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Selzentry (Maraviroc)
Selzentry
Tablet

Articles on Selzentry
Full US Prescribing Information
U.S. Medication Guide
www.selzentry.com

Patient Information
What is Selzentry?
What is known about Selzentry?
What about drug interactions?
Dosing Information
Adverse Events
Medication Guide
Clinical Trials
www.selzentry.com


Articles on Selzentry


Maraviroc
Failure with Co-receptor Switch Does Not Lead to HIV Disease Progression
9-21-2010

Maraviroc (Selzentry)
Not Associated with Elevated Cancer Risk in Clinical Development Program
8-17-2010

ART Intensification with Maraviroc (Selzentry) or Raltegravir (Isentress) May Improve Immune Activation and Inflammation
3-16-2010

Treatment Intensification with Maraviroc (Selzentry) Did Not Raise CD4 Cell Counts in Small Study

2-23-2010

Maraviroc (Selzentry) Produces Superior CD4 Cell Recovery after 48 Weeks
1-05-2010

FDA Advisory Committee Recommends Approval of CCR5 Antagonist Maraviroc (Selzentry) for Treatment-naive Patients

10-13-2009

Treatment-naive Patients with Confirmed CCR5-tropic HIV Continue to Respond Well to
Maraviroc (Selzentry) at 96 Weeks in the MERIT Study
8-4-2009

Genotypic Testing Predicts Response to Maraviroc (Selzentry) as well as Viral Tropism Testing
8-4-2009

CCR5 Antagonist Maraviroc (Selzentry) Appears Safe -- but No More Effective than Placebo -- in People with CXCR4-tropic HIV
6-5-2009


GlaxoSmithKline and Pfizer Agree to Create a New HIV-focused Company
4/17/2009

CCR5 Antagonist
Maraviroc (Selzentry) Receives Full FDA Approval
12/02/2008


Excellent Response with a PI- and NRTI-sparing Regimen of Raltegravir (Isentress), Maraviroc (Selzentry), and Etravirine (Intelence)
11/14/2008

Weighted OBT Susceptibility Score (wOBTSS) is a Stronger Predictor of Virologic Response at 48 Weeks than Baseline Tropism Result in MOTIVATE 1 and 2
11/05/2008

Reanalysis of the MERIT Study with the Enhanced Trofile Assay (MERIT-ES)
11/05/2008

CD4+ Cell Increases at 48 Weeks in the Maraviroc Treatment-naive MERIT Trial - 11/05/2008

Adverse Event Profile of Maraviroc in Treatment-experienced Patients Infected with R5 HIV-1
11/05/2008

A Pharmacokinetic Study to Evaluate an Interaction between Maraviroc and Raltegravir in Healthy Adults
11/05/2008


CCR5 Antagonist Maraviroc (Selzentry)
Suppresses HIV in Treatment-experienced Patients with Drug-resistant Virus
10/03/08




What is Selzentry?

Selzentry is a CCR5-blocking entry inhibitor manufactured by Pfizer. 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. It is not yet approved 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 (T-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.


What is known about Selzentry?

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 dose will need to be carefully determined by your healthcare provider.

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 not yet approved for people with HIV that have no, or limited, resistance to other available antiretroviral drugs. This includes HIV-positive people beginning treatment for the first time. Preliminary data from a study evaluating the drug in patients new to HIV treatment suggest that Selzentry is somewhat inferior to standard-of-care Sustiva (efavirenz). However, moderate CD4 count and side-effect benefits were found to be associated with the drug, compared to Sustiva.

Selzentry will only be effective at reducing viral load in people with HIV that uses the CCR5 receptor. It will not be effective against virus that uses another CD4 cell coreceptor, called CXCR4 (and the drug will have a limited effect against HIV with that uses both receptors). Because CXCR4-"tropic" and "dual-tropic" HIV is more common in people who have been infected with HIV for several years—the people who are most likely going to be using Selzentry—a laboratory test called a tropism assay is necessary before Selzentry can be used, to determine if treatment with the drug will be useful.

