Generic Name
PARACETAMOL TABLET (Acetaminophen) Physical Properties Of The Chemical Entity1
a. Structural Formula
b. Molecular Formula C8H9NO2
c. Molecular Weight 151.16
d. Macroscopic Appearance
Acetaminophen is a white, crystalline powder.
e. Solubility water 1:70
boiling water 1:20 alcohol 1:10 chloroform 1:50 glycerin 1:40
ether slightly soluble Chemical Properties
a. Structural Similarities/Differences of the Drug to Other Available Compounds or Groups of Compounds
Acetaminophen is a synthetic, nonopiate, centrally acting analgesic derived from p-aminophenol. The full chemical name is N-acetyl-p-p-aminophenol.
b. pKa
The pKa of acetaminophen is 9.51 at 25°C.
c. Stability of the Drug to Temperature, Light, and Moisture
Acetaminophen is stable to temperature, light, and moisture.
d. pH Range Over Which Drug is Stable in Solution Acetaminophen is stable at a pH between 4 and 7 at 25°C.
e. pH of Commercially Available Liquid Products
Acetaminophen oral solution (ie, elixir, adult liquid) has a pH of 3.8 to 6.1 and the oral suspension (ie, infants' drops, children's suspension) has a pH of 5.4 to 6.9.
f. Osmolarity/Osmolality of Commercially Available Solutions
Extra Strength PARACETAMOL acetaminophen Adult Liquid: 3058 ± 152 mmol/kg Children's PARACETAMOL acetaminophen Elixir: 6040 ± 25 mmol/kg
Because of the nature of suspension formulations, osmolarity of the PARACETAMOL acetaminophen suspension products cannot be determined.
References
1. Remington's Pharmaceutical Sciences. 23rd ed. Easton, PA: Mack Publishing Company;
1995:1109-1110.
*Permission to use the Product Information Form for the American Hospital Formulary Service as modified by McNeil Consumer Healthcare has been granted by the American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, MD 20814.
The answers to all questions are prepared and furnished by the manufacturer. The answers were not supplied by the Society nor are they intended to imply the endorsement of the American Society of Health-System Pharmacists; neither does the Society affirm or deny the accuracy of the answers contained herein. Copyright© 1985, American Society of Health-System Pharmacists, Inc., all rights reserved.
INDICATIONS
DOSAGE RANGE a. Administration
PARACETAMOL acetaminophen products are only administered orally. They are available in a variety of convenient dosage forms as listed in Tables 2 and 3. For ease of administration for young children, Infants' f Concentrated Drops are more concentrated than the Children's PARACETAMOL liquid formulations. Infants' PARACETAMOL Concentrated Drops
51 b. Adult Dosage
For adults and children 12 years of age and older, the recommended dose of acetaminophen is 650 to 1000 mg every 4 to 6 hours as needed, not to exceed 4000 mg in 24 hours (Table 2).
For extended-release acetaminophen, the dose is 1300 mg every 8 hours as needed, not to exceed 3900 mg in 24 hours. Some adult products (Extra Strength PARACETAMOL, PARACETAMOL Arthritis Extended Relief Formula) are not intended for use in children under 12 years of age.
c. Pediatric Dosage
For children under 12 years of age, the recommended dose of acetaminophen is 10 to 15 mg/kg every 4 to 6 hours,47 not to exceed five doses (50-75 mg/kg) in 24 hours (Table 3).
Age-Related Dosing Schedule
The age-related schedule is based on standard age divisions proposed by the United States Food and Drug Administration (FDA) and used in the development of an acetaminophen dosing schedule.47
TABLE 4. Recommended pediatric dosing of acetaminophen by weight and age (adapted from reference 47, with permission)*
Weight
36-47 16.0 - 21.9 4-5 years 240 1200
48-59 22.0 -26.9 6-8 years 320 1600
60-71 27.0 - 31.9 9-10 years 400 2000
72-95 32.0 -43.9 11 years 480 2400
* Refer to package label for more specific information related to dosing.
a For adults and children 12 years of age and older see Table 2.
b Doses may be repeated every 4 hours but not more than five times daily
c Data not available to define appropriate adjustments, if any, needed for the immediate neonatal period. Use of antipyretics in the immediate neonatal period is extremely limited.
Weight-Related Dosing Schedule
This weight-related dosing schedule was developed and recommended by McNeil Consumer Healthcare when dosing by weight. The weight-related schedule is based on weight ranges that are consistent with the use of a standard 80-mg dosage unit.47 Using this method, the weight-related dosage schedule provides a dose of 10 to 15 mg/kg body weight for a single dose. The weight-related schedule most closely approximates this dose, so that when possible, consumers should be instructed to use weight to calculate dose; otherwise, age may be used (Table 4).
The label for Regular Strength PARACETAMOL acetaminophen products recommends that children 6 to 11 years old take 325 mg every 4 to 6 hours, not to exceed five doses in 24 hours.
d. Use of Recommended Doses for Longer Than 10 Days
Clinical studies have evaluated the use of acetaminophen in adult patients with osteoarthritis of the knee at recommended doses of 4000 mg/d for up to 4 weeks.48,49 Williams and colleagues50 evaluated the use of acetaminophen in doses up to 2600 mg/d for up to 2 years.
In these studies, acetaminophen was well tolerated.
The package label for adult PARACETAMOL acetaminophen products instructs adults not to take PARACETAMOL for pain for more than 10 days or for fever for more than 3 days unless directed by a doctor. The package label for Children's PARACETAMOL products instructs parents not to administer PARACETAMOL to children for pain for more than 5 days or for fever for more than 3 days unless directed by a doctor. As with all over-the-counter (OTC) analgesics, this warning is necessary so that patients and parents will seek appropriate medical evaluation of their condition if it persists beyond these time periods.
e. Alternate/Concomitant Dosing
Concomitant or alternate dosing with more than one antipyretic agent is not recommended.
There are no studies to support alternate dosing of acetaminophen and ibuprofen or other nonsteroidal anti-inflammatory drugs (NSAIDs). Studies have demonstrated that single-dose concurrent administration of aspirin and acetaminophen produced a more prolonged
temperature decrement than when either antipyretic was given alone.51,52 f. Recommended Storage Conditions
Storage requirements for all PARACETAMOL acetaminophen drops, liquids, and solid formulations are as follows: store at room temperature. It is recommended that high humidity and excessive heat (ie, ≥ 40°C [104°F]) be avoided for the gelatin-coated formulations (eg, gelcaps, geltabs). Freezing of the liquid or suspension formulations should be avoided.
g. Expiration Dating Periods for Commercially Available Products
Under room temperature storage conditions, PARACETAMOL acetaminophen solid
formulations are generally stable for 3 years and liquid formulations are generally stable for 2 years from the date of manufacture. Refer to product package for specific expiration date.
References
47. Temple AR. Pediatric dosing of acetaminophen. Pediatr Pharmacol. 1983;3:321-327.
48. Amadio P, Cummings DM. Evaluation of acetaminophen in the management of osteoarthritis of the knee. Curr Ther Res. 1983;34:59-66.
49. Bradley J D, Brandt KD, Katz BP, Kalasinski LA, Ryan SI. Comparison of an anti-inflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the
53 52. Steele RW, Young FH, Bass JW, Shirkey HC. Oral antipyretic therapy: evaluation of aspirin-acetaminophen combination. Am J Dis Child. 1972;123:204-206.