Prezcobix FACTSHEET. Summary. What is Prezcobix. How do people with HIV use Prezcobix? How does Prezcobix work?

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1 FACTSHEET Prezcobix Summary Prezcobix is the brand name of a product that contains two drugs darunavir (also known as Prezista) and cobicistat. Darunavir belongs to a group of anti-hiv drugs called protease inhibitors. Cobicistat helps to raise and maintain levels of darunavir in the blood. Prezcobix is meant to be taken as part of a regimen of anti-hiv drugs by adults. Prezcobix should be taken with food. Although Prezcobix is generally well tolerated, side effects can include headache, nausea, vomiting, diarrhea and rash. What is Prezcobix Prezcobix is the brand name of a product containing two drugs darunavir (also known as Prezista) and cobicistat. Darunavir belongs to a group of anti-hiv drugs called protease inhibitors. Cobicistat helps to boost or raise and maintain levels of darunavir in the blood so that Prezcobix can be taken once daily. Prezcobix is used in combination with other anti-hiv drugs to treat HIV in adults. How does Prezcobix work? When HIV infects a cell, it takes control of that cell. HIV then forces the cell to make many more copies of the virus. To make these copies, the cell uses proteins called enzymes. When the activity of these enzymes is reduced the production of HIV slows. Darunavir (in Prezcobix) belongs to a group or class of drugs called protease inhibitors. Darunavir interferes with an enzyme called protease, which is used by HIV-infected cells to make new viruses. Since darunavir inhibits, or reduces, the activity of this enzyme, this drug causes HIV-infected cells to slow down or stop producing new viruses. How do people with HIV use Prezcobix? Prezcobix is used in combination with at least two other anti-hiv drugs, usually nukes (nucleoside analogues), and sometimes including drugs from other classes such as nonnukes (non-nucleoside reverse transcriptase inhibitors). Combinations such as this are called antiretroviral therapy, or ART. For more information on ART, see CATIE s A Practical Guide to HIV Drug Treatment. For adults prescribed Prezcobix, the recommended dose is one tablet per day taken with food; the type and amount of food does not matter. To help integrate Prezcobix into your life, it may be simplest to take it with a meal. You can also take Prezcobix with a snack a piece of fruit, a few crackers, a slice of bread with margarine, peanut butter or butter, PREZCOBIX page 1 of 6

2 vegetables, a chocolate bar, a granola bar, a sandwich, a bowl of soup and so on. For many people with HIV, the use of ART has increased their CD4+ cell counts and decreased the amount of HIV in their blood (viral load). These beneficial effects help to reduce the risk of developing a life-threatening infection. Neither darunavir (in Prezcobix) nor any other anti-hiv medication is a cure for HIV. It is therefore important that you do the following: See your doctor regularly so that he/she monitors your health. Continue to practise safer sex and take other precautions so as not to pass HIV on to other people and to protect yourself from new strains of HIV and other germs. Warnings 1. Pregnancy The safety of Prezcobix in pregnant women has not been studied. Therefore, its safety in this population is not known. The manufacturer recommends that Prezcobix should not be used during pregnancy unless the potential benefit justifies the risk. 2. Hepatitis B and C viruses Co-infection with hepatitis B and/or C virus occurs among some HIV-positive people. The manufacturer of Prezcobix, Janssen, notes that generally patients with pre-existing liver dysfunction including chronic hepatitis B or C have an increased frequency of [elevated levels of liver enzymes in their blood] during combination [anti-hiv therapy]. Janssen recommends that doctors consider increased monitoring if Prezcobix is prescribed in patients with the following medical issues: elevated liver enzymes in the blood prior to starting Prezcobix active hepatitis B and/or C virus underlying liver disease Janssen says that if cases of new or worsening liver dysfunction, including clinically significant elevation of liver enzymes and/ or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness and [swollen liver and/or spleen] occur in patients taking Prezcobix, doctors should be prompted to consider interrupting or discontinuing treatment. 