Ketoconazole

Mechanism

Ketoconazole strongly inhibits CYP3A4, the enzyme that breaks down alprazolam in the liver. Alprazolam levels rise and its sedative effect is enhanced (FDA labels of both drugs).

Symptoms

Drowsiness, deep sedation, slowed thinking, impaired coordination and speech; in older people, a risk of falls.

Management

The combination is contraindicated: the FDA alprazolam label prohibits use with strong CYP3A4 inhibitors, including ketoconazole, and the FDA ketoconazole label lists alprazolam among contraindicated drugs. The Spanish alprazolam SmPC does not recommend it with ketoconazole and other azole antifungals (alprazolam SmPC). If a patient on alprazolam needs a systemic antifungal, choose one that does not inhibit CYP3A4.

Mechanism

Colchicine is cleared via CYP3A4 and P-glycoprotein. Ketoconazole strongly inhibits both. Colchicine plasma levels rise several-fold. FDA Colcrys carries a boxed warning for fatal toxicity.

Symptoms

Profuse diarrhoea, vomiting, abdominal pain – first signs of toxicity. Pancytopenia (drop in leukocytes, erythrocytes, platelets), muscle weakness, peripheral neuropathy, hepatic and renal injury follow. Fatal cases have been reported.

Management

For patients with renal or hepatic impairment, the combination is not prescribed. With preserved function, use colchicine 0.3 mg every other day, no more than 5 days. Alternative antifungals: terbinafine or echinocandins.

Mechanism

Ketoconazole strongly blocks P-glycoprotein, the main transporter of dabigatran. Dabigatran plasma levels double, especially in renal impairment.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage. Risk rises in patients over 65 and with prior peptic ulcer disease.

Management

The AEMPS label for dabigatran lists systemic ketoconazole as a contraindicated combination. The combination is not prescribed. Alternative antifungals: terbinafine (no P-glycoprotein use) for dermatophytosis, or echinocandins for systemic mycoses.

Mechanism

Ketoconazole inhibits CYP3A4 (dofetilide metabolism) and OCT2. Dofetilide rises 4-fold. FDA Tikosyn Section 4.3.

Symptoms

Torsades de pointes.

Management

Combination contraindicated.

Mechanism

Ketoconazole is a strong CYP3A4 inhibitor, the main dronedarone clearance route. Dronedarone plasma levels rise 17-fold. FDA Multaq Section 4.3 specifically lists strong CYP3A4 inhibitors.

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 rises with hypokalaemia and hypomagnesaemia.

Management

The combination is not prescribed. Alternative antifungals: echinocandins (micafungin, caspofungin) or fluconazole for candidiasis (weaker CYP3A4 effect). Alternative antiarrhythmic: amiodarone or catheter ablation.

Mechanism

The liver breaks down eletriptan mainly through the enzyme CYP3A4, and ketoconazole strongly inhibits this enzyme. In a clinical study, ketoconazole 400 mg raised the peak eletriptan concentration (Cmax) 2.7-fold and the area under the curve (AUC) 5.9-fold. It also lengthened the eletriptan half-life from 4.8 to 8.3 hours. According to the ketoconazole summary of product characteristics of the European Medicines Agency (EMA), ketoconazole interactions can be stronger with a higher dose or a shorter dosing interval. Like other triptans, eletriptan can cause coronary artery spasm. In clinical trials, doses of 60 mg or more caused short-lived rises in blood pressure. At clinical doses, eletriptan neither inhibits nor induces cytochrome P450 enzymes, so it does not affect ketoconazole.

Symptoms

Tightness, pain or pressure in the chest, throat, neck and jaw is common after eletriptan. It is usually not cardiac but can be a sign of coronary artery spasm. Myocardial infarction, ventricular tachycardia and ventricular fibrillation have been reported within a few hours of triptan use, sometimes in people without known heart disease. Rarely, blood pressure rises sharply, even to a hypertensive crisis. Spasm of other arteries can cause Raynaud's syndrome or bowel ischaemia with abdominal pain and bloody diarrhoea. Stroke and brain haemorrhage have occurred after triptans.

