Telzir

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

1. NAME OF THE MEDICINAL PRODUCT 
 
Telzir 700 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 700 mg of fosamprenavir as fosamprenavir calcium (equivalent to 
approximately 600 mg of amprenavir). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet 
 
Pink film coated, capsule shaped, biconvex tablets, marked with GXLL7 on one side. 
 
 
4. CLINICAL PARTICULARS 
 
4.1  Therapeutic indications 
 
Telzir in combination with low dose ritonavir is indicated for the treatment of Human 
Immunodeficiency Virus Type 1 (HIV-1) infected adults, adolescents and children of 6 years and 
above in combination with other antiretroviral medicinal products. 
 
In moderately antiretroviral experienced adults, Telzir in combination with low dose ritonavir has not 
been shown to be as effective as lopinavir / ritonavir. No comparative studies have been undertaken in 
children or adolescents. 
 
In heavily pretreated patients the use of Telzir in combination with low dose ritonavir has not been 
sufficiently studied. 
 
In protease inhibitor (PI) experienced patients the choice of Telzir should be based on individual viral 
resistance testing and treatment history (see section 5.1). 
 
4.2 Posology and method of administration 
 
Telzir must only be given with low dose ritonavir as a pharmacokinetic enhancer of amprenavir and in 
combination with other antiretroviral medicinal products. The Summary of Product Characteristics of 
ritonavir must therefore be consulted prior to initiation of therapy with Telzir. 
 
Therapy should be initiated by a physician experienced in the management of HIV infection. 
 
Fosamprenavir is a pro-drug of amprenavir and must not be administered concomitantly with other 
medicinal products containing amprenavir. 
 
The importance of complying with the full recommended dosing regimen should be stressed to all 
patients. 
 
Caution is advised if the recommended doses of Telzir with ritonavir detailed below are exceeded (see 
section 4.4). 
 



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Telzir tablet is administered orally.  
Telzir tablet can be taken with or without food. 
 
Telzir is also available as an oral suspension for use in patients unable to swallow tablets, and in 
paediatric patients less than 39 kg (please refer to the Summary of Product Characteristics for Telzir 
oral suspension). 
 
Adults 
 
The recommended dose is 700 mg fosamprenavir twice daily with 100 mg ritonavir twice daily. 
 
Paediatric patients from 6 years of age 
 
The adult dose of Telzir tablet 700 mg twice daily with ritonavir 100 mg twice daily may be used in 
children weighing at least 39 kg and able to swallow tablets. 
For children weighing less than 39 kg, Telzir oral suspension is the recommended option for the most 
accurate dosing in children based on body weight (please refer to the Summary of Product 
Characteristics for Telzir oral suspension). 
 
Children less than 6 years of age  
 
Telzir with ritonavir is not recommended in children below 6 years due to insufficient data on 
pharmacokinetics, safety and antiviral response (see section 5.2). 
 
Elderly (over 65 years of age) 
 
The pharmacokinetics of fosamprenavir have not been studied in this patient population (see section 
5.2). Therefore, no recommendations can be made in this patient population. 
 
Renal impairment 
 
No dose adjustment is considered necessary in patients with renal impairment (see section 5.2). 
 
Hepatic impairment 
 
For adults with mild hepatic impairment (Child-Pugh score: 5-6) the recommended dose is 700 mg 
fosamprenavir twice daily with 100 mg ritonavir once daily. 
 
For adults with moderate hepatic impairment (Child-Pugh score: 7-9) the recommended dose is 
450 mg fosamprenavir twice daily with 100 mg ritonavir once daily. This adjusted dose has not been 
evaluated in a clinical study and has been derived from extrapolation (see section 5.2). As it is not 
possible to achieve this fosamprenavir dose using the tablet formulation, these patients should be 
treated with fosamprenavir oral suspension. 
 
For adults with severe hepatic impairment (Child-Pugh score: 10-15): fosamprenavir should be used 
with caution and at a reduced dose of 300 mg fosamprenavir twice daily with 100 mg ritonavir once 
daily. As it is not possible to achieve this fosamprenavir dose using the tablet formulation, these 
patients should be treated with fosamprenavir oral suspension. 
 
Overall, even with these dose adjustments for adults with hepatic impairment, some patients may have 
higher or lower than anticipated amprenavir and/or ritonavir plasma concentrations as compared to 
patients with normal hepatic function, due to increased inter-patient variability (see section 5.2), 
therefore close monitoring of safety and virologic response is warranted. 
 
No dose recommendation can be made for children and adolescents with hepatic impairment as no 
studies have been conducted in these age groups. 



4 

 
4.3 Contraindications 
 
Hypersensitivity to fosamprenavir, amprenavir, or ritonavir, or to any of the excipients listed in section 
6.1. 
 
Telzir must not be administered concurrently with medicinal products with narrow therapeutic 
windows that are substrates of cytochrome P450 3A4 (CYP3A4), e.g. alfuzosin, amiodarone, 
astemizole, bepridil, cisapride, dihydroergotamine, ergotamine, pimozide, quetiapine, quinidine, 
terfenadine, oral midazolam (for caution on parenterally administered midazolam, see section 4.5), 
oral triazolam, sildenafil used for the treatment of pulmonary arterial hypertension (for use of 
sildenafil in patients with erectile dysfunction, see sections 4.4 and 4.5). 
 
Co-administration of the antipsychotic medicinal product lurasidone and fosamprenavir/ritonavir 
(FPV/RTV) is contraindicated (see section 4.5).  
 
 
Co-administration of paritaprevir and fosamprenavir/ritonavir (FPV/RTV) is contraindicated due to 
the expected increase of paritaprevir exposure and the lack of clinical data assessing the magnitude of 
this increase (see section 4.5). 
 
Concomitant use of Telzir with simvastatin or lovastatin is contraindicated because of increased 
plasma concentrations of lovastatin and simvastatin which can increase the risk of myopathy, 
including rhabdomyolysis (see section 4.5). 
Telzir with ritonavir must not be co-administered with medicinal products with narrow therapeutic 
windows that are highly dependent on CYP2D6 metabolism, e.g. flecainide and propafenone (see 
section 4.5). 
 
Combination of rifampicin with Telzir with concomitant low-dose ritonavir is contraindicated (see 
section 4.5). 
 
Herbal preparations containing St John’s wort (Hypericum perforatum) must not be used while taking 
Telzir due to the risk of decreased plasma concentrations and reduced clinical effects of amprenavir 
(see section 4.5). 
 
4.4 Special warnings and precautions for use 
 
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.  
 
Patients should be advised that treatment with Telzir, or any other current antiretroviral therapy, does 
not cure HIV and that they may still develop opportunistic infections and other complications of HIV 
infection.  
 
Fosamprenavir contains a sulphonamide moiety. The potential for cross-sensitivity between medicinal 
products in the sulphonamide class and fosamprenavir is unknown. In the pivotal studies of Telzir, in 
patients receiving fosamprenavir with ritonavir there was no evidence of an increased risk of rashes in 
patients with a history of sulphonamide allergy versus those who did not have a sulphonamide allergy. 
Yet, Telzir should be used with caution in patients with a known sulphonamide allergy. 
 
Co-administration of Telzir 700 mg twice daily with ritonavir in doses greater than 100 mg twice daily 
has not been clinically evaluated. The use of higher ritonavir doses might alter the safety profile of the 
combination and therefore is not recommended. 
 
Liver disease 



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Telzir with ritonavir should be used with caution and at reduced doses in adults with mild, moderate, 
or severe hepatic impairment (see section 4.2).  
 
Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an 
increased risk of severe and potentially fatal hepatic adverse reactions. In case of concomitant antiviral 
therapy for hepatitis B or C, please refer also to the relevant Summary of Product Characteristics 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. 
 
Medicinal products – interactions 
 
The use of Telzir concomitantly with halofantrine or lidocaine (systemic) is not recommended (see 
section 4.5). 
 
PDE5 inhibitors used for the treatment of erectile dysfunction: The use of Telzir concomitantly with 
PDE5 inhibitors (e.g. sildenafil, tadalafil, vardenafil) is not recommended (see section 4.5). 
Co-administration of Telzir with low dose ritonavir and these medicinal products is expected to 
substantially increase their concentrations and may result in PDE5 inhibitor-associated adverse events 
such as hypotension, visual changes and priapism (see section 4.5).  Note that co-administration of 
Telzir with low dose ritonavir with sildenafil used for the treatment of pulmonary arterial hypertension 
is contraindicated (see section 4.3). 
 
A reduction in the rifabutin dosage by at least 75 % is recommended when administered with Telzir 
with ritonavir. Further dose reduction may be necessary (see section 4.5). 
 
Because there may be an increased risk of hepatic transaminase elevations and hormonal levels may 
be altered with co-administration of fosamprenavir, ritonavir and oral contraceptives, alternative non-
hormonal methods of contraception are recommended for women of childbearing potential (see 
section 4.5). 
No data are available on the co-administration of fosamprenavir and ritonavir with oestrogens and/or 
progestogens when used as hormonal replacement therapies. The efficacy and safety of these therapies 
with fosamprenavir and ritonavir has not been established. 
 
Anticonvulsants (carbamazepine, phenobarbital) should be used with caution. Telzir may be less 
effective due to decreased amprenavir plasma concentrations in patients taking these medicinal 
products concomitantly (see section 4.5). 
 
Therapeutic concentration monitoring is recommended for immunosuppressant medicinal products 
(cyclosporine, tacrolimus, rapamycin) when co-administered with Telzir (see section 4.5). 
 
Therapeutic concentration monitoring is recommended for tricyclic antidepressants (e.g. desipramine 
and nortriptyline) when coadministered with Telzir (see section 4.5). 
 
When warfarin or other oral anticoagulants are coadministered with Telzir a reinforced monitoring of 
INR (International Normalised Ratio) is recommended (see section 4.5). 
 
Concomitant use of Telzir with ritonavir and fluticasone or other glucocorticoids that are metabolised 
by CYP3A4 is not recommended unless the potential benefit of treatment outweighs the risk of 
systemic corticosteroid effects, including Cushing’s syndrome and adrenal suppression (see section 
4.5). 



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Co-administration of fosamprenavir/ritonavir with other antineoplastics metabolised by CYP3A (for 
example dasatinib, nilotinib, ibrutinib, vinblastine and everolimus) may increase concentrations of 
these medicinal products, potentially increasing the risk of adverse events usually associated with 
these agents. Please refer to the relevant product information for these medications (see section 4.5).   
 
Hepatitis C virus (HCV) Direct-Acting Antivirals: When hepatitis C virus direct-acting antiviral 
(DAA) drugs, which are metabolised by CYP3A4 or are inducers/inhibitors of CYP3A4, are co-
administered with fosamprenavir/ritonavir, altered plasma concentrations of medications are expected 
due to inhibition or induction of CYP3A4 enzyme activity (see sections 4.3 and 4.5). 
 
Rash / cutaneous reactions 
 
Most patients with mild or moderate rash can continue Telzir. Appropriate antihistamines (e.g. 
cetirizine dihydrochloride) may reduce pruritus and hasten the resolution of rash. Severe and 
life-threatening skin reactions, including Stevens-Johnson syndrome, were reported in less than 1% of 
patients included in the clinical development programme. Telzir should be permanently discontinued 
in case of severe rash, or in case of rash of moderate intensity with systemic or mucosal symptoms 
(see section 4.8). 
 
Haemophiliac patients 
 
There have been reports of increased bleeding including spontaneous skin haematomas and 
haemarthroses in haemophiliac patients type A and B treated with protease inhibitors (PIs). In some 
patients administration of factor VIII was necessary. In more than half of the reported cases, treatment 
with protease inhibitors was continued, or reintroduced if treatment had been discontinued. A causal 
relationship has been evoked, although the mechanism of action has not been elucidated. 
Haemophiliac patients should therefore be informed of the possibility of increased bleeding. 
 
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. 
 
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 mycobacterium infections, 
and Pneumocystis carinii pneumonia. Any inflammatory symptoms should be evaluated and treatment 
instituted when necessary.  Autoimmune disorders (such as Graves’ disease) have also been reported 
to occur in the setting of immune reactivation; however, the reported time to onset is more variable 
and can occur many months after initiation of treatment. 
 
Osteonecrosis 
 
Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol 
consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been 
reported particularly in patients with advanced HIV-disease and/or long-term exposure to CART. 
Patients should be advised to seek medical advice if they experience joint aches and pain, joint 
stiffness or difficulty in movement. 
 



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4.5 Interaction with other medicinal products and other forms of interaction 
 
When fosamprenavir and ritonavir are co-administered, the ritonavir metabolic drug 
interaction profile may predominate because ritonavir is a more potent CYP3A4 inhibitor. The 
full prescribing information for ritonavir must therefore be consulted prior to initiation of 
therapy with Telzir with ritonavir. Ritonavir also inhibits CYP2D6 but to a lesser extent than 
CYP3A4. Ritonavir induces CYP3A4, CYP1A2, CYP2C9 and glucuronosyl transferase. 
 
Additionally, both amprenavir, the active metabolite of fosamprenavir, and ritonavir are primarily 
metabolised in the liver by CYP3A4. Therefore, any medicinal products that either share this 
metabolic pathway or modify CYP3A4 activity may modify the pharmacokinetics of amprenavir and 
ritonavir. Similarly administration of fosamprenavir with ritonavir may modify the pharmacokinetics 
of other active substances that share this metabolic pathway. 
 
Interaction studies have only been performed in adults. 
 
Unless otherwise stated, studies detailed below have been performed with the recommended dosage of 
fosamprenavir/ritonavir (i.e. 700/100 mg twice daily), and the interaction was assessed under steady-
state conditions where drugs were administered for 10 to 21 days.  
 

Drugs by Therapeutic Area Interaction 
 
Geometric mean change 
(%) 
 
(Possible mechanism) 

Recommendation 
concerning co-
administration 

ANTIRETROVIRAL 
MEDICINAL PRODUCTS 
 

  

Non-nucleoside reverse 
transcriptase inhibitors: 
 

  

Efavirenz  
600 mg once daily  
 

No clinically significant 
interaction is observed. 

No dosage adjustment 
necessary. 

Nevirapine  
200 mg twice daily  
 

No clinically significant 
interaction is observed. 
 

No dosage adjustment 
necessary. 
 

Etravirine 
 
 
(Study conducted in 8 
patients) 

Amprenavir AUC ↑ 69% 
Amprenavir Cmin ↑ 77% 
Amprenavir Cmax ↑ 62% 
 
Etravirine AUC ↔a 
Etravirine Cmin↔a 
Etravirine Cmax↔a 
 

 a Comparison based on 
historic control. 
 

Telzir may require dose 
reduction (using oral 
suspension). 

Nucleoside / Nucleotide 
reverse transcriptase 
inhibitors: 
 

  

Abacavir 
Lamivudine  

No clinically significant 
interaction is expected. 

No dosage adjustment 
necessary. 



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Zidovudine  
 
Study performed with 
amprenavir. 
 
No FPV/RTV drug 
interaction studies. 
 

  

Didanosine chewable tablet 
 
No drug interaction studies. 
 

No clinically significant 
interaction is expected. 
 

No dose separation or dosage 
adjustment necessary (see 
Antacids).  
 

Didanosine gastro-resistant 
capsule 
 
No drug interaction studies. 

No clinically significant 
interaction is expected. 
 
 

No dosage adjustment 
necessary. 

Tenofovir disoproxil 
245 mg once daily 
 

No clinically significant 
interaction observed. 
 

No dosage adjustment 
necessary. 

 
 

Protease Inhibitors: 
According to current treatment guidelines, dual therapy with protease inhibitors is generally 
not recommended. 
 
Lopinavir / ritonavir 
400 mg/100 mg  
twice daily  
 
 
 
 
 
 
 
 
 
 
 
 
 
Lopinavir / ritonavir 
533 mg/133 mg twice daily  
 
 
(Telzir 1400 mg twice daily) 
 

Lopinavir: Cmax↑ 30% 
Lopinavir: AUC ↑ 37% 
Lopinavir: Cmin ↑ 52% 
 
Amprenavir: Cmax ↓ 58% 
Amprenavir: AUC ↓ 63% 
Amprenavir: Cmin ↓ 65% 
 
Lopinavir: Cmax ↔* 
Lopinavir: AUC ↔* 
Lopinavir: Cmin ↔* 
* compared to lopinavir / 
ritonavir 400 mg/100 mg 
twice daily 
 
Amprenavir: Cmax ↓ 13%* 
Amprenavir: AUC ↓ 26%* 
Amprenavir: Cmin ↓ 42 %* 
* compared to fosamprenavir 
/ ritonavir 700 mg/100 mg 
twice daily  
 
(Mixed CYP3A4 
induction/inhibition, Pgp 
induction) 

Concomitant use is not 
recommended. 
 

Indinavir 
Saquinavir 
 
No drug interaction studies.  

 
 

No dose recommendations 
can be given. 



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Atazanavir 
 
300 mg once daily  
 
 

Atazanavir: Cmax ↓ 24%* 
Atazanavir: AUC↓ 22%*  
Atazanavir: Cmin↔* 
 *compared to atazanavir/ 
ritonavir 300 mg/ 100 mg 
once daily  
 
Amprenavir: Cmax ↔ 
Amprenavir: AUC ↔ 
Amprenavir: Cmin ↔ 
 

No dosage adjustment 
necessary. 

Integrase inhibitors 
 
Raltegravir 
 
400 mg twice daily 

Fasting state 
 
Amprenavir :  
Cmax ↓ 14% (-36%; +15%) 
AUC ↓ 16% (-36%; +8%) 
Cmin ↓ 19% (-42%; +13%)  
 
Raltegravir: 
Cmax ↓ 51% (-75%; -3%) 
AUC ↓ 55% (-76%; -16%) 
Cmin ↓ 36 % (-57%; -3%)  
 
Fed state 
 
Amprenavir: 
Cmax ↓ 25% (-41%; -4%) 
AUC ↓ 25% (-42%; -3%) 
Cmin ↓ 33% (-50%; -10%)  
 
Raltegravir:  
Cmax ↓ 56% (-70%; -34%) 
AUC ↓ 54% (-66%; -37%) 
Cmin ↓ 54 % (-74%; -18%)  
 

Concomitant use is not 
recommended.  Significant 
reductions in exposure and 
Cmin observed for both 
amprenavir and raltegravir 
(especially in fed conditions) 
may result in virological 
failure in patients. 

Dolutegravir 
 
50 mg once daily 

Dolutegravir 
 
Cmax ↓ 24%  
AUC ↓ 35% 
Cτ ↓ 49% 
 
Amprenavir: Cmax ↔ 
Amprenavir: AUC ↔ 
Amprenavir: Cmin ↔ 
 

No dosage adjustment of 
fosamprenavir or 
dolutegravir is recommended 
based on observed exposure-
response relationships of 
clinical data. Caution is 
warranted and close 
monitoring is recommended 
when this combination is 
given in integrase inhibitor-
resistant patients. 

CCR5-receptor antagonists 
 



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 Maraviroc  
 
300 mg twice daily 

Maraviroc: AUC12 ↑ 2.49 
Maraviroc: Cmax ↑ 1.52 
Maraviroc: C12 ↑ 4.74 
 
Amprenavir: AUC12 ↓ 0.65 
Amprenavir: Cmax ↓ 0.66 
Amprenavir: C12 ↓ 0.64 
 
Ritonavir AUC12 ↓ 0.66 
Ritonavir Cmax ↓ 0.61 
Ritonavir C12 ↔ 0.86 
 

Concomitant use is not 
recommended.  Significant 
reductions in amprenavir Cmin 
observed may result in 
virological failure in patients. 

 
Anti-hepatitis C virus medicinal products 
 
   
   
Simeprevir 
Daclatasvir 

Not studied.  
Results from studies with 
other HIV protease inhibitors 
and simeprevir or daclatasvir, 
suggest that co-
administration with 
fosamprenavir/ritonavir is 
likely to lead to increased 
plasma exposures of 
simeprevir or daclatasvir due 
to CYP3A4 enzyme 
inhibition. 

Not recommended. 

Paritaprevir  
(co-formulated with 
ritonavir and ombitasvir 
and co-administered with 
dasabuvir) 

Not studied.  
Results from studies with 
other HIV protease inhibitors 
and paritaprevir/ritonavir/ 
ombitasvir +/- dasabuvir 
suggest that co-
administration of 
fosamprenavir/ritonavir with 
paritaprevir/ritonavir/ 
ombitasvir+/-dasabuvir is 
likely to lead to increased 
plasma exposures of 
paritaprevir due to CYP3A4 
enzyme inhibition and higher 
ritonavir dose.  

Contraindicated (see section 
4.3). 

ANTIARRHYTHMICS 
 

  

Amiodarone 
Bepridil 
Quinidine 
Flecainide 
Propafenone 
 

Amiodarone: ↑ expected 
Bepridil: ↑ expected 
Quinidine: ↑ expected 
 
 
(CYP3A4 inhibition by 
FPV/RTV)  
 
Flecainide: ↑ expected 

Contraindicated (see section 
4.3). Potential for serious 
and/or life-threatening 
reactions such as cardiac 
arrhythmias. 



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Propafenone: ↑ expected 
 
(CYP2D6 inhibition by 
RTV) 

ERGOT DERIVATIVES 
 

  

Dihydroergotamine 
Ergotamine 
Ergonovine 
Methylergonovine 

Dihydroergotamine: ↑ 
expected 
Ergonovine: ↑ expected 
Ergotamine: ↑ expected 
Methylergonovine: ↑ 
expected 
 
(CYP3A4 inhibition by 
FPV/RTV) 

Contraindicated (see section 
4.3). Potential for serious 
and/or life-threatening 
reactions such as acute ergot 
toxicity characterized by 
peripheral vasospasm and 
ischemia of the extremities 
and other tissues. 

GASTROINTESTINAL 
MOTILITY AGENTS 

  

Cisapride Cisapride: ↑ expected 
 
(CYP3A4 inhibition by 
FPV/RTV) 

Contraindicated (see section 
4.3). Potential for serious 
and/or life-threatening 
reactions such as cardiac 
arrhythmias. 

ANTIHISTAMINES 
(HISTAMINE H1 
RECEPTOR 
ANTAGONISTS) 

  

Astemizole 
Terfenadine 

Astemizole: ↑ expected 
Terfenadine: ↑ expected 
 
(CYP3A4 inhibition by 
FPV/RTV) 

Contraindicated (see section 
4.3). Potential for serious 
and/or life-threatening 
reactions such as cardiac 
arrhythmias. 

NEUROLEPTIC 
 

  

Pimozide Pimozide: ↑ expected 
 
(CYP3A4 inhibition by 
FPV/RTV) 

Contraindicated (see section 
4.3). Potential for serious 
and/or life-threatening 
reactions such as cardiac 
arrhythmias. 

ANTIPSYCHOTICS 
Quetiapine 
 
 

Due to CYP3A inhibition by 
Telzir, concentrations of 
quetiapine are expected to 
increase. 

Concomitant administration 
of Telzir and quetiapine is 
contra-indicated as it may 
increase quetiapine-related 
toxicity.  Increased plasma 
concentrations of quetiapine 
may lead to coma. 

Lurasidone 
 
 
 
 
No FPV/RTV drug 
interaction studies 

Lurasidone: ↑ expected 
(CYP3A4 inhibition) 

Concomitant administration 
of fosamprenavir /ritonavir 
with lurasidone is 
contraindicated due to the 
potential for serious and/or 
life-threatening reactions 
related to lurasidone (see 
section 4.3) 



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INFECTION 
 

  

Antibacterials: 
 

  

Clarithromycin 
 
Study performed with 
amprenavir. 
 
No FPV/RTV drug 
interaction studies. 

Clarithromycin: moderate ↑ 
expected 
 
(CYP3A4 inhibition) 

Use with caution. 
 

Erythromycin 
 
No drug interaction studies. 
 
 

Erythromycin: ↑ expected 
 
(CYP3A4 inhibition by 
FPV/RTV) 

Use with caution. 

Anti-mycobacterial: 
 

  

Rifabutin 
150 mg every other day  
 
 
 

Rifabutin: Cmax ↓ 14%* 
Rifabutin: AUC(0-48) ↔* 
 
25-O-desacetylrifabutin:  
Cmax ↑ 6-fold* 
25-O-desacetylrifabutin: 
AUC(0-48) ↑ 11-fold* 
*compared to rifabutin 
300 mg once daily  
 
Amprenavir exposure 
unchanged when compared 
to historical data. 
 
(Mixed CYP3A4 
induction/inhibition) 
 

The increase of 25-O-
desacetylrifabutin (active 
metabolite) could potentially 
lead to an increase of 
rifabutin related adverse 
events, notably uveitis. 
 
A 75 % reduction of the 
standard rifabutin dose (i.e. 
to 150 mg every other day) is 
recommended. Further dose 
reduction may be necessary 
(see section 4.4). 
 

