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 Diprofol 2% 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 nutrition disorders Frequency not known Metabolic acidosis (5), (9)
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) 
System Organ Class                    Frequency            Undesirable Effects 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 dependent)
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 disorders           Very rare            Discolouration of urine following prolonged administration

Not known (9)        Renal failure (5)
Reproductive system and breast        Very rare            Sexual disinhibition disorders
Not known            Priapism

General disorders and administration Very common           Local pain on induction (4) 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 procedural      Very rare            Postoperative fever 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 Diprofol 2%.
3.  Very rare reports of rhabdomyolysis have been received where
Diprofol 2% 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.
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