Azithromycin

Mechanism

Azithromycin is a macrolide, and its SmPC records prolonged cardiac repolarisation and QT with a risk of ventricular arrhythmia and torsade. The citalopram SmPC lists ongoing treatment with any drug capable of prolonging the QT interval among its contraindications, with no exceptions.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope. The end point is polymorphic ventricular tachycardia of the torsade type progressing to ventricular fibrillation. The risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, decompensated heart failure and in women.

Management

The pair sits in the citalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. A short azithromycin course tempts one to leave things as they are, but the SSRI ban carries no exception for course length. Potassium, magnesium and QTc are checked before the start, and the antibiotic is swapped if they are off.

Mechanism

Azithromycin is a macrolide, and its SmPC records prolonged cardiac repolarisation and QT with a risk of ventricular arrhythmia and torsade. The escitalopram SmPC contraindicates any QT-prolonging drug alongside it: the ban is written broadly, and the classes in brackets are examples.

Symptoms

QTc prolongation on ECG, palpitations, dizziness, syncope. The end point is polymorphic ventricular tachycardia of the torsade type progressing to ventricular fibrillation. The risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, decompensated heart failure and in women.

Management

The pair sits in the escitalopram SmPC contraindications, so the question is which drug stays, not how far to cut the dose. A short azithromycin course tempts one to leave things as they are, but the SSRI ban carries no exception for course length. Potassium, magnesium and QTc are checked before the start, and the antibiotic is swapped if they are off.

Mechanism

Both drugs prolong the QT interval on the electrocardiogram. The azithromycin SmPC reports QT prolongation and torsades de pointes with macrolides, azithromycin included. The haloperidol SmPC reports QT prolongation, ventricular arrhythmias and sudden death; the risk is higher with high doses, high plasma levels and parenteral use, especially intravenous. Together the effects add up.

Symptoms

QT prolongation on the electrocardiogram (ECG) causes no symptoms by itself. Palpitations, dizziness or fainting may occur. The dangerous complication is torsades de pointes, a ventricular tachycardia that can end in cardiac arrest (azithromycin SmPC). The risk is higher in women and older people, with low potassium or magnesium, marked bradycardia, heart disease or severe heart failure (azithromycin and haloperidol SmPCs).

Management

The combination is contraindicated: the Spanish haloperidol SmPC contraindicates haloperidol with drugs that prolong the QT interval and names azithromycin among them (haloperidol SmPC). The azithromycin SmPC asks for caution with such drugs, antipsychotics included (azithromycin SmPC), and the azithromycin label approved by the US Food and Drug Administration (FDA) advises weighing the risk of fatal QT prolongation in patients who take them (azithromycin FDA label). Before haloperidol is started, an electrocardiogram (ECG) is recorded and low potassium and magnesium are corrected; if the corrected QT interval (QTc) lengthens, the haloperidol dose is reduced, and haloperidol is stopped if QTc exceeds 500 ms (haloperidol SmPC).

Mechanism

Both drugs prolong the QT interval on the electrocardiogram (ECG). The pimozide label reports QT prolongation, torsade de pointes, ventricular tachycardia and ventricular fibrillation at therapeutic doses. The azithromycin label reports QT prolongation and torsade de pointes. According to the US pimozide label, macrolide use in patients with a prolonged QT interval, such as pimozide can produce, has rarely been associated with ventricular arrhythmias. Two sudden deaths were reported when clarithromycin was added to pimozide. The pharmacokinetic contribution of azithromycin is small. Its label calls it a weak cytochrome P450 inhibitor and finds no clinically significant inhibition of the enzyme CYP3A4, one of the two main routes of pimozide breakdown. The label does not fully rule such inhibition out, though. Azithromycin stays in the body for a long time: its terminal half-life is about 68 hours, and low concentrations persist after the course ends (azithromycin label). The labels give no study of this pair.

Symptoms

QT interval prolongation itself causes no symptoms and shows only on the electrocardiogram (ECG). The danger is ventricular arrhythmia: torsade de pointes, ventricular tachycardia and ventricular fibrillation, up to cardiac arrest and sudden death (pimozide and azithromycin labels). An arrhythmia episode presents as palpitations, dizziness or fainting. The risk is higher in women and older people and with low potassium or magnesium, clinically relevant bradycardia, arrhythmias or severe heart failure (azithromycin and pimozide labels).