Rifampicin  
600 mg once daily 
 
(Amprenavir without 
ritonavir) 
 
No FPV/RTV drug 
interaction studies 
 

Amprenavir: AUC ↓ 82% 
 
 
Significant ↓ APV expected 
 
 
(CYP3A4 induction by 
rifampicin) 

Contraindicated (see section 
4.3). 
 
The decrease in amprenavir 
AUC can result in virological 
failure and resistance 
development.  During 
attempts to overcome the 
decreased exposure by 
increasing the dose of other 
protease inhibitors with 
ritonavir, a high frequency of 
liver reactions was seen. 

 
Anti-fungals: 
 

  

Ketoconazole 
200 mg once daily for four 
days 
 

Ketoconazole: Cmax ↑ 25% 
Ketoconazole: AUC ↑ 2.69-
fold. 
 

High doses (> 200 mg/day) 
of ketoconazole or 
itraconazole are not 
recommended. 



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Itraconazole 
 
No drug interaction studies. 
 

Amprenavir: Cmax ↔ 
Amprenavir: AUC ↔ 
Amprenavir: Cmin ↔ 
 
 
Itraconazole: ↑ expected 
 
(CYP3A4 inhibition by 
FPV/RTV) 
 

ANTACIDS, HISTAMINE 
H2 RECEPTOR 
ANTAGONIST AND 
PROTON-PUMP 
INHIBITORS 
 

  

Single 30 ml dose of antacid 
suspension (equivalent to 
3.6 grams aluminium 
hydroxide and 1.8 grams 
magnesium hydroxide 
 
(Telzir 1400 mg single dose) 
 
 
Ranitidine 
300 mg single dose 
 
(Telzir 1400 mg single dose) 
 
Esomeprazole 
20 mg once daily 
 
 

Amprenavir: Cmax ↓ 35% 
Amprenavir: AUC ↓ 18% 
Amprenavir: Cmin (C12h) ↔ 
 
 
 
 
 
 
Amprenavir: Cmax ↓ 51% 
Amprenavir: AUC ↓ 30% 
Amprenavir: Cmin (C12h) ↔ 
 
 
Amprenavir Cmax ↔ 
Amprenavir AUC ↔ 
Amprenavir Cmin (C12h) ↔ 
 
(Increase in gastric pH) 

No dosage adjustment 
necessary with antacids, 
proton-pump inhibitors or 
histamine H2 receptor 
antagonists.  
 
 

ANTICONVULSANTS  
 

  

Phenytoin 
300 mg once daily 
 

Phenytoin: Cmax ↓ 20% 
Phenytoin: AUC ↓ 22% 
Phenytoin: Cmin ↓ 29% 
 
(Modest induction of 
CYP3A4 by FPV/RTV) 
 
Amprenavir: Cmax ↔ 
Amprenavir: AUC ↑ 20% 
Amprenavir: Cmin ↑ 19% 
 

It is recommended that 
phenytoin plasma 
concentrations be monitored 
and phenytoin dose increased 
as appropriate.  
 

 
Phenobarbital 
Carbamazepine 
 
No drug interaction studies. 
 

Amprenavir: ↓ expected 
 
(Modest CYP3A4 
induction) 
 

Use with caution (see 
section 4.4). 



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Lidocaine 
(by systemic route) 
 
No drug interaction studies. 

Lidocaine: ↑ expected 
 
(CYP3A4 inhibition by 
FPV/RTV) 
 

Concomitant use is not 
recommended.  It may cause 
serious adverse reactions 
(see section 4.4). 

Halofantrine 
 
No drug interaction studies. 

Halofantrine: ↑ expected 
 
(CYP3A4 inhibition by 
FPV/RTV) 
 

Concomitant use is not 
recommended.  It may cause 
serious adverse reactions 
(see section 4.4). 

 PDE5 INHIBITORS 
 

  

Sildenafil 
Vardenafil 
Tadalafil 
 
No drug interaction studies. 
 

PDE5 inhibitors: ↑ expected 
 
(CYP3A4 inhibition by 
FPV/RTV) 
 
 

Concomitant use is not 
recommended. It may result 
in an increase in PDE5 
inhibitor-associated adverse 
reactions, including 
hypotension, visual changes 
and priapism (refer to PDE5 
inhibitor prescribing 
information). Patients should 
be warned about these 
possible side effects when 
using PDE5 inhibitors with 
Telzir/ritonavir (see section 
4.4). Note that co-
administration of Telzir with 
low dose ritonavir with 
sildenafil used for the 
treatment of pulmonary 
arterial hypertension is 
contraindicated (see section 
4.3). 

INHALED/NASAL 
STEROIDS 
 

  

Fluticasone propionate  
50 µg intranasal 4 times daily) 
for 7 days 
 
(Ritonavir 100 mg capsules 
twice daily for 7 days) 
 

Fluticasone propionate: ↑ 
 
Intrinsic cortisol levels: ↓ 
86 %. 
 
The effects of high 
fluticasone systemic 
exposure on ritonavir 
plasma levels are unknown. 
 
Greater effects may be 
expected when fluticasone 
propionate is inhaled.  
 
(CYP3A4 inhibition by 
FPV/RTV) 

 Concomitant use is not 
recommended unless the 
potential benefit of treatment 
outweighs the risk of 
systemic corticosteroid 
effects (see section 4.4). A 
dose reduction of the 
glucocorticoid with close 
monitoring of local and 
systemic effects or a switch 
to a glucocorticoid, which is 
not a substrate for CYP3A4 
(e.g. beclomethasone) 
should be considered. In 
case of withdrawal of 
glucocorticoids, progressive 
dose reduction may have to 
be performed over a longer 
period (see section 4.4). 



15 

 
ALPHA 1-
ADRENORECEPTOR 
ANTAGONIST 

  

Alfuzosin, 
 
 
 

Potential for increased 
alfuzosin concentrations 
which can result in 
hypotension. The 
mechanism of interaction is 
CYP3A4 inhibition by 
fosamprenavir/ritonavir. 

Co-administration of 
TELZIR/ritonavir with 
alfuzosin is contraindicated 
(see section 4.3) 

 
 

HERBAL PRODUCTS 
 

  

St. John’s wort (Hypericum 
perforatum) 

Amprenavir ↓ expected 
 
(CYP3A4 induction by St. 
John’s wort) 
 

Herbal preparations 
containing St John’s wort 
must not be combined with 
Telzir (see section 4.3). If a 
patient is already taking St 
John’s wort, check 
amprenavir, ritonavir and 
HIV RNA and stop St John’s 
wort. Amprenavir and 
ritonavir levels may increase 
on stopping St John’s wort. 
The inducing effect may 
persist for at least 2 weeks 
after cessation of treatment 
with St John’s wort. 

HMG-COA REDUCTASE 
INHIBITORS 
 

  

Lovastatin 
Simvastatin 
 
 
No drug interaction studies. 
 

Lovastatin: ↑ expected 
 
Simvastatin: ↑ expected 
 
(CYP3A4 inhibition by 
FPV/RTV) 
 
 

Contraindicated (see section 
4.3). 
 
Increased concentrations of 
HMG-CoA reductase 
inhibitors may cause 
myopathy, including 
rhabdomyolysis. 
 
Pravastatin or fluvastatin are 
recommended because their 
metabolism is not dependent 
on CYP 3A4 and 
interactions are not expected 
with protease inhibitors.  

Atorvastatin 
10 mg once daily for 4 days 
 
 

Atorvastatin: Cmax ↑ 184% 
Atorvastatin: AUC ↑ 153% 
Atorvastatin: Cmin ↑ 73% 
 
Amprenavir: Cmax ↔ 
Amprenavir: AUC ↔ 
Amprenavir: Cmin ↔ 

Doses of atorvastatin no 
greater than 20 mg/day 
should be administered, with 
careful monitoring for 
atorvastatin toxicity. 
 



16 

 
(CYP3A4 inhibition by 
FPV/RTV) 
 

IMMUNOSUPPRESSANTS 
 

  

Cyclosporin 
Rapamycin 
Tacrolimus 
 
No drug interaction studies. 
 

Cyclosporin: ↑ expected 
Rapamycin: ↑ expected 
Tacrolimus: ↑ expected  
 
(CYP3A4 inhibition by 
FPV/RTV) 

Frequent therapeutic 
concentration monitoring of 
immunosuppressant levels is 
recommended until levels 
have stabilised (see section 
4.4). 

 
BENZODIAZEPINES 
 

  

Midazolam 
 
No drug interaction studies. 

Midazolam: ↑ expected (3-4 
fold  for parenteral 
midazolam)  
 
Based on data with other 
protease inhibitors plasma 
concentrations of 
midazolam are expected to 
be significantly higher when 
midazolam is given orally. 
 
(CYP3A4 inhibition by 
FPV/RTV) 
 

Telzir/ritonavir should not 
be co-administered with 
orally administered 
midazolam (see section 4.3), 
whereas  
caution should be used with 
co-administration of 
Telzir/ritonavir and 
parenteral midazolam. 
 
If Telzir/ritonavir is co-
administered with parenteral 
midazolam, it should be 
done in an intensive care 
unit (ICU) or similar setting 
which ensures close clinical 
monitoring and appropriate 
medical management in case 
of respiratory depression 
and/or prolonged sedation. 
Dosage adjustment for 
midazolam should be 
considered, especially if 
more than a single dose of 
midazolam is administered. 

TRICYCLIC 
ANTIDEPRESSANTS 
 

  

Desipramine 
Nortriptyline 
 
No drug interaction studies. 

Tricyclic antidepressant: ↑ 
expected 
 
(Mild CYP2D6 inhibition 
by RTV) 
 

Careful monitoring of the 
therapeutic and adverse 
reactions of tricyclic 
antidepressants is 
recommended (see section 
4.4).  
 

OPIOIDS 
 

  

Methadone 
≤ 200 mg once daily 
 

(R-) methadone: Cmax ↓  
21% 

The decrease of (R-) 
methadone (active 



17 

(R-) methadone: AUC ↓ 
18% 
 
 (CYP induction by 
FPV/RTV) 

enantiomer) is not expected 
to be clinically significant.   
As a precaution, patients 
should be monitored for 
withdrawal syndrome. 
 

 
ORAL ANTICOAGULANTS 
 
Warfarin 
Other oral anticoagulants 
 
No drug interaction studies. 

Possible ↓ or ↑ of 
antithrombotic effect. 
 
(Induction and/or 
inhibition of CYP2C9 by 
RTV) 
 

Reinforced monitoring of the 
International Normalised 
Ratio is recommended (see 
section 4.4). 
 

ORAL CONTRACEPTIVES 
 

  

Ethinyl estradiol 0.035 
mg/norethisterone 0.5 mg once 
daily  
 
 

Ethinyl estradiol: Cmax 
↓28% 
Ethinyl estradiol: AUC 
↓37% 
 
Norethisterone: Cmax 
↓38% 
Norethisterone: AUC 
↓34% 
Norethisterone: Cmin ↓ 26 
 
(CYP3A4 induction by 
FPV/RTV) 
 
Amprenavir: Cmax ↔* 
Amprenavir: AUC ↔* 
Amprenavir: Cmin ↔* 
* compared to historical 
data 
 
Ritonavir: Cmax ↑ 63%* 
Ritonavir: AUC ↑ 45%* 
* compared to historical 
data 
 
Clinically significant 
hepatic transaminase 
elevations occurred in 
some subjects.  

Alternative non-hormonal 
methods of contraception are 
recommended for women of 
childbearing potential (see 
section 4.4). 

SELECTIVE SEROTONIN 
REUPTAKE INHIBITORS 
(SSRIS) 
 

  

Paroxetine 
 
20 mg once daily 
 

Paroxetine: Cmax ↓ 51% 
Paroxetine: AUC ↓55% 
 
Amprenavir: Cmax ↔* 

Dose titration of paroxetine 
based on a clinical assessment 
of antidepressant response is 
recommended. Patients on 



18 

 Amprenavir: AUC ↔* 
Amprenavir: Cmin ↔* 
* compared to historical 
data 
 
Mechanism unknown. 

stable dose of paroxetine who 
start treatment with Telzir and 
ritonavir should be monitored 
for antidepressant response. 

ANTINEOPLASTIC AGENTS           
METABOLISED BY CYP3A 

  

Examples of antineoplastic 
agents:  
dasatinib  
nilotinib  
ibrutinib  
vinblastine 
 everolimus 
 
No FPV/RTV drug interaction 
studies 

dasatinib: ↑ expected 
nilotinib: ↑ expected 
ibrutinib: ↑ expected 
vinblastine: ↑ expected 
 everolimus: ↑ expected 
(CYP3A4 inhibition) 

When antineoplastic agents 
that are metabolised by 
CYP3A are co-administered 
with fosamprenavir/ritonavir, 
plasma concentrations of 
these antineoplastic 
medications may be increased 
and could increase the risk of 
adverse events usually 
associated with these 
antineoplastic agents. In case 
of concomitant administration 
with antineoplastic agents 
metabolized by CYP3A, 
please refer to the relevant 
product information for these 
medications. 
 

 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
As a general rule, when deciding to use antiretroviral agents for the treatment of HIV infection in 
pregnant women and consequently for reducing the risk of HIV vertical transmission to the newborn, 
the animal data (see section 5.3) as well as the clinical experience in pregnant women should be taken 
into account. 
 
There is limited clinical experience (less than 300 pregnancy outcomes) from the use of fosamprenavir 
in pregnant women. Placental transfer of amprenavir has been shown to occur in humans. 
 
In animal studies at systemic plasma exposures (AUC) to amprenavir lower than therapeutic exposure 
in patients treated with Telzir, some developmental toxicity was observed (see section 5.3). In view of 
the low exposure in reproductive toxicity studies, the potential developmental toxicity of Telzir has 
not been fully determined. 
 
Telzir should be used during pregnancy only if the potential benefit justifies the potential risk to the 
foetus. 
 
Breast-feeding 
 
Amprenavir-related material was found in rat milk, but it is not known whether amprenavir is excreted 
in human milk. Rat pups exposed pre and post-natally to amprenavir and fosamprenavir showed 
developmental toxicity (see section 5.3). 
 



19 

It is recommended that HIV-infected women must not breast-feed under any circumstances to avoid 
transmission of HIV. 
 
Fertility 
 
No human data on the effect of fosamprenavir on fertility are available. In rats, there was no major 
effect on fertillty or reproductive performance with fosamprenavir (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects of Telzir in combination with ritonavir on the ability to drive and use 
machines have been performed. The adverse reaction profile of Telzir should be borne in mind when 
considering the patient’s ability to drive or operate machinery (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of safety profile 

The adverse reaction profile was similar across all the respective adult studies: antiretroviral naïve 
patients (APV30002, ESS100732), protease inhibitor experienced (twice daily dosing, APV30003) 
patients. This is based on safety data from a total of 864 patients exposed to fosamprenavir/ritonavir in 
these three studies. 
 
The most frequently (> 5% of adult subjects treated) reported adverse reactions with 
fosamprenavir/ritonavir combination were gastrointestinal reactions (nausea, diarrhoea, abdominal 
pain and vomiting) and headache. Most adverse reactions associated with fosamprenavir/ritonavir 
combination therapies were mild to moderate in severity, early in onset and rarely treatment limiting. 
More serious adverse reactions such as serious skin rashes and hepatic transaminase elevations have 
also been reported (cf paragraph Description of selected adverse reactions). 
 
Tabulated summary of adverse reactions 

Adverse reactions are listed by MedDRA system organ class and absolute frequency. Frequencies are 
defined as: Very common (≥ 1/10), Common (≥ 1/100 to < 1/10), Uncommon (≥ 1/1,000 to < 1/100), 
Rare (≥ 1/10,000 to < 1/1,000) or Very rare (< 1/10,000), or Not known. 
 
Frequency categories for the reactions below have been based on clinical trials and postmarketing 
data. 
 
Most of the adverse reactions below were reported from three large clinical studies in adults, where 
the adverse events were of at least moderate intensity (Grade 2 or more) occurring in at least 1% of 
patients and reported by investigators as being attributable to the medicinal products used in the 
studies.  
 



20 

Body System Adverse reaction Frequency 
 
Nervous system disorders 
 

 
Headache, dizziness, oral 
paraesthesia 
 

 
Common 

 
Gastrointestinal disorders 

 
Diarrhoea 

 
Very common 

  
Loose stools, nausea, vomiting, 
abdominal pain 

 
Common 

 
Skin and subcutaneous tissue 
disorders 
 

 
Stevens Johnson syndrome 
 
Angioedema 
 
Rash (see text below 
“rash/cutaneous reactions”) 
 

 
Rare  
 
Uncommon 
 
Common 
 
 

 
General disorders and 
administration site conditions 
 

 
Fatigue 

 
Common 

Investigations Blood cholesterol increased  
 
Blood triglycerides increased 
 
Alanine aminotransferase 
increased 
 
Aspartate aminotransferase 
increased 
 
Lipase increased 
 
 

Very common 
 
Common 
 
Common 
 
 
Common 
 
 
Common 
 
 

 
Description of selected adverse reactions 

 
Rash / cutaneous reactions: erythematous or maculopapular cutaneous eruptions, with or without 
pruritus, may occur during therapy. The rash generally will resolve spontaneously without the 
necessity of discontinuing treatment with the fosamprenavir with ritonavir. 
 
Severe or life-threatening cases of rash, including Stevens-Johnson syndrome are rare. Fosamprenavir 
with ritonavir therapy should be definitively stopped in case of severe rash or in case of rash of mild or 
moderate intensity associated with systemic or mucosal signs (see section 4.4). 
 
Clinical chemistry abnormalities: clinical chemistry abnormalities (Grade 3 or 4) potentially related to 
treatment with fosamprenavir with ritonavir and reported in greater than or equal to 1 % of adult 
patients, included: increased ALT (common), AST (common), serum lipase (common) and 
triglycerides (common).  
 
Metabolic parameters: Weight and levels of blood lipids and glucose may increase during 
antiretroviral therapy (see section 4.4). 
 



21 

Rhabdomyolysis: an increase in CPK, myalgia, myositis, and rarely, rhabdomyolysis, have been 
reported with protease inhibitors, more specifically in association with nucleoside analogues. 
 
Immune Reactivation Syndrome: in HIV-infected patients with severe immune deficiency at the time 
of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic 
or residual opportunistic infections may arise.  Autoimmune disorders (such as Graves’ disease) 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 (see section 4.4). 
 
Osteonecrosis: cases of osteonecrosis have been reported, particularly in patients with generally 
acknowledged risk factors, advanced HIV disease or long-term exposure to CART. The frequency of 
this is unknown (see section 4.4). 
 
Paediatric / other populations 

Children and adolescents: The adverse reaction profile in children and adolescents is based on 
integrated safety data from two studies (APV29005 Week 24 data and APV20003 Week 168 data 
[final data]) in which 158 HIV-1 infected subjects 2 to 18 years of age received fosamprenavir with 
ritonavir with background nucleoside reverse transcriptase inhibitor therapy (see section 5.1 for 
information on dosing regimens applied for each age group). 79 % of subjects received greater than 48 
weeks of exposure. 
Overall the safety profile in these 158 children and adolescents was similar to that observed in the 
adult population.  Vomiting occurred more frequently amongst paediatric patients. Drug-related 
adverse reactions were more common in APV20003 (57%) where subjects received once daily 
fosamprenavir / ritonavir when compared to APV29005 (33%) where subjects received twice daily 
fosamprenavir / ritonavir. 
No new safety concerns were identified from analyses of 48 week data from studies APV29005 or 
APV20002, in which 54 subjects 4 weeks to <2 years of age received twice daily fosamprenavir / 
ritonavir with background nucleoside reverse transcriptase inhibitor therapy and 5 subjects received 
only single doses of fosamprenavir with or without ritonavir. 
 
Haemophiliac patients: There have been reports of increased spontaneous bleeding in haemophiliac 
patients receiving antiretroviral protease inhibitors (see section 4.4). 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
There is no known antidote for Telzir. It is not known whether amprenavir can be removed by 
peritoneal dialysis or haemodialysis. If overdose occurs, the patient should be monitored for evidence 
of toxicity (see section 4.8) and standard supportive treatment applied as necessary. 
 
 
5.  PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antivirals for systemic use, protease inhibitor, ATC Code: J05AE07 
 
Mechanism of action 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
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22 

The in vitro antiviral activity observed with fosamprenavir is due to the presence of trace amounts of 
amprenavir. Amprenavir is a competitive inhibitor of the HIV-1 protease. Amprenavir binds to the 
active site of HIV-1 protease and thereby prevents the processing of viral gag and gag-pol polyprotein 
precursors, resulting in the formation of immature non-infectious viral particles. 
 
Administration of fosamprenavir 700 mg twice daily with ritonavir 100 mg twice daily results in 
plasma amprenavir concentrations (data from study APV30003 in antiretroviral experienced patients) 
which results in protein adjusted median ratios of Cmin/IC50 and Cmin/IC95 of 21.7 (range 1.19-240) and 
3.21 (range 0.26-30.0), respectively. 
 
Antiviral activity in vitro 
 
The in vitro antiviral activity of amprenavir was evaluated against HIV-1 IIIB in both acutely and 
chronically infected lymphoblastic cell lines (MT-4, CEM-CCRF, H9) and in peripheral blood 
lymphocytes. The 50% inhibitory concentration (IC50) of amprenavir ranged from 0.012 to 0.08 µM in 
acutely infected cells and was 0.41 µM in chronically infected cells (1 µM = 0.50 µg/ml). The 
relationship between in vitro anti-HIV-1 activity of amprenavir and the inhibition of HIV-1 replication 
in humans has not been defined. 
 
Resistance 
 
In vivo 
 

a) ART-naïve or PI-naïve patients 
 

Various regimens have been assessed in the amprenavir/fosamprenavir development programs with 
and without co-administration of ritonavir. Analysis of the virological failure samples across these 
regimens defined four main resistance pathways: V32I+I47V, I50V, I54L/M and I84V.  Additional 
mutations observed which may contribute to resistance were: L10V/F/R, I13V, K20R/T, L33F/V, 
M36I, M46I/L, I47V/L Q58E, I62V, L63P, V77I, I85V, and I93L.   

 
When ART naïve adult patients were treated with the currently approved doses of 
fosamprenavir/ritonavir, as for other ritonavir boosted PI regimens, the mutations described were 
infrequently observed. Sixteen of 434 ART-naïve patients who received fosamprenavir 700 
mg/ritonavir 100 mg twice daily in ESS100732 experienced virological failure by Week 48 with 14 
isolates genotyped. Three of 14 isolates had protease resistance mutations. One resistance mutation 
was observed in each of 3 isolates: K20K/R, I54I/L and I93I/L respectively  
 
Among the 81 PI-naïve paediatric patients treated with fosamprenavir / ritonavir, 15 patients met 
protocol-defined virological failure through 48 weeks in APV29005 and up to 108 weeks in 
APV20003.  Treatment-emergent major or APV-associated protease mutations were observed in virus 
isolated from 2 patients. Resistance patterns were similar to those observed in adults. 
 

b) PI-experienced patients 
 
Amprenavir  
 
In the studies of PI-experienced adult patients, PRO30017 (amprenavir 600 mg / ritonavir 100 mg 
twice daily in sub-study A and B with 80 and 37 patients respectively), the following mutations 
emerged in patients with virological failure: L10F/I/V, V11I, I13V, K20R, V32I, L33F, E34Q, M36I, 
M46I/L, I47V, G48V, I50V, I54L/M/T/V, Q58E, D60E, I62V, A71V, V77I, V82A/I, I84V, I85V, 
L90M and I93L/M. 
 
Fosamprenavir 
 



23 

In the studies of PI-experienced adult patients, APV30003 and its extension, APV30005 
(fosamprenavir 700 mg / ritonavir 100 mg twice daily: n=107), the following mutations emerged in 
patients experiencing virological failure through 96 weeks: L10F/I, L24I, V32I, L33F, M36I, M46I/L, 
I47V, I50V, I54L/M/S, A71I/T/V, G73S, V82A, I84V, and L90M.  
 
In the paediatric studies APV20003 and APV29005, 77 PI-experienced patients were treated with 
fosamprenavir / ritonavir-based regimens and 43 patients met study-defined virologic failure criteria 
through 48 weeks in APV29005 and up to 108 weeks in APV20003. Treatment-emergent major 
protease or APV-associated mutations were observed in virus isolated from 1 patient in APV29005 
and 6 patients from APV20003.  The mutational profiles were similar to those described for PI-
experienced adults treated with fosamprenavir / ritonavir. 
 
Antiviral activity according to genotypic/phenotypic resistance 
 
Genotypic resistance testing 
 
Genotypic interpretation systems may be used to estimate the activity of amprenavir / ritonavir or 
fosamprenavir / ritonavir in subjects with PI-resistant isolates. The current (July 2006) ANRS AC-11 
algorithm for fosamprenavir / ritonavir defines resistance as the presence of the mutations 
V32I+I47A/V, or I50V, or at least four mutations among: L10F/I/V, L33F, M36I, I54A/L/M/S/T/V, 
I62V, V82A/C/F/G, I84V and L90M and is associated with increased phenotypic resistance to 
fosamprenavir with ritonavir as well as reduced likelihood of virological response (resistance). 
Conclusions regarding the relevance of particular mutations or mutational patterns are subject to 
change with additional data, and it is recommended to always consult current interpretation systems 
for analysing resistance test results. 
 
