Zerit

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ANNEX I 

SUMMARY OF PRODUCT CHARACTERISTICS 

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1. NAME OF THE MEDICINAL PRODUCT 

Zerit 15 mg hard capsules 
Zerit 20 mg hard capsules 
Zerit 30 mg hard capsules 
Zerit 40 mg hard capsules 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

Zerit 15 mg hard capsules 
Each hard capsule contains 15 mg of stavudine. 

Excipients with known effect  
Each hard capsule contains 80.84 mg of lactose anhydrous. 
Each hard capsule contains 40.42 mg of lactose monohydrate. 

Zerit 20 mg hard capsules 
Each hard capsule contains 20 mg of stavudine. 

Excipients with known effect  
Each hard capsule contains 121.30 mg of lactose anhydrous. 
Each hard capsule contains 60.66 mg of lactose monohydrate. 

Zerit 30 mg hard capsules 
Each hard capsule contains 30 mg of stavudine. 

Excipients with known effect  
Each hard capsule contains 121.09 mg of lactose anhydrous. 
Each hard capsule contains 60.54 mg of lactose monohydrate. 

Zerit 40 mg hard capsules 
Each hard capsule contains 40 mg of stavudine. 

Excipients with known effect  
Each hard capsule contains 159.06 mg of lactose anhydrous. 
Each hard capsule contains 79.53 mg of lactose monohydrate. 

For the full list of excipients, see section 6.1. 

3. PHARMACEUTICAL FORM 

Hard capsule. 

Zerit 15 mg hard capsules 
The hard capsule is red and yellow, opaque and imprinted with “BMS” over a BMS code “1964” on 
one side and “15” on the other side. 

Zerit 20 mg hard capsules 
The hard capsule is brown, opaque and imprinted with “BMS” over a BMS code “1965” on one side 
and “20” on the other side. 

Zerit 30 mg hard capsules 
The hard capsule is light and dark orange, opaque and imprinted with “BMS” over a BMS code 
“1966” on one side and “30” on the other side. 

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Zerit 40 mg hard capsules 
The hard capsule is dark orange, opaque and imprinted with “BMS” over a BMS code “1967” on one 
side and “40” on the other side. 

4. CLINICAL PARTICULARS 

4.1 Therapeutic indications 

Zerit is indicated in combination with other antiretroviral medicinal products for the treatment of HIV 
infected adult patients and paediatric patients (over the age of 3 months) only when other 
antiretrovirals can not be used. The duration of therapy with Zerit should be limited to the shortest 
time possible (see section 4.2). 

4.2 Posology and method of administration 

The therapy should be initiated by a doctor experienced in the management of HIV infection (see also 
section 4.4). 

For patients starting therapy with Zerit, the duration should be limited to the shortest time possible 
followed by a switch to an alternative appropriate therapy whenever possible. Patients continuing 
treatment with Zerit should be assessed frequently and switched to an alternative appropriate therapy 
whenever possible (see section 4.4). 

Posology 

Adults: the recommended oral dosage is 

Patient weight Zerit dosage
< 60 kg 
≥ 60 kg

30 mg twice daily (every 12 hours) 
40 mg twice daily (every 12 hours)

Paediatric population 

Adolescents, children and infants over the age of 3 months: the recommended oral dosage is 

Patient weight Zerit dosage
< 30 kg 
≥ 30 kg

1 mg/kg twice daily (every 12 hours) 
adult dosing

The powder formulation of ZERIT should be used for infants under the age of 3 months. Adult 
patients that have problems swallowing capsules should ask their doctor about the possibility of 
changing to the powder formulation of this medicine. 

Please refer to the Summary of Product Characteristics of the powder formulation.  

Dose adjustments 

Peripheral neuropathy: if symptoms of peripheral neuropathy develop (usually characterised by 
persistent numbness, tingling, or pain in the feet and/or hands) (see section 4.4) patients should be 
switched to an alternative treatment regimen, if appropriate. In the rare cases when this is 
inappropriate, dose reduction of stavudine may be considered, while the symptoms of peripheral 
neuropathy are under close monitoring and satisfactory virological suppression is maintained.  
The possible benefits of a dose reduction should be balanced in each case against the risks - which 
may result from this measure (lower intracellular concentrations). 

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Special populations 

Elderly: Zerit has not been specifically investigated in patients over the age of 65.

Hepatic impairment: no initial dosage adjustment is necessary. 

Renal impairment: the following dosages are recommended 

Zerit dosage (according to creatinine clearance) 

Patient weight 26-50 ml/min ≤ 25 ml/min 
(including dialysis dependence*)

< 60 kg 15 mg twice daily 15 mg every 24 hours 

≥ 60 kg 20 mg twice daily 20 mg every 24 hours 

* Patients on haemodialysis should take Zerit after the completion of 
haemodialysis, and at the same time on non-dialysis days. 

Since urinary excretion is also a major route of elimination of stavudine in paediatric patients, the 
clearance of stavudine may be altered in paediatric patients with renal impairment. Although there are 
insufficient data to recommend a specific dosage adjustment of Zerit in this patient population, a 
reduction in the dose and/or an increase in the interval between doses proportional to the reduction for 
adults should be considered. There are no dosage recommendations for paediatric patients under the 
age of 3 months with renal impairment. 

Method of administration 

For optimal absorption, Zerit should be taken on an empty stomach (i.e. at least 1 hour prior to meals) 
but, if this is not possible, it may be taken with a light meal. Zerit may also be administered by 
carefully opening the hard capsule and mixing the contents with food. 

4.3 Contraindications 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
Co-administration with didanosine due to the potential for serious and/or life-threatening events 
notably lactic acidosis, liver function abnormalities, pancreatitis and peripheral neuropathy (see 
sections 4.4 and 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.  

Stavudine therapy is associated with several severe side effects, such as lactic acidosis, lipoatrophy 
and polyneuropathy, for which a potential underlying mechanism is mitochondrial toxicity. Given 
these potential risks, a benefit-risk assessment for each patients should be made and an alternative 
antiretroviral should be carefully considered (see Lactic acidosis, Lipoatrophy, and Peripheral 
neuropathy below and section 4.8). 

Lactic acidosis: lactic acidosis, usually associated with hepatomegaly and hepatic steatosis has been 
reported with the use of stavudine. Early symptoms (symptomatic hyperlactatemia) include benign 
digestive symptoms (nausea, vomiting and abdominal pain), non-specific malaise, loss of appetite, 
weight loss, respiratory symptoms (rapid and/or deep breathing) or neurological symptoms (including 
motor weakness). Lactic acidosis has a high mortality and may be associated with pancreatitis, liver 
failure, renal failure, or motor paralysis. 

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Lactic acidosis generally occurred after a few or several months of treatment. 
Treatment with stavudine should be discontinued if there is symptomatic hyperlactatemia and 
metabolic/lactic acidosis, progressive hepatomegaly, or rapidly elevating aminotransferase levels. 
Caution should be exercised when administering stavudine to any patient (particularly obese women) 
with hepatomegaly, hepatitis or other known risk factors for liver disease and hepatic steatosis 
(including certain medicinal products and alcohol). Patients co-infected with hepatitis C and treated 
with alpha interferon and ribavirin may constitute a special risk. 
Patients at increased risk should be followed closely (see also section 4.6). 

Liver disease: hepatitis or liver failure, which was fatal in some cases, has been reported. The safety 
and efficacy of stavudine has not been established in patients with significant underlying liver 
disorders. Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy 
are at 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 product information for these 
medicinal products. 

Patients with pre-existing liver dysfunction including chronic active hepatitis have an increased 
frequency of liver function abnormalities during combination antiretroviral therapy and should be 
monitored according to standard practice. If there is evidence of worsening liver disease in such 
patients, interruption or discontinuation of treatment must be considered. 

In the event of rapidly elevating transaminase levels (ALT/AST, > 5 times upper limit of normal, 
ULN), discontinuation of Zerit and any potentially hepatotoxic medicinal products should be 
considered. 

Lipoatrophy: on the basis of mitochondrial toxicity stavudine has been shown to cause loss of 
subcutaneous fat, which is most evident in the face, limbs and buttocks.  

