Potential Dosing Errors With Oseltamivir in Children

Laurie Barclay, MD
Published: 09/24/2009
September 24, 2009 — Prescribers and pharmacists should be vigilant to avoid and detect potential
dosing errors with oseltamivir (Tamiflu, Roche) oral suspension formulation, according to an alert
sent today from the US Food and Drug Administration (FDA) Division of Drug Information and a
letter published online September 23 in the New England Journal of Medicine.

The FDA notes that US clinicians usually prescribe liquid medicines in milliliters (mL) or teaspoons,
but oseltamivir is dosed in milligrams (mg), and the dosing dispenser prepackaged with oseltamivir
is marked only at 30, 45, and 60 mg. Errors that have occurred because patient dosing instructions
for oseltamivir oral suspension do not correspond with the numbers on the dosing dispenser have
been reported to the FDA.

"Health care providers should write doses in mg if the dosing dispenser with the drug is in mg,"
according to the FDA. "Pharmacists should ensure that the units of measure on the prescription
instructions match the dosing device provided with the drug. If prescription instructions specify
administration using mL, the dosing device accompanying the product should be replaced with a
measuring device (e.g., a syringe) calibrated in mL."

A letter to the editor published online September 23 in the New England Journal of Medicine by Ruth
M. Parker, MD, from the Emory School of Medicine in Atlanta, Georgia, and colleagues, provides a
case report. A 6-year-old diagnosed with novel H1N1 influenza was prescribed oseltamivir oral
suspension (12 mg/mL) at a dose of 3/4 teaspoon by mouth twice daily. The child's parents had
great difficulty in determining the correct dose, even though one of the parents is a primary care
physician and the other is one of the letter's authors.

Although the pharmacy's prescription label specified the dose in volume units ("3/4 teaspoonful"),
the medication bottle was accompanied by a prepackaged syringe that had markings of 30, 45, and
60 mg. Using 1 of 10 tables in the portion of the package insert intended for prescribers, the parents
finally calculated the correct dose by solving the following equation for the mg equivalent of the 3/4-
tsp dose: 5 mL (volume of a teaspoon) × 0.75 × 12 mg/mL oseltamivir suspension = 45 mg on the
syringe.

The letter's authors note that the instructions on the pharmacy label, on the manufacturer's printed
label, and in the accompanying consumer medication information and the prepackaged dosing
syringe are misaligned. They warn that most families and caregivers would have extreme difficulty in
finding and solving the equation needed to calculate the correct dose.

"Thus, there is a high chance for dosing errors, compromised treatment, or toxic effects," the letter's
authors write. "Even more complex dosing and measurement calculations will be required under the
Emergency Use Authorization, which has extended the use of oseltamivir to children under the age
of 1 year. Unless immediate steps are taken to improve the prescribing instructions for this drug in
children, its safe use will be compromised."

The letter's authors recommend that all pharmacies ensure that the label instructions correspond to
the same dosing units as those on the measurement device prepackaged with oseltamivir, or that if
a prescription specifies the dose in teaspoons, only a syringe calibrated in fractions of a teaspoon
should be dispensed and the instructions adjusted accordingly. Similarly, if the prescription specifies
the dose in mL, only a syringe calibrated in mL should be used.
"In addition, the Consumer Medication Information must be improved and the public alerted to the
potential for oseltamivir dosing errors," the letter's authors write. "In the future, all measuring devices
for use in children should be marked with volumetric doses (milliliters or teaspoons)."

Some of the letter's authors have disclosed various financial relationships with Abbott, Pfizer, McNeil
Pharmaceuticals, Symphony Capital, Oxigene Pharmaceuticals, and/or International Reinsurance
companies.

N Engl J Med. Published online September 23, 2009.

FDA Division of Drug Information, September 24, 2009.