Beclomethasone dipropionate

What it is

Beclomethasone dipropionate is a man-made corticosteroid, a chemical relative of the hormone cortisol. It is a prodrug: it is rapidly broken down by water-splitting enzymes to its active form, beclomethasone-17-monopropionate, which binds the human glucocorticoid receptor roughly 25 times more tightly than beclomethasone dipropionate itself. It is designed to act where it lands rather than throughout the body, and is given as an asthma inhaler, a nasal spray, and in some countries as a prolonged-release oral tablet or a rectal enema or foam for bowel inflammation.

What the research says

Inhaled beclomethasone is one of the best-tested asthma preventers there is: a Cochrane review of 60 trials in 6542 people found clear improvements in lung function and far fewer trial withdrawals for asthma attacks against placebo, and in people on oral steroids it cut prednisolone use by about 4.91 mg a day. It is not a rescue inhaler and the label says so. The harms are the ones you would expect from a steroid, scaled down: thrush in the mouth, more upper-airway infections, measurable cortisol suppression at the top of the dose range, and in children a mean reduction in growth velocity of about 0.48 cm in the first year of inhaled-steroid treatment.

Evidence grade: Well established.

How it works

Drug class: Glucocorticoid (inhaled, intranasal, oral and rectal corticosteroid; prodrug activated to beclomethasone-17-monopropionate)

Beclomethasone dipropionate is a corticosteroid with strong anti-inflammatory activity. It is a prodrug, rapidly split by enzymes into the active form beclomethasone-17-monopropionate, which locks on to the glucocorticoid receptor inside cells. Corticosteroids damp down several inflammatory cell types, including mast cells, eosinophils, lymphocytes, macrophages and neutrophils, and reduce the release of inflammatory mediators such as histamine, leukotrienes and cytokines. The label is candid that the precise mechanism of corticosteroid action in asthma is not known. (Source 1)

What it is used for

• A Cochrane review of 60 trials in 6542 participants found that at 400 mcg a day or less, beclomethasone improved FEV1 by 360 mL (95% CI 260 to 460) against placebo, improved morning peak flow by 35.95 L/min and cut the relative risk of dropping out of a trial because of an asthma attack to 0.25 (95% CI 0.12 to 0.51). In people also taking oral steroids it reduced prednisolone use by 4.91 mg/day. Evidence: established. (Source 2)
• The label states a Limitation of Use: the inhaler is not indicated for relief of acute bronchospasm. It is a preventer, taken regularly, not a rescue inhaler. Evidence: not-supported. (Source 3)
• In a 12-week placebo-controlled trial, fluticasone nasal spray was significantly better than placebo and no better than beclomethasone dipropionate nasal spray 200 mcg twice daily for the nasal symptoms of rhinitis, and beclomethasone was as well tolerated as placebo. We did not find a placebo-controlled trial of beclomethasone nasal spray from the modern era with a stated effect size, so this use rests on older and indirect evidence. Evidence: limited. (Source 4)
• In a randomised, double-blind, placebo-controlled study of 40 children given nebulised beclomethasone 800 mcg a day or placebo for 4 weeks, the drug beat placebo on lung function, cough, wheeze and sleep disturbance, but no difference was seen between nebulised beclomethasone and placebo for the rhinitis symptom score. Evidence: not-supported. (Source 5)
• In a double-blind randomised trial of 282 patients, oral prolonged-release beclomethasone 5 mg daily was non-inferior to prednisone: Disease Activity Index response at week 4 was 64.6% with beclomethasone and 66.2% with prednisone (delta -1.56; 95% CI -13.00 to 9.88, P=0.78). This formulation is not an approved product in the United States. Evidence: limited. (Source 6)
• In a small randomised placebo-controlled phase, 13 of 22 patients (59.1%) given beclomethasone 5 mg a day for 4 weeks reached faecal calprotectin below 100 mcg/g against 3 of 21 (17.6%) on placebo (p=0.010), and no patient on beclomethasone relapsed against 4 on placebo (p=0.049). The trial randomised only 22 patients to beclomethasone and 21 to placebo, and measured a surrogate marker rather than symptoms. Evidence: limited. (Source 7)

