Adverse reactions : תופעות לוואי

ADVERSE REACTIONS

Adults
TIENAM I.V. is generally well tolerated. Many of the 1,723 patients treated in clinical trials were severely ill and had multiple background diseases and physiological impairments, making it difficult to determine causal relationship of adverse experiences to therapy with TIENAM I.V.
Local Adverse Reactions
Adverse local clinical reactions that were reported as possibly, probably, or definitely related to therapy with TIENAM I. V. were:
Phlebitis/thrombophlebitis — 3.1%
Pain at the injection site — 0.7%
Erythema at the injection site — 0.4%
Vein induration — 0.2%
Infused vein infection — 0.1%
Systemic Adverse Reactions
The most frequently reported systemic adverse clinical reactions that were reported as possibly, probably, or definitely related to TIENAM I.V. were nausea (2.0%), diarrhea (1.8%), vomiting (1.5%), rash (0.9%), fever (0.5%), hypotension (0.4%), seizures (0.4%) (see PRECAUTIONS), dizziness (0.3%), pruritus (0.3%), urticaria (0.2%), somnolence (0.2%).
Additional adverse systemic clinical reactions reported as possibly, probably, or definitely drug related occurring in less than 0.2% of the patients or reported since the drug was marketed are listed within each body system in order of decreasing severity:
Gastrointestinal — pseudomembranous colitis (the onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment, see WARNINGS), hemorrhagic colitis, hepatitis (including fulminant hepatitis), hepatic failure, jaundice, gastroenteritis, abdominal pain, glossitis, tongue papillar hypertrophy, staining of the teeth and/or tongue, heartburn, pharyngeal pain, increased salivation; Hematologic — pancytopenia, bone marrow depression, thrombocytopenia, neutropenia, leukopenia, hemolytic anemia;
CNS — encephalopathy, tremor, confusion, myoclonus, paresthesia, vertigo, headache, psychic disturbances including hallucinations, dyskinesia, agitation;
Special Senses — hearing loss, tinnitus, taste perversion;
Respiratory — chest discomfort, dyspnea, hyperventilation, thoracic spine pain; Cardiovascular — palpitations, tachycardia;
Skin — Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, angioneurotic edema, flushing, cyanosis, hyperhidrosis, skin texture changes, candidiasis, pruritus vulvae; Body as a whole — polyarthralgia, asthenia/weakness, drug fever;
Renal — acute renal failure, oliguria/anuria, polyuria, urine discoloration. The role of TIENAM I.V. in changes in renal function is difficult to assess, since factors predisposing to pre-renal azotemia or to impaired renal function usually have been present.
Adverse Laboratory Changes
Adverse laboratory changes without regard to drug relationship that were reported during clinical trials or reported since the drug was marketed were:
Hepatic: Increased ALT (SGPT), AST (SGOT), alkaline phosphatase, bilirubin, and LDH Hemic: Increased eosinophils, positive Coombs test, increased WBC, increased platelets, decreased hemoglobin and hematocrit, agranulocytosis, increased monocytes, abnormal prothrombin time, increased lymphocytes, increased basophils
Electrolytes: Decreased serum sodium, increased potassium, increased chloride Renal: Increased BUN, creatinine
Urinalysis: Presence of urine protein, urine red blood cells, urine white blood cells, urine casts, urine bilirubin, and urine urobilinogen.
Pediatric Patients
In studies of 178 pediatric patients 3 months of age, the following adverse events were noted: 
The Most Common Clinical Adverse Experiences Without Regard to Drug Relationship
(Patient Incidence >1%)
Adverse Experience                         No. of Patients (%)
Digestive System
Diarrhea                                                   7* (3.9)
Gastroenteritis                                            2 (1.1)
Vomiting                                                   2* (1.1)
Skin
Rash                                                        4 (2.2)
Irritation, I. V. site                                      2 (1.1)
Urogenital System
Urine discoloration                                         2 (1.1)
Cardiovascular System
Phlebitis                                                   4 (2.2)
* One patient had both vomiting and diarrhea and is counted in each category.

In studies of 135 patients (newborn to 3 months of age), the following adverse events were noted: The Most Common Clinical Adverse Experiences Without Regard to Drug Relationship (Patient Incidence >1%)

Adverse Experience                                      No. of Patients (%) Digestive System
Diarrhea                                                   4 (3.0%)
Oral Candidiasis                                           2 (1.5%)
Skin
Rash                                                       2 (1.5%)
Urogenital System
Oliguria/anuria                                            3 (2.2%)
Cardiovascular System
Tachycardia                                                2 (1.5%)
Nervous System
Convulsions                                                8 (5.9%)

Patients (3 Months of Age) With Normal Pretherapy but Abnormal During Therapy Laboratory Values 
Laboratory Parameter                          Abnormality                              No. of Patients With Abnormalities/
No. of Patients With Lab Done
(%)
Hemoglobin                  Age           <5 mos.:               <10 gm %                19/129       (14.7) 6 mos.- 12 yrs.:   <11.5 gm %
Hematocrit                  Age           <5 mos.:              <30 vol %                23/129     (17.8) 6 mos.- 12 yrs.:   <34.5 vol %
3
Neutrophils                                     1000/ mm (absolute)                      4/123      (3.3) Eosinophils                 7%                                      15/117     (12.8) Platelet Count              500 ths/mm 3                           16/119      (13.4)
Urine Protein               1                                        8/97     (8.2) Serum Creatinine                                >1.2 mg/dL                                 0/105       (0) BUN                                             >22 mg/dL                                  0/108       (0) AST (SGOT)                                      >36 IU/L                                 14/78      (17.9) ALT (SGPT)                                      >30 IU/L                                 10/93      (10.8) 

Patients (<3 Months of Age) With Normal Pretherapy but Abnormal
During Therapy Laboratory Values
No. of Patients With
Laboratory Parameter                 Abnormalities * (%)
Eosinophil Count                                  11 (9.0%)
Hematocrit                                         3 (2.0%)
Hematocrit                                         1 (1.0%)
Platelet Count                                    5 (4.0%)
Platelet Count                                     2 (2.0%)
Serum Creatinine                                   5 (5.0%)
3 (3.0%)
Bilirubin 
1 (1.0%)
Bilirubin 
5 (6.0%)
AST (SGOT)                                         3 (3.0%)
ALT (SGPT)                                         2 (3.0%)
Serum Alkaline Phosphate 
* The denominator used for percentages was the number of patients for whom the test was performed during or post-treatment and, therefore, varies by test.


Examination of published literature and spontaneous adverse event reports suggested a similar spectrum of adverse events in adult and pediatric patients.

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
http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic@moh.gov.il