Dosing and uses of Ofirmev (acetaminophen IV)
Adult dosage forms and strengths
injectable solution
- 10mg/mL
Pain & Fever
Indicated for mild-to-moderate pain and moderate-to-severe pain with adjunctive opioid analgesics
<50 kg: 12.5 mg/kg IV q4hr OR 15 mg/kg IV q6hr; not to exceed 750 mg/dose or 3.75 g/day
≥50 kg: 650 mg IV q4hr OR 1000 mg IV q6hr; not to exceed 4 g/day
Infuse IV over at least 15 minutes
Renal Impairment
CrCl <10 mL/min: Administer q8hr
CrCl 10-50 mL/min: Administer q6hr
Pediatric dosage forms and strengths
injectable solution
- 10mg/mL
Pain & Fever
<2 years: Safety and efficacy not established
2-12 years (<50 kg): 12.5 mg/kg IV q4hr OR 15 mg/kg IV q6hr; not to exceed 75 mg/kg/day
>12 years
- <50 kg: 12.5 mg/kg IV q4hr OR 15 mg/kg IV q6hr; not to exceed 750 mg/dose or 3.75 g/day
- ≥50 kg: 650 mg IV q4hr OR 1000 mg IV q6hr; not to exceed 4 g/day
Infuse IV over 15 minutes
Renal Impairment
CrCl <10 mL/min: Administer q8hr
CrCl 10-50 mL/min: Administer q6hr
Geriatric dosage forms and strengths
Reduced dose or dosage interval may be warranted in elderly patients with decreased renal or hepatic function
Ofirmev (acetaminophen IV) adverse (side) effects
>10%
Nausea (34%)
Vomiting (15%)
1-10%
Headache (10%)
Insomnia (7%)
Pediatrics
- Nausea (≥ 5%)
- Vomiting (≥ 5%)
- Constipation (≥ 5%)
- Pruritus (≥ 5%)
- Agitation (≥ 5%)
- Atelectasis (≥ 5%)
- Headache (≥ 1%)
Frequency not defined
Edema
Hypervolemia
Fatigue
Hypokalemia
Hypophosphatemia
Hypomagnesemia
Hypoalbuminemia
Increased transaminase levels
Anemia
Infusion site pain
Warnings
Black box warnings
Medication errors and hepatotoxicity
- Take care when prescribing, preparing, and administering acetaminophen IV to avoid dosing errors which could result in accidental overdose and death
- In particular, be careful to ensure that
- The dose in milligrams (mg) and milliliters (mL) is not confused
- The dosing is based on weight for patients <50 kg
- Infusion pumps are properly programmed
- The total daily dose of acetaminophen from all sources does not exceed maximum daily limits
- Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death
- Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed the maximum daily limits, and often involve more than one acetaminophen-containing product
Contraindications
Hypersensitivity
Severe hepatic impairment or severe active liver disease
Cautions
Doses higher than recommended may result in hepatic injury, including risk of severe hepatotoxicity and death
Do not exceed the maximum recommended daily dose
Caution with the following conditions: hepatic impairment or active hepatic disease, in cases of alcoholism, chronic malnutrition, severe hypovolemia, G6PD deficiency, hypovolemia, or severe renal impairment (CrCl <30 mL/min)
Discontinue immediately if symptoms associated with allergy or hypersensitivity occur
Rare serious skin reactions reported including acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal; discontinued at the first appearance of skin rash or any other sign of hypersensitivity
Pregnancy and lactation
Pregnancy category: C
Lactation: Excreted in breast milk in small quantities following oral administration, caution advised; estimated percentage in breastfed infant is 1-2% of maternal dose
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Ofirmev (acetaminophen IV)
Mechanism of action
Inhibits prostaglandin synthesis in the CNS and works peripherally to block pain impulse generation; acts on hypothalamus to produce antipyresis
Pharmacokinetics
Half-Life: 2.4 hr (adolescents); 2-3 hr (adults); 2-5 hr (children); 4-10 hr (neonates)
Vd: 0.8 L/kg
Peak plasma time: 0.25 hr (at end of infusion)
Peak plasma concentration: 28 mcg/mL
Metabolism: by conjugation with glucuronide, conjugation with sulfate, and oxidation via the cytochrome P450 enzyme pathway, primarily CYP2E1, to form a reactive intermediate metabolite (N-acetyl-p-benzoquinone imine or NAPQI)
Clearance: 0.27 L/hr/kg
Protein binding: 10-25% (therapeutic concentrations); 8-43% (toxic concentrations)
Excretion: <5% is excreted in the urine as unconjugated (free) acetaminophen and 60-80% as glucuronide metabolites
Administration
IV Incompatibilities
Additive: chlorpromazine, diazepam
Syringe: chlorpromazine, diazepam
Y-site: chlorpromazine, diazepam
IV Preparation
1 gram dose: Insert a vented IV set through septum of the 100 mL vial; may be administered without further dilution
Dose <1 gram: Using aseptic technique, withdraw the appropriate dose (650 mg or weight-based) from the intact sealed vial and place the measured dose in a separate empty, sterile container (eg, glass bottle, plastic IV container, or syringe) to avoid inadvertent delivery and administration of the total volume of the commercially available container
Place small volume pediatric doses up to 60 mL in volume in a syringe and administer over 15 minutes
Vial is for single use; discard any unused portion
IV Administration
Administer by IV infusion over 15 minutes
Storage
Store at room temperature 20-25°C (68-77°F); do not refrigerate or freeze
For single use only; discard any unused portion
Once the vacuum seal of the glass vial has been penetrated, or the contents transferred to another container, administer the dose within 6 hr
