Table 2.
List of registered potential interactions associated with LPV/r by drug, therapeutic group, severity, frequency, interaction mechanism, effect, and recommendation.
| Drug (ATC) | Risk level | N (%) | Mechanism | Effect | Recommendationa |
|---|---|---|---|---|---|
| Antiemetics | |||||
| Domperidone | X | 3 (0.82) | CYP3A4 inhibition. QT prolongation | ↑ Dc. Cardiovascular toxicity risk, ventricular arrhythmia (TdP) | Contraindicated. Consider change to metoclopramide |
| Antidiabetic | |||||
| Glibenclamide | C | 2 (0.54) | CYP3A4 and 2D6 inhibitionb | ↑ Dc. Risk of hypoglycaemia | Reduce dosage. Monitor glucose. |
| Gliclazide | C | 1 (0.27) | Induction of CYP2C9 and 2C19b | ↓ Dc. Risk of hyperglycaemia | Increase dosage. Monitor glucose. |
| Repaglinide | C | 1 (0.27) | Inhibition of CYP3A4 and OATP1B1 transporter inhibition. | ↑ Dc. Risk of hypoglycaemia | Reduce dosage. Monitor glucose. |
| Canagliflozin | D | 1 (0.27) | Induction of UGT1A9 and 2B4 | ↓ Dc. Risk of hyperglycaemia | If GFR > 60 mL/min, increase dose to 200 mg or 300 mg. Monitor glucose. |
| If GFR < 60 mL/min, consider another antidiabetic. | |||||
| Anticoagulants | |||||
| Apixaban | D | 5 (1.36) | CYP3A4 inhibition. P-glycoprotein inhibition | ↑ Dc. Risk of bleeding | Change to LMWH at therapeutic doses. |
| Rivaroxaban | X | 3 (0.82) | Contraindicated. Change to LMWH at therapeutic doses. | ||
| Edoxaban | D | 3 (0.82) | P-glycoprotein inhibition | Reduce dose to 30 mg or switch to LMWH at therapeutic doses. | |
| Acenocoumarol | C | 11 (2.99) | CYP2C9 induction | ↓ Dc. Thrombotic risk | Change to LMWH at therapeutic doses. |
| Antiplatelet | |||||
| Clopidogrel | C | 15 (4.08) | Inhibition of CYP3A4, (2B6, 2C9 and 1A2)b | ↓ Dc (active metabolite). Thrombotic risk | Switch to ASA (monotherapy), switch to prasugrel (dual therapy) |
| Ticagrelor | X | 2 (0.54) | CYP3A4 inhibition | Dc. Risk of bleeding | Contraindicated. Switch to ASA monotherapy, switch to prasugrel (dual therapy) |
| Antihypertensive | |||||
| Doxazosin | D | 4 (1.09) | CYP3A4 inhibition | ↑ Dc. Risk of hypotension | Reduce dosage. Monitor BP |
| Amlodipine | C | 24 (6.52) | CYP3A4 inhibition. Prolonged PR | ↑ Dc. Risk of hypotension and AV block | Reduce dose 50%. Monitor BP and ECG. |
| Nifedipine | D | 5 (1.36) | Reduce dosage. Monitor BP and ECG. | ||
| Manidipine | D | 3 (0.82) | Reduce dosage. Monitor BP and ECG. | ||
| Lercanidipine | X | 2 (0.54) | Contraindicated. Change to amlodipine with a 50% dose reduction. | ||
| Other cardiovascular drugs | |||||
| Digoxin | D | 2 (0.54) | P-glycoprotein inhibition. Prolonged PR | ↑ Dc. Risk of digitalis poisoning | Reduce dose between 30%−50% or reduce frequency. Monitor for digoxin levels. |
| Ivabradine | X | 1 (0.27) | CYP3A4 inhibition | ↑ Dc. Bradycardia risk | Contraindicated. |
