Efavirenz Teva

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Efavirenz Teva 600 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 600 mg efavirenz. 
 
Excipients with known effect  
 
Each film-coated tablet contains 9.98 mg lactose (as monohydrate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet 
Yellow, capsule-shaped, film-coated tablet debossed with “Teva” on one side and “7541” on the other 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Efavirenz is indicated in antiviral combination treatment of human immunodeficiency virus-1 (HIV-1) 
infected adults, adolescents and children 3 years of age and older. 
 
Efavirenz has not been adequately studied in patients with advanced HIV disease, namely in patients 
with CD4 counts < 50 cells/mm3, or after failure of protease inhibitor (PI)-containing regimens. 
Although cross-resistance of efavirenz with PIs has not been documented, there are at present 
insufficient data on the efficacy of subsequent use of PI-based combination therapy after failure of 
regimens containing efavirenz. 
 
For a summary of clinical and pharmacodynamic information, see section 5.1. 
 
4.2 Posology and method of administration 
 
 
Therapy should be initiated by a physician experienced in the management of HIV infection. 
 
Posology 
 
Efavirenz must be given in combination with other antiretroviral medicines (see section 4.5). 
 
In order to improve the tolerability of nervous system adverse reactions, bedtime dosing is 
recommended (see section 4.8). 
 
Adults and adolescents over 40 kg 
The recommended dose of efavirenz in combination with nucleoside analogue reverse transcriptase 
inhibitors (NRTIs) with or without a PI (see section 4.5) is 600 mg orally, once daily. 
 
Efavirenz film-coated tablets are not suitable for children weighing less than 40 kg. Other 
formulations are available for these patients. 
 

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Dose adjustment 
If efavirenz is co-administered with voriconazole, the voriconazole maintenance dose must be 
increased to 400 mg every 12 hours and the efavirenz dose must be reduced by 50%, i.e. to 300 mg 
once daily. When treatment with voriconazole is stopped, the initial dose of efavirenz should be 
restored (see section 4.5). 
 
If efavirenz is co-administered with rifampicin to patients weighing 50 kg or more, an increase in the 
dose of efavirenz to 800 mg/day may be considered (see section 4.5). 
 
Special populations 
 
Renal impairment 
The pharmacokinetics of efavirenz have not been studied in patients with renal insufficiency; however, 
less than 1% of an efavirenz dose is excreted unchanged in the urine, so the impact of renal 
impairment on efavirenz elimination should be minimal (see section 4.4). 
 
Hepatic impairment 
Patients with mild liver disease may be treated with their normally recommended dose of efavirenz. 
Patients should be monitored carefully for dose-related adverse reactions, especially nervous system 
symptoms (see sections 4.3 and 4.4). 
 
Method of administration 
 
It is recommended that efavirenz be taken on an empty stomach. The increased efavirenz 
concentrations observed following administration of efavirenz with food may lead to an increase in 
frequency of adverse reactions (see sections 4.4 and 5.2). 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
Patients with severe hepatic impairment (Child Pugh Class C) (see section 5.2). 
 
Co-administration with terfenadine, astemizole, cisapride, midazolam, triazolam, pimozide, bepridil, 
or ergot alkaloids (for example, ergotamine, dihydroergotamine, ergonovine, and methylergonovine) 
because competition for CYP3A4 by efavirenz could result in inhibition of metabolism and create the 
potential for serious and/or life-threatening adverse reactions [for example, cardiac arrhythmias, 
prolonged sedation or respiratory depression] (see section 4.5). 
 
Co-administration with elbasvir (EBR) and grazoprevir (GZR) due to the potential for significant 
decreases in plasma concentrations of EBR and GZR (see section 4.5). 
 
Herbal preparations containing St. John's wort (Hypericum perforatum) due to the risk of decreased 
plasma concentrations and reduced clinical effects of efavirenz (see section 4.5). 
 
Patients with: 
- a family history of sudden death or of congenital prolongation of the QTc interval on 

electrocardiograms, or with any other clinical condition known to prolong the QTc interval. 
- a history of symptomatic cardiac arrhythmias or with clinically relevant bradycardia or with 

congestive cardiac failure accompanied by reduced left ventricle ejection fraction. 
- severe disturbances of electrolyte balance e.g. hypokalemia or hypomagnesemia. 
 
Patients taking drugs that are known to prolong the QTc interval (proarrythmic).  
These drugs include: 
- antiarrhythmics of classes IA and III, 
- neuroleptics, antidepressive agents, 

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- certain antibiotics including some agents of the following classes: macrolides, fluoroquinolones, 
imidazole and triazole antifungal agents, 

- certain non-sedating antihistamines (terfenadine, astemizole), 
- cisapride, 
- flecainide, 
- certain antimalarials, 
- methadone. 
 
4.4 Special warnings and precautions for use 
 
Efavirenz must not be used as a single agent to treat HIV or added on as a sole agent to a failing 
regimen. Resistant virus emerges rapidly when efavirenz is administered as monotherapy. The choice 
of new antiretroviral agent(s) to be used in combination with efavirenz should take into consideration 
the potential for viral cross-resistance (see section 5.1). 
 
Co-administration of efavirenz with the fixed-combination tablet containing efavirenz, emtricitabine, 
and tenofovir disoproxil is not recommended, unless needed for dose adjustment (for example, with 
rifampicin). 
 
Coadministration of sofosbuvir/velpatasvir with efavirenz is not recommended (see section 4.5). 
Concomitant administration of velpatasvir/sofosbuvir/voxilaprevir with efavirenz is not recommended 
(see section 4.5). 
 
Coadministration of glecaprevir/pibrentasvir with efavirenz may significantly decrease plasma 
concentrations of glecaprevir and pibrentasvir, leading to reduced therapeutic effect. Co-
administration of glecaprevir/pibrentasvir with efavirenz is not recommended (see section 4.5). 
 
Concomitant use of Ginkgo biloba extracts is not recommended (see section 4.5). 
 
When prescribing medicinal products concomitantly with efavirenz, physicians should refer to the 
corresponding Summary of Product Characteristics. 
 
While effective viral suppression with antiretroviral therapy, has been proven to substantially reduce 
the risk of sexual transmission, a residual risk cannot be excluded. Precautions  to prevent 
transmission should be taken in accordance with national guidelines. 
 
If any antiretroviral medicinal product in a combination regimen is interrupted because of suspected 
intolerance, serious consideration should be given to simultaneous discontinuation of all antiretroviral 
medicinal products. The antiretroviral medicinal products should be restarted at the same time upon 
resolution of the intolerance symptoms. Intermittent monotherapy and sequential reintroduction of 
antiretroviral agents is not advisable because of the increased potential for selection of resistant virus. 
 
Rash 
 
Mild-to-moderate rash has been reported in clinical studies with efavirenz and usually resolves with 
continued therapy. Appropriate antihistamines and/or corticosteroids may improve the tolerability and 
hasten the resolution of rash. Severe rash associated with blistering, moist desquamation or ulceration 
has been reported in less than 1% of patients treated with efavirenz. The incidence of erythema 
multiforme or Stevens-Johnson syndrome was approximately 0.1%. Efavirenz must be discontinued in 
patients developing severe rash associated with blistering, desquamation, mucosal involvement or 
fever. If therapy with efavirenz is discontinued, consideration should also be given to interrupting 
therapy with other antiretroviral agents to avoid development of resistant virus (see section 4.8). 
Experience with efavirenz in patients who discontinued other antiretroviral agents of the NNRTI class 
is limited (see section 4.8). Efavirenz is not recommended for patients who have had a life-threatening 
cutaneous reaction (e.g., Stevens-Johnson syndrome) while taking another NNRTI. 
 

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Psychiatric symptoms 
 
Psychiatric adverse reactions have been reported in patients treated with efavirenz. Patients with a 
prior history of psychiatric disorders appear to be at greater risk of these serious psychiatric adverse 
reactions. In particular, severe depression was more common in those with a history of depression. 
There have also been post-marketing reports of severe depression, death by suicide, delusions, 
psychosis-like behaviour and catatonia. Patients should be advised that if they experience symptoms 
such as severe depression, psychosis or suicidal ideation, they should contact their doctor immediately 
to assess the possibility that the symptoms may be related to the use of efavirenz, and if so, to 
determine whether the risks of continued therapy outweigh the benefits (see section 4.8). 
 
Nervous system symptoms 
 
Symptoms including, but not limited to dizziness, insomnia, somnolence, impaired concentration and 
abnormal dreaming are frequently reported adverse reactions in patients receiving efavirenz 600 mg 
daily in clinical studies (see section 4.8). Nervous system symptoms usually begin during the first one 
or two days of therapy and generally resolve after the first 2-4 weeks. Patients should be informed that 
if they do occur, these common symptoms are likely to improve with continued therapy and are not 
predictive of subsequent onset of any of the less frequent psychiatric symptoms. 
 
Seizures 
 
Convulsions have been observed in adult and paediatric patients receiving efavirenz, generally in the 
presence of known medical history of seizures. Patients who are receiving concomitant anticonvulsant 
medicinal products primarily metabolised by the liver, such as phenytoin, carbamazepine and 
phenobarbital, may require periodic monitoring of plasma levels. In a drug interaction study, 
carbamazepine plasma concentrations were decreased when carbamazepine was co-administered with 
efavirenz (see section 4.5). Caution must be taken in any patient with a history of seizures. 
 
Hepatic events 
 
A few of the postmarketing reports of hepatic failure occurred in patients with no pre-existing hepatic 
disease or other identifiable risk factors (see section 4.8). Liver enzyme monitoring should be 
considered for patients without pre-existing hepatic dysfunction or other risk factors. 
 
QTc Prolongation 
 
QTc prolongation has been observed with the use of efavirenz (see sections 4.5 and 5.1). 
 
Consider alternatives to efavirenz for coadministration with a drug with a known risk of Torsade de 
Pointes or when to be administered to patients at higher risk of Torsade de Pointes. 
 
Effect of food 
 
The administration of efavirenz with food may increase efavirenz exposure (see section 5.2) and may 
lead to an increase in the frequency of adverse reactions (see section 4.8). It is recommended that 
efavirenz be taken on an empty stomach, preferably at bedtime. 
 
Immune Reactivation Syndrome 
 
In HIV infected patients with severe immune deficiency at the time of institution of combination 
antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic 
pathogens may arise and cause serious clinical conditions, or aggravation of symptoms. Typically, 
such reactions have been observed within the first few weeks or months of initiation of CART. 
Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, 
and pneumonia caused by Pneumocystis jiroveci (formerly known as Pneumocystis carinii). Any 
inflammatory symptoms should be evaluated and treatment instituted when necessary. Autoimmune 

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disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported to occur in the 
setting of immune reactivation; however, the reported time to onset is more variable and these events 
can occur many months after initiation of treatment. 
 
Weight and metabolic parameters 
 
Weight and levels of blood lipids and glucose may increase during antiretroviral therapy. Such 
changes may in part be linked to disease control and life style. For lipids, there is in some cases 
evidence for a treatment effect, while for weight gain there is no strong evidence relating this to any 
particular treatment. For monitoring of blood lipids and glucose reference is made to established HIV 
treatment guidelines. Lipid disorders should be managed as clinically appropriate 
 
Osteonecrosis 
 
Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol 
consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been 
reported particularly in patients with advanced HIV disease and/or long-term exposure to combination 
antiretroviral therapy (CART). Patients should be advised to seek medical advice if they experience 
joint aches and pain, joint stiffness or difficulty in movement. 
 
Special populations 
 
Liver disease 
Efavirenz is contraindicated in patients with severe hepatic impairment (see sections 4.3 and 5.2) and 
not recommended in patients with moderate hepatic impairment because of insufficient data to 
determine whether dose adjustment is necessary. Because of the extensive cytochrome P450-mediated 
metabolism of efavirenz and limited clinical experience in patients with chronic liver disease, caution 
must be exercised in administering efavirenz to patients with mild hepatic impairment. Patients should 
be monitored carefully for dose-related adverse reactions, especially nervous system symptoms. 
Laboratory tests should be performed to evaluate their liver disease at periodic intervals (see section 
4.2). 
 
The safety and efficacy of efavirenz has not been established in patients with significant underlying 
liver disorders. Patients with chronic hepatitis B or C and treated with combination antiretroviral 
therapy are at increased risk for severe and potentially fatal hepatic adverse reactions. Patients with 
pre-existing liver dysfunction including chronic active hepatitis have an increased frequency of liver 
function abnormalities during combination antiretroviral therapy and should be monitored according 
to standard practice. If there is evidence of worsening liver disease or persistent elevations of serum 
transaminases to greater than 5 times the upper limit of the normal range, the benefit of continued 
therapy with efavirenz needs to be weighed against the potential risks of significant liver toxicity. In 
such patients, interruption or discontinuation of treatment must be considered (see section 4.8). 
 
In patients treated with other medicinal products associated with liver toxicity, monitoring of liver 
enzymes is also recommended. In case of concomitant antiviral therapy for hepatitis B or C, please 
refer also to the relevant product information for these medicinal products. 
 
Renal impairment 
The pharmacokinetics of efavirenz have not been studied in patients with renal insufficiency; however, 
less than 1% of an efavirenz dose is excreted unchanged in the urine, so the impact of renal 
impairment on efavirenz elimination should be minimal (see section 4.2). There is no experience in 
patients with severe renal failure and close safety monitoring is recommended in this population. 
 
Elderly patients 
Insufficient numbers of elderly patients have been evaluated in clinical studies to determine whether 
they respond differently than younger patients. 
 

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Paediatric population 
 
Rash was reported in 59 of 182 children (32%) treated with efavirenz and was severe in six patients. 
Prophylaxis with appropriate antihistamines prior to initiating therapy with efavirenz in children may 
be considered. 
 
Excipients 
Lactose 
Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-
galactose malabsorption should not take this medicinal product. 
 
Sodium 
This medicine contains less than 1 mmol sodium (23 mg) per tablet that is to say essentially ‘sodium-
free’. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Efavirenz is an in vivo inducer of CYP3A4, CYP2B6 and UGT1A1. Compounds that are substrates of 
these enzymes may have decreased plasma concentrations when co-administered with efavirenz. In 
vitro efavirenz is also an inhibitor of CYP3A4. Theoretically, efavirenz may therefore initially 
increase the exposure to CYP3A4 substrates and caution is warranted for CYP3A4 substrates with 
narrow therapeutic index (see section 4.3). Efavirenz may be an inducer of CYP2C19 and CYP2C9; 
however inhibition has also been observed in vitro and the net effect of co-administration with 
substrates of these enzymes is not clear (see section 5.2). 
 
