Extemporaneous hydrochlorothiazide suspension for a 5.2 kg infant in a soum hospital
A 4-month-old girl weighing 5.2 kg is admitted to a soum hospital 180 km from the aimag centre with oedema from newly diagnosed nephrotic syndrome. The paediatrician prescribes hydrochlorothiazide 2 mg/kg/day in two divided doses alongside prednisolone. The hospital pharmacy stocks only hydrochlorothiazide 25 mg tablets; no oral liquid is available and the next aimag delivery is in ten days. The treatment room has a small vaccine refrigerator with a temperature log, but no air conditioning and no analytical balance beyond a Class III dispensing balance. Stock on hand: hydrochlorothiazide 25 mg tablets (in date), methylcellulose powder, glycerol, potassium sorbate, purified water, sucrose, and 100 mL amber PET bottles with child-resistant closures. The nurse asks you for a 100 mL bottle at 2.5 mg/mL so that doses can be measured with a 5 mL oral syringe.
1. Calculate how many tablets are needed for 100 mL of a 2.5 mg/mL suspension, and state the volume of each dose in mL. Show your working and comment on the measuring device available.
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Target concentration and quantity
- 2.5 mg/mL × 100 mL = 250 mg of hydrochlorothiazide needed.
- 250 mg ÷ 25 mg per tablet = 10 tablets.
Dose calculation
- Daily dose: 2 mg/kg/day × 5.2 kg = 10.4 mg/day.
- Divided into two doses: 5.2 mg per dose.
- 5.2 mg ÷ 2.5 mg/mL = 2.08 mL, so 2.1 mL twice daily.
Check the arithmetic is clinically usable
- A 5 mL oral syringe usually has 0.2 mL graduations, so the nurse would deliver either 2.0 mL (5.0 mg) or 2.2 mL (5.5 mg) - a ±4–6% error. That is acceptable for a diuretic but avoidable: supply a 3 mL oral syringe with 0.1 mL graduations so 2.1 mL is exact, and mark the dose on the label and the chart in both mL and mg to prevent a unit mix-up.
- Total volume check: the infant needs 4.16 mL/day, so 100 mL covers about 24 days - longer than the assigned beyond-use date (see next task). Consider dispensing 50 mL (5 tablets, 125 mg) to avoid waste and reduce the risk of using an expired bottle.
2. Propose a vehicle composition, the compounding steps, and a beyond-use date with justification, given the storage conditions actually available in this hospital.
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Vehicle
- Purified water to 100 mL as the base.
- Methylcellulose 1% w/v (1 g) as the suspending agent - disperse the powder in about 30 mL of hot (~80 °C) purified water to hydrate it, then make up with cold water.
- Glycerol 5–10 mL as a wetting agent and viscosity modifier so the dispersed tablets do not sediment into a hard cake.
- Potassium sorbate 0.1% w/v as preservative; note that a sucrose-based syrup would be self-preserving but is hyperosmolar and can cause osmotic diarrhoea in a 4-month-old, so avoid strong syrup.
Steps
- Triturate the 10 tablets to a fine, smooth powder in a dry mortar (tablets containing only the drug plus standard diluents are suitable; do not use modified-release or enteric-coated tablets).
- Add glycerol and mix to a smooth paste, then add a small volume of vehicle and mix to a uniform slurry (geometric dilution).
- Transfer to a graduated cylinder with rinsings, make to 100 mL, mix, bottle in amber PET, label 'shake well', 'oral use', dose in mL and mg, date prepared, and initials.
- Record in the compounding log: drug, batch, tablets used, vehicle, final volume, preparer, checker.
Beyond-use date Water-containing oral liquids prepared from tablets are assigned a conservative default of 14 days stored at 2–8 °C. The vaccine refrigerator gives you that storage, so label 'refrigerate, do not freeze' and discard 14 days after preparation. If the refrigerator fails or the bottle is kept at room temperature, shorten to about 7 days and inspect daily for caking, colour change, or gas. Do not extend to the 24 days the volume would allow.
3. What would you hand over to the nursing staff, and which observations would tell you the preparation is not performing?
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Handover points
- Shake vigorously for 10–15 seconds before each dose; the drug settles.
- Measure with the 3 mL syringe provided, never a teaspoon or a 5 mL syringe with coarse graduations.
- Give directly into the mouth, not into a full bottle of milk or formula - if the feed is not finished the dose is lost, and in a 4-month-old the diuretic effect then fluctuates.
- Do not add the drug to the whole day's feed.
- Store in the refrigerator, out of the freezer compartment and away from the vaccine boxes; write the discard date on the bottle and start a new bottle rather than topping up an old one.
Monitoring for failure
- Efficacy: daily weight (same scale, same time), urine output, oedema, respiratory rate. Hydrochlorothiazide acts within 1–2 hours; if diuresis falls sharply on a fresh bottle, suspect under-dosing from a settled suspension or a preparation error and check the compounding record.
- Safety: serum sodium and potassium, creatinine, and signs of dehydration (sunken fontanelle, dry mucosa, tachycardia) - infants on diuretics plus prednisolone are at risk of hypokalaemia and volume depletion.
- Stability signals: visible caking that does not redisperse, colour change, or a bottle that has been out of the refrigerator for more than a few hours - discard and prepare fresh.