| Ranolazine (C01EB18) | X | 2 (0.54) | CYP3A4 inhibition. QT prolongation | ↑ Dc. Risk of bradycardia, hypotension, ventricular arrhythmia (TdP) | Contraindicated. |
| Antiarrhythmics | |||||
| Amiodarone | X | 5 (1.36) | CYP3A4 inhibition. QT prolongation | ↑ Dc. Risk of ventricular arrhythmia | Contraindicated. Close monitoring, ECG |
| Flecainide | X | 1 (0.27) | |||
| Propafenone | X | 3 (0.82) | CYP3A4 and 2D6 inhibitionb | Close monitoring, ECG | |
| Diltiazem | D | 2 (0.54) | CYP3A4 inhibition. Prolonged PR | ↑ Dc. Risk of AV block, bradycardia and increased negative inotropic effect | Reduce dosage. ECG. |
| Verapamil | D | 6 (1.63) | |||
| Lipid-lowering drugs (statins) | |||||
| Atorvastatin | D | 26 (7.07) | CYP3A4 inhibition | ↑ Dc. Risk of liver toxicity and rhabdomyolysis | Maximum dose 20 mg |
| Lovastatin | X | 1 (0.27) | Contraindicated. Switch to pravastatin or pitavastatin | ||
| Simvastatin | X | 35 (9.51) | Contraindicated. Switch to pravastatin or pitavastatin | ||
| Rosuvastatin | D | 3 (0.82) | BCRP and OATP1B1 transporter inhibition | Maximum dose 10 mg | |
| Urological | |||||
| Tamsulosin | X | 18 (4.89) | CYP3A4 and 2D6 inhibitionb | ↑ Dc. Risk of hypotension | Maximum dose of 0.4 mg/day. Monitor BP |
| Solifenacin | D | 1 (0.27) | CYP3A4 inhibition. | ↑ Dc. Risk of anticholinergic toxicity | Maximum dose 5 mg/day. Monitor anticholinergic effects |
| Corticosteroids | |||||
| Methylprednisolone | D | 23 (6.25) | CYP3A4 inhibition | ↑ Dc. Risk of Cushing's syndrome | Reduce dose |
| Prednisone | C | 5 (1.36) | |||
| Dexamethasone | D | 1 (0.27) | CYP3A4 inhibition (LPV/r) | ||
| CYP3A4 induction (dexamethasone) | ↓ LPV/r. Decreased efficacy | ||||
| Antimicrobial | |||||
| Clarithromycin | D | 6 (1.63) | CYP3A4 inhibition. QT prolongation | ↑ Dc. Risk of ventricular arrhythmia (TdP) | If GFR 30−60 ml/min, reduce dose to 500 mg/24 h |
| If GFR < 30 mL/min, reduce the dose to 250 mg/24 h | |||||
| Metronidazole | X | 1 (0.27) | LPV/r oral solution contains alcohol. | Disulfiram reaction risk | Contraindicated with the oral solution. No tablets |
| Antioestrogens | |||||
| Tamoxifen | D | 3 (0.82) | CYP3A4 and 2D6 inhibitionb | ↓ AMC. Decreased oestrogen modulating effect | |
| Muscle relaxants | |||||
| Fentanyl iv | D | 4 (1.09) | CYP3A4 inhibition | ↑ Dc. Risk of respiratory depression | Reduce dose to 25−50 mcg/h. Monitor pain (ANI, NOL) |
| Midazolam iv | D | 24 (6.52) | ↑ Dc. Risk of respiratory depression and excess sedation. | Do not exceed > 25 mg/kg/h). Monitor depth of sedation (BIS). | |
| Opioid pain relievers | |||||
| Fentanyl oral/patch | D | 2 (0.54) | CYP3A4 inhibition | ↑ Dc. Risk of sedation and respiratory depression. | Reduce dose |
| Oxycodone | D | 1 (0.27) | CYP3A4 and 2D6 inhibitionb | ↑ Dc. Risk of sedation and respiratory depression. | |
| Anticonvulsants | |||||
