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LETTER TO EDITOR
Year : 2021  |  Volume : 22  |  Issue : 2  |  Page : 179-180

The cyclosporine syringe: A pragmatic approach for accurate calibration of cyclosporine dosing in children


1 Department of Paediatric Dermatology, Institute of Child Health, Kolkata, West Bengal, India
2 Department of Dermatology, Shree Guru Gobind Singh Tricentenary Medical College and Research Institute, Gurugram, Haryana, India

Date of Submission28-May-2020
Date of Decision02-Jul-2020
Date of Acceptance18-Sep-2020
Date of Web Publication31-Mar-2021

Correspondence Address:
Shikhar Ganjoo
Associate Professor, Department of Dermatology, Shree Guru Gobind Singh Tricentenary Medical College and Research Institute, Gurugram, Haryana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijpd.IJPD_95_20

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How to cite this article:
Dhar S, Ganjoo S. The cyclosporine syringe: A pragmatic approach for accurate calibration of cyclosporine dosing in children. Indian J Paediatr Dermatol 2021;22:179-80

How to cite this URL:
Dhar S, Ganjoo S. The cyclosporine syringe: A pragmatic approach for accurate calibration of cyclosporine dosing in children. Indian J Paediatr Dermatol [serial online] 2021 [cited 2021 Apr 22];22:179-80. Available from: https://www.ijpd.in/text.asp?2021/22/2/179/312832



Sir,

Cyclosporine A (CsA), a calcineurin inhibitor, has been widely used for a variety of pediatric dermatoses that include atopic dermatitis, psoriasis, alopecia areata, lichen planus, chronic idiopathic urticaria, rapidly spreading vitiligo, diffuse cutaneous mastocytosis, widespread vasculitis, and a few more conditions. The weight-dependent doses range from 3 to 5 mg/kg body weight and cyclosporine is commercially available as a gelatine capsule (25 mg, 50 mg, and 100 mg), an oral solution in syrup form as 100 mg/ml and as an intravenous preparation.[1]

CsA, an 11-amino acid cyclic peptide and appears as white prismatic needles. It is only slightly soluble in water, and to remain in solution at room temperature, it must be dissolved in ethanol or olive oil. For dispersion of the solution, milk and juice are preferred. Oral absorption is dependent on emulsification of oil by bile in gut and hence has a lot of interindividual variation. Since CsA is an extremely hydrophobic molecule it is not metabolized at physiologic pH. This phenomenon is responsible for its high concentration in fats and internal organs like pancreas, liver, kidney, breast and lymphoid tissues. This also explains the variable efficacy and toxicity in patients with altered lipoprotein and haematocrit values. The inter subject variability is so large that individual monitoring is ideally required.[2]

Cyclosporine is well tolerated by the pediatric population as compared to the adult population.[3] Children show excellent responses with a very low incidence of adverse effects. Hence, frequent monitoring is not routinely required. The American academy of dermatology recommends monitoring whole-blood cyclosporine trough levels in children only if there is an inadequate clinical response or concomitant use of potentially interacting drugs.[4]

The most frequent adverse effects noted among children include hypertrichosis and gingival hypertrophy.[5] The major drawback is dose-dependent nephrotoxicity. Acute nephrotoxicity occurs within days to months of initiation of therapy and is reversible upon decreasing the dose. Chronic nephrotoxicity occurs within the first few years of therapy and is irreversible as it leads to tubular atrophy and interstitial fibrosis.[6]

A wide range of nanoparticles have been explored for the delivery of highly hydrophobic drugs. Goyal et al. compared two polymeric nanospheres-polylactic-co-glycolic acid (PLGA) nanoparticles and nanospheres made from tyrosine-derived tri-block copolymers (termed Tyro Spheres) for their respective performance as carriers for CsA. Their methods of preparation are different, self-assembly for Tyro Spheres and emulsion-diffusion-evaporation process for PLGA. Futhermore, the Tyro Spheres provide a 7-day diffusion-controlled release, whereas PLGA nanoparticles provide a >21 days erosion-controlled release.[7] The microemulsified form of CsA has been shown to be safe and effective in the pediatric population.

There is a practical difficulty in giving CsA to an infant, particularly an underweight infant. The dose quantification from the routinely available oral solution can be quite problematic in small babies who fail conventional therapy and require CsA as a treatment option. The oral solution is commercially available as 100 mg per ml of CsA. There is hardly any other pediatric drug in solution which is dispensed in so much of a concentrated formulation. Hence utmost care needs to be taken to calculate the proper dose of CsA because just an error of 1 ml means a difference of 100 mg. We advocate the use of an insulin syringe for dose titration. In an insulin syringe, 1 ml is divided into 40 equal units [Figure 1]a and [Figure 1]b. Each unit is, therefore of 0.025 ml. Thus, each unit represents 2.5 mg of CsA. The use of insulin syringe for dose calculation helps to achieve accurate calibration to as low as 2.5 mg of CsA oral solution, which is otherwise not possible routinely with cyclosporine (syringe provided with the drug).
Figure 1: (a) A 2 ml and 4 ml syringe. Least dose calibration that can be achieved is 5 mg and 10 mg of CsA respectively. (b) An insulin syringe alongside the syringes in Figure 1. Least dose calibration that can be achieved is 2.5 mg of CsA. CsA . Cyclosporine A

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The left-over preparation should be discarded. The easy operation of an insulin syringe in terms of drawing a very small amount for the underweight infant makes it pertinent and useful as far as accurate dosing is concerned. A clinical demonstration should be given to parents to facilitate home preparation and administration. The desired weight-dependent dose should be administered within 10 min of preparation of the final formulation to prevent any contamination.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Available from: https://www.medicines.org.uk/emc/ingredient/792. [Last accesed on 2021 Mar 12].  Back to cited text no. 1
    
2.
Kauvar AB, Stiller MJ. Cyclosporine in dermatology: Pharmacology and clinical use. Int J Dermatol 1994;33:86-95.  Back to cited text no. 2
    
3.
Hernández-Martín A, Noguera-Morel L, Bernardino-Cuesta B, Torrelo A, Pérez-Martin MA, Aparicio-López C, et al. Cyclosporine A for severe atopic dermatitis in children. efficacy and safety in a retrospective study of 63 patients. J Eur Acad Dermatol Venereol 2017;31:837-42.  Back to cited text no. 3
    
4.
Menter A, Cordoro KM, Davis DMR, Kroshinsky D, Paller AS, Armstrong AW, et al. Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis in pediatric patients. J Am Acad Dermatol. 2020;82:161-201. doi: 10.1016/j.jaad.2019.08.049. Epub 2019 Nov 5. Erratum in: J Am Acad Dermatol 2020;82:574.  Back to cited text no. 4
    
5.
Morris RG. Cyclosporin therapeutic drug monitoring An established service revisited. Clin Biochem Rev 2003;24:33-46.  Back to cited text no. 5
    
6.
Calne RY, White DJ, Thiru S, Evans DB, McMaster P, Dunn DC, et al. Cyclosporin A in patients receiving renal allografts from cadaver donors. Lancet 1978;2:1323-7.  Back to cited text no. 6
    
7.
Ishikura K, Yoshikawa N, Hattori S, Sasaki S, Iijima K, Nakanishi K, et al. Treatment with microemulsified cyclosporine in children with frequently relapsing nephrotic syndrome. Nephrol Dial Transplant 2010;25:3956-62.  Back to cited text no. 7
    


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