Interactions

• Ritonavir (a strong CYP3A4 inhibitor used to boost HIV drugs) (pharmacokinetic study): Ritonavir alone roughly doubled blood levels of the active metabolite of inhaled beclomethasone, but no fall in cortisol was seen in any group, so the authors called the rise statistically significant but clinically inconsequential. This contrasts with reports of Cushing's syndrome when ritonavir is combined with some other inhaled steroids. (Source 8)
• Darunavir boosted with ritonavir (pharmacokinetic study): Adding darunavir/ritonavir did not increase exposure to the active metabolite of inhaled beclomethasone (geometric mean ratio 0.89, 90% CI 0.68 to 1.09, P = 0.61), and cortisol did not fall. (Source 8)
• Systemically active corticosteroids (oral steroids such as prednisone) (label): Switching from oral steroids to the inhaler is the dangerous moment, not the inhaler itself. The label records that deaths from adrenal insufficiency have happened during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids, and that HPA recovery takes months. (Source 9)
• Anticonvulsants and other corticosteroids (drugs that reduce bone mass) (label): The label groups inhaled corticosteroids with other drugs that can reduce bone mass and advises monitoring in people with major risk factors for low bone mineral content. It also says the clinical significance of small bone-density changes for fracture is unknown. (Source 10)

Stopping it

• Coming off systemic steroids onto the inhaler is the step that has killed people. The label tells prescribers to taper slowly, because deaths from adrenal insufficiency have occurred during and after that transfer and recovery of the adrenal axis takes a number of months. (Source 9)
• The label also says that if signs of hypercorticism or adrenal suppression appear, the inhaler should be discontinued slowly rather than stopped abruptly. (Source 11)
• Halving the dose in people on high-dose inhaled beclomethasone did not cost them control. In a one-year randomised double-blind trial in adults on high-dose inhaled beclomethasone, exacerbations occurred in 31% of the step-down group and 26% of controls (P=0.354), with no difference in health status or visits, while the step-down group took 348 mcg a day less. (Source 12)
• Stopping an inhaled steroid does not reliably undo growth suppression in children. Of four trials in the Cochrane review that followed growth after treatment stopped, three did not describe statistically significant catch-up growth two to four months later. (Source 13)

What goes wrong

Inhaled corticosteroids slow children's growth by about half a centimetre in the first year of treatment, and the suppression is largest in year one. (Source 13)

• Meta-analysis, Moderate certainty.
• Size: 25 trials, 8471 children (5128 on inhaled corticosteroids, 3343 control)
• Who: children with mild to moderate persistent asthma; beclomethasone dipropionate was one of six molecules studied.
• How long: three months to four to six years.
• Result: Linear growth velocity MD -0.48 cm/y (95% CI -0.65 to -0.30) over one year, and change from baseline in height MD -0.61 cm/y (95% CI -0.83 to -0.38); no significant difference in year two (MD -0.19 cm/y, 95% CI -0.48 to 0.11, P value 0.22)
• Funding: the review reports 68% of the included trials were financially supported by pharmaceutical companies.

Compared with placebo or non-steroidal drugs, ICS produced a statistically significant reduction in linear growth velocity (14 trials with 5717 participants, MD -0.48 cm/y, 95% CI -0.65 to -0.30, moderate quality evidence) and in the change from baseline in height (15 trials with 3275 participants; MD -0.61 cm/y, 95% CI -0.83 to -0.38, moderate quality evidence) during a one-year treatment period.

One trial following children into adulthood found a lasting height reduction, although with budesonide rather than beclomethasone. (Source 13)

• Randomized trial, Low certainty.
• Size: one trial within a 25-trial review.
• Who: children of prepubertal age with persistent asthma treated with budesonide 400 mcg/day.
• How long: mean 4.3 years of treatment, followed into adulthood.
• Result: Mean reduction of 1.20 cm (95% CI -1.90 to -0.50) in adult height compared with placebo.
• Funding: the review reports 68% of the included trials were financially supported by pharmaceutical companies.

One trial with follow-up into adulthood showed that participants of prepubertal age treated with budesonide 400 μg/d for a mean duration of 4.3 years had a mean reduction of 1.20 cm (95% CI -1.90 to -0.50) in adult height compared with those treated with placebo.

Adrenal insufficiency was found in 6.8% of adults treated with inhaled corticosteroids for asthma, and the risk rose with dose and duration. (Source 14)

• Meta-analysis, Moderate certainty.
• Size: 74 articles, 3753 participants.
• Who: adult corticosteroid users tested for adrenal insufficiency, grouped by route and by disease.
• How long: from under 28 days to over 1 year.
• Result: 6.8% for asthma with inhalation corticosteroids only (95% CI 3.8-12.0) and 4.2% for nasal administration (95% CI 0.5-28.9); by dose 2.4% (95% CI 0.6-9.3) low to 21.5% (95% CI 12.0-35.5) high; by duration 1.4% (95% CI 0.3-7.4) under 28 days to 27.4% (95% CI 17.7-39.8) over 1 year in asthma patients.
• Funding: not stated in the abstract.

