Review articles

By Dr. Balasubramanian Thiagarajan , Prof. Geetha Ramamoorthy
Corresponding Author Dr. Balasubramanian Thiagarajan
Department of Otolaryngology, Stanley Medical College, Chennai Tamilnadu, Sreemagal, 20 I Street, Officers Colony, Rajaram Metha Nagar - India 600029
Submitting Author Dr. Balasubramanian Thiagarajan
Other Authors Prof. Geetha Ramamoorthy
Stanle Medical College, - India 600029


Gingival overgrowth, Drug induced, Gingival hyperplasia

Thiagarajan B, Ramamoorthy G. Drug Induced Gingival Overgrowth. WebmedCentral OTORHINOLARYNGOLOGY 2012;3(11):WMC003829
doi: 10.9754/journal.wmc.2012.003829

This is an open-access article distributed under the terms of the Creative Commons Attribution License(CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Submitted on: 15 Nov 2012 10:49:58 AM GMT
Published on: 16 Nov 2012 01:41:04 PM GMT


Gingival hyperplasia / hypertrophy is a rather common condition. This article reviews literature pertaining only to gingival overgrowth following drug ingestion. A wide range of causes have been attributed to gingival overgrowth. Drug induced overgrowth commonly occurs following medications prescribed for non dental causes. Pathogenesis of gingival overgrowth following ingestion of certain drugs is still unsure. Certain high risk co existant factors like presence of gingivitis has been implicated. Management of this condition should take into consideration the condition for which the offending drug has been prescribed. Physicians should be aware of drugs that could cause gingival overgrowth in order to identify and manage this problem.


A large number of drugs have been implicated as cause for gingival hypertrophy / hyperplasia. Use of the term hypertrophy / hyperplasia is rather controversial. These terms do not accurately reflect the current understanding of the current histopathological scenario. Gingival enlargement in these patients is not due to increase in the number of periodontal cells but due to an increase in the extracellular volume 1. This increase in the extracellular volume is caused by hyperplasia involving fibroblasts.

Gingival overgrowth was first described in dental literature of 1960?s2 w hen case reports started appearing about children who developed enlarged gingiva due to treatment of epilepsy using phenytoin. This condition was also described in children born of epileptic mothers who were being treated with sodium valproate. These children were branded to be suffering from fetal valproate syndrome 3. Fetal valproate syndrome was first described by Di Liberti in 1984 4. These children also had neurodevelopmental problems. Associated congenital defects in this syndrome include Neural tube defects, congenital heart defects, orofacial clefts, and limb defects.

Drugs involved in causing gingival enlargement:

Three types of drug categories 6hav e been implicated as causative factors of gingival enlargement. They include:

1. Anti epileptic drugs – Phenytoin, Phenobarbitone, Valproic acid, Primidone, Vigabatrin and carbamazepine.

2. Calcium channel blockers – Nifidepine, Verapamil, Diltiazem and Amlodepin

3. Immunosuppresive drugs – Cyclosporine

Studies reveal that drug induced gingival overgrowth usually occurs within first three months of starting drug therapy with the offending drug. This usually begins as an enlargement involving Interdental papillae.


Review of literature shows a wide variation in prevalance rates 7. A high figure of 50% has been quoted for the drug phenytoin, where as for cyclosporin it is 30% and for calcium channel blockers 10%. Recent studies have demonstrated the synergistic effect of cyclosporin with calcium channel blockers in causing gingival overgrowth 8. Indian statistics are rather sketchy in this aspect. One study reports that 57% of epileptic children in the age group 8-13 on phenytoin developed gingival overgrowth within the first 3 months of starting the treatment9.


Etiology although enough pointers are there to point fingers at an offending drug, is still considered to be multifactorial. The relationship between the drug dosage, duration of therapy and sex prediliction is still not clear. There is still a raging debate going on as to whether drug induced gingival hyperplasia could be caused by hyperplasia of gum epithelium or of subcutaneous connective tissue or both.

Certain predisposing risk factors have been indentified and documented. They include:

Poor oral hygiene: Presence of dental plaque can provide a reservoir for accumulation of drugs like phenytoin / cyclosporin8.

In patients who have undergone orthodontic procedures the presence of nickel could predispose to formation of gingival over growth

Susceptibility of some subpopulation of fibroblasts and keratinocytes to phenytoin, cyclosporin and other drugs which could cause gingival overgrowth

Number of langhans cells10p resent in the oral epithelium is another risk factor. More the number worse the risk. These drugs have a tendency to accumulate inside these cells causing prolonged effect on the gums.