Management

The combination is contraindicated (eletriptan label, US Food and Drug Administration, FDA). The eletriptan summary of product characteristics (SmPC) says not to use eletriptan with ketoconazole or other strong inhibitors of the enzyme CYP3A4 (Spanish Agency of Medicines and Medical Devices, AEMPS). The ketoconazole SmPC also lists the combination as not recommended (European Medicines Agency, EMA). Wait at least 72 hours after the last dose of ketoconazole before giving eletriptan (eletriptan and ketoconazole tablet labels, FDA). This concerns oral ketoconazole. In the European Union, its tablets are indicated for endogenous Cushing's syndrome (ketoconazole SmPC, EMA). After a cream is applied to the skin, ketoconazole is not measurable in plasma and no systemic effects are expected (ketoconazole cream SmPC, AEMPS). If eletriptan has been taken during ketoconazole treatment and chest pain or tightness suggesting cardiac ischaemia appears, give no further doses and evaluate the heart (eletriptan SmPC, AEMPS). Stop eletriptan if arrhythmias occur and monitor blood pressure during treatment (eletriptan label, FDA). If signs of spasm in other arteries appear, such as abdominal pain with blood in the stool or white, cold fingers, rule out vasospasm before the next dose (eletriptan label, FDA).

Mechanism

CYP3A4 is the main route of eplerenone clearance, and oral ketoconazole is one of the strongest inhibitors of this enzyme. With ketoconazole 200 mg twice daily, eplerenone AUC rose by 441% (5.4-fold) and Cmax 1.7-fold (Inspra SmPC, AEMPS, section 4.5; Inspra prescribing information, FDA, section 12.3). Eplerenone blocks mineralocorticoid receptors, so this rise in exposure strengthens potassium retention and the fall in blood pressure. Eplerenone does not affect ketoconazole: it inhibits no CYP enzymes and is neither a substrate nor an inhibitor of P-glycoprotein (Inspra SmPC, AEMPS, section 4.5).

Symptoms

The main danger is hyperkalemia: the FDA ketoconazole tablets label names the risk of hyperkalemia and hypotension when eplerenone concentrations rise. High potassium shows as muscle weakness, bradycardia and arrhythmias up to cardiac arrest, with peaked T waves and a widened QRS on the ECG. Hypotension brings dizziness, weakness and fainting, especially on standing. The risk of hyperkalemia is higher in older patients, in patients with reduced renal function or diabetes, and with concurrent ACE inhibitors or angiotensin receptor blockers (Inspra SmPC, AEMPS, section 4.4).

Management

The combination is contraindicated. The eplerenone SmPC bars it in patients receiving strong CYP3A4 inhibitors and names ketoconazole explicitly (Inspra SmPC, AEMPS, sections 4.3 and 4.5). The FDA Inspra label says the same (section 4), as does the FDA ketoconazole tablets label (Contraindications). The ban also covers the week after stopping ketoconazole (ketoconazole tablets, FDA, Precautions). This concerns oral ketoconazole: after a cream or gel, ketoconazole is not measurable in plasma, and the label expects no systemic effects from topical forms (ketoconazole cream SmPC, AEMPS, section 5.2). If a systemic azole is needed, the eplerenone SmPC classes fluconazole as a weak-to-moderate CYP3A4 inhibitor and allows it with an eplerenone ceiling of 25 mg daily (Inspra SmPC, AEMPS, section 4.5; FDA, sections 2.4 and 7.1). Itraconazole, like ketoconazole, is contraindicated. If the patient has already taken the two drugs together, stop one of them and check potassium and creatinine at once. The eplerenone label requires potassium monitoring at any change of regimen and within 3–7 days of adding even a moderate CYP3A4 inhibitor (Inspra SmPC, AEMPS, section 4.4; FDA, section 2.3).

Mechanism

Ketoconazole is a strong CYP3A4 inhibitor. Ergotamine rises 15-fold, fatal ergotism.

Symptoms

Limb ischaemia within 24 hours.

Management

Combination contraindicated.

Mechanism

Ketoconazole is a strong CYP3A4 inhibitor. Pimozide rises 8-fold, QT extends past 500 ms. FDA Orap Section 4.

Symptoms

Progressive QT prolongation within 5 days, torsades de pointes risk.

Management

Combination contraindicated. Alternative: terbinafine or fluconazole for limited infections (fluconazole is a weaker CYP3A4 inhibitor but still requires ECG monitoring).

Mechanism

Ketoconazole is a potent CYP3A4 inhibitor – the main quetiapine metabolic route. Quetiapine plasma levels rise 6- to 7-fold. Marked sedation, orthostatic hypotension, QT prolongation emerge.

Symptoms

Deep sedation, orthostatic hypotension with syncope, tachycardia, QT prolongation on ECG. Older patients: fall risk.

Management

The AEMPS label for quetiapine lists the combination with ketoconazole as contraindicated: quetiapine exposure rises 5 to 8 times. The FDA label reduces the quetiapine dose sixfold with ECG monitoring instead. Alternative antifungals: terbinafine or echinocandins. Alternative antipsychotics without CYP3A4 dependence: olanzapine or aripiprazole.

