Módulo 1 – Curso pós-graduado – VIH e Envelhecimento

Drug-drug Interactions and Polypharmacy in Older HIV Persons

Polymedication and drug metabolism in aging patients

Autor: Marta Boffito, MD PhD (Chelsea and Westminster Hospital, London, UK)

Clinical approach to the polymedicated patient (an example)

In a first consultation of a polymedicated patient, it is advisable to perform a medication review to identify potential interactions or other drug-related events. Table I shows an example of a case in which medication review is particularly relevant.

Table I. Clinical case (example)

tudo sobre o hiv, sintomas do hiv e prevenção - vihda
tudo sobre o hiv, sintomas do hiv e prevenção - vihda

The evaluation of drug-drug interactions is particularly relevant for patients on regimens with ritonavir. In this case, the patient presents hypertension that needs to be treated. According to the National Institute for Health and Care Excellence (NICE) recommendations, calcium-channel blockers (CCB) are the pre- ferred class in patients over 55 years. However, there is little information about interactions of this class of antihypertensive with antiretroviral drugs.

  • The interaction between ATV and diltiazem is known and probably due to inhibition of CYP3A4, thus resulting in increased diltiazem levels with the unboosted ATV and marked decrease of diltiazem when ATV is boosted with ritonavir;4
  • Co-administration of boosted protease inhibitors (PI) and amlodipine may induce an increase in amlodipine concentrations that require dose adjustment – because the adverse effects of amlodipine are mostly dose dependent.5 Thus, it is important to monitor effectiveness (for low doses) and toxicity of amlodipine 10 mg daily;
  • A pharmacokinetic study showed no interaction between raltegravir (RAL) and amlodipine.6

By consulting the University of Liverpool website (http://www. hiv-druginteractions.org/Interactions.aspx), we can confirm that co-administration of CCB and PI, non-nucleoside reverse transcriptase inhibitors or elvitegravir (EVG) /cobicistat (cobicistat inhibits CYP3A4) should be cautious and monitored. Interactions are less likely to occur with concomitant use of integrase inhibitors. Other antihypertensive drugs, such as ramipril, enalapril, perindopril, seem to be safer when used concomitantly with different antiretroviral classes.

In our case, the patient had untreated hay fever. The use of corticosteroids with ritonavir increases the risk of iatrogenic Cushing. The fluticasone or mometasone, used in nasal sprays are absorbed systemically and partly metabolized by CYP3A4. In the presence of ritonavir, the prolonged use of steroids for two to four weeks may lead to an increase in systemic levels of these drugs. Beclomethasone is the only corticosteroid with a good safety profile when used with ritonavir.

The use of steroids in the treatment of joint inflammatory pain of inflammatory is also complex. For example, the intra-articular administered triamcinolone is also metabolized by CYP3A4, and has resulted in serious cases of toxicity and iatrogenic Cushing with concomitant use of ritonavir. This effect is very long and it is questionable whether it is preferable to discontinue ritonavir.

The inter-individual variability can affect the outcome of a given interaction. Furthermore, the number of medications which the patient takes also affects this variability. Thus, despite the information available on the University of Liverpool website be a useful tool, clinical experience is key.

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