Drug-Drug Interactions Clinically Manageable With PREZISTA(TM)

Glasgow, Scotland, November 14 (ots/PRNewswire) -

- Data Presented at HIV 8 Conference -

New studies on the use of PREZISTA(TM), an investigationalanti-HIV medication, suggest that it can be co-administered with manycommon medications taken by people with HIV, including otherantiretrovirals, proton pump inhibitors, H2 blockers and selectiveserotonin reuptake inhibitors. According to current HIV treatmentguidelines, potential drug interactions between HIV antiretroviralsand other necessary drugs can be dangerous and require specialmonitoring(i).

Three studies, including one oral poster, on the co-administrationof PREZISTA, were presented at the Eighth Annual InternationalCongress on Drug Therapy in HIV Infection (HIV 8) taking place inGlasgow, Scotland from 12 - 16 November.

PREZISTA (darunavir, also known by the investigational compoundnumber TMC114), co-administered with 100 mg ritonavir(darunavir/rtv), is being studied for the treatment of humanimmunodeficiency virus (HIV) infection in antiretroviraltreatment-experienced adult patients. It is currently approved in theUnited States, Canada and Russia. An application for marketingauthorization was filed with the European Agency for the Evaluationof Medicinal Products in January 2006.

"With many HIV-infected people taking multiple medications, theincreased potential for drug interactions poses a serious challengein finding a safe and effective antiretroviral treatment regimen,"said David J. Back, Ph.D., Professor, Department of Pharmacology,University of Liverpool. "These data are important because theyprovide information on the interactions between PREZISTA/rtv andother medications commonly used in patients with HIV."

Use of PREZISTA with common medications (Oral poster PL 5.1)

Location and time: Clyde Auditorium; Tuesday, November 14,10:30 - 10:45 a.m. GMT

Dr. Back reported results in an oral presentation from clinicalstudies evaluating the pharmacokinetic interactions betweendarunavir/rtv and a variety of drugs including antiretrovirals suchas atazanavir, indinavir, lopinavir/ritonavir, saquinavir/ritonavir,efavirenz, nevirapine, tenofovir disoproxil fumarate; antibioticssuch as clarithromycin and ketoconazole; and other medications forvarious conditions including atorvastatin, omeprazole, ranitidine,sildenafil, sertraline, paroxetine and oral contraceptives. Resultsshowed that darunavir/rtv may be combined with many drugs with nodose adjustments. Some co-administered drugs, such as indinavir,sildenafil and atorvastatin may require dose adjustments. In general,the study found that drug interactions between darunavir/rtv anddrugs commonly used in patients with HIV are manageable.

Pharmacokinetic interaction between PREZISTA with SSRIs assessed(Poster # P295)

Location and time: Exhibition Hall 4; Monday, November 13 toWednesday, November 15, 10:00 a.m. - 7:00 p.m. GMT

The pharmacokinetic interaction between darunavir/rtv and theselective serotonin reuptake inhibitors (SSRIs), paroxetine andsertraline, were assessed in a phase I, open-label, two-panel,randomised, crossover study in 36 HIV-negative, healthy volunteerspresented by Vanitha Sekar, Ph.D. of Tibotec Pharmaceuticals. Safetyand tolerability also were assessed. The study found that thepharmacokinetics of darunavir/rtv were not significantly affected inthe presence of sertraline or paroxetine, and that darunavir/rtv wasgenerally well tolerated. Paroxetine and sertraline totalconcentrations were decreased in the presence of darunavir/rtv.Clinical monitoring is recommended when co-administeringdarunavir/rtv with SSRIs, although studies have not shown acorrelation between plasma concentration of SSRIs and antidepressantresponse.

Co-administration of PREZISTA with methadone (Poster # P294)

Location and time: Exhibition Hall 4; Monday, November 13 toWednesday, November 15, 10:00 a.m. - 7:00 p.m. GMT

Dr. Sekar also conducted a trial assessing the effect of multipledoses of darunavir/rtv on plasma concentrations of methadone sinceadministration of boosted protease inhibitors has been shown todecrease methadone plasma concentrations. Results of the open-label,add-on trial involving 16 patients found co-administration of thetreatment with methadone did not adversely affect the blood plasmaconcentrations of methadone, methadone adjustment was not requiredwhen administered with darunavir/rtv, and withdrawal syndrome wasuncommon, occurring in one patient (1/16 patients, 6 percent) duringthe co-administration period.