Phenotypic resistance testing 
 
Clinically validated phenotypic interpretation systems may be used in association with the genotypic 
data to estimate the activity of amprenavir / ritonavir or fosamprenavir / ritonavir in patients with PI-
resistant isolates.  Resistance testing diagnostic companies have developed clinical phenotypic cut-offs 
for FPV/RTV that can be used to interpret resistance test results. 
 
Clinical experience 
 
Clinical experience with fosamprenavir boosted with ritonavir is mainly based on two open label 
studies one in antiretroviral naïve patients (study ESS100732), and one study in antiretroviral 
experienced patients (study APV30003).  Both of these studies compared fosamprenavir/ritonavir with 
lopinavir / ritonavir. 
 
Antiretroviral Naïve Adult Patients 
 
In a randomised open-label study (ESS100732 - KLEAN) in antiretroviral naïve patients, 
fosamprenavir (700 mg) co-administered with low dose ritonavir (100 mg) in a twice daily regimen 
including abacavir / lamivudine (600 mg / 300 mg) fixed dose combination tablet once daily showed 
comparable efficacy over 48 weeks to lopinavir / ritonavir (400 mg / 100 mg) given twice daily in 
combination with abacavir / lamivudine (600 mg / 300 mg once daily). 
 
Non-inferiority was demonstrated between fosamprenavir co-administered with ritonavir and lopinavir 
/ ritonavir based on the proportions of patients achieving plasma HIV-1 RNA levels < 400 copies/ml at 
48 weeks (primary endpoint). In the Time to loss of virological response (TLOVR) analysis for the 
ITT(E) population, the proportion of patients achieving <400 copies/ml was 73 % (315 / 434) in the 
fosamprenavir with ritonavir group compared to 71 % (317 / 444) of patients receiving lopinavir / 
ritonavir, with a 95 % confidence interval of the difference of [-4,84%; 7;05%].  
 
Efficacy outcomes by subgroups are described in the table below. 



24 

 
Table 1   Efficacy Outcome at Week 48 in ESS100732 (ART-Naïve Patients) 

 FPV/RTV 700 mg/100 mg 
BID (n= 434) 

LPV/RTV 400 mg/100 mg BID 
(n=444) 

ITT-E Population 
TLOVR analysis 

Proportion with HIV-1 RNA < 400 copies/ml 

All Subjects 72.5 % 71.4% 

Baseline HIV-1 RNA 
 < 100,000 copies/ml 

69.5 % (n=197) 69.4% (n=209) 

Baseline HIV-1 RNA  
≥ 100,000 copies/ml 

75.1% (n=237) 73.2% (n=235) 

 Proportion with HIV-1 RNA < 50 copies/ml 

All Subjects 66% 65% 

Baseline HIV-1 RNA  
< 100,000 copies/ml 

67% (n=197) 64% (n=209) 

Baseline HIV-1 RNA  
≥ 100,000 copies/ml 

65% (n=237) 66% (n=235) 

 Median Change from baseline in CD4 cells (cells/µl) 

ITT-E observed 
analysis 

176 (n=323) 191 (n=336) 

 
Following completion of the 48 week treatment period, subjects at European and Canadian sites were 
eligible to participate in a study extension to Week 144 maintaining their treatment regimen as per the 
original randomisation. Only 22% of the original population of the KLEAN study was enrolled in the 
study extension.  
 
Efficacy outcomes are described in the table below. 
 
Table 2   Efficacy Outcome at Weeks 96 and 144 in ESS100732 Extension (ART-Naïve Patients) 

 FPV/RTV 700 mg/100 mg 

BID (n= 105) 

LPV/RTV 400 mg/100 mg BID 

(n=91) 

ITT (Ext) Population 

TLOVR analysis 

Proportion with HIV-1 RNA < 400 copies/ml 

Week 96 93% 87% 

Week 144 83% 70% 

 Proportion with HIV-1 RNA < 50 copies/ml 

Week 96 85% 75% 



25 

Week 144 73% 60% 

ITT (Ext)  

Observed analysis 
Median Change from baseline in CD4 cells (cells/µl) 

Week 96 292 (n=100) 286 (n=84) 

Week 144 300 (n=87)  335 (n=66) 

 
Antiretroviral Experienced Adult Patients 
 
In a randomised open-label study (APV30003) in protease inhibitor experienced patients with 
virological failure (less than or equal to two PIs) the fosamprenavir with ritonavir combination (700 / 
100 mg twice daily or 1400 / 200 mg once daily) did not demonstrate non-inferiority to lopinavir / 
ritonavir with regard to viral suppression as measured by the average area under the curve minus 
baseline (AAUCMB) for plasma HIV-1 RNA over 48 weeks (the primary end point). Results were in 
favour of the lopinavir / ritonavir arm as detailed below. 
 
All patients in this study had failed treatment with a previous protease inhibitor regimen (defined as 
plasma HIV-1 RNA that never went below 1,000 copies/ml after at least 12 consecutive weeks of 
therapy, or initial suppression of HIV-1 RNA which subsequently rebounded to ≥ 1,000 copies/ml). 
However, only 65 % of patients were receiving a PI based regimen at study entry. 
 
The population enrolled mainly consisted of moderately antiretroviral experienced patients. The 
median durations of prior exposure to NRTIs were 257 weeks for patients receiving fosamprenavir 
with ritonavir twice daily (79 % had ≥ 3 prior NRTIs) and 210 weeks for patients receiving 
lopinavir/ritonavir (64 % had ≥ 3 prior NRTIs). The median durations of prior exposure to protease 
inhibitors were 149 weeks for patients receiving fosamprenavir with ritonavir twice daily (49 % 
received ≥ 2 prior PIs) and 130 weeks for patients receiving lopinavir/ritonavir (40 % received 
≥ 2 prior PIs). 
 
The mean AAUCMBs (log10 c/ml) in the ITT (E) population (Observed analysis) at 48 weeks (primary 
end-point) and other efficacy outcomes by subgroup are described in the tables below: 
 
Table 3   Efficacy at Week 48 Outcomes in APV30003 ITT(E) Population (ART-experienced 
Patients) 

 FPV/RTV BID 

(N=107) 

LPV/RTV BID 

(N=103) 

AAUCMB Observed Analysis Mean (n) Mean (n) 

All Patients -1.53 (105) -1.76 (103) 

     1000 – 10,000 copies/ml -1.53 (41) -1.43 (43) 

     >10,000 – 100,000 copies/ml -1.59 (45) -1.81 (46) 

     >100,000 copies/ml -1.38 (19) -2.61 (14) 

FPV/RTV BID vs LPV/RTV BID AAUCMB Mean Diff (97.5% CI) 

All Patients 0.244 (-0.047, 0.536) 



26 

     1000 – 10,000 copies/ml -0.104 (-0.550, 0.342) 

     >10,000 – 100,000 copies/ml 0.216 (-0.213, 0.664) 

     >100,000 copies/ml 1.232 (0.512, 1.952) 

AAUCMB Observed Analysis Mean (n) Mean (n) 

All Patients -1.53 (105) -1.76 (103) 

         CD4-count    <50 -1.28 (7) -2.45 (8) 

                              ≥50 -1.55 (98) -1.70 (95) 

                              <200 -1.68 (32) -2.07 (38) 

                             ≥ 200  -1.46 (73) -1.58 (65) 

         GSS to OBT1       0 -1.42 (8) -1.91 (4) 

                                     1 -1.30 (35) -1.59 (23) 

                                   ≥ 2 -1.68 (62) -1.80 (76) 

All Patients, RD=F Analysis2  n (%) n(%) 

Subjects (%) with plasma HIV-1 RNA 
<50 copies/ml 

49 (46%) 52 (50%) 

Subjects (%) with plasma HIV-1 RNA 
<400 copies/ml 

62 (58%) 63 (61%) 

Subjects with >1 log10 change from 
baseline in plasma  HIV-
1 RNA 

62 (58%) 71 (69%) 

Change from baseline in CD4 cells 
(cells/µl) 

Median (n) Median (n) 

All Patients 81 (79) 91 (85) 

Key: 1GSS to OBT: Genotypic Sensitivity Score to Optimised Background. GSS was derived using 
ANRS 2007 guidelines. 2RD=F: Rebound or discontinuation equal failure analysis which is equivalent to 
TLOVR. FPV/RTV BID – Fosamprenavir with ritonavir twice daily, LPV/RTV BID – Lopinavir / 
ritonavir twice daily 
 
Table 4   AAUCMB at Week 48 by genotypic sensitivity score in OBT and baseline resistance to 
FPV/RTV 

 Week 48 AAUCMB 

(n) 

Genotypic 
Sensitivity Score 
in OBT 

All Subjects Susceptiple to 
FPV/RTV 

Resistant to 
FPV/RTV 



27 

< 4 mutations from 
score 

≥ 4 mutations from 
score 

0 -1.42 (8) -1.83 (4) -1.01 (4) 

1 -1.30 (35) -1.42 (29) -0.69 (6) 

≥ 2 -1.68 (62) -1.76 (56) -0.89 (6) 

All patients -1.53 (105) -1.65 (89) -0.85 (16) 

 
As shown in the above table, there were only 16 patients harbouring baseline virus with resistance to 
FPV/RTV according to the ANRS score. Data from this small number further analysed by GSS 
subgroups need to be interpreted with caution. 
 
There are insufficient data to recommend the use of fosamprenavir with ritonavir in heavily pre-treated 
patients. 
 
Children and adolescent patients above the age of six 
 
Fosamprenavir tablets and oral suspension with ritonavir in combination with NRTIs have been 
evaluated in protease inhibitor naïve and experienced children and adolescent patients. The benefit in 
this age group has mainly been derived from study APV29005, an open label 48 week study 
evaluating the pharmacokinetic profiles, safety, and antiviral activity of fosamprenavir with ritonavir 
administered twice daily to HIV 1 protease inhibitor experienced and naive patients 2 to 18 years of 
age. Results through 48 weeks of treatment are provided below. 
 
APV29005 enrolled 30 patients aged 6 to 11 (the majority of whom were treated with fosamprenavir / 
ritonavir 18/3 mg/kg twice daily or the adult tablet regimen), and 40 patients aged 12 to 18 (the 
majority of whom were treated with the adult tablet regimen). 
 
Table 5   Baseline Characteristics and Efficacy Outcomes at Week 48 in APV29005 ITT(E) 
Population 

 Patients aged 6 to 11 
N=30 

Patients aged 12 to 18 
N=40 

Baseline Characteristics   
ART/PI status, n (%)   

ART-naïve 2 (7) 14 (35) 
ART-experienced, PI-naïve 8 (27) 12 (30) 
PI-experienced 20 (67) 14 (35) 

Median duration of prior ART exposure, weeks   
NRTI 386        409 
PI 253 209 

Median plasma HIV-1 RNA log10 copies/mL 4.6 (n=29) 4.7 
>100,000 copies/ml, n (%) 9 (31) 13 (33) 
Median CD4 cells/μl 470 250 

CD4 count < 350 cells/μl, n (%) 10 (33) 27 (68) 
Efficacy Outcomes   
Patients with plasma HIV-1 RNA <400 
copies/ml, Snapshot analysis 

16 (53%) 25 (63%) 

Median change from baseline in CD4 cells 
(cells/μl), observed analysis 

210 (n=21) 140 (n=35) 

 
These data were further substantiated by the supportive study APV20003; however, a different dosage 
regimen than that of study APV29005 was used. 



28 

 
5.2 Pharmacokinetic properties 
 
After oral administration, fosamprenavir is rapidly and almost completely hydrolysed to amprenavir 
and inorganic phosphate prior to reaching the systemic circulation. The conversion of fosamprenavir 
to amprenavir appears to primarily occur in the gut epithelium. 
 
The pharmacokinetic properties of amprenavir following co-administration of Telzir with ritonavir 
have been evaluated in healthy adult subjects and HIV-infected patients and no substantial differences 
were observed between these two groups. 
 
Telzir tablet and oral suspension formulations, both given fasted, delivered equivalent plasma 
amprenavir AUC∞ values and the Telzir oral suspension formulation delivered a 14 % higher plasma 
amprenavir Cmax as compared to the oral tablet formulation. 
 
Absorption 
 
After single dose administration of fosamprenavir, amprenavir peak plasma concentrations are 
observed approximately 2 hours after administration. Fosamprenavir AUC values are, in general, less 
than 1 % of those observed for amprenavir. The absolute bioavailability of fosamprenavir in humans 
has not been established. 
 
After multiple dose oral administration of equivalent fosamprenavir and amprenavir doses, 
comparable amprenavir AUC values were observed; however, Cmax values were approximately 30 % 
lower and Cmin values were approximately 28 % higher with fosamprenavir.  
 
Co-administration of ritonavir with fosamprenavir increase plasma amprenavir AUC by approximately 
2-fold and plasma Cτ,ss by 4- to 6-fold, compared to values obtained when fosamprenavir is 
administered alone. 
 
After multiple dose oral administration of fosamprenavir 700 mg with ritonavir 100 mg twice daily, 
amprenavir was rapidly absorbed with a geometric mean (95 % CI) steady state peak plasma 
amprenavir concentration (Cmax) of 6.08 (5.38-6.86) µg/ml occurring approximately 1.5 (0.75-5.0) 
hours after dosing (tmax). The mean steady state plasma amprenavir trough concentration (Cmin) was 
2.12 (1.77-2.54) µg/ml and AUC0-tau was 39.6 (34.5–45.3) h*µg/ml. 
 
Administration of the fosamprenavir tablet formulation in the fed state (standardised high fat meal: 
967 kcal, 67 grams fat, 33 grams protein, 58 grams carbohydrate) did not alter plasma amprenavir 
pharmacokinetics (Cmax, tmax or AUC0-∞) compared to the administration of this formulation in the 
fasted state. Telzir tablets may be taken without regard to food intake. 
 
Co-administration of amprenavir with grapefruit juice was not associated with clinically significant 
changes in plasma amprenavir pharmacokinetics. 
 
Distribution 
 
The apparent volume of distribution of amprenavir following administration of Telzir is approximately 
430 l (6 l/kg assuming a 70 kg body weight), suggesting a large volume of distribution, with 
penetration of amprenavir freely into tissues beyond the systemic circulation. This value is decreased 
by approximately 40 % when Telzir is co-administered with ritonavir, most likely due to an increase in 
amprenavir bioavailability. 
 
In in vitro studies, the protein binding of amprenavir is approximately 90 %. It is bound to the alpha-1-
acid glycoprotein (AAG) and albumin,but has a higher affinity for AAG. Concentrations of AAG have 
been shown to decrease during the course of antiretroviral therapy. This change will decrease the total 



29 

active substance concentration in the plasma, however the amount of unbound amprenavir, which is 
the active moiety, is likely to be unchanged. 
 
CSF penetration of amprenavir is negligible in humans. Amprenavir appears to penetrate into semen, 
though semen concentrations are lower than plasma concentrations. 
 
Biotransformation 
 
Fosamprenavir is rapidly and almost completely hydrolysed to amprenavir and inorganic phosphate as 
it is absorbed through the gut epithelium, following oral administration. Amprenavir is primarily 
metabolised by the liver with less than 1 % excreted unchanged in the urine. The primary route of 
metabolism is via the cytochrome P450 3A4 enzyme. Amprenavir metabolism is inhibited by 
ritonavir, via inhibition of CYP3A4, resulting in increased plasma concentrations of amprenavir. 
Amprenavir in addition is also an inhibitor of the CYP3A4 enzyme, although to a lesser extent than 
ritonavir. Therefore medicinal products that are inducers, inhibitors or substrates of CYP3A4 must be 
used with caution when administered concurrently with Telzir with ritonavir (see sections 4.3 and 4.5). 
 
Elimination 
 
Following administration of Telzir, the half-life of amprenavir is 7.7 hours. When Telzir is 
co-administered with ritonavir, the half-life of amprenavir is increased to 15 – 23 hours. 
The primary route of elimination of amprenavir is via hepatic metabolism with less than 1 % excreted 
unchanged in the urine and no detectable amprenavir in faeces. Metabolites account for approximately 
14 % of the administered amprenavir dose in the urine, and approximately 75 % in the faeces. 
 
Special populations 
 
Paediatrics 
 
In a clinical study on pharmacokinetics of fosamprenavir in paediatric patients, eight subjects 12 to 18 
years of age received the standard fosamprenavir adult tablet dose of 700 mg twice daily (with 
ritonavir 100 mg twice daily). Compared to the historical adult population receiving fosamprenavir / 
ritonavir 700 / 100 mg twice daily, 12 to 18 year old subjects had 20 % lower plasma APV AUC(0-
24), 23 % lower Cmax, and 20 % lower Cmin values. Children 6 to 11 years of age  (n=9) receiving 
fosamprenavir / ritonavir 18 / 3 mg/kg twice daily had 26 % higher AUC(0-24) and similar Cmax and 
Cmin values when compared to the historical adult population receiving fosamprenavir / ritonavir 700 / 
100 mg twice daily. 
 
APV20002 is a 48 week, Phase II, open label study designed to evaluate the pharmacokinetics, safety, 
tolerability and antiviral activity of fosamprenavir with and without ritonavir in paediatric subjects 4 
weeks to < 2 years of age. Compared to the historical adult population receiving fosamprenavir with 
ritonavir 700 mg / 100 mg twice daily, a subset of five pediatric subjects ages 6 to < 24-months 
receiving fosamprenavir / ritonavir 45/7 mg/kg twice daily demonstrated that despite an approximate 
5-fold increase in fosamprenavir and ritonavir doses on a mg/kg basis, plasma amprenavir AUC(0-τ) 
was approximately 48 % lower, Cmax 26 % lower, and Cτ 29 % lower in the paediatric subjects. No 
dosing recommendations can be made for the very young (children < 2 years of age) and Telzir with 
ritonavir is not recommended for this patient population (see section 4.2). 
 
Elderly 
 
The pharmacokinetics of fosamprenavir in combination with ritonavir has not been studied in patients 
over 65 years of age. 
 
Renal impairment 
 



30 

Patients with renal impairment have not been specifically studied. Less than 1 % of the therapeutic 
dose of amprenavir is excreted unchanged in the urine. Renal clearance of ritonavir is also negligible, 
therefore the impact of renal impairment on amprenavir and ritonavir elimination should be minimal 
 
Hepatic impairment 
 
Fosamprenavir is converted in man to amprenavir. The principal route of amprenavir and ritonavir 
elimination is hepatic metabolism. 
 
The plasma amprenavir pharmacokinetics were evaluated in a 14 day repeat-dose study in HIV-1 
infected adult subjects with mild, moderate, or severe hepatic impairment receiving fosamprenavir 
with ritonavir compared to matched control subjects with normal hepatic function. 
 
In subjects with mild hepatic impairment (Child-Pugh score of 5-6), the dosage regimen of 
fosamprenavir 700 mg twice daily with a reduced dosing frequency of ritonavir 100 mg once daily 
provided slightly higher plasma amprenavir Cmax (17 %), slightly higher plasma amprenavir 
AUC(0-12) (22 %), similar plasma total amprenavir C12 values and approximately 117 % higher 
plasma unbound amprenavir C12 values compared to subjects with normal hepatic function receiving 
the standard fosamprenavir / ritonavir 700 mg /100 mg twice daily regimen.  
 
In subjects with moderate hepatic impairment (Child-Pugh score of 7-9), a reduced dose of 
fosamprenavir 450 mg twice daily with a reduced dosing frequency of ritonavir 100 mg once daily is 
predicted to deliver similar plasma amprenavir Cmax and AUC(0-12), but approximately 35 % lower 
plasma total amprenavir C12 values and approximately 88 % higher plasma unbound amprenavir C12 
values than achieved in subjects with normal hepatic function receiving the standard fosamprenavir 
with ritonavir 700 mg / 100 mg twice daily regimen. Predicted exposures are based on extrapolation 
from data observed following administration of fosamprenavir 300 mg twice daily with ritonavir 
100 mg once daily in subjects with moderate hepatic impairment. 
 
In subjects with severe hepatic impairment (Child-Pugh score of 10-13), a reduced dose of 
fosamprenavir 300 mg twice daily with a reduced dosing frequency of ritonavir 100 mg once daily 
delivered 19% lower plasma amprenavir Cmax, 23% lower AUC(0-12), and 38% lower C12 values, but 
similar unbound plasma amprenavir C12 values than achieved in subjects with normal hepatic 
function receiving the standard fosamprenavir with ritonavir 700 mg / 100 mg twice daily regimen. 
Despite reducing the dosing frequency of ritonavir, subjects with severe hepatic impairment had 64% 
higher ritonavir Cmax, 40% higher ritonavir AUC(0-24), and 38% higher ritonavir C12 than achieved in 
subjects with normal hepatic function receiving the standard fosamprenavir with ritonavir 700 mg / 
100 mg twice daily regimen.   
 
Fosamprenavir with ritonavir was generally well-tolerated in subjects with mild, moderate, or severe 
hepatic impairment, and these regimens had similar adverse event and clinical laboratory profiles as 
previous studies of HIV-1 infected subjects with normal hepatic function. 
 
Pregnancy 
 
Amprenavir (APV) pharmacokinetics were studied in pregnant women receiving FPV/RTV 700/100 
mg twice daily during the second trimester (n=6) or third trimester (n=9) and postpartum. APV 
exposure was 25-35% lower during pregnancy. APV geometric mean (95% CI) and Ctau values were 
1.31 (0.97, 1.77), 1.34 (0.95, 1.89), and 2.03 (1.46, 2.83) µg/mL for the second trimester, third 
trimester, and postpartum, respectively and within the range of values in non-pregnant patients on the 
same FPV/RTV containing regimens.  

 
5.3 Preclinical safety data 
 



31 

Toxicity was similar to that of amprenavir and occurred at amprenavir plasma exposure levels below 
human exposure after treatment with fosamprenavir in combination with ritonavir at the recommended 
dose. 
 
In repeated dose toxicity studies in adult rats and dogs, fosamprenavir produced evidence of 
gastrointestinal disturbances (salivation, vomiting and soft to liquid faeces), and hepatic changes 
(increased liver weights, raised serum liver enzyme activities and microscopic changes, including 
hepatocyte necrosis). Toxicity was not aggravated when juvenile animals were treated as compared 
with adult animals, but the data did indicate a steeper dose response. 
 
In reproductive toxicity studies with fosamprenavir in rats, male fertility was not affected. In females, 
at the high dose, there was a reduction in the weight of gravid uterus (0 to 16%) probably due to a 
reduction of the number of ovarian corporea lutea and implantations. In pregnant rats and rabbits there 
were no major effects on embryo-foetal development. However, the number of abortions increased. In 
rabbits, systemic exposure at the high dose level was only 0.3 times human exposure at the maximum 
clinical dose and thus the developmental toxicity of fosamprenavir has not been fully determined. In 
rats exposed pre- and post-natally to fosamprenavir, pups showed impaired physical and functional 
development and reduced growth. Pup survival was decreased. In addition, decreased number of 
implantation sites per litter and a prolongation of gestation were seen when pups were mated after 
reaching maturity. 
 
Fosamprenavir was not mutagenic or genotoxic in a standard battery of in vitro and in vivo assays. In 
long-term carcinogenicity studies with fosamprenavir in mice and rats, there were increases in 
hepatocellular adenomas and hepatocellular carcinomas in mice at exposure levels equivalent to 0.1 to 
0.3-fold those in humans given 700 mg of fosamprenavir plus 100 mg ritonavir twice daily, and 
increases in hepatocellular adenomas and thyroid follicular cell adenomas in rats at exposure levels 
equivalent to 0.3 to 0.6-fold those in humans given 700 mg of fosamprenavir plus 100 mg ritonavir 
twice daily. The relevance of the hepatocellular findings in the rodents for humans is uncertain; 
however, there is no evidence from clinical trials or marketed use to suggest that these findings are of 
clinical significance. Repeat dose studies with fosamprenavir in rats produced effects consistent with 
hepatic enzyme induction, which predisposes rats to thyroid neoplasms. The thyroid tumorigenic 
potential is regarded to be species-specific. The clinical relevance of these findings is unknown. In rats 
only there was an increase in interstitial cell hyperplasia in males at exposure levels equivalent to 0.5-
fold those in humans, and an increase in uterine endometrial adenocarcinoma in females at an 
exposure level equivalent to 1.1-fold those in humans. The incidence of endometrial findings was 
slightly increased over concurrent controls, but within background range for female rats. The 
relevance of the uterine endometrial adenocarcinomas for humans is uncertain; however there is no 
evidence from clinical trials or marketed use to suggest that these findings are of clinical significance. 
 