Stratified by disease, percentages ranged from 6.8% for asthma with inhalation corticosteroids only (95% CI, 3.8-12.0) to 60.0% for hematological malignancies (95% CI, 38.0-78.6). The risk also varied according to dose from 2.4% (95% CI, 0.6-9.3) (low dose) to 21.5% (95% CI, 12.0-35.5) (high dose), and according to treatment duration from 1.4% (95% CI, 0.3-7.4) (<28 d) to 27.4% (95% CI, 17.7-39.8) (>1 year) in asthma patients.

Inhaled corticosteroids increase upper respiratory tract infections in asthma, at both low and high doses. (Source 15)

• Meta-analysis, Moderate certainty.
• Size: Seventeen trials, 15,336 subjects.
• Who: people with asthma in randomised trials of any inhaled corticosteroid against a control treatment.
• How long: long-term use, not further specified in the abstract.
• Result: Peto odds ratio 1.24 (95% CI 1.08-1.42; I2 = 5%, p = 0.002); high dose 1.46 (95% CI 1.05-2.03; p = 0.03); low dose 1.20 (95% CI 1.04-1.39; p = 0.01)
• Funding: not stated in the abstract.

Compared with non-ICS treatment, ICSs were associated with a significantly increased risk of URTI (Peto OR, 1.24; 95% CI 1.08-1.42; I2 = 5%, p = 0.002). Subgroup analyses were performed for different dose, both high- and low-dose ICSs were associated with a significantly increased risk of URTI (high dose: Peto OR, 1.46; 95% CI 1.05-2.03; I2 = 0%; p = 0.03) (low dose: Peto OR, 1.20; 95% CI 1.04-1.39; I2 = 25%; p = 0.01).

People with asthma on the highest-strength inhaled corticosteroid prescriptions had about twice the odds of pneumonia or lower respiratory tract infection. (Source 16)

• Case-control study, Low certainty.
• Size: not stated in the abstract.
• Who: people with asthma in UK primary care records from The Health Improvement Network, with age- and sex-matched controls.
• How long: exposure window of the previous 90 days.
• Result: Highest strength of inhaled corticosteroid (1,000 mcg or more) associated with 2.04 (95% CI 1.59-2.64) increased risk of pneumonia or lower respiratory tract infection; P < .001 for trend across dose.
• Funding: not stated in the abstract.

A dose-response relationship was found between the strength of inhaled corticosteroid dose and risk of pneumonia or lower respiratory tract infection (P < .001 for trend) such that after adjusting for confounders, people receiving the highest strength of inhaled corticosteroid (≥ 1,000 μg) had a 2.04 (95% CI, 1.59-2.64) increased risk of pneumonia or lower respiratory tract infection compared with those with asthma who did not have a prescription for inhaled corticosteroids within the previous 90 days.

Candida in the throat was more common in people using inhaled steroids than in those not using them, and more with fluticasone than with beclomethasone. (Source 17)

• Survey study, Low certainty.
• Size: 143 asthmatic patients on inhaled steroids, 11 asthmatic patients not on them, and 86 healthy volunteers.
• Who: asthmatic patients treated with inhaled fluticasone or beclomethasone, untreated asthmatic patients, and healthy volunteers.
• How long: single quantitative fungal culture of a retropharyngeal wall swab.
• Result: Candida amount significantly greater in patients on inhaled steroids than not, and significantly greater with fluticasone than with beclomethasone; Candida did not correlate with the inhaled dose of beclomethasone but increased with the dose of fluticasone.
• Funding: not stated in the abstract.

The amount of Candida spp. was significantly greater in asthmatic patients taking inhaled steroids compared with those who were not. It was also significantly greater in patients with oral symptoms than asymptomatic patients and significantly greater in asthmatic patients treated with fluticasone than in those treated with beclomethasone. Although the presence of Candida did not correlate with the inhaled dose of beclomethasone, it did increase with the dose of fluticasone.