Management

The combination is contraindicated. The US pimozide label names azithromycin among the macrolide antibiotics that must not be given with pimozide (pimozide label, US Food and Drug Administration, FDA). The Spanish pimozide summary of product characteristics (SmPC) contraindicates pimozide with any drug known to prolong the QT interval and with macrolide antibiotics (pimozide SmPC, Spanish Agency of Medicines and Medical Devices, AEMPS). Azithromycin's own label puts it in the QT-prolonging group: it reports QT prolongation and torsade de pointes (azithromycin SmPC, AEMPS). The azithromycin labels are softer. The Spanish one asks for caution with such drugs and gives pimozide as an example, and the US one asks prescribers to weigh benefits and risks (azithromycin labels, AEMPS and FDA). The strictest document applies. If a patient taking pimozide needs an antibiotic, do not prescribe azithromycin. Clarithromycin and erythromycin are also contraindicated, and the US pimozide label also rules out sparfloxacin, gatifloxacin and moxifloxacin with pimozide (pimozide label, FDA). If a patient already takes both drugs, stop one of them. For any pimozide treatment, record an electrocardiogram (ECG) before the start and repeat it during treatment. Keep potassium and magnesium in the normal range, and stop pimozide if the QT or corrected QT (QTc) interval exceeds 500 ms (pimozide labels, AEMPS and FDA).

Mechanism

Additive QT prolongation. Azithromycin received a 2013 FDA warning for fatal ventricular arrhythmia risk, particularly in patients with risk factors. Amiodarone is a potent QT-prolonging drug.

Symptoms

QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.

Management

Avoid the combination. Alternative antibiotics: doxycycline or a cephalosporin. If azithromycin is needed, ECG before start and potassium and magnesium in range.

Mechanism

Both drugs prolong the QT interval. Azithromycin, like other macrolides, prolongs cardiac repolarisation and the QT interval, which carries a risk of torsades de pointes (azithromycin SmPC). QT prolongation and arrhythmias have been reported with amitriptyline, and its SmPC lists QT-prolonging drugs among combinations that are not recommended: with tricyclic antidepressants they increase the likelihood of ventricular arrhythmias (amitriptyline SmPC).

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 amitriptyline SmPC lists QT-prolonging drugs among combinations that are not recommended (amitriptyline SmPC). Azithromycin is used with caution in patients who take QT-prolonging drugs and in those with QT prolongation, low potassium or magnesium, clinically relevant bradycardia, arrhythmia, severe heart failure and in older people (azithromycin SmPC). The US Food and Drug Administration (FDA) asks prescribers to weigh the risk of QT prolongation against the benefit of azithromycin in these patients (azithromycin FDA label). Avoid the combination where possible. If it is still needed, keep in mind that with amitriptyline the arrhythmia risk is higher with marked bradycardia, uncompensated heart failure and potassium or magnesium disturbances (amitriptyline SmPC).

Mechanism

Both antibiotics prolong the QT interval on the electrocardiogram, and taken together they raise the risk of arrhythmias, including torsades de pointes (azithromycin and ciprofloxacin SmPCs).

Symptoms

QT prolongation on the electrocardiogram (ECG), palpitations, dizziness, fainting. Rarely, torsades de pointes, which can lead to cardiac arrest (azithromycin SmPC). The risk is higher in older patients and women, with hypokalaemia or hypomagnesaemia, bradycardia, heart failure and after myocardial infarction (azithromycin and ciprofloxacin SmPCs).

Management

Avoid the combination: the ciprofloxacin label of the US Food and Drug Administration (FDA) says to avoid ciprofloxacin in patients taking macrolides and other drugs that prolong the QT interval (ciprofloxacin FDA label). The Spanish SmPCs of both antibiotics allow the combination only with caution (azithromycin and ciprofloxacin SmPCs). If the combination cannot be avoided, note that the FDA label also says to avoid ciprofloxacin with known QT prolongation, uncorrected hypokalaemia or hypomagnesaemia, heart failure, myocardial infarction or bradycardia (ciprofloxacin FDA label). Older patients and women are more sensitive to QT prolongation (azithromycin and ciprofloxacin SmPCs).

Mechanism

Colchicine is cleared with the help of the P-glycoprotein transporter and the CYP3A4 enzyme (colchicine SmPC). Azithromycin inhibits P-glycoprotein and increases colchicine exposure: the area under the curve (AUC) rises by 57% and the peak concentration by 22% (azithromycin SmPC). Colchicine has a narrow therapeutic index and azithromycin has a long half-life, so its effect persists after the course ends (azithromycin SmPC).

Symptoms

Profuse diarrhoea, vomiting, abdominal pain as first signs. With prolonged combination, muscle weakness, peripheral neuropathy, and pancytopenia follow.

Management

Monitor the patient clinically during the azithromycin course and after it ends (azithromycin SmPC) and, where possible, check colchicine blood concentrations (colchicine SmPC). Azithromycin inhibits P-glycoprotein, and in renal or hepatic impairment colchicine should not be combined with such drugs whenever possible; if colchicine is continued, reduce its dose substantially and monitor the patient closely (colchicine SmPC). Colchicine itself is contraindicated in severe renal or hepatic impairment (colchicine SmPC). In older patients and in renal impairment, the total colchicine dose over a 4-day gout attack should not exceed 3 mg (colchicine SmPC). At the first sign of nausea, vomiting, abdominal pain or diarrhoea, stop colchicine; the patient needs urgent care (colchicine SmPC).

