efavirenz

[E(THYNE) + F(LUORO)- + VIR(US) + (B)ENZ(YL).]

Brand names: Sustiva®

Chemical formula:

Drug Forms:
• Efavirenz Oral capsule (below)
• Efavirenz Oral tablet

Español:
• Efavirenz, Cápsula oral
• Efavirenz, Tableta oral

Efavirenz Oral capsule

What is this medicine?

EFAVIRENZ (e fa VEER ens) is an antiretroviral medicine. It is used with other medicines to treat HIV. This medicine is not a cure for HIV. It will not stop the spread of HIV to others.
 
This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
•history of a drug or alcohol abuse problem
•history of depression or other mental illness
•liver disease
•seizures
•taking any other medicines
•an unusual or allergic reaction to efavirenz, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I use this medicine?

Take this medicine by mouth with a glass of water. Follow the directions on the prescription label. Take this medicine on an empty stomach, at least 30 minutes before or 2 hours after food. Do not take with food. Take your dose at bedtime. Take your medicine at regular intervals. Do not take your medicine more often than directed. For your anti-HIV therapy to work as well as possible, take each dose exactly as prescribed. Do not skip doses or stop your medicine even if you feel better. Skipping doses may make the HIV virus resistant to this medicine and other medicines. Do not stop taking except on your doctor's advice.

Talk to your pediatrician regarding the use of this medicine in children. While this drug may be prescribed for children as young as 3 years old for selected conditions, precautions do apply.

A patient information sheet for the product will be given with each prescription and refill. Read this sheet carefully each time. The sheet may change frequently.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.

What may interact with this medicine?

Do not take this medicine with any of the following medications:
•cerviastatin
•cisapride
•disopyramide
•medicines for headaches like dihydroergotamine, ergonovine, ergotamine, methylergonovine
•midazolam
•pimozide
•rifapentine
•St. John's Wort
•triazolam
•voriconazole

This medicine may also interact with the following medications:
•amiodarone
•clarithromycin
•female hormones, like estrogens or progestins and birth control pills, patches, rings, or injections
•medicines for blood pressure like diltiazem, nifedipine, verapamil
•medicines for cholesterol like simvastatin
•medicines for depression, anxiety, or psychotic disturbances
•medicines for fungal infections like ketoconazole, itraconazole, and posaconazole
•medicines for seizures like carbamazepine, phenobarbital, phenytoin
•medicines for sleep
•methadone
•other medicines for HIV
•red yeast rice
•rifabutin
•rifampin
•sirolimus
•tacrolimus
•warfarin

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Visit your doctor or health care professional for regular check ups. Discuss any new symptoms with your doctor. You will need to have important blood work done while on this medicine.

HIV is spread to others through sexual or blood contact. Talk to your doctor about how to stop the spread of HIV.

You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how this medicine affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells. Avoid alcohol and mood altering (street) drugs while taking this medicine because they can make these side effects worse.

Birth control pills may not work properly while you are taking this medicine. Talk to your doctor about using an extra method of birth control. Women who can still have children must use a reliable form of barrier contraception, like a condom or diaphragm.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:
•allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
•changes in behavior like severe depression, strange thoughts, thoughts of suicide, or angry behavior
•hallucinations

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
•diarrhea
•difficulty sleeping, strange dreams
•dizziness
•trouble concentrating
•unusually tired
•upset stomach, vomiting
•weight gain around waist, back, or thinning of face, arms, legs

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of the reach of children.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Throw away any unused medicine after the expiration date.

Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

Efavirenz
Systematic (IUPAC) name
(4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one
Identifiers
CAS number	154598-52-4
ATC code	J05AG03
PubChem	64139
DrugBank	APRD00059
ChemSpider	57715
Chemical data
Formula	C14H9ClF3NO2
Mol. mass	315.675 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	?
Protein binding	99.5-99.75%
Metabolism	Hepatic (CYP3A4 and CYP2B6-mediated)
Half life	40-55 hours
Excretion	Renal and fecal
Therapeutic considerations
Pregnancy cat.	D (U.S.)
Legal status	POM (UK), ℞-only (U.S.)
Routes	Oral
Y(what is this?)  (verify)

Efavirenz (brand names Sustiva and Stocrin) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and is used as part of highly active antiretroviral therapy (HAART) for the treatment of a human immunodeficiency virus (HIV) type 1.

For HIV infection that has not previously been treated, the United States Department of Health and Human Services Panel on Antiretroviral Guidelines currently recommends the use of efavirenz in combination with lamivudine/zidovudine (Combivir) or tenofovir/emtricitabine (Truvada) as the preferred NNRTI-based regimens in adults and adolescents.

Efavirenz is also used in combination with other antiretroviral agents as part of an expanded postexposure prophylaxis regimen to reduce the risk of HIV infection in people exposed to a significant risk (e.g. needlestick injuries, certain types of unprotected sex etc.).

The usual adult dose is 600 mg once a day. It is usually taken on an empty stomach at bedtime to reduce neurological and psychiatric adverse effects.

Efavirenz was combined with the popular HIV medication Truvada, which consists of tenofovir and emtricitabine, all of which are reverse transcriptase inhibitors. This combination of three medications approved by the U.S. Food and Drug Administration (FDA) in July 2006 under the brand name Atripla, provides HAART in a single tablet taken once a day. It results in a simplified drug regimen for many patients.

Contents 1 History 2 Indications 3 Mode of action 4 Dosing 5 Drug interactions 6 Adverse effects 7 Recreational use 8 Pricing information 9 Chemical properties 10 References 11 External links

History

Efavirenz was approved by the FDA on September 21, 1998, making it the 14th approved antiretroviral drug.