Inhaled beclomethasone measurably suppresses cortisol production in a dose-related way, and the effect is bigger at the top of the recommended range. (Source 18)

• Randomized trial, Low certainty.
• Size: 40 corticosteroid-naive patients in the dose study; 354 patients in the one-year open-label study.
• Who: corticosteroid-naive asthma patients, and asthma patients given the inhaler at recommended doses for a year.
• How long: the open-label study assessed the HPA axis over one year.
• Result: 24-hour urinary free cortisol fell 12.2% at 80 mcg twice daily, 24.6% at 160 mcg twice daily and 37.3% at 320 mcg twice daily, against 47.3% with 336 mcg twice daily of the older CFC formulation; less than 1% of patients treated for one year had an abnormal short-cosyntropin response (peak less than 18 mcg/dL)
• Funding: manufacturer label (Teva Respiratory, LLC)

Patients treated with the highest dose recommended of QVAR MDI (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 MDI and a 24.6% reduction in the group of patients that received 160 mcg twice daily.

Psychiatric and behavioural changes, including aggression, depression, sleep disorders and suicidal ideation, have been reported after approval, mainly in children. (Source 19)

• Official position, Very low certainty.
• Size: not estimable; voluntary postmarketing reports.
• Who: people using beclomethasone dipropionate or other orally inhaled corticosteroids.
• How long: post-approval use.
• Result: No rates can be given: the label says that because reports are voluntary from a population of uncertain size it is not always possible to estimate frequency or establish causation.
• Funding: manufacturer label (Teva Respiratory, LLC)

Psychiatric and Behavioral Changes: Aggression, depression, sleep disorders, psychomotor hyperactivity, and suicidal ideation have been reported (primarily in children). Eye Disorders: Blurred vision, central serous chorioretinopathy (CSC).

Oral thrush is among the most common adverse reactions of the inhaler, occurring in more than 3% of patients and more often than with placebo. (Source 11)

• Official position, Certainty not rated.
• Size: not stated in the Highlights section.
• Who: people using the beclomethasone dipropionate inhaler in the clinical development programme.
• How long: not stated.
• Result: Oral candidiasis, upper respiratory tract infection, nasopharyngitis, allergic rhinitis, oropharyngeal pain and sinusitis each at more than 3% and more than placebo.
• Funding: manufacturer label (Teva Respiratory, LLC)

Most common adverse reactions (incidence >3% and > placebo) include oral candidiasis, upper respiratory tract infection, nasopharyngitis, allergic rhinitis, oropharyngeal pain and sinusitis. (6.1)

What the evidence supports

Inhaled beclomethasone improved lung function and reduced withdrawal for asthma attacks compared with placebo in people not on oral steroids. (Source 2)

• Systematic review, High certainty.
• Size: 60 studies recruiting 6542 participants.
• Who: children and adults with chronic asthma in randomised parallel-group trials of at least four weeks.
• How long: at least four weeks; the reviewers found more than four weeks needed for the fuller effect.
• Result: At 400 mcg/day or less: FEV1 360 ml (95% CI 260 to 460); FEV1 percent predicted WMD 12.41% (95% CI 8.18 to 16.64); morning peak expiratory flow WMD 35.95 L/min (95% CI 27.85 to 44.04); rescue beta-2 agonist use -2.32 puffs/d (95% CI -2.55 to -2.09); relative risk of trial withdrawal due to an asthma exacerbation 0.25 (95% CI 0.12 to 0.51)
• Funding: not stated in the abstract.

at doses of 400 mcg/day or less CFC-BDP produced significant improvements from baseline in a number of efficacy measures compared with placebo, including forced expiratory volume in one second (FEV1) 360 ml (95% CI 260 to 460); FEV1 (% predicted) WMD 12.41% (95% CI 8.18 to 16.64) and morning peak expiratory flow rate (am PEF) WMD 35.95 L/min (95% CI 27.85 to 44.04). BDP also led to reductions in rescue beta-2 agonist use compared with placebo of -2.32 puffs/d (95% CI -2.55 to -2.09) and reduced the relative risk (RR) of trial withdrawal due to an asthma exacerbation 0.25 (95% CI 0.12 to 0.51).

In people already taking oral steroids for asthma, inhaled beclomethasone let them take less prednisolone and made coming off oral steroids more likely. (Source 2)

• Systematic review, Moderate certainty.
• Size: part of 60 studies recruiting 6542 participants.
• Who: people with chronic asthma who were also taking oral corticosteroids.
• How long: at least four weeks.
• Result: Oral prednisolone use WMD -4.91 mg/d (95% CI -5.88 to -3.94 mg/d); relative risk of withdrawing oral steroid treatment 8.02 (95% CI 3.23 to 19.92)
• Funding: not stated in the abstract.

In oral steroid treated patients BDP led to significantly greater reductions in oral prednisolone use WMD -4.91 mg/d (95% CI -5.88 to -3.94 mg/d) and greater likelihood of withdrawing oral steroid treatment RR 8.02 (95% CI 3.23 to 19.92).

