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20 September 2011

Dear Editor

The letter from Greenhill et al.1 reinforces the continuing ‘therapeutic orphan’ status of children described by Shirkey more than 40 years ago.2 Because there is no authorised liquid preparation of propranolol (and no authorised indication for propranolol tablets in the treatment of infant hemangioma) in Australia, carers are expected to manipulate tablets to ‘compound’ a solution at the point of administration. A portion of the compounded solution must be measured to obtain the required dose, and administration is made more acceptable by addition of the measured dose to food or liquid.

Such manipulations are rarely required of medicines for adult patients and run the risk of inaccurate dose, altered bioavailability and medication error. To their credit, Greenhill et al. attempted to demonstrate that the practice yields the correct dose. Their summary of results suggests that propranolol hydrochloride (solubility 1 in 20) can be recovered from the filtrate when soaking 10 mg propranolol tablets in 10 mL of water for 1 min before crushing. However, their summary provides no information on the overall accuracy of dose when a proportion of the volume is measured under ‘in use’ conditions. Experiments with dispersible aspirin tablets (solubility 1 in 100) by Broadhurst et al.3 suggest that dispersion and dissolution time are critical, concentration gradients may exist in the resulting solution and even the size of syringe used to measure the dose are important for dose accuracy. Add to this the risk of medication error if a different strength of tablet is used, inconvenience for the carer and acceptability issues for the patient, such manipulations are far from the standards we expect for ‘adult’ medicines.

The UK is fortunate in having the option to use commercially manufactured solution of propranolol which has been quality assured through the medicines licensing process (Syprol™, Rosemont Pharmaceuticals, Leeds, UK http://www.rosemontpharma.com). However, the product is not authorised for the treatment of infant hemangioma (use is ‘off-label’) and contains excipients such as propyl parahydroxybenzoate and maltitol, which have not been fully evaluated for infants.

Recently, Starkey and Shahidullah4 reported widespread use of propranolol for infant hemangioma and noted several studies that may provide evidence of safety and efficacy. If children are to move away from their ‘therapeutic orphan’ status, clinicians need to link with an appropriate pharmaceutical manufacturer to ensure that the indication and a suitable age – appropriate formulation receive a Marketing Authorisation in all relevant countries.

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