Extemporaneous spironolactone suspension for a 14 kg child: dose, formula and beyond-use date

Calculation. Total daily dose = 1.5 mg/kg/day x 14 kg = 21 mg/day. Divided into two doses = 10.5 mg per dose. A practical strength is 5 mg/mL (20 tablets of 25 mg made up to 100 mL), so each dose is 10.5 / 5 = 2.1 mL twice daily. One 100 mL bottle contains 100/2.1 = about 47 doses, i.e. roughly 23 days of treatment at two doses a day.

Why a suspension rather than a solution:

• Spironolactone is practically insoluble in water. A 5 mg/mL solution would need co-solvents or surfactants that are not available here and would not be appropriate for a 3-year-old with heart failure (solvent load, palatability, osmotic effects).
• A suspension delivers the same fine drug particles as the tablet, so the biopharmaceutic behaviour is closer to the product with known bioavailability; a hastily solubilised formulation would have unknown absorption.
• Practically, a suspension is made from the registered tablet with simple excipients and equipment available in a hospital dispensary, and can be made at the exact strength needed.

Before compounding, two checks: confirm from the DDA register that no commercial oral liquid is available for import or supply (use a registered product if there is one), and confirm the tablets are immediate-release spironolactone and not a combination product. Also confirm with the prescriber that 2.1 mL is a workable volume; if not, a 3 mg/mL strength would give 3.5 mL per dose, which is easier to measure accurately with a 5 mL syringe.

Procedure (for 100 mL of 5 mg/mL):

1. Clean the work area; assemble a mortar and pestle, graduated cylinder, amber bottle and oral syringes; record the tablet batch number and expiry in a compounding record.
2. Weigh/count 20 tablets (500 mg spironolactone). Check the count and the calculation independently with a second person.
3. Triturate to a fine, smooth powder, then reduce to a paste with a small quantity of methylcellulose mucilage; add the mucilage in geometric portions so that the powder is never dry and lumpy.
4. Add Simple Syrup BP containing sorbic acid 0.1% in portions, transferring and rinsing the mortar to lose no drug.
5. Make to 100 mL in a graduated cylinder, mix by inversion, transfer to an amber bottle, and label with strength, dose, and the beyond-use date.

Checks:

• In-process: absence of grit on the pestle, no visible agglomerates, uniform colour, correct final volume, and correct tablet count.
• Finished product: pH (record it - sorbic acid is only effective at acid pH), appearance, resuspendability after standing (invert and check for a uniform dispersion and no cake), and fill volume. If the hospital has a validated HPLC or UV method, assay a sample against a standard; if not, retain 20 mL as a retention sample for the duration of the BUD plus one month.
• Label with 'shake well', 'keep refrigerated', 'do not freeze', dose in mL, and the discard date.
• Dispense with a 5 mL oral syringe marked in 0.2 mL divisions, and show the parents how to use it; a household teaspoon is not acceptable for a 2.1 mL dose in a child on an ACE inhibitor, where an error of a millilitre changes potassium handling.

Beyond-use date. There is no product-specific stability data, so the BUD has to be set from a default framework rather than from evidence about this formula. USP <795> assigns up to 35 days refrigerated for water-containing oral liquids prepared from non-sterile components when a preservative is present, and 14 days when it is not. Here there is a preservative (sorbic acid 0.1%), but it is a preservative whose activity depends on pH, the vehicle is a sugar syrup, the drug is light-sensitive, and the preparation is made from crushed tablets with no stability data at all. A conservative 14 days, refrigerated, in an amber bottle is the defensible choice; document that the 35-day default was considered and why the shorter period was adopted, and check whether the hospital's own policy sets a shorter maximum. Never assign a BUD longer than the expiry of the tablet batch used.

Counselling: shake vigorously each time; measure with the oral syringe, not a spoon; keep in the refrigerator, never frozen; discard after 14 days or sooner if the liquid separates and does not resuspend, smells odd, or changes colour; keep out of the child's reach; do not add to feeds unless advised.

Monitoring: potassium and creatinine before starting, at 3-5 days after starting or changing dose, and periodically thereafter - the child is on an ACE inhibitor and furosemide, so the risk of hyperkalaemia is real and is the main hazard of adding spironolactone. Watch for vomiting, poor feeding, drowsiness or irregular heartbeat (features of hyperkalaemia), monitor weight and urine output for the heart failure, and check for gynaecomastia on long-term use. Report any suspected reaction to the hospital's ADR unit, and supply the family with a medicine chart in Nepali.