Efavirenz: profile and news
Balloon can put a heart in order 07 Mar 2006
...be treated. I have no doubt that Mr Martin has been given a diet and prescribed an anti-cholesterol tablet like simvastatin. Most ... - Scotsman,
Keep your cholesterol in check with Simvastatin Feb 9, 2006
...levels. The most prominent cholesterol drugs belong to the statin family, including Simvastatin and Atorvastatin to name a few. ... - LiveArticles.org,
Anti-cholesterol drug combo okay for muscles Feb 22, 2006
NEW YORK (Reuters Health) - Ezetimibe plus simvastatin, a combination of two anti-cholesterol drugs marketed by Merck/Schering-Plough Pharmaceuticals as Vytorin ... - Reuters
How can I prevent my children from becoming travel sick? Mar 2, 2006
...from Romford in which the reader is so attached to grapefruit for breakfast that he is not certain that he wouldn’t rather give up simvastatin (Zocor and ... - Times Online,
Kos Reports 2005 Fourth Quarter and Full Year Results, Forecasts ... Feb 23, 2006
In addition, during 2005 Kos announced the commencement of the AIM-HIGH morbidity/mortality study with Niaspan/simvastatin, jointly sponsored with National ... - Genetic Engineering News,
Romania: Sicomed Takeover Raises Zentiva's Turnover Mar 1, 2006
...product promoting teams.". Simvastatin is the market leader in its respective sector, according to company estimates. Zentiva intends ... - Reporter.gr,
Health Alert: Statin Power Feb 14, 2006
Letcher. He's in a study to see if a statin drug, Simvastatin, sold as Zocor, can boost his brain power and slow the disease. Dr ... - WIS,
Cholesterol drug OK opens cash artery for Genepharm Feb 1, 2006
By Rebecca Urban. GENERIC drug maker Genepharm will be able to sell its own version of lucrative cholesterol treatment Simvastatin from April. ... - The Age,
1 From the Harvard Medical School and Brigham and Women's Hospital ... Feb 17, 2006
Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. ... - Am J Clin Nutr (subscription),
Nutrition: Red Grapefruit Earns a Star on Cholesterol Test Feb 20, 2006
The researchers tested 57 patients ages 39 to 72 who had undergone coronary bypass surgery and had found that Zocor, or simvastatin, was ineffective. ... - New York Times,
Red grapefruit earns a star on cholesterol test Feb 22, 2006
The researchers tested 57 patients ages 39 to 72 who had undergone coronary bypass surgery and had found that Zocor, or simvastatin, was ineffective. ... - International Herald Tribune,
Prescription at a cost Feb 20, 2006
The two top-selling statins - atorvastatin sold as Lipitor and simvastatin sold as Lipex and Zocor - cost the Government more than $770 million in the past ... - Australian,
Statins To Reduce Cholesterol Levels Feb 24, 2006
...for use in the US: Lipitor® (atorvastatin), Lescol® (fluvastatin), Mevacor® (lovastatin), Pravachol® (pravastatin), Zocor® (simvastatin) and Crestor ... - WSOCtv.com,
Dr Reddy`s to sell 2 Merck generics Feb 1, 2006
...s Laboratories has signed an agreement with Merck & Co of the US to sell and distribute generic versions of two of its drugs, Zocor (simvastatin) and Proscar ... - Business Standard,
Cutting Certain Pills in Half Can Help Reduce Costs Feb 19, 2006
...experiment by the US Department of Veterans Affairs health system in which eligible patients split tablets of the cholesterol-lowering drug simvastatin in half ... - International News Service,
Case 4-2006 — A 79-Year-Old Woman with Myalgias, Fatigue, and ... Feb 9, 2006
Hyperlipidemia had been diagnosed six years earlier and had been controlled with simvastatin. Three years before admission, treatment ... - New England Journal of Medicine (subscription),
Stock Watch Feb 23, 2006
The organisation has signed an agreement with Merck to sell and distribute generic versions of two of its drugs, Zocor (simvastatin) and Proscar (finasteride ... - Express Pharma Pulse,
Study: Red grapefruit helps heart Feb 21, 2006
The researchers tested 57 patients, ages 39 to 72, who had undergone coronary bypass surgery and had found that Zocor, or simvastatin, was ineffective. ... - Los Angeles Daily News,
Biotech on high Feb 1, 2006
The Melbourne company told the Australian Stock Exchange the drug, known as simvastatin, had reached the final stage before sales begin. ... - Melbourne Herald Sun,
Drug sales boost shares 13pc Feb 1, 2006
Genepharm directors told the stock exchange the drug - known as simvastatin - had reached the final stage before sales begin. Simvastatin ... - Daily Telegraph,
Pfizer Driving Performance Through Growth of Current and New ... Feb 10, 2006
...benefits. In addition, Lipitor is performing well against generic simvastatin in many markets where the two medicines compete. This ... - MSN Money
