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 1% 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 
Anaphylaxis – may include
Immune system disorders          Very rare             angioedema, bronchospasm, erythema and hypotension
(9)   Metabolic acidosis (5), hyperkalaemia
Metabolism and nutrition disorders Not known           (5)
, hyperlipidaemia (5)
Euphoric mood. Drug abuse and
Psychiatric disorders            Not known (9)
drug dependence (8)
Nervous system disorders         Common                Headache during recovery phase Epileptiform movements,
including convulsions and
Rare
opisthotonus during induction,
maintenance and recovery
Very rare             Postoperative unconsciousness
Not known (9) Involuntary movements
Cardiac disorders                Common                Bradycardia (1) Very rare             Pulmonary oedema
Cardiac arrhythmia (5), cardiac failure
Not known (9)         (5), (7)

Vascular disorders               Common                Hypotension (2) Uncommon              Thrombosis and phlebitis
Respiratory, thoracic and
Common                Transient apnoea during induction
mediastinal disorders
Not known (9) Respiratory depression (dose
d
Nausead and
t) vomiting during recovery
Gastrointestinal disorders       Common
phase
Very rare     Pancreatitis
Hepatobiliary disorders          Not known (9) Hepatomegaly (5)
Musculoskeletal and connective
tissue disorders                 Not known (9) Rhabdomyolysis (3), (5) 
Discolouration of urine following
Very rare
Renal and urinary disorders                            prolonged administration Not known (9)         Renal failure (5)

Very rare             Sexual disinhibition
Reproductive system and
breast disorders
Not known             Priapism

General disorders and
Very common Local pain on induction (4)
administration site conditions
Tissue necrosis (10) following
Very rare             accidental extravascular
d i ipain,i swelling, following
Local
Not known (9)         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 Diprofol.
(3)
Very rare reports of rhabdomyolysis have been received where Diprofol 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 Diprofol 1% 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 Diprofol 1% 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 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