Efavirenz exposure may be increased when given with medicinal products (for example, ritonavir) or 
food (for example, grapefruit juice), which inhibit CYP3A4 or CYP2B6 activity. Compounds or 
herbal preparations (for example Ginkgo biloba extracts and St. John’s wort) which induce these 
enzymes may give rise to decreased plasma concentrations of efavirenz. Concomitant use of St. John’s 
wort is contraindicated (see section 4.3). Concomitant use of Ginkgo biloba extracts is not 
recommended (see section 4.4). 
 
QT Prolonging Drugs 
Efavirenz is contraindicated with concomitant use of drugs (they may cause prolonged QTc interval 
and Torsade de Pointes) such as: antiarrhythmics of classes IA and III, neuroleptics and antidepressant 
agents, certain antibiotics including some agents of the following classes: macrolides, 
fluoroquinolones, imidazole, and triazole antifungal agents, certain non-sedating antihistaminics 
(terfenadine, astemizole), cisapride, flecainide, certain antimalarials and methadone (see section 4.3). 
 
Paediatric population 
 
Interaction studies have only been performed in adults. 
 
Contraindications of concomitant use 
 
Efavirenz must not be administered concurrently with terfenadine, astemizole, cisapride, midazolam, 
triazolam, pimozide, bepridil, or ergot alkaloids (for example, ergotamine, dihydroergotamine, 
ergonovine, and methylergonovine), since inhibition of their metabolism may lead to serious, 
life-threatening events (see section 4.3). 
 
Elbasvir/grazoprevir 
Concomitant administration of efavirenz with elbasvir/grazoprevir is contraindicated because it may 
lead to loss of virologic response to elbasvir/grazoprevir. This loss is due to significant decreases in 
elbasvir and grazoprevir plasma concentrations caused by CYP3A4 induction. (see section 4.3). 
 

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St. John’s wort (Hypericum perforatum) 
Co-administration of efavirenz and St. John’s wort or herbal preparations containing St. John’s wort is 
contraindicated. Plasma levels of efavirenz can be reduced by concomitant use of St. John’s wort due 
to induction of drug-metabolising enzymes and/or transport proteins by St. John’s wort. If a patient is 
already taking St. John’s wort, stop St. John’s wort, check viral levels and if possible efavirenz levels. 
Efavirenz levels may increase on stopping St. John’s wort and the dose of efavirenz may need 
adjusting. The inducing effect of St. John’s wort may persist for at least 2 weeks after cessation of 
treatment (see section 4.3). 
 
Other interactions 
 
Interactions between efavirenz and protease inhibitors, antiretroviral agents other than protease 
inhibitors and other non-antiretroviral medicinal products are listed in Table 1 below (increase is 
indicated as “↑”, decrease as “↓”, no change as “↔”, and once every 8 or 12 hours as “q8h” or 
“q12h”). If available, 90% or 95% confidence intervals are shown in parentheses. Studies were 
conducted in healthy subjects unless otherwise noted. 
 
Table 1: Interactions between efavirenz and other medicinal products in adults 
Medicinal product by 
therapeutic areas 
(dose) 

Effects on drug levels 
Mean percent change in AUC, 
Cmax, Cmin with confidence 
intervals if availablea 
(mechanism) 

Recommendation concerning 
co-administration with 
efavirenz 

ANTI-INFECTIVES 
HIV antivirals 
Protease inhibitors (PI) 
Atazanavir/ritonavir/efavirenz 
(400 mg once daily/100 mg once 
daily/600 mg once daily, all 
administered with food) 
 

Atazanavir (pm): 
AUC: ↔* (↓ 9 to ↑ 10) 
Cmax: ↑ 17%* (↑ 8 to ↑ 27) 
Cmin: ↓ 42%* (↓ 31 to ↓ 51) 

Co-administration of efavirenz 
with atazanavir/ritonavir is not 
recommended. If the 
co-administration of atazanavir 
with an NNRTI is required, an 
increase in the dose of both 
atazanavir and ritonavir to 400 mg 
and 200 mg, respectively, in 
combination with efavirenz could 
be considered with close clinical 
monitoring. 

Atazanavir/ritonavir/efavirenz 
(400 mg once daily/200 mg once 
daily/600 mg once daily, all 
administered with food) 

Atazanavir (pm): 
AUC: ↔*/** (↓ 10 to ↑ 26) 
Cmax: ↔*/** (↓ 5 to ↑ 26) 
Cmin: ↑ 12%*/** (↓ 16 to ↑ 49) 
(CYP3A4 induction) 
* When compared to atazanavir 
300 mg/ritonavir 100 mg once daily 
in the evening without efavirenz. This 
decrease in atazanavir Cmin might 
negatively impact the efficacy of 
atazanavir. 
** Based on historical comparison 

Darunavir/ritonavir/efavirenz 
(300 mg twice daily*/100 mg 
twice daily/600 mg once daily) 
*lower than recommended doses, 
similar findings are expected with 
recommended doses 

Darunavir: 
AUC: ↓ 13% 
Cmin: ↓ 31% 
Cmax: ↓ 15% 
(CYP3A4 induction) 
Efavirenz: 
AUC: ↑ 21% 
Cmin: ↑ 17% 
Cmax: ↑ 15% 
(CYP3A4 inhibition) 

Efavirenz in combination with 
darunavir/ritonavir 800/100 mg 
once daily may result in 
suboptimal darunavir Cmin. If 
efavirenz is to be used in 
combination with 
darunavir/ritonavir, the 
darunavir/ritonavir 600/100 mg 
twice daily regimen should be 
used. This combination should be 
used with caution. See also 
ritonavir row below. 

Fosamprenavir/ritonavir/ 
efavirenz 
(700 mg twice daily/100 mg twice 
daily/600 mg once daily) 

No clinically significant 
pharmacokinetic interaction 

No dose adjustment is necessary 
for any of these medicinal 
products. See also ritonavir row 
below. 

Fosamprenavir/nelfinavir/ Interaction not studied No dose adjustment is necessary 

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Medicinal product by 
therapeutic areas 
(dose) 

Effects on drug levels 
Mean percent change in AUC, 
Cmax, Cmin with confidence 
intervals if availablea 
(mechanism) 

Recommendation concerning 
co-administration with 
efavirenz 

efavirenz 
 

for any of these medicinal 
products.  
Not recommended as the 
exposure to both PIs is expected 
to be significantly decreased. 

Fosamprenavir/saquinavir/ 
efavirenz 

Interaction not studied 

Indinavir/efavirenz 
(800 mg q8h/200 mg once daily) 

Indinavir: 
AUC: ↓ 31% (↓ 8 to ↓47) 
Cmin: ↓ 40% 
A similar reduction in indinavir 
exposures was observed when 
indinavir 1000 mg q8h was given 
with efavirenz 600 mg daily. 
(CYP3A4 induction) 
 
Efavirenz: 
No clinically significant 
pharmacokinetic interaction 

While the clinical significance of 
decreased indinavir 
concentrations has not been 
established, the magnitude of the 
observed pharmacokinetic 
interaction should be taken into 
consideration when choosing a 
regimen containing both efavirenz 
and indinavir. 
 
No dose adjustment is necessary 
for efavirenz when given with 
indinavir or indinavir/ritonavir. 
 
See also ritonavir row below. 

Indinavir/ritonavir/efavirenz 
(800 mg twice daily/100 mg twice 
daily/600 mg once daily) 

Indinavir: 
AUC: ↓ 25% (↓ 16 to ↓32) b 
Cmax: ↓ 17% (↓ 6 to ↓ 26) b 
Cmin: ↓ 50% (↓ 40 to ↓ 59) b 
Efavirenz: 
No clinically significant 
pharmacokinetic interaction 
The geometric mean Cmin for 
indinavir (0.33 mg/l) when given 
with ritonavir and efavirenz was 
higher than the mean historical Cmin 
(0.15 mg/l) when indinavir was given 
alone at 800 mg q8h. In HIV-1 
infected patients (n=6), the 
pharmacokinetics of indinavir and 
efavirenz were generally comparable 
to these uninfected volunteer data. 

Lopinavir/ritonavir soft capsules 
or oral solution/ efavirenz 
 
Lopinavir/ritonavir tablets/ 
efavirenz 

Substantial decrease in lopinavir 
exposure. 

With efavirenz, an increase of the 
lopinavir/ritonavir soft capsule or 
oral solution doses by 33% should 
be considered (4 capsules/ 
~6.5 ml twice daily instead of 3 
capsules/5 ml twice daily). 
Caution is warranted since this 
dose adjustment might be 
insufficient in some patients. The 
dose of lopinavir/ritonavir tablets 
should be increased to 
500/125 mg twice daily when 
co-administered with efavirenz 
600 mg once daily. 
See also ritonavir row below. 

(400/100 mg twice daily/ 600 mg 
once daily) 

Lopinavir concentrations: ↓ 30-40% 

(500/125 mg twice daily/ 600 mg 
once daily) 

Lopinavir concentrations: similar to 
lopinavir/ritonavir 400/100 mg twice 
daily without efavirenz 

Nelfinavir/efavirenz 
(750 mg q8h/600 mg once daily) 

Nelfinavir: 
AUC: ↑ 20% (↑ 8 to ↑ 34) 
Cmax: ↑ 21% (↑ 10 to ↑ 33) 
The combination was generally well 
tolerated. 

No dose adjustment is necessary 
for either medicinal product. 

Ritonavir/efavirenz 
(500 mg twice daily/600 mg once 
daily) 

Ritonavir: 
Morning AUC: ↑ 18% (↑ 6 to ↑ 33) 
Evening AUC: ↔ 

When using efavirenz with 
low-dose ritonavir, the possibility 
of an increase in the incidence of 

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Medicinal product by 
therapeutic areas 
(dose) 

Effects on drug levels 
Mean percent change in AUC, 
Cmax, Cmin with confidence 
intervals if availablea 
(mechanism) 

Recommendation concerning 
co-administration with 
efavirenz 

Morning Cmax: ↑ 24% (↑ 12 to ↑ 38) 
Evening Cmax: ↔ 
Morning Cmin: ↑ 42% (↑ 9 to ↑ 86) b 
Evening Cmin: ↑ 24% (↑ 3 to ↑ 50) b 
 
Efavirenz: 
AUC: ↑ 21% (↑ 10 to ↑ 34) 
Cmax: ↑ 14% (↑ 4 to ↑ 26) 
Cmin: ↑ 25% (↑ 7 to ↑ 46) b 
(Inhibition of CYP-mediated 
oxidative metabolism) 
When efavirenz was given with 
ritonavir 500 mg or 600 mg twice 
daily, the combination was not well 
tolerated (for example, dizziness, 
nausea, paraesthesia and elevated 
liver enzymes occurred). Sufficient 
data on the tolerability of efavirenz 
with low-dose ritonavir (100 mg, 
once or twice daily) are not available. 

efavirenz-associated adverse 
events should be considered, due 
to possible pharmacodynamic 
interaction. 

Saquinavir/ritonavir/efavirenz Interaction not studied No data are available to make a 
dose recommendation. See also 
ritonavir row above. Use of 
efavirenz in combination with 
saquinavir as the sole protease 
inhibitor is not recommended. 

CCR5 antagonist 
Maraviroc/efavirenz 
(100 mg twice daily/600 mg once 
daily) 

Maraviroc: 
AUC12: ↓ 45% (↓ 38 to ↓ 51) 
Cmax: ↓ 51% (↓ 37 to ↓ 62) 
Efavirenz concentrations not 
measured, no effect is expected. 

Refer to the Summary of Product 
Characteristics for the medicinal 
product containing maraviroc. 

Integrase strand transfer inhibitor 
Raltegravir/efavirenz 
(400 mg single dose/ -) 

Raltegravir: 
AUC: ↓ 36% 
C12: ↓ 21% 
Cmax: ↓ 36% 
(UGT1A1 induction) 

No dose adjustment is necessary 
for raltegravir. 

NRTIs and NNRTIs 
NRTIs/efavirenz Specific interaction studies have not 

been performed with efavirenz and 
NRTIs other than lamivudine, 
zidovudine and tenofovir disoproxil. 
Clinically significant interactions are 
not expected since the NRTIs are 
metabolised via a different route than 
efavirenz and would be unlikely to 
compete for the same metabolic 
enzymes and elimination pathways. 

No dose adjustment is necessary 
for either medicinal product. 

NNRTIs/efavirenz Interaction not studied Since use of two NNRTIs proved 
not beneficial in terms of efficacy 
and safety, co-administration of 
efavirenz and another NNRTI is 
not recommended. 

Hepatitis C antivirals 
Boceprevir/efavirenz 
(800 mg 3 times daily/600 mg 

Boceprevir: 
AUC: ↔ 19%* 

Plasma trough concentrations of 
boceprevir were decreased when 

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Medicinal product by 
therapeutic areas 
(dose) 

Effects on drug levels 
Mean percent change in AUC, 
Cmax, Cmin with confidence 
intervals if availablea 
(mechanism) 

Recommendation concerning 
co-administration with 
efavirenz 

once daily) 
 

Cmax: ↔ 8% 
Cmin: ↓ 44% 
Efavirenz: 
AUC: ↔ 20% 
Cmax: ↔ 11% 
(CYP3A induction - effect 
on boceprevir) 
*0-8 hours 

No effect (↔) equals a decrease in 
mean ratio estimate of ≤20% or 
increase in mean ratio estimate of 
≤25% 

administered with efavirenz. The 
clinical outcome of this observed 
reduction of boceprevir trough 
concentrations has not been 
directly assessed. 

Telaprevir/efavirenz 
(1,125 mg q8h/600 mg once 
daily) 
 

Telaprevir (relative to 
750 mg q8h): 
AUC: ↓ 18% (↓ 8 to ↓ 27) 
Cmax: ↓ 14% (↓ 3 to ↓ 24) 
Cmin: ↓ 25% (↓ 14 to ↓ 34)% 
Efavirenz: 
AUC: ↓ 18% (↓ 10 to ↓ 26) 
Cmax: ↓ 24% (↓ 15 to ↓ 32) 
Cmin: ↓ 10% (↑ 1 to ↓ 19)% 

(CYP3A induction by efavirenz) 

If efavirenz and telaprevir are co-
administered, telaprevir 1,125 mg 
every 8 hours should be used. 

Simeprevir/efavirenz 
(150 mg once daily /600 mg once 
daily) 

Simeprevir:  
AUC: ↓71% (↓67 to ↓74)  
Cmax: ↓51% (↓46 to ↓56)  
Cmin: ↓91% (↓88 to ↓92)  
Efavirenz: 
AUC: ↔  
Cmax: ↔ 
Cmin: ↔ 
No effect (↔) equals a decrease in 
mean ratio estimate of ≤20% or 
increase in mean ratio estimate of 
≤25% 
(CYP3A4 enzyme induction) 

Concomitant administration of 
simeprevir with efavirenz resulted 
in significantly decreased plasma 
concentrations of simeprevir due 
to CYP3A induction by efavirenz, 
which may result in loss of 
therapeutic effect of simeprevir. 
Co-administration of simeprevir 
with efavirenz is not 
recommended. 

