthma being treated with as-needed beta-agonist bronchodilators, were randomized to receive either 40 mcg twice daily of QVAR, 80 mcg twice daily of QVAR, or placebo. Both doses of QVAR were effective in improving asthma control with significantly greater improvements in FEV₁, AM PEF, and asthma symptoms than with placebo. Shown below is the change from baseline in AM PEF during this trial.

In a 6-week clinical trial, 256 patients with symptomatic asthma being treated with as-needed beta-agonist bronchodilators, were randomized to receive either 160 mcg twice daily of QVAR (delivered as either 40 mcg/actuation or 80 mcg/actuation) or placebo. Treatment with QVAR significantly improved asthma control, as assessed by FEV₁, AM PEF, and asthma symptoms, when compared to treatment with placebo. Comparable improvement in AM PEF was seen for patients receiving 160 mcg twice daily QVAR from the 40 mcg and 80 mcg strength products.

In another clinical trial, 347 patients with symptomatic asthma, being treated with as-needed inhaled beta-agonist bronchodilators and, in some cases, inhaled corticosteroids, were given a 7-12 day course of oral corticosteroids and then randomized to receive either 320 mcg daily of QVAR, 672 mcg of CFC-BDP, or placebo. Patients treated with either QVAR or CFC-BDP had significantly better asthma control, as assessed by AM PEF, FEV₁ and asthma symptoms, and fewer study withdrawals due to asthma symptoms, than those treated with placebo over 12 weeks of treatment. A daily dose of 320 mcg QVAR administered in divided doses provided comparable control of AM PEF and FEV₁ as 672 mcg of CFC-BDP. Shown below are the mean AM PEF results from this trial.

In a 6-week clinical trial, 323 patients, who exhibited a deterioration in asthma control during an inhaled corticosteroid washout period, were randomized to daily treatment with either 40, 160, or 320 mcg twice daily QVAR or 42, 168, or 336 mcg twice daily CFC-BDP. Treatment with increasing doses of both QVAR and CFC-BDP resulted in increased improvement in FEV₁, FEF_25-75% (forced expiratory flow over 25-75% of the vital capacity), and asthma symptoms. Shown below is the change from baseline in FEV₁ as percent predicted after 6 weeks of treatment.

Clinical experience has shown that some patients with asthma who require oral corticosteroid therapy for control of symptoms can be partially or completely withdrawn from oral corticosteroids if therapy with beclomethasone dipropionate aerosol is substituted. Inhaled corticosteroids may not be effective for all patients with asthma or at all stages of the disease in a given patient.

In one 12-week clinical trial, pediatric patients (age 5-12 years) with symptomatic asthma (N=353) being treated with as-needed beta-agonist bronchodilators were randomized to receive either 40 mcg or 80 mcg twice daily of HFA beclomethasone dipropionate or placebo. Both doses were effective in improving asthma control with significantly greater improvements in FEV₁ (9% and 10% predicted change from baseline at week 12 in FEV₁ percent predicted, respectively) than with placebo (4% predicted change).

QVAR INDICATIONS AND USAGE

QVAR is indicated in the maintenance treatment of asthma as prophylactic therapy in patients 5 years of age and older. QVAR is also indicated for asthma patients who require systemic corticosteroid administration, where adding QVAR may reduce or eliminate the need for the systemic corticosteroids.

Beclomethasone dipropionate is NOT indicated for the relief of acute bronchospasm.

QVAR CONTRAINDICATIONS

QVAR is contraindicated in the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required. Hypersensitivity to any of the ingredients of this preparation contraindicates its use.

WARNINGS

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

Patients who have been previously maintained on 20 mg or more per day of prednisone (or its equivalent) may be most susceptible, particularly when their systemic corticosteroids have been almost completely withdrawn. During this period of HPA suppression, patients may exhibit signs and symptoms of adrenal insufficiency when exposed to trauma, surgery, or infections (particularly gastroenteritis) or other conditions with severe electrolyte loss. Although QVAR may provide control of asthmatic symptoms during these episodes, in recommended doses it supplies less than normal physiological amounts of glucocorticoid systemically and does NOT provide the mineralocorticoid that is necessary for coping with these emergencies.