Cytochrome P-450 gene polymorphism 11c an cause individual variations in drug metabolism predisposing to gingival overgrowth

In patients using calcium channel blockers gingival overgrowth could be caused by:

Defective collagenase activity

Blockage of aldosterone synthesis from adrenal cortex followed by feedback increase in the secretion of ACTH

Upregulation of keratinocytes growth factor

Upregulation of transforming growth factor alpha12< /p>


The tissue overgrowth is classically of dense collagen tissue and other connective tissue elements. Scattered inflammatory cells can also be seen. Classically gingival tissue adjacent to anterior teeth is more commonly affected than the posterior ones. Presence of bacterial plaque in the teeth is essential for gingival overgrowth to occur. Histology of overgrowth revealed hyperplasia of connctive tissue, epithelial acanthosis and elongated rete ridges.


Stopping / substituting the offending medicine. Gingival overgrowth reverts back to normal within 3 months.
Maintenance of strict oral hygiene
Regular mouth wash using cholorhexidine
Oral metronidazole for 21 days
Surgical removal of the gingival overgrowth (gingivectomy)


1. Desai P, Silver JG. Drug induced gingival enlargement. J Can Dent Assoc 1998; 64: 263-8.
2. Kimbal OP. The treatment of epilepsy with sodium diphenyl hydantoinate. J Am Med Assoc 1939; 112: 1244-5.
3. Rodriguaz-Vazquez M, Carrascosa-Romero MC, Parddal-Fernandoz M, et al. Congenital gingival hyperplasia in a neonate with foetal valproate syndrome Neuropediatrics 2007; 38: 251-2.
4. DiLiberti JH, Farndon PA, Dennis NR, Curry CJ. The fetal valproate syndrome. Am J Med Genet 1984;19:473-481
5. Perlik F, Kolinova M, Zvarova J, et al. Phenytoin as a risk factor in gingival hyperplasia. Therap Drug Monitor 1995; 17: 445-8.
6. Perlik F, Kolinova M, Zvarova J, et al. Phenytoin as a risk factor in gingival hyperplasia. Therap Drug Monitor 1995; 17: 445-8.
7. Ellis JS, Seymour RA, Steele JG, et al. Prevalence of gingival overgrowth induced by calcium channel blockers: a community based study. J Periodontol. 1999; 70: 63-7.
8. Spratt H, Boomer S, Irwin CR, et al. Cyclosporin associated gingival overgrowth in renal transplant recipients. Oral Dis 1999; 5 : 27- 31.
9. Mejia LM, Lozada-Nur F. Drug induced gingival hyperplasia. E medicins . Medscope. com 2009; article / 1076264
10. Kinane DF, Drummond JR, Chisholm DM. Langerhans cells in human chronic gingivitis and phenytoin induced gingival hyperplasia. Arch Oral Biol 1990; 35: 561-4.
11. Seymour RA, Ellis JS, Thomason JM. Risk factors for drug induced gingival overgrowth . J Clin Periodontol. 2000; 27 : 217-23.
12. Lafzi A, Farahani RMZ, Shoja MM. Amlodipine induced gingival hyperplasia. Oral Med Pathol Oral Cir Buccal 2006; 11: E480-2.

Source(s) of Funding


Competing Interests



This article has been downloaded from WebmedCentral. With our unique author driven post publication peer review, contents posted on this web portal do not undergo any prepublication peer or editorial review. It is completely the responsibility of the authors to ensure not only scientific and ethical standards of the manuscript but also its grammatical accuracy. Authors must ensure that they obtain all the necessary permissions before submitting any information that requires obtaining a consent or approval from a third party. Authors should also ensure not to submit any information which they do not have the copyright of or of which they have transferred the copyrights to a third party.
Contents on WebmedCentral are purely for biomedical researchers and scientists. They are not meant to cater to the needs of an individual patient. The web portal or any content(s) therein is neither designed to support, nor replace, the relationship that exists between a patient/site visitor and his/her physician. Your use of the WebmedCentral site and its contents is entirely at your own risk. We do not take any responsibility for any harm that you may suffer or inflict on a third person by following the contents of this website.

0 reviews posted so far

0 comments posted so far

Please use this functionality to flag objectionable, inappropriate, inaccurate, and offensive content to WebmedCentral Team and the authors.


Author Comments
0 comments posted so far


WebmedCentral Article: Drug Induced Gingival Overgrowth

What is article Popularity?

Article popularity is calculated by considering the scores: age of the article
Popularity = (P - 1) / (T + 2)^1.5
P : points is the sum of individual scores, which includes article Views, Downloads, Reviews, Comments and their weightage

Scores   Weightage
Views Points X 1
Download Points X 2
Comment Points X 5
Review Points X 10
Points= sum(Views Points + Download Points + Comment Points + Review Points)
T : time since submission in hours.
P is subtracted by 1 to negate submitter's vote.
Age factor is (time since submission in hours plus two) to the power of 1.5.factor.

How Article Quality Works?

For each article Authors/Readers, Reviewers and WMC Editors can review/rate the articles. These ratings are used to determine Feedback Scores.

In most cases, article receive ratings in the range of 0 to 10. We calculate average of all the ratings and consider it as article quality.

Quality=Average(Authors/Readers Ratings + Reviewers Ratings + WMC Editor Ratings)