In randomized controlled trials of treatment-naive patients, clinical lipoatrophy developed in a higher 
proportion of patients treated with stavudine compared to other nucleosides (tenofovir or abacavir).  
Dual energy x-ray absorptiometry (DEXA) scans demonstrated overall limb fat loss in stavudine 
treated patients compared to limb fat gain or no change in patients treated with other NRTIs (abacavir, 
tenofovir or zidovudine). The incidence and severity of lipoatrophy are cumulative over time with 
stavudine-containing regimens.  In clinical trials, switching from stavudine to other nucleosides 
(tenofovir or abacavir) resulted in increases in limb fat with modest to no improvements in clinical 
lipoatrophy. Given the potential risks of using Zerit including lipoatrophy, a benefit-risk assessment 
for each patient should be made and an alternative antiretroviral carefully considered. Patients 
receiving Zerit should be frequently examined and questioned for signs of lipoatrophy. When such 
development is found, discontinuation of Zerit should  be considered. 

Weight and metabolic parameters: an increase in weight and in levels of blood lipids and glucose may 
occurr 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. 

Peripheral neuropathy: up to 20% of patients treated with Zerit will develop peripheral neuropathy, 
often starting after some months of treatment. Patients with a history of neuropathy, or with other risk 
factors (for example alcohol, medicines such as isoniazid) are at particular risk. Patients should be 
monitored for symptoms (persistent numbness, tingling or pain in feet/hands) and if present patients 
should be switched to an alternate treatment regimen (see section 4.2 and Not recommended 
combinations, below). 

Pancreatitis: patients with a history of pancreatitis had an incidence of approximately 5% on Zerit, as 
compared to approximately 2% in patients without such a history. Patients with a high risk of 

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pancreatitis or those receiving products known to be associated with pancreatitis should be closely 
followed for symptoms of this condition. 

Immune reactivation syndrome: in HIV-infected patients with severe immune deficiency at the time of 
institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic 
or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of 
symptoms. Typically, such reactions have been observed within the first few weeks or months of 
initiation of CART. Relevant examples are cytomegalovirus retinitis, generalised and/or focal 
mycobacterial infections, and Pneumocystis carinii pneumonia. Any inflammatory symptoms should 
be evaluated and treatment instituted when necessary. Autoimmune disorders (such as Graves' disease 
and autoimmune hepatitis) have also been reported to occur in the setting of immune reactivation; 
however, the reported time to onset is more variable and these events can occur many months after 
initiation of treatment. 

Osteonecrosis: although the etiology is considered to be multifactorial (including corticosteroid use, 
alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis 
have been reported particularly in patients with advanced HIV-disease and/or long-term exposure to 
combination antiretroviral therapy (CART). Patients should be advised to seek medical advice if they 
experience joint aches and pain, joint stiffness or difficulty in movement. 

Lactose intolerance: the hard capsule contains lactose. Patients with rare hereditary problems of 
galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption, should not take 
this medicine. 

Not recommended combinations: pancreatitis (fatal and nonfatal) and peripheral neuropathy (severe in 
some cases) have been reported in HIV infected patients receiving stavudine in association with 
hydroxyurea and didanosine (see section 4.3). Hepatotoxicity and hepatic failure resulting in death 
were reported during postmarketing surveillance in HIV infected patients treated with antiretroviral 
agents and hydroxyurea; fatal hepatic events were reported most often in patients treated with 
stavudine, hydroxyurea and didanosine. Hence, hydroxyurea should not be used in the treatment of 
HIV infection. 

Elderly: Zerit has not been specifically investigated in patients over the age of 65. 

Paediatric population 

Infants under the age of 3 months: safety data are available from clinical trials up to 6 weeks of 
treatment in 179 newborns and infants < 3 months of age (see section 4.8). 
Special consideration should be given to the antiretroviral treatment history and the resistance profile 
of the HIV strain of the mother. 

Mitochondrial dysfunction following exposure in utero: nucleos(t)ide analogues may impact 
mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and 
zidovudine. There have been reports of mitochondrial dysfunction in HIV-negative infants exposed in 
utero and/or post-natally to nucleoside analogues (see also section 4.8); these have predominantly 
concerned treatment with regimens containing zidovudine. The main adverse reactions reported are 
haematological disorders (anaemia, neutropenia) and metabolic disorders (hyperlactatemia, 
hyperlipasemia). These events have often been transitory. Late-onset neurological disorders have been 
reported rarely (hypertonia, convulsion, abnormal behaviour). Whether such neurological disorders are 
transient or permanent is currently unknown. These findings should be considered for any child 
exposed in utero to nucleos(t)ide analogues, that present with severe clinical findings of unknown 
etiology, particularly neurologic findings. These findings do not affect current national 
recommendations to use antiretroviral therapy in pregnant women to prevent vertical transmission of 
HIV. 

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4.5 Interaction with other medicinal products and other forms of interaction 

The combination of stavudine with didanosine is contraindicated given that both drugs exhibits high 
risk of mitochondrial toxicity (see sections 4.3 and 4.4). 

Since stavudine is actively secreted by the renal tubules, interactions with other actively secreted 
medicinal products are possible, e.g. with trimethoprim. No clinically relevant pharmacokinetic 
interaction has, however, been seen with lamivudine. 

Zidovudine and stavudine are phosphorylated by the cellular enzyme (thymidine kinase), which 
preferentially phosphorylates zidovudine, thereby decreasing the phosphorylation of stavudine to its 
active triphosphate form. Zidovudine is therefore not recommended to be used in combination with 
stavudine. 

In vitro studies indicate that the activation of stavudine is inhibited by doxorubicin and ribavirin but 
not by other medicinal products used in HIV infection which are similarly phosphorylated, 
(e.g. didanosine, zalcitabine, ganciclovir and foscarnet) therefore, coadministration of stavudine with 
either doxorubicin or ribavirin should be undertaken with caution. Stavudine’s influence on the 
phosphorylation kinetics of nucleoside analogues other than zidovudine has not been investigated. 

Clinically significant interactions of stavudine or stavudine plus didanosine with nelfinavir have not 
been observed. 

Stavudine does not inhibit the major cytochrome P450 isoforms CYP1A2, CYP2C9, CYP2C19, 
CYP2D6, and CYP3A4; therefore, it is unlikely that clinically significant drug interactions will occur 
with medicines metabolised through these pathways. 

Because stavudine is not protein-bound, it is not expected to affect the pharmacokinetics of 
protein-bound medicines. 

There have been no formal interaction studies with other medicinal products. 

Paediatric population 

Interaction studies have only been performed in adults.

4.6 Fertility, pregnancy and lactation 

Pregnancy 

Zerit should not be used during pregnancy unless clearly necessary.  
Clinical experience in pregnant women is limited, but congenital anomalies and abortions have been 
reported. 

In study AI455-094, performed in South-Africa, 362 mother-infant pairs were included in a prevention 
of mother-to-child-transmission study. Treatment naive pregnant women were enrolled into the study 
at gestation week 34-36 and given antiretroviral treatment until delivery. Antiretroviral prophylaxis, 
the same medications as given to the mother, was given to the new-born infant within 36 hours of 
delivery and continued for 6 weeks. In the stavudine containing arms, the neonates were treated 
for 6 weeks with stavudine 1 mg/kg BID. The follow-up time was up to 24 weeks of age. 
The mother-infant pairs were randomised to receive either stavudine (N= 91), didanosine (N= 94), 
stavudine + didanosine (N= 88) or zidovudine (N= 89). 
95% Confidence intervals for the mother-to-child-transmission rates were 5.4-19.3% 
(stavudine), 5.2-18.7% (didanosine); 1.3-11.2% (stavudine + didanosine); and 1.9-12.6% for 
zidovudine. 

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Preliminary safety data from this study (see also section 4.8), showed an increased infant mortality in 
the stavudine + didanosine (10%) treatment group compared to the stavudine (2%), didanosine (3%) 
or zidovudine (6%) groups, with a higher incidence of stillbirths in the stavudine + didanosine group. 
Data on lactic acid in serum were not collected in this study. 

However lactic acidosis, sometimes fatal, has been reported in pregnant women who received the 
combination of didanosine and stavudine with or without other anti-retroviral treatment (see sections 
4.3 and 4.4). Embryo-foetal toxicities were seen only at high exposure levels in animals. Preclinical 
studies showed placental transfer of stavudine (see section 5.3). Until additional data become 
available, Zerit should be given during pregnancy only after special consideration; there is insufficient 
information to recommend Zerit for prevention of mother-to-child transmission of HIV.  

Breast-feeding 

It is recommended that HIV infected women should not breast-feed under any circumstances in order 
to avoid transmission of HIV. 
The data available on stavudine excretion into human breast milk are insufficient to assess the risk to 
the infant. Studies in lactating rats showed that stavudine is excreted in breast milk. Therefore, 
mothers should be instructed to discontinue breast-feeding prior to receiving Zerit. 

