Extemporaneous Spironolactone Suspension for a Child with Ascites
You are the pharmacist in a hospital dispensary in Abuja. A 5-year-old girl weighing 18 kg has been prescribed spironolactone 2 mg/kg/day in two divided doses for ascites due to chronic liver disease. The hospital has no commercial spironolactone suspension. Stock available: spironolactone 25 mg tablets, methylcellulose 1% w/v suspension, simple syrup BP, purified water, a calibrated electronic balance, a mortar and pestle, graduated cylinders, amber PET bottles, and oral dosing syringes. The child's mother has limited literacy and cares for the child alone. The prescriber asks for a 30-day supply and wants the child to start today. The pharmacy has no published stability data for this exact formulation on file, and the next supply of commercial suspension is not expected for six weeks. The hospital's extemporaneous dispensing protocol requires a written master formula, a second-person check, and a beyond-use date based on the best available evidence.
1. Calculate the dose, the number of tablets, and the volume of a 5 mg/mL suspension needed for 30 days. Show your working and identify the practical formulation problem.
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Dose calculation
- Prescribed dose: 2 mg/kg/day × 18 kg = 36 mg/day.
- Divided into two doses: 18 mg per dose.
- At a concentration of 5 mg/mL: 18 mg ÷ 5 mg/mL = 3.6 mL per dose, given twice daily.
- Daily volume: 3.6 mL × 2 = 7.2 mL/day.
Thirty-day requirement
- Total drug: 36 mg/day × 30 days = 1,080 mg.
- Tablets needed: 1,080 mg ÷ 25 mg = 43.2, so 44 tablets (1,100 mg).
- Volume at 5 mg/mL: 1,080 mg ÷ 5 mg/mL = 216 mL. A practical batch of 220 mL would contain 1,100 mg, which is 44 tablets, giving exactly 5 mg/mL and about 30.5 days at 7.2 mL/day.
Practical problem
There is no on-file stability data for this exact formulation. A 30-day supply may exceed a defensible beyond-use date. The correct response is not to invent a 30-day expiry. Prepare a smaller batch with a conservative beyond-use date, arrange a repeat supply, or obtain published stability data for a validated formula. The calculation is straightforward; the stability and documentation judgement is the hard part.
2. Describe how you would compound and quality-check the suspension, including the beyond-use date decision.
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Compounding method
- Write and approve a master formula for 5 mg/mL spironolactone suspension. Record the batch number, tablet batch, vehicle, final volume, and the identity of the second checker.
- Count or weigh 44 spironolactone 25 mg tablets. Crush them to a fine, uniform powder in a mortar.
- Levigate the powder with a small amount of methylcellulose 1% w/v to form a smooth paste. This helps suspend the hydrophobic drug and prevents caking.
- Add simple syrup BP in small geometric portions, mixing thoroughly between additions. Transfer the mixture to a graduated cylinder, rinse the mortar with vehicle, and add the rinsings to the cylinder.
- Bring the final volume to 220 mL with the vehicle. Mix gently but thoroughly, avoiding excessive foaming.
- Transfer to an amber PET bottle, label with the concentration (5 mg/mL), dose volume (3.6 mL twice daily), 'shake well before use', storage conditions, and the beyond-use date. A second person checks the calculation, ingredients, volume, and label.
Quality checks
Check for uniform appearance, absence of lumps, correct final volume, and a clean label. Record the preparation. If the hospital has an analytical laboratory, a periodic assay or uniformity check is desirable, but do not imply that a visual check is a potency test.
Beyond-use date
Without published stability data for this exact formula, use a conservative beyond-use date, such as 14 days refrigerated, and arrange a repeat supply. If validated published data support a longer period, attach the reference to the master formula. Do not assign 30 days simply because the prescription asks for it.
3. What counselling and monitoring would you provide to the mother, and how would you document the preparation?
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Counselling
- Demonstrate how to shake the bottle well and draw exactly 3.6 mL into the oral syringe. Give twice daily, preferably with food to improve absorption and reduce gastric irritation.
- Explain that the medicine is for fluid build-up in the abdomen. Do not stop it because the abdomen looks smaller; the prescriber will adjust it.
- Warn about dizziness, tiredness, muscle weakness, palpitations, or confusion, which may suggest electrolyte disturbance or dehydration. Report vomiting, diarrhoea, or poor drinking promptly.
- Keep the bottle refrigerated, do not freeze it, and discard any remaining suspension after the beyond-use date.
- If a dose is missed, do not double the next dose. Give the next scheduled dose and record the miss.
- Because the mother has limited literacy, use pictures, a marked syringe, and a simple dosing chart. Ask her to repeat back the instructions.
Monitoring
Ask about daily urine output, body weight, abdominal girth, and general energy. The prescriber should monitor electrolytes and renal function, especially potassium and sodium, because spironolactone is potassium-sparing and the child has liver disease.
Documentation
File the master formula, the batch record, the tablet batch and quantity, the vehicle and final volume, the beyond-use date, the second-person check, the label copy, and a note of the counselling given. Keep a dispensing record so that the batch can be traced if an adverse event occurs.