 
6.  PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core: 
Microcrystalline cellulose 
Croscarmellose sodium 
Povidone K30 
Magnesium stearate 
Colloidal anhydrous silica 
 
Tablet film-coat: 
Hypromellose 
Titanium dioxide (E171) 
Glycerol triacetate 
Iron oxide red (E172) 



32 

 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
3 years. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5 Nature and contents of container 
 
HDPE bottles with a child resistant polypropylene closure containing 60 tablets. 
 
6.6 Special precautions for disposal 
 
Any unused medicinal product should be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
8. MARKETING AUTHORISATION NUMBER 
 
EU/1/04/282/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 12 July 2004 
Date of renewal of authorisation: 15 May 2009. 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMA) http://www.ema.europa.eu



33 

1. NAME OF THE MEDICINAL PRODUCT 
 
Telzir 50 mg/ml oral suspension 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each ml of oral suspension contains 50 mg fosamprenavir as fosamprenavir calcium (equivalent to 
approximately 43 mg amprenavir). 
 
Excipients: 
Methyl parahydroxybenzoate (E218)  1.5 mg/ml 
Propyl parahydroxybenzoate (E216)   0.2 mg/ml  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Oral suspension 
 
The suspension is white to off-white in colour. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Telzir in combination with low dose ritonavir is indicated for the treatment of Human 
Immunodeficiency Virus Type 1 (HIV-1) infected adults, adolescents and children of 6 years and 
above in combination with other antiretroviral medicinal products. 
 
In moderately antiretroviral experienced adults, Telzir in combination with low dose ritonavir has not 
been shown to be as effective as lopinavir / ritonavir. No comparative studies have been undertaken in 
children or adolescents. 
 
In heavily pretreated patients the use of Telzir in combination with low dose ritonavir has not been 
sufficiently studied. 
 
In protease inhibitor (PI) experienced patients, the choice of Telzir should be based on individual viral 
resistance testing and treatment history (see section 5.1). 
 
4.2 Posology and method of administration 
 
Telzir must only be given with low dose ritonavir as a pharmacokinetic enhancer of amprenavir and in 
combination with other antiretroviral medicinal products. The Summary of Product Characteristics of 
ritonavir must therefore be consulted prior to initiation of therapy with Telzir. 
 
Therapy should be initiated by a physician experienced in the management of HIV infection. 
 
Fosamprenavir is a pro-drug of amprenavir and must not be administered concomitantly with other 
medicinal products containing amprenavir. 
 
The importance of complying with the full recommended dosing regimen should be stressed to all 
patients. 



34 

 
Caution is advised if the recommended dose of fosamprenavir with ritonavir detailed below are 
exceeded (see section 4.4). 
 
Telzir suspension is administered orally.  
 
Shake the bottle vigorously for 20 seconds before first dose is removed and 5 seconds before each 
subsequent dose. 
 
Telzir is also available as 700 mg film-coated tablets. 
 
Adults 
 
In adults, the oral suspension should be taken without food and on an empty stomach. 
 
Please refer to the table below for the dosing recommendations in adults. 
 
Paediatric patients (from 6 years of age) 
 
In paediatric patients, the oral suspension should be taken with food in order to aid palatability and 
assist compliance (see section 5.2). 
 
Telzir oral suspension is the recommended option for the most accurate dosing in children based on 
body weight. 
 
Please refer to the table below for the dosing recommendations in paediatric patients. 
 
No dosing recommendations can be made for children weighing less than 25 kg. 
 
Children less than 6 years of age 
 
Telzir with ritonavir is not recommended in children below 6 years due to insufficient data on 
pharmacokinetics, safety and antiviral response (see section 5.2). 
 
Dosing recommendations for Telzir with ritonavir 
 

Age  Body 
weight 

Telzir dose  
(TWICE DAILY) 
 

Ritonavir dose 
(TWICE DAILY) 

Adult 
(>18 
years) 

 Tablet or Oral suspension  
 
700 mg (1 tablet or 14 ml 
suspension) 
 
Oral suspension should be 
taken without food 

Capsule or Solution 
 
100 mg  

6-17 years >39 kg Tablet or Oral suspension  
 
700 mg (1 tablet or 14 ml 
suspension) 
 
Oral suspension should be 
taken with food 

Capsule or Solution 
 
100 mg 

 



35 

 33-38 kg Oral suspension 
 
18 mg/kg (0.36 ml/kg );  
maximum 700 mg or 14 ml 
 
Oral suspension should be 
taken with food 

Capsule or Solution 
 
100 mg 

25-32 kg Oral suspension 
 
18 mg/kg (0.36 ml/kg ) 
 
Oral suspension should be 
taken with food 

Solution 
 
3 mg/kg 
 

<25 kg No dosing recommendations 
 

 

<6 years  Not recommended 
 

 

 
Elderly (over 65 years of age) 
 
The pharmacokinetics of fosamprenavir have not been studied in this patient population (see section 
5.2).  Therefore, no recommendations can be made in this patient population. 
 
Renal impairment 
 
No dose adjustment is considered necessary in patients with renal impairment (see section 5.2). 
 
Hepatic impairment 
 
For adults with mild hepatic impairment (Child-Pugh score: 5-6) the recommended dose is 700 mg 
fosamprenavir twice daily with 100 mg ritonavir once daily. 
 
For adults with moderate hepatic impairment (Child-Pugh score: 7-9) the recommended dose is 
450 mg fosamprenavir (i.e. 9 ml Telzir oral suspension) twice daily with 100 mg ritonavir once daily. 
This adjusted dose has not been evaluated in a clinical study and has been derived from extrapolation 
(see section 5.2). 
 
For adults with severe hepatic impairment (Child-Pugh score: 10-15): fosamprenavir should be used 
with caution and at a reduced dose of 300 mg fosamprenavir twice daily with 100 mg ritonavir once 
daily.  
 
Overall, even with these dose adjustments for adults with hepatic impairment, some patients may have 
higher or lower than anticipated amprenavir and/or ritonavir plasma concentrations as compared to 
patients with normal hepatic function, due to increased inter-patient variability (see section 5.2), 
therefore close monitoring of safety and virologic response is warranted. 
 
In this patient population, the oral suspension should be taken without food and on an empty stomach. 
 
No dose recommendation can be made for children and adolescents with hepatic impairment as no 
studies have been conducted in these age groups. 
 
4.3 Contraindications 
 
Hypersensitivity to fosamprenavir, amprenavir, or ritonavir, or to any of the excipients listed in section 
6.1. 



36 

 
Telzir must not be administered concurrently with medicinal products with narrow therapeutic 
windows that are substrates of cytochrome P450 3A4 (CYP3A4), e.g. alfuzosin, amiodarone, 
astemizole, bepridil, cisapride, dihydroergotamine, ergotamine, pimozide, quetiapine, quinidine, 
terfenadine, oral midazolam (for caution on parenterally administered midazolam, see section 4.5), 
oral triazolam, sildenafil used for the treatment of pulmonary arterial hypertension (for use of 
sildenafil in patients with erectile dysfunction, see sections 4.4 and 4.5). 
 
Co-administration of the antipsychotic medicinal product lurasidone and fosamprenavir/ritonavir 
(FPV/RTV) is contraindicated (see section 4.5).   
 
Co-administration of paritaprevir and fosamprenavir/ritonavir (FPV/RTV) is contraindicated due to 
the expected increase of paritaprevir exposure and the lack of clinical data assessing the magnitude of 
this increase (see section 4.5). 
 
Concomitant use of Telzir with simvastatin or lovastatin is contraindicated because of increased 
plasma concentrations of lovastatin and simvastatin which can increase the risk of myopathy, 
including rhabdomyolysis (see section 4.5). 
 
Telzir with ritonavir must not be co-administered with medicinal products with narrow therapeutic 
windows that are highly dependent on CYP2D6 metabolism e.g. flecainide and propafenone (see 
section 4.5). 
 
Combination of rifampicin with Telzir with concomitant low-dose ritonavir is contraindicated (see 
section 4.5). 
 
Herbal preparations containing St John’s wort (Hypericum perforatum) must not be used while taking 
Telzir due to the risk of decreased plasma concentrations and reduced clinical effects of amprenavir 
(see section 4.5). 
 
4.4 Special warnings and precautions for use 
 
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.  
 
Patients should be advised that treatment with the Telzir, or any other current antiretroviral therapy, 
does not cure HIV and that they may still develop opportunistic infections and other complications of 
HIV infection.  
 
Fosamprenavir contains a sulphonamide moiety. The potential for cross-sensitivity between medicinal 
products in the sulphonamide class and fosamprenavir is unknown. In the pivotal studies of Telzir, in 
patients receiving fosamprenavir with ritonavir there was no evidence of an increased risk of rashes in 
patients with a history of sulphonamide allergy versus those who did not have a sulphonamide allergy. 
Yet, Telzir should be used with caution in patients with a known sulphonamide allergy. 
 
The Telzir oral suspension contains propyl and methyl parahydroxybenzoate. These products may 
cause an allergic reaction in some individuals. This reaction may be delayed. 
 
Co-administration of Telzir 700 mg twice daily with ritonavir in doses greater than 100 mg twice daily 
has not been clinically evaluated. The use of higher ritonavir doses might alter the safety profile of the 
combination and therefore is not recommended. 
 
 
Liver disease 
 



37 

Telzir with ritonavir should be used with caution and at reduced doses in adults with mild, moderate or 
severe hepatic impairment (see section 4.2). 
 
Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an 
increased risk of severe and potentially fatal hepatic adverse reactions. In case of concomitant antiviral 
therapy for hepatitis B or C, please refer also to the relevant Summary of Product Characteristics 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. 
 
Medicinal products – interactions 
 
The use of Telzir concomitantly with halofantrine or lidocaine (systemic) is not recommended. 
 
PDE5 inhibitors used for the treatment of erectile dysfunction: The use of Telzir concomitantly with 
PDE5 inhibitors (e.g. sildenafil, tadalafil, vardenafil) is not recommended (see section 4.5). 
Co-administration of Telzir with low dose ritonavir and these medicinal products is expected to 
substantially increase their concentrations and may result in PDE5 inhibitor-associated adverse events 
such as hypotension, visual changes and priapism (see section 4.5). Note that co-administration of 
Telzir with low dose ritonavir with sildenafil used for the treatment of pulmonary arterial hypertension 
is contraindicated (see section 4.3). 
 
A reduction in the rifabutin dosage by at least 75 % is recommended when administered with Telzir 
with ritonavir. Further dose reduction may be necessary (see section 4.5). 
 
Because there may be an increased risk of hepatic transaminase elevations and hormonal levels may 
be altered with co-administration of fosamprenavir, ritonavir and oral contraceptives, alternative non-
hormonal methods of contraception are recommended for women of childbearing potential (see 
section 4.5). 
No data are available on the co-administration of fosamprenavir and ritonavir with oestrogens and/or 
progestogens when used as hormonal replacement therapies. The efficacy and safety of these therapies 
with fosamprenavir and ritonavir has not been established. 
 
Anticonvulsants (carbamazepine, phenobarbital) should be used with caution. Telzir may be less 
effective due to decreased amprenavir plasma concentrations in patients taking these medicinal 
products concomitantly (see section 4.5). 
 
Therapeutic concentration monitoring is recommended for immunosuppressant medicinal products 
(cyclosporine, tacrolimus, rapamycin) when co-administered with Telzir (see section 4.5). 
 
Therapeutic concentration monitoring is recommended for tricyclic antidepressants (e.g. desipramine 
and nortriptyline) when co-administered with Telzir (see section 4.5). 
 
When warfarin or other oral anticoagulants are co-administered with Telzir a reinforced monitoring of 
INR (International normalised ratio) is recommended (see section 4.5). 
 
Concomitant use of Telzir with ritonavir and fluticasone or other glucocorticoids that are metabolised 
by CYP3A4 is not recommended unless the potential benefit of treatment outweighs the risk of 
systemic corticosteroid effects, including Cushing’s syndrome and adrenal suppression (see section 
4.5). 
 
 



38 

Co-administration of fosamprenavir/ritonavir with other antineoplastics metabolised by CYP3A (for 
example dasatinib, nilotinib, ibrutinib, vinblastine and everolimus) may increase concentrations of 
these medicinal products, potentially increasing the risk of adverse events usually associated with 
these agents. Please refer to the relevant product information for these medications (see section 4.5).   
 
Hepatitis C virus (HCV) Direct-Acting Antivirals: When hepatitis C virus direct-acting antiviral 
(DAA) drugs, which are metabolised by CYP3A4 or are inducers/inhibitors of CYP3A4, are co-
administered with fosamprenavir/ritonavir, altered plasma concentrations of medications are expected 
due to inhibition or induction of CYP3A4 enzyme activity (see section 4.3 and 4.5). 
 
Rash / cutaneous reactions 
 
Most patients with mild or moderate rash can continue Telzir. Appropriate antihistamines (e.g. 
cetirizine dihydrochloride) may reduce pruritus and hasten the resolution of rash. Severe and 
life-threatening skin reactions, including Stevens-Johnson syndrome, were reported in less than 1% of 
patients included in the clinical development programme. Telzir should be permanently discontinued 
in case of severe rash, or in case of rash of moderate intensity with systemic or mucosal symptoms 
(see section 4.8). 
 
Haemophiliac patients 
 
There have been reports of increased bleeding including spontaneous skin haematomas and 
haemarthroses in haemophiliac patients type A and B treated with protease inhibitors (PIs). In some 
patients administration of factor VIII was necessary. In more than half of the reported cases, treatment 
with protease inhibitors was continued, or reintroduced if treatment had been discontinued. A causal 
relationship has been evoked, although the mechanism of action has not been elucidated. 
Haemophiliac patients should therefore be informed of the possibility of increased bleeding. 
 
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. 
 
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 mycobacterium infections, 
and Pneumocystis carinii pneumonia. Any inflammatory symptoms should be evaluated and treatment 
instituted when necessary. Autoimmune disorders (such as Graves’ disease) have also been reported to 
occur in the setting of immune reactivation; however, the reported time to onset is more variable and 
can occur many months after initiation of treatment. 
 
Osteonecrosis 
 
Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol 
consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been 
reported particularly in patients with advanced HIV-disease and/or long-term exposure to CART. 
Patients should be advised to seek medical advice if they experience joint aches and pain, joint 
stiffness or difficulty in movement. 
 



39 

4.5 Interaction with other medicinal products and other forms of interaction 
 
When fosamprenavir and ritonavir are co-administered, the ritonavir metabolic drug 
interaction profile may predominate because ritonavir is a more potent CYP3A4 inhibitor. The 
full prescribing information for ritonavir must therefore be consulted prior to initiation of 
therapy with Telzir with ritonavir. Ritonavir also inhibits CYP2D6 but to a lesser extent than 
CYP3A4. Ritonavir induces CYP3A4, CYP1A2, CYP2C9 and glucuronosyl transferase. 
 
Additionally, both amprenavir, the active metabolite of fosamprenavir, and ritonavir are primarily 
metabolised in the liver by CYP3A4. Therefore, any medicinal products that either share this 
metabolic pathway or modify CYP3A4 activity may modify the pharmacokinetics of amprenavir and 
ritonavir. Similarily, administration of fosamprenavir with ritonavir may modify the pharmacokinetics 
of other active substances that share this metabolic pathway. 
 
Interaction studies have only been performed in adults. 
 
Unless otherwise stated, studies detailed below have been performed with the recommended dosage of 
fosamprenavir/ritonavir (i.e. 700/100 mg twice daily), and the interaction was assessed under steady-
state conditions where drugs were administered for 10 to 21 days, 
 
 

Drugs by Therapeutic Area Interaction 
 
Geometric mean change 
(%) 
 
(Possible mechanism) 

Recommendation 
concerning co-
administration 

ANTIRETROVIRAL 
MEDICINAL PRODUCTS 
 

  

Non-nucleoside reverse 
transcriptase inhibitors: 
 

  

Efavirenz  
600 mg once daily  
 

No clinically significant 
interaction is observed. 

No dosage adjustment 
necessary. 

Nevirapine  
200 mg twice daily  
 

No clinically significant 
interaction is observed. 
 

No dosage adjustment 
necessary. 
 

Etravirine 
 
 
(Study conducted in 8 
patients) 

Amprenavir AUC ↑↑ 69% 
Amprenavir Cmin ↑ 77% 
Amprenavir Cmax ↑ 62% 
 
Etravirine AUC ↔a 
Etravirine Cmin↔a 
Etravirine Cmax↔a 
 

 a Comparison based on 
historic control. 

Telzir may require dose 
reduction (using oral 
suspension). 

Nucleoside / Nucleotide 
reverse transcriptase 
inhibitors: 
 

  

Abacavir 
Lamivudine  

No clinically significant 
interaction is expected. 

No dosage adjustment 
necessary. 



40 

Zidovudine  
 
Study performed with 
amprenavir. 
 
No FPV/RTV drug 
interaction studies. 
 

  

Didanosine chewable tablet 
 
No drug interaction studies. 
 

No clinically significant 
interaction is expected. 
 

No dose separation or dosage 
adjustment necessary (see 
Antacids).  
 
 

Didanosine gastro-resistant 
capsule 
 
No drug interaction studies. 
 

No clinically significant 
interaction is expected. 
 
 

No dosage adjustment 
necessary. 

Tenofovir disoproxil 
245 mg once daily 
 

No clinically significant 
interaction observed. 
 
 

No dosage adjustment 
necessary. 

 
 

Protease Inhibitors: 
According to current treatment guidelines, dual therapy with protease inhibitors is generally 
not recommended. 
Lopinavir / ritonavir 
400 mg/100 mg  
twice daily  
 
 
 
 
 
 
 
 
 
 
 
 
 
Lopinavir / ritonavir 
533 mg/133 mg twice daily  
 
 
(Telzir 1400 mg twice daily) 
 

Lopinavir: Cmax ↑ 30% 
Lopinavir: AUC ↑ 37% 
Lopinavir: Cmin ↑ 52% 
 
Amprenavir: Cmax ↓ 58% 
Amprenavir: AUC ↓ 63% 
Amprenavir: Cmin ↓ 65% 
 
Lopinavir: Cmax ↔* 
Lopinavir: AUC ↔* 
Lopinavir: Cmin ↔* 
* compared to lopinavir / 
ritonavir 400 mg/100 mg 
twice daily 
 
Amprenavir: Cmax ↓ 13%* 
Amprenavir: AUC ↓ 26%* 
Amprenavir: Cmin ↓ 42 %* 
* compared to fosamprenavir 
/ ritonavir 700 mg/100 mg 
twice daily  
 
(Mixed CYP3A4 
induction/inhibition, Pgp 
induction) 

Concomitant use is not 
recommended. 
 

Indinavir 
Saquinavir 
 

 No dose recommendations 
can be given. 



41 

 
No drug interaction studies.  
 
Atazanavir 
 
300 mg once daily  
 
 

Atazanavir: Cmax ↓ 24%* 
Atazanavir: AUC ↓ 22%*  
Atazanavir: Cmin↔* 
 *compared to atazanavir/ 
ritonavir 300 mg/ 100 mg 
once daily  
 
Amprenavir: Cmax ↔ 
Amprenavir: AUC ↔ 
Amprenavir: Cmin ↔ 
 

No dosage adjustment 
necessary. 

Integrase inhibitors 
 
Raltegravir 
 
400 mg twice daily 

Fasting state 
 
Amprenavir :  
Cmax ↓ 14% (-36%; +15%) 
AUC ↓ 16% (-36%; +8%) 
Cmin ↓ 19% (-42%; +13%)  
 
Raltegravir: 
Cmax ↓ 51% (-75%; -3%) 
AUC ↓ 55% (-76%; -16%) 
Cmin ↓ 36 % (-57%; -3%)  
 
Fed state 
 
Amprenavir: 
Cmax ↓ 25% (-41%; -4%) 
AUC ↓ 25% (-42%; -3%) 
Cmin ↓ 33% (-50%; -10%)  
 
Raltegravir:  
Cmax ↓ 56% (-70%; -34%) 
AUC ↓ 54% (-66%; -37%) 
Cmin ↓ 54 % (-74%; -18%)  
 

Concomitant use is not 
recommended. Significant 
reductions in exposure and 
Cmin observed for both 
amprenavir and raltegravir 
(especially in fed conditions) 
may result in virological 
failure in patients. 

Dolutegravir 
 
50 mg once daily 

Dolutegravir 
 
Cmax ↓ 24%  
AUC ↓ 35% 
Cτ ↓ 49% 
 
Amprenavir: Cmax ↔ 
Amprenavir: AUC ↔ 
Amprenavir: Cmin ↔ 
 

No dosage adjustment of 
fosamprenavir or 
dolutegravir is recommended 
based on observed exposure-
response relationships of 
clinical data. Caution is 
warranted and close 
monitoring is recommended 
when this combination is 
given in integrase inhibitor-
resistant patients. 

CCR5-receptor antagonists 
 



42 

 Maraviroc  
 
300 mg twice daily 

Maraviroc: AUC12 ↑ 2.49 
Maraviroc: Cmax ↑ 1.52 
Maraviroc: C12 ↑ 4.74 
 
Amprenavir: AUC12 ↓ 0.65 
Amprenavir: Cmax ↓ 0.66 
Amprenavir: C12 ↓ 0.64 
 
Ritonavir AUC12 ↓ 0.66 
Ritonavir Cmax ↓ 0.61 
Ritonavir C12 ↔ 0.86 
 

Concomitant use is not 
recommended.  Significant 
reductions in amprenavir Cmin 
observed may result in 
virological failure in patients. 

 
Anti-hepatitis C virus medicinal products 
 
   
   
Simeprevir 
Daclatasvir 

Not studied.  
Results from studies with 
other HIV protease inhibitors 
and simeprevir or daclatasvir, 
suggest that co-
administration with 
fosamprenavir/ritonavir is 
likely to lead to increased 
plasma exposures of 
simeprevir or daclatasvir due 
to CYP3A4 enzyme 
inhibition. 

Not recommended. 

Paritaprevir  
(co-formulated with 
ritonavir and ombitasvir 
and co-administered with 
dasabuvir) 

Not studied.  
Results from studies with 
other HIV protease inhibitors 
and paritaprevir/ritonavir/ 
ombitasvir +/- dasabuvir 
suggest that co-
administration of 
fosamprenavir/ritonavir with 
paritaprevir/ritonavir/ 
ombitasvir +/- dasabuvir is 
likely to lead to increased 
plasma exposures of 
paritaprevir due to CYP3A4 
enzyme inhibition and higher 
ritonavir dose.  

Contraindicated (see section 
4.3). 

ANTIARRHYTHMICS 
 

  

Amiodarone 
Bepridil 
Quinidine 
Flecainide 
Propafenone 
 

Amiodarone: ↑ expected 
Bepridil: ↑ expected 
Quinidine: ↑ expected 
 
(CYP3A4 inhibition by 
FPV/RTV)   
 
Flecainide: ↑ expected 
Propafenone: ↑ expected 

Contraindicated (see section 
4.3). Potential for serious 
and/or life-threatening 
reactions such as cardiac 
arrhythmias. 



43 

 
 (CYP2D6 inhibition by 
RTV) 

ERGOT DERIVATIVES 
 

  

Dihydroergotamine 
Ergotamine 
Ergonovine 
Methylergonovine 

Dihydroergotamine: ↑ 
expected 
Ergonovine: ↑ expected 
Ergotamine: ↑ expected 
Methylergonovine: ↑ 
expected 
 
(CYP3A4 inhibition by 
FPV/RTV) 

Contraindicated (see section 
4.3). Potential for serious 
and/or life-threatening 
reactions such as acute ergot 
toxicity characterized by 
peripheral vasospasm and 
ischemia of the extremities 
and other tissues. 

GASTROINTESTINAL 
MOTILITY AGENTS 
 

  

Cisapride Cisapride: ↑ expected 
 
(CYP3A4 inhibition by 
FPV/RTV) 

Contraindicated (see section 
4.3). Potential for serious 
and/or life-threatening 
reactions such as cardiac 
arrhythmias. 

ANTIHISTAMINES 
(HISTAMINE H1 
RECEPTOR 
ANTAGONISTS) 

  

Astemizole 
Terfenadine 

Astemizole: ↑ expected 
Terfenadine: ↑ expected 
 
(CYP3A4 inhibition by 
FPV/RTV) 

Contraindicated (see section 
4.3). Potential for serious 
and/or life-threatening 
reactions such as cardiac 
arrhythmias. 

NEUROLEPTIC 
 

  

Pimozide Pimozide: ↑ expected 
 
(CYP3A4 inhibition by 
FPV/RTV) 

Contraindicated (see section 
4.3). Potential for serious 
and/or life-threatening 
reactions such as cardiac 
arrhythmias. 

ANTIPSYCHOTICS 
Quetiapine 
 
 

Due to CYP3A inhibition by 
Telzir, concentrations of 
quetiapine are expected to 
increase. 