Fertility 

No evidence of impaired fertility was seen in rats at high exposure levels (up to 216 times that 
observed at the recommended clinical dose). 

4.7 Effects on ability to drive and use machines 

No studies on the effects on the ability to drive and use machines have been performed. Stavudine may 
cause dizziness and/or somnolence. Patients should be instructed that if they experience these 
symptoms they should avoid potentially hazardous tasks such as driving or operating machinery. 

4.8 Undesirable effects 

Summary of the safety profile 

Stavudine therapy is associated with several severe adverse reactions, such as lactic acidosis, 
lipoatrophy and polyneuropathy, for which a potential underlying mechanism is mitochondrial 
toxicity. Given these potential risks, a benefit-risk assessment for each patient should be made and an 
alternative antiretroviral should be carefully considered (see section 4.4 and below). 

Cases of lactic acidosis, sometimes fatal, usually associated with severe hepatomegaly and hepatic 
steatosis, have been reported in < 1% of patients taking stavudine in combination with other 
antiretrovirals (see section 4.4). 

Motor weakness has been reported rarely in patients receiving combination antiretroviral therapy 
including Zerit. Most of these cases occurred in the setting of symptomatic hyperlactatemia or lactic 
acidosis syndrome (see section 4.4). The evolution of motor weakness may mimic the clinical 
presentation of Guillain-Barré syndrome (including respiratory failure). Symptoms may continue or 
worsen following discontinuation of therapy. 

Hepatitis or liver failure, which was fatal in some cases, has been reported with the use of stavudine 
(see section 4.4). 

Lipoatrophy was commonly reported in patients treated with stavudine in combination with other 
antiretrovirals (see section 4.4). 

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Peripheral neuropathy was seen in combination studies of Zerit with lamivudine plus efavirenz; the 
frequency of peripheral neurologic symptoms was 19% (6% for moderate to severe) with a rate of 
discontinuation due to neuropathy of 2%. The patients usually experienced resolution of symptoms 
after dose reduction or interruption of stavudine. 

Pancreatitis, occasionally fatal, has been reported in up to 2-3% of patients enrolled in monotherapy 
clinical studies (see section 4.4). Pancreatitis was reported in < 1% of patients in combination therapy 
studies with Zerit. 

Tabulated summary of adverse reactions 

Adverse reactions of moderate or greater severity with at least a possible relationship to treatment 
regimen (based on investigator attribution) reported from 467 patients treated with Zerit in 
combination with lamivudine and efavirenz in two randomised clinical trials and along-term follow-up 
study (follow-up: median 56 weeks ranging up to 119 weeks) are listed below. Also listed are adverse 
reactions observed post-marketing in association with stavudine-containing antiretroviral treatment. 
The frequency of adverse reactions listed below is defined using the following convention: very 
common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to 
< 1/1,000); very rare (< 1/10,000). Within each frequency grouping, undesirable effects are presented 
in order of decreasing seriousness. 

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Blood and lymphatic system 
disorders: 

rare: anaemia* 
very rare: neutropenia *, thrombocytopenia* 

Endocrine disorders: uncommon: gynaecomastia 

Metabolism and nutrition 
disorders: 

common: lipoatrophy**, asymptomatic hyperlactatemia 
uncommon: lactic acidosis (in some cases involving motor 

weakness), anorexia 
rare: hyperglycaemia* 
very rare: diabetes mellitis*  

Psychiatric disorders: common: depression 
uncommon: anxiety, emotional lability 

Nervous system disorders: common: peripheral neurologic symptoms including peripheral 
neuropathy, paresthesia, and peripheral neuritis; 
dizziness; abnormal dreams; headache, insomnia; 
abnormal thinking; somnolence 

very rare: motor weakness* (most often reported in the setting of 
symptomatic hyperlactatemia or lactic acidosis syndrome) 

Gastrointestinal disorders: common: diarrhoea, abdominal pain, nausea, dyspepsia 
uncommon: pancreatitis, vomiting 

Hepatobiliary disorders: uncommon: hepatitis or jaundice 
rare: hepatic steatosis* 
very rare: liver failure* 

Skin and subcutaneous tissue 
disorders:

common: rash, pruritus 
uncommon: urticaria

Musculoskeletal and connective 
tissue disorders: 

uncommon: arthralgia, myalgia 

General disorders and 
administration site conditions: 

common: fatigue 
uncommon: asthenia 

* Adverse reactions observed post-marketing in association with stavudine-containing antiretroviral    
treatment 

** See Section Description of selected adverse reactions for more details. 

Description of selected adverse reactions 

Immune reactivation syndrome: in HIV-infected patients with severe immune deficiency at the time of 
initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or 
residual opportunistic infections may arise. Autoimmune disorders (such as Graves' disease and 
autoimmune hepatitis) have also been reported; however, the reported time to onset is more variable 
and these events can occur many months after initiation of treatment (see section 4.4). 

Lipoatrophy: stavudine has been shown to cause loss of subcutaneous fat, which is most evident in the 
face, limbs and buttocks.  The incidence and severity of lipoatrophy are related to cumulative 
exposure, and is often not reversible when stavudine treatment is stopped. Patients receiving Zerit 
should be frequently examined and questioned for signs of lipoatrophy. When such development is 
found, treatment with Zerit should not be continued (see section 4.4). 

Metabolic parameters: weight and levels of blood lipids and glucose may increase during 
antiretroviral therapy (see section 4.4). 

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Osteonecrosis: cases of osteonecrosis have been reported, particularly in patients with generally 
acknowledged risk factors, advanced HIV disease or long-term exposure to combination antiretroviral 
therapy (CART). The frequency of this is unknown (see section 4.4). 

Laboratory abnormalities: laboratory abnormalities reported in these two trials and an ongoing 
follow-up study included elevations of ALT (> 5 x ULN) in 3%, of AST (> 5 x ULN) in 3%, of lipase 
(≥ 2.1 ULN) in 3% of the patients in the Zerit group. Neutropenia (< 750 cells/mm3) was reported 
in 5%, thrombocytopenia (platelets < 50,000/mm3) in 2%, and low haemoglobin (< 8 g/dl) in < 1% of 
patients receiving Zerit. 
Macrocytosis was not evaluated in these trials, but was found to be associated with Zerit in an earlier 
trial (MCV > 112 fl occurred in 30% of patients treated with Zerit). 

Paediatric population 

Adolescents, children and infants: adverse reactions and serious laboratory abnormalities reported to 
occur in paediatric patients ranging in age from birth through adolescence who received stavudine in 
clinical studies were generally similar in type and frequency to those seen in adults. However, 
clinically significant peripheral neuropathy is less frequent. These studies include ACTG 240, 
where 105 paediatric patients ages 3 months to 6 years received Zerit 2 mg/kg/day for a median 
of 6.4 months; a controlled clinical trial where 185 newborns received Zerit 2 mg/kg/day either alone 
or in combination with didanosine from birth through 6 weeks of age; and a clinical trial 
where 8 newborns received Zerit 2 mg/kg/day in combination with didanosine and nelfinavir from 
birth through 4 weeks of age. 

In study AI455-094 (see also section 4.6), the safety follow-up period was restricted to only six 
months, which may be insufficient to capture long-term data on neurological adverse events and 
mitochondrial toxicity. Relevant grade 3-4 laboratory abnormalities in the 91 stavudine treated infants 
were low neutrophils in 7%, low hemoglobin in 1%, ALT increase in 1% and no lipase abnormality. 
Data on lactic acid in serum were not collected. No notable differences in the frequency of adverse 
drug reactions were seen between treatment groups. There was, however, an increased infant mortality 
in the stavudine + didanosine (10%) treatment group compared to the stavudine (2%), didanosine (3%) 
or zidovudine (6%) groups, with a higher incidence of stillbirths in the stavudine + didanosine group. 

Mitochondrial dysfunction: review of the postmarketing safety database shows that adverse reactions 
indicative of mitochondrial dysfunction have been reported in the neonate and infant population 
exposed to one or more nucleoside analogues (see also section 4.4). The HIV status for the newborns 
and infants ≤ 3 months of age was negative, for older infants it tended to be positive. The profile of the 
adverse events for newborns and infants ≤ 3 months of age showed increases in lactic acid levels, 
neutropenia, anaemia, thrombocytopenia, hepatic transaminase increases and increased lipids, 
including hypertriglyceridaemia. The number of reports in older infants was too small to identify a 
pattern. 

