Applies to ceftriaxone: injection powder for solution.

Serious side effects of Ceftriaxone

Along with its needed effects, ceftriaxone may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking ceftriaxone:

More common

• Black, tarry stools
• chest pain
• chills
• cough
• fever
• painful or difficult urination
• shortness of breath
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• swollen glands
• unusual bleeding or bruising
• unusual tiredness or weakness

Less common

• Diarrhea

Rare

• Abdominal or stomach cramps or tenderness
• back, leg, or stomach pains
• bleeding gums
• bloating
• blood in the urine or stools
• bloody nose
• bluish color
• changes in skin color
• clay-colored stools
• convulsions
• cough or hoarseness
• dark urine
• diarrhea, watery and severe, which may also be bloody
• difficulty with breathing
• difficulty with swallowing
• dizziness
• fast, irregular, pounding, or racing heartbeat or pulse
• feeling of discomfort
• feeling of warmth
• fever with or without chills
• general body swelling
• general feeling of tiredness or weakness
• headache
• hives
• increased sweating
• increased thirst
• inflammation of the joints
• itching
• loss of appetite
• lower back or side pain
• muscle aches
• nausea or vomiting
• noisy breathing
• nosebleeds
• pain
• pale skin
• pinpoint red spots on the skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rash
• redness of the face, neck, arms, and occasionally, upper chest
• shortness of breath
• skin rash
• swelling of the foot or leg
• swollen lymph glands
• tenderness
• tightness in the chest
• troubled breathing with exertion
• unpleasant breath odor
• unusual weight loss
• vomiting of blood
• watery or bloody diarrhea
• wheezing
• yellowing of the eyes or skin

Incidence not known

• Blistering, peeling, or loosening of the skin
• chest pain
• coughing up blood
• decrease in the amount of urine
• excessive muscle tone
• increased menstrual flow or vaginal bleeding
• muscle stiffness, tension, or tightness
• nosebleeds
• paralysis
• prolonged bleeding from cuts
• red irritated eyes
• red or black, tarry stools
• red or dark brown urine
• red skin lesions, often with a purple center
• restlessness
• skin rash with a general disease
• swelling
• trouble sitting still
• unpleasant breath odor

Other side effects of Ceftriaxone

Some side effects of ceftriaxone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Rare

• Acid or sour stomach
• belching
• bloated
• change in taste
• dizziness
• excess air or gas in the stomach or intestines
• full feeling
• headache
• heartburn
• indigestion
• itching of the vagina or genital area
• loss of taste
• pain during sexual intercourse
• passing gas
• stomach discomfort, upset, or pain
• thick, white vaginal discharge with no odor or with a mild odor

Incidence not known

• Hives or welts
• redness, swelling, or soreness of the tongue
• swelling or inflammation of the mouth

For Healthcare Professionals

Applies to ceftriaxone: injectable powder for injection, intramuscular kit, intravenous powder for injection, intravenous solution.

General

This drug was generally well tolerated. The most common side effects were eosinophilia, leukopenia, thrombocytopenia, diarrhea, rash, and increased hepatic enzymes. Incidence of side effects was somewhat higher in children and with higher doses.^[Ref]

Local

Very common (10% or more): Warmth/tightness/induration with IM injection (up to 17%)

Uncommon (0.1% to 1%): Injection site pain/discomfort, injection site induration, injection site tenderness, phlebitis after IV administration^[Ref]

Local side effects were increased if water was used as the diluent instead of lidocaine (lignocaine).

IM injection has been associated with warmth, tightness, and induration in 17% of patients receiving the 350 mg/mL solution and 5% of patients receiving the 250 mg/mL solution.^[Ref]

Hematologic

Nineteen cases (10 adults, 9 children) of immune hemolytic anemia have been reported, 9 of which were fatal. Symptoms occurred within minutes or weeks of drug administration. Initial symptoms included tachycardia, hypotension, dyspnea, pallor, back or leg pain, and decreased hemoglobin levels. Most of these patients had preexisting hematologic or immunodeficiency disorders, and 1 had Crohn's disease.

