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Nifedipine‑Induced Gingival Enlargement: A Case Report with Review

Article  in  Current Medical Issues · January 2021

DOI: 10.4103/cmi.cmi_136_20

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Renita Castelino Sajad Buch

A.B. Shetty Memorial Institute of Dental Science Yenepoya University
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Case Report

Nifedipine‑Induced Gingival Enlargement: A Case Report with

Review
Renita Lorina Castelino, Sajad Ahmad Buch1, Anusha Rangare Laxmana2
Department of Oral Medicine and Radiology, AB Shetty Memorial Institute of Dental Sciences, NITTE (Deemed to be University),1Department of Oral Medicine and
Radiology, Yenepoya Dental College, Yenepoya (Deemed to be University), Mangalore, Karnataka, 2Department of Oral Medicine and Radiology, Century Dental
College, Poinachi, Kerala, India

Abstract
Calcium‑channel blockers (CCBs) are widely used for the treatment of various cardiac conditions. Although CCBs have gained mass acceptance
and popularity among the medical fraternity, their effect on the oral cavity is often under‑reported and rarely debated. This group of medication
causes gingival enlargement in some patients, affecting normal practice of oral hygiene, masticatory functions, besides causing esthetic concerns.
A severe case of gingival enlargement is presented in a 53‑year‑old female patient with a history of nifedipine use.

Key words: Calcium channel blockers, drug‑induced gingival enlargement, gingival hyperplasia, nifedipine

Address for correspondence: Dr. Sajad Ahmad Buch, Department of Oral Medicine and Radiology, Yenepoya Dental College, Yenepoya (Deemed to be University),
Mangalore ‑ 575 018, Karnataka, India. E‑Mail: buchh.sajad@gmail.com

Introduction
Gingival enlargement, also called as gingival hyperplasia or gingival hypertrophy, can have a myriad of implicating factors. The
various factors causing enlargement of gingiva can be included into four groups, namely inflammatory gingival enlargements,
drug‑induced gingival hyperplasia  (DIGH), systemic causes, and hereditary gingival fibromatosis. Drug‑induced gingival
enlargement mainly results from the drugs that are intended for the disorders of nondental origin. The class of drugs usually
implicated in gingival enlargement, in the form of their adverse drug reactions, includes immunosuppressants, anticonvulsants,
and calcium channel blockers (CCBs). The various drugs belonging to these groups and often implicated in gingival enlargement
are summarized in Table 1.[1] DIGH, depending upon its severity may cause difficulty in chewing, phonetics, and oral hygiene
measures, and can lead to the disfigurement of the gingival tissue. Occasionally, it may lead to increased mobility and migration
of the teeth due to alveolar bone loss.
Fatt and Katz, initiated the work on calcium channels by working on muscle cells of crab, and a further research by Fleckenstein
led to the development of a new class of drugs, CCBs, useful in patients with cardiac disorders.[2] CCBs inhibit influx of calcium
ion through cell membranes and act on vascular smooth muscles, the cardiac nodes (sinoatrial and atrioventricular nodes), and
the cardiac myocytes. They act on L‑type calcium channels of these tissues, thereby causing coronary and peripheral arterial
vasodilation, reduced heart rate, reduction in myocardial contractibility and oxygen utilization by the myocardium, and slow
conduction at atrioventricular nodes.[2,3] The aforementioned actions of these drugs mandate their use for the management
of hypertension, cardiac arrhythmias, angina pectoris, and coronary artery spasms.[3] The pathogenesis underlying gingival

Date of Submission: 05‑Oct‑2020 Date of Review:  02-Nov-2020

Date of Acceptance: 06‑Nov‑2020 Date of Web Publication: 13-Jan-2021

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DOI: How to cite this article: Castelino RL, Buch SA, Laxmana AR.
10.4103/cmi.cmi_136_20 Nifedipine-induced gingival enlargement: A case report with review. Curr
Med Issues 2021;19:54-7.

