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 1% 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 Organ Class             Frequency                Undesirable Effects Immune system disorders:       Very rare                Anaphylaxis – may include angioedema, bronchospasm,
erythema and hypotension
Metabolism and Nutritional Not known (9)                Metabolic acidosis (5), disorder:                                               hyperkalaemia (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,
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 and           Common                          Transient apnoea, during mediastinal disorders:                                              induction Not known (9)                   Respiratory depression (dose dependant)
Gastrointestinal disorders:         Common                          Nausea and vomiting during 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 disorders                                                           following prolonged administration
Not known (9)                   Renal failure(5)

Reproductive system and             Very rare                       Sexual disinhibition 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.
(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 1 % Fresenius 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 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 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 1% Fresenius anaesthesia can be minimised by the co-administration of lidocaine (see "Dosage and Administration") 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 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