PRILOTEKAL Solution for injection Ref.[9271] Active ingredients: Prilocaine

Due to the glucose content Prilotekal is only to be used for spinal anaesthesia. It is not recommended for the use in epidural anaesthesia.

Prilocaine may potentiate the formation of methemoglobin by medicinal products known to induce methemoglobin (see section 4.5).

Spinal anaesthesia must only be administered by (or under the supervision of) specialist medical personnel with the necessary knowledge and experience. The doctor in charge is responsible for taking the measures needed to avoid an intravascular injection.

In addition, it is essential for the doctor to know how to recognize and treat undesirable effects, systemic toxicity and other complications. If signs of acute systemic toxicity or total spinal block are observed, the injection of the local anaesthetic must be stopped immediately (see section 4.9).

Some patients require special attention in order to reduce the risk of serious undesirable effects, even when locoregional anaesthesia constitutes the optimum choice for the surgical intervention:

• Patients with total or partial heart block, since local anaesthetics can suppress myocardial conduction.
• Patients with high grade cardiac decompensation. The risk of methemoglobinemia must also be taken into consideration (see section 4.8).
• Patients with advanced liver or kidney damage.
• Elderly patients and patients in reduced general condition.
• Patients treated with class III antiarrhythmic agents (e.g. amiodarone). These patients should be subjected to careful observation and ECG monitoring, since cardiac effects may be added (see section 4.5).
• In patients with acute porphyria, Prilotekal should only be administered when there is a compelling indication for its use, as Prilotekal may potentially precipitate porphyria. Appropriate precaution should be taken in all patients with porphyria.

Ensuring the presence of reliable venous access is recommended.

As with all local anaesthetics, a drop in arterial pressure may occur and cardiac frequency may slow.

In high risk patients, the recommendation is to improve their general condition prior to the intervention.

A rare, but serious, undesirable effect of spinal anaesthesia is high or total spinal block, with consequent cardiovascular and respiratory depression. Cardiovascular depression is induced by an extended block of the sympathetic nervous system, which may induce severe hypotension and bradycardia to the point of cardiac arrest. Respiratory depression is induced by the block of the respiratory musculature and the diaphragm.

Especially in elderly patients and patients in the final period of pregnancy there is an increased risk of high or total spinal block: consequently it is advisable to reduce the anaesthetic dose.

Particularly in the case of elderly patients, an unexpected drop in arterial pressure may occur as a complication of spinal anaesthesia.

Rarely, neurological damage may occur after spinal anaesthesia, manifesting as paresthesia, loss of sensitivity, motor weakness and paralysis. Occasionally these symptoms persist.

There is no evidence that neurological disorder, such as multiple sclerosis, hemiplegia, paraplegia or neuromuscular disorders may be negatively influenced by spinal anaesthesia. Nevertheless, it should be used with care. Careful evaluation of the risk-benefit ratio is recommended prior to treatment.

This medicinal product contains less than 1 mmol sodium (23 mg) per dose (maximum dose equal to 4 ml of Prilotekal), i.e. essentially “sodium-free”.

Prilocaine may potentiate the formation of methemoglobin by medicinal products known to induce methemoglobin (e.g. sulfonamides, antimalarials, sodium nitroprussiate and nitroglycerin).

In the event of the concomitant use of prilocaine and other local anaesthetics or medicinal products with a chemical structure similar to prilocaine, e.g. certain antiarrhythmics such as aprindine, lidocaine, mexiletine and tocainide, it is possible for undesirable effects to be added. No studies have been performed on interactions between prilocaine and class III antiarrhythmics (e.g. amiodarone), but care must also be taken in this case (also see section 4.4).

The combination of various local anaesthetics induces additional effects which affect the cardiovascular system and the CNS.