During periods of stress or a severe asthmatic attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physician for further instruction. These patients should also be instructed to carry a warning card indicating that they may need supplementary systemic steroids during periods of stress or a severe asthma attack.

Transfer of patients from systemic steroid therapy to QVAR may unmask allergic conditions previously suppressed by the systemic steroid therapy, e.g., rhinitis, conjunctivitis, and eczema.

Persons who are on drugs which 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 non-immune children or adults on corticosteroids. In such children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. It is not known how the dose, route and duration of corticosteroid administration affects the risk of developing a disseminated infection. Nor is the contribution of the underlying disease and/or prior corticosteroid treatment known. If exposed to chickenpox, prophylaxis with varicella-zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered.

QVAR is not a bronchodilator and is not indicated for rapid relief of bronchospasm.

As with other inhaled asthma medications, bronchospasm, with an immediate increase in wheezing, may occur after dosing. If bronchospasm occurs following dosing with QVAR, it should be treated immediately with a short acting inhaled bronchodilator. Treatment with QVAR should be discontinued and alternate therapy instituted. Patients should be instructed to contact their physician immediately when episodes of asthma, which are not responsive to bronchodilators, occur during the course of treatment with QVAR. During such episodes, patients may require therapy with oral corticosteroids.

PRECAUTIONS

Oral inhaled corticosteroids have been shown to cause a reduction in growth velocity in children and teenagers with extended use. If a child or teenager on any corticosteroid appears to have growth suppression, the possibility that they are particularly sensitive to this effect of corticosteroids should be considered (see PRECAUTIONS, General).

QVAR ADVERSE REACTIONS

The following reporting rates of common adverse experiences are based upon four clinical trials in which 1196 Patients (671 female and 525 male adults previously treated with as-needed bronchodilators and/or inhaled corticosteroids) were treated with QVAR (doses of 40, 80, 160, or 320 mcg twice daily) or CFC-BDP (doses of 42, 168, or 336 mcg twice daily) or placebo. The table below includes all events reported by patients taking QVAR (whether considered drug related or not) that occurred at a rate over 3% for either QVAR or CFC-BDP. In considering these data, difference in average duration of exposure and clinical trial design should be taken into account.

Other adverse events that occurred in these clinical trials using QVAR with an incidence of 1% to 3% and which occurred at a greater incidence than placebo were: dysphonia, dysmenorrhea and coughing.

No patients treated with QVAR in the clinical development program developed symptomatic oropharyngeal candidiasis.

If such an infection develops, treatment with appropriate antifungal therapy or discontinuance of treatment with QVAR may be required.

In two 12-week placebo controlled studies in steroid naive pediatric patients 5 to 12 years of age, no clinically relevant differences were found in the pattern, severity, or frequency of adverse events compared with those reported in adults, with the exception of conditions which are more prevalent in a pediatric population generally.

Rare cases of immediate and delayed hypersensitivity reactions, including urticaria, angioedema, rash, and bronchospasm, have been reported following the oral and intranasal inhalation of beclomethasone dipropionate.

OVERDOSAGE

There were no deaths over 15 days following the oral administration of a single dose of 3000 mg/kg in mice, 2000 mg/kg in rats, and 1000 mg/kg in rabbits. The doses in mice, rats, and rabbits were 19,000, 25,000, and 25,000 times, respectively, the maximum recommended daily inhalation in adults or 36,000, 48,000, and 48,000 times, respectively the maximum recommended daily inhalation dose in children on a mg/m² basis.

