Adverse reactions : תופעות לוואי

4.8     Undesirable effects

General
Induction and maintenance of anaesthesia or sedation is generally smooth with minimal evidence of excitation.

Side effects during induction, maintenance and recovery occur uncommonly.
The most commonly reported ADRs are pharmacologically predictable side effects of an anaesthet- ic/sedative agent, such as hypotension. The nature, severity and incidence of adverse events observed in patients receiving Propofol-Lipuro 2% may be related to the condition of the recipients and the op- erative 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 Organ Class              Frequency       Undesirable Effects
Immune system disorders         Very rare       Anaphylaxis – may include angi- oedema, bronchospasm, erythema and hypotension
Metabolism and Nutritional      Not known (9)   Metabolic acidosis (5), hyper- disorder                                        kalaemia (5), hyperlipidaemia (5) Psychiatric disorders           Not known (9)   Euphoric mood. Drug abuse and drug dependence (8)
Nervous system disorders        Common          Headache during recovery phase 
Rare            Epileptiform movements, includ- ing 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 and me-   Common          Transient apnoea during induction diastinal disorders
Not known (9)   Respiratory depression (dose- dependent)
Gastrointestinal disorders      Common          Nausea and vomiting during re- covery phase
Very rare       Pancreatitis

Hepatobiliary disorders         Not known (9)   Hepatomegaly (5), Hepatitis, acute hepatic failure (11)
Musculoskeletal and connec-     Not known (9)   Rhabdomyolysis (3), (5) tive tissue disorders
Renal and urinary disorders     Very rare       Discolouration of urine following prolonged administration
Not known (9)   Renal failure(5)
Reproductive system and             Very rare                       Sexual disinhibition breast disorders
Not known                       Priapism
General disorders and admin-        Very common                     Local pain on induction (4) istration site conditions
Very rare                       Tissue necrosis (10) following ac- cidental extravascular administra- tion
Not known (9)                   Local pain, swelling, following accidental extravascular admin- istration
Investigations                      Not known (9)                   Brugada type ECG (5), (6) Injury, poisoning and proce-        Very rare                       Postoperative fever dural 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.
3
Very rare reports of rhabdomyolysis have been received where Propofol has been given at doses greater than 4 mg/kg/hr for ICU sedation.
4
May be minimised by using the larger veins of the forearm and antecubital fossa. With Propofol-Lipuro 2% local pain can also be minimised by the co-administration of lidocaine.
5
Combinations of these events, reported as “Propofol infusion syndrome”, may be seen in seriously ill pa- tients 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 health care 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.
11
After both long- and short-term treatment and in patients without underlying risk factors.

Dystonia/dyskinesia have been reported.

Local
The local pain which may occur during the induction phase can be minimised by the use of the larger veins of the forearm and antecubital fossa. Thrombosis and phlebitis are rare. Accidental clinical ex- travasation 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 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).