Ceftriaxone and Lidocaine Mixing for IM Injection
Yes, ceftriaxone (Rocephin) can and should be mixed with 1% lidocaine for intramuscular administration to significantly reduce injection pain, and this practice is explicitly supported by FDA labeling and clinical guidelines. 1
FDA-Approved Mixing Practice
- The FDA drug label for ceftriaxone explicitly permits reconstitution with lidocaine solution for intramuscular injection, with the critical caveat that intravenous administration of ceftriaxone-lidocaine solutions is absolutely contraindicated. 1
- When using lidocaine as a diluent for IM ceftriaxone, you must exclude all contraindications to lidocaine per its prescribing information before mixing. 1
Clinical Benefits and Tolerability
- The CDC notes that reconstitution with lidocaine significantly improves tolerability of IM ceftriaxone administration and reduces injection discomfort. 2
- Multiple controlled studies demonstrate that lidocaine as a diluent reduces both the intensity and frequency of injection site pain considerably compared to sterile water. 3, 4
- Pain reduction is clinically significant at multiple time points: immediately post-injection, at 10 minutes, 20 minutes, and even at 6 hours after administration. 4
Pharmacokinetic Equivalence
- Lidocaine does not alter the bioavailability or elimination parameters of ceftriaxone when used as a diluent. 3
- Studies show identical mean peak plasma concentrations (42-45 mcg/mL), time to peak (2.5-3 hours), area under the curve (577-578 mcg·h/mL), and elimination half-life (7.0-7.1 hours) whether ceftriaxone is reconstituted in water or 1% lidocaine. 3
- Different concentrations of ceftriaxone in lidocaine (250 mg/mL vs 350 mg/mL) are bioequivalent, allowing flexibility in preparation. 5
Practical Preparation Guidelines
- Use 1% lidocaine solution (without epinephrine) as the standard diluent for IM ceftriaxone. 3, 6
- Buffered lidocaine (lidocaine mixed with sodium bicarbonate) provides equivalent pain reduction to unbuffered 1% lidocaine for ceftriaxone injections. 6
- The typical reconstitution uses 2 mL of 1% lidocaine for 500 mg ceftriaxone (250 mg/mL concentration) or 1.4 mL for a more concentrated 350 mg/mL solution. 5
Critical Safety Contraindications
- Never administer ceftriaxone-lidocaine mixtures intravenously—this is an absolute FDA contraindication. 1
- Do not use lidocaine diluent in neonates ≤28 days old who require or may require calcium-containing IV solutions due to fatal precipitation risk. 1
- Exclude lidocaine in premature neonates up to 41 weeks postmenstrual age and hyperbilirubinemic neonates. 1
- Screen for lidocaine allergy and cardiac conduction abnormalities before using lidocaine as a diluent. 1
Clinical Experience
- Home parenteral therapy studies demonstrate excellent tolerability when lidocaine is used for ceftriaxone reconstitution, with cure rates of 97% (30/31 patients) and universal patient acceptance of the IM route. 7