Cholesterol drug move Feb 1, 2006
Genepharm Australia has reached the final stage of approval from the Therapeutic Goods Administration to sell its version of the drug simvastatin, the company ... - Advertiser Adelaide,
Splitting pills slices costs Feb 13, 2006
Veterans Affairs said it saved $46.5 million in 2003 by having eligible patients split pills for the cholesterol-lowering drug simvastatin, commercially sold ... - Poughkeepsie Journal,
Roche to Focus Resources on Availability of Invirase, Now ... Feb 6, 2006
...saquinavir in this population. Concomitant use of Invirase with lovastatin or simvastatin is not recommended. Caution should be ... - DG News
Volunteers needed for drug study Feb 17, 2006
Additional volunteers are being sought for a study into possible interaction between vitamin E and the cholesterol-reducing drugs simvastatin (often marketed ... - Corvallis Gazette Times,
Medicine return haul a huge waste Feb 14, 2006
Lipex, also known as simvastatin, has joined the top four medicines most often wasted, along with the stomach acidity regulator losec, 300mg aspirin and the ... - Manawatu Standard,
Research and Markets: Pfizer's Atorvastatin + Torcetrapib ... Feb 17, 2006
...combination is expected to have a major impact on the dyslipidemia market and is expected to compete with both atorvastatin and Vytorin (simvastatin + ezetimibe ... - Genetic Engineering News,
Pill-splitting plan could be a big cost saver Feb 5, 2006
The department of Veteran s Affairs saved $46.5 million in 2003 by encouraging eligible patients who took simvastatin, commercially sold as Zocor, to split ... - Portsmouth Herald News,
Medical Spending To Treat Hyperlipidemia Up 350% 1996-2003, USA Feb 14, 2006
Total expenditures for Lipitor (Atorvastatin), the top-selling drug, were 7.8 billion, while expenditures for Zocor (Simvastatin) totaled 5.5 billion. ... - Medical News Today (press release),
Strong demand for statin drugs pushes up sales Feb 14, 2006
Known as “statin drugs� or “statins,� Lipitor (atorvastatin) and Zocor (simvastatin) work by blocking the liver enzyme responsible for the production ... - Wilkes Barre Times-Leader,
Do Lackluster Trial Findings Mean New Avenues Are Needed for Heart ... Feb 9, 2006
...in reducing the risk of major coronary events among patients with previous myocardial infarction, compared with usual-dose (20 mg/d) simvastatin (Pedersen TR ... - Journal of American Medical Association (subscription),
Boehringer Ingelheim Announces 48-week Results from Aptivus(R) ... Feb 9, 2006
Taking APTIVUS/r with rifampin, St. John's wort, lovastatin, or simvastatin is not recommended. This list of medications is not complete. ... - PR Newswire (press release),
Toprol XL uncertainty weighs heavy on AstraZeneca Feb 3, 2006
...although it remains to be seen whether it will be able to maintain this growth rate once generic versions of Merck & Co's Zocor (simvastatin) and Bristol-Myers ... - Pharma Times (subscription),
Merck profits edge ahead in fourth quarter Feb 1, 2006
...helped by a 12% hike in revenues from asthma drug Singulair (montelukast) to $819 million, as well as a contribution from Vytorin (simvastatin and ezetimibe). ... - Pharma Times (subscription),
Pfizer's updated 2006 forecast disappoints Feb 13, 2006
...drug, the cholesterol-lowerer Lipitor (atorvastatin), are likely to be dented by competition in the form of Merck & Co's rival Zocor (simvastatin), which is ... - Pharma Times (subscription),
The Market for Metabolic Syndrome Therapies is Forecast to ... Feb 1, 2006
Some of the most widely prescribed drugs for constituents of the metabolic syndrome (eg, metformin, glibenclamide, simvastatin, lovastatin, pravastatin ... - International News Service,
Pharmac Agrees To Fund Vytorin Cholestrol Drug Feb 1, 2006
Merck Sharp and Dohme, says one part of the drug, ezetimibe, inhibits absoprtion of cholesterol, while the more common statin, simvastatin, lowers cholesterol. ... - newswire.co.nz,
Other information
Indication
For use in combination treatment of HIV infection (AIDS)
Pharmacology
Efavirenz (dideoxyinosine, ddI) is an oral nucleoside reverse transcriptase inhibitor (NRTI). It is a synthetic purine derivative and, similar to zidovudine, zalcitabine, and stavudine. Efavirenz was originally approved specifically for the treatment of HIV infections in patients who failed therapy with zidovudine. Currently, the CDC recommends that Efavirenz be given as part of a three-drug regimen that includes another nucleoside reverse transcriptase inhibitor (e.g., lamivudine, stavudine, zidovudine) and a protease inhibitor or efavirenz when treating HIV infection.
