Adverse reactions : תופעות לוואי

4.8. Undesirable effects
Potential undesirable effects may occur as a result of inappropriate use : for example, overdose, excessively fast administration rate (see sections 4.4. and 4.9.).
At the beginning of the infusion, any abnormal signs or symptoms of an allergic reaction (e.g. sweating, fever, shivering, headache, skin rashes, dyspnoea, bronchospasm) should be cause for immediate discontinuation of the infusion.
Oliclinomel N4-550E, N7-1000E, and N8-800E (not registered in Israel) have been used in three (3) clinical trials to evaluate the ease of use, safety and nutritional efficacy of the product.
One trial was a randomized, double-blind, active-controlled, efficacy and safety study conducted with Oliclinomel N8-800. 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 Oliclinomel group received drug product up to 40 mL/kg/d over 5 days.
The other two trials were open-label, non-comparative studies to evaluate the ease of use, safety and efficacy of Oliclinomel in gastrointestinal surgery patients. In these trials, a total of 36 patients received drug product up to 40 mL/kg/d over 5 days in Oliclinomel N4-550E study (N = 20), and up to 36 mL/kg/d over 5 days in Oliclinomel N7-1000E study (N = 16)
The pooled data (64 patients) from these 3 clinical trials and the postmarketing experience indicate the following adverse drug reactions (ADRs) related to Oliclinomel



Oliclinomel N7- 1000 E,                    9. 6. 2015, RH                                    Page 7 of 14 System Organ Class (SOC)                            Preferred MedDRA Term                     Frequencya b
IMMUNE SYSTEM DISORDERS            Hypersensitivity                                                      common c
Bronchospasm (as part of allergic reaction)                          Not known b
NERVOUS SYSTEM DISORDERS           Headache                                                              common Tremor                                                               Not knownc b
GASTROINTESTINAL DISORDERS         Diarrhea                                                              common Abdominal pain                                                       Not knownc Vomiting                                                             Not knownc Nausea                                                               Not knownc b
RENAL AND URINARY DISORDERS        Azotemia                                                              common HEPATO-BILIARY DISORDERS           Hepatitis cholestatic                                                Not knownc Cholestasis                                                          Not knownc Jaundice                                                             Not knownc SKIN AND SUBCUTANEOUS TISSUE       Erythema *                                                           Not knownc DISORDERS                          Hyperhydrosis                                                        Not knownc MUSCULOSKELETAL, CONNECTIVE TISSUE Musculoskeletal pain                                                 Not knownc AND BONE DISORDERS                 Back pain                                                            Not knownc Chest pain                                                           Not knownc Pain in extremity                                                    Not knownc Muscle spasm                                                         Not knownc b
GENERAL DISORDERS AND              Chills                                                                common ADMINISTRATION SITE CONDITIONS     Infusion site extravasation                                                  b common
Infusion site pain *                                                  common b

Infusion site swelling *                                              common b

Infusion site vesicles *                                              common b

Catheter site phlebitis *                                            Not knownc Injection site oedema *                                              Not knownc Localized oedema *                                                   Not knownc Oedema peripherial *                                                 Not knownc Pyrexia                                                              Not knownc Feeling hot *                                                        Not knownc Hyperthermia                                                         Not knownc Malaise                                                              Not knownc Inflammation                                                         Not knownc c
Necrosis/ulcer *                                                     Not known INVESTIGATIONS                     Blood bilirubin increased                                            Not knownc b
Hepatic enzyme increased                                              common Gamma-glutamyltransferase increased                                          b common
Blood triglycerides increased                                         common b
Blood alkaline phosphatase increased                                  common b
Blood glucose increased                                              Not knownc Hyperglycaemia                                                       Not knownc 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); and not known (cannot be estimated from the available data).
b: ADR reported during clinical trials. These studies included only 64 patients who were exposed to Oliclinomel.
c: ADR reported during postmarketing experience with Oliclinomel
*: Adverse reactions that can be associated with extravasation



Oliclinomel N7- 1000 E,                       9. 6. 2015, RH                                         Page 8 of 14 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; 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 OliClinomel, 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 characterised by findings such as hyperlipidaemia, fever, liver fatty infiltration (hepatomegaly), deteriorating liver function, anaemia, leucopoenia, thrombocytopenia, coagulation disorders, and central nervous system manifestations (e.g.
coma), requiring hospitalization. The syndrome is usually reversible when the infusion of the lipid emulsion is stopped.


Pediatric population
Thrombocytopenia has been reported in children receiving lipid infusions.
Reporting of suspected adverse reactions
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.health.g ov.il ) or by email (adr@MOH.HEALTH.GOV.IL ).