Pregnancy

There are no adequate data from the use of prilocaine in pregnant women. Prilocaine is able to cross the placenta. Cases of neonatal methaemoglobinaemia requiring treatment have been reported following paracervical block or pudendal anaesthesia with prilocaine during obstetric use. Cases of foetal bradycardia with fatalities have occurred with other local amide-type anaesthetics following paracervical block. Studies in animals have shown developmental toxicity (see section 5.3).

Prilotekal may therefore only be administered in cases where there is a compelling indication for its use. Use of prilocaine for paracervical block or pudendal anaesthesia should be avoided.

Breast-feeding

It is not known whether prilocaine passes into breast milk. If administration is required during lactation, breast-feeding can be resumed approximately 24 hours after treatment.

Fertility

No human data on the effect of prilocaine on fertility are available. Prilocaine had no effect on the fertility of male and female rat. (see section 5.3).

In the case of using Prilotekal, the doctor is responsible for deciding in each individual case if the patient can drive or use machines.

The possible undesirable effects due to the use of Prilotekal are generally similar to the undesirable effects of other local anaesthetics for spinal anaesthesia from the amide group. The undesirable effects induced by the medicinal product are difficult to distinguish from the physiological effects of the nerve block (e.g. reduction in arterial pressure, bradycardia, temporary urine retention), from direct effects (e.g. spinal hematoma) or the indirect effects (e.g. meningitis) of the injection or from the effects due to the loss of cerebrospinal liquid (e.g. post-spinal headache).

The frequency of onset of undesirable effects is classified as follows: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000), very rare (<1/10000).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Blood and lymphatic system disorders

Rare: Methemoglobinemia, Cyanosis

Immune system disorders

Rare: Anaphylactic shock, Anaphylactic reactions, Allergic reactions, Itching

Nervous system Disorders

Common: Paresthesia, Dizziness

Uncommon: Signs and symptoms of CNS toxicity (convulsions, circumoral paresthesia, loss of consciousness, shaking, feeling of numbness affecting the tongue, speech problems, hearing problems, tinnitus, visual problems)

Rare: Arachnoiditis, Neuropathy, Lesions of peripheral nerves

Eye disorders

Rare: Diplopia

Cardiac disorders

Uncommon: Bradycardia

Rare: Cardiac arrest, Arrhythmia

Vascular disorders

Very common: Hypotension

Uncommon: Hypertension

Respiratory, thoracic and mediastinal disorders

Rare: Respiratory depression

Musculoskeletal and connective tissue disorders

Uncommon: Back pain, temporary muscle weakness

Gastrointestinal disorders

Very common: Nausea

Common: Vomiting

The signs of intoxication from local anaesthetics are similar for any injected preparation, both in the way in which they manifest, and in their treatment.

In spite of the demonstrated high clinical tolerability of Prilotekal, undesirable toxic effects cannot be excluded in the presence of plasma levels above a critical threshold. These undesirable effects mainly manifest as symptoms affecting the central nervous and cardiovascular system.

The most effective prophylactic measures are scrupulous compliance with the recommended posology for Prilotekal, with it being essential for the doctor to check its action (visual and verbal contact with the patient), as well as careful aspiration prior to injecting the solution.

Mild undesirable effects (feeling dizzy or dazed) can be attributed to moderate overdose and generally resolve rapidly after reducing the dose or halting administration of Prilotekal.

Serious undesirable effects are attributable to significant overdose and/or accidental injection of local aesthetic into a blood vessel. They manifest as symptoms affecting the central nervous system (restlessness, speech problems, disorientation, dizziness, muscle contractions, cramps, vomiting, loss of consciousness, respiratory arrest and mydriasis) and the cardiocirculatory system (raised arterial pressure and pulse frequency, arrhythmia, drop in arterial pressure, asystole) following irritation and/or depression of the cerebral cortex and the cerebral marrow (see section 4.9).

In addition, following inhibition or block of the cardiac conduction system, cardiac frequency may slow down and myocardial depression may occur.

Any problems relating to metabolism (liver) or excretion (kidney) of Prilotekal should also be considered as other possible causes of undesirable 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. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

Not applicable.