Sofosbuvir/velpatasvir ↔sofosbuvir 
↓velpatasvir 
↔efavirenz 

Concomitant administration of 
sofosbuvir/velpatasvir with 
efavirenz resulted in a 
reduction (approximately 
50%) in the systemic exposure 
of velpatasvir. The mechanism 
of the effect on velpatasvir is 
induction of CYP3A and 
CYP2B6 by efavirenz. 
Coadministration of 
sofosbuvir/velpatasvir with 
efavirenz is not recommended. 
Refer to the prescribing 
information for 
sofosbuvir/velpatasvir for 
more information. 

 11 



Medicinal product by 
therapeutic areas 
(dose) 

Effects on drug levels 
Mean percent change in AUC, 
Cmax, Cmin with confidence 
intervals if availablea 
(mechanism) 

Recommendation concerning 
co-administration with 
efavirenz 

Velpatasvir/sofosbuvir/voxilap
revir 

↓velpatasvir 
↓voxilaprevir 

Concomitant administration of 
velpatasvir/sofosbuvir/ 
voxilaprevir with efavirenz is 
not recommended, as it may 
decrease concentrations of 
velpatasvir and voxilaprevir. 
Refer to the prescribing 
information for 
velpatasvir/sofosbuvir/ 
voxilaprevir for more 
information. 

Protease inhibitor : 
Elbasvir/grazoprevir 
 

↓elbasvir 
↓grazoprevir 

↔efavirenz 

Concomitant administration of 
efavirenz with 
elbasvir/grazoprevir is 
contraindicated because it may 
lead to loss of virologic 
response to 
elbasvir/grazoprevir. This loss 
is due to significant decreases 
in elbasvir and grazoprevir 
plasma concentrations caused 
by CYP3A4 induction. Refer 
to the prescribing information 
for elbasvir/grazoprevir for 
more information. 

Glecaprevir/pibrentasvir ↓glecaprevir 
↓ pibrentasvir 

Concomitant administration of 
glecaprevir/pibrentasvir with 
efavirenz may significantly 
decrease plasma 
concentrations of glecaprevir 
and pibrentasvir, leading to 
reduced therapeutic effect. 
Coadministration of 
glecaprevir/pibrentasvir with 
efavirenz is not recommended. 
Refer to the prescribing 
information for 
glecaprevir/pibrentasvir for 
more information. 

Antibiotics 
Azithromycin/efavirenz 
(600 mg single dose/400 mg once 
daily) 

No clinically significant 
pharmacokinetic interaction 

No dose adjustment is necessary 
for either medicinal product. 

Clarithromycin/efavirenz 
(500 mg q12h/400 mg once daily) 

Clarithromycin: 
AUC: ↓ 39% (↓ 30 to ↓ 46) 
Cmax: ↓ 26% (↓ 15 to ↓ 35) 
 
Clarithromycin 
14-hydroxymetabolite: 
AUC: ↑ 34% (↑ 18 to ↑ 53) 
Cmax: ↑ 49% (↑ 32 to ↑ 69) 
 
Efavirenz: 

The clinical significance of these 
changes in clarithromycin plasma 
levels is not known. Alternatives 
to clarithromycin (e.g. 
azithromycin) may be considered. 
No dose adjustment is necessary 
for efavirenz. 

 12 



Medicinal product by 
therapeutic areas 
(dose) 

Effects on drug levels 
Mean percent change in AUC, 
Cmax, Cmin with confidence 
intervals if availablea 
(mechanism) 

Recommendation concerning 
co-administration with 
efavirenz 

AUC: ↔ 
Cmax: ↑ 11% (↑ 3 to ↑19) 
(CYP3A4 induction) 
Rash developed in 46% of uninfected 
volunteers receiving efavirenz and 
clarithromycin. 

Other macrolide antibiotics (e.g. 
erythromycin)/efavirenz 

Interaction not studied No data are available to make a 
dose recommendation. 

Antimycobacterials 
Rifabutin/efavirenz 
(300 mg once daily/600 mg once 
daily) 

Rifabutin: 
AUC: ↓ 38% (↓ 28 to ↓ 47) 
Cmax: ↓ 32% (↓ 15 to ↓ 46) 
Cmin: ↓ 45% (↓ 31 to ↓ 56) 
 
Efavirenz: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↓ 12% (↓ 24% to ↑ 1%) 
(CYP3A4 induction) 

The daily dose of rifabutin should 
be increased by 50% when 
administered with efavirenz. 
Consider doubling the rifabutin 
dose in regimens where rifabutin 
is given 2 or 3 times a week in 
combination with efavirenz. The 
clinical effect of this dose 
adjustment has not been 
adequately evaluated. Individual 
tolerability and virological 
response should be considered 
when making the dose adjustment 
(see section 5.2). 

Rifampicin/efavirenz 
(600 mg once daily/600 mg once 
daily) 

Efavirenz: 
AUC: ↓ 26% (↓ 15 to ↓ 36) 
Cmax: ↓ 20% (↓ 11 to ↓ 28) 
Cmin: ↓ 32% (↓ 15 to ↓ 46) 
(CYP3A4 and CYP2B6 induction) 

When taken with rifampicin in 
patients weighing 50 kg or 
greater, increasing efavirenz daily 
dose to 800 mg may provide 
exposure similar to a daily dose of 
600 mg when taken without 
rifampicin. The clinical effect of 
this dose adjustment has not been 
adequately evaluated. Individual 
tolerability and virological 
response should be considered 
when making the dose adjustment 
(see section 5.2). No dose 
adjustment is necessary for 
rifampicin, including 600 mg. 

Antifungals 
Itraconazole/efavirenz 
(200 mg q12h/600 mg once daily) 

Itraconazole: 
AUC: ↓ 39% (↓ 21 to ↓ 53) 
Cmax: ↓ 37% (↓ 20 to ↓ 51) 
Cmin: ↓ 44% (↓ 27 to ↓ 58) 
(Decrease in itraconazole 
concentrations: CYP3A4 induction) 
 
Hydroxyitraconazole: 
AUC: ↓ 37% (↓ 14 to ↓ 55) 
Cmax: ↓ 35% (↓ 12 to ↓ 52) 
Cmin: ↓ 43% (↓ 18 to ↓ 60) 
 
Efavirenz: 
No clinically significant 
pharmacokinetic change. 

Since no dose recommendation 
for itraconazole can be made, 
alternative antifungal treatment 
should be considered. 

Posaconazole/efavirenz 
(--/400 mg once daily) 

Posaconazole: 
AUC: ↓ 50% 
Cmax: ↓ 45% 

Concomitant use of posaconazole 
and efavirenz should be avoided 
unless the benefit to the patient 

 13 



Medicinal product by 
therapeutic areas 
(dose) 

Effects on drug levels 
Mean percent change in AUC, 
Cmax, Cmin with confidence 
intervals if availablea 
(mechanism) 

Recommendation concerning 
co-administration with 
efavirenz 

(UDP-G induction) outweighs the risk. 
Voriconazole/efavirenz 
(200 mg twice daily/400 mg once 
daily) 

Voriconazole: 
AUC: ↓ 77% 
Cmax: ↓ 61% 
 
Efavirenz: 
AUC: ↑ 44% 
Cmax: ↑ 38% 
 

When efavirenz is 
co-administered with 
voriconazole, the voriconazole 
maintenance dose must be 
increased to 400 mg twice daily 
and the efavirenz dose must be 
reduced by 50%, i.e. to 300 mg 
once daily. When treatment with 
voriconazole is stopped, the initial 
dosage of efavirenz should be 
restored. 

Voriconazole/efavirenz 
(400 mg twice daily/300 mg once 
daily) 

Voriconazole: 
AUC: ↓ 7% (↓ 23 to ↑ 13) * 
Cmax: ↑ 23% (↓ 1 to ↑ 53) * 
 
Efavirenz: 
AUC: ↑ 17% (↑ 6 to ↑ 29) ** 
Cmax: ↔** 
*compared to 200 mg twice daily 
alone 
** compared to 600 mg once daily 
alone 
(Competitive inhibition of oxidative 
metabolism) 

Fluconazole/efavirenz 
(200 mg once daily/400 mg once 
daily) 

No clinically significant 
pharmacokinetic interaction 

No dose adjustment is necessary 
for either medicinal product. 

Ketoconazole and other imidazole 
antifungals 

Interaction not studied No data are available to make a 
dose recommendation. 

Antimalarials 
Artemether/lumefantrine/efaviren
z 
(20/120 mg tablet, 6 doses of 4 
tablets each over 3 days/600mg 
once daily) 

Artemether: 
AUC: ↓ 51%  
Cmax: ↓ 21%  
Dihydroartemisinin: 
AUC: ↓ 46% 
Cmax: ↓ 38%  
Lumefantrine: 
AUC: ↓ 21%  
Cmax: ↔ 
Efavirenz: 
AUC: ↓ 17% 
Cmax: ↔ 
(CYP3A4 induction) 

Since decreased concentrations of 
artemether, dihydroartemisinin, or 
lumefantrine may result in a 
decrease of antimalarial efficacy, 
caution is recommended when 
efavirenz and 
artemether/lumefantrine tablets 
are coadministered. 

Atovaquone and proguanil 
hydrochloride/efavirenz 
(250/100 mg single dose/600 mg 
once daily) 

Atovaquone: 
AUC: ↓ 75% (↓ 62 to ↓ 84) 
Cmax: ↓ 44% (↓ 20 to ↓ 61) 
 
Proguanil: 
AUC: ↓ 43% (↓ 7 to ↓ 65) 
Cmax: ↔ 
 

Concomitant administration of 
atovaquone/proguanil with 
efavirenz should be avoided. 

 14 



Medicinal product by 
therapeutic areas 
(dose) 

Effects on drug levels 
Mean percent change in AUC, 
Cmax, Cmin with confidence 
intervals if availablea 
(mechanism) 

Recommendation concerning 
co-administration with 
efavirenz 

ACID-REDUCING AGENTS 
Aluminium hydroxide-
magnesium hydroxide-
simethicone antacid/efavirenz 
(30 ml single dose/400 mg single 
dose) 
 

Neither aluminium/magnesium 
hydroxide antacids nor famotidine 
altered the absorption of efavirenz. 

Co-administration of efavirenz 
with medicinal products that alter 
gastric pH would not be expected 
to affect efavirenz absorption. 

Famotidine/efavirenz 
(40 mg single dose/400 mg single 
dose) 
ANTIANXIETY AGENTS 
Lorazepam/efavirenz 
(2 mg single dose/600 mg once 
daily) 

Lorazepam: 
AUC: ↑ 7% (↑ 1 to ↑ 14) 
Cmax: ↑ 16% (↑ 2 to ↑ 32) 
These changes are not considered 
clinically significant. 

No dose adjustment is necessary 
for either medicinal product. 

ANTICOAGULANTS 
Warfarin/efavirenz 
Acenocoumarol/efavirenz 
 

Interaction not studied. Plasma 
concentrations and effects of warfarin 
or acenocoumarol are potentially 
increased or decreased by efavirenz. 

Dose adjustment of warfarin or 
acenocoumarol may be required. 

ANTICONVULSANTS 
Carbamazepine/efavirenz 
(400 mg once daily/600 mg once 
daily) 

Carbamazepine: 
AUC: ↓ 27% (↓ 20 to ↓ 33) 
Cmax: ↓ 20% (↓ 15 to ↓ 24) 
Cmin: ↓ 35% (↓ 24 to ↓ 44) 
 
Efavirenz: 
AUC: ↓ 36% (↓ 32 to ↓ 40) 
Cmax: ↓ 21% (↓ 15 to ↓ 26) 
Cmin: ↓ 47% (↓ 41 to ↓ 53) 
(decrease in carbamazepine 
concentrations: CYP3A4 induction; 
decrease in efavirenz concentrations: 
CYP3A4 and CYP2B6 induction) 
 
The steady-state AUC, Cmax and Cmin 
of the active carbamazepine epoxide 
metabolite remained unchanged. 
Co-administration of higher doses of 
either efavirenz or carbamazepine has 
not been studied. 

No dose recommendation can be 
made. An alternative 
anticonvulsant should be 
considered. Carbamazepine 
plasma levels should be 
monitored periodically. 

Phenytoin, phenobarbital, and 
other anticonvulsants that are 
substrates of CYP450 isoenzymes 

Interaction not studied. There is a 
potential for reduction or increase in 
the plasma concentrations of 
phenytoin, phenobarbital and other 
anticonvulsants that are substrates of 
CYP450 isoenzymes when 
co-administered with efavirenz. 

When efavirenz is 
co-administered with an 
anticonvulsant that is a substrate 
of CYP450 isoenzymes, periodic 
monitoring of anticonvulsant 
levels should be conducted. 

Valproic acid/efavirenz 
(250 mg twice daily/600 mg once 
daily) 

No clinically significant effect on 
efavirenz pharmacokinetics. Limited 
data suggest there is no clinically 
significant effect on valproic acid 
pharmacokinetics. 

No dose adjustment is necessary 
for efavirenz. Patients should be 
monitored for seizure control. 

Vigabatrin/efavirenz 
Gabapentin/efavirenz 

Interaction not studied. Clinically 
significant interactions are not 
expected since vigabatrin and 

No dose adjustment is necessary 
for any of these medicinal 
products. 

 15 



Medicinal product by 
therapeutic areas 
(dose) 

Effects on drug levels 
Mean percent change in AUC, 
Cmax, Cmin with confidence 
intervals if availablea 
(mechanism) 

Recommendation concerning 
co-administration with 
efavirenz 

gabapentin are exclusively eliminated 
unchanged in the urine and are 
unlikely to compete for the same 
metabolic enzymes and elimination 
pathways as efavirenz. 

ANTIDEPRESSANTS 
Selective Serotonin Reuptake Inhibitors (SSRIs) 
Sertraline/efavirenz 
(50 mg once daily/600 mg once 
daily) 

Sertraline: 
AUC: ↓ 39% (↓ 27 to ↓ 50) 
Cmax: ↓ 29% (↓ 15 to ↓ 40) 
Cmin: ↓ 46% (↓ 31 to ↓ 58) 
 
Efavirenz: 
AUC: ↔ 
Cmax: ↑ 11% (↑ 6 to ↑ 16) 
Cmin: ↔ 
(CYP3A4 induction) 

Sertraline dose increases should 
be guided by clinical response. 
No dose adjustment is necessary 
for efavirenz. 