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 

Experience in adults treated with up to 12 times the recommended daily dosage revealed no acute 
toxicity. Complications of chronic overdosage could include peripheral neuropathy and hepatic 
dysfunction. The mean haemodialysis clearance of stavudine is 120 ml/min. The contribution of this to 
the total elimination in an overdose situation is unknown. It is not known whether stavudine is 
removed by peritoneal dialysis. 

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5. PHARMACOLOGICAL PROPERTIES 

5.1 Pharmacodynamic properties 

Pharmacotherapeutic group: antivirals for systemic use, nucleoside and nucleotide reverse 
transcriptase inhibitors, ATC code: J05AF04 

Mechanism of action

Stavudine, a thymidine analogue, is phosphorylated by cellular kinases to stavudine triphosphate 
which inhibits HIV reverse transcriptase by competing with the natural substrate, thymidine 
triphosphate. It also inhibits viral DNA synthesis by causing DNA chain termination due to a lack of 
the 3’-hydroxyl group necessary for DNA elongation. Cellular DNA polymerase γ is also sensitive to 
inhibition by stavudine triphosphate, while cellular polymerases α and β are inhibited at 
concentrations 4,000-fold and 40-fold higher, respectively, than that needed to inhibit HIV reverse 
transcriptase. 

Resistance

Stavudine treatment can select for and/or maintain thymidine analogue mutations (TAMs) associated 
with zidovudine resistance. The decrease of susceptibility in vitro is subtle requiring two or more 
TAMs (generally M41L and T215Y) before stavudine susceptibility is decreased (> 1.5 fold).
These TAMs are seen at a similar frequency with stavudine and zidovudine in virological treatment. 
The clinical relevance of these findings suggest that stavudine should be generally avoided in the 
presence of TAMs, especially M41L and T215Y. 
The activity of stavudine is also affected by multi-drug resistance associated mutations such as 
Q151M. In addition, K65R has been reported in patients receiving stavudine/didanosine or 
stavudine/lamivudine, but not in patients receiving stavudine monotherapy. V75T is selected in vitro
by stavudine and reduces susceptibility to stavudine by 2-fold. It occurs in ~1% of patients receiving 
stavudine. 

Clinical efficacy and safety 

Zerit has been studied in combination with other antiretroviral agents, e.g. didanosine, lamivudine, 
ritonavir, indinavir, saquinavir, efavirenz, and nelfinavir. 

In antiretroviral naive patients 

Study AI455-099 was a 48-week, randomised, double-blind study with Zerit (40 mg twice daily), in 
combination with lamivudine (150 mg twice daily) plus efavirenz (600 mg once daily), 
in 391 treatment-naive patients, with a median CD4 cell count of  272 cells/mm3

(range 61 to 1,215 cells/mm3) and a median plasma HIV-1 RNA of 4.80 log10 copies/ml 
(range 2.6 to 5.9 log 10 copies/ml) at baseline. Patients were primarily males (70%) and non-white 
(58%) with a median age of 33 years (range 18 to 68 years). 

Study AI455-096 was a 48-week, randomised, double-blind study with Zerit (40 mg twice daily), in 
combination with lamivudine (150 mg twice daily) plus efavirenz (600 mg once daily), 
in 76 treatment-naive patients, with a median CD4 cell count of 261 cells/mm3

(range 63 to 962 cells/mm3) and a median plasma HIV-1 RNA of  4.63 log10 copies/ml 
(range 3.0 to 5.9 log10 copies/ml) at baseline. Patients were primarily males (76%) and white (66%) 
with a median age of 34 years (range 22 to 67 years). 

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The results of AI455-099 and AI455-096 are presented in Table 1. Both studies were designed to 
compare two formulations of Zerit, one of which was the marketed formulation dosed as currently 
approved in product labelling. Only the data from the marketed formulation are presented. 

Table 1:  Efficacy Outcomes at Week 48 (Studies AI455-099 and AI455-096) 

Parameter 

AI455-099 AI455-096 

Zerit + lamivudine + 

efavirenz

n=391

Zerit + lamivudine + 

efavirenz

 n=76 

HIV RNA < 400 copies/ml, treatment response, %
All patients 73 66
HIV RNA < 50 copies/ml, treatment response, %
All patients 55 38
HIV RNA Mean Change from Baseline, log10 copies/ml 
All patients -2.83 (n=321a) -2.64 (n=58)
CD4 Mean Change from Baseline, cells/mm3

All patients 182 (n=314) 195 (n=55)
a Number of patients evaluable. 

Paediatric population 

The use of stavudine in adolescents, children and infants is supported by pharmacokinetic and safety 
data in paediatric patients (see also sections 4.8 and 5.2). 

5.2 Pharmacokinetic properties 

Absorption 

The absolute bioavailability is 86±18%. After multiple oral administration of 0.5-0.67 mg/kg doses, a 
Cmax value of 810±175 ng/ml was obtained. Cmax and AUC increased proportionally with dose in the 
dose ranges, intravenous 0.0625-0.75 mg/kg, and oral 0.033-4.0 mg/kg. 
In eight patients receiving 40 mg twice daily in the fasted state, steady-state AUC0-12h 
was 1284±227 ng⋅h/ml (18%) (mean ± SD [% CV]), Cmax was 536±146 ng/ml (27%), and Cmin
was 9±8 ng/ml (89%). A study in asymptomatic patients demonstrated that systemic exposure is 
similar while Cmax is lower and Tmax is prolonged when stavudine is administered with a standardised, 
high-fat meal compared with fasting conditions. The clinical significance of this is unknown. 

Distribution

The apparent volume of distribution at steady state is 46±21 l. It was not possible to detect stavudine 
in cerebrospinal fluid until at least 2 hours after oral administration. Four hours after administration, 
the CSF/plasma ratio was 0.39±0.06. No significant accumulation of stavudine is observed with 
repeated administration every 6, 8, or 12 hours. 
Binding of stavudine to serum proteins was negligible over the concentration range 
of 0.01 to 11.4 µg/ml. Stavudine distributes equally between red blood cells and plasma. 

Metabolism 

Unchanged stavudine was the major drug-related component in total plasma radioactivity circulating 
after an oral 80 mg dose of 14C-stavudine in healthy subjects. The AUC(inf) for stavudine was 61% of 
the AUC(inf) of the total circulating radioactivity. Metabolites include oxidised stavudine, glucuronide 
conjugates of stavudine and its oxidised metabolite, and an N-acetylcysteine conjugate of the ribose 
after glycosidic cleavage, suggesting that thymine is also a metabolite of stavudine. 

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Elimination 

Following an oral 80-mg dose of 14C-stavudine to healthy subjects, approximately 95% and 3% of the 
total radioactivity was recovered in urine and faeces, respectively.  Approximately 70% of the orally 
administered stavudine dose was excreted as an unchanged drug in urine. Mean renal clearance of the 
parent compound is approximately 272 ml/min, accounting for approximately 67% of the apparent 
oral clearance, indicating active tubular secretion in addition to glomerular filtration.  

In HIV-infected patients,total clearance of stavudine is 594±164 ml/min, and renal clearance 
is 237±98 ml/min. The total clearance of stavudine appears to be higher in HIV-infected patients, 
while the renal clearance is similar between healthy subjects and HIV-infected patients.  The 
mechanism and clinical significance of this difference are unknown. After intravenous 
administration, 42% (range: 13% to 87%) of dose is excreted unchanged in the urine. The 
corresponding values after oral single and multiple dose administration are 35% (range: 8% to 72%) 
and 40% (range: 12% to 82%), respectively. The mean terminal elimination half-life of stavudine 
is 1.3 to 2.3 hours following single or multiple doses, and is independent of dose. In vitro, stavudine 
triphosphate has an intracellular half-life of 3.5 hours in CEM T-cells (a human T-lymphoblastoid cell 
line) and peripheral blood mononuclear cells, supporting twice daily dosing. 
The pharmacokinetics of stavudine was independent of time, since the ratio between AUC(ss) at steady 
state and the AUC(0-t) after the first dose was approximately 1. Intra- and interindividual variation in 
pharmacokinetic characteristics of stavudine is low, approximately 15% and 25%, respectively, after 
oral administration. 

Special Populations 

Renal impairment: the clearance of stavudine decreases as creatinine clearance decreases; therefore, it 
is recommended that the dosage of Zerit be adjusted in patients with reduced renal function (see 
section 4.2). 