3. Rash Historically, about 10% of people who have used darunavir with ritonavir in clinical trials have developed rash. Janssen states that this rash was mostly mild-to-moderate, often occurring within the first four weeks of [initiating] treatment and resolving with continued dosing. Less than 1% of patients who developed this rash have had to stop taking darunavir. In rare cases, severe rash may be accompanied by one or more of the following symptoms: fever lack of energy achy muscles or joints blisters on the skin peeling skin oral lesions eye inflammation belly pain If you are taking Prezcobix and these symptoms occur, call your doctor right away. If your doctor is not available go immediately to the emergency room of the nearest hospital. If you are unable to do this, dial 911. Prezcobix should not be used in people with severe liver damage. 4. Medicines and kidney injury The kidneys filter the blood, putting waste materials into urine and reabsorbing nutrients and other useful material back into the blood. PREZCOBIX page 2 of 6

3 Prezcobix contains cobicistat, which can interfere with the ability of the kidneys to release the waste product creatinine into urine. Therefore, a small but persistent increase of creatinine can be detected in the blood of Prezcobix users. This small increase is generally not considered harmful. Furthermore, the small increase in creatinine does not appear to affect the kidneys ability to filter other substances from the blood. A similar effect on the kidneys is seen with the anti-hiv medicines Stribild (which contains cobicistat) and dolutegravir (Tivicay and in Triumeq), as well as in the anti-ulcer medicine cimetidine (Tagamet). 5. Monitoring kidney health Janssen has stated that kidney injury can sometimes occur or grow worse when the anti- HIV drug tenofovir (in Viread and Truvada) is taken by people who are also taking Prezcobix. The pharmaceutical company makes the following recommendations for physicians concerning Prezcobix and monitoring the kidneys: Do not initiate cobicistat as part of a regimen containing tenofovir in patients who have [an egfr (estimated glomerular filtration rate)] below 70 ml/min. Assess the amount of glucose and protein in the urine before starting therapy and then perform routine monitoring [egfr, glucose and protein in urine] during treatment when cobicistat is used with tenofovir. Assess the amount of phosphorus in the blood of patients at risk for renal impairment. Avoid the use of cobicistat with tenofovir in combination with drugs that have the potential to injure the kidney, or in patients who have recently used drugs with the potential to injure the kidneys. 6. Age Prezcobix is meant for use in adults. The manufacturer notes that in clinical trials only a relatively small number of participants over the age of 65 have used Prezcobix. In general, the major organ systems heart and circulatory system, lungs, liver, kidneys may not work as well in older people as they do in healthy younger people. Janssen provides the following advice: In general, caution should be exercised in the administration and monitoring of Prezcobix in elderly patients. Side effects 1. General In clinical trials Prezcobix has been generally well tolerated. Side effects that have been reported by some Prezcobix users included the following: nausea diarrhea vomiting rash headache Most of these side effects were either mild or moderate in severity. Also, if they did occur, these side effects happened early in the course of darunavir therapy. 2. HIV lipodystrophy syndrome The HIV lipodystrophy syndrome is the name given to a range of symptoms that can develop over time when people use ART. Some features of the lipodystrophy syndrome include: loss of fat just under the skin (subcutaneous fat) in the face, arms, and legs bulging veins in the arms and/or legs due to the loss of fat under the skin increased waist and belly size PREZCOBIX page 3 of 6

4 fat pads at the back of the neck ( buffalo hump ) or at the base of the neck ( horse collar ) small lumps of fat in the abdomen increased breast size (in women) Together with these physical changes, lab tests of your blood may detect the following: increased levels of fatty substances called triglycerides increased levels of LDL-cholesterol (lowdensity lipoprotein), or bad cholesterol decreased levels of HDL-cholesterol (highdensity lipoprotein), or good cholesterol increased levels of sugar (glucose) increased levels of the hormone insulin decreased sensitivity to insulin (insulin resistance) The precise causes of the HIV lipodystrophy syndrome are not clear and are difficult to understand because in some people with HIV there may be one or more aspects of the syndrome taking place. For instance, some people may experience fat wasting, others