Concomitant administration 
of Telzir and quetiapine is 
contra-indicated as it may 
increase quetiapine-related 
toxicity.  Increased plasma 
concentrations of quetiapine 
may lead to coma. 

Lurasidone 
 
 
 
 
No FPV/RTV drug 
interaction studies 

Lurasidone: ↑ expected 
(CYP3A4 inhibition) 

Concomitant administration 
of fosamprenavir /ritonavir 
with lurasidone is 
contraindicated due to the 
potential for serious and/or 
life-threatening reactions 
related to lurasidone (see 
section 4.3) 

 



44 

INFECTION 
 

  

Antibacterials: 
 

  

Clarithromycin 
 
Study performed with 
amprenavir. 
 
No FPV/RTV drug 
interaction studies. 

Clarithromycin: moderate ↑ 
expected 
 
(CYP3A4 inhibition) 

Use with caution. 
 

Erythromycin 
 
No drug interaction studies. 
 

Erythromycin: ↑ expected 
 
(CYP3A4 inhibition by 
FPV/RTV 

Use with caution. 

Anti-mycobacterial: 
 

  

Rifabutin 
150 mg every other day  
 
 
 

Rifabutin: Cmax ↓ 14%* 
Rifabutin: AUC(0-48) ↔* 
 
25-O-desacetylrifabutin: Cmax 
↑ 6-fold* 
25-O-desacetylrifabutin: 
AUC(0-48) ↑ 11-fold* 
*compared to rifabutin 
300 mg once daily  
 
Amprenavir exposure 
unchanged when compared 
to historical data. 
 
(Mixed CYP3A4 
induction/inhibition) 

The increase of 25-O-
desacetylrifabutin (active 
metabolite) could potentially 
lead to an increase of 
rifabutin related adverse 
events, notably uveitis. 
 
A 75 % reduction of the 
standard rifabutin dose (i.e. 
to 150 mg every other day) is 
recommended. Further dose 
reduction may be necessary 
(see section 4.4). 
 

Rifampicin  
600 mg once daily 
 
(Amprenavir without 
ritonavir) 
 
No FPV/RTV drug 
interaction studies 
 

Amprenavir: AUC ↓ 82% 
 
 
Significant ↓ APV expected 
 
 
(CYP3A4 induction by 
rifampicin) 

Contraindicated (see section 
4.3.) 
 
The decrease in amprenavir 
AUC can result in virological 
failure and resistance 
development.  During 
attempts to overcome the 
decreased exposure by 
increasing the dose of other 
protease inhibitors with 
ritonavir, a high frequency of 
liver reactions was seen. 

 
Anti-fungals: 
 

  

Ketoconazole 
200 mg once daily for four 
days 
 
 
 

Ketoconazole: Cmax ↑ 25% 
Ketoconazole: AUC ↑ 2.69-
fold. 
 
Amprenavir: Cmax ↔ 
Amprenavir: AUC ↔ 

High doses (> 200 mg/day) 
of ketoconazole or 
itraconazole are not 
recommended. 



45 

 
 
 
Itraconazole 
 
No drug interaction studies. 
 

Amprenavir: Cmin ↔ 
 
 
Itraconazole: ↑ expected 
 
(CYP3A4 inhibition by 
FPV/RTV) 
 

ANTACIDS, HISTAMINE 
H2 RECEPTOR 
ANTAGONIST AND 
PROTON-PUMP 
INHIBITORS 
 

  

Single 30 ml dose of antacid 
suspension (equivalent to 
3.6 grams aluminium 
hydroxide and 1.8 grams 
magnesium hydroxide 
 
(Telzir 1400 mg single dose) 
 
 
Ranitidine 
300 mg single dose 
 
(Telzir 1400 mg single dose) 
 
Esomeprazole 
20 mg once daily 
 
 

Amprenavir: Cmax ↓ 35% 
Amprenavir: AUC ↓ 18% 
Amprenavir: Cmin (C12h) ↔ 
 
 
 
 
 
 
Amprenavir: Cmax ↓ 51% 
Amprenavir: AUC ↓ 30% 
Amprenavir: Cmin (C12h) ↔ 
 
 
Amprenavir Cmax ↔ 
Amprenavir AUC ↔ 
Amprenavir Cmin (C12h) ↔ 
 
(Increase in gastric pH) 

No dosage adjustment 
necessary with antacids, 
proton-pump inhibitors or 
histamine H2 receptor 
antagonists.  
 
 

ANTICONVULSANTS  
 

  

Phenytoin 
300 mg once daily 
 

Phenytoin: Cmax ↓ 20% 
Phenytoin: AUC ↓ 22% 
Phenytoin: Cmin ↓ 29% 
 
(Modest induction of 
CYP3A4 by FPV/RTV) 
 
Amprenavir: Cmax ↔ 
Amprenavir: AUC ↑ 20% 
Amprenavir: Cmin ↑ 19% 

It is recommended that 
phenytoin plasma 
concentrations be monitored 
and phenytoin dose increased 
as appropriate.  
 

 
Phenobarbital 
Carbamazepine 
 
No drug interaction studies. 
 

Amprenavir: ↓ expected 
 
(Modest CYP3A4 
induction) 
 

Use with caution (see 
section 4.4). 

Lidocaine 
(by systemic route) 
 
No drug interaction studies. 

Lidocaine: ↑ expected 
 
(CYP3A4 inhibition by 
FPV/RTV) 

Concomitant use is not 
recommended.  It may cause 
serious adverse reactions 
(see section 4.4). 



46 

 
Halofantrine 
 
No drug interaction studies. 

Halofantrine: ↑ expected 
 
(CYP3A4 inhibition by 
FPV/RTV) 
 

Concomitant use is not 
recommended.  It may cause 
serious adverse reactions 
(see section 4.4). 

 PDE5 INHIBITORS 
 

  

Sildenafil 
Vardenafil 
Tadalafil 
 
No drug interaction studies. 
 

PDE5 inhibitors: ↑ expected 
 
(CYP3A4 inhibition by 
FPV/RTV) 
 
 

Concomitant use is not 
recommended. It may result 
in an increase in PDE5 
inhibitor associated adverse 
reactions, including 
hypotension, visual changes 
and priapism (refer to PDE5 
inhibitor prescribing 
information). Patients should 
be warned about these 
possible side effects when 
using PDE5 inhibitors with 
Telzir/ritonavir (see section 
4.4). Note that co-
administration of Telzir with 
low dose ritonavir with 
sildenafil used for the 
treatment of pulmonary 
arterial hypertension is 
contraindicated (see section 
4.3). 

INHALED/NASAL 
STEROIDS 
 

  

Fluticasone propionate  
50 µg intranasal 4 times daily) 
for 7 days 
 
(Ritonavir 100 mg capsules 
twice daily for 7 days) 
 

Fluticasone propionate: ↑ 
 
Intrinsic cortisol levels: ↓ 
86 %. 
 
The effects of high 
fluticasone systemic 
exposure on ritonavir 
plasma levels are unknown. 
 
Greater effects may be 
expected when fluticasone 
propionate is inhaled.  
 
(CYP3A4 inhibition by 
FPV/RTV) 

 Concomitant use is not 
recommended unless the 
potential benefit of treatment 
outweighs the risk of 
systemic corticosteroid 
effects (see section 4.4). A 
dose reduction of the 
glucocorticoid with close 
monitoring of local and 
systemic effects or a switch 
to a glucocorticoid, which is 
not a substrate for CYP3A4 
(e.g. beclomethasone) 
should be considered. In 
case of withdrawal of 
glucocorticoids, progressive 
dose reduction may have to 
be performed over a longer 
period (see section 4.4). 

ALPHA 1-
ADRENORECEPTOR 
ANTAGONIST 

  



47 

Alfuzosin, 
 
 
 

Potential for increased 
alfuzosin concentrations 
which can result in 
hypotension. The 
mechanism of interaction is 
CYP3A4 inhibition by 
fosamprenavir/ritonavir. 

Co-administration of 
TELZIR/ritonavir with 
alfuzosin is contraindicated 
(see section 4.3). 

 
HERBAL PRODUCTS 
 

  

St. John’s wort (Hypericum 
perforatum) 

Amprenavir ↓ expected 
 
(CYP3A4 induction by St. 
John’s wort) 
 

Herbal preparations 
containing St John’s wort 
must not be combined with 
Telzir (see section 4.3). If a 
patient is already taking St 
John’s wort, check 
amprenavir, ritonavir and 
HIV RNA and stop St John’s 
wort. Amprenavir and 
ritonavir levels may increase 
on stopping St John’s wort. 
The inducing effect may 
persist for at least 2 weeks 
after cessation of treatment 
with St John’s wort. 

HMG-COA REDUCTASE 
INHIBITORS 
 

  

Lovastatin 
Simvastatin 
 
 
No drug interaction studies. 
 

Lovastatin: ↑ expected 
 
Simvastatin: ↑ expected 
 
(CYP3A4 inhibition by 
FPV/RTV) 
 
 

Contraindicated (see section 
4.3). 
Increased concentrations of 
HMG-CoA reductase 
inhibitors may cause 
myopathy, including 
rhabdomyolysis. 
 
Pravastatin or fluvastatin are 
recommended because their 
metabolism is not dependent 
on CYP 3A4 and 
interactions are not expected 
with protease inhibitors.  

Atorvastatin 
10 mg once daily for 4 days 
 
 

Atorvastatin: Cmax ↑ 184% 
Atorvastatin: AUC ↑ 153% 
Atorvastatin: Cmin ↑ 73% 
 
Amprenavir: Cmax ↔ 
Amprenavir: AUC ↔ 
Amprenavir: Cmin ↔ 
 
(CYP3A4 inhibition by 
FPV/RTV) 
 

Doses of atorvastatin no 
greater than 20 mg/day 
should be administered, with 
careful monitoring for 
atorvastatin toxicity. 
 

IMMUNOSUPPRESSANTS  
 

 



48 

Cyclosporin 
Rapamycin 
Tacrolimus 
 
No drug interaction studies. 
 

Cyclosporin: ↑ expected 
Rapamycin: ↑ expected 
Tacrolimus: ↑ expected  
 
(CYP3A4 inhibition by 
FPV/RTV) 

Frequent therapeutic 
concentration monitoring of 
immunosuppressant levels is 
recommended until levels 
have stabilised (see section 
4.4). 

 
BENZODIAZEPINES 
 

  

Midazolam 
 
No drug interaction studies. 

Midazolam: ↑ expected (3-4 
fold  for parenteral 
midazolam)  
 
Based on data with other 
protease inhibitors plasma 
concentrations of 
midazolam are expected to 
be significantly higher when 
midazolam is given orally. 
 
(CYP3A4 inhibition by 
FPV/RTV) 
 

Telzir/ritonavir should not 
be co-administered with 
orally administered 
midazolam (see section 4.3), 
whereas  
caution should be used with 
co-administration of 
Telzir/ritonavir and 
parenteral midazolam. 
 
If Telzir/ritonavir is co-
administered with parenteral 
midazolam, it should be 
done in an intensive care 
unit (ICU) or similar setting 
which ensures close clinical 
monitoring and appropriate 
medical management in case 
of respiratory depression 
and/or prolonged sedation. 
Dosage adjustment for 
midazolam should be 
considered, especially if 
more than a single dose of 
midazolam is administered. 

TRICYCLIC 
ANTIDEPRESSANTS 
 

  

Desipramine 
Nortriptyline 
 
No drug interaction studies. 

Tricyclic antidepressant: ↑ 
expected 
 
(Mild CYP2D6 inhibition 
by RTV) 
 

Careful monitoring of the 
therapeutic and adverse 
reactions of tricyclic 
antidepressants is 
recommended (see section 
4.4).  

OPIOIDS 
 

  

Methadone 
≤ 200 mg once daily 
 

(R-) methadone: Cmax ↓  
21% 
(R-) methadone: AUC ↓ 
18% 
 
 (CYP induction by 
FPV/RTV) 

The decrease of (R-) 
methadone (active 
enantiomer) is not expected 
to be clinically significant.   
As a precaution, patients 
should be monitored for 
withdrawal syndrome. 

ORAL ANTICOAGULANTS 
 



49 

Warfarin 
Other oral anticoagulants 
 
No drug interaction studies. 

Possible ↓ or ↑ of 
antithrombotic effect. 
 
(Induction and/or inhibition 
of CYP2C9 by RTV) 

Reinforced monitoring of the 
International Normalised 
Ratio is recommended (see 
section 4.4). 
 

 
ORAL CONTRACEPTIVES 
 

  

Ethinyl estradiol 0.035 
mg/norethisterone 0.5 mg 
once daily  
 
 

Ethinyl estradiol: Cmax 
↓28% 
Ethinyl estradiol: AUC 
↓37% 
 
Norethisterone: Cmax ↓ 38% 
Norethisterone: AUC ↓ 34% 
Norethisterone: Cmin ↓ 26 
 
(CYP3A4 induction by 
FPV/RTV) 
 
Amprenavir: Cmax ↔* 
Amprenavir: AUC ↔* 
Amprenavir: Cmin ↔* 
* compared to historical 
data 
 
Ritonavir: Cmax ↑ 63%* 
Ritonavir: AUC ↑ 45%* 
* compared to historical 
data 
 
Clinically significant hepatic 
transaminase elevations 
occurred in some subjects.  
 

Alternative non-hormonal 
methods of contraception are 
recommended for women of 
childbearing potential (see 
section 4.4). 

SELECTIVE SEROTONIN 
REUPTAKE INHIBITORS 
(SSRIS) 
 

  

Paroxetine 
 
20 mg once daily 
 
 

Paroxetine: Cmax ↓ 51% 
Paroxetine: AUC ↓ 55% 
 
Amprenavir: Cmax ↔* 
Amprenavir: AUC ↔* 
Amprenavir: Cmin ↔* 
* compared to historical 
data 
 
Mechanism unknown. 

Dose titration of paroxetine 
based on a clinical 
assessment of antidepressant 
response is recommended. 
Patients on stable dose of 
paroxetine who start 
treatment with Telzir and 
ritonavir should be 
monitored for antidepressant 
response. 

ANTINEOPLASTIC AGENTS  
METABOLISED BY CYP3A 
Examples of antineoplastic 
agents:  
dasatinib  
nilotinib  

dasatinib: ↑ expected 
nilotinib: ↑ expected 
ibrutinib: ↑ expected 
vinblastine: ↑ expected 

When antineoplastic agents 
that are metabolised by 
CYP3A are co-administered 
with 



50 

ibrutinib  
vinblastine 
 everolimus 
 
No FPV/RTV drug interaction 
studies 

 everolimus: ↑ expected 
(CYP3A4 inhibition) 

fosamprenavir/ritonavir, 
plasma concentrations of 
these antineoplastic 
medications may be 
increased and could increase 
the risk of adverse events 
usually associated with these 
antineoplastic agents. In case 
of concomitant 
administration with 
antineoplastic agents 
metabolized by CYP3A, 
please refer to the relevant 
product information for 
these medications. 
 

 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
As a general rule, when deciding to use antiretroviral agents for the treatment of HIV infection in 
pregnant women and consequently for reducing the risk of HIV vertical transmission to the newborn, 
the animal data (see section 5.3) as well as the clinical experience in pregnant women should be taken 
into account.  
 
There is limited clinical experience (less than 300 pregnancy outcomes) from the use of fosamprenavir 
in pregnant women. Placental transfer of amprenavir has been shown to occur in humans. 
 
In animal studies at systemic plasma exposures (AUC) to amprenavir lower than therapeutic exposure 
in patients treated with Telzir, some developmental toxicity was observed (see section 5.3). In view of 
the low exposure in reproductive toxicity studies, the potential developmental toxicity of Telzir has 
not been fully determined. 
 
Telzir should be used during pregnancy only if the potential benefit justifies the potential risk to the 
foetus. 
 
Breast-feeding 
 
Amprenavir-related material was found in rat milk, but it is not known whether amprenavir is excreted 
in human milk. Rat pups exposed pre and post-natally to amprenavir and fosamprenavir showed 
developmental toxicity (see section 5.3). 
 
It is recommended that HIV-infected women must not breast-feed under any circumstances to avoid 
transmission of HIV. 
 
Fertility 
 
No human data on the effect of fosamprenavir on fertility are available. In rats, there was no major 
effect on fertillty or reproductive performance with fosamprenavir (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 



51 

No studies on the effects of Telzir in combination with ritonavir on the ability to drive and use 
machines have been performed. The adverse reaction profile of Telzir should be borne in mind when 
considering the patient’s ability to drive or operate machinery (see section 4.8). 
 
4.8 Undesirable effects 
 
It should be noted that the Telzir oral suspension has not been evaluated clinically in adults and that 
the adverse reaction profile detailed in this section is based on the experience in adults with the Telzir 
film coated tablets. 
 
Summary of safety profile 

The adverse reaction profile was similar across all the respective adult studies: antiretroviral naïve 
patients (APV30002, ESS100732), protease inhibitor experienced (twice daily dosing, APV30003) 
patients. This is based on safety data from a total of 864 patients exposed to fosamprenavir/ritonavir in 
these three studies. 
 
The most frequently (> 5% of adult subjects treated) reported adverse reactions with 
fosamprenavir/ritonavir combination were gastrointestinal reactions (nausea, diarrhoea, abdominal 
pain and vomiting) and headache. Most adverse reactions  associated with fosamprenavir/ritonavir 
combination therapies were mild to moderate in severity, early in onset and rarely treatment limiting. 
More serious adverse reactions such as serious skin rashes and hepatic transaminase elevations have 
also been reported (cf paragraph Description of selected adverse reactions). 
 
Tabulated summary of adverse reactions 

Adverse reactions are listed by MedDRA system organ class and absolute frequency. Frequencies are 
defined as: Very common (≥ 1/10), Common (≥ 1/100 to < 1/10), Uncommon (≥ 1/1,000 to < 1/100), 
Rare (≥ 1/10,000 to < 1/1,000) or Very rare (< 1/10,000), or Not known. 
 
Frequency categories for the reactions below have been based on clinical trials and postmarketing 
data. 
 
Most of the adverse reactions below were reported from three large clinical studies in adults, where 
the adverse events were of at least moderate intensity (Grade 2 or more) occurring in at least 1% of 
patients and reported by investigators as being attributable to the medicinal products used in the 
studies.  
 

Body System Adverse reaction Frequency 
 
Nervous system disorders 
 

 
Headache, dizziness, oral 
paraesthesia 
 

 
Common 

 
Gastrointestinal disorders 

 
Diarrhoea 

 
Very common 

  
Loose stools, nausea, vomiting, 
abdominal pain 

 
Common 

 
Skin and subcutaneous tissue 
disorders 
 

 
Stevens Johnson syndrome 
 
Angioedema 
 
Rash (see text below 
“rash/cutaneous reactions”) 
 

 
Rare 
 
Uncommon 
 
Common 
 
 



52 

 
 

 
 

 
General disorders and 
administration site conditions 
 

 
Fatigue 

 
Common 

Investigations Blood cholesterol increased 
 
Blood triglycerides increased 
 
Alanine aminotransferase 
increased 
 
Aspartate aminotransferase 
increased 
 
Lipase increased 

Very common 
 
Common 
 
Common 
 
 
Common 
 
 
Common 

 
Description of selected adverse reactions 

 
Rash / cutaneous reactions: erythematous or maculopapular cutaneous eruptions, with or without 
pruritus, may occur during therapy. The rash generally will resolve spontaneously without the 
necessity of discontinuing treatment with the fosamprenavir with ritonavir. 
 
Severe or life-threatening cases of rash, including Stevens-Johnson syndrome are rare. Fosamprenavir 
with ritonavir therapy should be definitively stopped in case of severe rash or in case of rash of mild or 
moderate intensity associated with systemic or mucosal signs (see section 4.4). 
 
Clinical chemistry abnormalities: clinical chemistry abnormalities (Grade 3 or 4) potentially related to 
treatment with fosamprenavir with ritonavir and reported in greater than or equal to 1 % of adult 
patients, included:  
increased ALT (common), AST (common), serum lipase (common) and triglycerides (common).  
 
Metabolic parameters: weight and levels of blood lipids and glucose may increase during antiretroviral 
therapy (see section 4.4). 
 
Rhabdomyolysis: an increase in CPK, myalgia, myositis, and rarely, rhabdomyolysis, have been 
reported with protease inhibitors, more specifically in association with nucleoside analogues. 
 
Immune Reactivation Syndrome: in HIV-infected patients with severe immune deficiency at the time 
of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic 
or residual opportunistic infections may arise.  Autoimmune disorders (such as Graves’ disease) 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 (see section 4.4). 
 
Osteonecrosis: cases of osteonecrosis have been reported, particularly in patients with generally 
acknowledged risk factors, advanced HIV disease or long-term exposure to CART. The frequency of 
this is unknown (see section 4.4). 
 
Paediatric / other populations 

Children and adolescents: the adverse reaction profile in children and adolescents is based on 
integrated safety data from two studies (APV29005 Week 24 data and APV20003 Week 168 data 
[final data]) in which 158 HIV-1 infected subjects 2 to 18 years of age received fosamprenavir with 
ritonavir with background nucleoside reverse transcriptase inhibitor therapy (see section 5.1 for 



53 

information on dosing regimens applied for each age group). 79 % of subjects received greater than 48 
weeks of exposure. 
Overall the safety profile in these 158 children and adolescents was similar to that observed in the 
adult population. Vomiting occurred more frequently amongst paediatric patients. Drug-related 
adverse reactions were more common in APV20003 (57%) where subjects received once daily 
fosamprenavir / ritonavir when compared to APV29005 (33%) where subjects received twice daily 
fosamprenavir / ritonavir. 
No new safety concerns were identified from analyses of 48 week data from studies APV29005 or 
APV20002, in which 54 subjects 4 weeks to <2 years of age received twice daily fosamprenavir / 
ritonavir with background nucleoside reverse transcriptase inhibitor therapy and 5 subjects received 
only single doses of fosamprenavir with or without ritonavir. 
 
Haemophiliac patients: there have been reports of increased spontaneous bleeding in haemophiliac 
patients receiving antiretroviral protease inhibitors (see section 4.4). 
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
There is no known antidote for Telzir. It is not known whether amprenavir can be removed by 
peritoneal dialysis or haemodialysis. If overdose occurs, the patient should be monitored for evidence 
of toxicity (see section 4.8) and standard supportive treatment applied as necessary. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antivirals for systemic use, protease inhibitor, ATC Code: J05AE07 
 
Mechanism of action 
 
The in vitro antiviral activity observed with fosamprenavir is due to the presence of trace amounts of 
amprenavir. Amprenavir is a competitive inhibitor of the HIV-1 protease. Amprenavir binds to the 
active site of HIV-1 protease and thereby prevents the processing of viral gag and gag-
pol polyprotein precursors, resulting in the formation of immature non-infectious viral 
particles. 
 
Administration of fosamprenavir 700 mg twice daily with ritonavir 100 mg twice daily results in 
plasma amprenavir concentrations (data from study APV30003 in antiretroviral experienced patients) 
which results in protein adjusted median ratios of Cmin/IC50 and Cmin/IC95 of 21.7 (range 1.19-240) and 
3.21 (range 0.26-30.0), respectively. 
 
Antiviral activity in vitro 
 
The in vitro antiviral activity of amprenavir was evaluated against HIV-1 IIIB in both acutely and 
chronically infected lymphoblastic cell lines (MT-4, CEM-CCRF, H9) and in peripheral blood 
lymphocytes. The 50% inhibitory concentration (IC50) of amprenavir ranged from 0.012 to 0.08 µM in 
acutely infected cells and was 0.41 µM in chronically infected cells (1 µM = 0.50 µg/ml). The 
relationship between in vitro anti-HIV-1 activity of amprenavir and the inhibition of HIV-1 replication 
in humans has not been defined. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


54 

Resistance 
 
In vivo 
 

a)ART-naïve or PI-naïve patients 
 
Various regimens have been assessed in the amprenavir/fosamprenavir development programs with 
and without co-administration of ritonavir. Analysis of the virological failure samples across these 
regimens defined four main resistance pathways: V32I+I47V, I50V, I54L/M and I84V.  Additional 
mutations observed which may contribute to resistance were: L10V/F/R, I13V, K20R/T, L33F/V, 
M36I, M46I/L, I47V/L Q58E, I62V, L63P, V77I, I85V, and I93L.   

