amiodarone

Mechanism

Amiodarone inhibits CYP3A4 and P-glycoprotein – apixaban exposure rises by approximately 40–50 %. Bleeding risk increases, especially in older patients with body weight under 60 kg and eGFR below 50 mL/min.

Management

Formal dose reduction is not mandatory but is advised – in the presence of any of the criteria (age ≥ 80, weight ≤ 60 kg, creatinine ≥ 133 µmol/L), use apixaban 2.5 mg twice daily. Strengthen bleeding surveillance and check hemoglobin and creatinine at 2–4 weeks after initiation.

Mechanism

Amiodarone inhibits CYP3A4, which partially metabolizes atorvastatin. Atorvastatin concentration rises and myopathy risk increases. The effect is less dramatic than for simvastatin or lovastatin but is clinically meaningful.

Management

Cap atorvastatin at ≤ 40 mg/day. If muscle pain appears, check CK and temporarily withhold the statin. Alternatives include pravastatin or rosuvastatin (not CYP3A4-metabolized).

Mechanism

Аддитивное удлинение QT-интервала, риск Torsades de Pointes.

Management

ЭКГ исходно и на 2–3-й день, контроль электролитов. У пожилых с CV-патологией – избегать.

Mechanism

Additive QT prolongation: amiodarone strongly blocks IKr potassium channels and ciprofloxacin does the same more mildly. Risk of torsades de pointes. FDA black-box warning for all fluoroquinolones regarding QT prolongation (2016 update).

Management

Avoid the combination where possible. If ciprofloxacin is essential, obtain an ECG at baseline and on day 2–3 and keep potassium above 4.0 mmol/L and magnesium in the upper-normal range. Alternatives are non-fluoroquinolone antibiotics where susceptibility allows.

Mechanism

Аддитивное удлинение QT-интервала + ингибиция CYP3A4 кларитромицином увеличивает экспозицию амиодарона.

Management

Сочетание избегать. Если без него нельзя – ЭКГ исходно и через 48 часов, контроль электролитов (K, Mg).

Mechanism

Амиодарон ингибирует P-gp и почечную секрецию дигоксина, концентрация дигоксина растет в 1.5–2 раза.

Management

Уменьшить дозу дигоксина на 50% при старте амиодарона, контроль уровня через 7 и 14 дней.

Mechanism

Dual mechanism: 1) additive AV conduction slowing and heart rate reduction (amiodarone non-competitively blocks β-receptors, metoprolol selectively blocks β1); 2) amiodarone inhibits CYP2D6, doubling metoprolol concentration. Risk of symptomatic bradycardia, AV block, and hypotension.

Management

The combination is often justified in AF. Start metoprolol at a low dose (12.5–25 mg twice daily) and titrate by heart rate and BP. Monitor ECG (QT, AV conduction) every 3–6 months. In older adults, reduce the dose when resting heart rate drops below 55/min.

Mechanism

Both drugs prolong the QT interval (amiodarone strongly via IKr potassium channel blockade; sertraline modestly). Additive QT prolongation increases the risk of torsades de pointes, especially with hypokalemia and hypomagnesemia.

Management

Obtain a baseline ECG (QTc) and repeat 1–2 weeks after starting or increasing sertraline. QTc > 500 ms or an increase > 60 ms warrants reassessment. Keep potassium ≥ 4.0 mmol/L and magnesium ≥ 1.0 mmol/L. Antidepressant alternatives with minimal QT effect include mirtazapine and bupropion.

Mechanism

Amiodarone inhibits CYP3A4, the enzyme responsible for simvastatin metabolism. Active simvastatin acid concentrations rise 2–3-fold, and the risk of myopathy and rhabdomyolysis increases proportionally. The FDA caps simvastatin at 20 mg/day when used with amiodarone.

Management

Do not exceed 20 mg simvastatin per day. If intolerance occurs or more intensive lipid lowering is needed, switch to pravastatin, fluvastatin, or rosuvastatin (not metabolized by CYP3A4), or use moderate-dose atorvastatin with caution.

Mechanism

Amiodarone potently inhibits CYP2C9 (the main enzyme metabolizing S-warfarin) and, to a lesser extent, CYP3A4 (R-warfarin metabolism). Warfarin concentration rises, with INR doubling or tripling. The effect develops gradually over 1–7 weeks and persists for weeks after amiodarone discontinuation due to its long half-life.

Management

When starting amiodarone in a patient on warfarin, empirically reduce the warfarin dose by 30–50 %. Monitor INR weekly for the first 6–8 weeks, then every 2 weeks until stable. After amiodarone discontinuation, expect warfarin requirements to rise for several more months.