What advice should be given to people with porphyria who are undergoing dental procedures?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
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Date prepared:17/03/2017
Background
The porphyrias can be split into two types according to whether they cause acute attacks or whether they have mainly skin effects. This advice is intended for patients with an acute type of porphyria (acute intermittent porphyria, ALA dehydratase deficiency porphyria, hereditary coproporphyria, variegate porphyria) in whom some medicines can precipitate a painful acute attack(1). Generally, in patients with the following types of porphyria: congenital erythropoietic porphyria, erythropoietic protoporphyria and porphyria cutanea tarda all medicines are considered safe (1), except oestrogens and large doses of chloroquine if the patients receiving them have active porphyria cutanea
tarda (2, 3).
This Q&A looks at the safety in patients with acute porphyria of medicines commonly used by dentists. Other factors that should be considered in patients with acute porphyria who are undergoing dental procedures are also covered.
Answer
The Dental Practitioners’ Formulary in the British National Formulary (BNF) lists medicines and preparations that can be prescribed by dental practitioners on NHS prescription forms FP10D (England), WP10D (Wales) and GP14 (Scotland), and this Q&A focuses on those preparations. The Dental Practitioners’ Formulary covers antibiotics, antivirals, analgesics, anxiolytics, hydrocortisone and local anaesthetics, as well as artificial saliva, fluoride and mouthwashes (4).
Providing there are no other complications to take into consideration, any medicine listed as safe or likely safe in the tables below would be a good first line choice for a patient with acute porphyria. In cases in which the safety in porphyria of a medicine is uncertain, individual risk factors should be taken into account and clinical expert opinion, ideally from a porphyria specialist, should be
sought (5).
Since fasting and stress (emotional and physical) can trigger acute attacks in patients with acute forms of porphyria, measures to avoid these circumstances are advisable. Stress can be minimised by using adequate pain relief and treating infection promptly. Patients should be encouraged to maintain adequate calorie intake (6).
Topical preparations
Local expert opinion is that all topical preparations are considered safe in patients with acute porphyria, when applied to intact skin or mucosa. In this context, ‘topical preparations’ include skin creams, ointments and local anaesthetics in small amounts (2). Where damage to the oral mucosa is known or suspected then higher systemic exposure should be taken into account.
Mouth ulcer preparations
Many mouth ulcer preparations contain more than one active ingredient. As well as individual patient variations (e.g. whether patient is at high-risk of having an acute attack for any reason, how much of the preparation is likely to be swallowed), factors which should be taken into account include the safety of each of the active ingredients, and the extent to which each of the ingredients will be absorbed through the buccal mucosa. Not all this information is always available. At the time of writing, the safety in porphyria of cetalkonium chloride, cetylpyridinium chloride, chlorocresol, menthol and aminoacridine could not be determined.
Local Anaesthetics and combinations
In the UK, local anaesthetics that are commonly used in primary care dentistry are lidocaine, articaine, mepivacaine and prilocaine. Many of these preparations also contain adrenaline (epinephrine) or felypressin (7). Adrenaline/felypressin are used to prolong the effect of the local anaesthetic, and to reduce hepatic exposure and increase tolerance (8). Both adrenaline (9) and felypressin(2) are considered safe(8).
Preparation / Safety(8,9) / CommentsBupivacaine / Safe
Prilocaine / Safe
Lidocaine / Safe / Intravenous doses should be used with caution, but intravenous use in dentistry would not be expected (9).
Articaine / Safe
Mepivacaine / Safe
Antibiotics/Antifungals/Antivirals/Antiseptics
The following preparations are considered safe to prescribe or take and should be the preferred choices for treating an infection.
Preparation / Safety(8,9) / CommentsAciclovir (cream ortablet/suspension) / Safe
Amoxicillin / Safe
Azithromycin / Safe
Cefalexin / Safe
Cefradine / Safe
Chlorhexidine (gel, mouthwash, spray) / Safe / Chlorhexidine preparations often contain alcohol, which can be a risk when taken in excess. An alcohol-free preparation would be ideal, but the low intake of alcohol expected with mouthwashes is not likely to pose a significant risk.
