Azithromycin

Mechanism

Azithromycin weakly prolongs QT, additively with the TCA amitriptyline (a pronounced QT prolonger). Clinically significant arrhythmia is rare in young patients without cardiovascular disease.

Symptoms

QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

For short azithromycin courses (3–5 days) in young patients, the combination is acceptable. In older patients, cardiac disease, or hypokalaemia: ECG before start, alternative antibiotics (doxycycline, a cephalosporin), or replace amitriptyline with gabapentin/pregabalin for neuropathic pain.

Mechanism

Dual antibiotic therapy with additive QT prolongation. Used in severe infections (e.g., empirical therapy for community-acquired pneumonia in older patients at risk of atypical flora).

Symptoms

QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

The combination is appropriate in inpatient settings for indications (severe pneumonia, abdominal sepsis). ECG before start and at day 2 of therapy. Maintain potassium and magnesium. Avoid dual therapy in outpatient infections.

Mechanism

Dual macrolide therapy – doubled QT effect and redundant antibacterial activity without clinical rationale.

Symptoms

QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

The combination is not prescribed. Choose one macrolide: azithromycin for upper respiratory infections and chlamydia (short course); clarithromycin for H. pylori and atypical pneumonia. When choosing, mind the interaction profile (clarithromycin is a strong CYP3A4 inhibitor).

Mechanism

Macrolides suppress the gut bacteria Eggerthella lenta that inactivate digoxin. Digoxin plasma levels rise within days of co-administration.

Symptoms

Nausea, anorexia, visual disturbances (yellow-green halos around lights), arrhythmias. Older patients: confusion.

Management

For short azithromycin courses (3–5 days), check digoxin level at 5–7 days. If it rises, temporarily reduce digoxin. Alternative antibiotics without gut flora effect: a cephalosporin or doxycycline.

Mechanism

Both prolong QT. Escitalopram dose-dependently (FDA Lexapro caps at 20 mg/day), azithromycin dose-dependently (FDA warning 2013).

Symptoms

QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

For short azithromycin courses (3–5 days) with normal potassium and magnesium, the combination is acceptable. In atrial fibrillation, hypokalaemia, or prior QT prolongation: alternative antibiotics (doxycycline, a cephalosporin).

Mechanism

Additive QT prolongation – both drugs prolong QTc dose-dependently.

Symptoms

QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

For short courses of both (azithromycin 3–5 days, fluconazole single dose for candidiasis), the combination is acceptable. For prolonged systemic fluconazole therapy: alternative antibiotics (doxycycline, a cephalosporin) or antifungals (terbinafine, echinocandins).

Mechanism

Additive QT prolongation (fluoxetine weakly prolongs QT at high doses).

Symptoms

QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

For short azithromycin courses (3–5 days) with normal potassium and magnesium, the combination is acceptable. In cardiovascular disease or fluoxetine doses above 40 mg: ECG before start or alternative antibiotics (doxycycline, a cephalosporin).

Mechanism

Additive QT prolongation.

Symptoms

QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

Avoid the combination. Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses. Alternative antibiotics: a cephalosporin or doxycycline (no QT effect).

Mechanism

Antibiotics may affect methotrexate gut absorption. Low clinical significance at rheumatological methotrexate doses (5–25 mg weekly).

Symptoms

Mostly no changes. At high oncologic methotrexate doses: risk of rising levels with toxicity symptoms (stomatitis, diarrhoea, falling leukocyte count).

Management

At low rheumatological methotrexate doses, the combination is acceptable without adjustment. At high oncologic doses: avoid azithromycin; alternative antibiotics (a cephalosporin, nitrofurantoin for UTI).

Mechanism

Additive QT prolongation (mirtazapine weakly prolongs QT, especially above 30 mg).

Symptoms

QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

For short azithromycin courses (3–5 days) with mirtazapine ≤30 mg, the combination is acceptable. In older patients and cardiovascular disease: ECG before start or alternative antibiotics (doxycycline, a cephalosporin).

Mechanism

Additive QT prolongation (quetiapine prolongs QT at high doses).

Symptoms

QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

For short azithromycin courses (3–5 days) with quetiapine ≤300 mg, the combination is acceptable. On high quetiapine doses or cardiovascular disease: ECG before start or alternative antibiotics.

Mechanism

Azithromycin is a weak P-glycoprotein inhibitor; rivaroxaban is a P-glycoprotein substrate. Rivaroxaban plasma levels may rise modestly, raising bleeding risk.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, black or tarry stools. Higher risk in older patients and chronic kidney disease.

Management

For short azithromycin courses (3–5 days), the combination is acceptable without dose change. In older patients and creatinine clearance below 50 mL/min: monitor for bleeding signs. Alternative antibiotics without P-glycoprotein effect: a cephalosporin, amoxicillin-clavulanate, doxycycline.

Mechanism

Additive QT prolongation (sertraline minimally prolongs QT at standard doses, azithromycin dose-dependently).

Symptoms

QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

For short azithromycin courses (3–5 days) with sertraline ≤150 mg, the combination is acceptable. In cardiovascular disease: ECG before start or alternative antibiotics (doxycycline, a cephalosporin).

Mechanism

Additive QT prolongation (tacrolimus prolongs QT in hypomagnesaemia, common on calcineurin inhibitors).

Symptoms

QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

For short azithromycin courses post-transplant: check magnesium and replete if needed. ECG before start if other QT-prolonging drugs are on board. Alternative antibiotics: a cephalosporin or doxycycline.

Mechanism

Azithromycin is a weak CYP1A2 inhibitor (theophylline is a substrate). Theophylline plasma levels may rise slightly. The effect is much smaller than with erythromycin or clarithromycin.

Symptoms

Mostly no changes. In patients with borderline theophylline levels: rare nausea, tachycardia, insomnia.

Management

For short azithromycin courses (3–5 days), no special adjustment. In patients on high theophylline doses (or with renal/hepatic impairment): check theophylline level at 3–5 days.

Mechanism

Additive QT prolongation (tramadol weakly prolongs QT). Weak serotonergic risk (tramadol inhibits serotonin reuptake).

Symptoms

QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

For short azithromycin courses (3–5 days) in patients without cardiovascular disease, the combination is acceptable. In epilepsy: watch tramadol-related seizure threshold reduction. Alternative analgesic: paracetamol or morphine/oxycodone (no QT effect).

Mechanism

Additive QT prolongation (venlafaxine prolongs QT at doses above 150 mg).

Symptoms

QT prolongation on ECG. Dizziness, syncope, palpitations. Rarely: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

For short azithromycin courses (3–5 days) with venlafaxine ≤150 mg, the combination is acceptable. At higher venlafaxine doses or cardiovascular disease: ECG before start or alternative antibiotics.

Mechanism

Azithromycin suppresses vitamin K-producing gut flora, raising INR. Bleeding cases have been reported.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, black or tarry stools. Higher risk in older patients and prior peptic ulcer disease.

Management

For short azithromycin courses (3–5 days), check INR 3–5 days after start and 5 days after stopping the antibiotic. If INR rises above target, reduce warfarin by 10–20%. Alternative antibiotics: a cephalosporin (minimal gut flora effect).