Indications

Efavirenz is used to treat HIV infection. It is never used alone and is always given in combination with other drugs. The decision on when to start treatment should take into account CD4 count, HIV viral load, treatment history, resistance profiles and patient preference.

Since the preliminary publication of the results of the ACTG 5142 trial in 2006 which compared efavirenz against lopinavir, efavirenz has been used as first line treatment in preference to the protease inhibitors. The ACTG 5095 trial showed that the potency of efavirenz is maintained at all CD4 counts and HIV viral loads.

Mode of action

Efavirenz falls in the NNRTI class of antiretrovirals. Both nucleoside and non-nucleoside RTIs inhibit the same target, the reverse transcriptase enzyme, an essential viral enzyme which transcribes viral RNA into DNA. Unlike nucleoside RTIs, which bind at the enzyme's active site, NNRTIs act allosterically by binding to a distinct site away from the active site known as the NNRTI pocket.

Efavirenz is not effective against HIV-2, as the pocket of the HIV-2 reverse transcriptase has a different structure, which confers intrinsic resistance to the NNRTI class.^[1]

As most NNRTIs bind within the same pocket, viral strains which are resistant to efavirenz are usually also resistant to the other NNRTIs, nevirapine and delavirdine. The most common mutation observed after efavirenz treatment is K103N, which is also observed with other NNRTIs.^[2]

Dosing

The usual adult dose of efavirenz is 600 mg per day (usually given at bedtime); or 800 mg daily when given concurrently with rifampicin as part of treatment of co-infection with tuberculosis.

Drug interactions

• Efavirenz is metabolized in the liver, and possesses both inhibitory and inducing effects on the 3A4 isoform of the cytochrome P450 system. This means efavirenz may interact with other drugs metabolized in the liver, requiring either increased or decreased dosages.
• Efavirenz lowers blood levels of most protease inhibitors. Dosages of amprenavir, atazanavir, or indinavir may need to be increased. The blood levels of saquinavir are dramatically lowered, so that the two drugs cannot be used simultaneously.
• St John's wort and garlic supplements may decrease efavirenz blood levels.

Adverse effects

• Psychiatric symptoms, including insomnia, confusion, memory loss, and depression, are common,^[3] and more serious symptoms such as psychosis may occur in patients with compromised liver or kidney function.^[4][5]
• Rash, nausea, dizziness and headache may occur
• Efavirenz can cause birth defects and should not be used in women who might become pregnant^[6]
• Safety in children has not been established
• Use of efavirenz can produce a false positive result in some urine tests for marijuana ^[7][8]

Recreational use

• Abuse of efavirenz by crushing and smoking the tablets for supposed hallucinogenic and dissociative effects has been reported in South Africa ^[9][10][11]

Pricing information

As with most HIV treatments, efavirenz is quite expensive. A one month supply of 600 mg tablets cost approximately $550 in April 2008^[12]. Some emerging countries have opted to purchase Indian generics^[13] such as Efavir by Cipla Ltd^[14] for a fraction of the cost.

Chemical properties

Efavirenz is chemically described as (S)-6-chloro-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one. Its empirical formula is C₁₄H₉ClF₃NO₂. Efavirenz is a white to slightly pink crystalline powder with a molecular mass of 315.68 g/mol. It is practically insoluble in water (<10 µg/mL).

References

1. ^ Ren J, Bird LE, Chamberlain PP, et al. (2002). "Structure of HIV-2 reverse transcriptase at 2.35-A resolution and the mechanism of resistance to non-nucleoside inhibitors". Proc Natl Acad Sci USA 99: 14410–15. doi:10.1073/pnas.222366699. PMID 12386343. 
2. ^ Sustiva (efavirenz) capsules and tablets. Product information (April 2005)
3. ^ Cespedes MS, Aberg JA. Neuropsychiatric complications of antiretroviral therapy. Drug Safety. 2006;29(10):865-74. PMID 16970510
4. ^ Hasse B, Günthard HF, Bleiber G, Krause M. Efavirenz intoxication due to slow hepatic metabolism. Clinical Infectious Diseases. 2005 Feb 1;40(3):e22-3. PMID 15668854
5. ^ Lowenhaupt EA, Matson K, Qureishi B, Saitoh A, Pugatch D. Psychosis in a 12-year-old HIV-positive girl with an increased serum concentration of efavirenz. Clinical Infectious Diseases. 2007 Nov 15;45(10):e128-30. PMID 17968817
6. ^ DHHS panel. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (October 10, 2006). (Available for download from AIDSInfo)
7. ^ Rossi S, Yaksh T, Bentley H, van den Brande G, Grant I, Ellis R. Characterization of interference with 6 commercial delta9-tetrahydrocannabinol immunoassays by efavirenz (glucuronide) in urine. Clinical Chemistry. 2006 May;52(5):896-7. PMID 16638958
8. ^ Röder CS, Heinrich T, Gehrig AK, Mikus G. Misleading results of screening for illicit drugs during efavirenz treatment. AIDS. 2007 Jun 19;21(10):1390-1. PMID 17545727
9. ^ IOL: Thugs get high on stolen Aids drugs
10. ^ Getting high on HIV drugs in S Africa. BBC News, 8 December 2008.
11. ^ 'No Turning Back': Teens Abuse HIV Drugs. ABC News, April 6, 2009.
12. ^ Price listed on http://drugstore.com website, 4/20/2008
13. ^ IndiaDaily - A new trend in emerging nations - Brazil opts for Indian generic drug ignoring US pharmaceutical giant Merck’s patent on AIDS drug Efavirenz
14. ^ www.cipla.com

External links

• Manufacturer's site
• Prescribing information

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