Adverse reactions : תופעות לוואי

4.8   Undesirable Effects
Induction and maintenance of anaesthesia or sedation with propofol is generally smooth with minimal evidence of excitation. The most commonly reported ADRs are pharmacologically predictable side ef- fects of an anaesthetic/sedative agent, such as hypotension. The nature, severity and incidence of ad- verse events observed in patients receiving propofol may be related to the condition of the recipients and the operative or therapeutic procedures being undertaken.

Table of Adverse Drug Reactions

System Organ Class               Frequency                    Undesirable Effects Immune system disorders:         Very rare                    Anaphylaxis – may include angi- (<1/10 000)                  oedema, bronchospasm, erythema
and hypotension
Metabolism and Nutritional       Frequency not known (9)      Metabolic acidosis (5), hyper- disorder:                                                     kalaemia (5), hyperlipidaemia (5) Psychiatric disorders:           Frequency not known (9)      Euphoric mood, drug abuse and drug dependence (8)
Nervous system disorders:        Common                       Headache during recovery phase (>1/100, <1/10)
Rare                         Epileptiform movements, includ-
(>1/10 000, <1/1000)         ing convulsions and opisthotonus
during induction, maintenance
and recovery
Very rare                    Postoperative unconsciousness
(<1/10 000)
Frequency not known (9)      Involuntary movements
Cardiac disorders:               Common                       Bradycardia (1) (>1/100, <1/10)
Very rare                    Pulmonary oedema
(<1/10 000)
Frequency not known (9)      Cardiac arrhythmia (5), cardiac
failure (5), (7)
Vascular disorders:              Common                       Hypotension (2) (>1/100, <1/10)
Uncommon                     thrombosis and phlebitis
(>1/1000, <1/100)
Respiratory, thoracic and me-    Common                       Transient apnoea during induc- diastinal disorders:             (>1/100, <1/10)              tion
Frequency not known (9)      Respiratory depression (dose de-
pendent)
Gastrointestinal disorders:      Common                       Nausea and vomiting during re- (>1/100, <1/10)              covery phase
Very rare                    Pancreatitis
(<1/10 000)
Hepatobiliary disorders          Frequency not known (9)      Hepatomegaly (5) Musculoskeletal and connec-           Frequency not known (9)          Rhabdomyolysis (3), (5) tive tissue disorders:
Renal and urinary disorders           Very rare                        Discolouration of urine following (<1/10 000)                      prolonged administration
Frequency not known (9)          Renal failure(5)

Reproductive system and               Very rare                        Sexual disinhibition breast                                (<1/10 000)
General disorders and admin-          Very common                      Local pain on induction (4) istration site conditions:            (>1/10)
Very rare                        Tissue necrosis (10) following
accidental extravascular admin-
istration (11)
Frequency not known (9)          Local pain, swelling following
accidental extravascular admin-
istration
Investigations                        Frequency not known (9)          Brugada type ECG (5), (6) Injury, poisoning and proce-          Very rare                        Postoperative fever dural complications:                  (<1/10 000)

(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 10 mg/ml 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.

Dystonia/dyskinesia have been reported.
Local
The local pain which may occur during the induction phase of propofol anaesthesia can be minimised by the co-administration of lidocaine and 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 authorisation of the medicinal product is important. It al- lows 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.go v.il