In perennial rhinitis, fluticasone nasal spray beat placebo and was no better than beclomethasone nasal spray, and beclomethasone was as well tolerated as placebo. (Source 4)

• Randomized trial, Low certainty.
• Size: not stated in the abstract.
• Who: patients with allergic and non-allergic perennial rhinitis.
• How long: 12 weeks.
• Result: Fluticasone 200 mcg once or twice daily was significantly better than placebo but not better than beclomethasone dipropionate 200 mcg twice daily; beclomethasone was as well tolerated as placebo.
• Funding: not stated in the abstract.

FPANS 200 micrograms once or twice daily was significantly better than placebo but not better than BDP in relieving the nasal symptoms of rhinitis. FPANS at either dose was equally effective in the treatment of allergic and non-allergic perennial rhinitis. There were few adverse events and no treatment-related abnormalities in laboratory measurements in either FPANS-treated group. Comparison between treatment groups indicated that FPANS was as well tolerated as placebo and BDP at the doses studied.

Oral prolonged-release beclomethasone was non-inferior to prednisone for active mild-to-moderate ulcerative colitis. (Source 6)

• Randomized trial, Moderate certainty.
• Size: 282 patients randomised.
• Who: patients with active, mild-to-moderate ulcerative colitis.
• How long: 8-week study period, primary endpoint at week 4.
• Result: Disease Activity Index response at week 4 64.6% with beclomethasone versus 66.2% with prednisone (delta -1.56; 95% CI -13.00 to 9.88, P=0.78); steroid-related adverse events with cortisol below 150 nmol/l in 38.7% versus 46.9% (P=0.17)
• Funding: not stated in the abstract.

DAI response rates at week 4 were 64.6% and 66.2% with BDP and PD, respectively, demonstrating non-inferiority of BDP vs. PD (delta: -1.56; 95% confidence interval (CI) -13.00-9.88, P=0.78).

In a small randomised trial, oral beclomethasone lowered faecal calprotectin and prevented relapse in ulcerative colitis in remission. (Source 7)

• Randomized trial, Low certainty.
• Size: 22 patients randomised to beclomethasone and 21 to placebo.
• Who: patients with ulcerative colitis in clinical remission on 5-aminosalicylic acid with faecal calprotectin at or above 250 mcg/g.
• How long: 4 weeks double-blind.
• Result: Faecal calprotectin below 100 mcg/g in 13 of 22 (59.1%) versus 3 of 21 (17.6%), p=0.010; no relapses on beclomethasone versus 4 on placebo, p=0.049.
• Funding: not stated in the abstract.

Limit of this finding: The trial's own numbers do not line up. The abstract says 21 people were randomised to placebo, but reports the three who reached the target as 17.6%, which is 3 of 17, not 3 of 21 (14.3%). The percentage is quoted as the journal printed it; treat the counts (13 of 22 on beclomethasone, 3 on placebo) as the reliable figures and the placebo percentage as unexplained.

At week 4, 13 patients (59.1%) in group A and 3 (17.6%) in group B had FC levels <100 μg/g (p value = 0.010). In the double-blind phase of the study, no patient relapsed in group A and 4 in group B (p value = 0.049).

What the evidence does not support

Halving the dose of high-dose inhaled beclomethasone did not increase asthma exacerbations over a year. (Source 12)

• Randomized trial, Moderate certainty.
• Size: 259 adult patients.
• Who: adults with asthma in general practices in western and central Scotland, on high-dose inhaled corticosteroids (mean 1430 mcg beclomethasone dipropionate)
• How long: one year.
• Result: Exacerbations in 31% of the step-down group versus 26% of controls (P=0.354); no significant difference in general practice or hospital visits or health status; step-down group received 348 mcg/day less (95% CI 202 to 494 mcg), a difference of 25%.
• Funding: not stated in the abstract.

Similarly, the numbers of visits to general practice or hospital and the disease specific and generic measures of health status over the one year period were not significantly different. On average the stepdown group received 348 microg (95% confidence interval 202 microg to 494 microg) of beclomethasone dipropionate less per day than the controls (a difference of 25%), with no difference in the annual dose of oral corticosteroids between the two treatment regimens.

