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| Drugs | Risk level | N (%) | Interaction (potential) | Mechanism/effect |
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| Hydrochlorothiazide | C | 16 (26.2) | Lopinavir + ritonavir
Chloroquine
Interferon alpha-2b | Hydrochlorothiazide can cause electrolyte disturbances and thereby increase the risk of QT interval prolongation. Thus, caution and electrolyte monitoring are needed when administering lopinavir and chloroquine
The risk or severity of neutropenia and thrombocytopenia can be increased when hydrochlorothiazide is combined with interferon alpha-2b |
| Antihypertensive |
| Amlodipine | C | 7 (11.47) | Lopinavir + ritonavir
Chloroquine | Chloroquine will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or use an alternate drug
Lopinavir will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use caution/monitor |
| Propranolol | C | 1 (1.64) | Lopinavir + ritonavir | Propranolol is metabolized by 3 routes (aromatic hydroxylation by CYP2D6, N-dealkylation, followed by side chain hydroxylation via CYPs 1A2, 2C19, 2D6, and direct glucuronidation). Lopinavir could potentially increase propranolol concentrations, although to a moderate extent |
| Antianginas-coronary vasodilator |
| Dinitrate of isosorbide | D | 1 (1.64) | Lopinavir + ritonavir | Lopinavir will increase the level or effect of isosorbide dinitrate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or use an alternate drug |
| Anti-arrhythmic |
| Verapamil | D | 1 (1.64) | Lopinavir + ritonavir | Lopinavir will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or use an alternate drug |
| Propafenone | C | 1 (1.64) | Lopinavir + ritonavir
Chloroquine | Propafenone is metabolized mainly by CYP2D6 and to a lesser extent by CYP1A2 and CYP3A4. Use with caution and therapeutic monitoring of propafenone is recommended. Note that both drugs (ritonavir-lopinavir) have risks of QT prolongation and/or TdP
Chloroquine will increase the level or effect of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Use caution/monitor. Chloroquine increases the toxicity of propafenone by QTc interval. Use caution/monitor |
| Digoxin | C | 1 (1.64) | Lopinavir + ritonavir | P-glycoprotein inhibition. Prolonged PR clinical and therapeutic drug monitoring of digoxin concentrations is recommended |
| Platelet antiaggregate |
| Clopidogrel | D | 1 (1.64) | Lopinavir + ritonavir | Inhibition of CYP3A4, (2B6, 2C9, and 1A2) decreased the AUC and cmax of clopidogrel’s active metabolite by 51% and 48%. Thrombotic risk, an alternative antiplatelet agent should be considered |
| Hypoglycemic |
| Glimepiride | C | 2 (3.4) | Lopinavir + ritonavir
Chloroquine | Glimepiride is mainly metabolized by CYP2C9: lopinavir decreases the effects of glimepiride as a modest inducer of CYP2C9. Risk of hyperglycemia due to insulin resistance with protease inhibitors as chloroquine may enhance the effects of a hypoglycemic treatment, a decrease in doses of insulin or other antidiabetic drugs may be required |
| Glibenclamide | C | 1 (1.64) | Lopinavir + ritonavir
Chloroquine | Glibenclamide is mainly metabolized by CYP3A4 and, to a lesser extent, by CYP2C9. Lopinavir/ritonavir could potentially increase glibenclamide concentrations by CYP3A4 and 2D6 inhibition. Risk of hypoglycaemia as chloroquine may enhance the effects of a hypoglycemic treatment, a decrease in doses of insulin or other antidiabetic drugs may be required |
| Antihistaminic |
| Loratadine | C | 5 (8.19) | Lopinavir + ritonavir
Chloroquine | Lopinavir-ritonavir oral will increase the level or effect of loratadine oral by altering drug metabolism
Monitoring is required chloroquine metabolism can be decreased when combined with loratadine |
| Cimetidine | D | 1 (1.64) | Lopinavir + ritonavir | Cimetidine increases levels of chloroquine by decreasing metabolism. Avoid or use an alternate drug
Cimetidine will increase the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or use an alternate drug |
| Corticosteroid |
| Prednisone | C | 7 (11.47) | Lopinavir + ritonavir | Prednisone will decrease the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use caution/monitor |
| Hydrocortisone | C | 1 (1.64) | Lopinavir + ritonavir | Hydrocortisone will decrease the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use caution/monitor |