Mechanism

Both drugs prolong the QT interval. Dronedarone prolongs the corrected QT interval (QTc) by about 10 ms (dronedarone SmPC). The azithromycin SmPC reports QT prolongation and torsades de pointes with macrolides, azithromycin included. The effects add up, and the dronedarone SmPC warns that proarrhythmic effects may occur when it is combined with drugs that favour arrhythmias or with potassium and magnesium disorders.

Symptoms

QT prolongation on the electrocardiogram (ECG) causes no symptoms by itself. Palpitations, dizziness or fainting may occur. The dangerous complication is torsades de pointes, a ventricular tachycardia that can end in cardiac arrest (azithromycin SmPC). The risk is higher in women and older people, with low potassium or magnesium, marked bradycardia or severe heart failure (azithromycin SmPC).

Management

The dronedarone SmPC contraindicates it with drugs that can induce torsades de pointes and lists some oral macrolides, such as erythromycin; azithromycin is not named on that list (dronedarone SmPC). The azithromycin SmPC asks for caution in patients on class III antiarrhythmics, dronedarone among them, and in anyone taking QT-prolonging drugs (azithromycin SmPC). The azithromycin label approved by the US Food and Drug Administration (FDA) advises weighing the risk of fatal QT prolongation in these patients (azithromycin FDA label). If azithromycin is still given with dronedarone, potassium and magnesium deficits are corrected before and during treatment, the electrocardiogram (ECG) is checked during treatment, and dronedarone is stopped if the corrected QT interval (QTc) reaches 500 ms or more (dronedarone SmPC).

Mechanism

Both drugs prolong the QT interval. Sertraline does so in a concentration-dependent way: at twice the maximum recommended dose the largest mean increase was 10 ms (sertraline label of the US Food and Drug Administration, FDA). Azithromycin, like other macrolides, prolongs cardiac repolarisation and the QT interval, which carries a risk of torsades de pointes (azithromycin SmPC). The effects add up.

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 US Food and Drug Administration (FDA) label of sertraline says to avoid drugs known to prolong the QT interval; its examples include antibiotics such as the macrolide erythromycin (sertraline FDA label). The US azithromycin label asks prescribers to weigh the risk of QT prolongation in patients who already take such drugs (azithromycin FDA label). European SmPCs allow the combination with caution: azithromycin is used carefully in patients with QT prolongation, low potassium or magnesium, clinically relevant bradycardia, arrhythmia, severe heart failure and in older people, and sertraline in heart disease, low potassium or magnesium, a family history of QT prolongation and bradycardia (azithromycin and sertraline SmPCs). Avoid the combination where possible; if azithromycin is still needed, assess these risk factors before starting.

Mechanism

Atorvastatin is broken down by the CYP3A4 enzyme and carried by the transporter P-glycoprotein (atorvastatin SmPC). Azithromycin is a weak inhibitor of cytochrome P450 enzymes, but inhibition of CYP3A4 cannot be fully ruled out (azithromycin SmPC). In a study, azithromycin 500 mg daily for 3 days did not change blood levels of atorvastatin 10 mg (azithromycin labels). Even so, post-marketing cases of rhabdomyolysis have been reported in patients taking azithromycin with statins (azithromycin SmPC).

Symptoms

Muscle pain, weakness, cramps or tenderness, sometimes with malaise and fever. In rhabdomyolysis, urine turns dark from myoglobin and there is a risk of acute kidney injury (statin SmPCs).

Management

Use the combination with caution: post-marketing cases of rhabdomyolysis have been reported in patients taking azithromycin with statins (azithromycin SmPC). The atorvastatin label of the US Food and Drug Administration (FDA) advises weighing the risks and benefits of combining atorvastatin with macrolides and watching for signs of muscle damage, especially when starting treatment and when raising the dose of either drug. Ask the patient to report muscle pain, cramps or weakness at once, especially with fever or malaise. If these occur, measure creatine kinase (CK): stop atorvastatin if CK is above 5 times the upper limit of normal (atorvastatin SmPC).

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

Azithromycin inhibits P-glycoprotein (azithromycin SmPC). Digoxin is a P-glycoprotein substrate in the gut and kidneys, so its blood level may rise (both labels). There is a second route: in about 1 in 10 patients, gut bacteria break down 40% or more of an oral digoxin dose, and some antibiotics suppress these bacteria, so more digoxin is absorbed (US Food and Drug Administration (FDA) digoxin label). The level rises gradually as digoxin accumulates, not at once.