Mechanism

Ranolazine is a substrate of two proteins: the enzyme CYP3A4, which breaks it down in the gut and liver, and the transport protein P-glycoprotein (P-gp). Ketoconazole strongly inhibits both CYP3A4 and P-gp. At 200 mg twice daily, it raised the ranolazine area under the curve (AUC) 3.0–3.9-fold. In the European Union, ketoconazole tablets are used for Cushing's syndrome at 400–1200 mg a day. The European ketoconazole prescribing information warns that interactions may be stronger at doses above 200 mg. Both drugs prolong the QT interval on the electrocardiogram. The ketoconazole documents base the contraindication on the risk of serious cardiovascular events, up to life-threatening ventricular arrhythmias.

Symptoms

Excess ranolazine causes dizziness, nausea and vomiting, and at high concentrations double vision, lethargy, confusion and fainting. Reported effects of oral ranolazine overdose include low blood pressure, slow heart rate, QT interval prolongation on the electrocardiogram, severe tremor, unsteady gait and hallucinations. When ketoconazole is combined with QT-prolonging drugs, ventricular arrhythmias can occur, including life-threatening torsade de pointes.

Management

The combination is contraindicated (ketoconazole summary of product characteristics, SmPC, European Medicines Agency, EMA; ranolazine SmPC, EMA; labels of both drugs, US Food and Drug Administration, FDA). Do not give ranolazine during the week after ketoconazole is stopped (ketoconazole label, FDA). Review all concomitant medicines before starting ketoconazole (ketoconazole SmPC, EMA). Ketoconazole is contraindicated in documented congenital or acquired QT interval prolongation. Record an electrocardiogram before treatment, within the first week and then as clinically indicated (ketoconazole SmPC, EMA). If the patient also takes other QT-prolonging drugs, continue electrocardiogram monitoring (ketoconazole SmPC, EMA). The contraindication concerns oral ketoconazole. After adults applied ketoconazole gel to the scalp or skin, no measurable ketoconazole was found in plasma (ketoconazole gel SmPC, Spanish Agency of Medicines and Medical Devices, AEMPS). If a patient has taken both drugs and develops dizziness, vomiting, double vision or fainting, observe the patient closely and give symptomatic and supportive care (ranolazine SmPC, EMA). Monitor the electrocardiogram continuously if needed (ranolazine label, FDA).

Mechanism

Simvastatin clearance is 98% via hepatic CYP3A4. Ketoconazole is one of the strongest CYP3A4 inhibitors. Simvastatin plasma levels rise 10-fold or more. The FDA lists the combination as an absolute contraindication.

Symptoms

Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–2 weeks of co-prescription.

Management

The combination is not prescribed. Hold simvastatin during ketoconazole therapy or switch to pravastatin or rosuvastatin (no CYP3A4 use). Alternative antifungals: terbinafine or echinocandins.

Mechanism

Ketoconazole strongly inhibits CYP3A4 and P-glycoprotein, the routes that clear sirolimus. In the sirolimus SmPC (Rapamune), repeated ketoconazole doses raised sirolimus AUC 10.9-fold and Cmax 4.4-fold. The EMA label for oral ketoconazole (Ketoconazole Esteve) lists sirolimus among contraindicated combinations. The sirolimus SmPC does not recommend the pair, and the FDA sirolimus label says to avoid it.

Symptoms

Severe immunosuppression.

Management

Combination contraindicated.

Mechanism

Ketoconazole is a potent CYP3A4 inhibitor – the main tamsulosin metabolic route. Tamsulosin plasma levels rise 2- to 3-fold; orthostatic hypotension and syncope emerge.

Symptoms

Sudden blood pressure drop on standing, syncope, dizziness. Older patients: fall and fracture risk.

Management

The AEMPS label for tamsulosin says the drug must not be given with strong CYP3A4 inhibitors such as ketoconazole. Avoid the combination. Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses. Alternative for benign prostatic hyperplasia: a 5α-reductase inhibitor (finasteride, dutasteride).

Mechanism

Ketoconazole inhibits CYP3A4. Ticagrelor rises 7-fold – severe bleeding risk. FDA Brilinta Section 4.3 strict contraindication.

Symptoms

Spontaneous bleeding, including intracranial.

Management

Combination contraindicated.

Mechanism

Ketoconazole strongly blocks CYP3A4 – the N-deethylation pathway of amiodarone. Amiodarone and its active metabolite (N-desethyl-amiodarone) levels rise; QT effect intensifies.

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 antifungals: terbinafine (no CYP3A4 effect) for dermatophytosis or echinocandins for systemic mycoses.

