Nevirapine Teva

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Nevirapine Teva 200 mg tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each tablet contains 200 mg of nevirapine (as anhydrous). 
 
Excipient with known effect: Each tablet contains 168 mg of lactose (as monohydrate). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Tablet 
 
White, oval, biconvex tablets. One side is debossed with "N", a scoreline and "200". The opposite side 
is debossed with a scoreline. The score line is only to facilitate breaking for ease of swallowing and 
not to divide into equal doses. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Nevirapine Teva is indicated in combination with other anti-retroviral medicinal products for the 
treatment of HIV-1 infected adults, adolescents, and children of any age (see section 4.2). 
 
Most of the experience with nevirapine is in combination with nucleoside reverse transcriptase 
inhibitors (NRTIs). The choice of a subsequent therapy after nevirapine should be based on clinical 
experience and resistance testing (see section 5.1). 
 
4.2 Posology and method of administration 
 
Nevirapine Teva should be administered by physicians who are experienced in the  treatment of HIV 
infection.  
 
Posology 
 
Patients 16 years and older 
The recommended dose of Nevirapine Teva is one 200 mg tablet daily for the first 14 days (this lead-
in period should be used because it has been found to lessen the frequency of rash), followed by one 
200 mg tablet twice daily, in combination with at least two additional antiretroviral agents. 
 
For patients who are unable to swallow tablets or who weigh less than 50 kg or whose body surface 
area is below 1.25 m2 according to the Mosteller formula, other nevirapine containing oral 
formulations are available and should be used if appropriate. 
 
If a dose is recognized as missed within 8 hours of when it was due, the patient should take the missed 
dose as soon as possible. If a dose is missed and it is more than 8 hours later, the patient should only 
take the next dose at the usual time. 
 
Dose management considerations 
Patients experiencing rash during the 14-day lead-in period of 200 mg/day should not have their 
Nevirapine Teva dose increased until the rash has resolved. The isolated rash should be closely 



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monitored (see section 4.4). The 200 mg once daily dosing regimen should not be continued beyond 
28 days at which point in time an alternative treatment should be sought due to the possible risk of 
underexposure and resistance. 
 
Patients who interrupt nevirapine dosing for more than 7 days should restart the recommended dosing 
regimen using the two week lead-in period. 
 
There are toxicities that require interruption of Nevirapine Teva therapy (see section 4.4). 
 
Special populations 
 
Elderly 
Nevirapine has not been specifically investigated in patients over the age of 65. 
 
Renal impairment 
For patients with renal dysfunction requiring dialysis an additional 200 mg dose of nevirapine 
following each dialysis treatment is recommended. Patients with CLcr ≥ 20 ml/min do not require a 
dose adjustment, see section 5.2. 
 
Hepatic impairment 
Nevirapine should not be used in patients with severe hepatic impairment (Child-Pugh C, see section 
4.3). No dose adjustment is necessary in patients with mild to moderate hepatic impairment (see 
sections 4.4 and 5.2). 
  
Paediatric population 
Nevirapine Teva 200 mg tablets, following the dosing schedule described above, are suitable for larger 
children, particularly adolescents, below the age of 16 who weigh more than 50 kg or whose body 
surface area is above 1.25 m2 according to the Mosteller formula. 
 
Method of administration 
The tablets shall be taken with liquid, and should not be crushed or chewed. Nevirapine Teva may be 
taken with or without food. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
Readministration to patients who have required permanent discontinuation for severe rash, rash 
accompanied by constitutional symptoms, hypersensitivity reactions, or clinical hepatitis due to 
nevirapine. 
 
Patients with severe hepatic impairment (Child-Pugh C) or pre-treatment ASAT or ALAT > 5 ULN 
until baseline ASAT/ALAT are stabilised < 5 ULN. 
 
Readministration to patients who previously had ASAT or ALAT > 5 ULN during nevirapine therapy 
and had recurrence of liver function abnormalities upon readministration of nevirapine (see section 
4.4). 
 
Coadministration with herbal preparations containing St John’s wort (Hypericum perforatum) due to 
the risk of decreased plasma concentrations and reduced clinical effects of nevirapine (see section 4.5). 
 
4.4 Special warnings and precautions for use 
 
Nevirapine Teva should only be used with at least two other antiretroviral agents (see section 5.1). 
 
Nevirapine Teva should not be used as the sole active antiretroviral, as monotherapy with any 

antiretroviral has shown to result in viral resistance. 



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The first 18 weeks of therapy with nevirapine are a critical period which requires close 
monitoring of patients to disclose the potential appearance of severe and life-threatening skin 
reactions (including cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis 
(TEN)) and serious hepatitis/hepatic failure. The greatest risk of hepatic and skin reactions 
occurs in the first 6 weeks of therapy. However, the risk of any hepatic event continues past this 
period and monitoring should continue at frequent intervals. Female gender and higher CD4 
counts (>250/mm3 in adult females and >400/mm3 in adult males) at the initiation of nevirapine 
therapy are associated with a greater risk of hepatic adverse reactions if the patient has 
detectable plasma HIV-1 RNA - i.e. a concentration ≥ 50 copies/ml - at the initiation of 
nevirapine. As serious and life threatening hepatotoxicity has been observed in controlled and 
uncontrolled studies predominantly in patients with a plasma HIV-1 viral load of 50 copies/ml or 
higher, nevirapine should not be initiated in adult females with CD4 cell counts greater than 
250 cells/mm3 or in adult males with CD4 cell counts greater than 400 cells/mm3, who have a 
detectable plasma HIV-1 RNA unless the benefit outweighs the risk. 
In some cases, hepatic injury has progressed despite discontinuation of treatment. Patients 
developing signs or symptoms of hepatitis, severe skin reaction or hypersensitivity reactions 
must discontinue nevirapine and seek medical evaluation immediately. Nevirapine must not be 
restarted following severe hepatic, skin or hypersensitivity reactions (see section 4.3). 
 
The dose must be strictly adhered to, especially the 14-days lead-in period (see section 4.2). 
 
Cutaneous reactions 
 
Severe and life-threatening skin reactions, including fatal cases, have occurred in patients treated with 
nevirapine mainly during the first 6 weeks of therapy. These have included cases of Stevens-Johnson 
syndrome, toxic epidermal necrolysis and hypersensitivity reactions characterised by rash, 
constitutional findings and visceral involvement. Patients should be intensively monitored during the 
first 18 weeks of treatment. Patients should be closely monitored if an isolated rash occurs. Nevirapine 
must be permanently discontinued in any patient experiencing severe rash or a rash accompanied by 
constitutional symptoms (such as fever, blistering, oral lesions, conjunctivitis, facial oedema, muscle 
or joint aches, or general malaise), including Stevens-Johnson syndrome, or toxic epidermal 
necrolysis. Nevirapine must be permanently discontinued in any patient experiencing hypersensitivity 
reaction (characterised by rash with constitutional symptoms, plus visceral involvement, such as 
hepatitis, eosinophilia, granulocytopenia, and renal dysfunction), see section 4.4. 
 
Nevirapine Teva administration above the recommended dose might increase the frequency and 
seriousness of skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.  
 
Rhabdomyolysis has been observed in patients experiencing skin and/or liver reactions associated with 
nevirapine use.  
 
Concomitant prednisone use (40 mg/day for the first 14 days of nevirapine administration) has been 
shown not to decrease the incidence of nevirapine-associated rash, and may be associated with an 
increase in incidence and severity of rash during the first 6 weeks of nevirapine therapy.  
 
Some risk factors for developing serious cutaneous reactions have been identified; they include failure 
to follow the initial dosing of 200 mg daily during the lead-in period and a long delay between the 
initial symptoms and medical consultation. Women appear to be at higher risk than men of developing 
rash, whether receiving nevirapine or non- nevirapine containing therapy.  
 
Patients should be instructed that a major toxicity of nevirapine is rash. They should be advised to 
promptly notify their physician of any rash and avoid delay between the initial symptoms and medical 
consultation. The majority of rashes associated with nevirapine occur within the first 6 weeks of 
initiation of therapy. Therefore, patients should be monitored carefully for the appearance of rash 
during this period. Patients should be instructed that dose escalation is not to occur if any rash occurs 



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during the two-week lead-in dosing period, until the rash resolves. The 200 mg once daily dosing 
regimen should not be continued beyond 28 days at which point in time an alternative treatment 
should be sought due to the possible risk of underexposure and resistance. 
 
Any patient experiencing severe rash or a rash accompanied by constitutional symptoms such as fever, 
blistering, oral lesions, conjunctivitis, facial oedema, muscle or joint aches, or general malaise should 
discontinue the medicinal product and immediately seek medical evaluation. In these patients 
nevirapine must not be restarted.  
 
If patients present with a suspected nevirapine-associated rash, liver function tests should be 
performed. Patients with moderate to severe elevations (ASAT or ALAT > 5 ULN) should be 
permanently discontinued from nevirapine.  
 
If a hypersensitivity reaction occurs, characterised by rash with constitutional symptoms such as fever, 
arthralgia, myalgia and lymphadenopathy, plus visceral involvement, such as hepatitis, eosinophilia, 
granulocytopenia, and renal dysfunction, nevirapine must be permanently stopped and not be 
reintroduced (see section 4.3). 
 
Hepatic reactions 
 
Severe and life-threatening hepatotoxicity, including fatal fulminant hepatitis, has occurred in patients 
treated with nevirapine. The first 18 weeks of treatment is a critical period which requires close 
monitoring. The risk of hepatic reactions is greatest in the first 6 weeks of therapy. However the risk 
continues past this period and monitoring should continue at frequent intervals throughout treatment. 
 
Rhabdomyolysis has been observed in patients experiencing skin and/or liver reactions associated with 
nevirapine use. 
 
Increased ASAT or ALAT levels ≥ 2.5 ULN and/or co-infection with hepatitis B and/or C at the start 
of antiretroviral therapy is associated with greater risk of hepatic adverse reactions during 
antiretroviral therapy in general, including nevirapine containing regimens. 
 
Female gender and higher CD4 counts at the initiation of nevirapine therapy in treatment-naïve 
patients is associated with increased risk of hepatic adverse reactions. Women have a three fold higher 
risk than men for symptomatic, often rash-associated, hepatic events (5.8 % versus 2.2 %), and 
treatment-naïve patients of either gender with detectable HIV-1 RNA in plasma with higher CD4 
counts at initiation of nevirapine therapy are at higher risk for symptomatic hepatic events with 
nevirapine. In a retrospective review of predominantly patients with a plasma HIV-1 viral load of 50 
copies/ml or higher, women with CD4 counts > 250 cells/mm3 had a 12 fold higher risk of 
symptomatic hepatic adverse reactions compared to women with CD4 counts < 250 cells/mm3 (11.0 % 
versus 0.9 %). An increased risk was observed in men with detectable HIV-1 RNA in plasma and CD4 
counts > 400 cells/mm3 (6.3 % versus 1.2 % for men with CD4 counts < 400 cells/mm3). This 
increased risk for toxicity based on CD4 count thresholds has not been detected in patients with 
undetectable (i.e. < 50 copies/ml) plasma viral load. 
 
