3 Management Of HIV Infection Essays

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Management of HIV Infection – Exam 4 – April 5, 2012 [Lecture 3]

Note: This is a continuation of the Management of HIV Infection lecture on April 3rd. The lecture begins on the second slide of page 27 in the handout in class.

Side Effects of NNRTIs – Drug Specific
Sustiva (Efavirenz)
Sustiva is capable of causing CNS side effects: including dizziness, drowsiness, sleepiness, insomnia, vivid dreams, nightmares, and hallucinations
These side effects occur shortly after a patient initiates Sustiva base therapy and could last up to four weeks
After four weeks, these side effects usually subdue and the patient experiences these side effects less frequently tolerance
Individuals who have certain genomic polymorphisms, more specifically, mutations in the COIP OV 6 enzyme which is responsible for metabolizing Sustiva, may have longer duration of these side effects or may at be at higher risk for these side effects
If the enzyme COIP OV 6 is malfunctioning in anyway, this allows Sustiva to build up in the patient cause CNS side effects
It is important to counsel the patient to take Sustiva at bedtime so the side effects will be resolved by the time they are awake
It is also important to counsel the patient to take the drug on an empty stomach or space the meal out by about 1 to 2 hours
Sustiva is a very lipophilic drug, and is capable of crossing the blood brain barrier

Side effects of NNRTIs – Drug Specific
Edurant (Rilpivirine) and Intelence (Etravirine)
Unlike Sustiva, administration of Edurant and Intelence during consumption of a meal is actually beneficial
Concurrent administration of Edurant or Intelence during a meal helps enhance absorption of the drug
Without food, the absorption of the drug is actually 50% lower compared to concurrent administration with food
It is extremely important to inform the patient to take Edurant or Intelence shortly after consumption of a meal or with a meal

Pharmacokinetics of NNRTIs
All NNRTIs are substrates for the enzyme CYP3A4
This means that other medications which may be inhibitors or inducers of CYP3A4 are capable of altering NNRTI levels
All of the NNRTIs currently available are also inducers of the enzyme CYP3A4
Viramune and Edurant are used in smaller doses to prevent induction of CYP3A4
All other NNRTIs (excluding Viramune, and Edurant) are potent inducers
For instance, Sustiva has a potent inducer and has an extremely long half life, thus we can expect to see some of the induction effects of the medication weeks after the patient has stop taking the medication completely
Intelence, similar to Sustiva, is also a potent inducer of CYP3A4

Pharmacokinetics of NNRTIs
Edurant (Rilpivirine)
Edurant has a very specific requirement for absorption, more specifically it requires an acidic environment
This means that patients should take Edurant with a meal, or shortly following a meal

Drug Interactions with NNRTIs (TB Drugs)
Rifampin is an inducer
If a patient is on these medications along with an NNRTI such as Sustiva, then we could expect to see a decrease in Sustiva levels, and thus we may need to monitor the patient more closely and consider increasing the dose if need be
It is not recommended to take Viramune, Intelence, and Endurant with Rifampin due to the fact that it greatly decreases the levels of these drugs when used concurrently
Rifabutin is a derivative of Rifampin which has lower drug interaction capabilities
Patients made still need dose adjustments with this medication under certain circumstances
For instance, Sustiva can lower Rifabutin levels, and consequently the patient may require a higher dosing of Rifabutin
Similar to the case of Rifampin, it is not recommended to take rifabutin concurrently with Edurant
Voriconazole displays a bi-directional drug interaction
NNRTI’s such as Sustiva, plasmatic levels can increase by 44% in the presence of Voriconazole
Voriconazole plasmatic levels can also decrease by 77% in the presence of Sustiva
For
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