Resistance concerns are twofold:

1) mutations in HIV's gp120 protein can cause resistance to the drug (but not necessarily to other entry inhibitors); and

2) while taking a CCR5 inhibitor, it is possible that CXCR4-tropic virus will emerge and not be affected by the presence of Selzentry or any other CCR5-blocking entry inhibitor. More data from studies of Selzentry are needed to better understand the risk and impact of resistance-causing mutations and the emergence of CXCR4-tropic HIV while on treatment.


What about drug 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. If these medications are used, the maximum Selzentry dose (two 300 mg twice daily) may be necessary.

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:

CYP3A inhibitors: If Selzentry is combined with protease inhibitors (with the exception of Aptivus [tipranavir] plus Norvir [ritonavir]) or Rescriptor (delavirdine), the correct dose is one 150 mg tablet twice a day.

CYP3A Inducers: If Selzentry is combined with Sustiva and other medications—without CYP3A inhibitors—the correct dose is 600 mg (two 300 mg tablets) twice a day.

Other Antiretrovirals: If Selzentry is combined with Aptivus/Norvir, Viramune (nevirapine), Fuzeon (enfuvirtide), or any nucleoside reverse transcriptase inhibitors—without CYP3A inhibitors—the correct dose is one 300 mg tablet twice a day.

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.


Dosing Information

Table 1: Recommended Dosing Regimen

Concomitant Medications
Dose
CYP3A inhibitors (with or without a CYP3A inducer) including:
-protease inhibitors (except tipranavir/ritonavir)
- delavirdine
- ketoconazole, itraconazole, clarithromycin,
- other strong CYP3A inhibitors (e.g., nefazadone, telithromycin)
150 mg
twice daily
Other concomitant medications, including tipranavir/ritonavir, nevirapine, all NRTIs and enfuvirtide, and other drugs that are not strong CYP3A inhibitors or CYP3A inducers (2, 7.1)
300 mg
twice daily
With CYP3A inducers (without a strong CYP3A inhibitor) including
-efavirenz
- rifampin
- carbamazepine, phenobarbital, and phenytoin
600 mg
twice daily

Maraviroc is an orally administered drug available as 150 and 300 mg film-coated tablets. The current FDA-approved dosage of maraviroc is 300 mg twice daily. Maraviroc must be used in combination with other antiretroviral medications. Dosage adjustments are required when maraviroc is administered in combination with CYP inhibitors or inducers. The necessary dosing adjustments vary according to the coadministered medication. (See Table 1 of Selzentry Full Prescribing Information). See Table 6 of the drug's Prescribing Information for "Effect of Co-administered Agents on the Pharmacokinetics of Maraviroc."


Adverse Events

WARNINGS AND PRECAUTIONS

Use caution when administering SELZENTRY to patients with preexisting liver dysfunction or who are co-infected with viral hepatitis B or C (5.1)

More cardiovascular events including myocardial ischemia and/or infarction were observed in patients who received SELZENTRY. Use with caution in patients at increased risk of cardiovascular events (5.2)

From Selzentry Full Prescribing Information

In two Phase II/III studies, interim results reported adverse effects to similar those that occurred with optimized background therapy (OBT) alone. In these studies, 5% or less of study participants discontinued treatment because of adverse events in both placebo and treatment groups.

Two Phase III studies showed no increase in mortality or malignancy and no clear evidence of hepatotoxicity. However, these studies did indicate an increase in Candida, herpes, and influenza infections.

In 24-week analysis of these two ongoing Phase III clinical studies, the most common maraviroc-related adverse effects, occurring in >8% of patients and more often than in the placebo group, were cough, fever, upper respiratory infections, rash, musculoskeletal symptoms, abdominal pain, and dizziness.

Additional adverse effects noted with greater incidence in the once-daily arm included diarrhea, edema, sleep disorders, rhinitis, and urinary abnormalities.

Serious adverse events occurred in less than 2% of maraviroc-treatment patients and included cardiovascular abnormalities (e.g., angina, heart failure, myocardial infarction); hepatic cirrhosis or failure, cholestatic jaundice; viral meningitis; pneumonia; myositis; osteonecrosis, and rhabdomyolysis.

Grade 3-4, treatment-emergent laboratory abnormalities occurring in at least 2% of patients included increased bilirubin, increased amylase and lipase, and increased AST and ALT levels.