Paroxetine/efavirenz 
(20 mg once daily/600 mg once 
daily) 

No clinically significant 
pharmacokinetic interaction 

No dose adjustment is necessary 
for either medicinal product. 

Fluoxetine/efavirenz Interaction not studied. Since 
fluoxetine shares a similar metabolic 
profile with paroxetine, i.e. a strong 
CYP2D6 inhibitory effect, a similar 
lack of interaction would be expected 
for fluoxetine. 

No dose adjustment is necessary 
for either medicinal product. 

Norepinephrine and dopamine reuptake inhibitor 
Bupropion/efavirenz 
[150 mg single dose (sustained 
release)/600 mg once daily] 

Bupropion: 
AUC: ↓ 55% (↓ 48 to ↓ 62)  
Cmax: ↓ 34% (↓ 21 to ↓ 47)  
Hydroxybupropion:  
AUC: ↔ 
Cmax: ↑ 50% (↑ 20 to ↑ 80) 
(CYP2B6 induction) 

Increases in bupropion dosage 
should be guided by clinical 
response, but the maximum 
recommended dose of bupropion 
should not be exceeded. No dose 
adjustment is necessary for 
efavirenz. 

ANTIHISTAMINES 
Cetirizine/efavirenz 
(10 mg single dose/600 mg once 
daily) 

Cetirizine: 
AUC: ↔ 
Cmax: ↓ 24% (↓ 18 to ↓ 30) 
These changes are not considered 
clinically significant. 
 
Efavirenz: 
No clinically significant 
pharmacokinetic interaction 

No dose adjustment is necessary 
for either medicinal product. 

CARDIOVASCULAR AGENTS 
Calcium Channel Blockers 
Diltiazem/efavirenz 
(240 mg once daily/600 mg once 
daily) 

Diltiazem: 
AUC: ↓ 69% (↓ 55 to ↓ 79) 
Cmax: ↓ 60% (↓ 50 to ↓ 68) 
Cmin: ↓ 63% (↓ 44 to ↓ 75) 
 
Desacetyl diltiazem: 
AUC: ↓ 75% (↓ 59 to ↓ 84) 
Cmax: ↓ 64% (↓ 57 to ↓ 69) 
Cmin: ↓ 62% (↓ 44 to ↓ 75) 
 

Dose adjustments of diltiazem 
should be guided by clinical 
response (refer to the Summary of 
Product Characteristics for 
diltiazem). No dose adjustment is 
necessary for efavirenz. 

 16 



Medicinal product by 
therapeutic areas 
(dose) 

Effects on drug levels 
Mean percent change in AUC, 
Cmax, Cmin with confidence 
intervals if availablea 
(mechanism) 

Recommendation concerning 
co-administration with 
efavirenz 

N-monodesmethyl diltiazem: 
AUC: ↓ 37% (↓ 17 to ↓ 52) 
Cmax: ↓ 28% (↓ 7 to ↓ 44) 
Cmin: ↓ 37% (↓ 17 to ↓ 52) 
 
Efavirenz: 
AUC: ↑ 11% (↑ 5 to ↑ 18) 
Cmax: ↑ 16% (↑ 6 to ↑ 26) 
Cmin: ↑ 13% (↑ 1 to ↑ 26) 
(CYP3A4 induction) 
The increase in efavirenz 
pharmacokinetic parameters is not 
considered clinically significant. 

Verapamil, felodipine, nifedipine 
and nicardipine 

Interaction not studied. When 
efavirenz is co-administered with a 
calcium channel blocker that is a 
substrate of the CYP3A4 enzyme, 
there is a potential for reduction in 
the plasma concentrations of the 
calcium channel blocker. 

Dose adjustments of calcium 
channel blockers should be 
guided by clinical response (refer 
to the Summary of Product 
Characteristics for the calcium 
channel blocker). 

LIPID-LOWERING MEDICINAL PRODUCTS 
HMG CoA Reductase Inhibitors 
Atorvastatin/efavirenz 
(10 mg once daily/600 mg once 
daily) 

Atorvastatin: 
AUC: ↓ 43% (↓ 34 to ↓ 50) 
Cmax: ↓ 12% (↓ 1 to ↓ 26) 
 
2-hydroxy atorvastatin: 
AUC: ↓ 35% (↓ 13 to ↓ 40) 
Cmax: ↓ 13% (↓ 0 to ↓ 23) 
 
4-hydroxy atorvastatin: 
AUC: ↓ 4% (↓ 0 to ↓ 31) 
Cmax: ↓ 47% (↓ 9 to ↓ 51) 
 
Total active HMG CoA reductase 
inhibitors: 
AUC: ↓ 34% (↓ 21 to ↓ 41) 
Cmax: ↓ 20% (↓ 2 to ↓ 26) 

Cholesterol levels should be 
periodically monitored. Dose 
adjustment of atorvastatin may be 
required (refer to the Summary of 
Product Characteristics for 
atorvastatin). No dose adjustment 
is necessary for efavirenz. 

Pravastatin/efavirenz 
(40 mg once daily/600 mg once 
daily) 

Pravastatin: 
AUC: ↓ 40% (↓ 26 to ↓ 57) 
Cmax: ↓ 18% (↓ 59 to ↑ 12) 

Cholesterol levels should be 
periodically monitored. Dose 
adjustment of pravastatin may be 
required (refer to the Summary of 
Product Characteristics for 
pravastatin). No dose adjustment 
is necessary for efavirenz. 

Simvastatin/efavirenz 
(40 mg once daily/600 mg once 
daily) 

Simvastatin: 
AUC: ↓ 69% (↓ 62 to ↓ 73) 
Cmax: ↓ 76% (↓ 63 to ↓ 79) 
 
Simvastatin acid: 
AUC: ↓ 58% (↓ 39 to ↓ 68) 
Cmax: ↓ 51% (↓ 32 to ↓ 58) 
 
Total active HMG Co-A reductase 
inhibitors: 
AUC: ↓ 60% (↓ 52 to ↓ 68) 
Cmax: ↓ 62% (↓ 55 to ↓ 78) 

Cholesterol levels should be 
periodically monitored. Dose 
adjustment of simvastatin may be 
required (refer to the Summary of 
Product Characteristics for 
simvastatin). No dose adjustment 
is necessary for efavirenz. 

 17 



Medicinal product by 
therapeutic areas 
(dose) 

Effects on drug levels 
Mean percent change in AUC, 
Cmax, Cmin with confidence 
intervals if availablea 
(mechanism) 

Recommendation concerning 
co-administration with 
efavirenz 

 
(CYP3A4 induction) 
Co-administration of efavirenz with 
atorvastatin, pravastatin, or 
simvastatin did not affect efavirenz 
AUC or Cmax values. 

Rosuvastatin/efavirenz Interaction not studied. Rosuvastatin 
is largely excreted unchanged via the 
faeces, therefore interaction with 
efavirenz is not expected. 

No dose adjustment is necessary 
for either medicinal product. 

HORMONAL CONTRACEPTIVES 
Oral: 
Ethinyloestradiol + norgestimate / 
efavirenz 
(0.035 mg + 0.25 mg once 
daily/600 mg once daily) 

Ethinyloestradiol: 
AUC: ↔ 
Cmax: ↔ 
Cmin: ↓ 8% (↑ 14 to ↓ 25) 
 
Norelgestromin (active metabolite): 
AUC: ↓ 64% (↓ 62 to ↓ 67) 
Cmax: ↓ 46% (↓ 39 to ↓ 52) 
Cmin: ↓ 82% (↓ 79 to ↓ 85) 
 
Levonorgestrel (active metabolite): 
AUC: ↓ 83% (↓ 79 to ↓ 87) 
Cmax: ↓ 80% (↓ 77 to ↓ 83) 
Cmin: ↓ 86% (↓ 80 to ↓ 90) 
(induction of metabolism) 
 
Efavirenz: no clinically significant 
interaction. 
The clinical significance of these 
effects is not known. 

A reliable method of barrier 
contraception must be used in 
addition to hormonal 
contraceptives (see section 4.6). 

Injection: 
Depomedroxyprogesterone 
acetate (DMPA)/efavirenz 
(150 mg IM single dose DMPA) 

In a 3-month drug interaction study, 
no significant differences in MPA 
pharmacokinetic parameters were 
found between subjects receiving 
efavirenz-containing antiretroviral 
therapy and subjects receiving no 
antiretroviral therapy. Similar results 
were found by other investigators, 
although the MPA plasma levels were 
more variable in the second study. In 
both studies, plasma progesterone 
levels for subjects receiving efavirenz 
and DMPA remained low consistent 
with suppression of ovulation. 

Because of the limited 
information available, a reliable 
method of barrier contraception 
must be used in addition to 
hormonal contraceptives (see 
section 4.6). 

Implant: Etonogestrel/efavirenz Decreased exposure of etonogestrel 
may be expected (CYP3A4 
induction). There have been 
occasional postmarketing reports of 
contraceptive failure with 
etonogestrel in efavirenz-exposed 
patients. 

A reliable method of barrier 
contraception must be used in 
addition to hormonal 
contraceptives (see section 4.6). 

IMMUNOSUPPRESSANTS 
Immunosuppressants metabolized 
by CYP3A4 (e.g. cyclosporine, 
tacrolimus, sirolimus)/efavirenz 

Interaction not studied. Decreased 
exposure of the immunosuppressant 
may be expected (CYP3A4 
induction). These 

Dose adjustments of the 
immunosuppressant may be 
required. Close monitoring of 
immunosuppressant 

 18 



Medicinal product by 
therapeutic areas 
(dose) 

Effects on drug levels 
Mean percent change in AUC, 
Cmax, Cmin with confidence 
intervals if availablea 
(mechanism) 

Recommendation concerning 
co-administration with 
efavirenz 

immunosuppressants are not 
anticipated to affect exposure of 
efavirenz. 

concentrations for at least 2 weeks 
(until stable concentrations are 
reached) is recommended when 
starting or stopping treatment 
with efavirenz. 

OPIOIDS 
Methadone/efavirenz 
(stable maintenance, 35-100 mg 
once daily/600 mg once daily) 

Methadone: 
AUC: ↓ 52% (↓ 33 to ↓ 66) 
Cmax: ↓ 45% (↓ 25 to ↓ 59) 
(CYP3A4 induction) 
 
In a study of HIV infected 
intravenous drug users, 
co-administration of efavirenz with 
methadone resulted in decreased 
plasma levels of methadone and signs 
of opiate withdrawal. The methadone 
dose was increased by a mean of 22% 
to alleviate withdrawal symptoms. 

Concomitant administration with 
efavirenz should be avoided due 
to the risk for QTc prolongation 
(see section 4.3). 

Buprenorphine/naloxone/ 
efavirenz 

Buprenorphine: 
AUC: ↓ 50% 
 
Norbuprenorphine: 
AUC: ↓ 71% 
 
Efavirenz: 
No clinically significant 
pharmacokinetic interaction 

Despite the decrease in 
buprenorphine exposure, no 
patients exhibited withdrawal 
symptoms. Dose adjustment of 
buprenorphine or efavirenz may 
not be necessary when 
co-administered. 

a 90% confidence intervals unless otherwise noted. 
b 95% confidence intervals. 
 
Other interactions: efavirenz does not bind to cannabinoid receptors. False-positive urine cannabinoid 
test results have been reported with some screening assays in uninfected and HIV-infected subjects 
receiving efavirenz. Confirmatory testing by a more specific method such as gas 
chromatography/mass spectrometry is recommended in such cases. 
 
4.6 Fertility, pregnancy and lactation  
 
Women of childbearing potential 
 
See below and section 5.3. Efavirenz should not be used during pregnancy, unless the patient’s clinical 
condition requires such treatment. Women of childbearing potential should undergo pregnancy testing 
before initiation of efavirenz. 
 
Contraception in males and females 
 
Barrier contraception should always be used in combination with other methods of contraception (for 
example, oral or other hormonal contraceptives, see section 4.5). Because of the long half-life of 
efavirenz, use of adequate contraceptive measures for 12 weeks after discontinuation of efavirenz is 
recommended. 
 
Pregnancy 
 

 19 



 
There have been seven retrospective reports of findings consistent with neural tube defects, including 
meningomyelocele, all in mothers exposed to efavirenz-containing regimens (excluding any efavirenz-
containing fixed-dose combination tablets) in the first trimester. Two additional cases (1 prospective 
and 1 retrospective) including events consistent with neural tube defects have been reported with the 
fixed-dose combination tablet containing efavirenz, emtricitabine, and tenofovir disoproxil fumarate. 
A causal relationship of these events to the use of efavirenz has not been established, and the 
denominator is unknown. As neural tube defects occur within the first 4 weeks of foetal development 
(at which time neural tubes are sealed), this potential risk would concern women exposed to efavirenz 
during the first trimester of pregnancy. 
 
As of July 2013, the Antiretroviral Pregnancy Registry (APR) has received prospective reports of 904 
pregnancies with first trimester exposure to efavirenz-containing regimens, resulting in 766 live births. 
One child was reported to have a neural tube defect, and the frequency and pattern of other birth 
defects were similar to those seen in children exposed to non-efavirenz-containing regimens, as well 
as those in HIV negative controls. The incidence of neural tube defects in the general population 
ranges from 0.5-1 case per 1,000 live births.  
 
Malformations have been observed in foetuses from efavirenz-treated monkeys (see section 5.3). 
 
Breast-feeding 
 
Efavirenz has been shown to be excreted in human milk. There is insufficient information on the 
effects of efavirenz in newborns/infants. Risk to the infant cannot be excluded. Breast-feeding should 
be discontinued during treatment with efavirenz. It is recommended that HIV infected women do not 
breast-feed their infants under any circumstances in order to avoid transmission of HIV. 
 
Fertility 
 
The effect of efavirenz on male and female fertility in rats has only been evaluated at doses that 
achieved systemic drug exposures equivalent to or below those achieved in humans given 
recommended doses of efavirenz. In these studies, efavirenz did not impair mating or fertility of male 
or female rats (doses up to 100 mg/kg/bid), and did not affect sperm or offspring of treated male rats 
(doses up to 200 mg/bid). The reproductive performance of offspring born to female rats given 
efavirenz was not affected. 
 
4.7 Effects on ability to drive and use machines 
 
Efavirenz may cause dizziness, impaired concentration, and/or somnolence. Patients should be 
instructed that if they experience these symptoms they should avoid potentially hazardous tasks such 
as driving or operating machinery. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Efavirenz has been studied in over 9,000 patients. In a subset of 1,008 adult patients who received 
600 mg efavirenz daily in combination with PIs and/or NRTIs in controlled clinical studies, the most 
frequently reported adverse reactions of at least moderate severity reported in at least 5% of patients 
were rash (11.6%), dizziness (8.5%), nausea (8.0%), headache (5.7%) and fatigue (5.5%). The most 
notable adverse reactions associated with efavirenz are rash and nervous system symptoms. Nervous 
system symptoms usually begin soon after therapy onset and generally resolve after the first 2-
 4 weeks. Severe skin reactions such as Stevens-Johnson syndrome and erythema multiforme, 
psychiatric adverse reactions including severe depression, death by suicide, and psychosis-like 
behaviour, and seizures have been reported in patients treated with efavirenz. The administration of 
efavirenz with food may increase efavirenz exposure and may lead to an increase in the frequency of 
adverse reactions (see section 4.4). 

