Side Effects of Rocephin (Ceftriaxone)
Rocephin (ceftriaxone) can cause various side effects ranging from common mild reactions to rare but serious adverse events, with the most concerning being allergic reactions, biliary complications, and blood disorders.
Common Side Effects
Gastrointestinal effects:
- Diarrhea
- Nausea
- Vomiting
- Abdominal pain (<1%)
- Dyspepsia (rare)
Skin reactions:
- Rash
- Pruritus (itching)
- Exanthema
- Urticaria (hives)
- Diaphoresis (sweating) (<1%)
- Flushing (<1%)
Local reactions at injection site:
- Pain
- Induration
- Tenderness
- Phlebitis with IV administration
Laboratory abnormalities:
- Elevated liver enzymes (1-2%)
- Eosinophilia (blood count changes)
- Thrombocytosis (increased platelets)
- Leukocytosis
Serious Side Effects
Allergic Reactions
- Anaphylaxis or anaphylactoid reactions
- Serum sickness-like reactions
- Severe cutaneous adverse reactions (rare):
- Stevens-Johnson syndrome
- Toxic epidermal necrolysis (Lyell's syndrome)
- Erythema multiforme
- Acute generalized exanthematous pustulosis (AGEP)
Biliary Complications
- Biliary sludge/pseudolithiasis
- Gallbladder stones
- Symptomatic precipitation of ceftriaxone calcium salt in gallbladder 1
Hematologic Effects
- Hemolytic anemia
- Agranulocytosis (<500/mm³) - rare, usually after high doses (>20g) and prolonged treatment 1
- Isolated cases of aplastic anemia
Neurologic Effects
- Headache (<1%)
- Dizziness (<1%)
- Seizures (especially in patients with renal impairment)
- Encephalopathy
- Myoclonus
- Non-convulsive status epilepticus 1
Renal Effects
- Elevated creatinine (<1%)
- Presence of casts in urine
- Oliguria (rare)
- Renal precipitations
- Post-renal acute renal failure (rare)
- Nephrotoxicity (especially when combined with aminoglycosides)
Other Serious Effects
- Drug fever
- Superinfection
- Pancreatitis (rare)
- Pseudomembranous colitis
- Hepatic dysfunction including cholestasis
Special Considerations
Drug Interactions
- Calcium-containing products: Fatal reactions have been reported in neonates when ceftriaxone and calcium-containing solutions were administered together 1
- Anticoagulants: May increase prothrombin time
High-Risk Populations
- Patients with previous allergic reactions: Higher risk for allergic reactions, especially those with history of penicillin allergy 2
- Neonates: Risk of kernicterus and fatal reactions with calcium-containing products
- Patients with renal impairment: Higher risk of seizures if dosage not adjusted
- Patients with hepatobiliary disease: Increased risk of biliary complications
Administration Factors
- Rapid IV administration increases risk of adverse reactions 2
- Intramuscular administration can cause significant pain
Monitoring Recommendations
- Monitor for signs of allergic reactions, especially during first dose
- Periodic liver function tests during prolonged therapy
- Monitor renal function in patients with pre-existing renal disease
- Consider ultrasound for patients with right upper quadrant pain to assess for biliary sludge in prolonged therapy
Ceftriaxone is generally well-tolerated when used appropriately, but clinicians should be vigilant for these potential side effects, particularly in high-risk patients or those receiving prolonged therapy.