Patients should be informed that hepatic reactions are a major toxicity of nevirapine requiring close 
monitoring during the first 18 weeks. They should be informed that occurrence of symptoms 
suggestive of hepatitis should lead them to discontinue nevirapine and immediately seek medical 
evaluation, which should include liver function tests. 
 
Liver monitoring 
 
Clinical chemistry tests, which include liver function tests, should be performed prior to initiating 
nevirapine therapy and at appropriate intervals during therapy. 
 



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Abnormal liver function tests have been reported with nevirapine, some in the first few weeks of 
therapy.  
 
Asymptomatic elevations of liver enzymes are frequently described and are not necessarily a 
contraindication to use nevirapine. Asymptomatic GGT elevations are not a contraindication to 
continue therapy. 
 
Monitoring of hepatic tests should be done every two weeks during the first 2 months of treatment, at 
the 3rd month and then regularly thereafter. Liver test monitoring should be performed if the patient 
experiences signs or symptoms suggestive of hepatitis and/or hypersensitivity. 
 
If ASAT or ALAT ≥ 2.5 ULN before or during treatment, then liver tests should be monitored more 
frequently during regular clinic visits. Nevirapine must not be administered to patients with pre-
treatment ASAT or ALAT > 5 ULN until baseline ASAT/ALAT are stabilised < 5 ULN (see section 
4.3). 
 
Physicians and patients should be vigilant for prodromal signs or findings of hepatitis, such as 
anorexia, nausea, jaundice, bilirubinuria, acholic stools, hepatomegaly or liver tenderness. Patients 
should be instructed to seek medical attention promptly if these occur.  
 
If ASAT or ALAT increase to > 5 ULN during treatment, nevirapine should be immediately 
stopped. If ASAT and ALAT return to baseline values and if the patient had no clinical signs or 
symptoms of hepatitis, rash, constitutional symptoms or other findings suggestive of organ 
dysfunction, it may be possible to reintroduce nevirapine, on a case by case basis, at the starting 
dose regimen of 200 mg/day for 14 days followed by 400 mg/day. In these cases, more frequent 
liver monitoring is required. If liver function abnormalities recur, nevirapine should be 
permanently discontinued. 
 
If clinical hepatitis occurs, characterised by anorexia, nausea, vomiting, icterus AND laboratory 
findings (such as moderate or severe liver function test abnormalities (excluding GGT)), 
nevirapine must be permanently stopped. Nevirapine must not be readministered to patients 
who have required permanent discontinuation for clinical hepatitis due to nevirapine. 
 
Liver disease 
 
The safety and efficacy of nevirapine has not been established in patients with significant underlying 
liver disorders. Nevirapine is contraindicated in patients with severe hepatic impairment (Child-Pugh 
C, see section 4.3). Pharmacokinetic results suggest caution should be exercised when nevirapine is 
administered to patients with moderate hepatic dysfunction (Child-Pugh B). Patients with chronic 
hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk for severe 
and potentially fatal hepatic adverse reactions. In the case of concomitant antiviral therapy for 
hepatitis B or C, please refer also to the relevant product information for these medicinal products. 
 
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 in such 
patients, interruption or discontinuation of treatment must be considered. 
 
Other warnings 
 
Post-Exposure-Prophylaxis: Serious hepatotoxicity, including liver failure requiring transplantation, 
has been reported in HIV-uninfected individuals receiving multiple doses of nevirapine in the setting 
of post-exposure-prophylaxis (PEP), an unapproved use. The use of nevirapine has not been evaluated 
within a specific study on PEP, especially in term of treatment duration and therefore, is strongly 
discouraged. 



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Combination therapy with nevirapine is not a curative treatment of patients infected with HIV-1; 
patients may continue to experience illnesses associated with advanced HIV-1 infection, including 
opportunistic infections. 
 
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. 
 
Hormonal methods of birth control other than Depot-medroxyprogesterone acetate (DMPA) should 
not be used as the sole method of contraception in women taking Nevirapine Teva, since nevirapine 
might lower the plasma concentrations of these medicinal products. For this reason, and to reduce the 
risk of HIV transmission, barrier contraception (e.g., condoms) is recommended. Additionally, when 
postmenopausal hormone therapy is used during administration of nevirapine, its therapeutic effect 
should be monitored. 
 
Weight and metabolic parameters: 
An increase in weight and in levels of blood lipids and glucose may occur 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. 
 
In clinical studies, nevirapine has been associated with an increase in HDL- cholesterol and an overall 
improvement in the total to HDL-cholesterol ratio. However, in the absence of specific studies, the 
clinical impact of these findings is not known. In addition, nevirapine has not been shown to cause 
glucose disturbances. 
 
Osteonecrosis: Although the etiology 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. 
 
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 Pneumocystis jirovecii pneumonia. Any inflammatory symptoms 
should be evaluated and treatment instituted when necessary. Autoimmune 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. 
 
The available pharmacokinetic data suggest that the concomitant use of rifampicin and nevirapine is 
not recommended. Furthermore, combining the following compounds with Nevirapine Teva is not 
recommended: efavirenz, ketoconazole, delavirdine, etravirine, rilpivirine, elvitegravir (in 
combination with cobicistat), atazanavir (in combination with ritonavir), boceprevir; fosamprenavir (if 
not co-administered with low dose ritonavir) (see section 4.5). 
 
Granulocytopenia is commonly associated with zidovudine. Therefore, patients who receive 
nevirapine and zidovudine concomitantly and especially paediatric patients and patients who receive 
higher zidovudine doses or patients with poor bone marrow reserve, in particular those with advanced 
HIV disease, have an increased risk of granulocytopenia. In such patients haematological parameters 
should be carefully monitored. 



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Lactose: Nevirapine Teva tablets contain 336 mg of lactose per maximum recommended daily dose. 
Patients with rare hereditary problems of galactose intolerance e.g. galactosaemia, the Lapp lactase 
deficiency or glucose-galactose malabsorption should not take this medicine. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Nevirapine is an inducer of CYP3A and potentially CYP2B6, with maximal induction occurring 
within 2-4 weeks of initiating multiple-dose therapy. 
 
Compounds using this metabolic pathway may have decreased plasma concentrations when co-
administered with nevirapine. Careful monitoring of the therapeutic effectiveness of P450 metabolised 
medicinal products is recommended when taken in combination with nevirapine. 
 
The absorption of nevirapine is not affected by food, antacids or medicinal products which are 
formulated with an alkaline buffering agent. 
 
The interaction data is presented as geometric mean value with 90% confidence interval (90% CI) 
whenever these data were available. ND = Not Determined, ↑ = Increased, ↓ = Decreased, ↔ = No 
Effect  
 
Medicinal products 
by therapeutic areas 

Interaction  Recommendations concerning 
co-administration 

ANTI-INFECTIVES 
Antiretrovirals 
NRTIs 
Didanosine 
100-150 mg BID 
 

Didanosine AUC ↔ 1.08 (0.92-1.27) 
Didanosine Cmin ND 
Didanosine Cmax ↔ 0.98 (0.79-1.21) 
 

Didanosine and Nevirapine Teva 
can be co-administered without 
dose adjustments. 

Emtricitabine Emtricitabine is not an inhibitor of 
human CYP 450 enzymes. 

Nevirapine Teva and emtricitabine 
may be co-administered without 
dose adjustments. 
 

Abacavir 
 

In human liver microsomes, abacavir 
did not inhibit cytochrome P450 
isoforms. 
 

Nevirapine Teva and abacavir may 
be co-administered without dose 
adjustments. 

Lamivudine 
150 mg BID 
 

No changes to lamivudine apparent 
clearance and volume of distribution, 
suggesting no induction effect of 
nevirapine on lamivudine clearance. 
 

Lamivudine and Nevirapine Teva 
can be co-administered without 
dose adjustments. 

Stavudine: 
30/40 mg BID 
 

Stavudine AUC ↔ 0.96 (0.89-1.03) 
Stavudine Cmin ND 
Stavudine Cmax ↔ 0.94 (0.86-1.03) 
 
Nevirapine: compared to historical 
controls, levels appeared to be 
unchanged. 
 

Stavudine and Nevirapine Teva 
can be co-administered without 
dose adjustments. 

Tenofovir 
300 mg QD 
 

Tenofovir plasma levels remain 
unchanged when co-administered 
with nevirapine. 
 

Tenofovir and Nevirapine Teva 
can be co-administered without 
dose adjustments. 
 



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Nevirapine plasma levels were not 
altered by co-administration of 
tenofovir. 
 

Zidovudine 
100-200 mg TID 
 

Zidovudine AUC ↓ 0.72 (0.60-0.96) 
Zidovudine Cmin ND 
Zidovudine Cmax ↓ 0.70 (0.49-1.04) 
 
Nevirapine: Zidovudine had no effect 
on its pharmacokinetics. 
 

Zidovudine and Nevirapine Teva 
can be co-administered without 
dose adjustments 
 
Granulocytopenia is commonly 
associated with zidovudine. 
Therefore, patients who receive 
nevirapine and zidovudine 
concomitantly and especially 
paediatric patients and patients 
who receive higher zidovudine 
doses or patients with poor bone 
marrow reserve, in particular those 
with advanced HIV disease, have 
an increased risk of 
granulocytopenia. In such patients 
haematological parameters should 
be carefully monitored. 
 

NNRTIs 
Efavirenz 
600 mg QD 
 

Efavirenz AUC ↓ 0.72 (0.66-0.86) 
Efavirenz Cmin ↓ 0.68 (0.65-0.81) 
Efavirenz Cmax ↓ 0.88 (0.77-1.01) 
 

It is not recommended to 
coadminister efavirenz and 
Nevirapine Teva (see section 4.4), 
because of additive toxicity and no 
benefit in terms of efficacy over 
either NNRTI alone (for results of 
2NN study, see section 5.1). 
 

Delavirdine Interaction has not been studied. The concomitant administration of 
Nevirapine Teva with NNRTIs is 
not recommended (see section 
4.4). 
 

Etravirine Concomitant use of etravirine with 
nevirapine may cause a significant 
decrease in the plasma concentrations 
of etravirine and loss of therapeutic 
effect of etravirine. 
 

The concomitant administration of 
Nevirapine Teva with NNRTIs is 
not recommended (see section 
4.4). 

Rilpivirine Interaction has not been studied. The concomitant administration of 
Nevirapine Teva with NNRTIs is 
not recommended (see section 
4.4). 
 

PIs 
Atazanavir/ritonavir 
300/100 mg QD 
400/100 mg QD 
 

Atazanavir/r 300/100mg: 
Atazanavir/r AUC ↓ 0.58 (0.48-0.71) 
Atazanavir/r Cmin ↓ 0.28 (0.20-0.40) 
Atazanavir/r Cmax ↓ 0.72 (0.60-0.86) 
 
Atazanavir/r 400/100mg: 

It is not recommended to 
coadminister atazanavir/ritonavir 
and Nevirapine Teva (see section 
4.4). 
 