 20 



 
The long-term safety profile of efavirenz-containing regimens was evaluated in a controlled trial (006) 
in which patients received efavirenz + zidovudine + lamivudine (n = 412, median duration 
180 weeks), efavirenz + indinavir (n = 415, median duration 102 weeks), or indinavir + zidovudine + 
lamivudine (n = 401, median duration 76 weeks). Long-term use of efavirenz in this study was not 
associated with any new safety concerns. 
 
Tabulated list of adverse reactions 
 
Adverse reactions of moderate or greater severity with at least possible relationship to treatment 
regimen (based on investigator attribution) reported in clinical trials of efavirenz at the recommended 
dose in combination therapy (n = 1,008) are listed below. Also listed in italics are adverse reactions 
observed post-marketing in association with efavirenz-containing antiretroviral treatment regimens. 
Frequency is defined using the following convention: very common (≥ 1/10); common (≥ 1/100 to 
< 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); or very rare (< 1/10,000). 
 
Immune system disorders 
Uncommon Hypersensitivity 
Metabolism and nutrition disorders 
common hypertriglyceridaemia* 
uncommon hypercholesterolaemia* 
Psychiatric disorders 
Common Abnormal dreams, anxiety, depression, insomnia* 
Uncommon Affect lability, aggression, confusional state, euphoric mood, hallucination, mania, 

paranoia, psychosis†, suicide attempt, suicide ideation, catatonia* 
Rare Delusion ‡, neurosis ‡, completed suicide‡,* 
Nervous system disorders 
Common Cerebellar co-ordination and balance disturbances†, disturbance in attention 

(3.6%), dizziness (8.5%), headache (5.7%), somnolence (2.0%)* 
Uncommon Agitation, amnesia, ataxia, co-ordination abnormal, convulsions, thinking 

abnormal*, tremor† 
Eye disorders 
Uncommon Vision blurred 
Ear and labyrinth disorders 
Uncommon Tinnitus†, vertigo 
Vascular  disorders 
Uncommon Flushing† 
Gastrointestinal disorders 
Common Abdominal pain, diarrhoea, nausea, vomiting 
Uncommon Pancreatitis 
Hepatobiliary disorders 
common aspartate aminotransferase (AST) increased*, alanine aminotransferase (ALT) 

increased*, gamma-glutamyltransferase (GGT) increased* 
 

Uncommon Hepatitis acute 
Rare Hepatic failure‡,* 
Skin and subcutaneous tissue disorders 
Very common Rash (11.6%)* 
Common Pruritus 
Uncommon Erythema multiforme, Stevens-Johnson syndrome* 
Rare Photoallergic dermatitis† 
Reproductive system and breast disorders 
Uncommon Gynaecomastia 
General disorders and administration site conditions 
Common Fatigue 

*,†,  ‡ See section c. Description of selected adverse reactions for more details. 

 21 



 
Description of selected adverse reactions 
 
Information regarding post-marketing surveillance 
 
†These adverse reactions were identified through post-marketing surveillance; however, the 

frequencies were determined using data from 16 clinical trials (n=3,969).  
‡These adverse reactions were identified through post-marketing surveillance but not reported as 

drug-related events for efavirenz-treated patients in 16 clinical trials. The frequency category of 
"rare" was defined per A Guideline on Summary of Product Characteristics (SmPC) (rev. 2, 
Sept. 2009) on the basis of an estimated upper bound of the 95% confidence interval for 0 
events given the number of patients treated with efavirenz in these clinical trials (n=3,969). 

 
 
Rash 
In clinical studies, 26% of patients treated with 600 mg of efavirenz experienced skin rash compared 
with 17% of patients treated in control groups. Skin rash was considered treatment-related in 18% of 
patients treated with efavirenz. Severe rash occurred in less than 1% of patients treated with efavirenz, 
and 1.7% discontinued therapy because of rash. The incidence of erythema multiforme or 
Stevens-Johnson syndrome was approximately 0.1%. 
 
Rashes are usually mild-to-moderate maculopapular skin eruptions that occur within the first two 
weeks of initiating therapy with efavirenz. In most patients rash resolves with continuing therapy with 
efavirenz within one month. Efavirenz can be re-initiated in patients interrupting therapy because of 
rash. Use of appropriate antihistamines and/or corticosteroids is recommended when efavirenz is 
restarted. 
 
Experience with efavirenz in patients who discontinued other antiretroviral agents of the NNRTI class 
is limited. Reported rates of recurrent rash following a switch from nevirapine to efavirenz therapy, 
primarily based on retrospective cohort data from published literature, range from 13 to 18%, 
comparable to the rate observed in patients treated with efavirenz in clinical studies (see section 4.4). 
 
Psychiatric symptoms 
Serious psychiatric adverse reactions have been reported in patients treated with efavirenz. In 
controlled trials, the frequency of specific serious psychiatric events were: 
 
  Efavirenz regimen Control regimen 
  (n=1,008) (n=635) 
- severe depression 1.6% 0.6% 
- suicidal ideation 0.6% 0.3% 
- non-fatal suicide attempts 0.4% 0% 
- aggressive behaviour 0.4% 0.3% 
- paranoid reactions 0.4% 0.3% 
- manic reactions 0.1% 0% 
 
Patients with a history of psychiatric disorders appear to be at greater risk of these serious psychiatric 
adverse reactions with frequencies ranging from 0.3% for manic reactions to 2.0% for both severe 
depression and suicidal ideation. There have also been post-marketing reports of death by suicide, 
delusions, psychosis-like behaviour and catatonia. 
 
Nervous system symptoms 
In clinical controlled trials, frequently reported adverse reactions included, but were not limited to 
dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming. Nervous system 
symptoms of moderate-to-severe intensity were experienced by 19% (severe 2%) of patients compared 
to 9% (severe 1%) of patients receiving control regimens. In clinical studies 2% of patients treated 
with efavirenz discontinued therapy due to such symptoms. 
 

 22 



Nervous system symptoms usually begin during the first one or two days of therapy and generally 
resolve after the first 2 - 4 weeks. In a study of uninfected volunteers, a representative nervous system 
symptom had a median time to onset of 1 hour post-dose and a median duration of 3 hours. Nervous 
system symptoms may occur more frequently when efavirenz is taken concomitantly with meals 
possibly due to increased efavirenz plasma levels (see section 5.2). Dosing at bedtime seems to 
improve the tolerability of these symptoms and can be recommended during the first weeks of therapy 
and in patients who continue to experience these symptoms (see section 4.2). Dose reduction or 
splitting the daily dose has not been shown to provide benefit. 
 
Analysis of long-term data showed that, beyond 24 weeks of therapy, the incidences of new-onset 
nervous system symptoms among efavirenz-treated patients were generally similar to those in the 
control arm. 
 
Hepatic failure 
A few of the postmarketing reports of hepatic failure, including cases in patients with no pre-existing 
hepatic disease or other identifiable risk factors, were characterized by a fulminant course, progressing 
in some cases to transplantation or death. 
 
Immune Reactivation Syndrome 
 
In HIV infected patients with severe immune deficiency at the time of initiation of combination 
antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic 
infections may arise. Autoimmune disorders (such as Graves' disease and autoimmune hepatitis) have 
also been reported; however, the reported time to onset is more variable and these events can occur 
many months after initiation of treatment (see section 4.4). 
 
Osteonecrosis 
Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk 
factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy (CART). 
The frequency of this is unknown (see section 4.4). 
 
Laboratory test abnormalities 
 
Liver enzymes: Elevations of AST and ALT to greater than five times the upper limit of the normal 
range (ULN) were seen in 3% of 1,008 patients treated with 600 mg of efavirenz (5-8% after 
long-term treatment in study 006). Similar elevations were seen in patients treated with control 
regimens (5% after long-term treatment). Elevations of GGT to greater than five times ULN were 
observed in 4% of all patients treated with 600 mg of efavirenz and 1.5-2% of patients treated with 
control regimens (7% of efavirenz-treated patients and 3% of control-treated patients after long-term 
treatment). Isolated elevations of GGT in patients receiving efavirenz may reflect enzyme induction. 
In the long-term study (006), 1% of patients in each treatment arm discontinued because of liver or 
biliary system disorders. 
 
Amylase: In the clinical trial subset of 1,008 patients, asymptomatic increases in serum amylase levels 
greater than 1.5 times the upper limit of normal were seen in 10% of patients treated with efavirenz 
and 6% of patients treated with control regimens. The clinical significance of asymptomatic increases 
in serum amylase is unknown. 
 
Metabolic parameters 
Weight and levels of blood lipids and glucose may increase during antiretroviral therapy (see section 
4.4). 
 
Paediatric population 
 
Undesirable effects in children were generally similar to those of adult patients. Rash was reported 
more frequently in children (59 of 182 (32%) treated with efavirenz) and was more often of higher 

 23 



grade than in adults (severe rash was reported in 6 of 182 (3.3%) of children). Prophylaxis with 
appropriate antihistamines prior to initiating therapy with efavirenz in children may be considered.  
 
Other special populations 
 
Liver enzymes in hepatitis B or C co-infected patients 
In the long-term data set from study 006, 137 patients treated with efavirenz-containing regimens 
(median duration of therapy, 68 weeks) and 84 treated with a control regimen (median duration, 
56 weeks) were seropositive at screening for hepatitis B (surface antigen positive) and/or C (hepatitis 
C antibody positive). Among co-infected patients in study 006, elevations in AST to greater than five 
times ULN developed in 13% of efavirenz-treated patients and in 7% of control, and elevations in 
ALT to greater than five times ULN developed in 20% and 7%, respectively. Among co-infected 
patients, 3% of those treated with efavirenz and 2% in the control arm discontinued because of liver 
disorders (see section 4.4). 
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V  
 
 
4.9 Overdose 
 
Some patients accidentally taking 600 mg twice daily have reported increased nervous system 
symptoms. One patient experienced involuntary muscle contractions. 
 
Treatment of overdose with efavirenz should consist of general supportive measures, including 
monitoring of vital signs and observation of the patient’s clinical status. Administration of activated 
charcoal may be used to aid removal of unabsorbed efavirenz. There is no specific antidote for 
overdose with efavirenz. Since efavirenz is highly protein-bound, dialysis is unlikely to remove 
significant quantities of it from blood. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antivirals for systemic use, non-nucleoside reverse transcriptase 
inhibitors. ATC code: J05AG03 
 
Mechanism of action 
 
Efavirenz is a NNRTI of HIV-1. Efavirenz is a non-competitive inhibitor of HIV-1 reverse 
transcriptase (RT) and does not significantly inhibit HIV-2 RT or cellular DNA polymerases (α, β, γ or 
δ). 
 
Cardiac Electrophysiology 
 
The effect of efavirenz on the QTc interval was evaluated in an open-label, positive and placebo 
controlled, fixed single sequence 3-period, 3-treatment crossover QT study in 58 healthy subjects 
enriched for CYP2B6 polymorphisms. The mean Cmax of efavirenz in subjects with CYP2B6 *6/*6 
genotype following the administration of 600 mg daily dose for 14 days was 2.25-fold the mean Cmax 
observed in subjects with CYP2B6 *1/*1 genotype. A positive relationship between efavirenz 
concentration and QTc prolongation was observed. Based on the concentration-QTc relationship, the 
mean QTc prolongation and its upper bound 90% confidence interval are 8.7 ms and 11.3 ms in 

 24 



subjects with CYP2B6*6/*6 genotype following the administration of 600 mg daily dose for 14 days 
(see section 4.5).  

 
Antiviral activity 
 
The free concentration of efavirenz required for 90 to 95% inhibition of wild type or 
zidovudine-resistant laboratory and clinical isolates in vitro ranged from 0.46 to 6.8 nM in 
lymphoblastoid cell lines, peripheral blood mononuclear cells (PBMCs) and macrophage/monocyte 
cultures. 
 
Resistance 
 
The potency of efavirenz in cell culture against viral variants with amino acid substitutions at positions 
48, 108, 179, 181 or 236 in RT or variants with amino acid substitutions in the protease was similar to 
that observed against wild-type viral strains. The single substitutions which led to the highest 
resistance to efavirenz in cell culture correspond to a leucine-to-isoleucine change at position 100 
(L100I, 17 to 22-fold resistance) and a lysine-to-asparagine at position 103 (K103N, 18 to 33-fold 
resistance). Greater than 100-fold loss of susceptibility was observed against HIV variants expressing 
K103N in addition to other amino acid substitutions in RT. 
 
K103N was the most frequently observed RT substitution in viral isolates from patients who 
experienced a significant rebound in viral load during clinical studies of efavirenz in combination with 
indinavir or zidovudine + lamivudine. This mutation was observed in 90% of patients receiving 
efavirenz with virological failure. Substitutions at RT positions 98, 100, 101, 108, 138, 188, 190 or 
225 were also observed, but at lower frequencies, and often only in combination with K103N. The 
pattern of amino acid substitutions in RT associated with resistance to efavirenz was independent of 
the other antiviral medicines used in combination with efavirenz. 
 
Cross-resistance 
Cross-resistance profiles for efavirenz, nevirapine and delavirdine in cell culture demonstrated that the 
K103N substitution confers loss of susceptibility to all three NNRTIs. Two of three 
delavirdine-resistant clinical isolates examined were cross-resistant to efavirenz and contained the 
K103N substitution. A third isolate which carried a substitution at position 236 of RT was not 
cross-resistant to efavirenz. 
 
Viral isolates recovered from PBMCs of patients enrolled in efavirenz clinical studies who showed 
evidence of treatment failure (viral load rebound) were assessed for susceptibility to NNRTIs. Thirteen 
isolates previously characterised as efavirenz-resistant were also resistant to nevirapine and 
delavirdine. Five of these NNRTI-resistant isolates were found to have K103N or a 
valine-to-isoleucine substitution at position 108 (V108I) in RT. Three of the efavirenz treatment 
failure isolates tested remained sensitive to efavirenz in cell culture and were also sensitive to 
nevirapine and delavirdine. 
 
The potential for cross-resistance between efavirenz and PIs is low because of the different enzyme 
targets involved. The potential for cross-resistance between efavirenz and NRTIs is low because of the 
different binding sites on the target and mechanism of action. 
 
