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|Year : 2015 | Volume
| Issue : 3 | Page : 336--337
Dofetilide induced trigeminal neuralgia
Hayan Al Maluli
Department of Medicine, Cardiovascular Division, Temple University Hospital, Philadelphia, PA 19140, USA
Dr. Hayan Al Maluli
Department of Medicine, Cardiovascular Division, Temple University Hospital, Philadelphia, PA 19140
Anti-arrhythmic medications are uncommonly used due to their pro-arrhythmic effect. However, just like any other class of medication, they can cause idiosyncratic reactions that may or may not be related to their mechanism of action. Those reactions can be severe enough to warrant discontinuation of a successful therapeutic intervention. In this case, we present a case of trigeminal neuralgia caused by dofetilide.
|How to cite this article:|
Maluli HA. Dofetilide induced trigeminal neuralgia.Indian J Pharmacol 2015;47:336-337
|How to cite this URL:|
Maluli HA. Dofetilide induced trigeminal neuralgia. Indian J Pharmacol [serial online] 2015 [cited 2021 Jun 19 ];47:336-337
Available from: https://www.ijp-online.com/text.asp?2015/47/3/336/157138
Dofetilide-induced trigeminal neuralgia is rarely reported. , We present here a case of dofetilide induced trigeminal neuralgia. Dofetilide is a Class III anti-arrhythmic agent proven to be safe and effective in the treatment of atrial fibrillation (AF), including in patients with congestive heart failure (CHF).
A 71-year-old woman presented to our hospital with complaints of malaise, palpitations, and shortness of breath. She had a history of mitral regurgitation, AF, and chronic obstructive pulmonary disease. Her vital signs were: Temperature 37°C, heart rate 135 beats/min, blood pressure 152/68 mmHg, and oxygen saturation of 99% on 4 L of oxygen. On physical examination, the she appeared in mild respiratory distress and had crackles in both lung bases with diffuse wheezing. Cardiac auscultation was significant for an irregularly irregular rate and a grade 2/6 holosystolic murmur. Her initial laboratory tests were notable for the following: White blood cell (WBC) of 7400 cells/dL, hemoglobin of 13.4 mg/dL, creatinine 1.2 ng/mL and potassium of 3 mg/dL. Her B-type natriuretic peptide was 1597 ng/L. The electrocardiogram (ECG) revealed AF with a ventricular rate of 134/min, and ST segment depression in leads V5 and V6, which was unchanged from prior ECG's. Initial management for the patient included controlling the heart rate with a continuous diltiazem drip at a dose of 10 mg/h and correcting her hypokalemia. The patient was then admitted to a telemetry monitoring service. The patient had recently failed electrical cardioversion and propafenone, 450 mg daily, therapy for her AF. It was decided to attempt chemical cardioversion with dofetilide (Tikosyn) capsules at a dose of 250 mcg twice daily. Serial ECG's and creatinine levels were monitored. Five hours after the first dose of dofetilide the patient started complaining of sharp, rapidly progressing right-sided facial pain, 10/10 in intensity on the Functional Pain Scale. The temperature, blood pressure, and heart rate did not significantly change from before. At that time, she appeared to be in severe distress and avoided lying on her right side. She was unable to open her mouth or smile. No rash was noted on the face or in the ear canal. Mild swelling was noted on the right side of the face. She had severe tenderness over the entire right side of the face, unrelieved by a 4 mg of IV push of morphine. At this point, a work-up to exclude ischemic central nervous system pathology and maxillofacial disease, including temporomandibular joint (TMJ) disease, was initiated. Computed tomography scans of the brain and maxillofacial region did not reveal inflammation or other pathological processes. Some of her laboratory data were an erythrocyte sedimentation rate of 14 mm/h, C-reactive protein 5.75 mg/L, WBC of 11,400 k/mm3. No cause of the facial pain was identified. During this investigation, the patient was continued on dofetilide 250 mcg twice daily. She received a total of 3 doses, and after the second dose her rhythm converted to sinus on the ECG. However, the facial pain remained very difficult to control and was affecting her oral intake. At this point, it was decided to stop dofetilide therapy. In 12 h, the patient's facial pain started to improve. However, she converted back to AF with a rapid ventricular response, which required a dose of 360 mg of diltiazem CD daily for rate control. Twenty four hours after the last dose of dofetilide, the pain completely resolved.
Dofetilide (available as Tikosyn) is a Class III anti-arrhythmic agent that works by prolonging the effective refractory period in the action potential of atrial and ventricular myocytes, and accessory pathways. It does so by selectively blocking the rapidly activating component (Ikr) of the Delayed Rectifier Cardiac Potassium Channel. This leads to longer repolarization time.  Available in the US in oral preparations only, it has demonstrated efficacy in converting AF and flutter to sinus rhythm. With dosages of 125, 250 or 500 mcg twice daily the conversion rate is 6%, 10%, and 30%, respectively. It works even better in maintaining the sinus rhythm. With a chronic dose of 500 mg BID, its success rate is close to 60%. 
Dofetilide has gained acceptance in the guidelines because of its proven safety in patients with CHF with corrected QT interval of <429 ms. It is also safe in patients who have had a recent myocardial infarction.  However, dofetilide still carries a significant risk of provoking torsades de pointes (3%). More common, but less serious documented adverse effects of dofetilide include: Headache 11%, chest pain 10%, dizziness 8%, respiratory tract infection 7%, and dyspnea 6%. A rare but notable side effect is facial paralysis (<2%).  In our patient's case, there was a clear temporal association between the administration and termination of dofetilide with the onset and resolution of intense facial pain resembling trigeminal neuralgia. A relatively extensive work up to rule out coincidental pathologies, such as nervous system masses or infections, TMJ disease, and other inflammatory etiologies of this pain, was performed in consultation with neurology and included serological and imaging modalities. Rechallenging the patient with dofetilide was not performed, and hence this side effect would fall under the probable/likely category of the WHO-UMC causality assessment system. Whether dofetilide caused this by interfering with neural cells ion channels is not known. Although it is difficult to prove a direct causative relationship between the drug and this adverse effect, this case illustrates the importance of monitoring these symptoms and the early discontinuation of the drug because of the possibility of progression to trigeminal neuralgia or facial paralysis.
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