Medicine Dosing in Premature Infants

Premature infants (born under 37 weeks) have the least mature organs, so dose and interval are chosen by gestational age at birth, postnatal age and postmenstrual age (gestational age plus postnatal age), not by weight alone. Errors are common because clearance changes weekly and doses rarely scale with term values.

Pharmacokinetic features. Total body water is highest in the most premature infants, renal function is lowest, hepatic enzymes are least mature, protein binding is low and skin absorption is very high. Thin skin also leads to large insensible water loss, so fluid and drug concentrations change rapidly.

Reference points. Use postmenstrual age to set dosing interval bands. Re-evaluate at each week of postnatal age and at each change in weight.

• Caffeine citrate for apnoea of prematurity: 20 mg/kg orally or intravenously as a loading dose, then 5 to 10 mg/kg once daily. Caffeine base is half the citrate dose, a frequent prescribing error. Target level 8 to 20 mg/L.
• Ibuprofen for patent ductus arteriosus: 10 mg/kg intravenously, then 5 mg/kg at 24 and 48 hours. Avoid with creatinine rise, oliguria, thrombocytopenia under 50 x 10^9/L, necrotising enterocolitis or active bleeding.
• Paracetamol (alternative for ductus closure and analgesia): intravenous 10 mg/kg every 6 hours for infants 32 weeks or more, and 7.5 mg/kg every 8 to 12 hours for 28 to 32 weeks, with a maximum of 30 mg/kg/day below 32 weeks.
• Vitamin K: 0.5 mg intramuscularly at birth for infants under 1.5 kg.
• Gentamicin: 4 to 5 mg/kg intravenously with an interval of 36 to 48 hours for infants under 32 weeks of postmenstrual age, shortened to 24 to 36 hours by 34 weeks, adjusted to a pre-dose level under 1 mg/L.
• Surfactant (poractant): initial dose 100 to 200 mg/kg intratracheally given by trained staff; repeat 100 mg/kg at 6 to 12 hours if oxygen need persists.
• Antibiotics for late-onset sepsis: specialist choice by unit pattern, often flucloxacillin or vancomycin plus gentamicin. Vancomycin 10 to 15 mg/kg intravenously with interval set by postmenstrual age and trough level.

Contraindicated or avoided. Ceftriaxone, chloramphenicol, benzyl alcohol-containing preparations, hyperosmolar oral medicines (dilute), and routine non-steroidal drugs without the ductus indication.

Fluids and glucose. Day 1 fluids 60 to 80 mL/kg/day of 10% glucose for infants 28 to 34 weeks, and 80 to 100 mL/kg/day for extremely preterm infants, adjusted to weight loss, sodium and urine output. Glucose infusion rate 4 to 8 mg/kg/min.

Kidney impairment. Lengthen intervals for aminoglycosides, vancomycin and ibuprofen. Stop ibuprofen if urine output falls under 1 mL/kg/h.

Special groups. Kangaroo care is not a substitute for analgesia but reduces procedural pain. In East Africa, preterm units with no levels service should use the longer gentamicin intervals and avoid vancomycin unless level monitoring is possible.

Monitoring. Weigh daily, record urine output hourly in the first 3 days, measure glucose 4 to 6 hourly, and sodium, potassium, creatinine and bilirubin daily in unwell infants. Measure aminoglycoside, vancomycin and caffeine levels where available.

Referral and escalation. Prescribe under neonatologist direction. Escalate for apnoea unresponsive to caffeine, oliguria, abdominal distension, bilious aspirates, or rising creatinine on any nephrotoxic drug.

Stopping. Stop caffeine at about 33 to 34 weeks postmenstrual age once apnoea free for 5 to 7 days. Stop antibiotics at 48 hours if cultures are negative and the infant is well.