Co-amoxiclav / Safe
Demeclocycline (oral paste) / Likely safe
Doxycycline / Safe
Hydrogen peroxide (mouthwash) / Likely safe / Topical preparation. Encourage patient not to swallow.
Metronidazole / Safe
Miconazole (cream, gel, ointment) / Use of locally acting, oral preparations is generally safe in porphyria but some systemic absorption occurs so use of another preparation in high-risk patients may be preferable. / Systemic (oral or by injection) use of imidazole antifungals, including miconazole, is unsafe in
porphyria (4).
Nystatin / Safe
Phenoxymethylpenicillin / Safe
Sodium chloride (mouthwash) / Safe
Sodium fusidate (ointment) / Safe
Tetracycline / Likely safe
The following antibiotics/antifungalsare considered less suitable or should not be prescribed to a patient with porphyria without first seeking advice from a porphyria expert.
Preparation / Safety(8) / CommentsClarithromycin / Potentially unsafe / Seek advice before taking/prescribing
Clindamycin / Potentially unsafe / Seek advice before taking/prescribing
Erythromycin (systemic) / Unsafe / Seek advice before taking/prescribing
Fluconazole (systemic) / Probably unsafe / Seek advice before taking/prescribing
Oxytetracycline (systemic) / Safety unknown / Seek advicebefore taking/prescribing (10)
Analgesics
Preparation / Safety(8,9) / CommentsAspirin / Safe
Benzydamine (mouthwash, oromucosal spray) / Likely safe / Significant systemic absorption not expected with the mouthwash or oromucosal spray.
Carbamazepine / Unsafe / Seek advice before taking/prescribing
Choline salicylate (dental gel) / Safety unknown / There is little available information on the safety in porphyria of systemic choline salicylate or cetalkonium chloride (8, 9), which is also present in some choline salicylate dental gels. Absorption of choline salicylate across the buccal mucosa is
likely (11). A safer alternative would be preferable.
Diclofenac / Likely safe / Ibuprofen would be the preferred option.
Dihydrocodeine / Safe
Ibuprofen / Safe
Paracetamol / Safe
Corticosteroids
Preparation / Safety(8,9) / CommentsBeclometasone (inhaler) / Safe
Betamethasone / Safe
Hydrocortisone (cream or tablet) / Safe
Triamcinolone (oral paste) / Safe
Saliva substitutes
Several saliva substitute preparations are listed in the BNF, but not all can be prescribed on a dental NHS prescription (see UKMI Q&A on Saliva substitutes: Choosing and prescribing the right product for further information on prescribing issues (12)). Although sodium fluoride, potassium chloride, calcium chloride and potassium phosphate are known to be safe in porphyria (8), the safety in porphyria of all the ingredients in each of the listed preparations is not known (8).
Preparation / Safety(8) / CommentsArtificial saliva (spray, gel, pastilles) / Safety unknown / See notes above on saliva substitutes
Saliva stimulating tablets / Safety unknown / See notes above on saliva substitutes
Antihistamines, Sedatives and Other
Preparation / Safety(8,9) / CommentsCetirizine / Safe
Chlorphenamine / Safe
Diazepam / Safe
Ephedrine (nasal drops) / Likely safe / Ephedrine tablets areclassified as probably safe(8) and noradrenaline (same drug group) is classified as safe (9).
Lansoprazole / Safe
Loratadine / Safe
Omeprazole / Safe
Promethazine / Safe
Sodium fluoride (mouthwash, drops, toothpaste, tablets) / Safe
Temazepam / Safe
Summary
An indication of the safety of various medicines commonly used by dentists in patients with acute porphyria is given. When considering the safety of medicines in acute porphyria, individual patient factors should also be taken into account. Fasting, stressful situations, pain and infection can trigger acute attacks in patients with acute porphyria, and measures to avoid these circumstances are advisable.Local expert opinion is that all topical preparations are considered safe in patients with porphyria, when applied to intact skin or mucosa, but for topical dental preparations, it is often not possible to be certain that the mucosa within the oral cavity is intact, and systemic exposure through swallowing should be taken into account.
