Coronavirus Disease 2019 (COVID-19) outbreak caused by severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major
public health problem. The elderly people are the most affected
population by the COVID-19 outbreak in terms of mortality and morbidity.
Delirium caused by hypoxia, a prominent clinical feature of COVID-19,
may increase the need for treatment of Alzheimer’s disease (AD) patients
(1). Therefore, drug-drug interactions should be considered in AD
patients while receiving COVID-19 treatment.
AD treatment consists of cholinesterase inhibitors (ChEIs) (donepezil,
rivastigmine, galantamine) and memantine. In addition, antidepressants
and antipsychotics are used to control for behavioral and psychiatric
symptoms of patients (2). Despite ChEIs have few pharmacokinetic
drug-drug interactions, donepezil and galantamine can be affected by
specific substrates, inhibitors or inducers of the cytochrome P450
(CYP450) enzymes (such as CYP2D6, CYP3A4). Chloroquine (CQ) and
hydroxychloroquine (HCQ) are metabolized by CYP2C8, CYP2D6, CYP3A4 and
inhibits CYP2D6. Pharmacological effects of galantamine and donepezil
may increase during CQ/HCQ treatment. Azithromycin has a low risk for
CYP450 mediated drug interactions. Cardiac adverse effects (such as
bradycardia, heart block, and QT interval prolongation) may appear
related to both ChEIs and CQ/HCQ or azithromycin. Thus, more frequently
electrocardiography monitoring should be considered when concomitant
use. Lopinavir is primarily metabolized by CYP3A enzymes and ritonavir
is a potent inhibitor for CYP3A and CYP2D6. Additionally,
lopinavir-ritonavir are inhibitors of drug transporters such as
p-glycoprotein, breast cancer resistance protein, and inducers of
CYP1A2, CYP2B6, CYP2C19, CYP2C9, glucuronyl transferase enzymes.
Lopinavir-ritonavir may increase plasma concentrations of galantamine
and donepezil. Consequently, adverse reactions or toxicity risk of ChEIs
may increase. In addition, caution should be advised in terms of
bradycardia when using lopinavir-ritonavir and ChEIs together (2, 3).
Memantine undergoes limited hepatic metabolism and has a low risk for
pharmacokinetic/pharmacodynamic drug-drug interaction. Therefore,
memantine may be a safer alternative in COVID-19 treatment (2).
QT interval prolongation and ventricular arrhythmias (including Torsades
de Pointes) should be monitor in the use of azithromycin, CQ, HCQ and
lopinavir/ritonavir with antipsychotics, antidepressants. Caution may be
required when using strong CYP2D6 inhibitors (such as paroxetine and
fluoxetine) and CYP2D6 substrate CQ (2, 3). In addition, glycemic
control should be monitored as selective serotonin reuptake inhibitors
may increase the hypoglycemic effect of CQ and HCQ (4). Due to the
effect of ritonavir on a large number of drug-metabolizing enzymes, the
dose may need to be increased/decreased when used with antipsychotic and
antidepressant drugs that may potentially affect their metabolism (3,
5).
No potential interaction is expected between tocilizumab, ribavirin,
favipiravir and AD’ treatments (3). Drug interactions should be
evaluated in AD patient while receiving COVID-19 treatment. Principally,
safer COVID-19 and AD treatments should be preferred, otherwise the
patient should be closely monitored essential aspects.