Therapeutic

Class Medication

Mechanism of

Action Metabolism

Route of

Administration

(neonates) Dose and Frequency Reversal

Agent Comments

Nonopioid

analgesic

Acetaminophen

(paracetamol)

Inhibits peripheral

pain impulse

generation via

serotonergic

pathways.a

Hepatic: Cytochrome

P450 (CYP) enzymes;

sulfate and glucuronide metabolites

CYP2E1, 1A2, 3A4

metabolize small

amount to hepatotoxic

NAPQI “detoxified”

by glutathione

conjugation.b

Oral, rectal,

IV infusion

10-mg/mL

IV dose FDA

labeled for

>2 yr of age:

15 mg/kg q6h or

12.5 mg q4h

Limit: 75 mg/kg/d

Infuse dose over

15 min.

GA 28—32 wk:

Oral: 10–12 mg/kg/dose

q6–8hc

Rectal:

20 mg/kg/dose q12h

Limit: 40 mg/kg/d

GA 32–36 wk and term

≤10 d: Oral: 10–15 mg/

kg/dose q6h.

Rectal:

30 mg/kg then 15 mg/kg/

dose q8h

Limit: 60 mg/kg/d

Term ≥10 d:

Oral: 10–15 mg/kg/dose

q6h.

Rectal:

30 mg/kg then 20 mg/kg/

dose q6–8h

Limit: 75 mg/kg/d

None: GI decontamination/

acetylcysteine for

toxicity

Inducers of CYP2E, 1A2, 3A4: (phenobarbital, phenytoin, rifampin) alter

metabolism; ↑ hepatotoxicity

Neonates: ↓ CYP activity; ↓ toxicity

with ↑ serum concentrations.

Additive analgesic effect with opioid.

Ineffective for acute procedural pain.

Rectal absorption slow and unreliable

New IV form:

OFIRMEVd

1,000 mg/100 mL

AWP (USD)

$12.90/viale

Single-use vial

Expiration 6 h

Nonsteroidal antiinflammatory

drugs (NSAIDs)

Arylpropionic

Ibuprofen Inhibition of cyclooxygenase

enzyme and isoforms decreasing

prostaglandin

biosynthesis

(PGI2) resulting

in analgesia

Hepatic:

Phase I and II enzyme

biotransformation with

urinary and biliary

excretion. Metabolism

primarily by

CYP2C9 and CYP2C8.

↓ CYP2C9 activity in

newborn, increasing

over first year of life.

Polymorphisms

CYP2C9 may cause

ADRs.