 
When ART naïve adult patients were treated with the currently approved doses of 
fosamprenavir/ritonavir, as for other ritonavir boosted PI regimens, the mutations described were 
infrequently observed. Sixteen of 434 ART-naïve patients who received fosamprenavir 700 
mg/ritonavir 100 mg twice daily in ESS100732 experienced virological failure by Week 48 with 14 
isolates genotyped. Three of 14 isolates had protease resistance mutations. One resistance mutation 
was observed in each of 3 isolates: K20K/R, I54I/L and I93I/L respectively  
 
Among the 81 PI-naïve paediatric patients treated with fosamprenavir / ritonavir, 15 patients met 
protocol-defined virological failure through 48 weeks in APV29005 and up to 108 weeks in 
APV20003.  Treatment-emergent major or APV-associated protease mutations were observed in virus 
isolated from 2 patients. Resistance patterns were similar to those observed in adults. 
 
 b) PI-experienced patients 
 
Amprenavir  
 
In the studies of PI-experienced adult patients, PRO30017 (amprenavir 600 mg / ritonavir 100 mg 
twice daily in sub-study A and B with 80 and 37 patients respectively), the following mutations 
emerged in patients with virological failure: L10F/I/V, V11I, I13V, K20R, V32I, L33F, E34Q, M36I, 
M46I/L, I47V, G48V, I50V, I54L/M/T/V, Q58E, D60E, I62V, A71V, V77I, V82A/I, I84V, I85V, 
L90M and I93L/M. 
 
Fosamprenavir 
 
In the studies of PI-experienced adult patients, APV30003 and its extension, APV30005 
(fosamprenavir 700 mg / ritonavir 100 mg twice daily: n=107), the following mutations emerged in 
patients experiencing virological failure through 96 weeks: L10F/I, L24I, V32I, L33F, M36I, M46I/L, 
I47V, I50V, I54L/M/S, A71I/T/V, G73S, V82A, I84V, and L90M.  
 
In the paediatric studies APV20003 and APV29005, 77 PI-experienced patients were treated with 
fosamprenavir / ritonavir-based regimens and 43 patients met study-defined virologic failure criteria 
through 48 weeks in APV29005 and up to 108 weeks in APV20003. Treatment-emergent major 
protease or APV-associated mutations were observed in virus isolated from 1 patient in APV29005 
and 6 patients from APV20003.  The mutational profiles were similar to those described for 
PI-experienced adults treated with fosamprenavir / ritonavir. 
 
Antiviral activity according to genotypic/phenotypic resistance 
 
Genotypic resistance testing 
 
Genotypic interpretation systems may be used to estimate the activity of amprenavir / ritonavir or 
fosamprenavir / ritonavir in subjects with PI-resistant isolates. The current (July 2006) ANRS AC-11 
algorithm for fosamprenavir / ritonavir defines resistance as the presence of the mutations 
V32I+I47A/V, or I50V, or at least four mutations among: L10F/I/V, L33F, M36I, I54A/L/M/S/T/V, 



55 

I62V, V82A/C/F/G, I84V and L90M and is associated with increased phenotypic resistance to 
fosamprenavir with ritonavir as well as reduced likelihood of virological response (resistance). 
Conclusions regarding the relevance of particular mutations or mutational patterns are subject to 
change with additional data, and it is recommended to always consult current interpretation systems 
for analysing resistance test results. 
 
Phenotypic resistance testing 
 
Clinically validated phenotypic interpretation systems may be used in association with the genotypic 
data to estimate the activity of amprenavir / ritonavir or fosamprenavir / ritonavir in patients with PI-
resistant isolates.  Resistance testing diagnostic companies have developed clinical phenotypic cut-offs 
for FPV/RTV that can be used to interpret resistance test results. 
 
Clinical experience 
 
Clinical experience with fosamprenavir boosted with ritonavir is mainly based on two open label 
studies, one in antiretroviral naïve patients (study ESS100732), and one study in antiretroviral 
experienced patients (study APV30003). Both of these studies compared fosamprenavir/ritonavir with 
lopinavir / ritonavir. 
 
Antiretroviral Naïve Adult Patients 
 
In a randomised open-label study (ESS100732 - KLEAN) in antiretroviral naïve patients, 
fosamprenavir (700 mg) co-administered with low dose ritonavir (100 mg) in a twice daily regimen 
including abacavir / lamivudine (600 mg / 300 mg) fixed dose combination tablet once daily showed 
comparable efficacy over 48 weeks to lopinavir / ritonavir (400 mg / 100 mg) given twice daily in 
combination with abacavir / lamivudine (600 mg / 300 mg once daily). 
 
Non-inferiority was demonstrated between fosamprenavir co-administered with ritonavir and lopinavir 
/ ritonavir based on the proportions of patients achieving plasma HIV-1 RNA levels < 400 copies/ml at 
48 weeks (primary endpoint). In the Time to loss of virological response (TLOVR) analysis for the 
ITT(E) population, the proportion of patients achieving <400 copies/ml was 73 % (315 / 434) in the 
fosamprenavir with ritonavir group compared to 71 % (317 / 444) of patients receiving lopinavir / 
ritonavir, with a 95 % confidence interval of the difference of [-4,84%; 7;05%].  
 
Efficacy outcomes by subgroups are described in the table below. 
 
Table 1   Efficacy Outcome at Week 48 in ESS100732 (ART-Naïve Patients) 

 FPV/RTV 700 mg/100 mg 
BID (n= 434) 

LPV/RTV 400 mg/100 mg BID 
(n=444) 

ITT-E Population 
TLOVR analysis 

Proportion with HIV-1 RNA < 400 copies/ml 

All Subjects 72.5 % 71.4% 

Baseline HIV-1 RNA 
 < 100,000 copies/ml 

69.5 % (n=197) 69.4% (n=209) 

Baseline HIV-1 RNA 
 ≥ 100,000 copies/ml 

75.1% (n=237) 73.2% (n=235) 

 Proportion with HIV-1 RNA < 50 copies/ml 



56 

All Subjects 66% 65% 

Baseline HIV-1 RNA  
< 100,000 copies/ml 

67% (n=197) 64% (n=209) 

Baseline HIV-1 RNA  
≥ 100,000 copies/ml 

65% (n=237) 66% (n=235) 

 Median Change from baseline in CD4 cells (cells/µl) 

ITT-E observed 
analysis 

176 (n=323) 191 (n=336) 

 
Following completion of the 48 week treatment period, subjects at European and Canadian sites were 
eligible to participate in a study extension to Week 144 maintaining their treatment regimen as per the 
original randomisation. Only 22% of the original population of the KLEAN study was enrolled in the 
study extension 
 
Efficacy outcomes are described in the table below. 
 
Table 2   Efficacy Outcome at Weeks 96 and 144 in ESS100732 Extension (ART-Naïve Patients) 

 FPV/RTV 700 mg/100 mg 

BID (n= 105) 

LPV/RTV 400 mg/100 mg BID 

(n=91) 

ITT (Ext) Population 

TLOVR analysis 

Proportion with HIV-1 RNA < 400 copies/ml 

Week 96 93% 87% 

Week 144 83% 70% 

 Proportion with HIV-1 RNA < 50 copies/ml 

Week 96 85% 75% 

Week 144 73% 60% 

ITT (Ext)  

Observed analysis 
Median Change from baseline in CD4 cells (cells/µl) 

Week 96 292 (n=100) 286 (n=84) 

Week 144 300 (n=87)  335 (n=66) 

 
Antiretroviral Experienced Adult Patients 
 
In a randomised open-label study (APV30003) in protease inhibitor experienced patients with 
virological failure (less than or equal to two PIs) the fosamprenavir with ritonavir (700 / 100 mg twice 
daily or 1400 / 200 mg once daily) did not demonstrate non-inferiority to lopinavir / ritonavir with 
regard to viral suppression as measured by the average area under the curve minus baseline 
(AAUCMB) for plasma HIV-1 RNA over 48 weeks (the primary end point). Results were in favour of 
the lopinavir / ritonavir arm as detailed below. 



57 

 
All patients in this study had failed treatment with a previous protease inhibitor regimen (defined as 
plasma HIV-1 RNA that never went below 1,000 copies/ml after at least 12 consecutive weeks of 
therapy, or initial suppression of HIV-1 RNA which subsequently rebounded to ≥ 1,000 copies/ml). 
However, only 65 % of patients were receiving a PI based regimen at study entry. 
 
The population enrolled mainly consisted of moderately antiretroviral experienced patients. The 
median durations of prior exposure to NRTIs were 257 weeks for patients receiving fosamprenavir 
with ritonavir twice daily (79 % had ≥ 3 prior NRTIs) and 210 weeks for patients receiving 
lopinavir/ritonavir (64 % had ≥ 3 prior NRTIs). The median durations of prior exposure to protease 
inhibitors were 149 weeks for patients receiving fosamprenavir with ritonavir twice daily (49 % 
received ≥ 2 prior PIs) and 130 weeks for patients receiving lopinavir/ritonavir (40 % received 
≥2 prior PIs). 
The mean AAUCMBs (log10 c/ml) in the ITT (E) population (Observed analysis) at 48 weeks (primary 
end-point) and other efficacy outcomes by subgroup are described in the tables below: 
 
 
Table 3   Efficacy at Week 48 Outcomes in APV30003 ITT(E) Population (ART-experienced 
Patients) 

 FPV/RTV BID 

(N=107) 

LPV/RTV BID 

(N=103) 

AAUCMB Observed Analysis Mean (n) Mean (n) 

All Patients -1.53 (105) -1.76 (103) 

     1000 – 10,000 copies/ml -1.53 (41) -1.43 (43) 

     >10,000 – 100,000 copies/ml -1.59 (45) -1.81 (46) 

     >100,000 copies/ml -1.38 (19) -2.61 (14) 

FPV/RTV BID vs LPV/RTV BID AAUCMB Mean Diff (97.5% CI) 

All Patients 0.244 (-0.047, 0.536) 

     1000 – 10,000 copies/ml -0.104 (-0.550, 0.342) 

     >10,000 – 100,000 copies/ml 0.216 (-0.213, 0.664) 

     >100,000 copies/ml 1.232 (0.512, 1.952) 

AAUCMB Observed Analysis Mean (n) Mean (n) 

All Patients -1.53 (105) -1.76 (103) 

         CD4-count    <50 -1.28 (7) -2.45 (8) 

                              ≥50 -1.55 (98) -1.70 (95) 

                              <200 -1.68 (32) -2.07 (38) 

                             ≥ 200  -1.46 (73) -1.58 (65) 



58 

         GSS to OBT1       0 -1.42 (8) -1.91 (4) 

                                     1 -1.30 (35) -1.59 (23) 

                                   ≥ 2 -1.68 (62) -1.80 (76) 

All Patients, RD=F Analysis2  n (%) n(%) 

Subjects (%) with plasma HIV-1 RNA 
<50 copies/ml 

49 (46%) 52 (50%) 

Subjects (%) with plasma HIV-1 RNA 
<400 copies/ml 

62 (58%) 63 (61%) 

Subjects with >1 log10 change from 
baseline in plasma  HIV-
1 RNA 

62 (58%) 71 (69%) 

Change from baseline in CD4 cells 
(cells/µl) 

Median (n) Median (n) 

All Patients 81 (79) 91 (85) 

Key: 1GSS to OBT: Genotypic Sensitivity Score to Optimised Background. GSS was derived using 
ANRS 2007 guidelines. 2RD=F: Rebound or discontinuation equal failure analysis which is equivalent to 
TLOVR. FPV/RTV BID – Fosamprenavir with ritonavir twice daily, LPV/RTV BID – Lopinavir / 
ritonavir twice daily 
 
Table 4   AAUCMB at Week 48 by genotypic sensitivity score in OBT and baseline resistance to 

FPV/RTV 

 Week 48 AAUCMB 

(n) 

Genotypic Sensitivity 
Score in OBT 

All Subjects Susceptiple to 
FPV/RTV 

< 4 mutations from 
score 

Resistant to 
FPV/RTV 

≥ 4 mutations from 
score 

0 -1.42 (8) -1.83 (4) -1.01 (4) 

1 -1.30 (35) -1.42 (29) -0.69 (6) 

≥ 2 -1.68 (62) -1.76 (56) -0.89 (6) 

All patients -1.53 (105) -1.65 (89) -0.85 (16) 

 
As shown in the above table, there were only 16 patients harbouring baseline virus with resistance to 
FPV/RTV according to the ANRS score. Data from this small number further analysed by GSS 
subgroups need to be interpreted with caution. 
 
There are insufficient data to recommend the use of fosamprenavir with ritonavir in heavily pre-treated 
patients. 
 
Children and adolescent patients above the age of six 



59 

 
Fosamprenavir tablets and oral suspension with ritonavir in combination with NRTIs have been 
evaluated in protease inhibitor naïve and experienced children and adolescent patients.  The benefit in 
this age group has mainly been derived from study APV29005, an open label 48 week study 
evaluating the pharmacokinetic profiles, safety, and antiviral activity of fosamprenavir with ritonavir 
administered twice daily to HIV 1 protease inhibitor experienced and naive patients 2 to 18 years of 
age. Results through 48 weeks of treatment are provided below. 
 
APV29005 enrolled 30 patients aged 6 to 11 (the majority of whom were treated with fosamprenavir / 
ritonavir 18/3 mg/kg twice daily or the adult tablet regimen) and 40 patients aged 12 to 18 (the 
majority of whom were treated with the adult tablet regimen).  
 
Table 5. Baseline Characteristics and Efficacy Outcomes at Week 48 in APV29005 ITT(E) 
Population 

 Patients aged 6 to 11 
N=30 

Patients aged 12 to 18 
N=40 

Baseline Characteristics   
ART/PI status, n (%)   

ART-naïve 2 (7) 14 (35) 
ART-experienced, PI-naïve 8 (27) 12 (30) 
PI-experienced 20 (67) 14 (35) 

Median duration of prior ART exposure, weeks   
NRTI 386        409 
PI 253 209 

Median plasma HIV-1 RNA log10 copies/mL 4.6 (n=29) 4.7 
>100,000 copies/ml, n (%) 9 (31) 13 (33) 
Median CD4 cells/μl 470 250 

CD4 count < 350 cells/μl, n (%) 10 (33) 27 (68) 
Efficacy Outcomes   
Patients with plasma HIV-1 RNA <400 
copies/ml, Snapshot analysis 

16 (53%) 25 (63%) 

Median change from baseline in CD4 cells 
(cells/μl), observed analysis 

210 (n=21) 140 (n=35) 

 
These data were further substantiated by the supportive study APV20003; however, a different dosage 
regimen than that of study APV29005 was used. 
 
5.2 Pharmacokinetic properties 
 
After oral administration, fosamprenavir is rapidly and almost completely hydrolysed to amprenavir 
and inorganic phosphate prior to reaching the systemic circulation. The conversion of fosamprenavir 
to amprenavir appears to primarily occur in the gut epithelium. 
 
The pharmacokinetic properties of amprenavir following co-administration of Telzir with ritonavir 
have been evaluated in healthy adult subjects and HIV-infected patients and no substantial differences 
were observed between these two groups. 
 
Telzir tablet and oral suspension formulations, both given fasted, delivered equivalent plasma 
amprenavir AUC∞ values and the Telzir oral suspension formulation delivered a 14 % higher plasma 
amprenavir Cmax as compared to the oral tablet formulation. However, the bioequivalence could not be 
demonstrated when the oral suspension was given with food. Therefore for adult patients the Telzir 
oral suspension should be taken without food and on an empty stomach (see section 4.2). 
 
Absorption 
 



60 

After single dose administration of fosamprenavir, amprenavir peak plasma concentrations are 
observed approximately 2 hours after administration. Fosamprenavir AUC values are, in general, less 
than 1 % of those observed for amprenavir. The absolute bioavailability of fosamprenavir in humans 
has not been established. 
 
After multiple dose oral administration of equivalent fosamprenavir and amprenavir doses, 
comparable amprenavir AUC values were observed; however, Cmax values were approximately 30 % 
lower and Cmin values were approximately 28 % higher with fosamprenavir.  
 
Co-administration of ritonavir with fosamprenavir increase plasma amprenavir AUC by approximately 
2-fold and plasma Cτ,ss by 4- to 6-fold, compared to values obtained when fosamprenavir is 
administered alone. 
 
After multiple dose oral administration of fosamprenavir 700 mg with ritonavir 100 mg twice daily, 
amprenavir was rapidly absorbed with a geometric mean (95 % CI) steady state peak plasma 
amprenavir concentration (Cmax) of 6.08 (5.38-6.86) µg/ml occurring approximately 1.5 (0.75-5.0) 
hours after dosing (tmax). The mean steady state plasma amprenavir trough concentration (Cmin) was 
2.12 (1.77-2.54) µg/ml and AUC0-tau was 39.6 (34.5–45.3) h*µg/ml. 
 
Administration of the fosamprenavir oral suspension formulation with a high fat meal (967 kcal, 
67 grams fat, 33 grams protein, 58 grams carbohydrate) reduced plasma amprenavir AUC(0-∞) by 
28% and Cmax by 46% and delayed Tmax by 0.72 hours. For adult patients the fosamprenavir oral 
suspension should be taken without food and on an empty stomach. In children and adolescents the 
fosamprenavir oral suspension should be taken with food. The dose recommendations for this 
population therefore take into account the observed food effect (see section 4.2). 
 
Co-administration of amprenavir with grapefruit juice was not associated with clinically significant 
changes in plasma amprenavir pharmacokinetics. 
 
Distribution 
 
The apparent volume of distribution of amprenavir following administration of Telzir is approximately 
430 l (6 l/kg assuming a 70 kg body weight), suggesting a large volume of distribution, with 
penetration of amprenavir freely into tissues beyond the systemic circulation. This value is decreased 
by approximately 40 % when Telzir is co-administered with ritonavir, most likely due to an increase in 
amprenavir bioavailability. 
 
In in vitro studies, the protein binding of amprenavir is approximately 90 %. It is bound to the alpha-1-
acid glycoprotein (AAG) and albumin, but has a higher affinity for AAG. Concentrations of AAG 
have been shown to decrease during the course of antiretroviral therapy. This change will decrease the 
total active substance concentration in the plasma, however the amount of unbound amprenavir, which 
is the active moiety, is likely to be unchanged. 
 
CSF penetration of amprenavir is negligible in humans. Amprenavir appears to penetrate into semen, 
though semen concentrations are lower than plasma concentrations. 
 
Biotransformation 
 
Fosamprenavir is rapidly and almost completely hydrolysed to amprenavir and inorganic phosphate as 
it is absorbed through the gut epithelium, following oral administration. Amprenavir is primarily 
metabolised by the liver with less than 1 % excreted unchanged in the urine. The primary route of 
metabolism is via the cytochrome P450 3A4 enzyme. Amprenavir metabolism is inhibited by 
ritonavir, via inhibition of CYP3A4, resulting in increased plasma concentrations of amprenavir. 
Amprenavir in addition is also an inhibitor of the CYP3A4 enzyme, although to a lesser extent than 
ritonavir. Therefore medicinal products that are inducers, inhibitors or substrates of CYP3A4 must be 
used with caution when administered concurrently with Telzir with ritonavir (see sections 4.3 and 4.5). 



61 

 
Elimination 
 
Following administration of Telzir, the half-life of amprenavir is 7.7 hours. When Telzir is 
co-administered with ritonavir, the half-life of amprenavir is increased to 15 – 23 hours. 
The primary route of elimination of amprenavir is via hepatic metabolism with less than 1 % excreted 
unchanged in the urine and no detectable amprenavir in faeces. Metabolites account for approximately 
14 % of the administered amprenavir dose in the urine, and approximately 75 % in the faeces. 
 
Special populations 
 
Paediatrics 
 
In a clinical study on pharmacokinetics of fosamprenavir in paediatric patients, eight subjects 12 to 18 
years of age received the standard fosamprenavir adult tablet dose of 700 mg twice daily (with 
ritonavir 100 mg twice daily). Compared to the historical adult population receiving fosamprenavir / 
ritonavir 700 / 100 mg twice daily, 12 to 18 year old subjects had 20 % lower plasma APV AUC(0-
24), 23 % lower Cmax, and 20 % lower Cmin values. Children 6 to 11 years of age (n=9) receiving 
fosamprenavir / ritonavir 18 / 3 mg/kg twice daily had 26 % higher AUC(0-24) and similar Cmax and 
Cmin values when compared to the historical adult population receiving fosamprenavir / ritonavir 700 / 
100 mg twice daily. 
 
APV20002 is a 48 week, Phase II, open label study designed to evaluate the pharmacokinetics, safety, 
tolerability and antiviral activity of fosamprenavir with and without ritonavir in paediatric subjects 4 
weeks to < 2 years of age. Compared to the historical adult population receiving fosamprenavir with 
ritonavir 700 mg / 100 mg twice daily, a subset of five pediatric subjects ages 6 to < 24-months 
receiving fosamprenavir / ritonavir 45/7 mg/kg twice daily demonstrated that despite an approximate 
5-fold increase in fosamprenavir and ritonavir doses on a mg/kg basis, plasma amprenavir AUC(0-τ) 
was approximately 48 % lower, Cmax 26 % lower, and Cτ 29 % lower in the paediatric subjects. No 
dosing recommendations can be made for the very young (children < 2 years of age) and Telzir with 
ritonavir is not recommended for this patient population (see section 4.2). 
 
Elderly 
 
The pharmacokinetics of fosamprenavir in combination with ritonavir has not been studied in patients 
over 65 years of age. 
 
Renal impairment 
 
Patients with renal impairment have not been specifically studied. Less than 1 % of the therapeutic 
dose of amprenavir is excreted unchanged in the urine. Renal clearance of ritonavir is also negligible, 
therefore the impact of renal impairment on amprenavir and ritonavir elimination should be minimal 
 
Hepatic impairment 
 
Fosamprenavir is converted in man to amprenavir. The principal route of amprenavir and ritonavir 
elimination is hepatic metabolism. 
 
The plasma amprenavir pharmacokinetics were evaluated in a 14 day repeat-dose study in HIV-1 
infected adult subjects with mild, moderate, or severe hepatic impairment receiving fosamprenavir 
with ritonavir compared to matched control subjects with normal hepatic function. 
 
In subjects with mild hepatic impairment (Child-Pugh score of 5-6), the dosage regimen of 
fosamprenavir 700 mg twice daily with a reduced dosing frequency of ritonavir 100 mg once daily 
provided slightly higher plasma amprenavir Cmax (17 %), slightly higher plasma amprenavir 
AUC(0-12) (22 %), similar plasma total amprenavir C12 values and approximately 117 % higher 



62 

plasma unbound amprenavir C12 values compared to subjects with normal hepatic function receiving 
the standard fosamprenavir / ritonavir 700 mg /100 mg twice daily regimen.  
 
In subjects with moderate hepatic impairment (Child-Pugh score of 7-9), a reduced dose of 
fosamprenavir 450 mg twice daily with a reduced dosing frequency of ritonavir 100 mg once daily is 
predicted to deliver similar plasma amprenavir Cmax and AUC(0-12), but approximately 35 % lower 
plasma total amprenavir C12 values and approximately 88 % higher plasma unbound amprenavir C12 
values than achieved in subjects with normal hepatic function receiving the standard fosamprenavir 
with ritonavir 700 mg / 100 mg twice daily regimen. Predicted exposures are based on extrapolation 
from data observed following administration of fosamprenavir 300 mg twice daily with ritonavir 
100 mg once daily in subjects with moderate hepatic impairment. 
 
In subjects with severe hepatic impairment (Child-Pugh score of 10-13), a reduced dose of 
fosamprenavir 300 mg twice daily with a reduced dosing frequency of ritonavir 100 mg once daily 
delivered 19% lower plasma amprenavir Cmax, 23% lower AUC(0-12), and 38% lower C12 values, but 
similar unbound plasma amprenavir C12 values than achieved in subjects with normal hepatic 
function receiving the standard fosamprenavir with ritonavir 700 mg / 100 mg twice daily regimen. 
Despite reducing the dosing frequency of ritonavir, subjects with severe hepatic impairment had 64% 
higher ritonavir Cmax, 40% higher ritonavir AUC(0-24), and 38% higher ritonavir C12 than achieved in 
subjects with normal hepatic function receiving the standard fosamprenavir with ritonavir 700 mg / 
100 mg twice daily regimen.   
 
Fosamprenavir with ritonavir was generally well-tolerated in subjects with mild, moderate, or severe 
hepatic impairment, and these regimens had similar adverse event and clinical laboratory profiles as 
previous studies of HIV-1 infected subjects with normal hepatic function. 
 
Pregnancy 
 
Amprenavir (APV) pharmacokinetics were studied in pregnant women receiving FPV/RTV 700/100 
mg twice daily during the second trimester (n=6) or third trimester (n=9) and postpartum. APV 
exposure was 25-35% lower during pregnancy. APV geometric mean (95% CI) and Ctau values were 
1.31 (0.97, 1.77), 1.34 (0.95, 1.89), and 2.03 (1.46, 2.83) µg/mL for the second trimester, third 
trimester, and postpartum, respectively and within the range of values in non-pregnant patients on the 
same FPV/RTV containing regimens.  

 
5.3 Preclinical safety data 
 
Toxicity was similar to that of amprenavir and occurred at amprenavir plasma exposure levels below 
human exposure after treatment with fosamprenavir in combination with ritonavir at the recommended 
dose. 
 
In repeated dose toxicity studies in adult rats and dogs, fosamprenavir produced evidence of 
gastrointestinal disturbances (salivation, vomiting and soft to liquid faeces), and hepatic changes 
(increased liver weights, raised serum liver enzyme activities and microscopic changes, including 
hepatocyte necrosis). Toxicity was not aggravated when juvenile animals were treated as compared 
with adult animals, but the data did indicate a steeper dose response. 
 
