Mepivacaine

Reduced doses of mepivacaine should be used due to additive effects.

Mepivacaine is metabolised primarily by CYP1A2 enzyme. Inhibitors of this cytochrome (e.g. ciprofloxacin, enoxacin, fluvoxamine) may decrease its metabolism, increase the risk of adverse effects and contribute to prolonged or toxic blood levels. Increased serum levels of amide anaesthetics have also been reported after concomitant administration of cimetidine, which is probably due to the inhibitory effect of cimetidine on CYP1A2. Caution is advised when associating the product of interest with these medications as dizziness may last longer.

Due to the lack of clinical data, particular precaution should be used in order to administer the lowest dose leading to efficient anaesthesia in patients with hepatic impairment.

Due to the lack of clinical data, particular precaution should be used in order to administer the lowest dose leading to efficient anaesthesia in patients with renal impairment.

The increased risk of severe bleeding following accidental vessel puncture and during oromaxillo-facial surgery should be considered. INR monitoring should be increased in patients taking anticoagulants.

Patients who are being treated with antiarrhythmic drugs may encounter an accumulation of side effects after the use of mepivacaine due the similarity of structures (such as Class I drug i.e. lidocaine).

Increased serum levels of amide anaesthetics have been reported following concomitant administration of cimetidine.

The clearance of mepivacaine may be reduced when associated with propranolol and it may result in higher serum concentrations of the anaesthetic. Caution should be exercised when mepivacaine is administered concomitantly with propranolol.

Many drugs used during the conduct of anaesthesia are considered potential triggering agents for familial malignant hyperthermia. It has been shown that the use of amide local anaesthetics in malignant hyperthermia patients is safe. However, there is no guarantee that neural blockage will prevent the development of malignant hyperthermia during surgery. It is also difficult to predict the need for supplemental general anaesthesia. Therefore, a standard protocol for the management of malignant hyperthermia should be available.

Mepivacaine should be used cautiously.

Mepivacaine must be used with caution in patients with cardiovascular disorders:

• Peripheral vascular disease
• Arrhythmias particularly of ventricular origin
• Heart failure
• Hypotension

Mepivacaine should be administered with caution in patients with impaired cardiac function since they may be less able to compensate changes due to prolongation of atrio-ventricular conduction.

Caution should be given in the event of acidosis as in renal failure or inadequately controlled type 1 diabetes.

Because of their convulsive actions, all local anaesthetics should be used very cautiously.

No clinical studies were performed in pregnant women and no cases of pregnant women treated with injectable solution of mepivacaine 30 mg/ml were reported in literature. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Therefore, as a precautionary measure, it is preferable to avoid the use of mepivacaine during pregnancy.

No nursing mothers were included in clinical studies involving mepivacaine. Only literature data concerning lidocaine passage in milk are available showing no risk. However, considering the lack of data for mepivacaine, a risk to the newborns/infants cannot be excluded. Therefore, nursing mothers are advised not to breastfeed within 10 hours following anaesthesia with mepivacaine.

Fertility

No relevant data reported any toxic effects on fertility in animals with mepivacaine. To date, no data are available regarding humans.

Patients should not leave the dental office within 30 minutes following administration of mepivacaine.

Summary of the safety profile

Adverse reactions following the administration of mepivacaine are similar to those observed with other local amide anaesthetics. These adverse reactions are, in general, dose-related and may result from high plasma levels caused by overdose, rapid absorption or unintended intra-vascular injection. They may also result from hypersensitivity, idiosyncrasy, or diminished tolerance by patient.

Serious adverse reactions are generally systemic.

Tabulated list of adverse reactions

The reported adverse reactions come from spontaneous reporting and literature.

The frequencies classification follows the convention: Very common (≥ 1/10), Common (≥1/100 - <1/10), Uncommon (≥1/1,000 - <1/100), Rare (≥1/10,000 - <1/1,000) and Very rare (<1/10,000). Frequency “Not known”: “Not known (cannot be estimated from the available data)”.

The seriousness of adverse reactions is classified from 1 (most serious) to 3 (less serious) in the following table:

Description of selected adverse reactions

¹ Laryngo-pharyngeal oedema may characteristically occur with hoarseness and/or dysphagia.

² Bronchospasm (bronchoconstriction) may characteristically occur with dyspnoea.

³ These neural pathologies may occur with the various symptoms of abnormal sensations (i.e., paresthesia, hypoesthesia, dysesthesia, hyperesthesia, etc) of the lips, tongue and oral tissues. These data originated in post-marketings reports, mostly following nerve blocks in mandible, involving various branches of the trigeminal nerve.

⁴ This mostly occurs in patients with underlying cardiac disease or in patients receiving certain drugs.

⁵ This occurs in predisposed patients or in patients with risk factors of ischemic heart disease.

⁶ Hypoxia and hypercapnia are secondary to respiratory depression and/or to seizures and sustained muscular exertion.

⁷ This occurs by accidental biting or chewing of the lips or tongue while the anaesthesia persists.