Mechanism

Ketoconazole is a strong CYP3A4 inhibitor – the main amlodipine metabolic route. Amlodipine plasma levels rise 2- to 3-fold; symptomatic hypotension and acute kidney injury risk.

Symptoms

Blood pressure drop: postural dizziness, syncope. Ankle oedema (typical of amlodipine), facial flushing, reflex tachycardia are possible.

Management

Avoid the combination. Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses. If ketoconazole is needed, halve amlodipine.

Mechanism

Ketoconazole strongly inhibits both CYP3A4 and P-glycoprotein, the two clearance routes of apixaban. In the apixaban SmPC, ketoconazole 400 mg once daily doubled apixaban AUC and raised Cmax 1.6-fold. No label lists the pair as a contraindication: the EMA texts for both drugs advise against it, and the FDA label asks for a dose cut or avoidance.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage, gross haematuria with renal colic, spontaneous retroperitoneal haematomas. Symptoms may appear within days of co-prescription.

Management

The combination is not recommended. In the EU oral ketoconazole is authorised only for endogenous Cushing's syndrome, and ketoconazole cream gives no measurable plasma levels in adults according to its SmPC, so it does not form this pair. If oral ketoconazole is needed, apixaban is replaced for the course by a parenteral anticoagulant such as a low-molecular-weight heparin. The FDA label allows another route: an apixaban dose of 5 or 10 mg twice daily is halved, and at 2.5 mg twice daily the combination is avoided. With either plan the patient is told the signs of bleeding: black stools, blood in the urine, bruising without injury.

Mechanism

Ketoconazole strongly inhibits CYP3A4 – the main atorvastatin metabolic route. Atorvastatin plasma levels rise 3- to 4-fold. FDA Lipitor 2017 advises avoiding concomitant use.

Symptoms

Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–4 weeks of co-administration.

Management

During ketoconazole therapy, hold atorvastatin or switch to pravastatin/rosuvastatin (no CYP3A4 dependence). Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses.

Mechanism

Ketoconazole strongly blocks CYP3A4 – the main budesonide metabolic route. Systemic budesonide exposure (oral or inhaled) rises 6- to 12-fold. High Cushing's syndrome risk with prolonged combination.

Symptoms

Moon face, central obesity, abdominal striae, hypertension, hyperglycaemia. With prolonged combination and abrupt withdrawal: adrenal insufficiency risk.

Management

The combination is not prescribed. Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses. Alternative inhaled corticosteroid: fluticasone/mometasone (less CYP3A4-dependent).

Mechanism

Ketoconazole is a potent CYP3A4 and P-glycoprotein inhibitor – two main cyclosporine clearance routes. Cyclosporine plasma levels rise 2- to 3-fold; nephrotoxicity and neurotoxicity risk.

Symptoms

Acute nephrotoxicity: rising creatinine, hypertension, tremor, headache. In transplant patients: accelerated graft function decline.

Management

If unavoidable, reduce cyclosporine by 50–66% and check trough (C0) daily. Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses.

Mechanism

Ketoconazole is a potent CYP3A4 inhibitor. Effect on citalopram is moderate (CYP3A4 is a minor route), but ketoconazole itself prolongs QT, so additive torsades de pointes risk persists.

Symptoms

QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to 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. If ketoconazole is needed: ECG before start and at day 3 of therapy.

Mechanism

Ketoconazole prolongs the QT interval and strongly inhibits CYP3A4, one of the pathways that metabolise escitalopram. The escitalopram label contraindicates concomitant use with QT-prolonging drugs, and that is the main argument for this pair; the metabolic rise in concentration only adds to it. Topical ketoconazole – shampoo, cream – has minimal systemic absorption and this pair does not apply to it.

Symptoms

Palpitations, dizziness, syncope; on ECG, a prolonged QTc. From the escitalopram side, nausea, insomnia, tremor and sweating as signs of a high concentration.

Management

The combination is avoided. For dermatophyte infection terbinafine or topical treatment serves; for systemic mycosis, a different azole or an echinocandin depending on the fungus. If there is no alternative, an ECG before starting and a few days in, with potassium and magnesium corrected beforehand and the escitalopram dose at the low end.

Mechanism

Ketoconazole is a potent CYP3A4 inhibitor – the main haloperidol metabolic route. Haloperidol plasma levels rise 2- to 3-fold. Ketoconazole itself prolongs QT; effects add up.

Symptoms

QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.

Management

Avoid the combination. Alternative antifungals: terbinafine or echinocandins. Alternative antipsychotics: olanzapine or aripiprazole.