Clinical efficacy 
 
Efavirenz has not been studied in controlled studies in patients with advanced HIV disease, namely 
with CD4 counts < 50 cells/mm3, or in PI or NNRTI experienced patients. Clinical experience in 
controlled studies with combinations including didanosine or zalcitabine is limited. 
 
Two controlled studies (006 and ACTG 364) of approximately one-year duration with efavirenz in 
combination with NRTIs and/or PIs, have demonstrated reduction of viral load below the limit of 
quantification of the assay and increased CD4 lymphocytes in antiretroviral therapy-naïve and 
NRTI-experienced HIV infected patients. Study 020 showed similar activity in NRTI-experienced 

 25 



patients over 24 weeks. In these studies the dose of efavirenz was 600 mg once daily; the dose of 
indinavir was 1,000 mg every 8 hours when used with efavirenz and 800 mg every 8 hours when used 
without efavirenz. The dose of nelfinavir was 750 mg given three times a day. The standard doses of 
NRTIs given every 12 hours were used in each of these studies. 
 
Study 006, a randomized, open-label trial, compared efavirenz + zidovudine + lamivudine or efavirenz 
+ indinavir with indinavir + zidovudine + lamivudine in 1,266 patients who were required to be 
efavirenz-, lamivudine-, NNRTI-, and PI-naive at study entry. The mean baseline CD4 cell count was 
341 cells/mm3 and the mean baseline HIV-RNA level was 60,250 copies/ml. Efficacy results for study 
006 on a subset of 614 patients who had been enrolled for at least 48 weeks are found in Table 2. In 
the analysis of responder rates (the non-completer equals failure analysis [NC = F]), patients who 
terminated the study early for any reason, or who had a missing HIV-RNA measurement that was 
either preceded or followed by a measurement above the limit of assay quantification were considered 
to have HIV-RNA above 50 or above 400 copies/ml at the missing time points. 
 
Table 2: Efficacy results for study 006 
Treatment 
regimen d 

n Responder rates (NC = F a) 
Plasma HIV-RNA 

Mean change from 
baseline-CD4 cell count 

Cells/mm3 (S.E.M. c) < 400 copies/ml 
(95% C.I.b) 

<50 copies/ml 
(95% C.I.b) 

48 weeks 48 weeks 48 weeks 
EFV + 
ZDV + 3TC 

202 67% 
(60%, 73%) 

62% 
(55%, 69%) 

187 
(11.8) 

EFV + IDV 206 54% 
(47%, 61%) 

48% 
(41%, 55%) 

177 
(11.3) 

IDV + 
ZDV + 3TC 

206 45% 
(38%, 52%) 

40% 
(34%, 47%) 

153 
(12.3) 

a NC = F, noncompleter = failure. 
b C.I., confidence interval. 
c S.E.M., standard error of the mean. 
d EFV, efavirenz; ZDV, zidovudine; 3TC, lamivudine; IDV, indinavir. 
 
Long-term results at 168 weeks of study 006 (160 patients completed study on treatment with 
EFV+IDV, 196 patients with EFV+ZDV+3TC and 127 patients with IDV+ZDV+3TC, respectively), 
suggest durability of response in terms of proportions of patients with HIV-RNA < 400 copies/ml, 
HIV-RNA < 50 copies/ml and in terms of mean change from baseline CD4 cell count. 
 
Efficacy results for studies ACTG 364 and 020 are found in Table 3. Study ACTG 364 enrolled 196 
patients who had been treated with NRTIs but not with PIs or NNRTIs. Study 020 enrolled 327 
patients who had been treated with NRTIs but not with PIs or NNRTIs. Physicians were allowed to 
change their patient’s NRTI regimen upon entry into the study. Responder rates were highest in 
patients who switched NRTIs. 
 
Table 3: Efficacy results for studies ACTG 364 and 020 
  Responder rates (NC = Fa) 

Plasma HIV-RNA 
Mean change from 

baseline-CD4 cell count 
Study number/ 
Treatment 
regimensb 

n % (95% C.I.c) % (95% C.I.c) cells/mm3 (S.E.M.d) 

Study ACTG 364 
48 weeks 

 < 500 copies/ml < 50 copies/ml   

EFV + NFV + 
NRTIs 

65 70 (59, 82) --- --- 107 (17.9) 

EFV + NRTIs 65 58 (46, 70) --- --- 114 (21.0) 
NFV + NRTIs 66 30 (19, 42) --- --- 94 (13.6) 
Study 020 
24 weeks 

 < 400 copies/ml < 50 copies/ml   

 26 



  Responder rates (NC = Fa) 
Plasma HIV-RNA 

Mean change from 
baseline-CD4 cell count 

Study number/ 
Treatment 
regimensb 

n % (95% C.I.c) % (95% C.I.c) cells/mm3 (S.E.M.d) 

EFV + IDV + 
NRTIs 

157 60 (52, 68) 49 (41, 58) 104 (9.1) 

IDV + NRTIs 170 51 (43, 59) 38 (30, 45) 77 (9.9) 
a NC = F, noncompleter = failure. 
b EFV, efavirenz; ZDV, zidovudine; 3TC, lamivudine; IDV, indinavir; NRTI, nucleoside reverse 
transcriptase inhibitor; NFV, nelfinavir. 
c C.I., confidence interval for proportion of patients in response. 
d S.E.M., standard error of the mean. 
---, not performed. 
 
Paediatric population 
  
Study AI266922 was an open-label study to evaluate the pharmacokinetics, safety, tolerability, and 
antiviral activity of efavirenz in combination with didanosine and emtricitabine in antiretroviral-naive 
and -experienced paediatric patients. Thirty-seven patients 3 months to 6 years of age (median 0.7 
years) were treated with efavirenz. At baseline, median plasma HIV-1 RNA was 5.88 log10 
copies/mL, median CD4+ cell count was 1144 cells/mm3, and median CD4+ percentage was 25%. 
The median time on study therapy was 132 weeks; 27% of patients discontinued before Week 48. 
Using an ITT analysis, the overall proportions of patients with HIV RNA <400 copies/mL and <50 
copies/mL at Week 48 were 57% (21/37) and 46% (17/37), respectively. The median increase from 
baseline in 
CD4+ count at 48 weeks was 215 cells/mm3 and the median increase in CD4+ percentage was 6%. 
 
Study PACTG 1021 was an open-label study to evaluate the pharmacokinetics, safety, tolerability, and 
antiviral activity of efavirenz in combination with didanosine and emtricitabine in paediatric patients 
who were antiretroviral therapy naive. Forty-three patients 3 months to 21 years of age (median 
9.6 years) were dosed with efavirenz. At baseline, median plasma HIV-1 RNA was 
4.8 log10 copies/mL, median CD4+ cell count was 367 cells/mm3, and median CD4+ percentage was 
18%. The median time on study therapy was 181 weeks; 16% of patients discontinued before Week 
48. Using an ITT analysis, the overall proportions of patients with HIV RNA <400 copies/mL and 
<50 copies/mL at Week 48 were 77% (33/43) and 70% (30/43), respectively. The median increase 
from baseline in CD4+ count at 48 weeks of therapy was 238 cells/mm3 and the median increase in 
CD4+ percentage was 13%. 
 
Study PACTG 382 was an open-label study to evaluate the pharmacokinetics, safety, tolerability, and 
antiviral activity of efavirenz in combination with nelfinavir and an NRTI in antiretroviral-naive and 
NRTI-experienced paediatric patients. One hundred two patients 3 months to 16 years of age (median 
5.7 years) were treated with efavirenz. Eighty-seven percent of patients had received prior 
antiretroviral therapy. At baseline, median plasma HIV-1 RNA was 4.57 log10 copies/mL, median 
CD4+ cell count was 755 cells/mm3, and median CD4+ percentage was 30%. The median time on 
study therapy was 118 weeks; 25% of patients discontinued before Week 48. Using an ITT analysis, 
the overall proportion of patients with HIV RNA <400 copies/mL and <50 copies/mL at Week 48 
were 57% (58/102) and 43% (44/102), respectively. The median increase from baseline in CD4+ count 
at 48 weeks of therapy was 128 cells/mm3 and the median increase in CD4+ percentage was 5%.  
 
 
5.2 Pharmacokinetic properties 
 
Absorption 
 
Peak efavirenz plasma concentrations of 1.6-9.1 microM were attained by 5 hours following single 
oral doses of 100 mg to 1,600 mg administered to uninfected volunteers. Dose-related increases in 

 27 



Cmax and AUC were seen for doses up to 1,600 mg; the increases were less than proportional 
suggesting diminished absorption at higher doses. Time to peak plasma concentrations (3-5 hours) did 
not change following multiple dosing and steady-state plasma concentrations were reached in 6-
7 days. 
 
In HIV infected patients at steady-state, mean Cmax, mean Cmin, and mean AUC were linear with 
200 mg, 400 mg, and 600 mg daily doses. In 35 patients receiving efavirenz 600 mg once daily, 
steady-state Cmax was 12.9 ± 3.7 microM (29%) [mean ± S.D. (% C.V.)], steady-state Cmin was 
5.6 ± 3.2 microM (57%), and AUC was 184 ± 73 microM·h (40%). 
 
Effect of food 
 
The AUC and Cmax of a single 600 mg dose of efavirenz film-coated tablets in uninfected volunteers 
was increased by 28% (90% CI: 22-33%) and 79% (90% CI: 58-102%), respectively, when given with 
a high-fat meal, relative to when given under fasted conditions (see section 4.4). 
 
Distribution 
 
Efavirenz is highly bound (approximately 99.5-99.75%) to human plasma proteins, predominantly 
albumin. In HIV-1 infected patients (n = 9) who received efavirenz 200 to 600 mg once daily for at 
least one month, cerebrospinal fluid concentrations ranged from 0.26 to 1.19% (mean 0.69%) of the 
corresponding plasma concentration. This proportion is approximately 3-fold higher than the 
non-protein-bound (free) fraction of efavirenz in plasma. 
 
Biotransformation 
 
Studies in humans and in vitro studies using human liver microsomes have demonstrated that 
efavirenz is principally metabolised by the cytochrome P450 system to hydroxylated metabolites with 
subsequent glucuronidation of these hydroxylated metabolites. These metabolites are essentially 
inactive against HIV-1. The in vitro studies suggest that CYP3A4 and CYP2B6 are the major 
isozymes responsible for efavirenz metabolism and that it inhibited P450 isozymes 2C9, 2C19, and 
3A4. In in vitro studies efavirenz did not inhibit CYP2E1 and inhibited CYP2D6 and CYP1A2 only at 
concentrations well above those achieved clinically. 
 
Efavirenz plasma exposure may be increased in patients with the homozygous G516T genetic variant 
of the CYP2B6 isoenzyme. The clinical implications of such an association are unknown; however, 
the potential for an increased frequency and severity of efavirenz-associated adverse events cannot be 
excluded. 
 
Efavirenz has been shown to induce CYP3A4 and CYP2B6, resulting in the induction of its own 
metabolism which may be clinically relevant in some patients. In uninfected volunteers, multiple 
doses of 200-400 mg per day for 10 days resulted in a lower than predicted extent of accumulation 
(22-42% lower) and a shorter terminal half-life compared with single dose administration (see below). 
Efavirenz has also been shown to induce UGT1A1. Exposures of raltegravir (a UGT1A1 substrate) are 
reduced in the presence of efavirenz (see section 4.5, table 1). 
Although in vitro data suggest that efavirenz inhibits CYP2C9 and CYP2C19, there have been 
contradictory reports of both increased and decreased exposures to substrates of these enzymes when 
coadministered with efavirenz in vivo. The net effect of coadministration is not clear 
 
Elimination 
 
Efavirenz has a relatively long terminal half-life of at least 52 hours after single doses and 40-55 hours 
after multiple doses. Approximately 14-34% of a radiolabelled dose of efavirenz was recovered in the 
urine and less than 1% of the dose was excreted in urine as unchanged efavirenz. 
 

 28 



Hepatic impairment 
 
In a single-dose study, half-life was doubled in the single patient with severe hepatic impairment 
(Child Pugh Class C), indicating a potential for a much greater degree of accumulation. A 
multiple-dose study showed no significant effect on efavirenz pharmacokinetics in patients with mild 
hepatic impairment (Child-Pugh Class A) compared with controls.  There were insufficient data to 
determine whether moderate or severe hepatic impairment (Child-Pugh Class B or C) affects efavirenz 
pharmacokinetics. 
 
Gender, race, elderly 
 
Although limited data suggest that females as well as Asian and Pacific Island patients may have 
higher exposure to efavirenz, they do not appear to be less tolerant of efavirenz. Pharmacokinetic 
studies have not been performed in the elderly. 
 
Paediatric population 
 
The pharmacokinetic parameters for efavirenz at steady state in paediatric patients were predicted by a 
population pharmacokinetic model and are summarized in Table 4 by weight ranges that correspond to 
the recommended doses of the capsules. 
 
Table 4: Predicted steady-state pharmacokinetics of efavirenz (capsules/capsule sprinkles) in 

HIV-infected paediatric patients 
 

Body Weight Dose Mean AUC(0-24) 
µM·h 

Mean Cmax 
µg/mL 

Mean Cmin 
µg/mL 

3.5-5 kg 100 mg 220.52 5.81 2.43 
5-7.5 kg 150 mg 262.62 7.07 2.71 
7.5-10 kg 200 mg 284.28 7.75 2.87 
10-15 kg 200 mg 238.14 6.54 2.32 
15-20 kg 250 mg 233.98 6.47 2.3 
20-25 kg 300 mg 257.56 7.04 2.55 

25-32.5 kg 350 mg 262.37 7.12 2.68 
32.5-40 kg 400 mg 259.79 6.96 2.69 

>40 kg 600 mg 254.78 6.57 2.82 
 
5.3 Preclinical safety data 
 
Efavirenz was not mutagenic or clastogenic in conventional genotoxicity assays. 
 
Efavirenz induced foetal resorptions in rats. Malformations were observed in 3 of 20 
foetuses/newborns from efavirenz-treated cynomolgus monkeys given doses resulting in plasma 
efavirenz concentrations similar to those seen in humans. Anencephaly and unilateral anophthalmia 
with secondary enlargement of the tongue were observed in one foetus, microophthalmia was 
observed in another foetus, and cleft palate was observed in a third foetus. No malformations were 
observed in foetuses from efavirenz-treated rats and rabbits. 
 
Biliary hyperplasia was observed in cynomolgus monkeys given efavirenz for ≥ 1 year at a dose 
resulting in mean AUC values approximately 2-fold greater than those in humans given the 
recommended dose. The biliary hyperplasia regressed upon cessation of dosing. Biliary fibrosis has 
been observed in rats. Non-sustained convulsions were observed in some monkeys receiving efavirenz 
for ≥ 1 year, at doses yielding plasma AUC values 4- to 13-fold greater than those in humans given the 
recommended dose (see sections 4.4 and 4.8). 
 

