Calcium Channel Blocker Induced Gingival Overgrowth

Abstract

Gingival overgrowth occurs with phenytoin, cyclosporin, and calcium antagonists. It can be disfiguring and painful. The prevalence of gingival overgrowth with the use of calcium antagonists may be as high as 38%. The prevalence with nifedipine may be greater than with other calcium blockers. Overgrowth occurs 3.3‐times more commonly in men than in women. Plaque control is necessary. Some patients may require gingival surgery.

Gingival overgrowth (Figure 1) is a fibrotic enlargement of the gingiva that can be induced by various pharmacologic agents through poorly understood mechanisms. Proliferative overgrowth of the gingiva makes it more difficult for patients to maintain mouth hygiene. Changes in the gingiva can range from minor to complete coverage of the teeth. Such changes are unsightly and may result in pain, difficulty in eating, and an undesirable breath odor. ¹ Mechanical obstruction could prevent the eruption of developing teeth. ² There is a potential for candida overgrowth in patients who are being treated with immunosuppressants. ³

Figure 1.

Examine the gums. What drugs are associated with gingival overgrowth?

The three classes of drugs associated with gingival overgrowth are antiepileptics (especially phenytoin [Dilantin]), the immunosuppressant cyclosporin, ⁴ and calcium antagonists. ⁵ Dihydropyridines (including nifedipine, ⁶ , ⁷ , ⁸ , ⁹ felodipine, ¹⁰ nitrendipine, ¹¹ and amlodipine ¹² ) and nondihydropyridines, diltiazem, ¹³ and verapamil, ¹⁴ , ¹⁵ , ¹⁶ have been linked to gingival overgrowth.

PREVALENCE

The incidence of gingival overgrowth varies substantially depending on the drug category involved. Phenytoin is associated with the greatest incidence. ⁸ In an English periodontal screening project, ¹⁷ 911 subjects from general medical practices were studied to determine the prevalence of gingival overgrowth induced by calcium channel blockers. Included were subjects taking nifedipine (n=442), amlodipine (n=181), and diltiazem (n=186), or no calcium antagonist (n=102). The rate of overall clinical overgrowth is displayed in Figure 2. The prevalence of clinically significant gingival overgrowth was 6.3%, 1.7%, and 2.2% for nifedipine, amlodipine, and diltiazem, respectively. Only overgrowth for nifedipine‐treated subjects differed significantly from control subjects (p=0.012). Males were 3.3‐times more likely than females to develop gingival changes. ¹⁷ At a Veterans Affairs Hospital, the prevalence was highest with nifedipine compared to either nondihydropyridines or control subjects (Figure 3). ¹⁸ Coadministration of a calcium antagonist and cyclosporine does not consistently potentiate gingival overgrowth. ⁴ , ¹⁴ , ¹⁹

Figure 2.

Prevalence of gingival overgrowth in an English periodontal screening project ¹⁷

Figure 3.

Prevalence of gingival overgrowth in a Veterans Affairs Hospital clinic ¹⁸

PATHOGENESIS

Studies to date have not established a clear etiology or pathogenesis for drug‐induced gingival overgrowth. ²⁰ Theories have focused on the direct effects of the drug or its metabolites on gingival fibroblasts. A marked heterogeneity of response of gingival fibroblasts has been reported. None of the theories explain why only some patients are affected. It is likely that a variety of factors such as genetic predisposition, pharmacokinetic variables, and inflammatory factors are important.

TREATMENT

Meticulous plaque control is required for subjects treated with drugs that may cause gingival overgrowth. ²¹ Drug dosage reduction or discontinuation is the initial approach to treatment. Discontinuation of the calcium antagonist or switching to another drug often results in improvement of the hyperplasia obviating the need for dental intervention. In one study, ²² 60% of isradipine‐treated patients demonstrated regression of overgrowth while 66% of nifedipine‐treated patients progressed (p<0.05). In severe cases, gingivectomy may be needed. ²¹ An argon laser has been advocated to treat drug‐induced gingival overgrowth. ²³ , ²⁴