Mechanism Of Action
Similar to zidovudine, Efavirenz inhibits the activity of viral RNA-directed DNA polymerase (i.e., reverse transcriptase). Antiviral activity of Efavirenz is dependent on intracellular conversion to the active triphosphorylated form. The rate of Efavirenz phosphorylation varies, depending on cell type. It is believed that inhibition of reverse transcriptase interferes with the generation of DNA copies of viral RNA, which, in turn, are necessary for synthesis of new virions. Intracellular enzymes subsequently eliminate the HIV particle that previously had been uncoated, and left unprotected, during entry into the host cell. Thus, reverse transcriptase inhibitors are virustatic and do not eliminate HIV from the body. Even though human DNA polymerase is less susceptible to the pharmacologic effects of triphosphorylated Efavirenz, this action may nevertheless account for some of the drug's toxicity.
Drug Category
Anti-HIV Agents; Nonnucleoside Reverse Transcriptase Inhibitors; ATC:J05AG03
Brand Names/Synonyms
DMP 266; DMP-266; EFV; Efavirenz; Stocrin; Sustiva
Dosage Forms
TABLET, CAPSULE
Absorption
Not Available
Interactions
-->Interactions for Efavirenz:
Efavirenz has been shown in vivo to induce CYP3A4. Other compounds that are substrates of
CYP3A4 may have decreased plasma concentrations when coadministered with SUSTIVA (efavirenz). In vitro studies
have demonstrated that efavirenz inhibits 2C9, 2C19, and 3A4 isozymes in the range of observed efavirenz plasma
concentrations. Coadministration of efavirenz with drugs primarily metabolized by these isozymes may result in
altered plasma concentrations of the coadministered drug. Therefore, appropriate dose adjustments may be necessary
for these drugs.
Drugs which induce CYP3A4 activity (eg, phenobarbital, rifampin, rifabutin) would be expected to
increase the clearance of efavirenz resulting in lowered plasma concentrations. Drug interactions with SUSTIVA are
summarized in Table 5.
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Table 5a: Drugs That Should Not Be Coadministered With SUSTIVA
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Drug Class
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Drugs Within Class Not To Be Coadministered With SUSTIVA
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Antihistamines Benzodiazepines GI Motility Agents Anti-Migraine Antifungal
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astemizole midazolam, triazolam
cisapride ergot derivatives voriconazole
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Established Drug Interactions
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Drug Name
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Effect
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Clinical Comment
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Atazanavir
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¯atazanavir
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When coadministered with SUSTIVA in treatment-naive patients, the recommended dose of atazanavir
is 300 mg with ritonavir 100 mg and SUSTIVA 600 mg (all once daily). Dosing recommendations for SUSTIVA and
atazanavir in treatment-experienced patients have not been established.
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Established Drug Interactions (continued)
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Drug Name
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Effect
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Clinical Comment
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Clarithromycin
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¯clarithromycin concentration
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Plasma concentrations decreased by SUSTIVA; clinical significance unknown. In uninfected
volunteers, 46% developed rash while receiving SUSTIVA and clarithromycin. No dose adjustment of SUSTIVA is
recommended when given with clarithromycin. Alternatives to clarithromycin, such as azithromycin, should be
considered. Other macrolide antibiotics, such as erythromycin, have not been studied in combination with
SUSTIVA.