Mechanism

Ketoconazole strongly blocks CYP3A4 – the main methylprednisolone metabolic route. Methylprednisolone plasma levels rise 2- to 3-fold. Risk of iatrogenic Cushing's syndrome and adrenal insufficiency on withdrawal.

Symptoms

Moon face, central obesity, abdominal striae, hypertension, hyperglycaemia (Cushing's syndrome). With prolonged combination and abrupt withdrawal: adrenal insufficiency risk with hypotension and weakness.

Management

Avoid the combination. Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses. If ketoconazole is needed, halve the methylprednisolone dose.

Mechanism

Dual mechanism. Rifampicin strongly induces CYP3A4, which partly metabolises ketoconazole. Ketoconazole plasma levels fall by 50–80%; antifungal efficacy is lost.

Symptoms

Recurrence of mycosis symptoms: ongoing fever, skin or mucosal lesions; in immunocompromised patients, risk of systemic mycosis progression.

Management

The combination is not prescribed. Alternative antifungal during anti-TB therapy: echinocandins (micafungin, caspofungin; resistant to CYP3A4 induction) or terbinafine for dermatophytosis.

Mechanism

Dual potent CYP3A4 inhibition. Ketoconazole plasma levels may rise 3-fold. Hepatotoxicity and adrenal cortex suppression intensify.

Symptoms

Nausea, vomiting, abdominal pain and rising liver enzymes (ALT, AST); in severe cases jaundice and dark urine. Signs of adrenal insufficiency: weakness, fatigue, loss of appetite and weight, low blood pressure, low sodium and high potassium, low blood sugar. Ketoconazole itself prolongs the QT interval on the ECG.

Management

Ketoconazole tablets authorised by the European Medicines Agency (EMA) are indicated for Cushing's syndrome. With ritonavir alone the combination is not contraindicated, but the ketoconazole dose is kept lower than usual. The US ritonavir label (FDA) does not recommend ketoconazole doses above 200 mg a day, and the European ritonavir and ketoconazole SmPCs advise considering a dose reduction. While both drugs are taken, watch closely for signs of adrenal insufficiency and adjust the ketoconazole dose to cortisol levels (ketoconazole SmPC, EMA). Check liver enzymes and bilirubin before starting, weekly in the first month, then monthly for six months, and weekly for a month after each dose increase. Record an ECG before ketoconazole starts and within the first week (ketoconazole SmPC, EMA). If ritonavir boosts saquinavir or is part of paritaprevir/ombitasvir, ketoconazole is contraindicated with that regimen (ketoconazole SmPC, EMA).

Mechanism

Ketoconazole strongly inhibits CYP3A4 and P-glycoprotein, both clearance routes of rivaroxaban. Ketoconazole 400 mg daily raised rivaroxaban AUC 2.6-fold and peak concentration 1.7-fold. The EU SmPCs of rivaroxaban and oral ketoconazole do not recommend the combination, and the FDA labels say to avoid it. No label lists the pair as a contraindication.

Symptoms

Gum bleeding, epistaxis, bruising without trauma, blood in urine or stool, menorrhagia. Severe cases include gastrointestinal or intracranial haemorrhage, gross haematuria with renal colic, spontaneous retroperitoneal haematomas. Symptoms may appear within days of co-prescription.

Management

Avoid the combination. For dermatophytosis, terbinafine is the usual choice instead of oral ketoconazole; for systemic mycoses, echinocandins. If a short course of oral ketoconazole is needed, switch rivaroxaban to a parenteral anticoagulant for that period.

Mechanism

Ketoconazole strongly blocks CYP3A4 – the main sildenafil metabolic route. Sildenafil plasma levels rise 4- to 8-fold. The hypotensive effect surges; priapism and ischaemic optic neuropathy risks rise.

Symptoms

Sudden blood pressure drop: dizziness, syncope. Priapism – painful erection lasting more than 4 hours. Visual disturbances, tinnitus. Symptoms appear within hours of co-administration.

Management

Avoid the combination. Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses. If ketoconazole is needed, cap sildenafil at 25 mg and one dose per 24 hours.

Mechanism

Strong CYP3A4 inhibitor – tacrolimus rises 4-5 fold.

Symptoms

Nephrotoxicity.

Management

Reduce tacrolimus by 75%.

Mechanism

Ketoconazole blocks CYP3A4 (one of the amitriptyline metabolic routes). TCA plasma levels may rise.

Symptoms

Worsening anticholinergic symptoms, drowsiness, tachycardia. Older patients: delirium and fall risk.

Management

For short ketoconazole courses, reduce amitriptyline by 25% temporarily. Alternative antifungals without CYP3A4 effect: terbinafine for dermatophytosis or echinocandins for systemic mycoses.

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).