fat gain, and others may experience both fat gain and wasting. What is becoming increasingly clear is that unfavourable changes in the lab readings of glucose, cholesterol and triglycerides over a period of several years increase the risk of diabetes and cardiovascular disease. So far, however, the many benefits of ART are much greater than the increased risk of cardiovascular disease or other side effects. Maintaining a normal weight, eating a healthy diet, exercising regularly and quitting smoking are all important in helping you to reduce your risk of diabetes, heart disease and other complications. Regular visits to your doctor for checkups and blood tests are a vital part of staying healthy. If necessary, your doctor can prescribe lipid-lowering therapy. Researchers are studying the lipodystrophy syndrome to try to discover ways of helping HIV-positive people avoid or reduce this problem. So far Prezcobix has not been linked to the lipodystrophy syndrome. To find out more about options for managing aspects of the lipodystrophy syndrome, see CATIE s A Practical Guide to HIV Drug Side Effects. Drug interactions Always consult your doctor and pharmacist about taking any other prescription or nonprescription medication, including herbs, supplements and street drugs. Some drugs can interact with Prezcobix, increasing or decreasing the levels of darunavir and/or cobicistat in your body. Increased drug levels can cause you to experience side effects or make pre-existing side effects worse. On the other hand, if drug levels become too low, HIV can develop resistance and your future treatment options may be reduced. If you must take a drug that has the potential to interact with your existing medications, your doctor can do the following: adjust your dose of either your anti-hiv drugs or other medications prescribe different anti-hiv drugs for you The medicines in Prezcobix interfere with a key enzyme (called CYP3A4) in the liver and intestines. Many drugs are broken down by this enzyme. As Prezcobix slows the activity of this enzyme, it causes levels of other drugs in the body to increase. This can result in what Janssen calls serious and life-threatening reactions. Janssen warns that the following drugs should not be used by people who are also taking Prezcobix because of the high risk for severe reactions: other HIV drugs atazanavir (Reyataz), indinavir (Crixivan),lopinavir (Kaletra), ritonavir (Norvir), saquinavir (Invirase), Stribild (elvitegravir + cobicistat + tenofovir + FTC) PREZCOBIX page 4 of 6

5 abnormal heart rhythm drugs amiodarone, bepridil, dronedarone, lidocaine, quinidine drugs for asthma and bronchitis salmeterol (Advair, Serevent) anti-gout drugs colchicine antihistamines astemizole, terfenadine antibiotics rifampin drugs for enlarged prostate (benign prostatic hyperplasia, or BPH) alfuzosin ergot derivatives dihydroergotamine, ergonovine, ergotamine, methylergonovine herbs St. John s wort or its extracts (hypericin and hyperforin) can greatly reduce the amount of darunavir in the blood. Assume that other herbs can interact with Prezcobix and other medicines until clinical trials are done to assess their potential for interactions. drugs for treating pulmonary hypertension sildenafil (Revatio) statins (cholesterol-reducing drugs) lovastatin, simvastatin sleeping pills/sedatives midazolam, triazolam There may be other potential drug interactions with Prezcobix and doses of other drugs may need to be adjusted. Speak to your pharmacist and doctor for more information. Resistance and cross-resistance Over time, as new copies of HIV are made in the body, the virus changes its structure. These changes are called mutations and can cause HIV to resist the effects of anti-hiv drugs, which means those drugs will no longer work for you. Combining darunavir with at least two other anti-hiv drugs delays the development of drug resistance. To reduce the risk of developing drug resistance, all anti-hiv drugs should be taken every day exactly as prescribed and directed. If doses are delayed, missed, or not taken as prescribed, levels of darunavir in the blood may fall too low. If this happens, resistant virus can develop. If you find you are having problems taking your medications as directed, speak to your doctor and nurse about this. They can find ways to help you. When HIV becomes resistant to one drug in a class, it sometimes becomes resistant to other drugs in that class. This is called crossresistance. Feel free to talk with your doctor about your current and future treatment options. To help you decide what these future therapies might