Compounding a Paediatric Oral Suspension from Tablets
A 4-year-old child weighing 16 kg is prescribed carbamazepine 10 mg/kg/day in two divided doses for epilepsy. The hospital pharmacy stocks only 200 mg uncoated tablets and has no commercial oral liquid. The pharmacist decides to prepare an extemporaneous suspension at 20 mg/mL so that each 4 mL dose delivers 80 mg. The child is currently stable on this dose, and the prescriber wants a 14-day supply. The pharmacy has purified water, a commercial suspending vehicle containing xanthan gum and citric acid (pH 4.5), a mortar and pestle, graduated cylinders, and amber PET bottles. No preservative-free vehicle is available, and the child's parents report difficulty measuring small volumes with a teaspoon.
1. Calculate the number of tablets and total volume needed for a 14-day supply, and identify the main pharmaceutical problems with this preparation.
Read the worked answer
Daily dose = 10 mg/kg × 16 kg = 160 mg/day, given as two 80 mg doses. At 20 mg/mL each dose is 4 mL, so daily volume = 8 mL and a 14-day supply = 112 mL. Total carbamazepine needed = 160 mg × 14 = 2240 mg, which equals 2240/200 = 11.2 tablets, so 12 tablets are weighed out to allow for loss.
Key problems: (1) Carbamazepine is practically insoluble in water and is a narrow-therapeutic-index drug (therapeutic range roughly 4–12 mg/L), so content uniformity and accurate dosing are critical; a suspension must be shaken well and the vehicle must keep particles suspended. (2) The tablets contain excipients and the drug is poorly wetted, so the powder must be triturated to a fine, uniform powder before levigation. (3) There is no stability data for this extemporaneous product, so a short beyond-use date is prudent. (4) A teaspoon cannot measure 4 mL accurately; an oral syringe should be supplied.
2. State a defensible beyond-use date and the labelling and counselling you would provide.
Read the worked answer
Without published stability data, a conservative beyond-use date of 14 days stored at 2–8 °C (or according to local extemporaneous compounding guidance) is appropriate; the product should be discarded if discolouration or caking that does not redisperse on shaking occurs. Because the vehicle is acidic and contains xanthan gum, the pharmacist should verify that carbamazepine does not precipitate or degrade; in practice a freshly prepared suspension should be used within the shortest reasonable period, and the 14-day course matches the prescription.
Labelling: 'Shake well before use', 'Store in a refrigerator', 'For oral use only', the strength (20 mg/mL), the dose (4 mL twice daily), the date of preparation and the beyond-use date, and a batch number.
Counselling: demonstrate drawing up 4 mL with an oral dosing syringe; advise giving doses at consistent times, preferably with food to reduce gastrointestinal upset; warn parents not to substitute a kitchen spoon; explain that the child should not stop abruptly because of withdrawal seizures; and advise reporting rash, drowsiness, or worsening seizure control, since carbamazepine can cause serious hypersensitivity reactions and dose-related neurotoxicity.