Correction to: Older HIV-infected adults: complex patients (III)—polypharmacy
- 01.06.2019
- Correction
Erschienen in:
- Verfasst von
- Samuel F. Freedman
- Carrie Johnston
- John J. Faragon
- Eugenia L. Siegler
- Tessa Del Carmen
- Erschienen in
- European Geriatric Medicine | Ausgabe 3/2019
Auszug
The original version of this article unfortunately contained a mistake. In Table 2, the dosing of tenofovir-containing medication was incorrect: For TAF, no dose adjustment is required for patients with CrCl 30 ml/min or higher. When CrCl is < 30 ml/min, TAF is not recommended. For TDF, providers should dose adjust if CrCl is < 50 mL/min. The corrected Table 2 is given below.
…
Table 2
ARV adverse effects, geriatric considerations, and drug interactions by drug class
|
Drug class
|
Medication
|
Adverse effects
|
Geriatric considerations
|
Drug interactions
|
|---|---|---|---|---|
|
Integrase strand transfer inhibitors (INSTI)
|
Generally well tolerated as a class. Reports of 4–10% of patients with CNS and/or GI side effects in some series, Bictegravir with lowest side effect profile [21]
|
Oral absorption reduced when co-administered with calcium, aluminum or magnesium antacids, or calcium or iron supplements. If the above medications must be used, INSTI can be given while fasting 2 h before, or in some cases, given simultaneously with food [22]
|
||
|
Bictegravir
|
Few; < 2% of patients with side effects including dyspepsia, flatulence, vomiting, abdominal pain
|
Not recommended with CrCl < 30 mL/min
Increases tubular secretion of creatinine without changing GFR, therefore may have transient (< 4 week) increase in serum Cr
|
CYP3A4 substrate
Should not be used with rifamycins, St. John’s Wort, and anticonvulsants known to induce CYP3A4 [22]
Inhibits OCT2 and MATE1 drug transporters; contraindicated with the antiarrhythmic dofetilide, as it will increase the concentration of antiarrhythmic
Can increase concentration of metformin [20]
|
|
|
Dolutegravir
|
CNS
GI
|
Can cause sleep disturbances, headache, fatigue, malaise, altered mood, insomnia, nightmares
Lowest risk of GI side effects [21]
|
CYP3A4 substrate
Should not be used with rifampin, St. John’s Wort, and anticonvulsants known to induce CYP3A4 [22]
Inhibits OCT2 and MATE1 drug transporters; contraindicated with the antiarrhythmic dofetilide as it will increase the concentration of antiarrhythmic
Can significantly increase concentration of metformin, consider dosage reduction for metformin
|
|
|
Elvitegravir
|
GI Upset
CNS
|
GI side effects of nausea, vomiting and diarrhea
CNS fatigue, headache, sleep disturbance
|
Only available co-formulated with cobicistat pharmacokinetic enhancer, therefore CYP3A4 inhibition
Elvitegravir is a UGT1A1 substrate [20]
|
|
|
Raltegravir
|
GI upset
CNS
|
Lowest CNS side effect profile. GI side effects of nausea, vomiting and diarrhea
Rare reports of myopathy and rhabdomyolysis. Avoid in patients with history of myopathy
Nausea, headache, diarrhea, insomnia, depression
|
Lowest risk of drug interactions. Not a substrate of Cytochrome P450 system. Metabolized by UGT1A1-mediated glucuronidation
Co-administration of raltegravir with drug that is inducer of UGT1A1 may reduce plasma concentration of raltegravir (i.e. rifampin)
|
|
|
Nucleoside reverse transcriptase inhibitors (NRTI)
|
Most are renally metabolized and not affected by liver dysfunction
|
|||
|
Tenofovir
|
Rare lactic acidosis and hepatic failure
Also treats HBV, flare-up of HBV if tenofovir discontinued
|
TAF with improved GFR and hip/spine bone mineral density (BMD) compared to TDF [24]
|
||
|
Alafenamide (TAF)
|
Headache most common side effect. < 10% of patients with abdominal pain, fatigue, malaise
|
For TAF, no dose adjustment is required for patients with CrCl 30ml/min or higher. When CrCl is <30 ml/min, TAF is not recommended
|
Drugs which affect P-glycoprotein and BCRP will change tenofovir concentration. Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital and phenytoin will decrease concentration of tenofovir. Rifamycins and St. John’s Wort also decrease concentration of tenofovir [20]
|
|
|
Disoproxil fumarate (TDF)
|
Decreased GFR. Rare cases of acute renal failure and Fanconi syndrome
Reduced BMD and increased risk for osteoporotic fracture [23]
|
For TDF, providers should dose adjust if CrCl is <50 mL/min
|
||
|
Emtricitabine (FTC)
|
Rare lactic acidosis and hepatic failure
Also treats HBV, flare-up of HBV if emtricitabine discontinued