| Anticonvulsant |
| Carbamazepine | D | 2 (3.41) | Lopinavir
Chloroquine | Carbamazepine will decrease the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or use an alternate drug
Carbamazepine will decrease the level or effect of chloroquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use caution/monitor |
| Lamotrigine | C | 1 (1.64) | Lopinavir + ritonavir | Lopinavir will decrease the level or effect of lamotrigine by increasing metabolism. Use caution/monitor. Combination may decrease lamotrigine levels by 50%. Adjust lamotrigine dose as needed when starting, stopping, or changing lopinavir/ritonavir dose |
| Sodium valproate | D | 2 (3.41) | Lopinavir + ritonavir | Ritonavir may decrease the blood levels and effects of valproate. Moderately clinically significant. Usually avoid combinations; use it only under special circumstances |
| Clonazepam | D | 3 (4.92) | Lopinavir + ritonavir | Lopinavir increases levels of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify therapy/monitor closely. Potential for increased toxicity. Use alternatives if available. Consider lowering benzodiazepine dose |
| Hypnotic/sedatives |
| Chlordiazepoxide | D | 2 (3.41) | Lopinavir + ritonavir | Lopinavir increases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify therapy/monitor closely. Use alternatives if available. Consider lowering benzodiazepine dose |
| Alprazolam | D | 1 (1.64) | Lopinavir + ritonavir | Lopinavir will increase the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or use an alternate drug |
| Diazepam | D | 1 (1.64) | Lopinavir + ritonavir | Lopinavir increases levels of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify therapy/monitor closely. Use alternatives if available |
| Clobazam | D | 1 (1.64) | Lopinavir + ritonavir
Chloroquine | CYP3A4 inhibition by lopinavir/ritonavir may increase clobazam exposure and prolong the duration of its effect, clobazam will increase the level or effect of chloroquine by affecting hepatic enzyme CYP2D6 metabolism. Use caution/monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly |
| Antidepressant |
| Amitriptyline | D | 2 (3.41) | Lopinavir + ritonavir
chloroquine | Lopinavir/ritonavir could potentially increase amitriptyline exposure although to a moderate extent. No a priori dosage adjustment is recommended but monitor adverse effects
Chloroquine increases the toxicity of amitriptyline by QTc interval. Use caution/monitor |
| Sertraline | C | 1 (1.64) | Lopinavir + ritonavir | Lopinavir increases levels of sertraline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use caution/monitor. Potential for increased toxicity. Chloroquine increases the toxicity of sertraline by QTc interval. Minor/significance unknown |
| Antipsychotic |
| Pimozide | X | 1 (1.64) | Lopinavir + ritonavir
Chloroquine | Chloroquine increases toxicity of pimozide by QTc interval. Contraindicated
Lopinavir will increase the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated |
| Nonsteroidal anti-inflammatory drugs (NSAIDs) |
| Metamizole (dipirone) | C/D | 9 (14.75) | Lopinavir + ritonavir | Metamizole is a moderate inducer of CYP3A4 and a strong inducer of CYP2B6. The risk or severity of nephrotoxicity can be increased when lopinavir is combined with metamizole also increased risk of haematological toxicity had to be considered |
| Opioid |
| Tramadol | C | 1 (1.64) | Lopinavir + ritonavir
Chloroquine | Lopinavir will increase the level or effect of tramadol by affecting hepatic/intestinal enzyme CYP3A4 metabolism
Tramadol is metabolized by multiple CYPs 3A4, 2B6, and 2D6. Chloroquine is a moderate inhibitor of CYP2D6. It will also increase the level or effect of tramadol |
| Antimicrobial |
| Ciprofloxacin | C | 1 (1.64) | Chloroquine | Coadministration of ciprofloxacin (500 mg) with chloroquine (600 mg) decreased ciprofloxacin cmax and AUC by 18% and 43%, respectively. Chloroquine and ciprofloxacin both increase QTc interval. Use caution/monitor |
| Oral anticonceptive |
| Levonogestrel | D | 2 (3.27) | Lopinavir + ritonavir | Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent; coadministration is predicted to increase levonorgestrel |
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