In reproductive toxicity studies with fosamprenavir in rats, male fertility was not affected. In females, 
at the high dose, there was a reduction in the weight of gravid uterus (0 to 16%) probably due to a 
reduction of the number of ovarian corporea lutea and implantations. In pregnant rats and rabbits there 
were no major effects on embryo-foetal development. However, the number of abortions increased. In 
rabbits, systemic exposure at the high dose level was only 0.3 times human exposure at the maximum 
clinical dose and thus the development toxicity of fosamprenavir has not been fully determined. In rats 
exposed pre- and post-natally to fosamprenavir, pups showed impaired physical and functional 
development and reduced growth. Pup survival was decreased. In addition, decreased number of 



63 

implantation sites per litter and a prolongation of gestation were seen when pups were mated after 
reaching maturity. 
 
Fosamprenavir was not mutagenic or genotoxic in a standard battery of in vitro and in vivo assays. In 
long-term carcinogenicity studies with fosamprenavir in mice and rats, there were increases in 
hepatocellular adenomas and hepatocellular carcinomas in mice at exposure levels equivalent to 0.1 to 
0.3-fold those in humans given 700 mg of fosamprenavir plus 100 mg ritonavir twice daily, and 
increases in hepatocellular adenomas and thyroid follicular cell adenomas in rats at exposure levels 
equivalent to 0.3 to 0.6-fold those in humans given 700 mg of fosamprenavir plus 100 mg ritonavir 
twice daily. The relevance of the hepatocellular findings in the rodents for humans is uncertain; 
however, there is no evidence from clinical trials or marketed use to suggest that these findings are of 
clinical significance. Repeat dose studies with fosamprenavir in rats produced effects consistent with 
hepatic enzyme induction, which predisposes rats to thyroid neoplasms. The thyroid tumorigenic 
potential is regarded to be species-specific. The clinical relevance of these findings is unknown.  In 
rats only there was an increase in interstitial cell hyperplasia in males at exposure levels equivalent to 
0.5-fold those in humans, and an increase in uterine endometrial adenocarcinoma in females at an 
exposure level equivalent to 1.1-fold those in humans. The incidence of endometrial findings was 
slightly increased over concurrent controls, but within background range for female rats. The 
relevance of the uterine endometrial adenocarcinomas for humans is uncertain; however there is no 
evidence from clinical trials or marketed use to suggest that these findings are of clinical significance. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Hypromellose 
Sucralose 
Propylene glycol 
Methyl parahydroxybenzoate (E218) 
Propyl parahydroxybenzoate (E216) 
Polysorbate 80 
Calcium chloride dihydrate 
Artificial grape bubblegum flavour 
Natural peppermint flavour 
Purified water 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
2 years. 
Discard 28 days after first opening. 
 
6.4 Special precautions for storage 
 
Do not freeze. 
 
6.5 Nature and contents of container 
 
HDPE bottle with a child resistant polypropylene closure containing 225 millilitres oral suspension. 
The pack also includes a polyethylene syringe-adapter and a 10 ml oral dosing syringe comprised of a 
polypropylene barrel (with ml graduations) and a polyethylene plunger. 



64 

 
6.6 Special precautions for disposal 
 
Any unused medicinal product should be disposed of in accordance with local requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER 
 
EU/1/04/282/002 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 12 July 2004 
Date of renewal of authorisation: 15 May 2009. 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency (EMA) http://www.ema.europa.eu 

  



65 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
ANNEX II 

 
A. MANUFACTURER(S) 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 

 



66 

A MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturers responsible for batch release 
 
Film-coated tablets 
Glaxo Wellcome Operations, Priory Street, Ware, Hertfordshire SG12 0DJ, United Kingdom 
 
Glaxo Wellcome S.A., Avenida de Extremadura 3, 09400 Aranda de Duero Burgos, Spain 
 
Oral suspension 
 
Glaxo Operations UK Ltd (trading as GlaxoWellcome Operations), Harmire Road, Barnard Castle, 
Co. Durham DL12 8DT, United Kingdom 
 
or  
 
ViiV Healthcare Trading Services UK Limited, 12 Riverwalk, Citywest Business Campus  
Dublin 24, Ireland 
 
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) 
 
The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP.   
An updated RMP should be submitted 

• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
If the submission of a PSUR and the update of a RMP coincide, they can be submitted at the 
same time. 
 
  



67 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



68 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



69 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON FOR TABLETS 

 
 

1. NAME OF THE MEDICINAL PRODUCT 
 
Telzir 700 mg film-coated tablets 
Fosamprenavir 
 
 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 700 mg fosamprenavir as fosamprenavir calcium (equivalent to 
approximately 600 mg of amprenavir) 
 
 

3. LIST OF EXCIPIENTS 
 
 

4. PHARMACEUTICAL FORM AND CONTENTS 
 
60 film-coated tablets 
 
 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use 
 
Read the package leaflet before use 
 
 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 

8. EXPIRY DATE 
 
EXP 
 
 

9. SPECIAL STORAGE CONDITIONS 
 
 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

  



70 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 

12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/282/001 
 
 

13. BATCH NUMBER 
 
Lot 
 
 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 

15. INSTRUCTIONS ON USE 
 
 

16. INFORMATION IN BRAILLE 
 
telzir 700 mg 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
  



71 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
BOTTLE LABEL FOR TABLETS 

 
 

1. NAME OF THE MEDICINAL PRODUCT 
 
Telzir 700 mg film-coated tablets 
Fosamprenavir 
 
 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 700 mg fosamprenavir as fosamprenavir calcium (equivalent to 
approximately 600 mg of amprenavir) 
 
 

3. LIST OF EXCIPIENTS 
 
 

4. PHARMACEUTICAL FORM AND CONTENTS 
 
60 film-coated tablets 
 
 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use 
 
Read the package leaflet before use 
 
 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 

8. EXPIRY DATE 
 
EXP 
 
 

9. SPECIAL STORAGE CONDITIONS 
 
 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



72 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 

12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/282/001  
 
 

13. BATCH NUMBER 
 
Lot 
 
 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 

15. INSTRUCTIONS ON USE 
 
 
 

16. INFORMATION IN BRAILLE 
 
Only applicable to outer carton 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
  



73 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON FOR ORAL SUSPENSION 

 
 

1. NAME OF THE MEDICINAL PRODUCT 
 
Telzir 50 mg/ml oral suspension 
Fosamprenavir 
 
 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml of oral suspension contains 50 mg fosamprenavir as fosamprenavir calcium (equivalent to 
approximately 43 mg of amprenavir) 
 
 

3. LIST OF EXCIPIENTS 
 
This product also contains preservatives:  
methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate (E216), see leaflet for further 
information 
 
 

4. PHARMACEUTICAL FORM AND CONTENTS 
 
Bottle with 225 ml oral suspension 
A 10 ml graduated dosing syringe and adapter are also provided in the pack 
 
 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use 
 
Read the package leaflet before use 
 
Shake bottle vigorously before use 
 
 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 

8. EXPIRY DATE 
 
EXP 
 
Discard 28 days after first opening 
 



74 

 
9. SPECIAL STORAGE CONDITIONS 

 
Do not freeze 
 
 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 

12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/282/002 
 
 

13. BATCH NUMBER 
 
Lot 
 
 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 

15. INSTRUCTIONS ON USE 
 
 

16. INFORMATION IN BRAILLE 
 
telzir 50 mg/ml 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC:  
SN:  
NN:  
  



75 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
BOTTLE LABEL FOR ORAL SUSPENSION 

 
 

1. NAME OF THE MEDICINAL PRODUCT 
 
Telzir 50 mg/ml oral suspension 
Fosamprenavir 
 
 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each ml of oral suspension contains 50 mg fosamprenavir as fosamprenavir calcium (equivalent to 
approximately 43 mg of amprenavir) 
 
 

3. LIST OF EXCIPIENTS 
 
This product also contains preservatives:  
methyl parahydroxybenzoate (E218) and propyl parahydroxybenzoate (E216), see leaflet for further 
information 
 
 

4. PHARMACEUTICAL FORM AND CONTENTS 
 
225 ml oral suspension 
A 10 ml graduated dosing syringe and adapter are also provided in the pack 
 
 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use 
 
Read the package leaflet before use 
 
Shake bottle vigorously before use 
 
 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
 OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 

8. EXPIRY DATE 
 
EXP 
 
Discard 28 days after first opening 
 



76 

 
9. SPECIAL STORAGE CONDITIONS 

 
Do not freeze 
 
 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 

12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/04/282/002 
 
 

13. BATCH NUMBER 
 
Lot 
 
 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 

15. INSTRUCTIONS ON USE 
 
 
 

16. INFORMATION IN BRAILLE 
 
Only applicable to outer carton 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
   



77 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
B. PACKAGE LEAFLET 



78 

Package leaflet: Information for the user 
 

Telzir 700 mg film-coated tablets 
Fosamprenavir 

 
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 Telzir is and what it is used for 
2.  What you need to know before you take Telzir 
3.  How to take Telzir 
4.  Possible side effects 
5.       How to store Telzir 
6.  Contents of the pack and other information 
 
 
1. What Telzir is and what it is used for 
 
Telzir is used to treat HIV (human immunodeficiency virus) infection.  
  
Telzir is a type of medicine known as an anti-retroviral.  It is taken with low doses of another 
medicine, ritonavir, which boosts the level of Telzir in the blood. Telzir belongs to a group of 
anti-retroviral medicines called protease inhibitors.  Protease is an enzyme produced by HIV which 
enables the virus to multiply in white blood cells (CD4 cells) in your blood.  By stopping protease 
from working, Telzir stops HIV multiplying and infecting more CD4 cells.    
 
Telzir with low doses of ritonavir is used in combination with other anti-retroviral medicines 
(‘combination therapy’) to treat adults, adolescents and children aged over 6 years infected with  
HIV.     
 
HIV can become resistant to anti-HIV medicines.  To avoid this happening, and to stop your illness 
getting worse, it is very important that you keep taking all your medicines exactly as prescribed.  
 
Telzir will not stop you passing on HIV.  HIV infection is spread by sexual contact with someone 
who’s got the infection, or by transfer of infected blood (for example by sharing needles).  
 
 
2. What you need to know before you take Telzir 
 
Telzir is to be taken in combination with low doses of ritonavir and other antiretroviral 
medicines. It is therefore important that you carefully read the package leaflet provided with these 
medicines. If you have any further questions about ritonavir or the other medicines prescribed, please 
ask your doctor or pharmacist. 
 
Do not take Telzir: 
• if you are allergic to fosamprenavir, amprenavir or any of the other ingredients of this medicine 

(listed in section 6), or to ritonavir. 
• if you are taking any of these medicines: 



79 

 
- alfuzosin (used to treat a prostate problem) 
- astemizole or terfenadine (commonly used to treat allergy symptoms – these medicines may be 

available without prescription) 
- pimozide (used to treat schizophrenia)  
- quetiapine (used to treat schizophrenia, bipolar disorder and major depressive disorder)                                                         
- lurasidone (used to treat schizophrenia and bipolar disorder)  
- cisapride (used to relieve indigestion) 
- ergot derivatives (used to treat headaches) 
- rifampicin (used to treat tuberculosis) 
- amiodarone, quinidine, flecainide and propafenone (heart medicines) 
- bepridil (used to treat high blood pressure) 
- oral midazolam or oral triazolam (used to treat anxiety)  
- products containing St John’s wort (Hypericum perforatum)  
- lovastatin, simvastatin (used to lower cholesterol)  
- sildenafil if used to treat pulmonary arterial hypertension, (a condition affecting the blood 

vessels to your lungs) 
- paritaprevir (used to treat hepatitis C virus infection) 

 
 
→Tell your doctor if any of these applies to you. 
 
Take special care with Telzir 
Talk to your doctor or pharmacist before taking Telzir:  
• If you have a known allergy to medicines containing sulphonamide.  You may also be allergic 

to Telzir. 
• If you have liver disease.  Your doctor may lower your dose of Telzir and ritonavir depending on 

the amount of liver damage. You will be monitored while you are taking Telzir. If your liver 
disease gets worse, you may need to stop taking Telzir for a while, or permanently. People with 
hepatitis B or C taking combination therapy are at increased risk of getting severe liver problems.    

• If you have haemophilia. Increased bleeding may occur while taking protease inhibitors (such as 
Telzir). The reason for this is not known. You may need additional factor VIII to control any 
bleeding. 

• If you have diabetes. In some patients taking antiretroviral medicines including protease 
inhibitors, there have been reports of increased sugar in the blood and diabetes getting worse. 
Also, some people have become diabetic while taking these medicines. 

• If you are taking any other medicines.  See section ‘Other medicines and Telzir’. 
 
→Tell your doctor if any of these apply to you.  You will need extra check-ups, including blood 
tests, while you’re taking your medication.   
 
Your doctor will monitor your blood glucose levels before and during treatment with Telzir. 
 
Look out for important symptoms 
Some people taking medicines for HIV infection develop other conditions, which can be serious.  
These include: 
• Flare up of old infections 
• Change in your body shape 
• Problems with your bones. 

You need to know about important signs and symptoms to look out for while you’re taking Telzir. 
Please read the information on ‘Other side effects of combination therapy for HIV’ in section 4 
of this leaflet.  If you have any questions about this information or the advice given: 
→Talk to your doctor.  
 



80 

You may get a skin rash.  However you can still continue to take Telzir. It can be treated with 
antihistamines. Rarely, the skin rash can be severe and serious (Stevens Johnson syndrome). If this 
happens, Telzir must be stopped immediately and you must never take it again. 
 
Protect other people.  HIV infection is spread by sexual contact with someone who has the infection, 
or by transfer of infected blood (for example, by sharing injection needles). 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. 
 
Other medicines and Telzir 
Tell your doctor or pharmacist if you’re taking or have recently taken any other medicines – 
these include herbal medicines or other medicines you bought without a prescription. Your doctor will 
decide if these medicines are suitable for you to take with Telzir and ritonavir. This is very 
important, as Telzir or ritonavir can strengthen or weaken the effects of other medicines.  This can 
sometimes lead to serious medical conditions.  
 
There are some medicines that must not be taken with Telzir. You must check the list of medicines 
under 'Don't take Telzir' at the beginning of section 2 of this leaflet.  
 
These medicines are not recommended with Telzir/ritonavir: 
• doses of ketoconazole and itraconazole greater than 200 mg per day (used to treat fungal 

infections)  
• doses of rifabutin greater than 150 mg every other day (an antibiotic) 
• lidocaine given by injection   
• halofantrine (used to treat malaria) 
• sildenafil, vardenafil or tadalafil (used to treat erectile dysfunction)  
• doses of atorvastatin greater than 20 mg per day (used to lower cholesterol)  
• fluticasone propionate and similar medicines used to treat asthma, unless considered essential. In 

this case close monitoring is required. 
• lopinavir/ritonavir combination (used to treat HIV infection) 
• raltegravir (used to treat HIV infection) 
• , , simeprevir, daclatasvir (used to treat hepatitis C virus infection) 
• maraviroc (used to treat HIV infection) 
 
You will be closely monitored if you are taking these medicines with Telzir/ritonavir: 
• atorvastatin up to 20 mg per day (used to lower cholesterol) 
• carbamazepine, phenobarbital, phenytoin (used to treat epilepsy) 
• cyclosporin, rapamycin, tacrolimus (used to suppress the immune system) 
• dolutegravir (used to treat HIV infection) 
• desipramine, nortriptyline, paroxetine and similar medicines (used to treat depression) 
• warfarin and other medicines that stop blood clotting 
• injectable midazolam (used to treat anxiety) 
• clarithromycin, erythromycin (an antibiotic) 
• methadone (a heroin substitute) 
• dasatinib, nilotinib, ibrutinib, vinblastine and everolimus  (used to treat several types of cancer) 

 
Your dose of Telzir may need to be changed if you are taking 
• etravirine (used to treat HIV infection) 
 
Hormonal contraception 
Taking Telzir and ritonavir while taking the contraceptive pill may harm your liver and may stop the 
contraceptive from working properly. 
→ Use an alternative non-hormonal type of contraception such as a condom. 
No studies have been done on the use of Telzir/ritonavir with other hormonal therapies, such as 
hormone replacement therapy (HRT). 



81 

 
Pregnancy  
If you are pregnant, think you may be pregnant, or are planning to have a baby: 
→Ask your doctor or pharmacist for advice before taking this medicine. 
 
 
Breast-feeding 
Women who are HIV-positive must not breast-feed because HIV infection can be passed on to the 
baby in breast milk. It is not known whether the ingredients in Telzir can also pass into your breast 
milk. If you are breast-feeding, or thinking about breast-feeding: 
→Talk to your doctor immediately.  
 
 
Driving and using machines 
Telzir can make you feel dizzy and have other side effects that make you less alert. 
→ Don’t drive or operate machinery unless you’re feeling well.  
 
Stay in regular contact with your doctor 
Telzir helps to control your condition, but it is not a cure for HIV infection.  You need to keep taking 
it every day to stop your illness getting worse.  You may still develop other infections and illnesses 
linked to HIV infection. 
→ Keep in touch with your doctor, and don’t stop taking Telzir without your doctor’s advice.   
 
 
3.  How to take Telzir 
Always take this medicine exactly as your doctor or pharmacist has told you.  It is very important 
that you take the full daily dose of Telzir and ritonavir as prescribed by your doctor. Do not take 
more than the recommended dose. Check with your doctor or pharmacist if you are not sure. 
 
Swallow the tablets whole, with some water or another drink.  Telzir tablets can be taken with or 
without food. Telzir is also available as a liquid (oral suspension) for people who are unable to 
swallow tablets. (Read the package leaflet of Telzir oral suspension for guidance on whether to take it 
with or without food.) 
 
Adults  
The recommended dose is one 700 mg Telzir tablet twice daily with 100 mg ritonavir twice daily.  
 
Children from 6 years of age and weighing at least 39 kg 
Children can take the adult tablet dose of one 700 mg Telzir tablet twice daily with ritonavir 100 mg 
twice daily if they can swallow the tablets whole.   
 
Children from 6 years of age and weighing less than 39 kg 
Use Telzir oral suspension. 
 
Adults with liver disease  
If you have mild liver disease, the dose is one Telzir tablet (700 mg) twice daily with 100 mg 
ritonavir only once daily.   If you have moderate or severe liver disease the dose of Telzir has to be 
lowered.  This dose adjustment cannot be made with Telzir tablets.  You must take Telzir oral 
suspension.  
 
If you take too much Telzir  
If you have taken more than the prescribed dose of Telzir: 
→Contact your doctor or pharmacist immediately for advice. 
 
If you forget to take Telzir 



82 

If you forget to take a dose of Telzir, take it as soon as you remember and then continue your 
treatment as before. Don’t take a double dose to make up for a missed dose. 
 
Don’t stop Telzir without advice 
Take Telzir for as long as your doctor recommends.  Don’t stop unless your doctor advises you to.  
 
4. Possible side effects 
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.  
 
Like all medicines, this medicine can cause side effects, but not everyone gets them. When treating 
HIV, it can be hard to tell whether side effects are caused by Telzir, by other medicines taken at the 
same time or by the HIV disease itself. For this reason, it is very important to talk to your doctor 
about any changes in your health. 
 
Very common side effects  
These may affect more than 1 in 10 people: 
• Diarrhoea 
• Increase in cholesterol (a type of blood fat). 
 
Common side effects  
These may affect up to 1 in 10 people: 
• Increases in triglycerides (a type of blood fat). 
• Feeling sick or being sick (nausea or vomiting), pain in the stomach, loose stools 
• Skin rashes (red, raised or itchy) – if the skin rash is severe, you may have to stop taking this 

medicine 
• Headache, feeling dizzy 
• Feeling tired 
• Increases in enzymes produced by the liver called transaminases, increases of an enzyme 

produced by the pancreas called lipase. 
• Tingling or numbness around the lips and mouth. 

 
Uncommon side effects  
These may affect up to 1 in 100 people: 
• Swelling of the face, lips and tongue (angioedema). 

 
Rare side effects  
These may affect up to 1 in 1000 people: 
• A severe or life-threatening skin reaction (Stevens Johnson syndrome). 
 
You may experience muscle problems 
There have been reports of muscle pain, tenderness or weakness, particularly with antiretroviral 
therapy including protease inhibitors and nucleoside analogues. On rare occasions, these muscle 
disorders have been serious (rhabdomyolysis).  If you notice any muscle problems: 
→Tell your doctor. 
 
Haemophiliacs may bleed more 
In patients with haemophilia type A and B, there have been reports of increased bleeding while 
taking protease inhibitors.  
If this happens to you: 
→Talk to your doctor immediately. 
 
If you get any side effects 



83 

→Talk to your doctor or pharmacist. This includes any possible side effects not listed in this 
leaflet.  
 
Other side effects of combination therapy for HIV 
 
Old infections may flare up 
People with advanced HIV infection (AIDS) have weak immune systems and are more likely to 
develop serious infections (opportunistic infections).  When these people start treatment, they may 
find that old, hidden infections flare up, causing signs and symptoms of inflammation.  These 
symptoms are probably caused by the body’s immune system becoming stronger, so that the body 
starts to fight these infections. 
 
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. 
 
If you get any symptoms of infection or signs of inflammation while you’re taking Telzir: 
→Tell your doctor immediately.  Don’t take other medicines for the infection without your 

doctor’s advice.  
 
 
You may have problems with your bones 
Some people taking combination therapy for HIV develop a condition called osteonecrosis. With this 
condition, parts of the bone tissue die because of reduced blood supply to the bone. 

People may be more likely to get this condition: 
• if they have been taking combination therapy for a long time 
• if they are also taking anti-inflammatory medicines called corticosteroids 
• if they drink alcohol 
• if their immune systems are very weak 
• if they are overweight. 

Signs to look out for include: 
• stiffness in the joints 
• aches and pains (especially in the hip, knee or shoulder) 
• difficulty moving. 
If you notice any of these symptoms: 
→Tell your doctor. 
 
 
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 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Telzir 
 
Keep this medicine out of the sight and reach of children.   

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


84 

 
Do not use this medicine after the expiry date which is stated on the carton and the bottle. 
 
Telzir 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 to protect the environment. 
 
6. Contents of the pack and other information 
 
What Telzir contains 
 
• The active substance is fosamprenavir. Each tablet contains 700 mg of fosamprenavir as 

fosamprenavir calcium (equivalent to approximately 600 mg amprenavir). 
 
• The other ingredients are: microcrystalline cellulose, croscarmellose sodium, povidone K30, 

magnesium stearate, colloidal anhydrous silica, hypromellose, titanium dioxide (E171), glycerol 
triacetate, iron oxide red (E172). 

 
What Telzir looks like and contents of the pack 
 
Telzir is supplied in plastic bottles containing 60 film-coated tablets. The tablets are capsule shaped, 
biconvex, pink coloured and marked with ‘GXLL7’ on one side. 
 
Telzir is also available as an oral suspension for those patients unable to swallow the tablets. 
 
Marketing Authorisation Holder and Manufacturer 
 

Manufacturer Marketing Authorisation Holder 
 

Glaxo Wellcome Operations  
Priory Street  
Ware  
Hertfordshire SG12 0DJ  
United Kingdom 

ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP Amersfoort 
Netherlands 
 
 

  Glaxo Wellcome S.A.  
  Avenida de Extremadura 3 
  09400 Aranda de Duero Burgos 
  Spain 
 
 
For any information about this medicinal product please contact the local representative of the 
Marketing Authorisation Holder. 
 