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Atazanavir/r AUC ↓ 0.81 (0.65-1.02) 
Atazanavir/r Cmin ↓ 0.41 (0.27-0.60) 
Atazanavir/r Cmax ↔ 1.02 (0.85– 
1.24) 
(compared to 300/100mg without 
nevirapine) 
 
Nevirapine AUC ↑ 1.25 (1.17-1.34) 
Nevirapine Cmin ↑ 1.32 (1.22–1.43) 
Nevirapine Cmax ↑ 1.17 (1.09-1.25) 
 

Darunavir/ritonavir 
400/100 mg BID 
 
 
 

Darunavir AUC ↑ 1.24 (0.97-1.57) 
Darunavir Cmin ↔ 1.02 (0.79-1.32) 
Darunavir Cmax ↑ 1.40 (1.14-1.73) 
 
Nevirapine AUC ↑ 1.27 (1.12-1.44) 
Nevirapine Cmin ↑ 1.47 (1.20-1.82) 
Nevirapine Cmax ↑ 1.18 (1.02-1.37) 
 

Darunavir and Nevirapine Teva 
can be co-administered without 
dose adjustments. 
 

Fosamprenavir 
1,400 mg BID 
 

Amprenavir AUC ↓ 0.67 (0.55-0.80) 
Amprenavir Cmin ↓ 0.65 (0.49-0.85) 
Amprenavir Cmax ↓ 0.75 (0.63-0.89) 
 
Nevirapine AUC ↑ 1.29 (1.19-1.40) 
Nevirapine Cmin ↑ 1.34 (1.21-1.49) 
Nevirapine Cmax ↑ 1.25 (1.14-1.37) 
 

It is not recommended to 
coadminister fosamprenavir and 
Nevirapine Teva if fosamprenavir 
is not co-administered with 
ritonavir (see section 4.4). 
 

Fosamprenavir/ritona 
vir 700/100 mg BID 
 

Amprenavir AUC ↔ 0.89 (0.77- 
1.03) 
Amprenavir Cmin ↓ 0.81 (0.69-0.96) 
Amprenavir Cmax ↔ 0.97 (0.85-1.10) 
 
Nevirapine AUC ↑ 1.14 (1.05-1.24) 
Nevirapine Cmin ↑ 1.22 (1.10-1.35) 
Nevirapine Cmax ↑ 1.13 (1.03-1.24) 
 

Fosamprenavir/ritonavir and 
Nevirapine Teva can be co-
administered without dose 
adjustments 
 

Lopinavir/ritonavir 
(capsules) 400/100 
mg BID 
 

Adult patients: 
Lopinavir AUC ↓ 0.73 (0.53-0.98) 
Lopinavir Cmin ↓ 0.54 (0.28-0.74) 
Lopinavir Cmax ↓ 0.81 (0.62-0.95) 
 

An increase in the dose of 
lopinavir/ritonavir to 533/133 mg 
(4 capsules) or 500/125 mg (5 
tablets with 100/25 mg each) twice 
daily with food is recommended in 
combination with Nevirapine 
Teva. Dose adjustment of 
Nevirapine Teva is not required 
when co-administered with 
lopinavir. 
 

Lopinavir/ritonavir 
(oral solution) 300/75 
mg/m2 BID  
 
 

Paediatric patients: 
Lopinavir AUC ↓ 0.78 (0.56-1.09) 
Lopinavir Cmin ↓ 0.45 (0.25-0.82) 
Lopinavir Cmax ↓ 0.86 (0.64-1.16) 

For children, increase of the dose 
of lopinavir/ritonavir to 300/75 
mg/m2 twice daily with food 
should be considered when used in 
combination with Nevirapine 
Teva, particularly for patients in 
whom reduced susceptibility to 
lopinavir/ritonavir is suspected. 



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Ritonavir 
600 mg BID 
 

Ritonavir AUC↔ 0.92 (0.79-1.07) 
Ritonavir Cmin ↔ 0.93 (0.76-1.14) 
Ritonavir Cmax ↔ 0.93 (0.78-1.07) 
 
Nevirapine: Co-administration of 
ritonavir does not lead to any 
clinically relevant change in 
nevirapine plasma levels. 
 

Ritonavir and Nevirapine Teva can 
be co-administered without dose 
adjustments. 
 

Saquinavir/ritonavir 
 

The limited data available with 
saquinavir soft gel capsule boosted 
with ritonavir do not suggest any 
clinically relevant interaction 
between saquinavir boosted with 
ritonavir and nevirapine 
 

Saquinavir/ritonavir and 
Nevirapine Teva can be co-
administered without dose 
adjustments. 
 

Tipranavir/ritonavir 
500/200 mg BID 
 

No specific drug-drug interaction 
study has been performed. 
The limited data available from a 
phase IIa study in HIV-infected 
patients have shown a clinically non 
significant 20% decrease of TPV 
Cmin. 
 

Tipranavir and Nevirapine Teva 
can be co-administered without 
dose adjustments. 
 

ENTRY INHIBITORS 
Enfuvirtide Due to the metabolic pathway no 

clinically significant 
pharmacokinetic interactions are 
expected between enfuvirtide and 
nevirapine. 
 

Enfuvirtide and Nevirapine Teva 
can be co-administered without 
dose adjustments. 
 

Maraviroc 
300 mg QD 
 

Maraviroc AUC ↔ 1.01 (0.6 -1.55) 
Maraviroc Cmin ND 
Maraviroc Cmax ↔ 1.54 (0.94-2.52) 
compared to historical controls 
 
Nevirapine concentrations not 
measured, no effect is expected. 
 

Maraviroc and Nevirapine Teva 
can be co-administered without 
dose adjustments. 
 

INTEGRASE INHIBITORS 
Elvitegravir/ 
cobicistat 

Interaction has not been studied. 
Cobicistat, a cytochrome P450 3A 
inhibitor significantly inhibits hepatic 
enzymes, as well as other metabolic 
pathways.  Therefore 
coadministration would likely result 
in altered plasma levels of cobicistat 
and Nevirapine Teva. 
 

Co-administration of Nevirapine 
Teva with elvitegravir in 
combination with cobicistat is not 
recommended (see section 4.4). 

Raltegravir 
400 mg BID 
 

No clinical data available. Due to the 
metabolic pathway of raltegravir no 
interaction is expected. 
 

Raltegravir and Nevirapine Teva 
can be co-administered without 
dose adjustments. 
 

ANTIBIOTICS 



12 

Clarithromycin 
500 mg BID 
 
 

Clarithromycin AUC ↓ 0.69 (0.62- 
0.76) 
Clarithromycin Cmin ↓ 0.44 (0.30- 
0.64) 
Clarithromycin Cmax ↓ 0.77 (0.69- 
0.86) 
 
Metabolite 14-OH clarithromycin 
AUC ↑ 1.42 (1.16-1.73) 
Metabolite 14-OH clarithromycin 
Cmin ↔ 0 (0.68-1.49) 
Metabolite 14-OH clarithromycin 
Cmax ↑ 1.47 (1.21-1.80) 
 
Nevirapine AUC ↑ 1.26 
Nevirapine Cmin ↑ 1.28 
Nevirapine Cmax ↑ 1.24 
compared to historical controls. 
 

Clarithromycin exposure was 
significantly decreased, 14-OH 
metabolite exposure increased. 
Because the clarithromycin active 
metabolite has reduced activity 
against Mycobacterium avium-
intracellulare complex overall 
activity against the pathogen may 
be altered. Alternatives to 
clarithromycin, such as 
azithromycin should be 
considered. Close monitoring for 
hepatic abnormalities is 
recommended 
 

Rifabutin 
150 or 300 mg QD 
 

Rifabutin AUC ↑ 1.17 (0.98-1.40) 
Rifabutin Cmin ↔ 1.07 (0.84-1.37) 
Rifabutin Cmax ↑ 1.28 (1.09-1.51) 
 
Metabolite 25-O-desacetylrifabutin 
AUC ↑ 1.24 (0.84-1.84) 
Metabolite 25-O-desacetylrifabutin 
Cmin ↑ 1.22 (0.86-1.74) 
Metabolite 25-O-desacetylrifabutin 
Cmax ↑ 1.29 (0.98-1.68) 
 
A clinically not relevant increase in 
the apparent clearance of nevirapine 
(by 9%) compared to historical data 
was reported. 
 

No significant effect on rifabutin 
and nevirapine mean PK 
parameters is seen. Rifabutin and 
Nevirapine Teva can be co-
administered without dose 
adjustments. However, due to the 
high interpatient variability some 
patients may experience large 
increases in rifabutin exposure and 
may be at higher risk for rifabutin 
toxicity. Therefore, caution should 
be used in concomitant 
administration. 
 

Rifampicin 
600 mg QD 
 

Rifampicin AUC ↔ 1.11 (0.96-1.28) 
Rifampicin Cmin ND 
Rifampicin Cmax ↔ 1.06 (0.91-1.22) 
 
Nevirapine AUC ↓ 0.42 
Nevirapine Cmin ↓ 0.32 
Nevirapine Cmax ↓ 0.50 
compared to historical controls. 
 

It is not recommended to co-
administer rifampicin and 
Nevirapine Teva (see section 4.4). 
Physicians needing to treat 
patients co-infected with 
tuberculosis and using a 
Nevirapine Teva containing 
regimen may consider 
coadministration of rifabutin 
instead. 
 

ANTIFUNGALS 
Fluconazole 
200 mg QD 
 

Fluconazole AUC ↔ 0.94 (0.88- 
1.01) 
Fluconazole Cmin ↔ 0.93 (0.86-1.01) 
Fluconazole Cmax ↔ 0.92 (0.85-0.99) 
 
Nevirapine: exposure: ↑100% 
compared with historical data where 
nevirapine was administered alone. 

Because of the risk of increased 
exposure to Nevirapine Teva, 
caution should be exercised if the 
medicinal products are given 
concomitantly and patients should 
be monitored closely. 
 



13 

 
Itraconazole 
200 mg QD 
 

Itraconazole AUC ↓ 0.39 
Itraconazole Cmin ↓ 0.13 
Itraconazole Cmax ↓ 0.62 
 
Nevirapine: there was no significant 
difference in nevirapine 
pharmacokinetic parameters. 
 

A dose increase for itraconazole 
should be considered when these 
two agents are administered 
concomitantly. 
 

Ketoconazole 
400 mg QD 
 

Ketoconazole AUC ↓ 0.28 (0.20- 
0.40) 
Ketoconazole Cmin ND 
Ketoconazole Cmax ↓ 0.56 (0.42- 
0.73) 
 
Nevirapine: plasma levels: ↑ 1.15- 
1.28 compared to historical controls. 
 

It is not recommended to co-
administer ketoconazole and 
Nevirapine Teva (see section 4.4). 
 

ANTIVIRALS FOR CHRONIC HEPATITIS B AND C 
Adefovir Results of in vitro studies showed a 

weak antagonism of nevirapine by 
adefovir (see section 5.1), this has 
not been confirmed in clinical trials 
and reduced efficacy is not expected. 
Adefovir did not influence any of the 
common CYP isoforms known to be 
involved in human drug metabolism 
and is excreted renally. No clinically 
relevant drug-drug interaction is 
expected. 
 

Adefovir and Nevirapine Teva 
may be co-administered without 
dose adjustments. 

Boceprevir Boceprevir is partly metabolized by 
CYP3A4/5. Co-administration of 
boceprevir with medicines that 
induce or inhibit CYP3A4/5 could 
increase or decrease exposure.  
Plasma trough concentrations of 
boceprevir were decreased when 
administered with an NNRTI with a 
similar metabolic pathway as 
nevirapine. The clinical outcome of 
this observed reduction of boceprevir 
trough concentrations has not been 
directly assessed.  
 