10–15% of patients report headache, diarrhea, nausea, fatigue, dizziness, abnormal dreams, abdominal pain, cough, rhinitis, rash
|
Dose adjust for GFR < 50 mL/min
|
||
|
Lamivudine (3TC)
|
Rare lactic acidosis and hepatic failure
Also treats HBV, flare-up of HBV if Lamivudine discontinued
Headache, nausea, malaise, fatigue, rhinorrhea, diarrhea, and cough most common side effects
|
Dose adjust for CrCl < 50 mL/min
|
||
|
Abacavir (ABC)
|
Hypersensitivity reaction, increased risk if HLA-B5701 (General prevalence ~ 5% of population, most common in Caucasian males) [25]
Cardiac riska: > 2-fold risk of CVD reported in case series [26]
|
Cardiac riska
Hypersensitivity reaction
|
||
|
Zidovudine
|
Anemia, neutropenia
Fatigue
Lipodystrophy
|
Rarely used
|
||
|
Non-nucleoside reverse transcriptase inhibitors (NNRTI)
|
CNS effects and rash most common
|
Generally act as CYP450 3A4 inducers, therefore interact with Rifampin, azoles, AEDs, statins, midazolam, ergotamines and other HIV medications when used concurrently [20]
Caution dosing antiplatelet agents i.e.: clopidogrel, prasugrel, ticagrelor with NNRTIs. Ticagrelor should not be given with any NNRTI
|
||
|
Efavirenz
|
CNS effects, suicidality, rash
|
Mental health, specifically suicidality increased in trial data of efavirenz as initial regimen [27]
Absorption improved when taken with a full meal
|
Inhibits CYP450 2C9, 2C19, and 3A4
Significant decreases in concentration of methadone, voriconazole, rifabutin
Reduces concentration of clopidogrel metabolite [28], consider prasugrel for platelet inhibition
|
|
|
Rilpivirine
|
Poor absorption with proton pump inhibitors (PPIs)
|
Avoid if VL > 100 k copies/mL or CD4 < 200 cells/mm3
Needs to be taken with food
|
Substrate of CYP450 system, low risk of drug interactions
Concurrent PPIs contraindicated
Can be given with clopidogrel without dose adjustment
|
|
|
Nevirapine
|
Hepatotoxicity
Hypersensitivity reaction
|
No longer used commonly
|
Can be given with clopidogrel without dose adjustment
|
|
|
Doravirine
|
Generally well tolerated. Nausea, dizziness, headache, fatigue, diarrhea, abdominal pain, abnormal dreams possible
|
Cannot be given with strong CYP3A4 inducers; anticonvulsants, enzalutamide (androgen receptor inhibitor), rifampin, St. John’s wort
|
||
|
Etravirine
|
Rash, rare cases of SJS.
Fat redistribution
Peripheral neuropathy
|
Inducer of CYP3A and inhibitor of CYP2C9, CYP2C19 and P-glycoprotein
Reduces concentration of active metabolite for clopidogrel, if platelet inhibitor needed consider prasugrel [20]
|
||
|
Protease inhibitors (PI)
|
Most common side effects in this class are GI and hyperlipidemia (HLD)
Most commonly in “boosted” formulations
|
PIs may be “boosted” with pharmacokinetic enhancers ritonavir or cobicistat, which are potent CYP450 inhibitors
|
Ritonavir and cobicistat are CYP450 3A4 inhibitors
See Table 3 for more detailed medication interactions
Warfarin can be used, INR may be decreased—requires close monitoring
Caution with concurrent use of Direct-Acting Oral Anticoagulants (DOACs)
|
|
|
Darunavir
|
Skin rash
Diarrhea
Nausea/vomiting
Headache
|
Dosed alone or “boosted”
Often used if high resistance or in very treatment-experienced patients
|
See Table 3 about “boosting” agents
Darunavir contains a sulfonamide moiety, use with caution in patients with sulfa allergy
|
|
|
Atazanavir
|
Increased indirect bilirubin
GI upset
Kidney stones
|
“Boosted” with ritonavir or cobicistat
|
See Table III about “boosting” agents
|
|
|
Lopinavir
|
Diarrhea
HLD
|
“Boosted” with ritonavir
|
See Table III about “boosting” agents
|
|
|
Fusion inhibitors
|
||||
|
Enfuvirtide Injection
|
Injection site reaction
|
Rarely used
May be difficult to inject into subcutaneous tissue in thin/frail individuals
|
||
|
CCR5 antagonist
|
||||
|
Maraviroc
|
Hepatotoxicity, in some cases preceded by allergic/IgE reaction
|
CYP450 substrate, therefore reduce dose when given with potent CYP3A4 inhibitor, increase dose when given with CYP3A4 inducer
|
||
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- Titel
- Correction to: Older HIV-infected adults: complex patients (III)—polypharmacy
- Verfasst von
-
Samuel F. Freedman
Carrie Johnston
John J. Faragon
Eugenia L. Siegler
Tessa Del Carmen
- Publikationsdatum
- 01.06.2019
- Verlag
- Springer International Publishing
- Erschienen in
-
European Geriatric Medicine / Ausgabe 3/2019
Elektronische ISSN: 1878-7657 - DOI
- https://doi.org/10.1007/s41999-019-00195-z