België/Belgique/Belgien 
ViiV Healthcare srl/bv 
Tél/Tel: + 32 (0) 10 85 65 00 
 

Lietuva 
GlaxoSmithKline Lietuva UAB 
Tel: + 370 5 264 90 00 
info.lt@gsk.com 
 

България 
ГлаксоСмитКлайн ЕООД 
Teл.: + 359 2 953 10 34 
 

Luxembourg/Luxemburg 
ViiV Healthcare srl/bv 
Belgique/Belgien 
Tél/Tel: + 32 (0) 10 85 65 00 
 



85 

Česká republika 
GlaxoSmithKline s.r.o. 
Tel: + 420 222 001 111 
cz.info@gsk.com 
 

Magyarország 
GlaxoSmithKline Kft. 
Tel.: + 36 1 225 5300 
 

Danmark 
GlaxoSmithKline Pharma A/S 
Tlf: + 45 36 35 91 00 
dk-info@gsk.com 
 

Malta 
GlaxoSmithKline (Malta) Limited 
Tel: + 356 21 238131 
 

Deutschland 
ViiV Healthcare GmbH  
Tel.: + 49 (0)89 203 0038-10 
viiv.med.info@viivhealthcare.com 
 

Nederland 
ViiV Healthcare BV  
Tel: + 31 (0) 33 2081199 
 

Eesti 
GlaxoSmithKline Eesti OÜ 
Tel: + 372 6676 900 
estonia@gsk.com 
 

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 

Ελλάδα 
GlaxoSmithKline  
Μονοπρόσωπη A.E.B.E. 
Τηλ: + 30 210 68 82 100 
 

Österreich 
GlaxoSmithKline Pharma GmbH 
Tel: + 43 (0)1 97075 0 
at.info@gsk.com 
 

España 
Laboratorios ViiV Healthcare, S.L.  
Tel: +34 900 923 501 
es-ci@viivhealthcare.com 
 

Polska 
GSK Services Sp. z o.o. 
Tel.: + 48 (0)22 576 9000 
 

France 
ViiV Healthcare SAS  
Tél: + 33 (0)1 39 17 6969 
Infomed@viivhealthcare.com 
 

Portugal 
VIIVHIV HEALTHCARE, UNIPESSOAL, 
LDA. 
Tel: + 351 21 094 08 01 
viiv.fi.pt@viivhealthcare.com 
 

Hrvatska 
GlaxoSmithKline d.o.o. 
Tel: + 385 1 6051 999 
 

România 
GlaxoSmithKline (GSK) S.R.L.  
Tel: + 4021 3028 208 

Ireland 
GlaxoSmithKline (Ireland) Limited 
Tel: + 353 (0)1 4955000 
 

Slovenija 
GlaxoSmithKline d.o.o. 
Tel: + 386 (0)1 280 25 00 
medical.x.si@gsk.com 
 

Ísland 
Vistor hf.  
Sími: +354 535 7000 
 

Slovenská republika 
GlaxoSmithKline Slovakia s. r. o. 
Tel: + 421 (0)2 48 26 11 11 
recepcia.sk@gsk.com 
 

Italia 
ViiV Healthcare S.r.l.  
Tel: + 39 (0)45 9212611 
 

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 (0)10 30 30 30 
Finland.tuoteinfo@gsk.com 
 

mailto:viiv.med.info@viivhealthcare.com
mailto:viiv.med.info@viivhealthcare.com
mailto:es-ci@viivhealthcare.com
mailto:es-ci@viivhealthcare.com
mailto:Infomed@viivhealthcare.com
mailto:Infomed@viivhealthcare.com
mailto:viiv.fi.pt@viivhealthcare.com
mailto:viiv.fi.pt@viivhealthcare.com


86 

Κύπρος 
GlaxoSmithKline (Cyprus ) Ltd 
Τηλ: + 357 22 39 70 00 
gskcyprus@gsk.com 
 

Sverige 
GlaxoSmithKline AB 
Tel: + 46 (0)8 638 93 00 
info.produkt@gsk.com 
 

Latvija 
GlaxoSmithKline Latvia SIA 
Tel: + 371 67312687 
lv-epasts@gsk.com 
 

United Kingdom 
ViiV Healthcare UK Ltd  
Tel: + 44 (0)800 221441 
customercontactuk@gsk.com 
 

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

mailto:gskcyprus@gsk.com
http://www.ema.europa.eu/
http://www.ema.europa.eu/


87 

Package leaflet: Information for the user 
 

Telzir 50 mg/ml oral suspension 
Fosamprenavir 

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 Telzir is and what it is used for 
2.  What you need to know before you take Telzir 
3.  How to take Telzir 
4.  Possible side effects 
5.       How to store Telzir 
6.  Contents of the pack and other information 
 
 
1. What Telzir is and what it is used for 
 
Telzir is used to treat HIV (human immunodeficiency virus) infection.  
 
Telzir is a type of medicine known as an anti-retroviral.  It is taken with low doses of another 
medicine, ritonavir, which boosts the level of Telzir in the blood. Telzir belongs to a group of 
anti-retroviral medicines called protease inhibitors.  Protease is an enzyme produced by HIV which 
enables the virus to multiply in white blood cells (CD4 cells) in your blood.  By stopping protease 
from working, Telzir stops HIV multiplying and infecting more CD4 cells 
 
Telzir with low doses of ritonavir is used in combination with other anti-retroviral medicines 
(‘combination therapy’) to treat adults, adolescents and children aged over 6 years infected with  
HIV.      
 
HIV can become resistant to anti-HIV medicines.  To avoid this happening, and to stop your illness 
getting worse, it is very important that you keep taking all your medicines exactly as prescribed.  
 
Telzir will not stop you passing on HIV.  HIV infection is spread by sexual contact with someone 
who’s got the infection, or by transfer of infected blood (for example by sharing needles).  
 
 
2. What you need to know before you take Telzir 
 
Telzir is to be taken in combination with low doses of ritonavir and other antiretroviral 
medicines. It is therefore important that you carefully read the package leaflet provided with these 
medicines. If you have any further questions about ritonavir or the other medicines prescribed, please 
ask your doctor or pharmacist. 
 
Do not take Telzir: 
• if you are allergic to fosamprenavir, amprenavir or any of the other ingredients of this medicine 

(listed in section 6), or to ritonavir. 

• if you are taking any of these medicines: 
 



88 

- alfuzosin (used to treat a prostate problem) 
- astemizole or terfenadine (commonly used to treat allergy symptoms – these medicines may be 

available without prescription) 
- pimozide (used to treat schizophrenia)  
- quetiapine (used to treat schizophrenia, bipolar disorder and major depressive disorder) 
- lurasidone (used to treat schizophrenia and bipolar disorder)  
- cisapride (used to relieve indigestion) 
- ergot derivatives (used to treat headaches) 
- rifampicin (used to treat tuberculosis) 
- amiodarone, quinidine, flecainide and propafenone (heart medicines) 
- bepridil (used to treat high blood pressure) 
- oral midazolam or oral triazolam (used to treat anxiety)  
- products containing St John’s wort (Hypericum perforatum) 
- lovastatin, simvastatin (used to lower cholesterol)  
- sildenafil if used to treat pulmonary arterial hypertension, (a condition affecting the blood 

vessels to your lungs) 
- paritaprevir (used to treat hepatitis C virus infection) 

 
 
→Tell your doctor if any of these applies to you. 
 
Take special care with Telzir 
Talk to your doctor or pharmacist before taking Telzir: 
• If you have a known allergy to medicines containing sulphonamide.  You may also be allergic 

to Telzir. 
• If you have liver disease. Your doctor may lower your dose of Telzir and ritonavir depending on 

the amount of liver damage. You will be monitored while you are taking Telzir. If your liver 
disease gets worse, you may need to stop taking Telzir for a while, or permanently. People with 
hepatitis B or C taking combination therapy are at increased risk of getting severe liver problems.  

• If you have haemophilia. Increased bleeding may occur while taking protease inhibitors (such as 
Telzir). The reason for this is not known. You may need additional factor VIII to control any 
bleeding. 

• If you have diabetes. In some patients taking antiretroviral medicines including protease 
inhibitors, there have been reports of increased sugar in the blood and diabetes getting worse.  
Also, some people have become diabetic while taking these medicines. 

• If you are taking any other medicines.  See section ‘Other medicines and Telzir’. 
 
→Tell your doctor if any of these apply to you.   You will need extra check-ups, including blood 
tests, while you’re taking your medication.   
 
Your doctor will monitor your blood glucose levels before and during treatment with Telzir. 
 
Look out for important symptoms 
Some people taking medicines for HIV infection develop other conditions, which can be serious.  
These include: 
• Flare up of old infections 
• Change in your body shape 
• Problems with your bones. 

You need to know about important signs and symptoms to look out for while you’re taking Telzir. 
Please read the information on ‘Other side effects of combination therapy for HIV’ in section 4 
of this leaflet.  If you have any questions about this information or the advice given: 
→Talk to your doctor.  
 
You may get a skin rash.  



89 

However you can still continue to take Telzir. It can be treated with antihistamines. Rarely, the skin 
rash can be severe and serious (Stevens Johnson syndrome). If this happens, Telzir must be stopped 
immediately and you must never take it again. 
 
Protect other people 
HIV infection is spread by sexual contact with someone who has the infection, or by transfer of infected 
blood (for example, by sharing injection needles). 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. 
 
Other medicines and Telzir 
Tell your doctor or pharmacist if you’re taking or have recently taken any other medicines – 
these include herbal medicines or other medicines you bought without a prescription.  
Your doctor will decide if these medicines are suitable for you to take with Telzir and ritonavir.  This 
is very important, as Telzir or ritonavir can strengthen or weaken the effects of other medicines.  This 
can sometimes lead to serious medical conditions.  
 
There are some medicines that must not be taken with Telzir. You must check the list of medicines 
under 'Don't take Telzir' at the beginning of section 2 of this leaflet.  
 
These medicines are not recommended with Telzir/ritonavir: 
- doses of ketoconazole and itraconazole greater than 200 mg per day (used to treat fungal 

infections)  
- doses of rifabutin greater than 150 mg every other day (an antibiotic) 
- lidocaine given by injection   
- halofantrine  (used to treat malaria) 
- sildenafil, vardenafil or tadalafil (used to treat erectile dysfunction)  
- doses of atorvastatin greater than 20 mg per day (used to lower cholesterol)  
- fluticasone propionate and similar medicines used to treat asthma, unless considered essential. In 

this case close monitoring is required. 
- lopinavir/ritonavir combination (used to treat HIV infection) 
- raltegravir (used to treat HIV infection) 
- , , simeprevir, daclatasvir (used to treat hepatitis C virus infection) 
- maraviroc (used to treat HIV infection) 
 
You will be closely monitored if you are taking these medicines with Telzir/ritonavir:  
• atorvastatin up to 20 mg per day (used to lower cholesterol) 
• carbamazepine, phenobarbital, phenytoin (used to treat epilepsy) 
• cyclosporin, rapamycin, tacrolimus (used to suppress the immune system) 
• dolutegravir (used to treat HIV infection)  
• desipramine, nortriptyline, paroxetine and similar medicines (used to treat depression) 
• warfarin and other medicines that stop blood clotting 
• injectable midazolam (used to treat anxiety) 
• clarithromycin, erythromycin (an antibiotic) 
• methadone (a heroin substitute)                                                                                                                                         
• dasatinib, nilotinib, ibrutinib, vinblastine and everolimus (used to treat several types of cancer) 

 
Your dose of Telzir may need to be changed if you are taking 
• etravirine (used to treat HIV infection) 
 
Hormonal contraception 
Taking Telzir and ritonavir while taking the contraceptive pill may harm your liver and may stop the 
contraceptive from working properly. 
→ Use an alternative non-hormonal type of contraception such as a condom. 



90 

No studies have been done on the use of Telzir/ritonavir with other hormonal therapies, such as 
hormone replacement therapy (HRT). 
 
Taking Telzir and food  
Adults should take the Telzir oral suspension without food and on an empty stomach. 
Children and adolescents should take the Telzir oral suspension with food. 
 
Pregnancy  
If you are pregnant, think you may be pregnant, or are planning to have a baby: 
→Ask your doctor or pharmacist for advice before taking this medicine. 
 
Breast-feeding 
Women who are HIV-positive must not breast-feed because HIV infection can be passed on to the 
baby in breast milk. It is not known whether the ingredients in Telzir can also pass into your breast 
milk. If you are breast-feeding, or thinking about breast-feeding: 
→Talk to your doctor immediately.  

 
Important information about ingredients of Telzir oral suspension 
Telzir oral suspension contains propyl and methyl parahydroxybenzoate. These ingredients may 
cause allergic reactions (sometimes delayed). 
 
Driving and using machines 
Telzir can make you feel dizzy and have other side effects that make you less alert. 
→ Don’t drive or operate machinery unless you’re feeling well.  
 
Stay in regular contact with your doctor 
Telzir helps to control your condition, but it is not a cure for HIV infection.  You need to keep taking 
it every day to stop your illness getting worse.  You may still develop other infections and illnesses 
linked to HIV infection. 
→ Keep in touch with your doctor, and don’t stop taking Telzir without your doctor’s advice.   
 
 
3.  How to take Telzir 
 
Always take this medicine exactly as your doctor or pharmacist has told you.  It is very important 
that you take the full daily dose of Telzir and ritonavir as prescribed by your doctor.  Do not take 
more than the recommended dose.  Check with your doctor or pharmacist if you are not sure. 
 
Shake the bottle for 20 seconds before the first use. Shake the bottle for 5 seconds before subsequent 
uses. 
 
A dosing syringe with a 10 ml graduation is supplied with the pack so you can measure your dose 
accurately. 
 
Adults 
Adults should take Telzir oral suspension without food and on an empty stomach. 
The recommended dose is 14 ml Telzir oral suspension (700 mg fosamprenavir) twice daily with 
100 mg ritonavir (as capsule or oral solution) twice daily.   
 
Children from 6 years of age and weighing at least 25 kg 
Children should take the Telzir oral suspension with food.   
 
Your doctor will work out the right dose based on your weight. 
 
The recommended dose is 0.36 ml/kg of Telzir oral suspension (18 mg per kg fosamprenavir) twice 
daily with 3 mg/kg ritonavir oral solution twice daily.   



91 

 
No dosing recommendations can be made for children weighing less than 25 kg. 
 
Children can take the adult dose of ritonavir capsules (100 mg twice daily) if they weigh at least 33 kg 
and can swallow the capsules whole. 
 
As an alternative to taking Telzir oral suspension: 
Children can take the adult dose of one 700 mg Telzir tablet twice daily (with ritonavir 100 mg twice 
daily) if they weigh at least 39 kg and can swallow the tablets whole.   
 
Children less than 6 years of age 
Telzir is not recommended for children less than 6 years old. 

 
Adults with liver disease 
If you have mild liver disease, the dose is 14 ml Telzir oral suspension (700 mg fosamprenavir) 
twice daily with 100 mg ritonavir only once daily.   If you have moderate liver disease the dose is 
9 ml Telzir oral suspension (450 mg fosamprenavir) twice daily with 100 mg ritonavir only once 
daily. If you have severe liver disease the dose is 6 ml Telzir oral suspension (300 mg fosamprenavir) 
twice daily with 100 mg ritonavir only once daily. 
 
Step by step instructions 
Do not mix Telzir with any other medicines in the bottle or the syringe. 
 
1. Shake the bottle vigorously before use. 
2. Remove the bottle cap and keep it safely. 
3. Push the plastic adapter into the neck of the bottle, while holding the bottle firmly. 
4. Insert the syringe firmly into the adapter. 
5. Turn the bottle upside down. 
6. Pull out the syringe plunger until the first portion of your full dose is withdrawn. 
7. Turn the bottle the right way up and remove the syringe from the adapter. 
8. Put the syringe into your mouth, placing the tip of the syringe against the inside of your cheek. 

Slowly push the plunger in, allowing time to swallow.  Don’t push too hard and squirt the liquid 
into the back of the throat or you may choke. 

9. Repeat steps 4 to 8 in the same way until you have taken the whole dose. 
10. Do not leave the syringe in the bottle. Take the syringe and the adapter off and wash them 

thoroughly in clean water. Let them dry completely before you use them again. 
11. Close the bottle tightly with the cap. 
 
If you take too much Telzir  
If you have taken more than the prescribed dose of Telzir: 
→Contact your doctor or pharmacist immediately for advice. 
 
If you forget to take Telzir 
If you forget to take a dose of Telzir, take it as soon as you remember and then continue your 
treatment as before. Don’t take a double dose to make up for a missed dose. 
 
Don’t stop Telzir without advice 
Take Telzir for as long as your doctor recommends.  Don’t stop unless your doctor advises you to.  
 
 



92 

4. Possible side effects 
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.  
 
Like all medicines, this medicine can cause side effects, but not everyone gets them. When treating 
HIV, it can be hard to tell whether side effects are caused by Telzir, by other medicines taken at the 
same time or by the HIV disease itself. For this reason, it is very important to talk to your doctor 
about any changes in your health. 
 
Very common side effects  
These may affect more than 1 in 10 people: 
• Diarrhoea 
• Increase in cholesterol (a type of blood fat).  

 
Common side effects  
These may affect up to 1 in 10 people: 
• Increases in triglycerides (a type of blood fat). 
•  Feeling sick or being sick (nausea or vomiting), pain in the stomach, loose stools 
• Skin rashes (red, raised or itchy) – if the skin rash is severe, you may have to stop taking this 

medicine 
• Headache, feeling dizzy 
• Feeling tired 
• Increases in enzymes produced by the liver called transaminases, increases of an enzyme 

produced by the pancreas called lipase. 
• Tingling or numbness around the lips and mouth. 

 
Uncommon side effects  
These may affect up to 1 in 100 people: 
• Swelling of the face, lips and tongue (angioedema). 

 
Rare side effects  
These may affect up to 1 in 1000 people: 
• A severe or life-threatening skin reaction (Stevens Johnson syndrome). 
 
You may experience muscle problems 
There have been reports of muscle pain, tenderness or weakness, particularly with antiretroviral 
therapy including protease inhibitors and nucleoside analogues. On rare occasions, these muscle 
disorders have been serious (rhabdomyolysis).  If you notice any muscle problems: 
→Tell your doctor. 
 
Haemophiliacs may bleed more 
In patients with haemophilia type A and B, there have been reports of increased bleeding while taking 
protease inhibitors. If this happens to you: 
→Talk to your doctor immediately. 
 
If you get any side effects 
→Talk to your doctor or pharmacist. This includes any possible side effects not listed in this 
leaflet.  
 
Other side effects of combination therapy for HIV 
 
Old infections may flare up 
People with advanced HIV infection (AIDS) have weak immune systems and are more likely to 
develop serious infections (opportunistic infections).  When these people start treatment, they may 



93 

find that old, hidden infections flare up, causing signs and symptoms of inflammation.  These 
symptoms are probably caused by the body’s immune system becoming stronger, so that the body 
starts to fight these infections. 
 
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. 
 
If you get any symptoms of infection or signs of inflammation while you’re taking Telzir: 
→Tell your doctor immediately.  Don’t take other medicines for the infection without your 
doctor’s advice.  
 
 
You may have problems with your bones 
Some people taking combination therapy for HIV develop a condition called osteonecrosis. With this 
condition, parts of the bone tissue die because of reduced blood supply to the bone. 

People may be more likely to get this condition: 
• if they have been taking combination therapy for a long time 
• if they are also taking anti-inflammatory medicines called corticosteroids 
• if they drink alcohol 
• if their immune systems are very weak 
• if they are overweight. 

Signs to look out for include: 
• stiffness in the joints 
• aches and pains (especially in the hip, knee or shoulder) 
• difficulty moving. 
If you notice any of these symptoms: 
Tell your doctor. 
 
 
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 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Telzir 
 
Keep this medicine out of the sight and reach of children.   
 
Do not freeze. Telzir does not require any other special storage conditions. 
 
Do not use this medicine after the expiry date which is stated on the carton and the bottle. 
 
Throw away the bottle 28 days after first opening it, but 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 to protect the environment. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


94 

 
 
6. Contents of the pack and other information 
 
What Telzir contains 
 
• The active substance is fosamprenavir. Each ml of suspension contains 50 mg of fosamprenavir 

as fosamprenavir calcium salt (equivalent to approximately 43 mg of amprenavir). 
 
• The other ingredients are: hypromellose, sucralose, polysorbate 80, calcium chloride dihydrate, 

artificial grape bubblegum flavour, natural peppermint flavour, purified water, propylene glycol, 
methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216). 

 
What Telzir looks like and contents of the pack 
 
Telzir is supplied in plastic bottles containing 225 ml oral suspension. A 10 ml graduated dosing 
syringe and an adapter are also included in the pack. The suspension is white to off-white. 
 
Telzir is also available as 700 mg film-coated tablets. 
 
Marketing Authorisation Holder and Manufacturer 
 

Manufacturer Marketing Authorisation Holder 
 

 
Glaxo Operations UK Ltd 
(trading as GlaxoWellcome 
Operations) 
Harmire Road 
Barnard Castle 
Co. Durham DL12 8DT 
United Kingdom 
 
or 
 
ViiV Healthcare Trading 
Services UK Limited  
12 Riverwalk,  
Citywest Business Campus  
Dublin 24, 
Ireland 
 
 

ViiV Healthcare BV 
Van Asch van Wijckstraat 55H 
3811 LP AmersfoortNetherlands 

  
For any information about this medicinal product please contact the local representative of the 
Marketing Authorisation Holder. 
 

België/Belgique/Belgien 
ViiV Healthcare srl/bv 
Tél/Tel: + 32 (0) 10 85 65 00 
 

Lietuva 
GlaxoSmithKline Lietuva UAB 
Tel: + 370 5 264 90 00 
info.lt@gsk.com 
 



95 

България 
ГлаксоСмитКлайн ЕООД 
Teл.: + 359 2 953 10 34 
 

Luxembourg/Luxemburg 
ViiV Healthcare srl/bv 
Belgique/Belgien 
Tél/Tel: + 32 (0) 10 85 65 00 
 

Česká republika 
GlaxoSmithKline s.r.o. 
Tel: + 420 222 001 111 
cz.info@gsk.com 
 

Magyarország 
GlaxoSmithKline Kft. 
Tel.: + 36 1 225 5300 
 

Danmark 
GlaxoSmithKline Pharma A/S 
Tlf: + 45 36 35 91 00 
dk-info@gsk.com 
 

 Malta 
GlaxoSmithKline (Malta) Limited             
Tel: + 356 21 238131 
 

Deutschland 
ViiV Healthcare GmbH 
Tel.: + 49 (0)89 203 0038-10 
viiv.med.info@viivhealthcare.com 

Nederland 
ViiV Healthcare BV  
Tel: + 31 (0) 33 2081199 
 

Eesti 
GlaxoSmithKline Eesti OÜ 
Tel: + 372 6676 900 
estonia@gsk.com 
 

Norge 
GlaxoSmithKline AS 
Tlf: + 47 22 70 20 00 
 

Ελλάδα 
GlaxoSmithKline  
Μονοπρόσωπη A.E.B.E. 
Τηλ: + 30 210 68 82 100 
 

Österreich 
GlaxoSmithKline Pharma GmbH 
Tel: + 43 (0)1 97075 0 
at.info@gsk.com 
 

España 
Laboratorios ViiV Healthcare, S.L.  
Tel: +34 900 923 501 
es-ci@viivhealthcare.com 
 

Polska 
GSK Services Sp. z o.o. 
Tel.: + 48 (0)22 576 9000 
 

France 
ViiV Healthcare SAS  
Tél: + 33 (0)1 39 17 6969 
Infomed@viivhealthcare.com 
 

Portugal 
VIIVHIV HEALTHCARE, UNIPESSOAL, 
LDA. 
Tel: + 351 21 094 08 01 
viiv.fi.pt@viivhealthcare.com 
 

Hrvatska 
GlaxoSmithKline d.o.o. 
Tel: + 385 1 6051 999 
 

România 
GlaxoSmithKline (GSK) S.R.L.  
Tel: + 4021 3028 208 
 

Ireland 
GlaxoSmithKline (Ireland) Limited 
Tel: + 353 (0)1 4955000 
 

Slovenija 
GlaxoSmithKline d.o.o. 
Tel: + 386 (0)1 280 25 00 
medical.x.si@gsk.com 
 

Ísland 
Vistor hf.  
Sími: +354 535 7000 
 

Slovenská republika 
GlaxoSmithKline Slovakia s. r. o. 
Tel: + 421 (0)2 48 26 11 11 
recepcia.sk@gsk.com 
 

mailto:viiv.med.info@viivhealthcare.com
mailto:viiv.med.info@viivhealthcare.com
mailto:es-ci@viivhealthcare.com
mailto:es-ci@viivhealthcare.com
mailto:Infomed@viivhealthcare.com
mailto:Infomed@viivhealthcare.com
mailto:viiv.fi.pt@viivhealthcare.com
mailto:viiv.fi.pt@viivhealthcare.com
mailto:recepcia.sk@gsk.com
mailto:recepcia.sk@gsk.com


96 

Italia 
ViiV Healthcare S.r.l.  
Tel: + 39 (0)45 9212611 
 

Suomi/Finland 
GlaxoSmithKline Oy 
Puh/Tel: + 358 (0)10 30 30 30 
Finland.tuoteinfo@gsk.com 
 

Κύπρος 
GlaxoSmithKline (Cyprus) Ltd 
Τηλ: + 357 22 39 70 00 
gskcyprus@gsk.com 
 

Sverige 
GlaxoSmithKline AB 
Tel: + 46 (0)8 638 93 00 
info.produkt@gsk.com 
 

Latvija 
GlaxoSmithKline Latvia SIA 
Tel: + 371 67312687 
lv-epasts@gsk.com 
 

United Kingdom 
ViiV Healthcare UK Ltd  
Tel: + 44 (0)800 221441 
customercontactuk@gsk.com 
 

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

 
 

mailto:gskcyprus@gsk.com
mailto:gskcyprus@gsk.com
http://www.ema.europa.eu/
http://www.ema.europa.eu/

	SUMMARY OF PRODUCT CHARACTERISTICS
	A MANUFACTURER(S) 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