One case of possible drug-associated hepatotoxicity with allergy has been reported in a study of healthy volunteers. Increased hepatic adverse events have been observed in treatment-experienced patients. To date, only 6% of patients in clinical studies have been coinfected with hepatitis B or C virus; larger populations are needed to determine the risk of hepatic adverse events in these patients.

Immune reconstitution syndrome has also been reported. In addition, patients taking maraviroc should be monitored for risk of infection because of CCR5-antagonism effects on some immune cells.

Cardiovascular events, including myocardial ischemia or infarction, have been observed at higher rates in maraviroc-treated patients than in placebo. QT prolongation has been observed in animal studies at up to 12 times the recommended human dosage, but no prolongation has been noted in treatment-experienced patients taking recommended dosages.

When given to HIV infected patients in Phase III studies at recommended dosages, no greater rates of postural hypotension were observed. However, the dose-limiting adverse effect in clinical studies, observed at daily doses of maraviroc 600 mg, is postural hypotension.

Selzentry (maraviroc) Medication Guide

Read the Medication Guide that comes with SELZENTRY before you start taking it and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or treatment.

What is the most important information I should know about SELZENTRY?

Liver problems

Liver problems (liver toxicity) have happened in patients taking SELZENTRY. An allergic reaction may happen before liver problems occur. Stop taking SELZENTRY and call your doctor right away if you get any of the following symptoms:

·         an itchy rash on your body (allergic reaction)

  • your skin or eyes look yellow and/or dark (tea-colored) urine
  • vomiting and/or upper right stomach area (abdominal) pain

You should see your doctor right away but continue taking SELZENTRY if you have any of the following other symptoms: nausea, fever, flu-like symptoms, fatigue

What is SELZENTRY?

  • SELZENTRY is an anti-HIV medicine called a CCR5 antagonist. HIV (Human Immunodeficiency Virus) is the virus that causes AIDS (Acquired Immune Deficiency Syndrome).
  • SELZENTRY is used with other anti-HIV medicines in adults with CCR5-tropic HIV-1 infection who are already taking anti-HIV medicines and the medicines are not controlling their HIV infection.
  • SELZENTRY will not cure HIV infection.
  • People taking SELZENTRY may still develop infections, including opportunistic infections or other conditions that happen with HIV infection.
  • It is very important that you stay under the care of your doctor during treatment with
  • SELZENTRY.
  • The long-term effects of SELZENTRY are not known at this time.
  • SELZENTRY has not been studied in children less than 16 years of age.

Does SELZENTRY lower the risk of passing HIV to other people?

No, SELZENTRY does not lower the risk of passing HIV to other people through sexual contact, sharing needles, or being exposed to your blood.

  • Continue to practice safer sex.
  • Use latex or polyurethane condoms or other barrier methods to lower the chance of sexual contact with any body fluids. This includes semen from a man, vaginal secretions from a woman, or blood.
  • Never re-use or share needles.
  • Ask your doctor if you have any questions about safer sex or how to prevent passing HIV to other people.

How does SELZENTRY work?

HIV enters cells in your blood by attaching itself to structures on the surface of the cell called receptors. SELZENTRY blocks a specific receptor called CCR5 that CCR5-tropic HIV-1 uses to enter CD4 or T cells in your blood. Your doctor will do a blood test to see if you have been infected with CCR5-tropic HIV-1 before prescribing SELZENTRY for you.

When used with other anti-HIV medicines, SELZENTRY may:

  • reduce the amount of HIV in your blood. This is called “viral load”.
  • increase the number of white blood cells called T (CD4) cells.

Both of these may keep your immune system healthy, so it can help fight infection.

SELZENTRY does not work in all patients with CCR5-tropic HIV-1 infection.

What should I tell my doctor before taking SELZENTRY?

Tell your doctor about all of your medical conditions, including if you:

  • have any allergies
  • have liver problems including a history of hepatitis B or C
  • have heart problems
  • have kidney problems
  • have low blood pressure or take medicines to lower blood pressure
  • are pregnant or planning to become pregnant. It is not known if SELZENTRY may harm your unborn baby. If you take SELZENTRY while you are pregnant, talk to your doctor about how you can be included in the Antiretroviral Pregnancy Registry.
  • are breast-feeding or planning to breast-feed. It is recommended that HIV-positive women should not breastfeed their babies. This is because of the chance of passing HIV to your baby. Talk with your doctor about the best way to feed your baby.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Certain other medicines may affect the levels of SELZENTRY in your blood. Your doctor may need to change your dose of SELZENTRY when you take it with certain medicines.

