Oral adverse drug reactions. Short review

Pages: 105-112

Ioanina Părlătescu *(1); Carmen Nicolae (2); Șerban Ţovaru (3) Corresponding author: Ioanina Părlătescu (4)

(1) Lecturer, Oral Medicine Department, Faculty of Dental Medicine, Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania; <br>(2)Assistant Professor, Oral Medicine Department, Faculty of Dental Medicine, Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania; <br>(3) Professor, Oral Medicine Department, Faculty of Dental Medicine, Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania; <br>(4) Address: 4 Eforie Street, 3rd floor, office 17, Bucharest <br>*Corresponding author: Ioanina Părlătescu; email: ioanina.parlatescu@umfcd.ro


A wide variety of medications can cause unwanted mucosal manifestations even when used in standard doses. These often clinically mimic the disorders of the oral mucosa and lead to diagnostic confusion.Thus a detailed medical history and drug intake together with the clinical manifestations are the starting points when suspecting oral manifestations of adverse drug reactions.


Adverse drug reactions, oral mucosa, medication, xerostomia


The oral adverse drug reactions(ADR) is a  controversial and difficult topic due to the lack of consensus in the literature on this topic and a multitude of local and general factors possibly involved. A multitude of classes of drugs and substances and combinations of substances are  administered generally or topically on the oral mucosa for therapeutic purposes, long-term use and have interactions with the oral mucosa. The patient’s associated diseases and genetics, the large variety of tissues of the dento-maxillary with different functions which can be altered easily, the polymorphism of clinical findings, the variation of oral microbiota and the complexity of the pathogenic mechanisms also contribute to the diagnosis difficulty.

Adverse drug reactions are defined as: “appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product, which predicts hazard from future administration and warrants prevention or specific treatment, or alteration of the dosage regimen, or withdrawal of the product”[1]. The terms adverse drug reaction and adverse drug effect have the same meaning but adverse drug event is considered an adverse manifestation when a patient is on a drug, but not caused by that substance.

In the general dental practice, the oral adverse drug reactions do not occur very often and their incidence is difficult to estimate as most go undiagnosed. Compared to the oral mucosa, the skin is more commonly affected by ADR [2].

The ADR incidence increases as a result of advancing age and polypharmacy. Polypharmacy is a term that defines the use of 5 or more classes of drug substances[3]. The incidence of multiple drug usage has the tendency to increase in time all over the world.

The diagnosis of oral ADR requires a complete anamnesis with a detailed medical history of the patient intended to determine the chronic and most recently used medication(including doses and timing), nutritional supplements, herbal products, and also associated recreational habits. The chronology of symptoms onset and clinical findings following medication administration facilitates the cause detection. The utility of laboratory tests is limited. The presence of the ADR is mainly based on the disappearance of symptoms upon discontinuation of treatment[4]. The individual variations of oral ADR is caused by drug interactions, dosage differences, and patient’s general factors[5].

The categories of ADR most commonly encountered in the oral cavity are xerostomia, taste disorders, oral burning sensation,  gingival overgrowth.


Hyposalivation or dry mouth is the most frequent oral ADR. It impacts the functions of mastication, deglutition, speech and swallowing and affects the quality of life in all patients. The main mechanisms of drug-induced xerostomia are the anticholinergic effect or sympathomimetic action. There are several hundred classes of drugs that can induce the reduction of saliva[6]. Some are the following: antidepressants, antipsychotics, antihistamines, antihypertensive agents, alpha receptor antagonists, benzodiazepines, diuretics, decongestants, hypnotics, opioids, drugs of abuse (cannabis,ecstasy), cytotoxic agents, muscarinic receptor antagonists, protease inhibitor[7]. This effect is most frequently noticed in middle-aged or elderly patients who generally use more classes of drugs (polypharmacy) and have a synergistic action of saliva reduction[8]. Xerostomia is a favoring factor for oral candidiasis or dental cavities. The clinical examination reveals an erythematous mucosa located mainly on the tongue surface. This mucosa is more susceptible to minor trauma and superficial ulcers are likely to occur.

Other effects on the salivary glands are salivary gland pain produced by antihypertensives, sulphonamides, enlargement of the salivary glands (phenylbutazone, oxyphenbutazone, chlorhexidine), hypersalivation (anticholinesterases)[7].

Taste disorders

Dysgeusia is a qualitative change in taste distortion that manifests as an unusual taste, bitter, metallic, a change in taste perception. It is caused by the following drug categories: antineoplastic and immunomodulating agents, and antiinfectives for systemic use[5].

Hypogeusia is the quantitative reduction of taste and can be induced by antibiotics (in many patients penicillin causes total or partial loss of taste, macrolides, lincosamides, and streptogramins), antineoplastic and immunomodulating agents, acetylcholinesterase inhibitors, aspirin, diclofenac, diltiazem, metronidazole, propranolol, and sulfonamides[5].

Saliva is the external environment of the taste receptors that influence the taste, thus drugs affecting saliva favor the taste disorders. Furthermore, 45% of the drugs which can induce dysgeusia, favor xerostomia, too[9].

Gingival overgrowth

Cyclosporins, calcium-channel blockers(amlodipine, diltiazem, felodipine, nifedipine and verapamil), and phenytoin are the drugs most frequently involved in gingival enlargement [10]. The gingival overgrowth can be localized or generalized, in connection with dental appliances or natural teeth. The dimension of the gingival involvement is related to the dose, the duration of the treatment, the serum concentration, and the dental hygiene[11].

Lichenoid reactions

The oral lichenoid reactions or lesions are diagnosed by the clinical and histological features. The clinical findings are sometimes indistinguishable from oral lichen planus and the term used is “clinically compatible with oral lichen planus”. These are white and erythematous lesions on the same location with typical oral lichen planus, involving bilateral buccal mucosa.  And the difference is given by the presence of possible medication and the pathological characteristics, which have very low sensitivity and specificity [12]. The most common agents associated with oral lichenoid lesions are nonsteroidal anti-inflammatory drugs(phenylbutazone, naproxen, rofecoxib, tolbutamide),  antihypertensives (angiotensin converting enzyme inhibitors (captopril, enalapril), and antimalarials(13). The etiopathogenic mechanism is not completely understood[2].

Other oral manifestations

Oral ulcers may be caused by local chemical irritation, chemotherapy, opportunistic infections, and fixed drug reactions[11]. The direct application of different substances can induce necrosis-burning after aspirin, Sodium lauryl sulfate, or other substances used in the dental office which accidentally reach oral mucosa. The drugs which are known to produce oral ulcers or mucositis are the following  cytotoxic agents (methotrexate, 5-fluorouracil), barbiturates, dapsone, tetracyclines, nonsteroidal anti-inflammatory drugs (indomethacin, salicylates, naproxen), immunosuppressive agents, nicorandil[11].

Vesiculobullous diseases with oral manifestations such as erythema multiforme or pemphigoid or pemphigus can be triggered by systemic medication. Sulfonamides, sulfonylureas and barbiturates agents are incriminated in 25% or erythema multiforme cases[11].

Burning mouth syndrome(BMS) is a multifactorial disorder characterized by persistent superficial oral mucosal pain lasting over 2 hours daily with no clinical detectable lesions. Oral burning sensations which mimic BMS can be induced by carbidopa/levodopa[13] or even triggered by angiotensin-converting enzyme inhibitors, or antidepressants agents[14].


The anamnestic data regarding medication is essential in the diagnostic process of the oral adverse effects.But the large diversity of drugs, the broad clinical manifestations, and the lack of specific investigations are a challenge for the dental practitioners.


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