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Short reports: M S Matharu, J A van Vliet, M D Ferrari, and P J Goadsby Verapamil induced gingival enlargement in cluster headache J Neurol Neurosurg Psychiatry 2005; 76: 124-127 [Abstract] [Full text] [PDF]

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The association between gingival hypertrophy and amlodipine use

Krishnakumar Nair, Nair MD, Krishnamoorthy K Mahadevan   (24 October 2005)

The association between gingival hypertrophy and amlodipine use 24 October 2005
Krishnakumar Nair, Assistant professor of cardiology Sree Chitra Institute of Medical Sciences and Technology, Trivandrum, Kerala-695011, Nair MD, Krishnamoorthy K Mahadevan Send letter to journal: Re: The association between gingival hypertrophy and amlodipine use drkn14{at}sify.com Krishnakumar Nair, et al.	Dear Editor, We read with great interest the case report titled “Verapamil induced gingival enlargement in cluster headache” by Matharu MS et al. in the Journal of Neurology, Neurosurgery and Psychiatry, year 2005, volume 76, pages 124-127. We wish to highlight an experience we had with another calcium channel blocker, amlodipine, whose association with gum hyperplasia is not clear from the available literature. Amlodipine is a dihydropyridine derivative calcium channel blocker. The drug is used widely for hypertension and angina pectoris. There are some reports of gingival hyperplasia following use of amlodipine.[1][2] Here, we report one patient with hypertension who developed gingival hyperplasia after use of amlodipine. Doctors using amlodipine should be aware of this side effect (which can even lead to dental loss), reversible with stopping the drug and preventable with dental hygiene.[3] A 64 year old female presented to our institute with a cerebrovascular accident. She was detected to have hypertension. She was started on amlodipine 2.5 mg/day and ecospirin 150 mg per day. Twenty months later she came with complaints of hypertrophy of both upper and lower gums. The enlarged gingiva was red, smooth and shiny. The hypertrophic area was painless and did not bleed on touch. There were no signs of inflammation, or discomfort during eating. She was not on any other drug. There was no evidence of any haematological malignancy. She did not have pallor, hepatosplenomegaly or lymphadenopathy. Hematological investigations including peripheral smear were normal. The patient was advised to stop the drug. Four months after discontinuation, the patient showed signs of regression of the gingival hyperplasia. We agree with the authors that the term "gingival hyperplasia" is inappropriate because enlargement results mainly from an increase in extracellular tissue volume with an inflammatory infiltrate, and not from an increase in the number of cells.[3] Gingival hyperplasia can occur during use of drugs such as diphenylhydantoin, cyclosporine and calcium channel blockers.[3][4] The most common cause of drug induced gum hyperplasia is diphenylhydantoin.[5] Exact cause of induction of the hyperplasia is not known. Individual variation in metabolism of the drug may be a factor.[4] The induction of gingival hyperplasia may not be always a class effect, because one report suggests that the gingival byperplasia disappeared in a person who was switched over to isradipine from nifedipine.[6] Local factors such as inflammation has been implicated,[6] but our patient did not had any feature of inflammation. It is believed that for some unknown reason these drugs may cause tissue collagen proliferation.[5] The prevalence of gingival overgrowth induced by chronic medication with calcium channel blockers is uncertain.[4] In spite of widespread use, only one report on gingival hyperplasia induced by calcium channel blockers had been received by the Norwegian Adverse drug reaction committee until 1992.[7] Although there have been several studies examining this question, the results are conflicting, with previous estimates ranging from 20% to 83%.[8] [9] Miller and Damm identified one patient with gingival enlargement out of 24 dentate patients who used verapamil for more than one year giving an incidence of 4.2%.[10] Until 1997, six cases had been published indicating that amlodipine may also promote gingival hyperplasia.[11] But, Jorgensen MG noted mild hyperplasia (less than one-third the clinical crown) in only five patients-a prevalence of 3.3%, out of one hundred and fifty dentate patients on amlodipine, 5 mg per day for at least 6 months . This is significantly less than the rates reported for patients taking nifedipine, and not significantly different from rates previously reported in control groups. Jorgensen concluded that amlodipine, 5 mg per day, did not induce gingival hyperplasia.[11] Similarly, Ellis JS et al. reported a community-based study on nine hundred eleven subjects (442 were taking nifedipine, 181 amlodipine, and 186 diltiazem) and 102 control subjects. 6.3% of subjects taking nifedipine were seen to have significant overgrowth. The prevalence of gingival overgrowth induced by amlodipine or diltiazem was not statistically significant when compared to the control group. The study concluded that the prevalence of clinically significant overgrowth related to chronic medication with calcium channel blockers is low, i.e., 6.3% for nifedipine. Males are 3 times as likely as females to develop clinically significant overgrowth.[8] Regarding other calcium channel blockers , one study looked at the prevalence of gum overgrowth induced by diltiazem and the estimate was a high 74%.[8] Shouda J reported gingival hyperplasia in three patients on long-acting nifedipine and one patient on felodipine out of a total of 54 continuous ambulatory peritoneal dialysis patients .No patients were taking other calcium antagonists. After discontinuation of calcium antagonists, gingival hyperplasia disappeared within 1 month. [9] Therapeutic options for drug related gum hypertrophy include drug discontinuation, providing supplements of folic acid and ascorbic acid, and reconstructive surgery.[5] The prevalence of gingival overgrowth induced by chronic medication with amlodipine is uncertain. However, physicians and cardiologists should be aware of this rare side effect of amlodipine therapy especially because it is eminently reversible with discontinuation of drug use. We suggest that it is important to routinely examine whether the gingiva is overgrown in all patients taking calcium channel antagonists. References 1. Seymour f.A. Ellis JS, Thomason JM, et al. Amlodipine-induced gingival overgrowth. J clin Periodontol 1994:21:281-3. 2. Infante Cossio P, Torello Iserte J, Espin Galvez F, et al. Gingival hyperplasia associated with amlodipine. An Med Interna 1997 ;14(2):83-5. 3. M S Matharu, J A van Vliet, M D Ferrari and P J Goadsby. Verapamil induced gingival enlargement in cluster headache. J Neurol Neurosurg Psychiatry 2005 ;76(1):124-7. 4. Routray SN, Mishra TK, Pattnaik UK, Satapathy C, Mishra CK, Behera M. Amlodipine-induced gingival hyperplasia. J Assoc Physicians India. 2003 Aug;51:818-9. 5. Sinha S, Kamath V, Arunodaya GR, Taly AB. Phenobarbitone induced gingival hyperplasia. J Neurol Neurosurg Psychiatry 2002;73(5):601. 6. Westbrook P, Bednarczyk EM, Carlson M, et al. Regression of nifedipine- induced gingival hyperplasia following switch to a same class calcium channel blocker isradipine. J Periodontol 1997;68:645-50. 7. Lokken P, Skomedal T. Gingival hyperplasia induced by calcium channel blockers. Rare or frequent in Norway? Tidsskr Nor Laegeforen 1992;112(15):1978-80. 8. 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(1):63-7. 9. Shouda J, Nakamoto H, Sugahara S, et al. Incidence of gingival hyperplasia caused by calcium antagonists in continuous ambulatory peritoneal dialysis patients. Adv Perit Dial 1999;15:153-5. 10. Miller CS, Damm DD. Incidence of verapamil-induced gingival hyperplasia in a dental population. J Periodontol 1992;63:453–6. 11. Jorgensen MG. Prevalence of amlodipine-related gingival hyperplasia. J Periodontol 1997;68(7):676-8.