Hepatic impairment: stavudine pharmacokinetics in patients with hepatic impairment were similar to 
those in patients with normal hepatic function. 

Paediatric population 

Adolescents, children and infants: total exposure to stavudine was comparable between adolescents, 
children and infants ≥ 14 days receiving the 2 mg/kg/day dose and adults receiving 1 mg/kg/day. 
Apparent oral clearance was approximately 14 ml/min/kg for infants ages 5 weeks 
to 15 years, 12 ml/min/kg for infants ages 14 to 28 days, and 5 ml/min/kg for infants on the day of 
birth. Two to three hours post-dose, CSF/plasma ratios of stavudine ranged from 16% to 125% (mean 
of 59%±35%). 

5.3 Preclinical safety data 

Animal data showed embryo-foetal toxicity at very high exposure levels. An ex vivo study using a 
term human placenta model demonstrated that stavudine reaches the foetal circulation by simple 
diffusion. A rat study also showed placental transfer of stavudine, with the foetal tissue concentration 
approximately 50% of the maternal plasma concentration. 
Stavudine was genotoxic in in vitro tests in human lymphocytes possessing triphosphorylating activity 
(in which no no-effect level was established), in mouse fibroblasts, and in an in vivo test for 
chromosomal aberrations. Similar effects have been observed with other nucleoside analogues. 
Stavudine was carcinogenic in mice (liver tumours) and rats (liver tumours: cholangiocellular, 
hepatocellular, mixed hepatocholangiocellular, and/or vascular; and urinary bladder carcinomas) at 
very high exposure levels. No carcinogenicity was noted at doses of 400 mg/kg/day in mice 
and 600 mg/kg/day in rats, corresponding to exposures ~ 39 and 168 times the expected human 
exposure, respectively, suggesting an insignificant carcinogenic potential of stavudine in clinical 
therapy. 

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6. PHARMACEUTICAL PARTICULARS 

6.1 List of excipients 

Capsule contents 
Lactose 
Magnesium stearate 
Microcrystalline cellulose 
Sodium starch glycolate 

Capsule shell 
Gelatin 
Iron oxide colorant (E172) 
Silicon dioxide 
Sodium laurilsulphate 
Titanium dioxide (E171) 

Black ink containing 
Shellac 
Propylene Glycol 
Purified Water 
Potassium Hydroxide 
Iron Oxide (E172) 

6.2 Incompatibilities 

Not applicable. 

6.3 Shelf life 

2 years. 

6.4 Special precautions for storage 

Store below 25°C (aclar/alu blisters). 
Do not store above 30°C (HDPE bottles). 
Store in the original package. 

6.5 Nature and contents of container 

HDPE bottles with child resistant screw cap (60 hard capsules per bottle). 

Aclar/aluminum blisters with 14 hard capsules per card and 4 cards (56 hard capsules) per carton. 

Not all pack sizes may be marketed. 

6.6 Special precautions for disposal 

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 

7. MARKETING AUTHORISATION HOLDER 

Bristol-Myers Squibb Pharma EEIG 
Plaza 254 

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Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland 

8. MARKETING AUTHORISATION NUMBER(S) 

EU/1/96/009/001 - 008 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

Date of first authorisation: 08 May 1996 
Date of last renewal: 20 April 2011 

10. DATE OF REVISION OF THE TEXT 

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu/. 

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1. NAME OF THE MEDICINAL PRODUCT 

Zerit 200 mg powder for oral solution 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

Each bottle contains 200 mg of stavudine. 
The reconstituted solution contains 1 mg of stavudine per ml. 

Excipients with known effect 
Each bottle contains 31.5 mg of propylhydroxybenzoate (E216) 
Each bottle contains 315 mg of methylhydroxybenzoate (E218) 
Each bottle contains 10.15 g of sucrose 

For the full list of excipients, see section 6.1. 

3. PHARMACEUTICAL FORM 

Powder for oral solution. 

Off-white to pale-pink, gritty powder. 

4. CLINICAL PARTICULARS 

4.1 Therapeutic indications 

Zerit is indicated in combination with other antiretroviral medicinal products for the treatment of HIV 
infected adult patients and paediatric patients (from birth) only when other antiretrovirals can not be 
used. The duration of therapy with Zerit should be limited to the shortest time possible (see section 
4.2). 

4.2 Posology and method of administration 

The therapy should be initiated by a doctor experienced in the management of HIV infection (see also 
section 4.4). 

For patients starting therapy with Zerit, the duration should be limited to the shortest time possible 
followed by a switch to an alternative appropriate therapy whenever possible. Patients continuing 
treatment with Zerit should be assessed frequently and switched to an alternative appropriate therapy 
whenever possible (see section 4.4). 

Posology 

Adults: the recommended oral dosage is 

Patient weight Zerit dosage
< 60 kg 
≥ 60 kg

30 mg twice daily (every 12 hours) 
40 mg twice daily (every 12 hours)

Paediatric population 

Adolescents, children and infants: the recommended oral dosage is 

Patient age and/or weight Zerit dosage
From birth* to 13 days old 0.5 mg/kg twice daily (every 12 hours) 

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At least 14 days old and < 30 kg 
≥ 30 kg

1 mg/kg twice daily (every 12 hours) 
adult dosing

*The reduced posology in neonates from 0 to 13 days is based on average 
study data and may not correspond to invidual variation in kidney maturation. 
Dosing recommendations are not available for neonates with a gestational 
age < 37 weeks. 

The powder formulation of Zerit should be used for infants under the age of 3 months. Adult patients 
that have problems swallowing capsules should ask their doctor about the possibility of changing to 
the powder formulation of this medicine. 

Instructions for preparation, see section 6.6. 

Dose adjustments 

Peripheral neuropathy: if symptoms of peripheral neuropathy develop (usually characterised by 
persistent numbness, tingling, or pain in the feet and/or hands) (see section 4.4), patients should be 
switched to an alternative treatment regimen, if appropriate. In the rare cases when this is 
inappropriate, dose reduction of stavudine may be considered, while the symptoms of peripheral 
neuropathy are under close monitoring and satisfactory virological suppression is maintained. 
The possible benefits of a dose reduction should be balanced in each case against the risks - which 
may result from this measure (lower intracellular concentrations). 

Special populations 

Elderly: Zerit has not been specifically investigated in patients over the age of 65.

Hepatic impairment: no initial dosage adjustment is necessary. 

Renal impairment: the following dosages are recommended 

Zerit dosage (according to creatinine clearance) 

Patient weight 26-50 ml/min ≤ 25 ml/min 
(including dialysis dependence*)

< 60 kg 15 mg twice daily 15 mg every 24 hours 

≥ 60 kg 20 mg twice daily 20 mg every 24 hours 

* Patients on haemodialysis should take Zerit after the completion of 
haemodialysis, and at the same time on non-dialysis days. 

Since urinary excretion is also a major route of elimination of stavudine in paediatric patients, the 
clearance of stavudine may be altered in paediatric patients with renal impairment. Although there are 
insufficient data to recommend a specific dosage adjustment of Zerit in this patient population, a 
reduction in the dose and/or an increase in the interval between doses proportional to the reduction for 
adults should be considered. There are no dosage recommendations for paediatric patients under the 
age of 3 months with renal impairment. 

Method of administration 

For optimal absorption, Zerit should be taken on an empty stomach (i.e. at least 1 hour prior to meals) 
but, if this is not possible, it may be taken with a light meal. 

4.3 Contraindications 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

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Co-administration with didanosine due to the potential for serious and/or life-threatening events 
notably lactic acidosis, liver function abnormalities, pancreatitis and peripheral neuropathy (see 
sections 4.4 and 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.  

Stavudine therapy is associated with several severe side effects, such as lactic acidosis, lipoatrophy 
and polyneuropathy, for which a potential underlying mechanism is mitochondrial toxicity. Given 
these potential risks, a benefit-risk assessment for each patients should be made and an alternative 
antiretroviral should be carefully considered (see Lactic acidosis, Lipoatrophy, and Peripheral 
neuropathy below and section 4.8). 