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14-OH metabolite concentration
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Indinavir
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¯indinavir concentration
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The optimal dose of indinavir, when given in combination with SUSTIVA, is not known. Increasing
the indinavir dose to 1000 mg every 8 hours does not compensate for the increased indinavir metabolism due to
SUSTIVA. When indinavir at an increased dose (1000 mg every 8 hours) was given with SUSTIVA (600 mg once
daily), the indinavir AUC and Cmin were decreased on average by 33-46% and 39-57%, respectively,
compared to when indinavir (800 mg every 8 hours) was given alone.
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Lopinavir/ritonavir
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¯lopinavir concentration
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A dose increase of lopinavir/ritonavir to 533/133 mg (4 capsules or 6.5 mL) twice daily taken
with food is recommended when used in combination with SUSTIVA.
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Methadone
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¯methadone concentration
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Coadministration in HIV-infected individuals with a history of injection drug use resulted in
decreased plasma levels of methadone and signs of opiate withdrawal. Methadone dose was increased by a mean of
22% to alleviate withdrawal symptoms. Patients should be monitored for signs of withdrawal and their methadone
dose increased as required to alleviate withdrawal symptoms.
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Ethinyl estradiol
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ethinyl estradiol concentration
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Plasma concentrations increased by SUSTIVA (efavirenz); clinical significance unknown. Because
the potential interaction of efavirenz with oral contraceptives has not been fully characterized, a reliable
method of barrier contraception should be used in addition to oral contraceptives.
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Rifabutin
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¯rifabutin concentration
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Increase daily dose of rifabutin by 50%. Consider doubling the rifabutin dose in regimens where
rifabutin is given 2 or 3 times a week.
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Rifampin
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¯efavirenz concentration
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Clinical significance of reduced efavirenz concentrations unknown.
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Ritonavir
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ritonavir concentration
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Combination was associated with a higher frequency of adverse clinical experiences (eg,
dizziness, nausea, paresthesia) and laboratory abnormalities (elevated liver enzymes). Monitoring of liver
enzymes is recommended when SUSTIVA is used in combination with ritonavir.
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efavirenz concentration
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Saquinavir
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¯saquinavir
concentration
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Should not be used as sole protease inhibitor in combination with SUSTIVA.
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Sertraline
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¯sertraline concentration
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Increases in sertraline dose should be guided by clinical response.
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Other Potentially Clinically Significant Drug or Herbal Product Interactions With
SUSTIVAb
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Anticoagulants: Warfarin
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Plasma concentrations and effects potentially increased or decreased by SUSTIVA.
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Anticonvulsants: Phenytoin Phenobarbital Carbamazepine
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Potential for reduction in anticonvulsant and/or efavirenz plasma levels; periodic monitoring of
anticonvulsant plasma levels should be conducted.
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Antifungals: Itraconazole Ketoconazole
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Drug interaction studies with SUSTIVA and these imidazole and triazole antifungals have not been
conducted. SUSTIVA has the potential to decrease plasma concentrations of itraconazole and ketoconazole.
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Anti-HIV protease inhibitors: Saquinavir/ritonavir combination
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No pharmacokinetic data are available.
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Amprenavir
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SUSTIVAhas the potential to decrease serum concentrations of amprenavir.
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Non-nucleoside reverse transcriptase inhibitors
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No studies have been performed with other NNRTIs.
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St. Johnís wort (Hypericum perforatum)
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Expected to substantially decrease plasma levels of efavirenz;has not been studied in
combination with SUSTIVA.
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a See Tables 1 and 2.
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b This table is not all-inclusive.
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Other Drugs: Based on the results of drug interaction studies, no dosage adjustment is
recommended when SUSTIVA (efavirenz) is given with the following: aluminum/magnesium hydroxide antacids,
azithromycin, cetirizine, famotidine, fluconazole, lamivudine, lorazepam, nelfinavir, paroxetine, and zidovudine.
Specific drug interaction studies have not been performed with SUSTIVA and NRTIs other than lamivudine
and zidovudine. Clinically significant interactions would not be expected since the NRTIs are metabolized via a
different route than efavirenz and would be unlikely to compete for the same metabolic enzymes and elimination
pathways.
Chemical IUPAC Name
8-chloro-5-(2-cyclopropylethynyl)-5-(trifluoromethyl)-4-oxa-2-azabicyclo[4.4.0]deca-7,9,11-trien-3-one
Chemical Formula
C14H9ClF3NO2
Half Life
40-55 hours
Drug Type
Approved Drug
# Accession No
APRD00059
CAS Registry Number
154598-52-4
