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4–28 | Clinical Manual for Management of the HIV-Infected Adult/2006
Table 1. Potential and Documented Drug Interactions between Recreational Drugs and Antiretroviral Agents
Pharmacokinetics Interactions Significance Comments
Alcohol
Principally
metabolized by alcohol
dehydrogenase, but
acute use can lead to
enzyme inhibition, and
chronic use may induce
activity of CYP2E1 and
CYP3A .
With induction of CYP3A, alcohol may
increase the metabolism of PIs and
NNRTIs.
Because a common metabolic
pathway is used by abacavir, there
is theoretical concern that alcohol
may compete for metabolism,
thus increasing abacavir serum
concentrations.
Amphetamine Compounds (crystal methamphetamine)
Primarily metabolized
by cytochrome P450
(CYP2D6).
Under normal conditions,
approximately 15% of
a dose is eliminated
renally, but as urine
becomes more acidic,
the proportion excreted
renally may increase to
55%.
Amyl Nitrate (poppers)
Completely and rapidly
metabolized in the liver
by first-pass mechanism.
Inhibition of CYP2D6 can interfere
significantly with hepatic metabolism
of the amphetamine compound. Such
inhibitors include:
• Ritonavir (increases amphetamine
levels 2- to 3-fold)
• Delavirdine
• Selective serotonin reuptake
inhibitors (SSRIs) (primarily
fluoxetine, fluvoxamine, sertraline,
paroxetine)
Pharmacodynamic property of this
agent creates rapid and systemwide
vasodilation. Agents that also cause
vasodilation may create an additive
effect.
The use of erectile dysfunction (ED)
agents such as sildenafil (Viagra),
tadalafil (Cialis), vardenafil (Levitra),
and amyl nitrate may significantly
decrease cardiac circulation.
Inducing metabolism of specific
medications may result in
subtherapeutic levels, predisposing to
resistance and decreasing efficacy.
Inhibition of amphetamine
metabolism leads to increased levels
of the compound. Effects similar
to those seen with large doses
may be anticipated. Response is
variable from patient to patient and
may include intense exhilaration,
euphoria, agitation, panic, angina,
cardiovascular collapse, convulsions,
and cerebral hemorrhage.
Amphetamines do not have any
significant effect on ARV agents.
Combinations of nitrates and ED
agents can cause severe hypotension
and may lead to loss of consciousness,
ischemic angina, unstable angina,
and myocardial infarction.
Although the possibility of CYP3A
induction is of theoretical concern, there
may be little or no actual interaction
between alcohol and ARV agents.
Alcohol abuse and concomitant use of
hepatotoxic agents may increase the
risk of early and severe liver damage.
Additionally, chronic alcohol abuse in
the presence of didanosine markedly
increases the risk of pancreatitis.
There is no evidence of increased
risk of abacavir-related toxicity or
hypersensitivity reaction.
Patients who are taking ritonavir or
other potent CYP2D6 inhibitors should
be strongly urged to avoid using
amphetamine compound(s).
Nitrates and nitric oxide compounds are
contraindicated with ED agents. Caution
should be exercised with concomitant
use of other vasodilators.