 29 



Carcinogenicity studies showed an increased incidence of hepatic and pulmonary tumours in female 
mice, but not in male mice. The mechanism of tumour formation and the potential relevance for 
humans are not known. 
 
Carcinogenicity studies in male mice, male and female rats were negative. While the carcinogenic 
potential in humans is unknown, these data suggest that the clinical benefit of efavirenz outweighs the 
potential carcinogenic risk to humans. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Core 
 
Cellulose, microcrystalline 
Hydroxypropylcellulose 
Sodium laurilsulfate 
Sodium starch glycolate (Type A) 
Poloxamer 407 
Magnesium stearate 
 
Film-coating 
 
 
Hypromellose 6cP (HPMC 2910) 
Lactose monohydrate 
Titanium dioxide 
Macrogol/PEG 3350 
Triacetin 3 
Iron oxide yellow 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
2 years 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 
White opaque PVC/PVdC-aluminium or aluminium-aluminium blisters in a carton containing 30 or 
90 film-coated tablets. 
 
30 x 1 film-coated tablet in white opaque PVC/PVdC-aluminium or aluminium-aluminium perforated 
unit-dose blisters. 
 
90 x 1 film-coated tablet in white opaque PVC/PVdC-aluminium perforated unit-dose blisters. 
 
Multipack (bundle) containing 90 film-coated tablets (3 packs of 30 x 1 film-coated tablet) in white 
opaque PVC/PVdC-aluminium or aluminium-aluminium perforated unit-dose blisters. 
 

 30 



Multipack (carton) containing 90 film-coated tablets (3 packs of 30 x 1 film-coated tablet) in white 
opaque PVC/PVdC-aluminium or aluminium-aluminium perforated unit-dose blisters. 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal 
 
No special requirements for disposal. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Teva B.V., Swensweg 5, 2031GA Haarlem, The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/742/001-011 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 9 January 2012  
Date of latest renewal: 9 September 2016 
 
10. DATE OF REVISION OF THE TEXT 
 
{MM/YYYY} 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu   

 31 



 

 

 

 

 

 

 

 

 

ANNEX II 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE  

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
 AUTHORISATION 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE 
AND EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 
 

 32 



A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
 
Name and address of the manufacturer responsible for batch release 
 
PLIVA Hrvatska d.o.o. (PLIVA Croatia Ltd.)  
Prilaz baruna Filipovića 25 
10000 Zagreb,  
Croatia 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 

 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
 AUTHORISATION  
 
• Periodic Safety Update Reports  
 

The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
 EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 

• Risk Management Plan (RMP) 
 
Not applicable. 
 
 
 
 
  

 33 



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  

 34 



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
A. LABELLING 

  

 35 



PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON FOR BLISTER PACK CONTAINING 
OF <30><30x1><90><90 x 1> EFAVIRENZ TEVA 600 mg FILM-COATED TABLETS 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Efavirenz Teva 600 mg film-coated tablets 
Efavirenz 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 600 mg efavirenz. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 film-coated tablets 
30 x 1 film-coated-tablets 
90 x 1 film-coated tablets 
90 film-coated tablets 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Oral use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP {MM/YYYY} 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 36 



 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Teva B.V., Swensweg 5, 2031GA Haarlem, The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/742/001 (30 x 1 – blister PVC/PVDC/alu) 
EU/1/11/742/002 (30 – blister PVC/PVDC/alu) 
EU/1/11/742/003 (90 – blister PVC/PVDC/alu) 
EU/1/11/742/006 (30 x 1 – blister alu/alu) 
EU/1/11/742/007 (30 – blister alu/alu) 
EU/1/11/742/008 (90 – blister alu/alu) 
EU/1/11/742/011 (90 x 1 – blister PVC/PVDC/alu) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE  
 
Efavirenz Teva 600 mg film-coated tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  

 37 



PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
OUTER BUNDLE LABEL FOR MULTIPACKS OF 90 (3 PACKS OF 30 x 1 FILM-COATED 
TABLET) - WITH THE BLUE BOX 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Efavirenz Teva 600 mg film-coated tablets 
Efavirenz 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 600 mg efavirenz. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Multipack: 90 (3 packs of 30 x 1) film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP {MM/YYYY} 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 

 38 



 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Teva B.V., Swensweg 5, 2031GA Haarlem, The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/742/004 (bundle multi-pack – blister PVC/PVDC/alu) 
EU/1/11/742/009 (bundle multi-pack – blister alu/alu) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
 
16. INFORMATION IN BRAILLE 
 
Efavirenz Teva 600 mg film-coated tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  

 39 



PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON FOR MULTIPACKS OF 90 (3 PACKS OF 30 x 1 FILM-COATED 
TABLETS) - WITH THE BLUE BOX  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Efavirenz Teva 600 mg film-coated tablets 
Efavirenz 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 600 mg efavirenz. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Multipack: 90 (3 packs of 30 x 1) film-coated tablets 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP {MM/YYYY} 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
 

 40 



 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Teva B.V., Swensweg 5, 2031GA Haarlem, The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/742/005 (carton multi-pack – blister PVC/PVDC/alu) 
EU/1/11/742/010 (carton multi-pack – blister alu/alu) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
 
16. INFORMATION IN BRAILLE 
 
Efavirenz Teva 600 mg film-coated tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  

 41 



PARTICULARS TO APPEAR ON THE OUTER CARTON 
 
COMPONENT OF MULTIPACK OF 90 (3 PACKS OF 30 x 1 FILM-COATED TABLETS) - 
WITHOUT BLUE BOX 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Efavirenz Teva 600 mg film-coated tablets 
Efavirenz 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 600 mg efavirenz. 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose. See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 x 1 film-coated tablets. Component of a multipack, can’t be sold separately. 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP {MM/YYYY} 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 
 
 
 

 42 



 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Teva B.V., Swensweg 5, 2031GA Haarlem, The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/11/742/001 (30 x 1 – blister PVC/PVDC/alu) 
EU/1/11/742/006 (30 x 1 – blister alu/alu) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
 
16. INFORMATION IN BRAILLE 
 
Efavirenz Teva 600 mg film-coated tablets 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 
  

 43 



MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
EFAVIRENZ TEVA 600 mg FILM-COATED TABLET: BLISTER FOIL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Efavirenz Teva 600 mg film-coated tablets 
Efavirenz 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Teva 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
Lot 
 
5. OTHER 
 
  

 44 



 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 

 45 



Package leaflet: information for the user 
 

Efavirenz Teva 600 mg film-coated tablets 
efavirenz 

 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.  
 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
- If you get any side effects talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet:  
1. What Efavirenz Teva is and what it is used for 
2. What you need to know before you take Efavirenz Teva 
3. How to take Efavirenz Teva 
4. Possible side effects 
5. How to store Efavirenz Teva 
6. Contents of the pack and other information 
 
 
1. What Efavirenz Teva is and what it is used for 
 
Efavirenz Teva, which contains the active substance efavirenz, belongs to a class of antiretroviral 
medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs). It is an antiretroviral 
medicine that fights human immunodeficiency virus (HIV-1) infection by reducing the amount of 
the virus in blood. It is used by adults, adolescents and children 3 years of age and older.  
 
 
Your doctor has prescribed Efavirenz Teva for you because you have HIV infection. Efavirenz Teva 
taken in combination with other antiretroviral medicines reduces the amount of the virus in the blood. 
This will strengthen your immune system and reduce the risk of developing illnesses linked to HIV 
infection. 
 
 
2. What you need to know before you take Efavirenz Teva 
 
Do NOT take Efavirenz Teva 
 
- If you are allergic to efavirenz or any of the other ingredients of this medicine (listed in section 

6). Contact your doctor or pharmacist for advice. 
- If you have severe liver disease. 
- If you have a heart condition, such as changes in the rhythm or rate of the heart beat, a 

slow heart beat, or severe heart disease. 
- If any member of your family (parents, grandparents, brothers or sisters) has died suddenly due 

to a heart problem or was born with heart problems. 
- If your doctor has told you that you have high or low levels of electrolytes such as potassium or 

magnesium in your blood. 
If you are currently taking any of the following medicines (see also “Other medicines and Efavirenz 

Teva): 
- Astemizole or terfenadine (used to treat allergy symptoms) 
- Bepridil (used to treat heart disease) 
- Cisapride (used to treat heartburn) 

 46 



- Ergot alkaloids (for example, ergotamine, dihydroergotamine, ergonovine, and 
methylergonovine) (used to treat migraine and cluster headaches) 

- Midazolam or triazolam (used to help you sleep) 
- Pimozide, imipramine, amitriptyline or clomipramine (used to treat certain mental 

conditions) 
- elbasvir or grazoprevir (used to treat hepatitis C) 
- St John's wort (Hypericum perforatum) (a herbal remedy used for depression and 

anxiety) 
- flecainide, metoprolol (used to treat irregular heart beat) 
- certain antibiotics (macrolides, fluoroquinolones, imidazole)  
- triazole antifungal agents 
- certain antimalarial treatments 

 - methadone (used to treat opiate addiction) 
 
If you are taking any of these medicines, tell your doctor immediately. Taking these 
medicines with Efavirenz Teva could create the potential for serious and/or life-threatening side 
effects or stop Efavirenz Teva from working properly. 

 
Warnings and precautions 
 
Talk to your doctor before taking Efavirenz Teva 
 
- Efavirenz Teva must be taken with other medicines that act against the HIV virus. If 

Efavirenz Teva is started because your current treatment has not prevented the virus from 
multiplying, another medicine you have not taken before must be started at the same time. 

- You can still pass on HIV when taking this medicine, although the risk is lowered by effective 
antiretroviral therapy. Discuss with your doctor the precautions needed to avoid infecting other 
people. This medicine is not a cure for HIV infection and you may continue to develop 
infections or other illnesses associated with HIV disease. 

- You must remain under the care of your doctor while taking Efavirenz Teva. 
- Tell your doctor: 

- if you have a history of mental illness, including depression, or of substance or alcohol 
abuse. Tell your doctor immediately if you feel depressed, have suicidal thoughts or have 
strange thoughts (see section 4, Possible side effects). 

- if you have a history of convulsions (fits or seizures) or if you are being treated with 
anticonvulsant therapy such as carbamazepine, phenobarbital and phenytoin. If you are 
taking any of these medicines, your doctor may need to check the level of anticonvulsant 
medicine in your blood to ensure that it is not affected while taking Efavirenz Teva. Your 
doctor may give you a different anticonvulsant. 

- if you have a history of liver disease, including active chronic hepatitis. Patients with 
chronic hepatitis B or C and treated with combination antiretroviral agents have a higher 
risk for severe and potentially life-threatening liver problems. Your doctor may conduct 
blood tests in order to check how well your liver is working or may switch you to another 
medicine. If you have severe liver disease, do not take Efavirenz Teva (see section 2, 
Do not take Efavirenz Teva). 

- if you have a heart disorder, such as abnormal electrical signal called prolongation 
of the QT interval.  

 
- Once you start taking Efavirenz Teva, look out for: 

- signs of dizziness, difficulty sleeping, drowsiness, difficulty concentrating or 
abnormal dreaming. These side effects may start in the first 1 or 2 days of treatment and 
usually go away after the first 2 to 4 weeks. 

- any signs of skin rash. If you see any signs of a severe rash with blistering or fever, stop 
taking Efavirenz Teva and tell your doctor at once. If you had a rash while taking another 
NNRTI, you may be at a higher risk of getting a rash with Efavirenz Teva. 

- any signs of inflammation or infection. In some patients with advanced HIV infection 
(AIDS) and a history of opportunistic infection, signs and symptoms of inflammation 

 47 



from previous infections may occur soon after anti-HIV treatment is started. It is believed 
that these symptoms are due to an improvement in the body’s immune response, enabling 
the body to fight infections that may have been present with no obvious symptoms. If you 
notice any symptoms of infection, please tell your doctor immediately. In addition to the 
opportunistic infections, autoimmune disorders (a condition that occurs when the immune 
system attacks healthy body tissue) may also occur after you start taking medicines for 
the treatment of your HIV infection. Autoimmune disorders may occur many months 
after the start of treatment. If you notice any symptoms of infection or other symptoms 
such as muscle weakness, weakness beginning in the hands and feet and moving up 
towards the trunk of the body, palpitations, tremor or hyperactivity, please inform your 
doctor immediately to seek necessary treatment. 

- bone problems. Some patients taking combination antiretroviral therapy may develop a 
bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to 
the bone). The length of combination antiretroviral therapy, corticosteroid use, alcohol 
consumption, severe immunosuppression, higher body mass index, among others, may be 
some of the many risk factors for developing this disease. Signs of osteonecrosis are joint 
stiffness, aches and pains (especially of the hip, knee and shoulder) and difficulty in 
movement. If you notice any of these symptoms please inform your doctor. 

 
Children and adolescents 
 
Efavirenz Teva film-coated tablets are not recommended for children under the age of 3 years or 
weighing less than 40 kg. 
 
Other medicines and Efavirenz Teva 
You must not take Efavirenz Teva with certain medicines. These are listed under "Do not take 
Efavirenz Teva", at the start of Section 2. They include some common medicines and a herbal remedy 
(St. John’s wort) which can cause serious interactions. 
 
Tell your doctor, pharmacist or nurse if you are taking, have recently taken, or might take any other 
medicines. 
 
Efavirenz Teva may interact with other medicines, including herbal preparations such as Ginkgo 
biloba extracts. As a result, the amounts of Efavirenz Teva or other medicines in your blood may be 
affected. This may stop the medicines from working properly, or may make any side effects worse. In 
some cases, your doctor may need to adjust your dose or check your blood levels. It is important to 
tell your doctor or pharmacist if you are taking any of the following: 
- Other medicines used for HIV infection: 

- protease inhibitors: darunavir, indinavir, lopinavir/ritonavir, ritonavir, ritonavir-boosted 
atazanavir, saquinavir or fosamprenavir/saquinavir. Your doctor may consider giving you 
an alternative medicine or changing the dose of the protease inhibitors. 

- maraviroc 
- the combination tablet containing efavirenz, emtricitabine, and tenofovir should not be 

taken with Efavirenz Teva unless recommended by your doctor since it contains 
efavirenz, the active ingredient of Efavirenz Teva. 

 
- Medicines used to treat infection with the hepatitis C virus: boceprevir, telaprevir, 

elbasvir/grazoprevir, simeprevir, sofosbuvir/velpatasvir, sofosbuvir/velpatasvir/voxilaprevir, 
glecaprevir/pibrentasvir. 

