INFANTS' FEVERALL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INFANTS' FEVERALL (INFANTS' FEVERALL).
Acetaminophen is a para-aminophenol derivative with analgesic and antipyretic activity. Its exact mechanism of action is not fully understood but is believed to involve inhibition of cyclooxygenase (COX) enzymes in the central nervous system, particularly COX-2, reducing prostaglandin synthesis. It has weak peripheral anti-inflammatory effects.
| Metabolism | Primarily metabolized in the liver via conjugation with glucuronic acid (UGT1A1, UGT1A6, UGT1A9) and sulfate (SULT1A1, SULT1A3). A minor pathway via CYP2E1 (and CYP1A2, CYP3A4) produces the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI), which is normally detoxified by glutathione. |
| Excretion | Renal excretion of metabolites (primarily glucuronide and sulfate conjugates): >90%. Biliary/fecal: <5%. |
| Half-life | Terminal elimination half-life: 2-4 hours in neonates and infants; prolonged in neonates due to immature hepatic glucuronidation. |
| Protein binding | 25-30% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | 0.9-1.2 L/kg; slightly larger in neonates due to increased total body water. |
| Bioavailability | Oral: 85-100%; rectal: 70-90%. |
| Onset of Action | Oral: 30-60 minutes; rectal: 60-120 minutes. |
| Duration of Action | 4-6 hours after oral administration; may be extended in neonates due to slower clearance. |
For fever or pain, 325-650 mg orally every 4-6 hours as needed, not to exceed 3250 mg/day. IV: 1000 mg every 6 hours or 650 mg every 4 hours, not to exceed 4000 mg/day.
| Dosage form | SUPPOSITORY |
| Renal impairment | CrCl 30-60 mL/min: No adjustment needed; use with caution. CrCl 10-30 mL/min: Extend dosing interval to every 8 hours. CrCl <10 mL/min: Extend interval to every 12 hours; maximum 2000 mg/day. |
| Liver impairment | Child-Pugh Class A: No adjustment. Class B: Reduce total daily dose by 50% (max 2000 mg/day). Class C: Avoid use or max dose 1000 mg/day; consider extended interval. |
| Pediatric use | Weight-based oral: 10-15 mg/kg/dose every 4-6 hours, maximum 75 mg/kg/day in divided doses. For preterm infants: 10-12 mg/kg/dose every 8-12 hours. IV: 7.5-15 mg/kg/dose every 6 hours, max 60 mg/kg/day. |
| Geriatric use | Initiate at lower end of dosing range (325 mg every 6 hours) due to decreased hepatic metabolism and renal function. Maximum daily dose 3000 mg. Avoid extended-release formulations. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for INFANTS' FEVERALL (INFANTS' FEVERALL).
| Breastfeeding | Excreted into breast milk in small amounts (M/P ratio 0.1-0.2). Considered compatible with breastfeeding; use lowest effective dose for shortest duration. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: limited data, possible association with neural tube defects with high doses. Second and third trimesters: low risk at therapeutic doses; high doses may cause premature closure of ductus arteriosus and oligohydramnios. |
| Fetal Monitoring |
■ FDA Black Box Warning
Acetaminophen has been associated with cases of acute liver failure, sometimes resulting in liver transplant and death. Most cases are associated with the use of acetaminophen in doses exceeding 4,000 mg per day, often involving more than one acetaminophen-containing product.
| Serious Effects |
["Hypersensitivity to acetaminophen or any components of the formulation","Severe hepatic impairment or active liver disease"]
| Precautions | ["Risk of severe hepatotoxicity with overdose; do not exceed recommended dose.","Do not use with other acetaminophen-containing products.","Avoid alcohol use while taking acetaminophen.","Instruct caregivers to calculate weight-based dose carefully.","Use caution in patients with hepatic impairment or severe renal impairment.","May cause serious skin reactions (e.g., Stevens-Johnson syndrome) – discontinue use if rash occurs."] |
Loading safety data…
| Monitor for maternal signs of toxicity (e.g., hepatotoxicity, rash). In third trimester, assess amniotic fluid index and fetal ductus arteriosus if use is prolonged or high-dose. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies show no impairment at therapeutic doses. |