QVAR DOSAGE AND ADMINISTRATION

Patients should prime QVAR by actuating into the air twice before using for the first time or if QVAR has not been used for over ten days. Avoid spraying in the eyes or face when priming QVAR. QVAR is a solution aerosol, which does not require shaking. Consistent dose delivery is achieved, whether using the 40 or 80 mcg strengths, due to proportionality of the two products (i.e., two actuations of 40 mcg strength should provide a dose comparable to one actuation of the 80 mcg strength).

QVAR should be administered by the oral inhaled route in patients 5 years of age and older. Use of QVAR with a spacer device in children less than 5 years of age is not recommended (see PRECAUTIONS, Pediatric Use). The onset and degree of symptom relief will vary in individual patients. Improvement in asthma symptoms should be expected within the first or second week of starting treatment, but maximum benefit should not be expected until 3-4 weeks of therapy. For patients who do not respond adequately to the starting dose after 3-4 weeks of therapy, higher doses may provide additional asthma control. The safety and efficacy of QVAR when administered in excess of recommended doses has not been established.

Recommended Dosage for QVAR:

As with any inhaled corticosteroid, physicians are advised to titrate the dose of QVAR downward over time to the lowest level that maintains proper asthma control. This is particularly important in children since a controlled study has shown that QVAR has the potential to affect growth in children. Patients should be instructed on the proper use of their inhaler.

Patients who require maintenance therapy of their asthma may benefit from treatment with QVAR at the doses recommended above. In patients who respond to QVAR, improvement in pulmonary function is usually apparent within 1 to 4 weeks after the start of therapy. Once the desired effect is achieved, consideration should be given to tapering to the lowest effective dose.

QVAR may be effective in the management of asthmatics maintained on systemic corticosteroids and may permit replacement or significant reduction in the dosage of systemic corticosteroids.

The patient's asthma should be reasonably stable before treatment with QVAR is started. Initially, QVAR should be used concurrently with the patient's usual maintenance dose of systemic corticosteroids. After approximately one week, gradual withdrawal of the systemic corticosteroids is started by reducing the daily or alternate daily dose. Reductions may be made after an interval of one or two weeks, depending on the response of the patient. A slow rate of withdrawal is strongly recommended. Generally these decrements should not exceed 2.5 mg of prednisone or its equivalent. During withdrawal, some patients may experience symptoms of systemic corticosteroid withdrawal, e.g. joint and/or muscular pain, lassitude and depression, despite maintenance or even improvement in pulmonary function. Such patients should be encouraged to continue with the inhaler but should be monitored for objective signs of adrenal insufficiency. If evidence of adrenal insufficiency occurs, the systemic corticosteroid doses should be increased temporarily and thereafter withdrawal should continue more slowly.

During periods of stress or a severe asthma attack, transfer patients may require supplementary treatment with systemic corticosteroids.

Illustrated Patient's Instructions for proper use accompany each package of QVAR.

HOW SUPPLIED

QVAR is supplied in two strengths:

The correct amount of medication in each inhalation cannot be assured after 100 actuations from the 7.3 g canister or 120 actuations from the 8.7 g canister even though the canister is not completely empty. The canister should be discarded when the labeled number of actuations have been used.

Mktd by:
Teva Respiratory, LLC– Horsham, PA 19044

© 2010 Teva Respiratory, LLC
639300
QVAR® is a registered trademark of IVAX LLC, a member of the TEVA Group.
Rev. 09/10

OptiChamber is a registered trademark of Respironics Healthscan, Inc. and AeroChamber Plus is a registered trademark of Trudell Medical International Trudell Partnership Holdings Limited and Packard Medical Supply Centre Ltd.

Relabeling of "Additional" barcode label by:
Physicians Total Care, Inc.
Tulsa, OK       74146

PATIENT'S INSTRUCTIONS

QVAR^®
(beclomethasone dipropionate HFA)
INHALATION AEROSOL

Attention Pharmacist: Detach "Patient's Instructions for Use" from package insert and dispense with the product.

PATIENT'S INSTRUCTIONS

It is important that you read these instructions before using QVAR.