Do not take products that contain St. John’s Wort (hypericum perforatum). St. John’s Wort may lower the levels of SELZENTRY in your blood so that it will not work to treat your CCR5-tropic HIV infection.

Know the medicines you take. Keep a list of your medicines. Show the list to your doctor and pharmacist when you get a new medicine.

How should I take SELZENTRY?

Take SELZENTRY exactly as prescribed by your doctor. SELZENTRY comes in 150 mg and 300 mg tablets. Your doctor will prescribe the dose that is right for you.

  • Take SELZENTRY twice a day.
  • Swallow SELZENTRY tablets whole. Do not chew the tablets.
  • Take SELZENTRY tablets with or without food.
  • Always take SELZENTRY with the other anti-HIV drugs prescribed by your doctor.

Do not change your dose or stop taking SELZENTRY or your other anti-HIV medicines without first talking with your doctor.

·         If you take too much SELZENTRY, call your doctor or the poison control center right away.

  • If you forget to take SELZENTRY, take the next dose of SELZENTRY as soon as possible and then take your next scheduled dose at its regular time. If it is less than 6 hours before your next dose, do not take the missed dose. Wait and take the next dose at the regular time. Do not take a double dose to make up for a missed dose.
  • It is very important to take all your anti-HIV medicines as prescribed and at the same time each day. This can help your medicines work better. It also lowers the chance that your medicines will stop working to fight HIV (drug resistance).
  • When your SELZENTRY supply starts to run low, ask your doctor or pharmacist for a refill. This is very important because the amount of virus in your blood may increase and SELZENTRY could stop working if it is stopped for even a short period of time. 

What are the possible side effects of SELZENTRY?

When SELZENTRY has been given with other anti-HIV drugs, there have been serious side effects including:

  • Liver problems. See “What is the most important information I should know about SELZENTRY?”
  • Heart problems including heart attack
  • Low blood pressure when standing up (postural hypotension). Low blood pressure when standing up can cause dizziness or fainting. Do not drive a car or operate heavy machinery if you have dizziness while taking SELZENTRY.
  • Changes in your immune system. A condition called Immune Reconstitution Syndrome can happen when you start taking HIV medicines. Your immune system may get stronger and could begin to fight infections that have been hidden in your body such as pneumonia, herpes virus or tuberculosis. Tell your doctor if you develop new symptoms after starting your HIV medicines.
  • Possible chance of infection or cancer. SELZENTRY affects other immune system cells and therefore may possibly increase your chance for getting other infections or cancer, although there is no evidence from the clinical trials of an increase in serious infections or cancer.

The most common side effects of SELZENTRY include cough, fever, colds, rash, muscle and joint pain, stomach pain, dizziness. Tell your doctor about any side effect that bothers you or does not go away.

These are not all of the side effects with SELZENTRY. For more information, ask your doctor or pharmacist.

How should I store SELZENTRY?

  • Store SELZENTRY tablets at room temperature from 59◦F to 86◦ (15◦Cto 30◦C)] .
  • Safely throw away medicine that is out of date or that you no longer need.
  • Keep SELZENTRY and all medicines out of the reach of children.

General information about SELZENTRY

Medicines are sometimes prescribed for conditions that are not mentioned in Medication Guides. Do not use SELZENTRY for a condition for which it was not prescribed. Do not give SELZENTRY to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide summarizes the most important information about SELZENTRY. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for more information about SELZENTRY that is written for health professionals. For more information go to www.selzentry.com.

What are the ingredients in SELZENTRY?

Active Ingredient: maraviroc

Inactive Ingredients:

Tablet core: microcrystalline cellulose, dibasic calcium phosphate (anhydrous), sodium starch glycolate, magnesium stearate

Film-coat: FD&C blue #2 aluminum lake, soya lecithin, polyethylene glycol (macrogol 3350), polyvinyl alcohol, talc and titanium dioxide

Issued August 2007

Distributed by Pfizer Labs
Division of Pfizer Inc, NY, NY 10017
LAB-0358-1.0

This Medication Guide has been approved by the US Food and Drug Administration.