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Castelino, et al.: Nifedipine‑induced gingival enlargement

enlargement under the influence of CCBs is not clear but blood count, bleeding time, clotting time, and platelet count
is considered as multifactorial. The extent of relationship were within the normal limits. The surgical excision of
between CCBs and the effect on gingival tissue depends on excess gingival tissue over the second quadrant of dentition
age, presence of preexisting plaque, gingival inflammation, was planned, but the preliminary phase of treatment began
and genetic predisposition.[4] with thorough oral prophylaxis, and extraction of 24, 25,
26, and 28, owing to the poor periodontal status of these
Case Report teeth, along with meticulous oral hygiene instructions. The
general medicine department of our hospital was consulted,
A 53‑year‑old female patient was referred from a rural health
and after patient’s evaluation, nifedipine was replaced with
clinic to our hospital with a 12‑month history of slow‑growing
enalapril 5 mg for hypertension. The patient was evaluated
mass on the gums. The patient was hypertensive and was on
after 1 week and marked improvement was noted except
20 mg nifedipine/day for the past 5 years. Intraoral examination
in the upper left quadrant. The excessive gingival tissue in
revealed generalized edema of gingival tissues, predominantly
the second quadrant of dentition and its extension on the
involving the interdental papillae, the gingival enlargement
posterior aspect of the palate were surgically removed in the
was severe in the second quadrant, almost covering the entire
second phase of treatment. Histopathology revealed stratified
crowns of teeth 22, 23, 24, 25, 26, and 28 [Figure 1a and b].
squamous epithelium with hyperplasia and acantholysis;
The enlarged gingiva was firm, nontender, pale pink in color
the underlying fibro‑collagenous connective tissue showed
and did not bleed easily on probing while the hard tissue
dense mixed inflammatory infiltrate with congested blood
examination revealed increased mobility in relation to 24,
vessels [Figure 2b]. The patient was recalled and followed at a
25, 26, and 28. Panoramic radiograph revealed generalized
1 week, 1 month, 2 months [Figure 3a and b], and 6 months
bone loss and floating tooth 26 [Figure 2a]. Patient’s complete
intervals. Extraction of the root stumps in the upper right
quadrant and that of impacted 48 was carried out during the
Table 1: Common drugs that cause gingival enlargement follow‑up period, and later, the patient was referred for the
Class of drugs Generic name restorative and prosthetic rehabilitation of the missing teeth.
The recall visits showed no signs of any recurrence.
Immunosuppressants Cyclosporine
Everolimus Informed consent was obtained from the patient for her images
Sirolimus and clinical information to be used in a journal publication.
Mycophenolate mofetil It was explained that while the patient’s name would not be
Calcium‑channel blockers Amlodipine published, complete anonymity could not be guaranteed.
Benidipine
Nicardipine Discussion
Nifedipine
Nifedipine is a very powerful and useful drug for hypertension,
Anticonvulsants Carbamazepine
but its long‑term use causes gingival enlargement in a significant
Diazepam
proportion of population. Among all CCBs, nifedipine is the
Phenytoin
most frequently involved in gingival enlargement. The first
Clobazam
reported case of gingival hyperplasia due to nifedipine use
Gabapentin
was reported by Lederman et  al. in 1984.[5] Further studies
Phenobarbital
reported, nifedipine‑induced gingival enlargement in the range
Topiramate
of 14% to 83%, much higher than other CCBs; verapamil and
Valproic acid
amlodipine with a prevalence of 4.2% and 3.3%, respectively.[2]
Primidone
The CCBs‑induced gingival overgrowth could be detected
Zonisamide
within the first 3 months of the starting dose. Clinically, it may
Levetiracetem
manifest as a localized or a generalized gingival enlargement,
involving the entire dentition. The DIGH usually affects the

a b a b
Figure 1: (a and b) Mild lobulated appearance of gingival papillae (lower Figure 2: (a and b) Panoramic radiograph shows generalized bone loss,
jaw); severe gingival overgrowth causing esthetic and functional which was more severe in the maxillary posterior regions. Histological
problems (upper jaw). picture of excised tissue.