It is not recommended to co-
administer boceprevir and 
Nevirapine Teva (see section 4.4). 

Entecavir Entecavir is not a substrate, inducer 
or an inhibitor of cytochrome P450 
(CYP450) enzymes. Due to the 
metabolic pathway of entecavir, no 
clinically relevant drug-drug 
interaction is expected. 
 

Entecavir and Nevirapine Teva 
may be co-administered without 
dose adjustments. 

Interferons (pegylated 
interferons alfa 2a and 
alfa 2b) 

Interferons have no known effect on 
CYP 3A4 or 2B6. No clinically 
relevant drug-drug interaction is 
expected. 

Interferons and Nevirapine Teva 
may be co-administered without 
dose adjustments. 



14 

 
Ribavirin Results of in vitro studies showed a 

weak antagonism of nevirapine by 
ribavirin (see section 5.1), this has 
not been confirmed in clinical trials 
and reduced efficacy is not expected. 
Ribavirin does not inhibit 
cytochrome P450 enzymes, and there 
is no evidence from toxicity studies 
that ribavirin induces liver enzymes. 
No clinically relevant drug-drug 
interaction is expected.  
 

Ribavirin and Nevirapine Teva 
may be co-administered without 
dose adjustments. 

Telaprevir Telaprevir is metabolised in the liver 
by CYP3A and is a P-glycoprotein 
substrate. Other enzymes may be 
involved in the metabolism. Co-
administration of telaprevir and 
medicinal products that induce 
CYP3A and/or P-gp may decrease 
telaprevir plasma concentrations. No 
drug-drug interaction study of 
telaprevir with nevirapine has been 
conducted, however, interaction 
studies of telaprevir with an NNRTI 
with a similar metabolic pathway as 
nevirapine demonstrated reduced 
levels of both. Results of DDI 
studies of telaprevir with efavirenz 
indicate that caution should be 
exercised when co-administering 
telaprevir with P450 inducers.  

Caution should be exercised when 
co-administering telaprevir with 
nevirapine.  
If co-administered with 
Nevirapine Teva, an adjustment in 
the telaprevir dose should be 
considered. 
 

Telbivudine Telbivudine is not a substrate, 
inducer or inhibitor of the 
cytochrome P450 (CYP450) enzyme 
system. Due to the metabolic 
pathway of telbivudine, no clinically 
relevant drug-drug interaction is 
expected. 
 

Telbivudine and Nevirapine Teva 
may be co-administered without 
dose adjustments. 

ANTACIDS 
Cimetidine 
 

Cimetidine: no significant effect on 
cimetidine PK parameters is seen. 
 
Nevirapine Cmin ↑ 1.07 
 

Cimetidine and Nevirapine Teva 
can be co-administered without 
dose adjustments. 
 

ANTITHROMBOTICS 
Warfarin 
 

The interaction between nevirapine 
and the antithrombotic agent 
warfarin is complex, with the 
potential for both increases and 
decreases in coagulation time when 
used concomitantly. 
 

Close monitoring of 
anticoagulation levels is 
warranted. 
 

CONTRACEPTIVES 



15 

Depot-
medroxyprogesterone 
acetate (DMPA) 
150 mg every 3 
months 
 

DMPA AUC ↔ 
DMPA Cmin ↔ 
DMPA Cmax ↔ 
 
Nevirapine AUC ↑ 1.20 
Nevirapine Cmax ↑ 1.20 
 

Nevirapine co-administration did 
not alter the ovulation suppression 
effects of DMPA. DMPA and 
Nevirapine Teva can be co-
administered without dose 
adjustments. 
 

Ethinyl estradiol (EE) 
0.035 mg 

EE AUC ↓ 0.80 (0.67 - 0.97) 
EE Cmin ND 
EE Cmax ↔ 0.94 (0.79 - 1.12) 
 

Oral hormonal contraceptives 
should not be used as the sole 
method of contraception in women 
taking Nevirapine Teva (see 
section 4.4). Appropriate doses for 
hormonal contraceptives (oral or 
other forms of application) other 
than DMPA in combination with 
nevirapine have not been 
established with respect to safety 
and efficacy. 
 

Norethindrone (NET) 
1.0 mg QD 
 

NET AUC ↓ 0.81 (0.70 - 0.93) 
NET Cmin ND 
NET Cmax ↓ 0.84 (0.73 - 0.97) 
 

ANALGESICS/OPIOIDS 
Methadone Individual 
Patient Dosing 

Methadone AUC ↓ 0.40 (0.31 - 0.51) 
Methadone Cmin ND 
Methadone Cmax ↓ 0.58 (0.50 - 0.67) 
 

Methadone-maintained patients 
beginning Nevirapine Teva 
therapy should be monitored for 
evidence of withdrawal and 
methadone dose should be 
adjusted accordingly. 
 

HERBAL PRODUCTS 
St. John's Wort 
 

Serum levels of nevirapine can be 
reduced by concomitant use of the 
herbal preparation St. John's Wort 
(Hypericum perforatum). This is due 
to induction of medicinal product 
metabolism enzymes and/or transport 
proteins by St. John’s Wort. 
 

Herbal preparations containing St. 
John‘s Wort and Nevirapine Teva 
must not be co-administered (see 
section 4.3). If a patient is already 
taking St. John‘s Wort check 
nevirapine and if possible viral 
levels and stop St John‘s Wort. 
Nevirapine levels may increase on 
stopping St John‘s Wort. The dose 
of Nevirapine Teva may need 
adjusting. The inducing effect may 
persist for at least 2 weeks after 
cessation of treatment with St. 
John‘s Wort. 
 

 
Other information: 
 
Nevirapine metabolites: Studies using human liver microsomes indicated that the formation of 
nevirapine hydroxylated metabolites was not affected by the presence of dapsone, rifabutin, 
rifampicin, and trimethoprim/sulfamethoxazole. Ketoconazole and erythromycin significantly 
inhibited the formation of nevirapine hydroxylated metabolites. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential / Contraception in males and females 



16 

Women of childbearing potential should not use oral contraceptives as the sole method for birth 
control, since nevirapine might lower the plasma concentrations of these medicinal products (see 
sections 4.4 & 4.5). 
 
Pregnancy 
Currently available data on pregnant women indicate no malformative or foeto/ neonatal toxicity. To 
date no other relevant epidemiological data are available. No observable teratogenicity was detected in 
reproductive studies performed in pregnant rats and rabbits (see section 5.3). There are no adequate 
and well-controlled studies in pregnant women. Caution should be exercised when prescribing 
nevirapine to pregnant women (see section 4.4). As hepatotoxicity is more frequent in women with 
CD4 cell counts above 250 cells/mm3 with detectable HIV-1 RNA in plasma (50 or more copies/ml), 
these conditions should be taken in consideration on therapeutic decision (see section 4.4). There is 
not enough evidence to substantiate that the absence of an increased risk for toxicity seen in pretreated 
women initiating nevirapine with an undetectable viral load (less than 50 copies/ml of HIV-1 in 
plasma) and CD4 cell counts above 250 cells/mm3 also applies to pregnant women. All the 
randomised studies addressing this issue specifically excluded pregnant women, and pregnant women 
were under-represented in cohort studies as well as in meta-analyses. 
 
Breast-feeding 
Nevirapine readily crosses the placenta and is found in breast milk. 
 
It is recommended that HIV-infected mothers do not breast-feed their infants to avoid risking postnatal 
transmission of HIV and that mothers should discontinue breast-feeding if they are receiving 
nevirapine. 
 
Fertility 
In reproductive toxicology studies, evidence of impaired fertility was seen in rats. 
 
4.7 Effects on ability to drive and use machines 
 
There are no specific studies about the ability to drive vehicles and use machinery. 
However, patients should be advised that they may experience adverse reactions such as fatigue during 
treatment with Nevirapine Teva. Therefore, caution should be recommended when driving a car or 
operating machinery. If patients experience fatigue they should avoid potentially hazardous tasks such 
as driving or operating machinery. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
The most frequently reported adverse reactions related to nevirapine therapy, across all clinical 
studies, were rash, allergic reactions, hepatitis, abnormal liver function tests, nausea, vomiting, 
diarrhoea, abdominal pain, fatigue, fever, headache and myalgia. 
 
The postmarketing experience has shown that the most serious adverse reactions are Stevens-Johnson 
syndrome/ toxic epidermal necrolysis, serious hepatitis/hepatic failure, and drug reaction with 
eosinophilia and systemic symptoms, characterised by rash with constitutional symptoms such as 
fever, arthralgia, myalgia and lymphadenopathy, plus visceral involvement, such as hepatitis, 
eosinophilia, granulocytopenia, and renal dysfunction. The first 18 weeks of treatment is a critical 
period which requires close monitoring (see section 4.4). 
 
Tabulated summary of adverse reactions 
The following adverse reactions which may be causally related to the administration of nevirapine 
have been reported. The frequencies estimated are based on pooled clinical study data for adverse 
reactions considered related to nevirapine treatment. 
 



17 

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); very rare (<1/10,000). 
 
Blood and lymphatic system disorders 
Common  granulocytopenia 
Uncommon  anaemia 
 
Immune system disorders 
Common  hypersensitivity (incl. anaphylactic reaction, angioedema, urticaria) 
Uncommon  anaphylactic reaction 
Rare   drug reaction with eosinophilia and systemic symptoms 
 
Nervous system disorders 
Common  headache 
 
Gastrointestinal disorders 
Common   nausea, vomiting, abdominal pain, diarrhoea  
 
Hepatobiliary disorders 
Common  hepatitis (including severe and life-threatening hepatotoxicity) (1.9%) 
Uncommon  jaundice 
Rare   hepatitis fulminant (which may be fatal) 
 
Skin and subcutaneous tissue disorders 
Very common  rash (12.5 %) 
Uncommon  Stevens-Johnson syndrome/toxic epidermal necrolysis (which may be fatal) 

(0.2 %), angioedema, urticaria 
 
Musculoskeletal and connective tissue disorders 
Uncommon   arthralgia, myalgia 
 
General disorders and administration site conditions 
Common   pyrexia, fatigue 
 
Investigations 
Common  liver function tests abnormal (alanine aminotransferase increased; transaminases 
   increased; aspartate aminotransferase increased; gamma-glutamyltransferase 
   increased; hepatic enzyme increased; hypertransaminasaemia) 
Uncommon  blood phosphorus decreased; blood pressure increased 
 
Description of selected adverse reactions 
In study 1100.1090, from which the majority of related adverse events (n=28) were received, patients 
on placebo had a higher incidence of events of granulocytopenia (3.3%) than patients on nevirapine 
(2.5%). 
 
Anaphylactic reaction was identified through post-marketing surveillance but not observed in 
randomised, controlled clinical studies. The frequency category was estimated from a statistical 
calculation based on the total number of patients exposed to nevirapine in randomised controlled 
clinical studies (n= 2,718). 
 
Decreased blood phosphorus and increased blood pressure were observed in clinical studies with co-
administration of tenofovir/emtricitabine. 
 