Lactic acidosis: lactic acidosis, usually associated with hepatomegaly and hepatic steatosis has been 
reported with the use of stavudine. Early symptoms (symptomatic hyperlactatemia) include benign 
digestive symptoms (nausea, vomiting and abdominal pain), non-specific malaise, loss of appetite, 
weight loss, respiratory symptoms (rapid and/or deep breathing) or neurological symptoms (including 
motor weakness). Lactic acidosis has a high mortality and may be associated with pancreatitis, liver 
failure, renal failure, or motor paralysis. 
Lactic acidosis generally occurred after a few or several months of treatment. 
Treatment with stavudine should be discontinued if there is symptomatic hyperlactatemia and 
metabolic/lactic acidosis, progressive hepatomegaly, or rapidly elevating aminotransferase levels. 
Caution should be exercised when administering stavudine to any patient (particularly obese women) 
with hepatomegaly, hepatitis or other known risk factors for liver disease and hepatic steatosis 
(including certain medicinal products and alcohol). Patients co-infected with hepatitis C and treated 
with alpha interferon and ribavirin may constitute a special risk. 
Patients at increased risk should be followed closely (see also section 4.6). 

Liver disease: hepatitis or liver failure, which was fatal in some cases, has been reported. The safety 
and efficacy of stavudine has not been established in patients with significant underlying liver 
disorders. Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy 
are at 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 product information for these 
medicinal products. 

Patients with pre-existing liver dysfunction including chronic active hepatitis have an increased 
frequency of liver function abnormalities during combination antiretroviral therapy and should be 
monitored according to standard practice. If there is evidence of worsening liver disease in such 
patients, interruption or discontinuation of treatment must be considered. 

In the event of rapidly elevating transaminase levels (ALT/AST, > 5 times upper limit of normal, 
ULN), discontinuation of Zerit and any potentially hepatotoxic medicinal products should be 
considered. 

Lipoatrophy: on the basis of mitochondrial toxicity stavudine has been shown to cause loss of 
subcutaneous fat, which is most evident in the face, limbs and buttocks.  

In randomized controlled trials of treatment-naive patients, clinical lipoatrophy developed in a higher 
proportion of patients treated with stavudine compared to other nucleosides (tenofovir or abacavir).  
Dual energy x-ray absorptiometry (DEXA) scans demonstrated overall limb fat loss in stavudine 
treated patients compared to limb fat gain or no change in patients treated with other NRTIs (abacavir, 
tenofovir or zidovudine). The incidence and severity of lipoatrophy are cumulative over time with 
stavudine-containing regimens.  In clinical trials, switching from stavudine to other nucleosides 
(tenofovir or abacavir) resulted in increases in limb fat with modest to no improvements in clinical 

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lipoatrophy. Given the potential risks of using Zerit including lipoatrophy, a benefit-risk assessment 
for each patient should be made and an alternative antiretroviral carefully considered. Patients 
receiving Zerit should be frequently examined and questioned for signs of lipoatrophy. When such 
development is found, discontinuation of Zerit should  be considered. 

Weight and metabolic parameters: an increase in weight and in levels of blood lipids and glucose may 
occurr 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. 

Peripheral neuropathy: up to 20% of patients treated with Zerit will develop peripheral neuropathy, 
often starting after some months of treatment. Patients with a history of neuropathy, or with other risk 
factors (for example alcohol, medicines such as isoniazid) are at particular risk. Patients should be 
monitored for symptoms (persistent numbness, tingling or pain in feet/hands) and if present patients 
should be switched to an alternate treatment regimen (see section 4.2 and Not recommended 
combinations, below). 

Pancreatitis: patients with a history of pancreatitis had an incidence of approximately 5% onZerit, as 
compared to approximately 2% in patients without such a history. Patients with a high risk of 
pancreatitis or those receiving products known to be associated with pancreatitis should be closely 
followed for symptoms of this condition. 

Immune reactivation syndrome: in HIV-infected patients with severe immune deficiency at the time of 
institution of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic 
or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of 
symptoms. Typically, such reactions have been observed within the first few weeks or months of 
initiation of CART. Relevant examples are cytomegalovirus retinitis, generalised and/or focal 
mycobacterial infections, and Pneumocystis carinii pneumonia. Any inflammatory symptoms should 
be evaluated and treatment instituted when necessary. Autoimmune disorders (such as Graves' disease 
and autoimmune hepatitis) have also been reported to occur in the setting of immune reactivation; 
however, the reported time to onset is more variable and these events can occur many months after 
initiation of treatment. 

Osteonecrosis: although the etiology is considered to be multifactorial (including corticosteroid use, 
alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis 
have been reported particularly in patients with advanced HIV-disease and/or long-term exposure to 
combination antiretroviral therapy (CART). Patients should be advised to seek medical advice if they 
experience joint aches and pain, joint stiffness or difficulty in movement. 

Excipients: the reconstituted powder for oral solution contains 50 mg sucrose per ml of reconstituted 
solution. This should be taken into account in patients with diabetes mellitus. Patients with rare 
hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase 
insufficiency should not take this medicine. May be harmful to the teeth. 
This product contains methylhydroxybenzoate (E218) and propylhydroxybenzoate (E216) that may 
cause allergic reactions (possibly delayed). 

Not recommended combinations: pancreatitis (fatal and nonfatal) and peripheral neuropathy (severe in 
some cases) have been reported in HIV infected patients receiving stavudine in association with 
hydroxyurea and didanosine (see section 4.3). Hepatotoxicity and hepatic failure resulting in death 
were reported during postmarketing surveillance in HIV infected patients treated with antiretroviral 
agents and hydroxyurea; fatal hepatic events were reported most often in patients treated with 
stavudine, hydroxyurea and didanosine. Hence, hydroxyurea should not be used in the treatment of 
HIV infection. 

Elderly: Zerit has not been specifically investigated in patients over the age of 65. 

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Paediatric population 

Infants under the age of 3 months: safety data are available from clinical trials up to 6 weeks of 
treatment in 179 newborns and infants < 3 months of age (see section 4.8). 
Special consideration should be given to the antiretroviral treatment history and the resistance profile 
of the HIV strain of the mother. 

Mitochondrial dysfunction following exposure in utero: nucleos(t)ide analogues may impact 
mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and 
zidovudine. There have been reports of mitochondrial dysfunction in HIV-negative infants exposed in 
utero and/or post-natally to nucleoside analogues (see also section 4.8); these have predominantly 
concerned treatment with regimens containing zidovudine. The main adverse reactions reported are 
haematological disorders (anaemia, neutropenia)  and metabolic disorders (hyperlactatemia, 
hyperlipasemia). These events have often been transitory. Late-onset neurological disorders have been 
reported rarely (hypertonia, convulsion, abnormal behaviour). Whether such neurological disorders are 
transient or permanent is currently unknown. These findings should be considered for any child 
exposed in utero to nucleos(t)ide analogues, that present with severe clinical findings of unknown 
etiology, particularly neurologic findings. These findings do not affect current national 
recommendations to use antiretroviral therapy in pregnant women to prevent vertical transmission of 
HIV. 

4.5 Interaction with other medicinal products and other forms of interaction 

The combination of stavudine with didanosine is contraindicated given that both drugs exhibits high 
risk of mitochondrial toxicity (see sections 4.3 and 4.4). 

Since stavudine is actively secreted by the renal tubules, interactions with other actively secreted 
medicinal products are possible, e.g. with trimethoprim. No clinically relevant pharmacokinetic 
interaction has, however, been seen with lamivudine. 

Zidovudine and stavudine are phosphorylated by the cellular enzyme (thymidine kinase), which 
preferentially phosphorylates zidovudine, thereby decreasing the phosphorylation of stavudine to its 
active triphosphate form. Zidovudine is therefore not recommended to be used in combination with 
stavudine. 

In vitro studies indicate that the activation of stavudine is inhibited by doxorubicin and ribavirin but 
not by other medicinal products used in HIV infection which are similarly phosphorylated, 
(e.g. didanosine, zalcitabine, ganciclovir and foscarnet) therefore, coadministration of stavudine with 
either doxorubicin or ribavirin should be undertaken with caution. Stavudine’s influence on the 
phosphorylation kinetics of nucleoside analogues other than zidovudine has not been investigated. 

Clinically significant interactions of stavudine or stavudine plus didanosine with nelfinavir have not 
been observed. 

Stavudine does not inhibit the major cytochrome P450 isoforms CYP1A2, CYP2C9, CYP2C19, 
CYP2D6, and CYP3A4; therefore, it is unlikely that clinically significant drug interactions will occur 
with medicines metabolised through these pathways. 

Because stavudine is not protein-bound, it is not expected to affect the pharmacokinetics of 
protein-bound medicines. 

There have been no formal interaction studies with other medicinal products. 