Bleeding and bruising (due to hypoprothrombinemia) may have been more prevalent in patients with liver or renal dysfunction, malnourished patients, patients with low vitamin K levels, and patients using this drug for a prolonged duration.

Hemolytic anemia and agranulocytosis have also been reported during postmarketing experience. Most cases of agranulocytosis (less than 500/mm3) were after 10 days of therapy and after total doses of at least 20 g.^[Ref]

Common (1% to 10%): Eosinophilia, thrombocytosis, leukopenia, thrombocytopenia, neutropenia

Uncommon (0.1% to 1%): Anemia, granulocytopenia, coagulopathy, hemolytic anemia, lymphopenia, prolonged prothrombin time

Rare (less than 0.1%): Agranulocytosis, lymphocytosis, leukocytosis, monocytosis, basophilia, decreased prothrombin time, hemolysis (fatal)

Frequency not reported: Bleeding, hypoprothrombinemia

Postmarketing reports: Coombs' test false positive

Cephalosporin class:

-Frequency not reported: Aplastic anemia, hemorrhage, positive direct Coombs' test^[Ref]

Hepatic

Shadows on sonograms of the gallbladder (mistaken for gallstones, but actually ceftriaxone-calcium precipitates) have been reported, primarily after doses higher than the standard recommended dose. Prospective studies showed variable incidence of precipitation with IV administration in children (more than 30% in some studies), but slow infusion (20 to 30 minutes) appeared to lower the incidence. Risk of forming precipitates was increased by duration of therapy exceeding 14 days, renal failure, dehydration, or total parenteral nutrition. Effect was usually asymptomatic, but clinical symptoms (e.g., pain, nausea, vomiting) have been reported. Precipitation was usually reversible upon drug discontinuation.

Both pseudocholelithiasis (biliary "sludging") and true cholelithiasis (ceftriaxone-containing gallstone) have been reported in association with doses greater than 2 g/day. A false-positive hepatobiliary scan occurred in a patient receiving this drug. A repeat test 2 weeks after this drug was discontinued was normal.

Hepatitis has also been reported during postmarketing experience.^[Ref]

Common (1% to 10%): Increased hepatic enzymes, increased ALT, increased AST

Uncommon (0.1% to 1%): Increased bilirubin

Rare (less than 0.1%): Hepatitis, jaundice, gallbladder sludge, biliary lithiasis, cholestatic jaundice

Frequency not reported: Transient elevations in liver function tests, shadows on sonograms of the gallbladder, cholelithiasis, pseudocholelithiasis, false-positive hepatobiliary scan

Postmarketing reports: Gallbladder precipitation

Cephalosporin class:

-Frequency not reported: Hepatic dysfunction, cholestasis^[Ref]

Gastrointestinal

The onset of pseudomembranous colitis symptoms has been reported during or after antimicrobial treatment.^[Ref]

Common (1% to 10%): Diarrhea/loose stools

Uncommon (0.1% to 1%): Nausea, vomiting

Rare (less than 0.1%): Colitis, flatulence, dyspepsia, abdominal pain, pseudomembranous colitis

Frequency not reported: Clostridium difficile-associated diarrhea

Postmarketing reports: Pancreatitis, stomatitis, glossitis^[Ref]

Dermatologic

Common (1% to 10%): Rash

Uncommon (0.1% to 1%): Pruritus, maculopapular rash/exanthema, allergic dermatitis, diaphoresis

Rare (less than 0.1%): Urticaria

Frequency not reported: Severe dermatitis, exfoliative erythroderma, bruising

Postmarketing reports: Exanthema, severe cutaneous reactions, erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome/toxic epidermal necrolysis, acute generalized exanthematous pustulosis (AGEP)

Cephalosporin class:

-Frequency not reported: Contact dermatitis^[Ref]

A case of AGEP has been reported after administration of this drug. This was characterized by the appearance of an erythematous and generalized scarlatiniform rash with plaques covered by small nonfollicular pustules on the thighs, abdomen, and lower extremities. This drug was discontinued and the AGEP was completely resolved after 2 weeks.

Allergic dermatitis and urticaria have also been reported during postmarketing experience.

