Although their pharmacokinetics are all similar, here's how they differ.
The 3 formulations available for acetaminophen are intravenous (IV), per oral (PO), and per rectal (PR). Although their pharmacokinetics are all similar, here’s how they differ:
A generic version of the Ofirmev prescription brand-name formulation isn’t available, making IV acetaminophen significantly more expensive than the PO or PR formulations.
The indications for IV acetaminophen include mild to moderate pain, the transient reduction of fever, or moderate to severe pain when taken in combination with opioids. The product comes with a black box warning about the risk of medication errors that could potentially result in unintentional overdose leading to death as well as risks for liver toxicity. Contraindications include hypersensitivity reactions and severe liver damage or active severe liver disease, while common adverse effects include nausea and vomiting, headache, and insomnia. More serious adverse reactions are liver injury, anaphylaxis, serious skin reactions (Steven Johnsons syndrome, toxic epidermal necrolysis), and hypersensitivity reactions.
IV administration decreases exposure to the liver by nearly half because of first-pass metabolism. Study results haven’t deemed IV acetaminophen more effective than the PR formulation for pain reduction in children post-tonsillectomy; however, the time to rescue takes longer with PR. IV acetaminophen also has a rapid onset of action compared to the same dose of oral acetaminophen, and the time to reach peak plasma concentration (Cmax) for IV administration is 30 minutes faster than the PO formulation. Study results have shown Cmax occurring near the end of 15 minutes with IV infusion, in which it can achieve 70% greater Cmax than the same dose of oral acetaminophen.
Overall, IV acetaminophen can provide significant pain relief within 15 minutes after initiating infusion, as well as significant fever reduction within 30 minutes after initiating infusion. Study results show the Cmax of IV acetaminophen is 76% greater than PO and 256% greater than PR. The peak cerebrospinal fluid concentrations are 60% greater with IV administration than with PO and 87% greater with IV administration than with PR.
For endotoxin-induced fever, IV is favored over PO acetaminophen in reducing temperature for up to 2 hours after administration. After 2 hours, however, there is no statistically significant difference.
The use of parenteral analgesia is clinically warranted when a patient has compromised gastrointestinal (GI) absorption or is unable to take oral analgesics, or when 100% bioavailability is wanted. It’s also recommended to transition from IV administration to PO when a patient can take or tolerate and absorb oral analgesics.
PO and PR Acetaminophen
These formulations are both available as inexpensive generics, though PO is also available OTC.
The indications for PO and PR acetaminophen include transient reduction of fever and transient relief of pains, minor aches, and headaches. Contraindications for both are to avoid use with any other medications that contain acetaminophen as an ingredient, or if a patient has any allergic reaction to acetaminophen. The many potential adverse reactions include liver toxicity, leukopenia, increased serum bilirubin, anemia, reduced serum bicarbonate, pancytopenia, skin rash, decreased serum calcium and sodium, hyperchloremia, hyperuricemia, increased serum glucose, renal toxicity generally with chronic overdose, neutropenia, increased serum alkaline phosphatase, and kidney disease.
Because altered gastric emptying changes the absolute absorption rate of oral medications, especially postsurgery, PO acetaminophen absorption decreases due to compromised GI function. For instance, study results show the Cmax oral acetaminophen concentration is significantly lower postoperatively in orthopedic surgery patients, and oral acetaminophen absorption is decreased in post nasogastric administration, specifically on day 1 postsurgery in cardiac surgery patients.
Overall, no significant difference is seen between PO and PR acetaminophen concerning peak cerebrospinal fluid concentrations. For analgesia duration postadministration of PR versus IV acetaminophen, the median time to first rescue for PR was 10 hours, compared with 7 hours for IV acetaminophen.