Brand name: Selzentry
Class: CCR5 antagonist (a type of entry inhibitor)
Manufacturer: ViiV Healthcare, www.viivhealthcare.com, (877) 844-8872
AWP: $1,199.84/month for 150 mg or 300 mg tablets
Standard Dose: Available in 150 mg and 300 mg tablets. Can be taken with or without food, with no dietary restrictions. The recommended dose varies, depending on other medications the patient is taking: 150 mg twice daily if taken with medications that increase the levels of Selzentry such as protease inhibitors (except for Aptivus) and Rescriptor; 300 mg twice daily if taken with Aptivus, Viramune, Fuzeon, and all of the NRTIs and medications that do not affect the levels of Selzentry; 600 mg twice daily if taken with medications that decrease the levels of Selzentry such as Sustiva, Intelence, rifampin, and some anti-convulsant medications such as phenobarbital, phenytoin, and carbamazepine. Dose change may be required if kidney function is less than 30 mL/min. Your doctor or pharmacist can determine which medications will affect Selzentry levels and recommend the appropriate dose for you. Before you start Selzentry, you will need a specific blood test (tropism assay, Trofile or Trofile ES) to determine if this medication will work for you. The results of this test may take up to a month. Selzentry only works for those people with CCR5-tropic virus.
Potential side effects and toxicity: Most common include cough, fever, cold, rash, muscle and joint pain, stomach pain, and dizziness. Other potential side effects may include liver toxicity; an allergic reaction may happen before the liver problems. It is recommended that Selzentry be stopped and your doctor contacted right away if you develop a rash, yellowing of your eyes or skin, and/or dark urine, vomiting, and upper stomach pain. Other rare side effects may include low blood pressure when standing up that could lead to dizziness or fainting. Should not be used in people with severe kidney problems or end-stage kidney disease who are taking medications that can increase or decrease the levels of Selzentry (check with your provider). While no increased risk of infections or cancer was seen in clinical trials, Selzentry affects other immune system cells and could possibly increase the risk of infections and cancer. See chart for potential drug class side effects.
Potential drug interactions: Selzentry interacts with many other drugs. See package insert for the most complete list. Tell your provider or pharmacist about all medications, herbs, and supplements you are taking or thinking of taking, prescribed or not. Not recommended with rifampin or St. John's wort. Dose adjustment needed for Biaxin, Dilantin (phenytoin), Tegretol (carbamazepine), phenobarbital, HIV NNRTIs and PIs, Mycobutin, Sporanox (itraconazole), Nizoral (ketoconazole), Vfend, oral contraceptives, and oral Versed (midazolam). See standard dose section for interactions with other anti-HIV medications.
More information: Selzentry is the only oral entry inhibitor available on the market. Originally approved for treatment-experienced patients infected only with CCR5-tropic virus (determined by the tropism assay), it has also been FDA approved for people starting HIV therapy for the first time. Complex dosing, the need for an expensive tropism test, and competition from newer drugs have dimmed some of the initial enthusiasm for this drug. The Trofile test needed, however, is now generally paid for by state public health departments, Medicare, and other private insurance coverage. ViiV may cover the payment if someone is ADAP-eligible and does not have insurance coverage for the Trofile test. Viral tropism refers to the types of HIV that a person can have: CCR5-tropic (R5) and/or CXCR4-tropic or (X4) virus. HIV attaches to the CD4 receptor on the surface of some T-cells (hence, CD4+ T-cells), and then it latches on to one or both of the two co-receptors on the surface of the cells, R5 or X4, thus gaining entry. As the name "CCR5 inhibitor" suggests, Selzentry inhibits (blocks) CCR5, shutting down this point of entry for the virus. X4 virus is usually associated with advanced HIV disease or extensive experience with taking HIV medications. Most people are infected with CCR5 virus, and then over time more CXCR4 and mixed viruses may accumulate. Results from various studies showed that blocking R5 with Selzentry does not cause virus to shift to X4 or show a negative effect on disease progression or CD4 count in so-called "dual tropic" people (their virus can use either R5 or X4). In 2007, the company reported that a switch to pre-existing X4 -- or dual-tropic virus -- was transient and reversible when people went off Selzentry. A sub-analysis reported that Selzentry seems to have minimal impact on lipid levels. Selzentry has been studied in treatment-naïve patients (first time on therapy) in the MERIT clinical trial. Although the initial analysis suggested that Selzentry was unable to match Sustiva's viral loads of less than 50 copies (undetectable), a re-analysis of the data using the enhanced Trofile test (Trofile ES) showed the regimens to be comparable (59% for Selzentry vs. 63% for Sustiva) in undetectable viral loads at 96 weeks. The follow-up results of 96-week data led to its FDA approval for this population. See package insert for more complete information on potential side effects and interactions.
Selzentry is an entry inhibitor that acts at an earlier stage of the entry process than Fuzeon: It blocks the binding of the virus to the CCR5 co-receptor on the CD4 cell surface. Some people have virus that can get into the cell using CXCR4, another co-receptor, and Selzentry won't work against that kind of virus. As a result, it's necessary to test the "tropism" of the virus before using Selzentry. Only those with purely "R5-tropic" virus should use the drug. The need for this test has been the main obstacle to widespread use of Selzentry, which is an effective, safe, and very well tolerated agent. The test currently in use in the United States, the Trofile assay, is expensive and time-consuming. Outside of the U.S., cheaper genotypic tests are being used. These may turn out to be good alternatives to Trofile, but we need more data on how well they measure tropism and predict success with Selzentry before they can be recommended. Selzentry has now been approved by the FDA for initial therapy, and people are more likely to have R5-tropic virus at early stages, before they've been treated. However, Selzentry is not yet being widely used for that purpose, and for initial therapy, it's categorized as "acceptable" or "alternative" in the DHHS and IAS-USA guidelines, respectively. Selzentry is taken twice a day, but once-daily dosing is being studied.
-- Joel Gallant, M.D., M.P.H.
One of my biggest disappointments, this new class of drugs, CCR5 antagonists, was a bust! Consider the fact that people have tropisms that can switch and add to that a tropism test that is more expensive than a month's supply of the drug itself, and you get a number of barriers and reasons this drug never took off. The mode of activity -- preventing fusion to occur in the first place -- and relatively few side effects means more research is needed to see how we can use this new class with a better method of detecting who will benefit from it, other than the company making the super expensive trofile assay!
-- Joey Wynn