What are the adverse reactions of ceftriaxone?

Adverse Reactions of Ceftriaxone

Common Adverse Reactions

Ceftriaxone is generally well tolerated, with the most frequent adverse reactions being gastrointestinal disturbances (2.7-3.45%), hypersensitivity reactions (1.7-2.99%), and local injection site reactions (1-1.86%). 1, 2

Gastrointestinal Effects

• Diarrhea/loose stools occur in 2.7% of patients and represent the most common adverse effect 1
• Nausea, vomiting, and dysgeusia occur in less than 1% of cases 1
• Pseudomembranous colitis can develop during or after treatment, requiring immediate discontinuation if suspected 1
• Pancreatitis, stomatitis, and glossitis have been reported in postmarketing surveillance 1, 3

Hypersensitivity Reactions

• Rash occurs in 1.7% of patients 1
• Pruritus, fever, and chills occur in less than 1% 1
• Severe cutaneous reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and acute generalized exanthematous pustulosis (AGEP) have been reported 3
• Anaphylaxis and anaphylactoid reactions are rare but potentially fatal 1, 3, 4
• Cross-reactivity with penicillin allergy is uncommon, but ceftriaxone is contraindicated in patients with IgE-mediated penicillin allergies (anaphylaxis, Stevens-Johnson syndrome, toxic epidermal necrolysis) 5

Local Injection Site Reactions

• Pain, induration, and tenderness occur in approximately 1% overall 1
• Phlebitis occurs in less than 1% with IV administration 1
• IM injection causes warmth, tightness, or induration in 5-17% depending on concentration used 1

Hematologic Adverse Reactions

Common Hematologic Changes

• Eosinophilia (6%) and thrombocytosis (5.1%) are the most frequent hematologic findings 1
• Leukopenia occurs in 2.1% of patients 1
• Granulocytopenia occurs in 0.9% 1

Serious Hematologic Complications

• Hemolytic anemia can occur and requires immediate discontinuation of ceftriaxone, with supportive care including transfusion support as needed 6, 1
• For severe cases of ceftriaxone-induced hemolytic anemia, corticosteroids and IVIG should be considered 6
• Thrombocytopenia has been reported, though bleeding is rare 7, 1
• Neutropenia, lymphopenia, and anemia occur in less than 1% 1
• Agranulocytosis (less than 500/mm³) has been reported, typically after 10 days of treatment with total doses exceeding 20g 3
• Prolongation of prothrombin time can occur 1
• Coagulopathy occurs in 0.4% of patients 1

Hepatobiliary Adverse Reactions

• Elevations of AST (3.1%) and ALT (3.3%) are common 1
• Elevations of alkaline phosphatase and bilirubin occur in less than 1% 1
• Biliary lithiasis and gallbladder sludge can develop, particularly with high doses 1, 3
• Liver function abnormalities with ceftriaxone are sometimes associated with "sludging" of drug in the gallbladder 5
• Cholestatic jaundice and hepatitis have been reported 1

Renal Adverse Reactions

• Elevations of BUN occur in 1.2% of patients 1
• Elevations of creatinine and presence of casts in urine occur in less than 1% 1, 3
• Blood creatinine increased in 0.6% 1
• Nephrolithiasis and renal precipitations have been reported 1, 3
• Oliguria, ureteric obstruction, and post-renal acute renal failure have been documented in postmarketing surveillance 3

Neurologic Adverse Reactions

• Headache and dizziness occur occasionally (less than 1%) 1, 3
• Serious neurologic complications including encephalopathy, seizures, myoclonus, and non-convulsive status epilepticus have been reported 3
• Seizures are particularly concerning in patients with renal impairment when dosage is not appropriately reduced 3

Fatal and Life-Threatening Reactions

Ceftriaxone was responsible for the highest number of deaths (49 cases) in the Iranian pharmacovigilance database over a 10-year period, with 30% of reported adverse events categorized as serious. 4

Neonatal Fatal Reactions

• Fatal outcomes with crystalline material observed in lungs and kidneys have been reported in neonates receiving ceftriaxone and calcium-containing fluids 1, 3
• This can occur even when ceftriaxone and calcium are administered at different time points via different IV lines 1, 3
• Ceftriaxone is contraindicated in neonates receiving or expected to receive calcium-containing IV solutions 1, 3

Cardiac and Anaphylactic Events

• Cardiac arrest has been reported 4
• Anaphylactic and anaphylactoid reactions represent serious adverse events requiring immediate intervention 1, 4

Other Adverse Reactions

• Genital fungal infections (moniliasis/vaginitis) occur in 0.1-1% 1, 3
• Diaphoresis and flushing occur occasionally (less than 1%) 1, 3
• Kernicterus has been reported 3
• Serum sickness has been documented 1

Risk Factors for Adverse Events

Three key risk factors significantly increase the likelihood of adverse reactions: 4

1. Previous history of allergic reactions to ceftriaxone, penicillin, or other beta-lactam antibiotics (9.6% of patients with adverse events had this history) 4
2. Rapid intravenous injection rather than slow infusion 4
3. Unlabeled use of the drug (2.9% of adverse events) 4

Comparative Safety Profile

• Ceftriaxone is more likely than oral antimicrobials to cause serious adverse effects, which is why it is not recommended for early Lyme disease without neurologic involvement 5
• When compared directly with other antibiotic regimens, the overall incidence of clinical adverse effects is similar 2
• The frequency of adverse effects for once-daily versus twice-daily dosing is comparable, except for a statistically significant increase in local reactions with twice-daily administration 2
• In the pediatric population specifically, gastrointestinal reactions occur in 5.63% and hypersensitivity reactions in 3.3% 2