PREZISTA (darunavir) is an investigational protease inhibitor thatis currently in Phase III comparative clinical trials versuslopinavir/ritonavir in treatment-naïve (ARTEMIS) andtreatment-experienced patients (TITAN).

PREZISTA does not cure HIV infection or AIDS, and does not preventpassing HIV to others.

In studies, darunavir/rtv was generally well tolerated. The mostcommon moderate to severe side effects associated with darunavirinclude headache (3.8 percent), diarrhoea (2.3 percent), abdominalpain (2.3 percent), constipation (2.3 percent), and vomiting (1.5percent). Mild to moderate rash was seen in 7 percent of patients.Severe skin rash, including erythema multiforme and Stevens-JohnsonSyndrome, has been reported in subjects receiving PREZISTA during theclinical development program. Four percent of patients discontinuedtreatment due to adverse events. People who are allergic to darunaviror any of its ingredients or ritonavir (Norvir) should not takedarunavir. It should be used with caution in patients with knownsulfonamide allergy.

There were few relevant drug-drug interactions with othermedications commonly used in HIV patient populations, such as otherantiretroviral medications, proton pump inhibitors, and H2 receptorantagonists. Patients should talk to their healthcare provider aboutall the medicines they are taking or plan to take, includingprescription and nonprescription medicines, vitamins, and herbalsupplements. Due to the need for co-administration of darunavir with100mg ritonavir, please refer to ritonavir prescribing informationfor a description of ritonavir contraindications.

Before taking darunavir, patients should tell their healthcareprovider if they have any medical conditions, including diabetes,liver problems, haemophilia, or allergy to sulfa medicines and shouldtell their doctor if they are pregnant or planning to becomepregnant, or are nursing. Darunavir should be used with caution inpatients with hepatic impairment.

High blood sugar, diabetes or worsening of diabetes, muscle pain,tenderness or weakness, and increased bleeding in people withhaemophilia have been reported in patients taking protease inhibitormedicines like darunavir. Changes in body fat have been seen in somepatients taking anti-HIV medicines, including loss of fat from legs,arms and face, increased fat in the abdomen and other internalorgans, breast enlargement and fatty lumps on the back of the neck.The cause and long-term health effects of these conditions are notknown at this time.

Clinical laboratory safety observed in the darunavir group wascomparable to the control group.

PREZISTA was developed by Tibotec Pharmaceuticals Ltd. In theU.S., it is marketed by Tibotec Therapeutics, a division of OrthoBiotech Products, L.P. In Canada, it is marketed by Tibotec, adivision of Janssen-Ortho Inc. Pending regulatory approval, Tibotec,a division of Janssen-Cilag, will commercialise PREZISTA in Europeand other countries.

For further information, please visit www.tibotec.com.

About Tibotec Pharmaceuticals Ltd.

Tibotec Pharmaceuticals Ltd., based in Cork, Ireland, is apharmaceutical research and development company. The Company's mainresearch and development facilities are in Mechelen, Belgium withoffices in Yardley, PA. Tibotec is dedicated to the discovery anddevelopment of innovative HIV/AIDS drugs and anti-infectives fordiseases of high unmet medical need.

Tibotec Pharmaceuticals is developing a Global Access Program tofacilitate access to its antiretrovirals for patients living withHIV/AIDS in developing countries. The Global Access Program forPREZISTA includes access pricing, registration, medical education forappropriate use and voluntary licensing.

About Tibotec

Tibotec, a division of Janssen-Cilag, will bring innovativeproducts for HIV/AIDS to patients in Europe, the Middle East andAfrica. This new division was created within the Janssen-Cilagcompanies in October 2005 to focus on patients' and health careproviders' specific needs in this disease domain. The company willalso commercialise medicine against other viral diseases in thefuture.


Janssen-Cilag is a leader in traditional and biological medicinesfor disorders such as in gastroenterology, women's health, mentalhealth and neurology as well as for pain, oncology, haematology andnephrology.

(i) "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents," DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents - A Working Group of the Office of AIDS Research Advisory Council (OARAC); Accessed at: http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf; last updated October 10, 2006.

Web site: http://www.tibotec.com

ots Originaltext: Tibotec Pharmaceuticals Ltd.Im Internet recherchierbar: http://www.presseportal.de

Contact:Kellie McLaughlin, mobile: +1-609-466-3808; or Hans Vanavermaete, mobile: +32-478-447-278

Tibotec Pharmaceuticals Ltd.

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Drug-Drug Interactions Clinically Manageable With PREZISTA(TM)