Metabolic parameters 
Weight and levels of blood lipids and glucose may increase during antiretroviral therapy (see 
section 4.4) 



18 

 
The following adverse reactions have also been reported when nevirapine has been used in 
combination with other anti-retroviral agents: pancreatitis, peripheral neuropathy and 
thrombocytopaenia. These adverse reactions are commonly associated with other antiretroviral agents 
and may be expected to occur when nevirapine is used in combination with other agents; however it is 
unlikely that these adverse reactions are due to nevirapine treatment. Hepatic-renal failure syndromes 
have been reported rarely.  
 
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). 
 
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). 
 
Skin and subcutaneous tissues 
 
The most common clinical toxicity of nevirapine is rash, with nevirapine attributable rash occurring in 
12.5 % of patients in combination regimens in controlled studies. 
 
Rashes are usually mild to moderate, maculopapular erythematous cutaneous eruptions, with or 
without pruritus, located on the trunk, face and extremities. Hypersensitivity (anaphylactic reaction, 
angioedema and urticaria) have been reported. Rashes occur alone or in the context of drug reaction 
with eosinophilia and systemic symptoms, characterised by rash with constitutional symptoms such as 
fever, arthralgia, myalgia and lympadenopathy, plus visceral involvement, such as hepatitis, 
eosinophilia, granulocytopenia, and renal dysfunction. 
 
Severe and life-threatening skin reactions have occurred in patients treated with nevirapine, including 
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Fatal cases of SJS, TEN and 
drug reaction with eosinophilia and systemic symptoms have been reported. The majority of severe 
rashes occurred within the first 6 weeks of treatment and some required hospitalisation, with one 
patient requiring surgical intervention (see section 4.4). 
 
Hepato-biliary 
 
The most frequently observed laboratory test abnormalities are elevations in liver function tests 
(LFTs), including ALAT, ASAT, GGT, total bilirubin and alkaline phosphatase. Asymptomatic 
elevations of GGT levels are the most frequent. Cases of jaundice have been reported. Cases of 
hepatitis (severe and life-threatening hepatotoxicity, including fatal fulminant hepatitis) have been 
reported in patients treated with nevirapine. The best predictor of a serious hepatic event was elevated 
baseline liver function tests. The first 18 weeks of treatment is a critical period which requires close 
monitoring (see section 4.4). 
 
Paediatric population 
 
Based on clinical study experience of 361 paediatric patients the majority of which received 
combination treatment with ZDV or/and ddI, the most frequently reported adverse events related to 
nevirapine were similar to those observed in adults. Granulocytopenia was more frequently observed 
in children. In an open-label clinical study (ACTG 180) granulocytopenia assessed as medicinal 
product-related occurred in 5/37 (13.5 %) of patients. In ACTG 245, a double-blind placebo controlled 
study, the frequency of serious medicinal product-related granulocytopenia was 5/305 (1.6 %). 
Isolated cases of Stevens-Johnson syndrome or Stevens-Johnson/toxic epidermal necrolysis transition 
syndrome have been reported in this population. 



19 

 
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 
 
There is no known antidote for nevirapine overdose. Cases of nevirapine overdose at doses ranging 
from 800 to 6,000 mg per day for up to 15 days have been reported. Patients have experienced 
oedema, erythema nodosum, fatigue, fever, headache, insomnia, nausea, pulmonary infiltrates, rash, 
vertigo, vomiting, increase in transaminases and weight decrease. All of these effects subsided 
following discontinuation of nevirapine. 
 
Paediatric population 
 
One case of massive accidental overdose in a newborn was reported. The ingested dose was 40 times 
the recommended dose of 2 mg/kg/day. Mild isolated neutropenia and hyperlactataemia was observed, 
which spontaneously disappeared within one week without any clinical complications. One year later, 
the child’s development remained normal. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antivirals for systemic use, non-nucleoside reverse transcriptase 
inhibitors, ATC code J05AG01. 
 
Mechanism of action 
 
Nevirapine is a NNRTI of HIV-1. Nevirapine is a non-competitive inhibitor of the HIV-1 reverse 
transcriptase, but it does not have a biologically significant inhibitory effect on the HIV-2 reverse 
transcriptase or on eukaryotic DNA polymerases α, β, γ, or δ. 
 
Antiviral activity in vitro  
 
Nevirapine had a median EC50 value (50% inhibitory concentration) of 63 nM against a panel of group 
M HIV-1 isolates from clades A, B, C, D, F, G, and H, and circulating recombinant forms (CRF), 
CRF01_AE, CRF02_AG and CRF12_BF replicating in human embryonic kidney 293 cells. In a panel 
of 2,923 predominantly subtype B HIV-1 clinical isolates, the mean EC50 value was 90 nM. Similar 
EC50 values are obtained when the antiviral activity of nevirapine is measured in peripheral blood 
mononuclear cells, monocyte derived macrophages or lymphoblastoid cell line. Nevirapine had no 
antiviral activity in cell culture against group O HIV-1 isolates or HIV-2 isolates. 
 
Nevirapine in combination with efavirenz exhibited a strong antagonistic anti-HIV-1 activity in vitro 
(see section 4.5) and was additive to antagonistic with the protease inhibitor ritonavir or the fusion 
inhibitor enfuvirtide. Nevirapine exhibited additive to synergistic anti-HIV-1 activity in combination 
with the protease inhibitors amprenavir, atazanavir, indinavir, lopinavir, saquinavir and tipranavir, and 
the NRTIs abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir and zidovudine. The 
anti-HIV-1 activity of nevirapine was antagonized by the anti-HBV medicinal product adefovir and by 
the anti-HCV medicinal product ribavirin in vitro. 
 
Resistance 
 



20 

HIV-1 isolates with reduced susceptibility (100-250-fold) to nevirapine emerge in cell culture. 
Genotypic analysis showed mutations in the HIV-1 RT gene Y181C and/or V106A depending upon 
the virus strain and cell line employed. Time to emergence of nevirapine resistance in cell culture was 
not altered when selection included nevirapine in combination with several other NNRTIs. 
 
Genotypic analysis of isolates from antiretroviral naïve patients experiencing virologic failure (n=71) 
receiving nevirapine once daily (n=25) or twice daily (n=46) in combination with lamivudine and 
stavudine for 48 weeks showed that isolates from 8/25 and 23/46 patients, respectively, contained one 
or more of the following NNRTI resistance-associated substitutions: 
Y181C, K101E, G190A/S, K103N, V106A/M, V108I, Y188C/L, A98G, F227L and M230L. 
 
Cross-resistance 
 
Rapid emergence of HIV-strains which are cross-resistant to NNRTIs has been observed in vitro. 
Cross resistance to delavirdine and efavirenz is expected after virologic failure with nevirapine. 
Depending on resistance testing results, an etravirine-containing regimen may be used subsequently. 
Cross-resistance between nevirapine and either HIV protease inhibitors, HIV integrase inhibitors or 
HIV entry inhibitors is unlikely because the enzyme targets involved are different. Similarly the 
potential for cross-resistance between nevirapine and NRTIs is low because the molecules have 
different binding sites on the reverse transcriptase.  
 
Clinical results 
 
Nevirapine has been evaluated in both treatment-naïve and treatment-experienced patients. 
 
Studies in treatment-naïve patients 
 
2NN study 
 
The double non-nucleoside study 2 NN was a randomised, open-label, multicentre prospective study 
comparing the NNRTIs nevirapine, efavirenz and both medicinal products given together. 
 
1,216 antiretroviral-therapy naïve patients with plasma HIV-1 RNA > 5,000 copies/ml at baseline 
were assigned to nevirapine 400 mg once daily, nevirapine 200 mg twice daily, efavirenz 600 mg once 
daily, or nevirapine (400 mg) and efavirenz (800 mg) once daily, plus stavudine and lamivudine for 48 
weeks. 
The primary endpoint, treatment failure, was defined as less than 1 log10 decline in plasma HIV-1 
RNA in the first 12 weeks, or two consecutive measurements of more than 50 copies/ ml from week 
24 onwards, or disease progression. 
 
Median age was 34 years and about 64% were male patients, median CD4 cell count was 170 and 
190 cells per mm3 in the nevirapine twice daily and efavirenz groups, respectively. There were no 
significant differences in demographic and baseline characteristics between the treatment groups. 
 
The predetermined primary efficacy comparison was between the nevirapine twice daily and the 
efavirenz treatment groups.  
 
The nevirapine twice daily regimen and the efavirenz regimen were not significantly different (p= 
0.091) in terms of efficacy as measured by treatment failure, or any component of treatment failure 
including virological failure. 
 
The simultaneous use of nevirapine (400 mg) plus efavirenz (800 mg) was associated with the highest 
frequency of clinical adverse events and with the highest rate of treatment failure (53.1%). As the 
regimen of nevirapine plus efavirenz did not have additional efficacy and caused more adverse events 
than each medicinal product separately, this regimen is not recommended. 
 



21 

Twenty per cent of patients assigned to nevirapine twice daily and 18% of patients assigned to 
efavirenz had at least one grade 3 or 4 clinical adverse event. Clinical hepatitis reported as clinical 
adverse event occurred in 10 (2.6%) and 2 (0.5%) patients in the nevirapine twice daily and efavirenz 
groups respectively. The proportion of patients with at least one grade 3 or 4 liver-associated 
laboratory toxicity was 8.3% for nevirapine twice daily and 4.5% for efavirenz. Of the patients with 
grade 3 or 4 liver-associated laboratory toxicity, the proportions coinfected with hepatitis B or 
hepatitis C virus were 6.7% and 20.0% in the nevirapine twice daily group, 5.6% and 11.1% in the 
efavirenz group. 
 
2NN Three-year follow-up-study 
 
This is a retrospective multicentre study comparing the 3-year antiviral efficacy of nevirapine and 
efavirenz in combination with stavudine and lamivudine in 2NN patients from week 49 to week 144. 
Patients who participated in the 2NN study and were still under active follow-up at week 48 when the 
study closed and were still being treated at the study clinic, were asked to participate in this study. 
Primary study endpoints (percentage of patients with treatment failures) and secondary study 
endpoints as well as backbone therapy were similar to the original 2NN study. 
 
A durable response to nevirapine for at least three years was documented in this study, and 
equivalence within a 10% range was demonstrated between nevirapine 200 mg twice daily and 
efavirenz with respect to treatment failure. Both, the primary (p = 0.92) and secondary endpoints 
showed no statistically significant differences between efavirenz and nevirapine 200 mg twice daily. 
 
Studies in treatment-experienced patients 
 
NEFA study 
 
The NEFA study is a controlled prospective randomised study which evaluated treatment options for 
patients who switch from protease inhibitor (PI) based regimen with undetectable load to either 
nevirapine, efavirenz or abacavir. 
The study randomly assigned 460 adults who were taking two nucleoside reverse-transcriptase 
inhibitors and at least one PI and whose plasma HIV-1 RNA levels had been less than 200 c/ml for at 
least the previous six months to switch from the PI to nevirapine (155 patients), efavirenz (156), or 
abacavir (149). 
The primary study endpoint was death, progression to the acquired immunodeficiency syndrome, or an 
increase in HIV-1 RNA levels to 200 copies or more per millilitre.  
 