The label expressly limits the inhaler from relieving acute bronchospasm; it is approved only as maintenance prophylactic therapy. (Source 3)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: adults and children 4 years of age and older with asthma.
• How long: maintenance use.
• Result: Indicated for maintenance treatment of asthma as prophylactic therapy; not indicated for the relief of acute bronchospasm.
• Funding: manufacturer label (Teva Respiratory, LLC)

QVAR REDIHALER is indicated in the maintenance treatment of asthma as prophylactic therapy in adults and pediatric patients 4 years of age and older. Limitations of Use: QVAR REDIHALER is not indicated for the relief of acute bronchospasm.

Where the evidence is mixed

Nebulised beclomethasone beat placebo on airway measures and several symptoms in children with asthma and rhinitis, but showed no difference from placebo for the rhinitis symptom score. (Source 5)

• Randomized trial, Low certainty.
• Size: 40 children, mean age 10.7 years.
• Who: children with allergic asthma and rhinitis.
• How long: 4 weeks of treatment after a 2-week run-in.
• Result: Nebulised beclomethasone 800 mcg daily beat placebo on nasal pH, oral IL-5, oral FeNO, FEV1, FEV1/FVC, peak expiratory flow, visual analogue scale, breathing difficulty, cough, wheezing and sleep disturbance; no difference versus placebo for rhinitis symptom score.
• Funding: not stated in the abstract.

No differences were observed between the nBDP and the placebo group for symptom score of rhinitis.

Ritonavir roughly doubled exposure to the active metabolite of inhaled beclomethasone without suppressing cortisol in healthy volunteers. (Source 8)

• Blood level study, Low certainty.
• Size: Thirty healthy volunteers randomised 1:1:1 into three groups.
• Who: healthy volunteers taking inhaled beclomethasone 160 mcg twice daily for 14 days, then randomised to beclomethasone alone, with ritonavir, or with darunavir/ritonavir for 28 days.
• How long: 42 days of dosing with cortisol testing on days 1, 14, 28 and 42.
• Result: Geometric mean ratios (day 28 to day 14) for 17-BMP AUC 0.93 (0.81 to 1.06, P = 0.27) control, 2.08 (1.52 to 2.65, P = 0.006) with ritonavir and 0.89 (0.68 to 1.09, P = 0.61) with darunavir/ritonavir; no significant reductions in serum cortisol within or between groups (P > 0.05)
• Funding: not stated in the abstract.

for 17-BMP area under the concentration-time curve in groups 1, 2, and 3, respectively, were 0.93 (0.81 to 1.06, P = 0.27), 2.08 (1.52 to 2.65, P = 0.006), and 0.89 (0.68 to 1.09, P = 0.61). There were no significant reductions in serum cortisol levels within or between groups (P > 0.05).

Where the research disagrees

How much the growth effect of inhaled steroids in children matters. The same Cochrane review reports a clear reduction in growth velocity in the first year of treatment and no statistically significant difference in the second

• Cochrane review authors (main results), systematic review and meta-analysis of 25 randomised trials in 8471 children; first-year result: Compared with placebo or non-steroidal drugs, ICS produced a statistically significant reduction in linear growth velocity (14 trials with 5717 participants, MD -0.48 cm/y, 95% CI -0.65 to -0.30, moderate quality evidence) (Source 13)
• The same review, on year two, systematic review and meta-analysis of 25 randomised trials in 8471 children; second-year result: No statistically significant difference in linear growth velocity was found between participants treated with ICS and controls during the second year of treatment (five trials with 3174 participants; MD -0.19 cm/y, 95% CI -0.48 to 0.11, P value 0.22). (Source 13)

Whether beclomethasone causes less oral thrush than other inhaled steroids. A culture study found less Candida with beclomethasone than with fluticasone, but a lower rate than fluticasone is not the same as a low rate: oral candidiasis is still on the inhaler label's own list of the most common adverse reactions

• Fukushima and colleagues, cross-sectional quantitative fungal culture study in asthmatic patients taking inhaled steroids, asthmatic patients not taking them, and healthy volunteers: It was also significantly greater in patients with oral symptoms than asymptomatic patients and significantly greater in asthmatic patients treated with fluticasone than in those treated with beclomethasone. (Source 17)
• The US beclomethasone inhaler label, regulatory position, US prescribing information for the inhaler, revised September 2025: Most common adverse reactions (incidence >3% and > placebo) include oral candidiasis, upper respiratory tract infection, nasopharyngitis, allergic rhinitis, oropharyngeal pain and sinusitis. (Source 11)

