Which drugs are most commonly associated with gingival hyperplasia and what is the initial management?

Medications That Cause Gingival Hyperplasia

Three main drug classes cause gingival hyperplasia: calcium channel blockers (particularly nifedipine and amlodipine), calcineurin inhibitors (cyclosporine more than tacrolimus), and anticonvulsants (phenytoin, with emerging evidence for lamotrigine, oxcarbazepine, and phenobarbital). 1, 2, 3

Primary Causative Medications

Calcium Channel Blockers

• Nifedipine and amlodipine are the most commonly implicated dihydropyridine calcium channel blockers causing gingival hyperplasia through altered collagen metabolism and fibroblast proliferation 4, 2
• Verapamil also causes gingival hyperplasia, though it is a non-dihydropyridine agent 1
• Concurrent use of nifedipine with cyclosporine increases the risk of gingival hyperplasia beyond either drug alone 1
• All dihydropyridine calcium channel blockers (including felodipine and isradipine) share this risk and should be avoided if gingival hyperplasia develops 5

Calcineurin Inhibitors (Immunosuppressants)

• Cyclosporine (CsA) is strongly associated with gingival hyperplasia and is more likely to cause this adverse effect than tacrolimus 1
• Cyclosporine causes gingival overgrowth in a substantial proportion of transplant patients, particularly when combined with calcium channel blockers 1
• Tacrolimus is NOT associated with gingival hyperplasia, making it the preferred calcineurin inhibitor when gingival overgrowth occurs 1

Anticonvulsants

• Phenytoin is the classic anticonvulsant causing gingival hyperplasia, first reported in 1939 3, 6
• Lamotrigine, oxcarbazepine, and phenobarbital are significantly associated with gingival overgrowth in 61%, 71%, and 53% of cases respectively 7
• Valproic acid and carbamazepine show lower but still notable associations (44% and 32% respectively) 7

Initial Management Algorithm

Step 1: Optimize Oral Hygiene

• Implement intensive oral hygiene with professional periodontal maintenance including scaling and root planing 1, 4
• Poor oral hygiene worsens drug-induced gingival hyperplasia; controlling the inflammatory component limits severity 2, 6
• Refer to a general dentist or periodontist for professional management 1, 2

Step 2: Medication Substitution (When Feasible)

For Cyclosporine:

• Switch from cyclosporine to tacrolimus to prevent further hyperplasia, as tacrolimus does not cause gingival overgrowth 1
• Contact the transplant center before making any changes to immunosuppression 1

For Calcium Channel Blockers:

• Switch to ACE inhibitors or ARBs as first-line alternatives, which do not cause gingival hyperplasia 5
• Benidipine can be used if a calcium channel blocker must be continued, as it does not cause gingival hyperplasia 5
• Avoid switching to other dihydropyridine calcium channel blockers (nifedipine, felodipine, isradipine), as they share the same risk 5

For Anticonvulsants:

• Consider alternative antiepileptic drugs that are less associated with gingival overgrowth 7
• Consult with neurology before changing seizure medications

Step 3: Surgical Intervention

• Periodontal surgery (gingivectomy) may be necessary if conservative measures fail and hyperplasia affects speech, mastication, tooth eruption, or aesthetics 1, 2
• Surgery should be performed only after optimizing oral hygiene and considering medication changes, as recurrence is common if the causative drug continues 1

Critical Clinical Pitfalls

• Do not assume antibiotic prophylaxis is needed for routine dental procedures in transplant patients taking cyclosporine; prophylaxis is only indicated for specific cardiac conditions (previous endocarditis, prosthetic valves, cardiac transplant with valvulopathy) 1, 8
• Gingival changes are typically reversible upon drug discontinuation, but this must be balanced against the need for continued therapy (e.g., preventing transplant rejection or controlling seizures) 4
• The combination of cyclosporine plus calcium channel blockers creates additive risk for severe gingival hyperplasia 1
• Generic formulations of cyclosporine require careful monitoring, as switching formulations can alter drug levels and potentially affect both efficacy and toxicity 1