Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Potential undesirable effects may occur as a result of inappropriate use (for example: overdose, excessively fast infusion rate) (see sections 4.4 and 4.9).

At the beginning of the infusion, any of the following abnormal signs (sweating, fever, shivering, headache, skin rashes, dyspnoea) should be cause for immediate discontinuation of the infusion.
The adverse drug reactions (ADRs) reported with TRIOMEL 9g/l nitrogen 1070 kcal/l in a randomized, double-blind, active-controlled, efficacy and safety study, are listed in the table below.
Twenty-eight patients with various medical conditions (i.e., postsurgical fasting, severe malnutrition, enteral intake insufficient or forbidden) were included and treated; patients in the TRIOMEL 9g/l nitrogen 1070 kcal/l group received drug product up to 40 ml /kg/d over 5 days.

The pooled data from clinical trials and the postmarketing experience indicate the following adverse drug reactions (ADRs) related to TRIOMEL.


System Organ Class                MedDRA Preferred Term              Frequencya Immune System Disorders           Hypersensitivity reactions         Not knownb including hyperhidrosis,
pyrexia, chills, headache, skin rash (erythematous, papular,
pustular, macular, generalised rash), pruritus, hot flush,
dyspnoea
Cardiac Disorders                 Tachycardia                        Commona Metabolism and Nutrition          Decreased appetite                 Commona Disorders
Hypertriglyceridemia               Commona
Gastrointestinal Disorders        Abdominal pain                     Commona Diarrhea                           Commona
Nausea                             Commona
Vomiting                           Not knownb
Vascular Disorders                Hypertension                       Commona General disorders and             Extravasation which may result     Not knownb administration site conditions    at infusion site level in: pain,
irritation, swelling/oedema,
erythema/warmth, skin necrosis, blisters/vesicles,
inflammation, induration, skin tightness
 a: Frequency is defined as very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); very rare (< 1/10,000); or not known (cannot be estimated from the available data).
b: ADRs reported during post-marketing experience with TRIOMEL.

The following class-like-adverse drug reactions (ADRs) have been described in other sources in relation to similar parenteral nutrition products; the frequency of these events is not known.
• Blood and Lymphatic System Disorders: Thrombocytopenia
• Hepatobiliary Disorders: Cholestasis, Hepatomegaly, Jaundice
• Immune System Disorders: Hypersensitivity
• Injury, poisoning and procedural complications: Parenteral nutrition associated liver disease (see section 4.4, sub-section “Hepatobiliary disorders”)
• Investigations: Blood alkaline phosphatase increased, Transaminases increased, Blood bilirubin increased, Elevated liver enzymes
• Renal and Urinary Disorders: Azotemia
• Vascular disorders: Pulmonary vascular precipitates (pulmonary vascular embolism and respiratory distress) (see section 4.4).

Fat overload syndrome (very rare)

Fat overload syndrome has been reported with similar products. This may be caused by inappropriate administration (e.g. overdose and/or infusion rate higher than recommended, see section 4.9); however, the signs and symptoms of this syndrome may also occur at the start of an infusion when the product is administered according to instructions. The reduced or limited ability to metabolize the lipids contained in TRIOMEL 5 g/l nitrogen 990 kcal/l with electrolytes, emulsion for infusion accompanied by prolonged plasma clearance may result in a “fat overload syndrome”.

This syndrome is associated with a sudden deterioration in the patient’s clinical condition and is characterized by findings such as fever, anemia, leukopenia, thrombocytopenia, coagulation disorders, hyperlipidemia, liver fatty infiltration (hepatomegaly), deteriorating liver function, and central nervous system manifestations (e.g. coma). The syndrome is usually reversible when infusion of the lipid emulsion is stopped.

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