N01BB58 - Articaine, Combinations |
Propably not porphyrinogenic |
PNP |
Rationale
Limitations: This safety classification applies only to preparations containing a combination of the two drugs articaine and adrenaline (epinephrine). The same ATC-code (N01BB58) can in some countries be used for different combinations of articaine and other drugs which in theory may be porphyrinogenic. Please refer to the classification and monograph of each individual substance. If the combination contains a substance which is not classified (NC) or has been classified as porphyrinogenic (PSP, PRP or P), the safety classification of such a combination as PNP is no longer valid.
As articaine is primarily metabolized by plasma esterases, and CYP affinity has not been reported (Rendic 2002), articaine can therefore on theoretical grounds be classified as probably not porphyrinogenic.
Adrenalin (epinephrine): Endogenous catecholamine. Metabolism is Not CYP-dependent . No data pointing to CYP-interaction.
Epinephrine is classified NP.
Chemical description
Articaine hydrochloride is a local anaesthetic of the amide type. Adrenaline is a catecholamine added for longer duration of local anaesthesia.
Therapeutic characteristics
Local anaesthetic. Administration in combination with adrenaline (epinephrine) (not porphyrinogenic) prolongs the effect of articaine, and reduces hepatic exposure and the risk of systemic reactions.
Metabolism and pharmakokinetics
Articaine, with its ester side chain, is hydrolyzed primarily by plasma esterases (Overman,P.R. 2007). Articaine hydrochloride is quickly metabolized by carboxyesterase to its primary metabolite articainic acid. In-vitro studies show that P450 isoenzymes found in the human hepatocytes microsomes metabolize approximately 5-10 % of available artecaine, converting the drug almost quantitatively to articainic acid. CYP affinity not reported by Rendic (2002).
Adrenalin (epinephrine) is an endogenous compound. It is very rapidly inactivated by processes which include uptake into adrenergic neurones, diffusion, and enzymatic degradation in the liver and body tissues. Metabolism involves monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT).
Personal communication
Thunell, S., study to be published: 2 AIP carriers reported uneventful use. Dentist reported uneventful use of articaine (Septocain®) in AIP patients.
IPNet drug reports
Uneventful use reported in 2 patients with acute porphyria. Also articaine (N01BB08) has been used uneventfully by one patient.
References
- Scientific articles
- Brown, G.J., Welbury, R.R. The management of porphyria in dental practice. British Dental Journal 2002; 193(3):145-6. PMID 12213008. #4645
- Overman, P.R. Articaine: a new alternative in dental hygiene pain control. J Dent Hyg 2007; 81: 66. PMID 17908422. #4646
- Rendic, S. Summery of information on human CYP enzymes: human P450 metabolism. Drug metabolism reviews 2002; 34(1&2), 83-448. #1025
- Thunell, Stig, Evidence-based porphyrogenicity assessment of seven local anasthetics (2009, to be published). #2510
- Drug reference publications
- Sweetman SC, editor. Martindale: The complete drug reference. Adrenaline. Pharmaceutical Press 2009. #1017
- Sweetman SC, editor. Martindale: The complete drug reference. Articaine Hydrochloride. Pharmaceutical Press 2009. #2509
- Summary of Product Characteristics
- Norwegian medicines agency. Summary of Product Characteristics (SPC). Septocaine. #2507
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