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Castelino, et al.: Nifedipine‑induced gingival enlargement
a b
Figure 3: (a and b) Two months postoperative follow‑up.
teeth in the anterior region than the posterior and also affects the
facial/buccal sides more than the lingual/palatal aspects.[6] The
severe cases present with complete involvement of the papillae
and surrounding gingival tissues, resulting in a lobulated
appearance. Similar appearance could be seen over the upper
left posterior aspect in this case report. The excessive gingival
growth creates areas that are difficult to clean during routine
tooth brushing. Consequently, the host becomes susceptible
to develop, tooth decay, oral infections, and alveolar bone
loss. The inability to maintain optimal oral hygiene leads to
plaque‑induced inflammation that compounds any existing
drug‑induced gingival enlargement. The importance of this
relationship is explained by the fact that the edentulous regions
are least affected by drug‑induced gingival enlargement. This
statement was substantiated in the present case report by the
absence of gingival overgrowth in the edentulous areas of the
lower jaw.
A number of pathways have been postulated, underlying
the pathogenesis of CCBs‑induced gingival enlargement.
The most credited mechanisms include the role of matrix
metalloproteinases, role of pro‑inflammatory cytokines, and
that of fibroblasts:  (1) As, CCBs reduce influx of cellular
calcium, the uptake of folic acid is affected, and thus limits
the formation of active collagenase;[7] therefore, reduction
of collagen degradation ensues, resulting in the increased
production of collagen. (2) Another proposed mechanism
implicates pro‑inflammatory cytokines  (interleukin‑1b and
interleukin‑6), enhancing collagen production by fibroblasts of
human gingiva.[8] (3) Since, a majority of people taking CCBs
show no signs of any gingival overgrowth; therefore, only a
subset of fibroblasts may retain the susceptibility to CCBs. In this
regards, human lymphocyte antigen may have a role in genetic
predisposition of different fibroblasts phenotypes to CCB.[9]
Nifedipine is most often implicated in the gingival overgrowth
than any other agent of its group. Patients under nifedipine
have a significantly higher rate of gingival overgrowth than
amlodipine. Nifedipine and amlodipine are similar structurally;
both dihydropyridines but differ in pharmacokinetics.
Amlodipine is polarized and is transported along the cell
membrane by a much complex transport mechanism,
whereas nifedipine is more lipophilic, and therefore, has easy
penetrability through the cell membrane. This suggests that
the underlying mechanism of drug‑cell interaction dictates
the pathogenesis of drug‑induced gingival enlargement. The
differences in the half life and the volume of distribution
56
of amlodipine (34 h and 21 L/kg) and nifedipine (7.5 h and
0.78 L/kg) may also have a role in the predictability of gingival
enlargement after their use. These values demonstrate that
most of the amlodipine is tissue bound, and hence inactive
and is not freely available in the circulation. A certain
plasma threshold level is suggested, beyond which gingival
overgrowth begins.[10] Nifedipine, unlike amlodipine, tends
to attain considerable plasma peak levels, possibly initiating
drug‑induced gingival enlargement.
The replacement of the offending drug plays a vital role in the
successful management of the gingival overgrowth. All the
possibilities should be discussed with the patient’s physician.
Mild‑to‑moderate overgrowth can be managed by nonsurgical
approaches that involve thorough scaling and root planning,
to eliminate the inflammatory component. This is followed
by a meticulous oral hygiene and home care, followed by
periodic professional scaling to prevent further inflammation.
Nonsurgical intervention combined with the replacement
of the drug can sometimes result in acceptable reduction in
the gingival overgrowth, only to be followed with good oral
hygiene and regular professional visits. Surgical approach
becomes necessary to remove excess tissue, regain appearance
and function, as well as to eliminate any pockets; the basic
surgical method involves gingivectomy and gingivoplasty.
The recurrence of gingival overgrowth can occur irrespective
of the treatment provided, if the offending drug is not stopped
or replaced with another class of drug.
Conclusion
The CCBs are effectively used for the management of various
cardiac conditions including hypertension, however, a serious
and often, overlooked side effect; gingival enlargement occurs
in a sizeable number of patients. The overgrowth can lead to
cosmetic and functional concerns, often affecting quality of life.
Replacement of the drug together with nonsurgical (scaling and
root planning) and/or surgical approaches should be followed
by a good oral hygiene, and home care to maintain the esthetics
and functional capacity.
Declaration of patient consent
The authors certify that they have obtained all appropriate
patient consent forms. In the form, the patient has given her
consent for her images and other clinical information to be
reported in the journal. The patient understands that name and
initial will not be published and due efforts will be made to
conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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