Correct and regular use of the inhaler will prevent or lessen the severity of asthma attacks.

1. Remove the plastic cap (see Figure 1) and be sure there are no foreign objects in the mouthpiece.

Figure 1

2. As with all aerosol medications, it is recommended to prime the QVAR inhaler before using for the very first time after purchase, and in cases where the inhaler has not been used for more than ten days. Prime by releasing two actuations into the air, away from your eyes and face. Be sure the canister is firmly seated in the plastic mouthpiece adapter before each use.

3. BREATHE OUT AS FULLY AS YOU COMFORTABLY CAN. Hold the inhaler as shown in Figure 2. Close your lips around the mouthpiece, keeping your tongue below it.

Figure 2

4. WHILE BREATHING IN DEEPLY AND SLOWLY, PRESS DOWN ON THE CAN WITH YOUR FINGER. When you have finished breathing in, hold your breath as long as you comfortably can (i.e., 5 - 10 seconds).

5. TAKE YOUR FINGER OFF THE CAN and remove the inhaler from your mouth. Breathe out gently.

6. If your physician has told you to take more than one inhalation per treatment repeat steps 3 through 5.

7. You should rinse your mouth with water after treatment.

8. For normal hygiene, the mouthpiece of your inhaler should be cleaned weekly with a clean, dry tissue or cloth.

DO NOT WASH OR PUT ANY PART OF YOUR INHALER IN WATER.

9. DISCARD THE CANISTER AFTER the date calculated by your physician or pharmacist. The correct amount of medication in each inhalation cannot be assured after 100 actuations from the 7.3 g canister even though the canister is not completely empty. The canister should be discarded when the labeled number of actuations have been used. Before the discard date you should consult your physician to determine whether a refill is needed. It is advisable to keep track of the number of doses taken from the canister to better predict when a refill is necessary. Just as you should not take extra doses without consulting your physician, you also should not stop taking QVAR without consulting your physician.

IMPORTANT QVAR is preventive therapy for asthma and must be used regularly and at the times your physician has prescribed.

DO NOT CONFUSE QVAR WITH OTHER ASTHMA MEDICATION. QVAR WILL NOT PROVIDE IMMEDIATE RELIEF IF YOU ARE HAVING AN ASTHMA ATTACK.

Your physician will decide whether other medication is needed should you require immediate relief. If you also use another medicine by inhalation, you should consult your physician for instructions on when to use it in relation to using QVAR. If this is the first time you will be using QVAR, it may take from 1 to 4 weeks before you feel the full benefits.

QVAR Inhalation Aerosol canister should only be used with the QVAR Inhalation Aerosol mouthpiece and the mouthpiece should not be used with any other inhalation drug product.

DOSAGE

Use only as directed by your physician.

CONTENTS UNDER PRESSURE

Do not puncture. Do not use or store near heat or open flame. Exposure to temperatures above 49°C (120°F) may cause bursting. Never throw container into fire or incinerator.

Keep out of reach of children.

Avoid spraying in eyes.

Store at 25°C (77°F). For optimal results, the canister should be at room temperature when used. Store QVAR Inhalation Aerosol when not being used, so that the product rests on the concave end of the canister with the plastic actuator on top.

Mktd by:
Teva Specialty Pharmaceuticals LLC
Horsham, PA 19044

Developed and Manufactured by:

3M Drug Delivery Systems
Northridge, CA  91324

or

3M Health Care, Ltd
Loughborough, UK

© 2008 Teva Specialty Pharmaceuticals LLC
QVAR® is a registered trademark of the IVAX Corporation, a member of the TEVA Group.

634600
Rev. 08/08

PRINCIPAL DISPLAY PANEL

QVAR^® 40mcg

(beclomethasone
dipropionate HFA, 40 mcg)
INHALATION AEROSOL

For oral inhalation with
QVAR^® Actuator only

100
Metered Inhalations
7.3g Net Contents

CFC FREE