be, at some point your doctor can have a small sample of your blood analysed using resistance testing. Should HIV in your body become resistant to darunavir (in Prezcobix), your doctor, with the help of resistance testing, can help put together a new treatment regimen for you. Dosage and formulations Each tablet of Prezcobix contains the following medicines: darunavir 800 mg cobicistat 150 mg For adults, the recommended dose is one tablet of Prezcobix taken once daily with food. Prezcobix is meant to be taken with other anti- HIV drugs. To help integrate Prezcobix into your life, it may be simplest to take it with a meal. You can also take Prezcobix with a snack a piece of fruit, a few crackers, a slice of bread with margarine, peanut butter or butter, vegetables, a chocolate bar, a granola bar, a sandwich, a bowl of soup and so on. Formulations can change, and dosages may need to be customized. All medications should always be taken as prescribed and directed. Availability Prezcobix is licensed in Canada for the treatment of HIV infection in adults. Prezcobix must be taken in combination with other anti-hiv drugs and with food (a meal or snack). Your doctor can tell you more about PREZCOBIX page 5 of 6

6 the availability and coverage of darunavir in your region. CATIE s online module Federal, Provincial and Territorial Drug Access Programs also contains information about Canadian drug coverage. Sean R. Hosein REFERENCES: Janssen. Prezcobix (darunavir/cobicistat). Product Monograph. 18 June Deeks ED. Cobicistat: a review of its use as a pharmacokinetic enhancer of atazanavir and darunavir in patients with HIV-1 infection. Drugs Feb;74(2): Spreen WR, Margolis DA, Pottage JC Jr. Long-acting injectable antiretrovirals for HIV treatment and prevention. Current Opinion in HIV/AIDS Nov;8(6): Kakuda TN, Van De Casteele T, Petrovic R, et al. Bioequivalence of a darunavir/cobicistat fixed-dose combination tablet versus single agents and food effect in healthy volunteers. Antiviral Therapy. 2014; in press. Kakuda TN, Brochot A, Tomaka FL, et al. Pharmacokinetics and pharmacodynamics of boosted once-daily darunavir. Antimicrobial Agents and Chemotherapy Oct;69(10): Pozniak A, Markowitz M, Mills A, et al. Switching to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of non-nucleoside reverse transcriptase inhibitor with emtricitabine and tenofovir in virologically suppressed adults with HIV (STRATEGY- NNRTI): 48 week results of a randomised, open-label, phase 3b non-inferiority trial. Lancet Infectious Diseases Jul;14(7): Contact us by telephone by fax Disclaimer by info@catie.ca by mail Richmond Street West Box 1104 Toronto ON M5V 3B1 Decisions about particular medical treatments should always be made in consultation with a qualified medical practitioner knowledgeable about HIV- and hepatitis C-related illness and the treatments in question. CATIE provides information resources to help people living with HIV and/or hepatitis C who wish to manage their own health care in partnership with their care providers. Information accessed through or published or provided by CATIE, however, is not to be considered medical advice. We do not recommend or advocate particular treatments and we urge users to consult as broad a range of sources as possible. We strongly urge users to consult with a qualified medical practitioner prior to undertaking any decision, use or action of a medical nature. CATIE endeavours to provide the most up-to-date and accurate information at the time of publication. However, information changes and users are encouraged to consult as broad a range of sources as possible. Users relying on this information do so entirely at their own risk. Neither CATIE, nor any of its partners, funders, employees, directors, officers or volunteers may be held liable for damages of any kind that may result from the use or misuse of any such information. The views expressed herein or in any article or publication accessed or published or provided by CATIE do not necessarily reflect the policies or opinions of CATIE nor the views of its partners and funders. Permission to reproduce This document is copyrighted. It may be reprinted and distributed in its entirety for non-commercial purposes without prior permission, but permission must be obtained to edit its content. The following credit must appear on any reprint: This information was provided by the Canadian AIDS Treatment Information Exchange (CATIE). For more information, contact CATIE at Funding has been provided by the Public Health Agency of Canada. CATIE fact sheets are available for free at PREZCOBIX page 6 of 6