At 12 months, the Kaplan–Meier estimates of the likelihood of reaching the endpoint were 10 % in the 
nevirapine group, 6 % in the efavirenz group, and 13 percent in the abacavir group (P=0.10 according 
to an intention-to-treat analysis). 
 
The overall incidence of adverse events was significantly lower (61 patients, or 41%) in the abacavir 
group than in the nevirapine group (83 patients, or 54%) or the efavirenz group (89 patients, or 57%). 
Significantly fewer patients in the abacavir group (9 patients, or 6%) than in the nevirapine group (26 
patients, or 17%) or the efavirenz group (27 patients, or 17%) discontinued the medicinal product 
because of adverse events. 
 
Perinatal Transmission 
 
Numerous studies have been performed examining the use of nevirapine in regards to perinatal 
transmission, most notably HIVNET 012. This study demonstrated a significant reduction in 
transmission using single dose nevirapine (13.1 % (n = 310) in the nevirapine group, versus 25.1 % (n 
= 308) in the ultra-short zidovudine group (p = 0.00063)). Monotherapy with nevirapine has been 
associated with the development of NNRTI resistance. Single dose nevirapine in mothers or infants 
may lead to reduced efficacy if an HIV treatment regimen using nevirapine is later instituted within 6 
months or less in these patients. Combination of other antiretrovirals with single-dose nevirapine 



22 

attenuates the emergence of nevirapine resistance. Where other antiretroviral medicines are accessible, 
the single dose nevirapine regimen should be combined with additional effective antiretroviral 
medicines (as recommended in internationally recognized guidelines).    
 
The clinical relevance of these data in European populations has not been established. Furthermore, in 
the case nevirapine is used as single dose to prevent vertical transmission of HIV-1 infection, the risk 
of hepatotoxicity in mother and child cannot be excluded. 
 
Paediatric population 
Results of a 48-week analysis of the South African study BI 1100.1368 confirmed that the 4/7 mg/kg 
and 150 mg/m2 nevirapine dose groups were well tolerated and effective in treating antiretroviral naive 
paediatric patients. A marked improvement in the CD4+ cell percent was observed through Week 48 
for both dose groups. Also, both dosing regimens were effective in reducing the viral load. In this 48-
week study no unexpected safety findings were observed in either dosing group. 
 
5.2 Pharmacokinetic properties 
 
Absorption: Nevirapine is readily absorbed (> 90 %) after oral administration in healthy volunteers 
and in adults with HIV-1 infection. Absolute bioavailability in 12 healthy adults following single-dose 
administration was 93 ± 9% (mean SD) for a 50 mg tablet and 91 ± 8 % for an oral solution. Peak 
plasma nevirapine concentrations of 2 ± 0.4 μg/ml (7.5 μM) were attained by 4 hours following a 
single 200 mg dose. Following multiple doses, nevirapine peak concentrations appear to increase 
linearly in the dose range of 200 to 400 mg/day. Data reported in the literature from 20 HIV-infected 
patients suggest a steady state Cmax of 5.74 μg/ml (5.00-7.44) and Cmin of 3.73 μg/ml (3.20-5.08) with 
an AUC of 109.0 h*μg/ml (96.0-143.5) in patients taking 200 mg of nevirapine bid. Other published 
data support these conclusions. Long-term efficacy appears to be most likely in patients whose 
nevirapine trough levels exceed 3.5 μg/ml. 
 
Distribution: Nevirapine is lipophilic and is essentially nonionized at physiologic pH. Following 
intravenous administration to healthy adults, the volume of distribution (Vdss) of nevirapine was 
1.21 ± 0.09 l/kg, suggesting that nevirapine is widely distributed in humans. Nevirapine readily 
crosses the placenta and is found in breast milk. Nevirapine is about 60 % bound to plasma proteins in 
the plasma concentration range of 1-10 μg/ml. Nevirapine concentrations in human cerebrospinal fluid 
(n = 6) were 45 % (± 5 %) of the concentrations in plasma; this ratio is approximately equal to the 
fraction not bound to plasma protein. 
 
Biotransformation and elimination: In vivo studies in humans and in vitro studies with human liver 
microsomes have shown that nevirapine is extensively biotransformed via cytochrome P450 
(oxidative) metabolism to several hydroxylated metabolites. In vitro studies with human liver 
microsomes suggest that oxidative metabolism of nevirapine is mediated primarily by cytochrome 
P450 isozymes from the CYP3A family, although other isozymes may have a secondary role. In a 
mass balance/excretion study in eight healthy male volunteers dosed to steady state with nevirapine 
200 mg given twice daily followed by a single 50 mg dose of 14C-nevirapine, approximately 
91.4 ± 10.5 % of the radiolabelled dose was recovered, with urine (81.3 ± 11.1 %) representing the 
primary route of excretion compared to faeces (10.1 ± 1.5%). Greater than 80 % of the radioactivity in 
urine was made up of glucuronide conjugates of hydroxylated metabolites. Thus cytochrome P450 
metabolism, glucuronide conjugation, and urinary excretion of glucuronidated metabolites represent 
the primary route of nevirapine biotransformation and elimination in humans. Only a small fraction 
(< 5 %) of the radioactivity in urine (representing < 3 % of the total dose) was made up of parent 
compound; therefore, renal excretion plays a minor role in elimination of the parent compound. 
 
Nevirapine has been shown to be an inducer of hepatic cytochrome P450 metabolic enzymes. The 
pharmacokinetics of autoinduction is characterised by an approximately 1.5 to 2 fold increase in the 
apparent oral clearance of nevirapine as treatment continues from a single dose to two-to-four weeks 
of dosing with 200-400 mg/day. Autoinduction also results in a corresponding decrease in the terminal 



23 

phase half-life of nevirapine in plasma from approximately 45 hours (single dose) to approximately 
25-30 hours following multiple dosing with 200-400 mg/day. 
 
Special populations: 
Renal dysfunction: The single-dose pharmacokinetics of nevirapine has been compared in 23 patients 
with either mild (50 ≤ CLcr < 80 ml/min), moderate (30 ≤ CLcr < 50 ml/min) or severe renal 
dysfunction (CLcr < 30 ml/min), renal impairment or end-stage renal disease (ESRD) requiring 
dialysis, and 8 patients with normal renal function (CLcr > 80 ml/min). Renal impairment (mild, 
moderate and severe) resulted in no significant change in the pharmacokinetics of nevirapine. 
However, patients with ESRD requiring dialysis exhibited a 43.5 % reduction in nevirapine AUC over 
a one-week exposure period. There was also accumulation of nevirapine hydroxy-metabolites in 
plasma. The results suggest that supplementing nevirapine therapy with an additional 200 mg dose of 
nevirapine following each dialysis treatment would help offset the effects of dialysis on nevirapine 
clearance. Otherwise patients with CLcr ≥ 20 ml/min do not require an adjustment in nevirapine 
dosing. 
 
Hepatic dysfunction: A steady state study comparing 46 patients with  
mild (n=17: Ishak Score 1-2), 
moderate (n=20; Ishak Score 3-4), 
or severe (n=9; Ishak Score 5-6, Child-Pugh A in 8 pts., for 1 Child-Pugh score not applicable) liver 
fibrosis as a measure of hepatic impairment was conducted.  
 
The patients studied were receiving antiretroviral therapy containing nevirapine 200 mg twice daily 
for at least 6 weeks prior to pharmacokinetic sampling, with a median duration of therapy of 3.4 years. 
In this study, the multiple dose pharmacokinetic disposition of nevirapine and the five oxidative 
metabolites were not altered. 
 
However, approximately 15 % of these patients with hepatic fibrosis had nevirapine trough 
concentrations above 9,000 ng/ml (2 fold the usual mean trough). Patients with hepatic impairment 
should be monitored carefully for evidence of medicinal product induced toxicity. 
 
In a 200 mg nevirapine single dose pharmacokinetic study of HIV-negative patients with mild and 
moderate hepatic impairment (Child-Pugh A, n=6; Child-Pugh B, n=4), a significant increase in the 
AUC of nevirapine was observed in one Child-Pugh B patient with ascites suggesting that patients 
with worsening hepatic function and ascites may be at risk of accumulating nevirapine in the systemic 
circulation. Because nevirapine induces its own metabolism with multiple dosing, this single dose 
study may not reflect the impact of hepatic impairment on multiple dose pharmacokinetics (see section 
4.4). 
 
Gender and older people 
In the multinational 2NN study, a population pharmacokinetic substudy of 1,077 patients was 
performed that included 391 females. Female patients showed a 13.8 % lower clearance of nevirapine 
than did male patients. This difference is not considered clinically relevant. Since neither body weight 
nor Body Mass Index (BMI) had influence on the clearance of nevirapine, the effect of gender cannot 
be explained by body size. Nevirapine pharmacokinetics in HIV-1 infected adults does not appear to 
change with age (range 19-68 years) or race (Black, Hispanic, or Caucasian).  
Nevirapine has not been specifically investigated in patients over the age of 65. 
 
Paediatric population 
Data concerning the pharmacokinetics of nevirapine have been derived from two major sources: a 48 
week paediatric study in South Africa (BI 1100.1368) involving 123 HIV-1 positive, antiretroviral 
naïve patients aged 3 months to 16 years; and a consolidated analysis of five Paediatric AIDS Clinical 
Trials Group (PACTG) protocols comprising 495 patients aged 14 days to 19 years. 
 
Pharmacokinetic data on 33 patients (age range 0.77 – 13.7 years) in the intensive sampling group 
demonstrated that clearance of nevirapine increased with increasing age in a manner consistent with 



24 

increasing body surface area. Dosing of nevirapine at 150 mg/m2 BID (after a two-week lead in at 
150 mg/m2 QD) produced geometric mean or mean trough nevirapine concentrations between 
4-6 μg/ml (as targeted from adult data). In addition, the observed trough nevirapine concentrations 
were comparable between the two methods. 
 
The consolidated analysis of Paediatric AIDS Clinical Trials Group (PACTG) protocols 245, 356, 366, 
377, and 403 allowed for the evaluation of paediatric patients less than 3 months of age (n=17) 
enrolled in these PACTG studies. The plasma nevirapine concentrations observed were within the 
range observed in adults and the remainder of the paediatric population, but were more variable 
between patients, particularly in the second month of age. 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans other than those observed in clinical studies 
based on conventional studies of safety, pharmacology, repeated dose toxicity, and genotoxicity. In 
carcinogenicity studies, nevirapine induces hepatic tumours in rats and mice. These findings are most 
likely related to nevirapine being a strong inducer of liver enzymes, and not due to a genotoxic mode 
of action. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Microcrystalline cellulose 
Lactose (as monohydrate) 
Povidone K25 
Sodium starch glycolate (Type A) 
Colloidal silicon dioxide 
Magnesium stearate 

 
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 
 
Treatment initiation pack 
White opaque PVC/PE/PVdC – Aluminium blisters or OPA/Alu/PVC – Aluminium blisters. Cartons 
containing 14 tablets (Calendar Pack). 
 
