- Ivabradine is extensively metabolized by CYP3A4 and has significant pharmacokinetic interactions with lopinavir/ritonavir, making concurrent use contraindicated.
- Combining these drugs can lead to significantly increased plasma concentrations of ivabradine, potentially causing severe bradycardia.

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- Anticoagulants and antiplatelet drugs
- Lipid lowering drugs
- Anti-hypertensives
- Drugs in heart failure
- Drugs in angina pectoris
- Anti-arrhythmic drugs
- Oral anti-diabetics

Drugs in Cardiovascular Disease

- Use of low molecular weight or unfractionated heparin recommended depending on the situation
- Antivitamin K and DOACs are not recommended 
- Effects of some drugs may be reduced in effect by combination with enzyme inhibitors like lopinavir

Anticoagulants and antiplatelet drugs

- Statin toxicity can be increased by additive effects in combination with lopinavir
- Monitoring is necessary and statin dosage may have to be reduced
- Pravastatin is least prone to interactions

Lipid lowering drugs

- Combining eplerenone with lopinavir/ritonavir (lopinavir/r) increases the plasma exposure of eplerenone.
- Replacing eplerenone with spironolactone is worth consideration to mitigate this drug-drug interaction.

Drugs in heart failure

Anti-hypertensive drugs exhibit varying pharmacokinetic interactions with COVID-19 treatments. While sartans and diuretics are not prone to significant interactions, combining calcium channel blockers (CCBs) or beta blockers with lopinavir/ritonavir (lopinavir/r) can increase the plasma exposure of the anti-hypertensives. Furthermore, hydroxychloroquine can also increase the exposure of beta blockers. The concurrent use of the beta blocker metoprolol with lopinavir/r is contraindicated.

Anti-hypertensive Interactions with Lopinavir/ritonavir and Hydroxychloroquine

Interaction of Ivabradine with Lopinavir/ritonavir

Lopinavir/ritonavir can increase exposure to the class I anti-arrhythmic drugs quinidine and propafenone, potentially causing cardiac disorders; ECG monitoring is required. Combining lopinavir/ritonavir with class III anti-arrhythmic drugs such as amiodarone is contraindicated because of the increased risk of torsades de pointes.

Interactions of Anti-arrhythmic Drugs with Lopinavir/Ritonavir

Lopinavir/ritonavir can cause hyperglycemia and increase the exposure and concentration of gliptins, while ritonavir can reduce sulfonylurea exposure. Hydroxychloroquine can worsen hypoglycemia. Oral antidiabetic treatment in patients with COVID-19 receiving these drugs therefore requires case-by-case assessment.

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