How much

• Reference intake: There is no reference intake: beclomethasone is a medicine, not a nutrient, and the dose is set by the prescriber. As a label position dated 2025, the US inhaler's recommended starting dose for people 12 years and older not already on an inhaled corticosteroid is 40 to 80 mcg twice daily, with the starting dose chosen from previous asthma therapy and disease severity. (Source 20)
• Upper limit: As a label position dated 2025, the maximum recommended dose of the US inhaler for people 12 years and older is 320 mcg twice daily. (Source 20)
• Studied: The Cochrane review's placebo comparisons found clear benefit at inhaled doses of 400 mcg a day or less, and the reviewers said the published data give little support for going above 400 mcg a day in mild to moderate asthma. (Source 2)
• Studied: A trial reported in the label compared inhaled doses of 80, 160 or 320 mcg twice daily against placebo and against 336 mcg twice daily of the older CFC formulation. (Source 18)
• Studied: The ulcerative colitis trials gave oral prolonged-release beclomethasone 5 mg once daily for 4 weeks, in one case then every other day for a further 4 weeks. (Source 21)
• Studied: A paediatric trial nebulised beclomethasone at a daily dose of 800 mcg, given twice daily for 4 weeks. (Source 5)

A common belief, and what the research shows

The belief: A steroid inhaler is a reliever, so you take it when you feel wheezy.

What the research shows: It is the opposite. The US label states as a Limitation of Use that "QVAR REDIHALER is not indicated for the relief of acute bronchospasm." The benefit comes from taking it regularly, and the Cochrane review found that subgroup analyses "provide support to the proposal that a treatment period of greater than four weeks is required to realise a fuller treatment effect" (sources: qvar-label-indications-2025, adams-2005-cochrane-bdp).

Questions and answers

What is it?

Beclomethasone dipropionate is a man-made corticosteroid, in the same family as cortisol. It is a prodrug: enzymes split it in the body into the active form, beclomethasone-17-monopropionate, which grips the human glucocorticoid receptor about 25 times more tightly than the parent drug. It comes as an asthma inhaler, a nasal spray, and in some countries oral tablets or a rectal preparation for bowel inflammation. (Source 1)

What does it do in the body?

It damps down inflammation where it lands. Corticosteroids suppress several inflammatory cell types, including mast cells, eosinophils, basophils, lymphocytes, macrophages and neutrophils, and reduce the release of mediators such as histamine, leukotrienes and cytokines. In asthma that means less airway inflammation and so fewer attacks, but the label is honest that the precise mechanism in asthma is not known. (Source 1)

Is it good or bad for you?

Good for prevention, with a real cost that depends on dose and on who is taking it. In asthma it reliably improves lung function and reduces attacks. In children, the trade-off that has been measured most carefully is growth: pooled randomised data show a reduction in linear growth velocity of 0.48 cm/y (95% CI -0.65 to -0.30) over a one-year treatment period, with no statistically significant difference in the second year (MD -0.19 cm/y, 95% CI -0.48 to 0.11, P value 0.22). (Source 13)

How do you get more of it?

It is not something to get more of from food or shops: it is a prescribed medicine, taken by inhaler, nasal spray, tablet or enema depending on the condition. If asthma is not controlled, the prescriber decides whether to increase the dose rather than the person taking more puffs. The label's own stepping rule is to review after 2 weeks of therapy before increasing. (Source 20)

If it is harmful, what reduces it?

Where it causes local harm, the main measures are simple. For oral thrush the label advises rinsing the mouth with water without swallowing after each inhalation, and treating established thrush with local or oral antifungal therapy while usually continuing the inhaler. Where the problem is systemic steroid effect, the dose is reduced slowly rather than stopped abruptly. (Source 22)

Why might someone be low in it or missing it?

Nobody is deficient in beclomethasone: it is a medicine, not a body substance. The useful version of this question is why someone with asthma may not be getting the protection it offers, and the answer is that it only works taken regularly as prophylaxis, not as needed. The label describes it as maintenance treatment taken as prophylactic therapy. (Source 3)

Which whole foods contain it or feed it?

No food contains beclomethasone and no diet supplies it. It is a synthetic corticosteroid made as a medicine. We searched Europe PMC for food or dietary sources and found none, and no food interaction is described in the US inhaler label we read, which contains no drug interactions section at all. (Source 1)

We searched: Europe PMC REST searches for beclomethasone combined with diet, food and dietary sources; the full US prescribing information for QVAR RediHaler, which has no section 7 Drug Interactions

What happens if you do not have it?