| Carbamazepine | D | 1 (0.27) | CYP3A4 inhibition (LPV/r) | ↑ Dc. CNS toxicity risk. | Administer LPV/r, at least 2 times a day and consider increasing the dose. Monitor carbamazepine levels and adjust dose. |
| CYP3A4 (carbamazepine) induction | ↓ LPV/r. Decreased antiviral effect | ||||
| Phenytoin | D | 1 (0.27) | CYP2C9 and 2C19 induction (LPV/r) | ↓ Dc. Decreased anticonvulsant effect | Administer LPV/r, at least 2 times a day and consider increasing the dose. Monitor phenytoin levels and adjust dose |
| CYP3A (phenytoin) induction | ↓ LPV/r. Decreased antiviral effect | ||||
| Clonazepam | D | 5 (1.36) | CYP3A4 inhibition | ↑ Dc. Risk of sedation and drowsiness. | Reduce dose |
| Hypnotic/sedatives | |||||
| Alprazolam | D | 10 (2.72) | Inhibition of CYP3A4 and P-glycoprotein | ↑ Dc. Risk of sedation and respiratory depression. | Start low dose and increase as needed. |
| Clorazepate | C | 3 (0.82) | Reduce dosage. | ||
| Diazepam | D | 15 (4.08) | CYP3A4 and C219 inhibitionb | Avoid. Reduce dosage. | |
| Neuroleptics | |||||
| Haloperidol | D | 8 (2.17) | CYP3A4, 2D6b inhibition and glucuronidation (UGT2B7 > 1A4 and 1A9). QT prolongation. | ↑ Dc. CNS toxicity risk. Risk of ventricular arrhythmia (TdP) | Avoid in the elderly. Reduce dosage. Monitor CNS effects. ECG. |
| Quetiapine | D | 11 (2.99) | CYP3A4 and 2D6 inhibitionb. QT prolongation | Avoid in the elderly. In schizophrenia, in young patients with high doses, consider reducing 1/6 of the dose. Monitor CNS effects. ECG | |
| Antidepressants | |||||
| Trazodone | D | 6 (1.63) | CYP3A4 inhibition. QT prolongation | ↑ Dc. Risk of CNS, gastric and cardiovascular toxicity. | Reduce 50%−75% dose |
| [0.1−6]Inhaled therapy | |||||
| Budesonide | D | 42 (11.41) | CYP3A4 inhibition | ↑ Dc. Risk of Cushing's syndrome. | Maximum dose 2 inhalations/12 h. Consider beclomethasone |
| Fluticasone | D | 1 (0.27) | Reduce dosage. Consider beclomethasone | ||
| Salmeterol | X | 1 (0.27) | CYP3A4 inhibition. QT prolongation | ↑ Dc. Cardiovascular toxicity risk: tachycardia and ventricular arrhythmia (TdP) | Contraindicated. Consider salbutamol |
| Antihistamines | |||||
| Ebastine | D | 1 (0.27) | CYP3A4 inhibition | ↑ Dc. Risk of drowsiness, xerostomia, and headache | Reduce dosage. Consider dexchlorpheniramine |
ASA: acetylsalicylic acid; ANI: analgesia nociception index; AV: atrioventricular; Dc: drug concentration; AMC: active metabolite concentration; CYP: cytochrome P450; ECG: electrocardiogram; GFR: glomerular filtration rate; LMWH: low molecular weight heparin; LPV/r: lopinavir/ritonavir; NOL: nociception index level; PR: PR interval; QT: QT interval; CNS: central nervous system; BP: blood pressure; TdP: torsade de pointes; UGT: UDP-glucuronyl transferases.
a
Recommendations for concomitant treatment with LPV/r.
b
At therapeutic concentrations LPV/r does not inhibit: CYP2D6, 2C9, 2C19, 2CE1, 2B6, and 1A2.