A case of occupational contact dermatitis has been reported in a nurse who prepared cephalosporin solutions for administration to patients. The dermatitis resolved after the nurse stopped preparing the solutions.^[Ref]

Renal

Common (1% to 10%): Increased BUN/serum urea

Uncommon (0.1% to 1%): Increased blood creatinine

Rare (less than 0.1%): Renal precipitations, nephrolithiasis, acute renal tubular necrosis

Postmarketing reports: Oliguria, ureteric obstruction, post-renal acute renal failure

Cephalosporin class:

-Frequency not reported: Renal dysfunction, toxic nephropathy^[Ref]

Cases of renal precipitation have been reported, primarily in children older than 3 years who received either high daily doses (e.g., at least 80 mg/kg/day) or total doses exceeding 10 g and who had other risk factors (e.g., fluid restrictions, confinement to bed). Risk of forming precipitates was increased in immobilized or dehydrated patients. Precipitation was reversible upon drug discontinuation.

Renal precipitation has also been reported during postmarketing experience.^[Ref]

Genitourinary

Uncommon (0.1% to 1%): Genital fungal infection, urinary casts, candidiasis, vaginitis

Rare (less than 0.1%): Glycosuria, hematuria, crystalluria^[Ref]

Other

Severe and sometimes fatal reactions have been reported in term and premature newborns (younger than 28 days) treated with IV ceftriaxone and calcium-containing IV solutions; a crystalline material (ceftriaxone-calcium precipitate) has been observed in the lungs and kidneys at autopsy. The same IV infusion line was used for this drug and calcium-containing solutions in some cases; precipitate was observed in the IV infusion line in some cases. Ceftriaxone and calcium-containing solutions infused at different times by different IV lines resulted in at least 1 neonate fatality; there was no crystalline material observed at autopsy.

Edema has also been reported during postmarketing experience.^[Ref]

Uncommon (0.1% to 1%): Pyrexia/fever, flushing

Rare (less than 0.1%): Edema, chills, drug fever, shivering

Postmarketing reports: Superinfection with nonsusceptible microorganisms, ceftriaxone-calcium precipitates/crystalline material

Cephalosporin class:

-Frequency not reported: Drug fever, superinfection^[Ref]

Nervous system

Uncommon (0.1% to 1%): Headache, dizziness, dysgeusia

Rare (less than 0.1%): Seizures

Postmarketing reports: Convulsion, vertigo, kernicterus

Cephalosporin class:

-Frequency not reported: Reversible hyperactivity, hypertonia, seizures triggered^[Ref]

Several cephalosporins have been implicated in triggering seizures, especially in patients with renal dysfunction when dose was not reduced.^[Ref]

Metabolic

Uncommon (0.1% to 1%): Increased alkaline phosphatase

Postmarketing reports: Galactosemia test false positive, false-positive test for urinary glucose (nonenzymatic methods)

Cephalosporin class:

-Frequency not reported: Increased LDH, false-positive test for urinary glucose^[Ref]

Hypersensitivity

Rare (less than 0.1%): Anaphylaxis/anaphylactic-type reactions (e.g., bronchospasms), serum sickness

Frequency not reported: Allergic reaction, cross-sensitivity

Postmarketing reports: Anaphylaxis (anaphylactic shock, transient leukopenia, neutropenia, agranulocytosis, thrombocytopenia), anaphylactic reaction, anaphylactoid reaction, hypersensitivity

Cephalosporin class:

-Frequency not reported: Allergic reactions, serum sickness-like reaction^[Ref]

An allergic reaction manifested by itching, maculopapular rash, hyperthermia, flushing has been reported in a patient with X-linked agammaglobulinemia in the absence of IgE. T cell involvement was proposed as the mechanism.

Cross-sensitivity with other cephalosporins and penicillins has occurred; however, the incidence is unknown.^[Ref]

Cardiovascular

Rare (less than 0.1%): Palpitations

Frequency not reported: Thrombus^[Ref]

Respiratory

Rare (less than 0.1%): Bronchospasm, epistaxis, allergic pneumonitis^[Ref]