Paediatric population 

Interaction studies have only been performed in adults.

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4.6 Fertility, pregnancy and lactation 

Pregnancy 

Zerit should not be used during pregnancy unless clearly necessary.  
Clinical experience in pregnant women is limited, but congenital anomalies and abortions have been 
reported. 

In study AI455-094, performed in South-Africa, 362 mother-infant pairs were included in a prevention 
of mother-to-child-transmission study. Treatment naive pregnant women were enrolled into the study 
at gestation week 34-36 and given antiretroviral treatment until delivery. Antiretroviral prophylaxis, 
the same medications as given to the mother, was given to the new-born infant within 36 hours of 
delivery and continued for 6 weeks. In the stavudine containing arms, the neonates were treated 
for 6 weeks with stavudine 1 mg/kg BID. The follow-up time was up to 24 weeks of age. 
The mother-infant pairs were randomised to receive either stavudine (N= 91), didanosine (N= 94), 
stavudine + didanosine (N= 88) or zidovudine (N= 89). 
95% Confidence intervals for the mother-to-child-transmission rates were 5.4-19.3% 
(stavudine), 5.2-18.7% (didanosine); 1.3-11.2% (stavudine + didanosine); and 1.9-12.6% for 
zidovudine. 

Preliminary safety data from this study (see also section 4.8), showed an increased infant mortality in 
the stavudine + didanosine (10%) treatment group compared to the stavudine (2%), didanosine (3%) 
or zidovudine (6%) groups, with a higher incidence of stillbirths in the stavudine + didanosine group. 
Data on lactic acid in serum were not collected in this study. 

However, lactic acidosis, sometimes fatal, has been reported in pregnant women who received the 
combination of didanosine and stavudine with or without other anti-retroviral treatment (see sections 
4.3 and 4.4). Embryo-foetal toxicities were seen only at high exposure levels in animals. Preclinical 
studies showed placental transfer of stavudine (see section 5.3). Until additional data become 
available, Zerit should be given during pregnancy only after special consideration; there is insufficient 
information to recommend Zerit for prevention of mother-to-child transmission of HIV.  

Breast-feeding 

It is recommended that HIV infected women should not breast-feed under any circumstances in order 
to avoid transmission of HIV. 
The data available on stavudine excretion into human breast milk are insufficient to assess the risk to 
the infant. Studies in lactating rats showed that stavudine is excreted in breast milk. Therefore, 
mothers should be instructed to discontinue breast-feeding prior to receiving Zerit. 

Fertility 

No evidence of impaired fertility was seen in rats at high exposure levels (up to 216 times that 
observed at the recommended clinical dose). 

4.7 Effects on ability to drive and use machines 

No studies on the effects on the ability to drive and use machines have been performed. Stavudine may 
cause dizziness and/or somnolence. Patients should be instructed that if they experience these 
symptoms they should avoid potentially hazardous tasks such as driving or operating machinery. 

4.8 Undesirable effects 

Summary of the safety profile 

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Stavudine therapy is associated with several severe adverse reactions, such as lactic acidosis, 
lipoatrophy and polyneuropathy, for which a potential underlying mechanism is mitochondrial 
toxicity. Given these potential risks, a benefit-risk assessment for each patient should be made and an 
alternative antiretroviral should be carefully considered (see section 4.4 and below). 

Cases of lactic acidosis, sometimes fatal, usually associated with severe hepatomegaly and hepatic 
steatosis, have been reported in < 1% of patients taking stavudine in combination with other 
antiretrovirals (see section 4.4). 

Motor weakness has been reported rarely in patients receiving combination antiretroviral therapy 
including Zerit. Most of these cases occurred in the setting of symptomatic hyperlactatemia or lactic 
acidosis syndrome (see section 4.4). The evolution of motor weakness may mimic the clinical 
presentation of Guillain-Barré syndrome (including respiratory failure). Symptoms may continue or 
worsen following discontinuation of therapy. 

Hepatitis or liver failure, which was fatal in some cases, has been reported with the use of stavudine 
(see section 4.4). 

Lipoatrophy was commonly reported in patients treated with stavudine in combination with other 
antiretrovirals (see section 4.4). 

Peripheral neuropathy was seen in combination studies of Zerit with lamivudine plus efavirenz; the 
frequency of peripheral neurologic symptoms was 19% (6% for moderate to severe) with a rate of 
discontinuation due to neuropathy of 2%. The patients usually experienced resolution of symptoms 
after dose reduction or interruption of stavudine. 

Pancreatitis, occasionally fatal, has been reported in up to 2-3% of patients enrolled in monotherapy 
clinical studies (see section 4.4). Pancreatitis was reported in < 1% of patients in combination therapy 
studies with Zerit. 

Tabulated summary of adverse reactions 

Adverse reactions of moderate or greater severity with at least a possible relationship to treatment 
regimen (based on investigator attribution) reported from 467 patients treated with Zerit in 
combination with lamivudine and efavirenz in two randomised clinical trials and along-term follow-up 
study (follow-up: median 56 weeks ranging up to 119 weeks) are listed below. Also listed are adverse 
reactions observed post-marketing in association with stavudine-containing antiretroviral treatment. 
The frequency of adverse reactions listed below is defined using the following convention: very 
common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to 
< 1/1,000); very rare (< 1/10,000). Within each frequency grouping, undesirable effects are presented 
in order of decreasing seriousness. 

Blood and lymphatic system 
disorders: 

rare: anaemia* 
very rare: neutropenia*, thrombocytopenia* 

Endocrine disorders: uncommon: gynaecomastia 

Metabolism and nutrition 
disorders: 

common: lipoatrophy**, asymptomatic hyperlactatemia 
uncommon: lactic acidosis (in some cases involving motor 

weakness), anorexia 
rare: hyperglycaemia* 
very rare: diabetes mellitis* 

Psychiatric disorders: common: depression 
uncommon: anxiety, emotional lability 

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Nervous system disorders: common: peripheral neurologic symptoms including peripheral 
neuropathy, paresthesia, and peripheral neuritis; 
dizziness; abnormal dreams; headache, insomnia; 
abnormal thinking; somnolence 

very rare: motor weakness* (most often reported in the setting of 
symptomatic hyperlactatemia or lactic acidosis syndrome) 

Gastrointestinal disorders: common: diarrhoea, abdominal pain, nausea, dyspepsia 
uncommon: pancreatitis, vomiting 

Hepatobiliary disorders: uncommon: hepatitis or jaundice 
rare: hepatic steatosis* 
very rare: liver failure* 

Skin and subcutaneous tissue 
disorders:

common: rash, pruritus 
uncommon: urticaria

Musculoskeletal and connective 
tissue disorders: 

uncommon: arthralgia, myalgia 

General disorders and 
administration site conditions: 

common: fatigue 
uncommon: asthenia 

* Adverse reactions observed post-marketing in association with stavudine-containing antiretroviral    
treatment 

** See Section Description of selected adverse reactions for more details. 

Description of selected adverse reactions 

Immune reactivation syndrome: in HIV-infected patients with severe immune deficiency at the time of 
initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or 
residual opportunistic infections may arise. Autoimmune disorders (such as Graves' disease and 
autoimmune hepatitis) have also been reported; however, the reported time to onset is more variable 
and these events can occur many months after initiation of treatment (see section 4.4). 

Lipoatrophy: stavudine has been shown to cause loss of subcutaneous fat, which is most evident in the 
face, limbs and buttocks.  The incidence and severity of lipoatrophy are related to cumulative 
exposure, and is often not reversible when stavudine treatment is stopped. Patients receiving Zerit 
should be frequently examined and questioned for signs of lipoatrophy. When such development is 
found, treatment with Zerit should not be continued (see section 4.4). 

Metabolic parameters: weight and levels of blood lipids and glucose may increase during 
antiretroviral therapy (see section 4.4). 

Osteonecrosis: cases of osteonecrosis have been reported, particularly in patients with generally 
acknowledged risk factors, advanced HIV disease or long-term exposure to combination antiretroviral 
therapy (CART). The frequency of this is unknown (see section 4.4). 

Laboratory abnormalities: laboratory abnormalities reported in these two trials and an ongoing 
follow-up study included elevations of ALT (> 5 x ULN) in 3%, of AST (> 5 x ULN) in 3%, of lipase 
(≥ 2.1 ULN) in 3% of the patients in the Zerit group. Neutropenia (< 750 cells/mm3) was reported 
in 5%, thrombocytopenia (platelets < 50,000/mm3) in 2%, and low haemoglobin (< 8 g/dl) in < 1% of 
patients receiving Zerit. 
Macrocytosis was not evaluated in these trials, but was found to be associated with Zerit in an earlier 
trial (MCV > 112 fl occurred in 30% of patients treated with Zerit). 