Symptoms

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

Management

The combination calls for digoxin level monitoring. Measure the serum digoxin concentration before azithromycin is started, keep monitoring and reduce the digoxin dose as needed (US Food and Drug Administration (FDA) digoxin label). During and after the azithromycin course, monitor the patient clinically and possibly the digoxin level (azithromycin SmPC). Draw the sample just before the next digoxin dose or at least 6 hours after the last one (FDA digoxin label). Older age, low body weight, reduced kidney function and electrolyte disorders raise the risk of toxicity, so these patients need monitoring most (FDA digoxin label).

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 the ECG, dizziness, fainting, a fast or irregular heartbeat. Rarely, polymorphic ventricular tachycardia (torsades de pointes) with a risk of cardiac arrest. Risk is higher with low potassium or magnesium, clinically relevant bradycardia, arrhythmias, severe heart failure, in women and in older patients (azithromycin SmPC).

Management

Both drugs prolong the QT interval (azithromycin SmPC; US ketoconazole label). Azithromycin is used with caution in patients taking other QT-prolonging drugs and in those with QT prolongation, low potassium or magnesium, clinically relevant bradycardia, arrhythmias or severe heart failure (azithromycin SmPC). In the EU, oral ketoconazole is authorised only for Cushing's syndrome; its SmPC asks for an ECG before the start and within the first week of treatment, and recommends ECG monitoring when a QT-prolonging drug is added (ketoconazole SmPC, EMA). Congenital or acquired QT prolongation is a contraindication to ketoconazole (ketoconazole SmPC, EMA). Tell the patient to report fainting, dizziness or a fast, irregular heartbeat at once (US ketoconazole label).

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

Rosuvastatin undergoes limited metabolism, about 10% of the dose, mainly by the CYP2C9 enzyme (rosuvastatin SmPC). Azithromycin is a weak inhibitor of cytochrome P450 enzymes (azithromycin SmPC). There are no data on higher rosuvastatin levels with this combination, but post-marketing cases of rhabdomyolysis have been reported in patients taking azithromycin with statins (azithromycin SmPC).

Symptoms

Muscle pain, weakness, cramps or tenderness, sometimes with malaise and fever. In rhabdomyolysis, urine turns dark from myoglobin and there is a risk of acute kidney injury (statin SmPCs).

Management

Use the combination with caution: post-marketing cases of rhabdomyolysis have been reported in patients taking azithromycin with statins (azithromycin SmPC). The documents do not require a change in the rosuvastatin dose. Ask the patient to report unexplained muscle pain, weakness or cramps at once, especially with malaise or fever. If these occur, measure creatine kinase (CK): stop rosuvastatin if CK is above 5 times the upper limit of normal or if muscle symptoms are severe (rosuvastatin SmPC).

Mechanism

Simvastatin is broken down by the CYP3A4 enzyme. Strong inhibitors of this enzyme, including erythromycin and clarithromycin, raise the risk of myopathy and rhabdomyolysis and are contraindicated with simvastatin (simvastatin SmPC). Azithromycin is not on this list: it is a weak inhibitor of cytochrome P450 enzymes, although inhibition of CYP3A4 cannot be fully ruled out (azithromycin SmPC). There are no data on higher simvastatin levels with azithromycin, but post-marketing cases of rhabdomyolysis have been reported in patients taking azithromycin with statins (azithromycin SmPC).

Symptoms

Muscle pain, weakness, cramps or tenderness, sometimes with malaise and fever. In rhabdomyolysis, urine turns dark from myoglobin and there is a risk of acute kidney injury (statin SmPCs).

Management

Use the combination with caution: post-marketing cases of rhabdomyolysis have been reported in patients taking azithromycin with statins (azithromycin SmPC). Azithromycin is not among the strong CYP3A4 inhibitors that are contraindicated with simvastatin (simvastatin SmPC). Warn patients who start simvastatin or raise its dose about the risk of myopathy and ask them to report unexplained muscle pain, tenderness or weakness at once. If these occur, measure creatine kinase (CK): stop simvastatin if CK is above 5 times the upper limit of normal (simvastatin SmPC).

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).

Mechanism

Azithromycin has minimal effect on CYP3A4 and does not affect hepatic oestradiol metabolism. No clinically significant reduction in menopausal hormone therapy efficacy has been reported.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

No dose adjustment needed. In women on menopausal hormone therapy, azithromycin remains an antibiotic of choice for respiratory infections.

Mechanism

Azithromycin has minimal effect on CYP3A4 (unlike clarithromycin and erythromycin). No clinically significant reduction in ethinylestradiol levels has been reported.

Symptoms

The combination usually causes no specific symptoms. Each drug's individual side effects remain.

Management

Additional contraception during short azithromycin courses (3–5 days) is not needed. In women on combined oral contraceptives with respiratory or urogenital infections, azithromycin remains an antibiotic of choice.