Latest News - Part 11
Side Effects With Inhaled Corticosteroids: Conclusion
How often do you monitor for (1) systemic or (2) local adverse events?
When asked to rate the overall safety of ICS on a scale of 1 (very safe) to 6 (dangerous), 25% of participants in this meeting rated ICS as very safe, most (40%) chose 2 on the scale, and 35% chose 3 or 4. Participants believed that local side effects were most likely to lead to discontinuation of therapy. Approximately two thirds of the participants monitored for local side effects at each visit; the remainder relied on the patient to alert them to any problems. Most of the group (50%) investigated systemic side effects only in the event of a patient indicating that there was a problem. The remainder monitored at regular periods: every 6 months (21%), every quarter (4%), or every visit (25%). Considerable reservations remain for parents and many pediatricians regarding the effect of ICS on linear growth in children: cataracts may be more common with ICS in older patients; bone density is a risk in postmenopausal women and elderly men; patients with a family history of glaucoma may be more at risk of this side effect with ICS; and skin bruising occurs even at moderate ICS doses. review
Side Effects With Inhaled Corticosteroids: Physician Perception of Side Effects With ICS Therapy
A survey of 429 US family physicians and pediatricians in managed-care organizations was conducted by the Pediatric Asthma Care Patient Outcomes Research Team. This survey focused on physicians’ concerns and perceptions. Although 26% of responders thought ICS were very safe and 66% thought they were safe, 47% were at least moderately concerned regarding one or more ICS side effects (Fig 3). Their greatest concern was regarding linear growth retardation in children. This survey predated the Food and Drug Administration requirement to include a warning on ICS labeling regarding linear growth retardation in children.
In a survey of 213 asthma specialists, 80% of whom were allergists/immunologists and 20% were pulmonologists, the aim was to determine the type and frequency of side effects due to ICS seen in their patients (Fig 4). Only 1% of physicians reported that they saw “short stature” in children either occasionally or frequently, and only 15% reported seeing it rarely. The only area of agreement between these two studies was for oral thrush/oropharyngeal symptoms.
There seems to be a disconnect between the level of concern regarding side effects with ICS and the actual frequency of these side effects noted in practice. However, it is likely that the family physicians were more concerned regarding the seriousness of potential side effects, rather than their frequency. canadian health care mall
Side Effects With Inhaled Corticosteroids: Systemic Side Effects
The only specific recommendation for monitoring systemic side effects made in the NAEPP 1997 guidelines was to monitor growth in children. However, based on the evidence available at the time, the guidelines recommended the following measures for minimizing potential systemic side effects with ICS: Here
• Use a spacer device and rinse the mouth after inhalation. Selroos and Halme demonstrated that systemic absorption of ICS was reduced by using a spacing device with a metered-dose inhaler after using a DPI.
• Use the lowest possible dose of ICS to maintain control. In children, step down ICS dose whenever possible.
• Add additional therapies (long-acting (32-agonist) before increasing the ICS dose.
• In postmenopausal women, consider calcium supplements (1,000 to 1,500 mg/d) and vitamin D (400 IU/d). Estrogen replacement therapy, when appropriate, may be considered for patients receiving ICS doses > 1,000 ^g/d. This recommendation is no longer up to date (see next paragraph).
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Side Effects With Inhaled Corticosteroids: Control and Monitoring of Side Effects Local Side Effects
The only other systemic side effect with ICS mentioned in the NAEPP 1997 guidelines was disseminated varicella infection. While oral corticosteroid use, with or without immunosuppression, has been associated with a high risk of severe varicella infection compared with case-matched control sub-jects, no causal relationship has been shown with ICS, despite sporadic case reports of severe varicella infections in patients receiving ICS.
The 1997 NAEPP guidelines suggested the following clinical interventions to mitigate the risk of, or treat, local side effects:
• Oral candidiasis (thrush): use a spacer/holding chamber, rinse mouth with water after inhalation, and administer ICS less frequently (twice daily vs four times daily). Topical or oral antifungal agents should be used to treat active infections. • Dysphonia: use a spacer/holding chamber, temporarily reduce dosage, or rest for vocal stress.
• Reflex cough and bronchospasm: use a slower inspiration rate and/or a spacer/holding chamber or pretreat with an inhaled (32-agonist.
Side Effects With Inhaled Corticosteroids: Systemic Side Effects in Children
Oral corticosteroids are a known risk factor for the development of subcapsular cataracts, with risk influenced by daily cumulative dose, age, and ethnic origin. The systematic review described above concluded that the risk of cataracts due to ICS was small and may only be relevant in elderly patients. Two studies not included in the systematic review generally support these findings. A study from 1993 found that the prevalence of subcapsular cataracts in 48 patients treated with long-term BUD or BDP (750 to 1,500 ^g/d) was 27%. However, the development of cataracts was correlated to prednisone but not ICS use. A study published in 2001, after the systematic review was compiled, suggested that the risk of cataracts with ICS may be related to age. An analysis of 103,289 subjects exposed to ICS vs 98,527 subjects in a control cohort found slightly higher incidence rates for cataracts in the ICS group compared with the nonexposed cohort (RR, 1.3; 95%, CI 1.1 to 1.5) after adjusting for age and gender. However, a relationship between heavy use of ICS and cataract risk that was most pronounced in subjects > 70 years old was also seen in subjects aged 40 to 49 years, but was absent in subjects aged < 40 years. add comment
Side Effects With Inhaled Corticosteroids: Risk of Systemic Side Effects
While safety data have been reported for many clinical trials, there are few studies that have been adequately powered, or have long enough follow-up periods, to assess long-term systemic side effects with ICS. A systematic review conducted in collaboration between the American College of Chest Physicians, the American Academy of Allergy, Asthma, and Immunology, and the American College of Allergy, Asthma, and Immunology examined the evidence for potential systemic complications of ICS therapy for asthma. Evidence published up to the end of the year 2000 was considered. The results are summarized in Table 2. In brief, there was relatively good evidence for the effect of ICS on skin thinning and bruising, with a dose-response relationship identified. In older adults, ICS appeared to reduce bone mineral density after long-term, high-dose therapy and increased the risk of cataracts and glaucoma, although the evidence was not conclusive. Click Here
Side Effects With Inhaled Corticosteroids: Asthma Clinical Research
Modern delivery systems, such as HFA-based pMDI inhalers, enhance drug targeting to the lungs. Thus, lower ICS doses can be used, such that the clinical response is maintained but systemic exposure reduced. For example, conversion from CFC to HFA as a propellant moved the dose-response curve for drugs delivered using the HFA device toward the left, so lower doses are required to achieve the same therapeutic effect.> Conversely, a 1:1 substitution of the CFC to the more recent HFA formulations may result in greater systemic exposure and a higher potential for side effects.> Therefore, recommended doses of HFA devices are lower than older CFC-containing formulations. Large-volume spacers have also been recommended as a means of improving lung deposition, allowing dose reduction and minimization of ICS systemic bioavailability in adults and children. this