People with persistent asthma who are not on an inhaled steroid have worse lung function and more attacks. In the Cochrane comparison against placebo, beclomethasone cut the relative risk of being withdrawn from a trial because of an asthma exacerbation to 0.25 (95% CI 0.12 to 0.51), which is another way of saying the placebo groups had roughly four times the rate of attacks severe enough to end their participation. (Source 2)

How can you test for it?

There is no routine blood test for the drug itself. What gets tested is its effect: lung function (FEV1 or peak flow) for benefit, and adrenal function for systemic effect. The label reports that 24-hour urinary free cortisol falls in a dose-related way, and that in a one-year study of 354 patients at recommended doses, fewer than 1% had an abnormal short-cosyntropin test result. That test is sensitive enough to detect suppression but does not by itself tell you whether a person will come to harm. (Source 18)

References

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2. Cochrane Database of Systematic Reviews. Inhaled beclomethasone versus placebo for chronic asthma.. 2005. PMID 15674896, DOI 10.1002/14651858.cd002738.pub2. Read the source
3. DailyMed / Teva Respiratory, LLC. QVAR REDIHALER (beclomethasone dipropionate HFA) inhalation aerosol — FDA prescribing information, section 1 Indications and Usage. 2025. Read the source
4. Clinical and Experimental Allergy. A placebo-controlled study of fluticasone propionate aqueous nasal spray and beclomethasone dipropionate in perennial rhinitis: efficacy in allergic and non-allergic perennial rhinitis. — abstract, Results. 1995. PMID 7584685, DOI 10.1111/j.1365-2222.1995.tb00011.x. Read the source
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6. American Journal of Gastroenterology. Oral prolonged release beclomethasone dipropionate and prednisone in the treatment of active ulcerative colitis: results from a double-blind, randomized, parallel group study. — abstract, Results. 2015. PMID 25869389, DOI 10.1038/ajg.2015.114. Read the source
7. Digestive Diseases. Efficacy of Beclomethasone Dipropionate in Lowering Fecal Calprotectin Levels in Patients with Ulcerative Colitis in Clinical Remission and at Risk of Relapse: The Becalcu Randomized, Controlled Trial. — abstract, Results. 2024. PMID 39173598, DOI 10.1159/000540792. Read the source
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9. DailyMed / Teva Respiratory, LLC. QVAR REDIHALER (beclomethasone dipropionate HFA) inhalation aerosol — FDA prescribing information, section 5.3 Transferring Patients from Systemic Corticosteroid Therapy. 2025. Read the source
10. DailyMed / Teva Respiratory, LLC. QVAR REDIHALER (beclomethasone dipropionate HFA) inhalation aerosol — FDA prescribing information, section 5.9 Reduction in Bone Mineral Density. 2025. Read the source
11. DailyMed / Teva Respiratory, LLC. QVAR REDIHALER (beclomethasone dipropionate HFA) inhalation aerosol — FDA prescribing information, Highlights: Warnings and Precautions and Adverse Reactions. 2025. Read the source
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15. Infection. Inhaled corticosteroids and risk of upper respiratory tract infection in patients with asthma: a meta-analysis.. 2019. PMID 30298471, DOI 10.1007/s15010-018-1229-y. Read the source
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17. Annals of Allergy, Asthma & Immunology. Oral candidiasis associated with inhaled corticosteroid use: comparison of fluticasone and beclomethasone. — abstract, Results. 2003. PMID 12839324, DOI 10.1016/s1081-1206(10)61870-4. Read the source
18. DailyMed / Teva Respiratory, LLC. QVAR REDIHALER (beclomethasone dipropionate HFA) inhalation aerosol — FDA prescribing information, section 12.2 Pharmacodynamics. 2025. Read the source
19. DailyMed / Teva Respiratory, LLC. QVAR REDIHALER (beclomethasone dipropionate HFA) inhalation aerosol — FDA prescribing information, section 6.2 Postmarketing Experience. 2025. Read the source
20. DailyMed / Teva Respiratory, LLC. QVAR REDIHALER (beclomethasone dipropionate HFA) inhalation aerosol — FDA prescribing information, section 2.2 Recommended Dosage. 2025. Read the source
21. American Journal of Gastroenterology. Oral prolonged release beclomethasone dipropionate and prednisone in the treatment of active ulcerative colitis: results from a double-blind, randomized, parallel group study. — abstract, Methods. 2015. PMID 25869389, DOI 10.1038/ajg.2015.114. Read the source
22. DailyMed / Teva Respiratory, LLC. QVAR REDIHALER (beclomethasone dipropionate HFA) inhalation aerosol — FDA prescribing information, section 5.1 Oropharyngeal Candidiasis. 2025. Read the source