Basic
Informations
Selzentry is a CCR5-blocking
entry inhibitor manufactured by ViiV Healthcare. It was approved by
the U.S. Food and Drug Administration (FDA) in August 2007.
Selzentry is approved for treatment-experienced people who have HIV
strains that are resistant to multiple antiretroviral drugs and for
people with drug-sensitive HIV strains, such as those starting
antiretroviral therapy for the first time.
In countries other than the U.S., maraviroc will be approved and
sold under the brand name Celsentri.
Selzentry binds to a protein on the membrane of CD4 cells (CD4
cells) called CCR5. Once it does this, HIV cannot successfully
attach itself to the surface of CD4 cells, and is thus prevented
from infecting healthy cells.
Selzentry must be combined with other HIV drugs.
In addition to Selzentry's proven antiviral efficacy, it continues
to be studied for its immune-based therapy potential, notably its
effects on CD4 cell counts and inflammation.
Selzentry is available in 150
mg and 300 mg tablets and must be taken twice a day. Because of
interactions with other medications, including some used to treat
HIV, the Selzentry dose will need to be carefully determined:
-
CYP3A inhibitors: If
Selzentry is combined with protease inhibitors (with the
exception of Aptivus [tipranavir] plus Norvir [ritonavir]); the
NNRTI Rescriptor (delavirdine); the antibiotics Biaxin (clarithromycin),
Ketek (telithromycin), Nizoral (ketoconazole), or Sporanox (itraconazole);
or the antidepressant Serzone (nefazodone), the correct dose is
one 150 mg tablet twice a day.
-
CYP3A Inducers: If
Selzentry is combined with the NNRTI Sustiva (efavirenz); the
anticonvulsant (anti-seizure) medications Tegretol (carbamazepine),
or phenobarbital; or the antibiotic Rifadin (rifampin), the
correct dose is two 300mg tablets twice a day.
-
Other Medications: If
Selzentry is combined with Aptivus/Norvir; the NNRTI Viramune (nevirapine);
the entry inhibitor Fuzeon (enfuvirtide); any nucleoside reverse
transcriptase inhibitors (without CYP3A inhibitors); the
antibiotic Bactrim or Septra (TMP/SMX); or the sedative Versed (midazolam),
the correct dose is one 300 mg tablet twice a day.
Selzentry holds promise for
HIV-positive patients who no longer respond to other HIV drugs.
Because Selzentry targets HIV differently than most currently
available antiretrovirals, chances are that many people living with
the virus—regardless of which drugs have failed them in the
past—will likely benefit from using Selzentry. Two large clinical
trials have determined that Selzentry, when combined with other
drugs, is effective for patients whose virus has adapted to other
HIV drugs used in the past. However, Selzentry worked best when it
was combined with at least two other drugs that the virus was
sensitive to (patients who used Selzentry in combination with drugs
that their virus was highly resistant to did not experience
decreases in their viral load for very long). For this reason, it is
best to use drug-resistance testing to determine which drugs your
virus is sensitive to; the results will show which antiretrovirals
are best to combine with Selzentry.
Selzentry is also approved for people with HIV that have no, or
limited, resistance to other available antiretroviral drugs.
Selzentry is not considered a "preferred" or "alternative" option
for first-time treatment takers by the U.S. Department of Health and
Human Services in its HIV treatment guidelines. Instead, the DHHS
considers Selzentry—combined with Combivir (zidovudine and
lamivudine)—to be an "acceptable option but more definitive data are
needed."
Drugs
Interactions
Selzentry is broken down
(metabolized) by the liver, like many medications used to treat HIV
and AIDS. This means that Selzentry can interact with other
medications. While it is not expected that the drug will lower or
raise the levels of any other medications in the body, studies have
shown that other drugs can affect levels of Selzentry in the body.
At the time of Selzentry's approval in August 2007, there were no
known "contraindications," meaning that there are no known
medications that must be avoided while taking Selzentry.
Anticonvulsants, such as Tegretol (carbamazepine), Luminal (phenobarbital),
and Dilantin (phenytoin), can decrease the amount of Selzentry in
the bloodstream.
Other HIV drugs can interact with Selzentry. Some HIV medications
are "CYP3A inhibitors," meaning that they slow the ability of
certain enzymes that are responsible for metabolizing, or breaking
down, Selzentry in the body. Some HIV medications are "CYP3A
inducers," meaning that they can speed up the metabolism of
Selzentry in the body. Still others do not have a significant effect
on CYP3A enzymes. The dose of Selzentry will need to be adjusted,
depending on which HIV medications are being used.
Selzentry can interact with some medications used to treat TB, MAC,
and other bacterial infections. Rifadin (rifampin) can decrease
Selzentry levels, meaning that the Selzentry dose (provided that
CYP3A inhibitors are not being used as well) should be 600 mg (two
300 mg tablets) twice a day. Biaxin (clarithromycin) increases
Selzentry levels, requiring a Selzentry dose of one 150 mg tablet
twice a day.
Selzentry can interact with some medications used to treat thrush (candidiasis)
and other fungal infections. Nizoral (ketoconazole) and Sporanox (itraconazole)
can increase Selzentry levels in the bloodstream. If these
medications are used, the Selzentry dose should be one 150 mg tablet
twice a day.
Other medications, including those known to have a strong inhibitory
effect on CYP3A enzymes, can interact with Selzentry and may require
dosing adjustments. Tell your doctors and pharmacists about all
medicines you take. This includes those you buy over-the-counter and
herbal or natural remedies. Bring all your medicines when you see a
doctor, or make a list of their names, how much you take, and how
often you take them. Your doctor can then tell you if you need to
change the dosages of any of your medications.
People with kidney problems may need to adjust their Selzentry dose
when they combine it with other medications. Both those that
increase and decrease CYP3A enzymes, and a host of other medications
that include Aptivus with Norvir, Viramune, Isentress, Fuzeon and
all nucleoside reverse transcriptase inhibitors (NRTIs).
Side
Effects
The most common side effects
associated with Selzentry therapy in clinical trials involving
treatment-experienced patients were cough, fever, colds, rash,
muscle and joint pain, stomach pain, and dizziness.
Although there hasn't been an overall increase in serious liver
problems in patients treated with Selzentry in clinical trials,
liver toxicity has been seen in some patients using the drug.
Certain allergy-like signs and symptoms—for example, rash, an
increase in the number of eosinophils (a type of white blood cell)
or elevated IgE antibodies—prior to the development of liver
toxicity may occur. If these signs or symptoms occur while taking
Selzentry, patients should be evaluated immediately.
People with severe kidney problems and end-stage kidney disease
should not take Selzentry if they are also taking other medication
that affects levels of the CYP3A liver enzyme.
In clinical trials, more cardiovascular events, including heart
attacks, were seen in patients receiving Selzentry as compared to
placebo. In turn, the manufacturer and the FDA are recommending that
the drug be used with caution in patients at increased risk for
cardiovascular events.
Because Selzentry blocks the CCR5 coreceptor located on some immune
system cells, there is a theoretical risk of developing infections
and cancers. However, rates of infections and cancer were no higher
among patients receiving Selzentry, versus those receiving placebo,
in year-long clinical trials.
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