Q-T Prolongation

In vitro estimates of risk for Q-T prolongation and in vivo assessments of hemodynamic interactions with cocaine and methamphetamine... 

Orlaam(tm) (Levomethadyl hydrochloride acetate) was discontinued in the spring of 2004 because it caused severe cardiac toxicity, including Q-T prolongation, Torsade des pointes and cardiac arrest. See http //www.fda.gov/cder/drug/ shortages / orlaam.htm. 

Adverse effects include abdominal cramps, diarrhoea, headache, convulsions and extrapyramidal effects. When used with imidazole antifungals/macrolide antibiotics, it may lead to Q-T prolongation and ventricular arrhythmias. 

Sotalol is a beta-blocker that also has class III antiarrhythmic effects, It causes prolongation of the Q-T interval and is recommended solely as an antiarrhythmic. It is included in this section because it is subject to interactions from its betablocking properties as well as its Q-T prolongation... 

For Q-T prolongation, see Clinical Features of Some Adverse Drug Reactions, Q-T interval prolongation. 

ADENOSINE ANTIPSYCHOTICS Risk of ventricular arrhythmias, particularly torsades de pointes, with phenothiazines and pimozide. There is also a theoretical risk of Q-T prolongation with the atypical antipsychotics All of these drugs prolong the Q-T interval Avoid co-administration of phenothiazines, amisulpride, pimozide or sertindole with adenosine. Monitor the ECG closely when adenosine is co-administered with atypical antipsychotics... 

AMIODARONE LITHIUM 1. Rare risk of ventricular ariythmias, particularly torsades de pointes 2. Risk of hypothyroidism 1. Additive effect lithium rarely causes Q-T prolongation 2. Additive effect both drugs can cause hypothyroidism 1. Manufacturer of amiodarone recommends avoiding co-administration 2. If co-administration is thought to be necessary, watch for symptoms/ signs of hypothyroidism check TFTs eveiy 3-6 months... 

MEXILETINE ANTIARRHYTHMICS Risk of bradycardia and 1 BP however, mexiletine 1 the Q-T prolongation of other antiarrhyth-mics so is often beneficial Additive effect antiarrhythmics are all myocardial depressants Monitor PR, BP and ECG closely... 

BETA-BLOCKERS MEFLOQUINE t risk of bradycardia Mefloquine can cause cardiac conduction disorders, e.g. bradycardia. Additive bradycardic effect. Single case report of cardiac arrest with co-administration of mefloquine and propanolol, possibly caused by Q-T prolongation Monitor PR closely... 

VENLAFAXINE ANTIPSYCHOTICS >- also Q-T-prolonging drugs, above ... 

IMATINIB ANALGESICS-OPIOIDS May cause t plasma concentrations, with a risk of toxic effects of codeine, dextromethorphan, hydroxycodone, methadone, morphine, oxycodone, pethidine and tramadol Inhibition of CYP2D6-mediated metabolism of these opioids Monitor for clinical efficacy and toxicity. Warn patients to report t drowsiness, malaise or anorexia. Measure amylase and lipase levels if toxicity is suspected. Tramadol causes less respiratory depression than other opiates, but need to monitor BP and blood counts, and advise patients to report wheezing, loss of appetite and fainting attacks. Need to consider 1 dose. Methadone may cause Q-T prolongation the CHM has recommended that patients with heart and liver disease who are on methadone should be carefully monitored for heart conduction abnormalities such as Q-T prolongation on ECG as they may lead to sudden death. Also need to monitor patients on more than 100 mg methadone daily and thus an t in plasma concentrations necessitates close monitoring of cardiac and respiratory function... 

Macrolides, particularly erythromycin and clarithromycin, inhibit CYP3A4. With erythromycin, the inhibition of CYP3A4 is non-competitive due to irreversible binding with the isoenzyme to form an inactive complex. Thus, unlike the case with inhibitors with a short half-life (e.g. cimetidine), the offset of inhibition is slow since new enzyme must be synthesized to replace the inactive complexes. Azithromycin, clarithromycin and erythromycin can prolong the Q-T interval and must not be co-administered with other Q-T-prolonging drugs. 

GRAPEFRUIT JUICE CISAPRIDE T plasma concentrations and likely T risk of adverse effects (e.g. cardiotoxicity, Q-T prolongation, torsade de pointes) t oral bioavailability and slight but significant t elimination half-life Although a study in volunteers did not show any changes in heart rate, PR or Q-T prolongation, avoid concurrent use... 

Ludomirsky, A., Klein, H.O., Sarelli, P., Becker, B., Hoffman, S., Taitelman, U., Barzilai, J., Lang, R., David, D., DiSegni, E., Kaplinsky, E. (1982). Q-T prolongation and polymorphous ( torsade de pointes ) ventricular arrhythmias associated with organophosphorus insecticide poisoning. Am. J. Cardiol. 49 1654-8. 

Schoenenberger RA, Haefeli WE, Weiss P, Ritz RE. Association of intravenous erythromycin and potentially fatal ventricular tachycardia with Q-T prolongation (torsades de pointes). BMJ 1990 300(6736) 1375-6. 

Riccioni N, Bartolomei C, Soldani S. Prenylamine-induced ventricular arrhythmias and syncopal attacks with Q-T prolongation. Report of a case and comment on therapeutic use of lignocaine. Cardiology 1980 66(4) 199-203. 

Ludomirsky A, Klein HO and Sarelli P (1982). Q-T Prolongations and polymorphous ( torsade de pointes ) ventricular arrhythmias associated with organophosphorus insecticide poisoning. Am J Cardiol, 49,1654-1658. 

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