Adverse reactions : תופעות לוואי

4.8 Undesirable effects

The most frequently reported adverse reactions for ceftriaxone are eosinophilia, leucopenia, thrombocytopenia, diarrhoea, rash, and hepatic enzymes increased.

Data to determine the frequency of ceftriaxone ADRs was derived from clinical trials.

The following convention has been used for the classification of frequency: - Very common (≥ 1/10);
- Common (≥ 1/100 to < 1/10);
- Uncommon (≥ 1/1,000 to < 1/100);
- Rare (≥ 1/10,000 to < 1/1,000);
- Not known (cannot be estimated from the available data);


System Organ Class         Common            Uncommon                    Rare                         Not Known a Infections and                            Genital fungal infection Pseudomembranous   colitisb   Superinfectionb infestations
Blood and lymphatic    Eosinophilia       Granulocytopenia                                       Haemolytic anaemiab system disorders       Leucopenia         Anaemia                                                Agranulocytosis Thrombocytopenia   Coagulopathy
Immune system disorders                                                                                 Anaphylactic shock Anaphylactic reaction
Anaphylactoid reaction
Hypersensitivityb
Jarisch-Herxheimer reactionb
Nervous system                                       Headache Dizziness         Encephalopathy          Convulsion disorders
Ear and                                                                                                 Vertigo labyrinth disorders
Respiratory, thoracic and                                                       Bronchospasm mediastinal disorders
Gastrointestinal disorders Diarrhoeab Loose stools   Nausea Vomiting                                    Pancreatitisb Stomatitis Glossitis
Hepatobiliary disorders     Hepatic enzyme                                                              Gall bladder precipitationb increased                                                                   Kernicterus Hepatitisc
Hepatitis cholestaticb,c
Skin and subcutaneous       Rash                     Pruritus                   Urticaria               Stevens Johnson Syndromeb tissue disorders                                                                                        Toxic epidermal necrolysisb Erythema multiform
Acute generalised exanthematous
Pustulosis
Drug reaction with eosinophilia and systemic symptoms (DRESS)b
Renal and urinary                                                               Haematuria Glycosuria   Oliguria disorders                                                                                               Renal precipitation (reversible)
General disorders and                                Phlebitis Injection site   Oedema Chills administration site                                  pain Pyrexia conditions
Investigations                                       Blood creatinine                                   Coombs test false positiveb increased                                          Galactosaemia test false positiveb
Non enzymatic methods for glucose determination false positiveb
 a
Based on post-marketing reports. Since these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency, which is therefore categorised as not known.
b
See section 4.4 c
Usually reversible upon discontinuation of ceftriaxone

Description of selected adverse reactions

Infections and infestations
Reports of diarrhoea following the use of ceftriaxone may be associated with Clostridium difficile. Appropriate fluid and electrolyte management should be instituted (see section 4.4).

Ceftriaxone-calcium salt precipitation
Rarely, severe, and in some cases, fatal, adverse reactions have been reported in pre-term and full-term neonates (aged < 28 days) who had been treated with intravenous ceftriaxone and calcium.

Precipitations of ceftriaxone-calcium salt have been observed in lung and kidneys post-mortem.
The high risk of precipitation in neonates is a result of their low blood volume and the longer half-life of ceftriaxone compared with adults (see sections 4.3, 4.4, and 5.2).

Cases of ceftriaxone precipitation in the urinary tract have been reported, mostly in children treated with high doses (e.g. ≥ 80 mg/kg/day or total doses exceeding 10 grams) and who have other risk factors (e.g. dehydration, confinement to bed). This event may be asymptomatic or symptomatic, and may lead to ureteric obstruction and postrenal acute renal failure, but is usually reversible upon discontinuation of ceftriaxone (see section 4.4).

Precipitation of ceftriaxone calcium salt in the gallbladder has been observed, primarily in patients treated with doses higher than the recommended standard dose. In children, prospective studies have shown a variable incidence of precipitation with intravenous application - above 30 % in some studies. The incidence appears to be lower with slow infusion (20 - 30 minutes).

This effect is usually asymptomatic, but the precipitations have been accompanied by clinical symptoms such as pain, nausea and vomiting in rare cases. Symptomatic treatment is recommended in these cases. Precipitation is usually reversible upon discontinuation of ceftriaxone (see section 4.4).

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il/ and emailed to the Registration Holder’s Patient Safety Unit at: drugsafety@neopharmgroup.com