Limitations
There is limited information in the literature about the use of some dental medicines in the acute porphyrias. Individual risk factors should be taken into account. Further information on the safety of medicines in acute porphyria, and a list of medicines that are safe in the acute porphyrias can be obtained from the UK Porphyria Medicines Information Service (UKPMIS); Tel: 029 2074 2251/029 2074 2979 or at
References
1.European Porphyria Network [cited 2017 Feb 13]. Available from:
2.Personal Communication Dr M Badminton Honorary Consultant and Clinical Lead National Acute Porphyria Service (Cardiff) University Hospital of Wales. (2017).
3.Porphyria South Africa. Porphyria cutanea tarda [cited 2016 Feb 28]. Available from:
4.Joint Formulary Committee. British National Formulary (online). London: BMJ Group and Pharmaceutical Press. Available from: [Accessed on 2017 Feb 13].
5.Lockett CD, Badminton MN. Safe prescribing in the autosomal dominant acute porphyrias: a practical approach: Part II. Adverse Drug React Bull.1135-8.
6.Lockett CD, Badminton MN. Safe prescribing in the autosomal dominant acute porphyrias: a practical approach: Part I. Adverse Drug React Bull. 2015;293:1131-4.
7.UKMi Q&A 152.4: What is the clinical significance of potential drug interactions with local anaesthetic preparations used in primary care dentistry? [cited 2017 Feb 28]. Available from:
8.The Norwegian Porphyria Centre and The Swedish Porphyria Centre. The Drug Database for Acute Porphyria [cited 2017 Feb 28]. Available from:
9.UK Porphyria Medicines Information Service (UKPMIS). Drugs that are considered to be SAFE for use in the acute porphyrias. Written May 2016 [cited 2017 Feb 13]. Available from:
10.UKMi Q&A 229.1: What is the most suitable treatment for acne in a patient with acute porphyria? [cited 2017 Feb 28]. Available from:
11.Summary of Product Characteristics – Bonjela (choline salicylate) [cited 2017 Feb 28]. Available from: [Date of revision of the text May 2015].
12.UKMI Q&A 190.8: Saliva substitutes: Choosing and prescribing the right product [cited Feb 14 2017]. Available from:
Quality Assurance
Prepared by
Alex Bailey, Welsh Medicines Information Centre
Date Prepared
17th March 2017
Checked by
Gail Woodland, Welsh Medicines Information Centre
Date of check
17th March 2017
Search strategy
Embase: (exp porphyria/ AND (exp sodium fluoride/ OR exp mouthwash/ OR mouthrinse.mp. OR exp local anesthetic agent/ OR exp local anesthesia/ OR hydrocortisone/ OR exp saliva substitute/ OR exp anxiolytic agent/ OR exp analgesic agent/ OR exp antiinfective agent/) AND dent*.mp.)
In-house database/ resources: dentist* AND porphyria (all fields); (drug name) (kw) AND porphyria (kw)
EMC: Daktarin oral gel; Benzydamine 0.15%w/v Oromucosal Spray; Benzydamine 0.15% w/v Mouthwash; Bonjela
WMIC Safe List: (drug name)
NAPOS: (drug name)
BNF (electronic): Dental Practitioner’s Formulary
NorthWest MI website: Browsed
SA porphyria site: ( (and general browse on site)
European Porphyria site (
Acknowledgements
We would like to thank Dr Mike Badminton, Honorary Consultant and Clinical Lead, National Acute Porphyria Service (Cardiff), University Hospital of Wales, for his comments.
1
Available throughNICE Evidence Search at