TIKOSYN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TIKOSYN (TIKOSYN).
Selective class III antiarrhythmic agent; blocks cardiac potassium channels (IKr), prolonging action potential duration and effective refractory period.
| Metabolism | Primarily metabolized by CYP3A4; also undergoes N-dealkylation and glucuronidation; renal excretion of unchanged drug (20-30%) and metabolites. |
| Excretion | Renal: 80% as unchanged drug; biliary/fecal: 20% (metabolites and minor parent drug). |
| Half-life | 10 hours (terminal) in patients with normal renal function; prolonged to up to 42 hours in severe renal impairment; clinically relevant for dosing interval adjustment. |
| Protein binding | 96% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | 3 L/kg (range 2-4 L/kg), indicating extensive tissue distribution, particularly to cardiac tissue. |
| Bioavailability | >90% after oral administration (approximately 93% with low first-pass metabolism). |
| Onset of Action | Oral: 2-3 hours (reduction in heart rate, conversion of atrial fibrillation/flutter). IV: not available clinically, but onset within 30 minutes if used. |
| Duration of Action | Up to 12 hours after a single oral dose; continuous daily dosing maintains therapeutic levels. Duration is dependent on renal clearance. |
500 mcg orally twice daily for atrial fibrillation/flutter conversion and maintenance of sinus rhythm.
| Dosage form | CAPSULE |
| Renal impairment | CrCl > 60 mL/min: 500 mcg BID. CrCl 40-60 mL/min: 250 mcg BID. CrCl < 40 mL/min: contraindicated. |
| Liver impairment | No formal Child-Pugh based adjustment; use caution in severe hepatic impairment due to limited data. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | Adjust based on renal function per CrCl; monitor QTc interval closely due to increased risk of toxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TIKOSYN (TIKOSYN).
| Breastfeeding | Not recommended. It is unknown if TIKOSYN is excreted in human milk. M/P ratio not available. Potential for serious adverse reactions in nursing infants; discontinue nursing or drug. |
| Teratogenic Risk | Pregnancy Category C. Animal studies have shown fetal toxicity (increased fetal loss, reduced fetal weight) at maternally toxic doses. No adequate and well-controlled studies in pregnant women. Potential fetal risks in all trimesters; use only if benefit justifies risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
Tikosyn can cause life-threatening ventricular arrhythmias (e.g., torsade de pointes) and must be initiated in a hospital setting with continuous ECG monitoring and dose adjustment based on creatinine clearance and QTc interval.
| Serious Effects |
Baseline QTc > 440 msec (500 msec in ventricular conduction abnormalities); severe renal impairment (CrCl < 20 mL/min); concurrent use of verapamil, cimetidine, ketoconazole, trimethoprim, or other drugs that prolong QT; congenital long QT syndrome; history of torsade de pointes; hypersensitivity to dofetilide.
| Precautions | QTc prolongation; hypokalemia; hypomagnesemia; renal impairment; bradycardia; concurrent use of other QT-prolonging drugs; drug interactions with CYP3A4 inhibitors. |
Loading safety data…
| Monitor maternal ECG for QTc prolongation, baseline and during therapy. Assess renal function (CrCl) prior to and during treatment. Monitor electrolytes (K+, Mg2+). Fetal monitoring not specifically required, but consider fetal heart rate monitoring if used near term. |
| Fertility Effects | No human data on fertility effects. In animal studies, no adverse effects on fertility were observed at clinically relevant doses. |