Maintenance packs 
White opaque PVC/PE/PVdC – Aluminium blisters or OPA/Alu/PVC – Aluminium blisters. Cartons 
containing 60 or 120 tablets.  
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal  



25 

 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Teva B.V. 
Swensweg 5 
2031GA Haarlem 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/598/001-006 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 30 November 2009 
Date of latest renewal: 26 August 2014 
 
 
10. DATE OF REVISION OF THE TEXT  
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu  
  



26 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURERS 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 

 
 



27 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturers responsible for batch release 
 
TEVA Pharmaceutical Works Private Limited Company  
Pallagi út 13,  
4042 Debrecen, 
Hungary 
 
TEVA Pharmaceutical Works Private Limited Company 
H-2100 Gödöllő,  
Táncsics Mihály út 82 
Hungary  
 
TEVA UK Ltd  
Brampton Road, Hampden Park 
Eastbourne 
East Sussex, BN22 9AG  
United Kingdom 
 
Pharmachemie B.V.  
Swensweg 5,  
2031 GA Haarlem  
The Netherlands   
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
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 marketing authorisation holder shall submit periodic safety update reports for this product in 
accordance with the requirements set out in the list of Union reference dates (EURD list) provided for 
under Article 107c(7) of Directive 2001/83/EC and 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 
 
 
  



28 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



29 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



30 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nevirapine Teva 200 mg tablets  
nevirapine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 200 mg of nevirapine (as anhydrous) 
 
 
3. LIST OF EXCIPIENTS 
 
Contains lactose: see leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
14 tablets 
60 tablets 
120 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 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 



31 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Teva B.V. 
Swensweg 5 
2031GA Haarlem 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/598/001  
EU/1/09/598/002  
EU/1/09/598/003  
EU/1/09/598/004 
EU/1/09/598/005 
EU/1/09/598/006  
 
 
13. BATCH NUMBER 
 
BN 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Nevirapine Teva 200 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC:  
SN: 
NN: 
 
 
  



32 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nevirapine Teva 200 mg tablets  
nevirapine 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Teva B.V. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
BN 
 
 
5. OTHER 
 
 
  



33 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER (CALENDAR PACK) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Nevirapine Teva 200 mg tablets  
nevirapine 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Teva B.V. 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
BN 
 
 
5. OTHER 
 
Monday Tuesday Wednesday Thursday Friday Saturday Sunday 
  



34 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 
  



35 

Package leaflet: Information for the patient 
 

 Nevirapine Teva 200 mg tablets  
nevirapine 

 
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 or pharmacist. 
- 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 or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet  
1. What Nevirapine Teva is and what it is used for 
2. What you need to know before you take Nevirapine Teva 
3. How to take Nevirapine Teva 
4. Possible side effects 
5. How to store Nevirapine Teva 
6. Contents of the pack and other information 
 
 
1. What Nevirapine Teva is and what it is used for 
 
Nevirapine Teva belongs to a group of medicines called antiretrovirals, used in the treatment of 
Human Immunodeficiency Virus (HIV-1) infection. 
 
The active substance of your medicine is called nevirapine. Nevirapine belongs to a class of anti-HIV 
medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs). Reverse transcriptase is an 
enzyme that HIV needs in order to multiply. Nevirapine stops reverse transcriptase from working. By 
stopping reverse transcriptase from working, Nevirapine Teva helps control HIV-1 infection. 
 
Nevirapine Teva is indicated for the treatment of HIV-1 infected adults, adolescents, and children of 
any age. You must take Nevirapine Teva together with other antiretroviral medicines. Your doctor will 
recommend the best medicines for you. 
 
If Nevirapine Teva has been prescribed for your child, please note that all information in this 
leaflet is addressed to your child (in this case please read “your child” instead of “you”). 
 
 
2. What you need to know before you take Nevirapine Teva 
 
Do not take Nevirapine Teva 
- if you are allergic to nevirapine or any of the other ingredients of this medicine (listed in section 

6). 
- if you have taken Nevirapine Teva before and had to stop the treatment because you suffered 

from: 
 -  severe skin rash 
 - skin rash with other symptoms for example: 
  - fever 
  - blistering 
  - mouth sores 
  - inflammation of the eye 
  - swelling of the face 
  - general swelling 
  - shortness of breath 



36 

  - muscle or joint pain 
  - general feelings of illness 
  - abdominal pain 
 - hypersensitivity (allergic) reactions 
 - inflammation of the liver (hepatitis) 
- if you have severe liver disease 
- if you have had to stop nevirapine treatment in the past because of changes in your liver 

function   
- if you are taking a medicine containing the herbal substance St John’s Wort (Hypericum 

perforatum). This herbal substance may stop Nevirapine Teva from working properly. 
 
Warnings and precautions 
 
Talk to your doctor or pharmacist before taking Nevirapine Teva 
During the first 18 weeks of treatment with Nevirapine Teva it is very important that you and 
your doctor watch out for signs of liver or skin reactions. These can become severe and even life 
threatening. You are at greatest risk of such a reaction during the first 6 weeks of treatment. 
 
I f you exper ience severe rash or  hypersensitivity (allergic reactions that may appear  in the form 
of rash) accompanied by other  side effects such as 
- fever ,  
- blister ing,  
- mouth sores,  
- inflammation of the eye,  
- swelling of the face,  
- general swelling,  
- shor tness of breath,  
- muscle or  joint pain,  
- general feelings of illness,  
- or  abdominal pain  
YOU SHOULD DISCONTINUE TAKING NEVIRAPINE TEVA AND YOU MUST CONTACT 
your  doctor  IMMEDIATELY as such reactions can be potentially life-threatening or  lead to 
death. I f you ever  have only mild rash symptoms without any other  reaction please inform your  
doctor immediately, who will advise you whether  you should stop taking Nevirapine Teva.  
 
I f you exper ience symptoms suggesting a damage of the liver , such as  
- loss of appetite,  
- feeling sick (nausea),  
- vomiting,  
- yellow skin (jaundice),  
- abdominal pain  
you should discontinue taking Nevirapine Teva and must contact your doctor immediately.  
 
If you develop severe liver, skin or hypersensitivity reactions whilst taking Nevirapine Teva, 
NEVER TAKE Nevirapine Teva again without referring to your doctor.  
You must take the dose of Nevirapine Teva as prescribed by your doctor. This is especially 
important within the first 14 days of treatment (see more information in “How to take Nevirapine 
Teva”). 
 
The following patients are at increased risk of developing liver problems:  
- women  
- infected with hepatitis B or C  
- abnormal liver function tests  
- treatment-naïve patients with higher CD4 cell counts at the start of Nevirapine Teva therapy 

(women more than 250 cells/mm³, men more than 400 cells/mm³)  
- pre-treated patients with detectable HIV-1 plasma viral load and higher CD4 cell counts at the  



37 

start of nevirapine therapy (women more than 250 cells/mm³, men more than 400 cells/mm³) 
 
In some patients with advanced HIV infection (AIDS) and a history of opportunistic infection (AIDS 
defining illness), signs and symptoms of inflammation 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 inform 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. 
 
Changes of body fat may occur in patients receiving combination antiretroviral therapy. Contact your 
doctor if you notice changes in body fat (see section 4 “Possible side effects”).   
 
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 weakness of the 
immune system and higher body mass index 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. 
 
If you are taking nevirapine and zidovudine concomitantly please inform your doctor since he might 
need to check your white blood cells. 
 
Do not take Nevirapine Teva after an exposure to HIV unless you have been diagnosed with HIV and 
instructed to do so by your doctor. Nevirapine Teva is not a cure for HIV infection. Therefore, you 
may continue to develop infections and other illnesses associated with HIV infection. You should 
therefore remain in regular contact with your doctor. 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. 
 
Prednisone should not be used to treat a rash related to Nevirapine Teva. 
 
If you are taking oral contraceptives (e.g. “pill“) or other hormonal methods of birth control during 
treatment with Nevirapine Teva you should use a barrier contraception (e.g. condoms) in addition to 
prevent pregnancy and further HIV transmission.  
If you are receiving post-menopausal hormone therapy, ask your doctor for advice before taking this 
medicine. 
 
If you are taking or are prescribed rifampicin to treat tuberculosis please inform your doctor before 
taking this medicine with Nevirapine Teva. 
 
Children and adolescents 
Nevirapine Teva tablets can be taken by: 
- children 16 years of age or older 
- children under 16 years of age who: 

- weigh 50 kg or more 
- or have a body surface area above 1.25 square metres. 

 
For children under 16 years of age who weigh less than 50 kg or whose body surface area is below 
1.25 m2 other nevirapine containing oral formulations are available and should be used if appropriate. 
 



38 

Other medicines and Nevirapine Teva 
 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. Inform your doctor about all other medicines you are taking before you start taking 
Nevirapine Teva. Your doctor might need to monitor whether your other medicines are still working 
and adjust doses. Carefully read the package leaflet of all other HIV medicinal products you are taking 
in combination with Nevirapine Teva.  
 
It is particularly important that you tell your doctor if you are taking or have recently taken:  
 
- St John’s Wort (Hypericum perforatum, medicine to treat depression) 
- rifampicin (medicine to treat tuberculosis)  
- rifabutin (medicine to treat tuberculosis)  
- macrolides e.g. clarithromycin (medicine to treat bacterial infections)  
- fluconazole (medicine to treat fungal infections)  
- ketoconazole (medicine to treat fungal infections)  
- itraconazole (medicine to treat fungal infections)  
- methadone (medicine used for treatment of opiate addicts)  
- warfarin (medicine to reduce blood clotting)  
- hormonal contraceptives (e.g. the “pill”) 
- atazanavir (another medicine to treat HIV-infection)  
- lopinavir/ritonavir (another medicine to treat HIV-infection)  
- fosamprenavir (another medicine to treat HIV-infection) 
- efavirenz (another medicine to treat HIV-infection)  
- etravirine (another medicine to treat HIV-infection) 
- rilpivirine (another medicine to treat HIV-infection) 
- delavirdine (another medicine to treat HIV-infection) 
- zidovudine (another medicine to treat HIV-infection) 
- boceprevir (medicine to treat hepatitis C) 
- telaprevir (medicine to treat hepatitis C) 
- elvitegravir/cobicistat (another medicine to treat HIV-infection) 
 
Your doctor will carefully monitor the effect of Nevirapine Teva and any of these medicines if you are 
taking them together.   
 
If you are undergoing kidney dialysis, your doctor may consider a dose adjustment of Nevirapine 
Teva. This is because Nivirapine Teva can be partly washed out of your blood by dialysis.  
 
Nevirapine Teva with food and drink 
There are no restrictions on taking Nevirapine Teva with food and drink.  
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
You should stop breast-feeding if you are taking Nevirapine Teva. It is in general recommended that 
you do not breast-feed if you have HIV infection because it is possible that your baby can become 
infected with HIV through your breast milk. 
 
Driving and using machines 
You may experience fatigue when taking Nevirapine Teva. Use caution when engaging in activities 
such as driving, using any tools or machines. If you experience fatigue you should avoid potentially 
hazardous tasks such as driving or using any tools or machines.  
 
Nevirapine Teva contains lactose  
Nevirapine Teva tablets contain lactose (milk sugar). 



39 

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking Nevirapine Teva. 
 