- Medicines used to treat bacterial infections including tuberculosis and AIDS-related 
mycobacterium avium complex: clarithromycin, rifabutin, rifampicin. Your doctor may 
consider changing your dose or giving you an alternative antibiotic. In addition, your doctor 
may prescribe a higher dose of Efavirenz Teva. 

- Medicines used to treat fungal infections (antifungals): 
- voriconazole. Efavirenz Teva may reduce the amount of voriconazole in your blood and 

voriconazole may increase the amount of efavirenz in your blood. If you take these two 

 48 



medicines together, the dose of voriconazole must be increased and the dose of efavirenz 
must be reduced. You must check with your doctor first. 

- itraconazole. Efavirenz Teva may reduce the amount of itraconazole in your blood.  
- posaconazole. Efavirenz Teva may reduce the amount of posaconazole in your blood. 

- Medicines used to treat malaria: 
artemether/lumefantrine: Efavirenz Teva may reduce the amount of artemether/lumefantrine in 
your blood 
- atovaquone/proguanil: Efavirenz Teva may reduce the amount of atovaquone/proguanil in 

your blood. 
- Medicines used to treat convulsions/seizures (anticonvulsants): carbamazepine, phenytoin, 

phenobarbital. Efavirenz Teva can reduce or increase the amount of anticonvulsant in your 
blood. Carbamazepine may make Efavirenz Teva less likely to work. Your doctor may need to 
consider giving you a different anticonvulsant. 

- Medicines used to lower blood fats (also called statins): atorvastatin, pravastatin, simvastatin. 
Efavirenz Teva can reduce the amount of statins in your blood. Your doctor will check your 
cholesterol levels and will consider changing the dose of your statin, if needed. 

- Methadone (a medicine used to treat opiate addiction): your doctor may recommend an 
alternative treatment. 

- Sertraline (a medicine used to treat depression): your doctor may need to change your dose of 
sertraline. 

- Bupropion (a medicine used to treat depression or to help you stop smoking): your doctor may 
need to change your dose of bupropion.   

- Diltiazem or similar medicines (called calcium channel blockers which are medicines 
typically used for high blood pressure or heart problems): when you start taking Efavirenz 
Teva, your doctor may need to adjust your dose of the calcium channel blocker. 

- Immunosuppressants such as cyclosporine, sirolimus, or tacrolimus (medicines used to 
prevent organ transplant rejection): when you start or stop taking Efavirenz Teva, your doctor 
will closely monitor your plasma levels of the immunosuppressant and may need to adjust its 
dose. 

- Hormonal contraceptive, such as birth control pills, an injected contraceptive (for 
example, Depo-Provera), or a contraceptive implant (for example, Implanon): you must 
also use a reliable barrier method of contraception (see Pregnancy, breast-feeding and fertility). 
Efavirenz Teva may make hormonal contraceptives less likely to work. Pregnancies have 
occurred in women taking Efavirenz Teva while using a contraceptive implant, although it has 
not been established that the Efavirenz Teva therapy caused the contraceptive to fail. 

- Warfarin or acenocoumarol (medicines used to reduce clotting of the blood): your doctor may 
need to adjust your dose of warfarin or acenocoumarol. 

- Ginkgo biloba extracts (a herbal preparation) 
- Medicines that impact heart rhythm: 

- Medicines used to treat heart rhythm problems: such as flecainide or metoprolol. 
- Medicines used to treat depression such as imipramine, amitriptyline or clomipramine 
- Antibiotics, including the following types: macrolides, fluoroquinolones or imidazole. 

 
 
Efavirenz Teva with food and drink 
 
Taking Efavirenz Teva on an empty stomach may reduce the undesirable effects. Grapefruit juice 
should be avoided when taking Efavirenz Teva. 
 
Pregnancy, breast-feeding and fertility 
 
Women should not get pregnant during treatment with Efavirenz Teva and for 12 weeks 
thereafter. Your doctor may require you to take a pregnancy test to ensure you are not pregnant 
before starting treatment with Efavirenz Teva. 
 
If you could get pregnant while receiving Efavirenz Teva, you need to use a reliable form of barrier 
contraception (for example, a condom) with other methods of contraception including oral (pill) or 

 49 



other hormonal contraceptives (for example, implants, injection). Efavirenz may remain in your blood 
for a time after therapy is stopped. Therefore, you should continue to use contraceptive measures, as 
above, for 12 weeks after you stop taking Efavirenz Teva. 
 
Tell your doctor immediately if you are pregnant or intend to become pregnant. If you are 
pregnant, you should take Efavirenz Teva only if you and your doctor decide it is clearly needed. Ask 
your doctor or pharmacist for advice before taking any medicine. 
 
Serious birth defects have been seen in unborn animals and in the babies of women treated with 
efavirenz or a combination medicine containing efavirenz, emtricitabine and tenofovir during 
pregnancy. If you have taken Efavirenz Teva or the combination tablet containing efavirenz, 
emtricitabine, and tenofovir during your pregnancy, your doctor may request regular blood tests and 
other diagnostic tests to monitor the development of your child. 
 
You should not breast-feed your baby if you are taking Efavirenz Teva. 
 
Driving and using machines 
 
Efavirenz Teva contains efavirenz and may cause dizziness, impaired concentration, and 
drowsiness. If you are affected, do not drive and do not use any tools or machines. 
 
Efavirenz Teva contains lactose 
This medicine contains 9.98 mg lactose (as monohydrate) per tablet.  
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicinal product.  
 
Efavirenz Teva contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per tablet that is to say essentially ‘sodium-
free’. 
 
3. How to take Efavirenz Teva 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. Your doctor will give you instructions for proper dosing. 
 
- The dose for adults is 600 mg once daily.  
- The dose for Efavirenz Teva may need to be increased or decreased if you are also taking 

certain medicines (see Other medicines and Efavirenz Teva). 
- Efavirenz Teva is for oral use. It is recommended to be taken on an empty stomach preferably at 

bedtime. This may make some side effects (for example, dizziness, drowsiness) less 
troublesome. An empty stomach is commonly defined as 1 hour before or 2 hours after a meal. 

- It is recommended that the tablet be swallowed whole with water. 
- Efavirenz Teva must be taken every day. 
- Efavirenz Teva should never be used alone to treat HIV. It must always be taken in combination 

with other anti-HIV medicines. 
 
Use in children and adolescents 
 
- Efavirenz Teva film-coated tablets are not suitable for children weighing less than 40 kg. 
- The dose for children weighing 40 kg or more is 600 mg once daily. 
 
If you take more Efavirenz Teva than you should 
 
If you take too much Efavirenz Teva, contact your doctor or nearest emergency department for advice. 
Keep the medicine container with you so that you can easily describe what you have taken. 
 

 50 



If you forget to take Efavirenz Teva 
 
Try not to miss a dose. If you do miss a dose, take the next dose as soon as possible, but do not take a 
double dose to make up for a forgotten dose. If you need help in planning the best times to take your 
medicine, ask your doctor or pharmacist. 
 
If you stop taking Efavirenz Teva 
 
When your Efavirenz Teva supply starts to run low, get more from your doctor or pharmacist. This 
is very important because the amount of virus may start to increase if the medicine is stopped for even 
a short time. The virus may then become harder to treat. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
When treating HIV infection, it is not always possible to tell whether some of the unwanted effects are 
caused by Efavirenz Teva or by other medicines that you are taking at the same time, or by the HIV 
disease itself. 
 
During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This 
is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV 
medicines themselves. Your doctor will test for these changes. 
 
The most notable unwanted effects reported with efavirenz in combination with other anti-HIV 
medicines are skin rash and nervous system symptoms. 
 
You should consult your doctor if you have a rash, since some rashes may be serious; however, most 
cases of rash disappear without any change to your treatment with Efavirenz Teva. Rash was more 
common in children than in adults treated with efavirenz. 
 
The nervous system symptoms tend to occur when treatment is first started, but generally decrease in 
the first few weeks. In one study, nervous system symptoms often occurred during the first 1-3 hours 
after taking a dose. If you are affected your doctor may suggest that you take Efavirenz Teva at 
bedtime and on an empty stomach. Some patients have more serious symptoms that may affect mood 
or the ability to think clearly. Some patients have actually committed suicide. These problems tend to 
occur more often in those who have a history of mental illness. Always notify your doctor 
immediately if you have these symptoms or any side effects while taking Efavirenz Teva. 
 
 
Tell your doctor if you notice any of the following side effects: 
 
Very common (affects more than 1 user in 10) 
- skin rash 
 
Common (affects 1 to 10 users in 100) 
- abnormal dreams, difficulty concentrating, dizziness, headache, difficulty sleeping, drowsiness, 

problems with coordination or balance 
- stomach pain, diarrhoea, feeling sick (nausea), vomiting 
- itching 
- tiredness 
- feeling anxious, feeling depressed 
Tests may show: 
- increased liver enzymes in the blood 
- increased triglycerides (fatty acids) in the blood 

 51 



 
Uncommon (affects 1 to 10 users in 1,000) 
- nervousness, forgetfulness, confusion, fitting (seizures), abnormal thoughts 
- blurred vision 
- a feeling of spinning or tilting (vertigo) 
- pain in the abdomen (stomach) caused by inflammation of the pancreas 
- allergic reaction (hypersensitivity) that may cause severe skin reactions (erythema multiforme, 

Stevens-Johnson syndrome) 
- yellow skin or eyes, itching, or pain in the abdomen (stomach) caused by inflammation of the 

liver 
- breast enlargement in males 
- angry behaviour, mood being affected, seeing or hearing things that are not really there 

(hallucinations), mania (mental condition characterised by episodes of overactivity, elation or 
irritability), paranoia, suicidal thoughts, catatonia (condition in which the patient is rendered 
motionless and speechless for a period) 

- whistling, ringing or other persistent noise in the ears 
- tremor (shaking) 
- flushing 
Tests may show: 
- increased cholesterol in the blood 
 
Rare (affects 1 to 10 users in 10,000) 
- itchy rash caused by a reaction to sunlight 
- liver failure, in some cases leading to death or liver transplant, has occurred with efavirenz. 

Most cases occurred in patients who already had liver disease, but there have been a few reports 
in patients without any existing liver disease. 

-  unexplained feelings of distress not associated with hallucinations, but it may be difficult to 
think clearly or sensibly 

- suicide  
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Efavirenz Teva 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the blister and on the carton after 
EXP. The expiry date refers to the last day of that month. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
6. Contents of the pack and other information 
 
What Efavirenz Teva contains 
 
- Each Efavirenz Teva film-coated tablet contains 600 mg of the active substance efavirenz. 
- The other ingredients are cellulose microcrystalline, hydroxypropylcellulose, sodium 

laurilsulfate, sodium starch glycolate (Type A), poloxamer 407 and magnesium stearate in the 
core. The film-coating agent contains hypromellose, lactose monohydrate, titanium dioxide, 
macrogol/PEG 3350, triacetin and iron oxide yellow. 

 

 52 



What Efavirenz Teva looks like and contents of the pack 
 
- Film-coated tablet: yellow, capsule-shaped, film-coated tablet debossed with “Teva” on one side 

and “7541” on the other 
- Efavirenz Teva is available in pack sizes of 30, 90 film-coated tablets or 30 x 1 / 90 x 1 

film-coated tablets (in perforated unit dose blisters) or a multi-pack bundle or carton containing 
90 film-coated tablets (3 packs of 30 x 1 film-coated tablet). Not all pack sizes may be 
marketed. 

 
 
Marketing Authorisation Holder 
 
Teva B.V., Swensweg 5, 2031GA Haarlem, The Netherlands 
 
Manufacturer 
 
PLIVA Hrvatska d.o.o. (PLIVA Croatia Ltd.), Prilaz baruna Filipovića 25, 10000 Zagreb, Croatia 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
Belgique/België/Belgien 
Teva Pharma Belgium N.V./S.A./AG 
Tél/Tel: +32 38207373 
 

Lietuva 
UAB Sicor Biotech  
Tel: +370 52660203 

България 
Актавис ЕАД 
Тел: +359 24899585 

Luxembourg/Luxemburg 
Teva Pharma Belgium N.V./S.A./AG 
Belgique/Belgien 
Tél/Tel: +32 38207373 
 

Česká republika 
Teva Pharmaceuticals CR, s.r.o  
Tel: +420 251007111 
 

Magyarország 
Teva Gyógyszergyár Zrt.  
Tel: +36 12886400 

Danmark 
Teva Denmark A/S 
Tlf: +45 44985511 
 

Malta 
Teva Pharmaceuticals Ireland 
L-Irlanda 
Tel: +353 19630330 
 

Deutschland 
ratiopharm GmbH 
Tel: +49 73140202 

Nederland 
Teva Nederland B.V. 
Tel: +31 8000228400 

Eesti 
UAB Sicor Biotech Eesti filiaal 
Tel: +372 6610801 
 

Norge 
Teva Norway AS 
Tlf: +47 66775590 
 

Ελλάδα 
Teva Ελλάς Α.Ε. 
Τηλ: +30 2118805000 
 

Österreich 
ratiopharm Arzneimittel Vertriebs-GmbH 
Tel: +43 1970070 

España 
Teva Pharma, S.L.U. 
Tel: +34 9138732 80 
 

Polska 
Teva Pharmaceuticals Polska Sp. z o.o  
Tel: +48 223459300 

France 
Teva Santé 
Tél: +33 155917800 

Portugal 
Teva Pharma - Produtos Farmacêuticos Lda. 
Tel: +351 214767550  

 53 



 
Hrvatska 
Pliva Hrvatska d.o.o. 
Tel:+ 385 13720000 
 

România 
Teva Pharmaceuticals S.R.L. 
Tel: +40 212306524 

Ireland 
Teva Pharmaceuticals Ireland 
Tel: +353 19630330 
 
 

Slovenija 
Pliva Ljubljana d.o.o. 
Tel: +386 15890390 

Ísland 
ratiopharm Oy 
Finnland 
Sími: +358 201805900 
  

Slovenská republika 
Teva Pharmaceuticals Slovakia s.r.o. 
Tel: +421 257267911 

Italia 
Teva Italia S.r.l. 
Tel: +39 028917981 
 

Suomi/Finland 
ratiopharm Oy 
Puh/Tel: +358 201805900 

Κύπρος 
Teva Ελλάς Α.Ε. 
Ελλάδα 
Τηλ: +30 2118805000 
 

Sverige 
Teva Sweden AB 
Tel: +46 42121100 

Latvija 
UAB Sicor Biotech filiāle Latvijā 
Tel: +371 67323666 
 

United Kingdom 
Teva UK Limited 
Tel: +44 1977628500 

 
This leaflet was last revised in 
 
Other sources of information 
Detailed information on this medicine is available on the European Medicines Agency website: 
http://www.ema.europa.eu 

 54 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING  AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND  EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET