Adverse reactions : תופעות לוואי

4.8 Undesirable effects

General
Induction and maintenance of anaesthesia or sedation is generally smooth with minimal evidence of excitation. The most commonly reported ADRs are pharmacologically predictable side effects of an anaesthetic/sedative agent, such as hypotension. The nature, severity and incidence of adverse events observed in patients receiving Propofol 2% MCT Fresenius may be related to the condition of the recipients and the operative or therapeutic procedures being undertaken. The following definitions of frequencies are used: 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), very rare (<1/10,000) and not known (cannot be estimated from the available data).

Table of Adverse Drug Reactions

System OrganClass         Frequency             Undesirable Effects Immune system             Very rare             Anaphylaxis – may include disorders                                       angioedema, bronchospasm, erythema and hypotension
Metabolism and nutrition Frequency not          Metabolic acidosis (5), disorders                known (9)              hyperkalaemia (5), hyperlipidaemia (5)
Psychiatric disorders     Not known (9)         Euphoric mood.
Drug abuse and drug dependence (8)
Nervous system            Common                Headache during recovery disorders                                       phase
Rare                  Epileptiform movements,
including convulsions and opisthotonus during induction,
maintenance and recovery
Very rare             Postoperative unconsciousness
Not known (9)         Involuntary movements
Cardiac disorders         Common                Bradycardia (1) Very rare             Pulmonary oedema
Not known (9)         Cardiac arrhythmia (5),cardiac failure (5),(7)
Vascular disorders        Common                Hypotension (2) Uncommon              Thrombosis and phlebitis
Respiratory, thoracic     Common                Transient apnoea during and mediastinal                                 induction disorders                 Not known (9)         Respiratory depression (dose dependent)
Gastrointestinal          Common                Nausea and vomiting during disorders                                       recovery phase Very rare             Pancreatitis
Hepatobiliary disorders   Not known (9)         Hepatomegaly (5) Musculoskeletal and       Not known (9)         Rhabdomyolysis (3),(5) connective tissue disorders
Renal and urinary         Very rare             Discolouration of urine following disorders                                       prolonged administration Not known (9)          Renal failure (5)
Reproductive system         Very rare              Sexual disinhibition and breast disorders        Not known              Priapism General disorders and       Very common            Local pain on induction (4) administration site conditions
Very rare              Tissue necrosis (10) following accidental extravascular administration
Not known (9)          Local pain, swelling, following accidental extravascular administration
Investigations              Not known (9)          Brugada type ECG (5),(6) Injury, poisoning and       Very rare              Postoperative fever procedural complications

1. Serious bradycardias are rare. There have been isolated reports of progression to asystole.
2. Occasionally, hypotension may require use of intravenous fluids and reduction of the administration rate of Propofol 2% MCT Fresenius.
3. Very rare reports of rhabdomyolysis have been received where Propofol 2% MCT Fresenius has been given at doses greater than 4 mg/kg/hr for ICU sedation.
4. May be minimized by using the larger veins of the forearm and antecubital fossa. With Propofol 1% MCT Fresenius local pain can also be minimized by the co-administration of lidocaine.
5. Combinations of these events, reported as “Propofol Infusion Syndrome”, may be seen in seriously ill patients who often have multiple risk factors for the development of the events, see section 4.4.
6. Brugada-type ECG- elevated ST- segment and coved T-wave in ECG.
7. Rapidly progressive cardiac failure (in some cases with fatal outcome) in adults. The cardiac failure in such cases was usually unresponsive to inotropic supportive treatment.
8. Abuse of and drug dependence on propofol, predominantly by healthcare professionals.
9. Not known as it cannot be estimated from the available clinical trial data.
10. Necrosis has been reported where tissue viability has been impaired.
Dystonia/dyskinesia have been reported.

Local
The local pain which may occur during the induction phase can be minimized by the use of the larger veins of the forearm and antecubital fossa.
Thrombosis and phlebitis are rare. Accidental clinical extravasation and animal studies showed minimal tissue reaction. Intra-arterial injection in animals did not induce local tissue effects.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization 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