HIV drug interactions Meds used in Neuropsych

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HIV drug interactionsMeds used in Neuropsych

• Joe Caperna, MD
• UCSD Owen Clinic
• Queenstown Feb 2008

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Cytochrome P450 Drug Interactions

• All Protease Inhibitors (PIs) Non-Nucleoside
  Reverse Transcriptase Inhibitors (NNRTIs) are
  substrates of cytochrome P450
• Therapeutic concerns some psychotropic
  medications (i.e. TCAs) and antiretrovirals
  (ARVs) may have narrow therapeutic indices
  (including PIs NNRTIs)
• Drug interactions b/n psychotropic medications
  ARVs may lead to resistance to not just the
  specific ARV, but all within the same drug class

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PI Drug Drug Interactions

• PI inhibition of 3A can lead to Fentanyl
  toxicity( a substrate for 3A )
• Ritonavir induces glucuronyl transferase (which
  metabolizes benzodiazepines), leading to
  decreased bioavailability of a benzo
• 3A inhibition by nefazodone and PIs lead to
  increased levels of benzos and sildenafil

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Cytochrome P450 Drug Interactions

• P450 Inhibitors (by level of potency)
• Significant ritonavir
• Moderate indinavir, nelfinavir, amprenavir,
  delaviridine
• Weak saquinavir
• P450 Inducer nevirapine (3A4)
• P450 Inhibitor Inducer efavirenz 3A4
• Co-administration of NNRTIs (efavirenz,
  delaviridine, nevirapine) and certain
  psychotropic medications (fluoxetine,
  fluvoxamine, nefazodone) may lead to toxic levels
  of NNRTIs

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Drug-drug Interactions and Norvir Kaletra

• lopinavir/ritonavir (Kaletra) , is the only
  combination PI, having ritonavir (Norvir ) as
  one of its components
• Ritonavir (Norvir ) is the ARV with the most
  potential for clinically significant psychotropic
  drug interactions
• Ritonavir is a potent cytochrome P450 3A4, 2D6,
  2C9, 2C19, 2A6, 1A2 2E1 inhibitor
• As with antipsychotic medications, when combining
  Norvir or Kaletra with psychotropics, it is
  safer to start low go slow

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Drug-drug Interactions and Ritonavir (Norvir )
Ritonavir/lopinavir (Kaletra)

• Psychotropics contraindicated due to risk of
  toxically increased drug levels
• clozapine, pimozide (incr. risk of QT interval
  prolongation), midazolam triazolam (incr. Risk
  CNS depression)
• Psychotropics with risk of increased drug levels
  reduce initial dose by at least 50
• TCAs, SSRI, bupropion, venlafaxine, maprotiline,
  trazodone, haloperidol, risperidone,
  thioridazine, chlorpromazine, ziprasidone,
  aripiprazole, buspirone, lamotrigine, zolpidem,
  diazepam, flurazepam
• nefazodone, sertraline (greater risk, reduce
  initial dose by 70)
• Psychotropics that may cause toxic Norvir or
  Kaletra drug levels via metabolic inhibition
• fluvoxamine, nefazodone, paroxetine, sertraline,
  venlafaxine, olanzapine, perphenazine,
  thioridazine

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Methadone

• Levels decreased by
• 53 Kaletra
• 60 Nevirapine
• 52 Efavirenz

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Pethadine

• Step 1 Searching by Lopinavir
• Step 2 Searching by Analgesics
• Step 3 Searching by Pethidine (Meperidine)
• Step 4 View results 
• Potential interaction that may require close
  monitoring, alteration of drug dosage or timing
  of administration
• Lopinavir Pethidine (Meperidine)
• Source hiv-druginteractions.org (liverpool)

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Warfarin

• NVP decreases INR
• EFV INR altered
• KLT INR altered

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Phenytoin

• Kaletra Decreases levels of kaletra by 33,
  decreases phenytoin by 31
• Efavirenz Decreases efavirenz, alters phenytoin
  levels
• NVP No significant interaction known
• Phenytoin contraindicated with all PIs and
  NNRTIs

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Carbemazapine

• Kaletra increased carbemazapine levels
• Nevirapine may decrease carbemazapine levels
• Efavirenz increases efv levels 36, decreases
  carbemazpine levels 27.

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Phenobarbitol

• Alters levels with kaletra efavirenz, but ?much
• ARV levels can be decreased, so contraindicated.
• No interaction with nevirapine