 
3. How to take Nevirapine Teva 
 
You should not use Nevirapine Teva on its own. You must take it with at least two other antiretroviral 
medicines. Your doctor will recommend the best medicines for you. 
 
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist 
if you are not sure.  
 
Dose: 
 
The dose is one 200 mg tablet per day for the first 14 days of treatment (“lead-in” period). After 
14 days, the recommended dose is one 200 mg tablet twice a day. 
 
It is very important that you take only one Nevirapine Teva tablet a day for the first 14 days (”lead-in” 
period) If you have any rash during this period, do not increase the dose but consult your doctor.  
 
The 14-day “lead-in” period has been shown to lower the risk of skin rash. 
 
As Nevirapine Teva must always be taken together with other HIV antiretroviral medicines, you 
should follow the instructions for your other medicines carefully. These are supplied in the package 
leaflets for those medicines. 
 
You should continue to take Nevirapine Teva for as long as instructed by your doctor.  
 
As explained in ”Warnings and precautions”, above, your doctor will monitor you with liver tests or 
for undesirable effects such as rash. Depending on the outcome your doctor may decide to interrupt or 
stop your Nevirapine Teva treatment. Your doctor might then decide to restart you on a lower dose.  
 
Only take Nevirapine Teva tablets by mouth. Do not chew your tablets. You may take Nevirapine 
Teva with or without food. 
 
If you take more Nevirapine Teva than you should  
Do not take more Nevirapine Teva than prescribed by your doctor and described in this leaflet. There 
is at present little information on the effects of Nevirapine Teva overdose. Consult your doctor if you 
have taken more Nevirapine Teva than you should.  
 
If you forget to take Nevirapine Teva  
Try not to miss a dose. If you notice that you have missed a dose within 8 hours of when it was due, 
take the missed dose as soon as possible. If it has been more than 8 hours since the dose was due only 
take the next dose at the usual time.  
 
If you stop taking Nevirapine Teva  
Taking all doses at the appropriate times: 
- greatly increases the effectiveness of your combination antiretroviral medicines. 
- reduces the chances of your HIV infection becoming resistant to your antiretroviral medicines. 
 
It is important that you continue taking Nevirapine Teva correctly, as described above, unless your 
doctor instructs you to stop. 
 
If you stop taking Nevirapine Teva for more than 7 days your doctor will instruct you to start the 14 
day 'lead-in' period (described above) once again, before returning to the twice daily dose.  
 



40 

If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
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. 
 
As mentioned in ‘Warnings and precautions ', above, the most important side effects of 
Nevirapine Teva are severe and life threatening skin reactions and serious liver damage. These 
reactions occur mainly in the first 18 weeks of treatment with Nevirapine Teva. This is therefore 
an important period which requires close monitoring by your doctor.  
 
If you ever observe any rash symptoms, inform your doctor immediately.  
 
When rash occurs it is normally mild to moderate. However, in some patients a rash, which appears as 
a blistering skin reaction, can be severe or life-threatening (Stevens-Johnson syndrome and toxic 
epidermal necrolysis) and deaths have been recorded. Most of the cases of both severe rash and 
mild/moderate rash occur in the first six weeks of treatment.   
 
If rash occurs and you also feel sick, you must stop treatment and visit your doctor immediately.  
 
Hypersensitivity (allergic) reactions can occur. Such reactions may appear in the form of anaphylaxis 
(a severe form of allergic reaction) with symptoms such as:  
- rash  
- swelling of the face  
- difficulty breathing (bronchial spasm) 
- anaphylactic shock 
Hypersensitivity reactions can also occur as rash with other side effects such as:  
- fever  
- blistering of your skin  
- mouth sores  
- inflammation of the eye  
- swelling of the face  
- general swelling  
- shortness of breath  
- muscle or joint pain  
- a reduction in the numbers of your white blood cells (granulocytopenia)  
- general feelings of illness  
- severe problems with liver or kidneys (liver or kidney failure). 
 
Tell your doctor immediately if you experience rash and any of the other side effects of a 
hypersensitivity (allergic) reaction. Such reactions can be life-threatening.  
 
Abnormal liver functioning has been reported with the use of Nevirapine Teva. This includes some 
cases of inflammation of the liver (hepatitis), which can be sudden and intense (fulminant hepatitis) 
and liver failure, which can be both fatal.  
 
Tell your doctor if you experience any of the following clinical symptoms of liver damage: 
- loss of appetite  
- feeling sick (nausea)  
- vomiting  
- yellow skin (jaundice)  



41 

- abdominal pain  
 
The side effects described below have been experienced by patients given nevirapine: 
 
Very common (may affect more than 1 in 10 people): 
- rash 
 
Common (may affect up to 1 in 10 people):  
- decreased numbers of white blood cells (granulocytopenia) 
- allergic reactions (hypersensitivity) 
- headache  
- feeling sick (nausea)  
- vomiting  
- abdominal pain  
- loose stools (diarrhoea)  
- inflammation of the liver (hepatitis)  
- feeling tired (fatigue)  
- fever  
- abnormal liver function tests  
 
Uncommon (may affect up to 1 in 100 people):  
- allergic reaction characterised by rash, swelling of the face, difficulty breathing (bronchial spasm) 

or anaphylactic shock   
- decreased numbers of red blood cells (anaemia)  
- yellow skin (jaundice)  
- severe and life-threatening skin rashes (Stevens-Johnson syndrome/toxic epidermal necrolysis)  
- hives (urticaria)  
- fluid under the skin (angioedema)  
- joint pain (arthralgia)  
- muscle pain (myalgia) 
- decreased blood phosphorus 
- increased blood pressure 
 
Rare (may affect up to 1 in 1000 people):  
- sudden and intense inflammation of the liver (fulminant hepatitis)  
- drug reaction with systemic symptoms (drug reaction with eosinophilia and systemic symptoms) 
 
The following events have also been reported when nevirapine has been used in combination with 
other antiretroviral agents:  
- decreased numbers of red blood cells or platelets  
- inflammation of the pancreas  
- decrease in or abnormal skin sensations. 
 
These events are commonly associated with other antiretroviral agents and may be expected to occur 
when Nevirapine Teva is used in combination with other agents; however, it is unlikely that these 
events are due to treatment with Nevirapine Teva. 
 
Additional side effects in children and adolescents  
A reduction in white blood cells (granulocytopenia) can occur, which is more common in children. A 
reduction in red blood cells (anaemia), which may be related to nevirapine therapy, is also more 
commonly observed in children. As with rash symptoms, please inform your doctor of any side 
effects.  
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 



42 

listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Nevirapine 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 carton and on the blister after 
EXP. The expiry date refers to the last day of that month.  
  
This medicinal product does not require any special storage conditions.  
 
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 Nevirapine Teva contains 
 
- The active substance is nevirapine. Each tablet contains 200 mg nevirapine (as nevirapine 

anhydrate). 
- The other ingredients are microcrystalline cellulose, lactose monohydrate, povidone K25, 

sodium starch glycolate (Type A), colloidal silicon dioxide and magnesium stearate.  
 
What Nevirapine Teva looks like and contents of the pack 
 
White, oval, biconvex tablets. One side is debossed with "N", a scoreline and "200". The opposite side 
is debossed with a scoreline. The score line is only to facilitate breaking for ease of swallowing and 
not to divide into equal doses. 
 
Nevirapine Teva tablets are supplied in blisters, with 14 (Calendar Pack), 60 or 120 tablets per carton. 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
 
Teva B.V. 
Swensweg 5 
2031GA Haarlem 
The Netherlands 
 
Manufacturer: 
 
TEVA Pharmaceutical Works Private Limited Company  
Pallagi út 13,  
4042 Debrecen, 
Hungary 
 
TEVA Pharmaceutical Works Private Limited Company 
H-2100 Gödöllő,  
Táncsics Mihály út 82 
Hungary  
 
TEVA UK Ltd  
Brampton Road,  
Hampden Park,  



43 

Eastbourne,  
East Sussex,  
BN22 9AG  
United Kingdom 
 
Pharmachemie B.V.  
Swensweg 5,  
2031 GA Haarlem  
The Netherlands   
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 

België/Belgique/Belgien  
Teva Pharma Belgium N.V./S.A./AG  
Tel/Tél: +32 3 820 73 73  

Lietuva 
UAB “Sicor Biotech” 
Tel: +370 5 266 02 03 

 
България  
Тева Фармасютикълс България ЕООД 
Teл: +359 2 489 95 82  

 
Luxembourg/Luxemburg  
Teva Pharma Belgium N.V./S.A./AG 
Tél: +32 3 820 73 73 

 
Česká republika  
Teva Pharmaceuticals CR, s.r.o.  
Tel: +420 251 007 111  

 
Magyarország  
Teva GyógyszergyárZrt  
Tel.: +36 1 288 64 00  

 
Danmark  
Teva Denmark A/S  
Tlf: +45 44 98 55 11  

 
Malta  
Teva Pharmaceuticals IrelandL-Irlanda 
Tel: +353 51 321740 

 
Deutschland 
TEVA GmbH 
Tel: (+49) 731 402 08 

 
Nederland  
Teva Nederland B.V. 
Tel: +31 (0) 800 0228400  

 
Eesti 
Teva Eesti esindus  
UAB Sicor Biotech Eesti filiaal 
Tel: +372 6610801 

 
Norge 
Teva Norway AS 
Tlf: + 47 66 77 55 90 

Ελλάδα 
Teva Ελλάς Α.Ε. 
Τηλ: +30 210 72 79 099 

Österreich 
ratiopharm Arzneimittel Vertriebs-GmbH 
Tel: +43 1 97007-0 

 
España 
Teva Pharma, S.L.U. 
Tél: +(34) 91 387 32 80   

 
Polska 
Teva Pharmaceuticals Polska Sp. z o.o. 
Tel.: +(48) 22 345 93 00 

 
France 
Teva Santé 
Tél: +(33) 1 55 91 7800 

 
Portugal 
Teva Pharma - Produtos Farmacêuticos Lda 
Tel: +351 21 476 75 50 

 
Hrvatska 
Pliva Hrvatska d.o.o. 
Tel:+ 385 1 37 20 000 

 
România 
Teva Pharmaceuticals S.R.L 
Tel: +4021 230 65 24 

 
Ireland 
Teva Pharmaceuticals Ireland 
Tel: +353 (0)51 321 740 

 
Slovenija 
Pliva Ljubljana d.o.o. 
Tel: +386 1 58 90 390 



44 

 
Ísland 
ratiopharm Oy 
Finland 
Puh/Tel: +358 20 180 5900 

 
Slovenská republika 
Teva Pharmaceuticals Slovakia s.r.o. 
Tel: +(421) 2 5726 7911 

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

 
Suomi/Finland 
ratiopharm Oy 
Puh/Tel: +358 20 180 5900 

 
Κύπρος 
Teva Ελλάς Α.Ε. 
Ελλάδα 
Τηλ: +30 210 72 79 099 

 
Sverige 
Teva Sweden AB 
Tel: +(46) 42 12 11 00 

 
Latvija 
Sicor Biotech filiāle Latvijā 
Tel: + 37167323666 

 
United Kingdom 
Teva UK Limited 
Tel: +44(0) 1977 628500 

 
This leaflet was last revised in {MM/YYYY}. 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/.  
  

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS 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