Paediatric population 

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Adolescents, children and infants: adverse reactions and serious laboratory abnormalities reported to 
occur in paediatric patients ranging in age from birth through adolescence who received stavudine in 
clinical studies were generally similar in type and frequency to those seen in adults. However, 
clinically significant peripheral neuropathy is less frequent. These studies include ACTG 240, 
where 105 paediatric patients ages 3 months to 6 years received Zerit 2 mg/kg/day for a median 
of 6.4 months; a controlled clinical trial where 185 newborns received Zerit 2 mg/kg/day either alone 
or in combination with didanosine from birth through 6 weeks of age; and a clinical trial 
where 8 newborns received Zerit 2 mg/kg/day in combination with didanosine and nelfinavir from 
birth through 4 weeks of age. 

In study AI455-094 (see also section 4.6), the safety follow-up period was restricted to only six 
months, which may be insufficient to capture long-term data on neurological adverse events and 
mitochondrial toxicity. Relevant grade 3-4 laboratory abnormalities in the 91 stavudine treated infants 
were low neutrophils in 7%, low hemoglobin in 1%, ALT increase in 1% and no lipase abnormality. 
Data on lactic acid in serum were not collected. No notable differences in the frequency of adverse 
drug reactions were seen between treatment groups. There was, however, an increased infant mortality 
in the stavudine + didanosine (10%) treatment group compared to the stavudine (2%), didanosine (3%) 
or zidovudine (6%) groups, with a higher incidence of stillbirths in the stavudine + didanosine group. 

Mitochondrial dysfunction: review of the postmarketing safety database shows that adverse reactions 
indicative of mitochondrial dysfunction have been reported in the neonate and infant population 
exposed to one or more nucleoside analogues (see also section 4.4). The HIV status for the newborns 
and infants ≤ 3 months of age was negative, for older infants it tended to be positive. The profile of the 
adverse events for newborns and infants ≤ 3 months of age showed increases in lactic acid levels, 
neutropenia, anaemia, thrombocytopenia, hepatic transaminase increases and increased lipids, 
including hypertriglyceridaemia. The number of reports in older infants was too small to identify a 
pattern. 

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 

Experience in adults treated with up to 12 times the recommended daily dosage revealed no acute 
toxicity. Complications of chronic overdosage could include peripheral neuropathy and hepatic 
dysfunction. The mean haemodialysis clearance of stavudine is 120 ml/min. The contribution of this to 
the total elimination in an overdose situation is unknown. It is not known whether stavudine is 
removed by peritoneal dialysis. 

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5. PHARMACOLOGICAL PROPERTIES 

5.1 Pharmacodynamic properties 

Pharmacotherapeutic group: antivirals for systemic use, nucleoside and nucleotide reverse 
transcriptase inhibitors, ATC code: J05AF04 

Mechanism of action

Stavudine, a thymidine analogue, is phosphorylated by cellular kinases to stavudine triphosphate 
which inhibits HIV reverse transcriptase by competing with the natural substrate, thymidine 
triphosphate. It also inhibits viral DNA synthesis by causing DNA chain termination due to a lack of 
the 3’-hydroxyl group necessary for DNA elongation. Cellular DNA polymerase γ is also sensitive to 
inhibition by stavudine triphosphate, while cellular polymerases α and β are inhibited at 
concentrations 4,000-fold and 40-fold higher, respectively, than that needed to inhibit HIV reverse 
transcriptase. 

Resistance 

Stavudine treatment can select for and/or maintain thymidine analogue mutations (TAMs) associated 
with zidovudine resistance. The decrease of susceptibility in vitro is subtle requiring two or more 
TAMs (generally M41L and T215Y) before stavudine susceptibility is decreased (>1.5 fold). 
These TAMs are seen at a similar frequency with stavudine and zidovudine in virological treatment. 
The clinical relevance of these findings suggest that stavudine should be generally avoided in the 
presence of TAMs, especially M41L and T215Y. 
The activity of stavudine is also affected by multi-drug resistance associated mutations such as 
Q151M. In addition, K65R has been reported in patients receiving stavudine/didanosine or 
stavudine/lamivudine, but not in patients receiving stavudine monotherapy. V75T is selected in vitro
by stavudine and reduces susceptibility to stavudine by 2-fold. It occurs in ~1% of patients receiving 
stavudine. 

Clinical efficacy and safety 

Zerit has been studied in combination with other antiretroviral agents, e.g. didanosine, lamivudine, 
ritonavir, indinavir, saquinavir, efavirenz, and nelfinavir. 

In antiretroviral naive patients 

Study AI455-099 was a 48-week, randomised, double-blind study withZerit  (40 mg twice daily), in 
combination with lamivudine (150 mg twice daily) plus efavirenz (600 mg once daily), 
in 391 treatment-naive patients, with a median CD4 cell count of 272 cells/mm3

(range 61 to 1,215 cells/mm3) and a median plasma HIV-1 RNA of 4.80 log10 copies/ml 
(range 2.6 to 5.9 log 10 copies/ml) at baseline. Patients were primarily males (70%) and non-white 
(58%) with a median age of 33 years (range 18 to 68 years). 

Study AI455-096 was a 48-week, randomised, double-blind study with Zerit (40 mg twice daily), in 
combination with lamivudine (150 mg twice daily) plus efavirenz (600 mg once daily), 
in 76 treatment-naive patients, with a median CD4 cell count of 261 cells/mm3 

(range 63 to 962 cells/mm3) and a median plasma HIV-1 RNA of 4.63 log10 copies/ml 
(range 3.0 to 5.9 log10 copies/ml) at baseline. Patients were primarily males (76%) and white (66%) 
with a median age of 34 years (range 22 to 67 years). 

The results of AI455-099 and AI455-096 are presented in Table 1. Both studies were designed to 
compare two formulations of Zerit, one of which was the marketed formulation dosed as currently 
approved in product labelling. Only the data from the marketed formulation are presented. 

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Table 1:  Efficacy Outcomes at Week 48 (Studies AI455-099 and AI455-096) 

Parameter 

AI455-099 AI455-096 

Zerit + lamivudine + 

efavirenz

n=391

Zerit + lamivudine + 

efavirenz

n=76 

HIV RNA < 400 copies/ml, treatment response, %
All patients 73 66
HIV RNA < 50 copies/ml, treatment response, %
All patients 55 38
HIV RNA Mean Change from Baseline, log10 copies/ml 
All patients -2.83 (n=321a) -2.64 (n=58)
CD4 Mean Change from Baseline, cells/mm3

All patients 182 (n=314) 195 (n=55)
a Number of patients evaluable. 

Paediatric population 

The use of stavudine in adolescents, children and infants is supported by pharmacokinetic and safety 
data in paediatric patients (see also sections 4.8 and 5.2). 

5.2 Pharmacokinetic properties 

Absorption 

The absolute bioavailability is 86±18%. After multiple oral administration of 0.5-0.67 mg/kg doses, a 
Cmax value of 810±175 ng/ml was obtained. Cmax and AUC increased proportionally with dose in the 
dose ranges, intravenous 0.0625-0.75 mg/kg, and oral 0.033-4.0 mg/kg. 
In eight patients receiving 40 mg twice daily in the fasted state, steady-state AUC0-12h 
was 1284±227 ng⋅h/ml (18%) (mean ± SD [% CV]), Cmax was 536±146 ng/ml (27%), and Cmin
was 9±8 ng/ml (89%). A study in asymptomatic patients demonstrated that systemic exposure is 
similar while Cmax is lower and Tmax is prolonged when stavudine is administered with a standardised, 
high-fat meal compared with fasting conditions. The clinical significance of this is unknown. 

Distribution

The apparent volume of distribution at steady state is 46±21 l. It was not possible to detect stavudine 
in cerebrospinal fluid until at least 2 hours after oral administration. Four hours after administration, 
the CSF/plasma ratio was 0.39±0.06. No significant accumulation of stavudine is observed with 
repeated administration every 6, 8, or 12 hours. 
Binding of stavudine to serum proteins was negligible over the concentration range 
of 0.01 to 11.4 µg/ml. Stavudine distributes equally between red blood cells and plasma. 

Metabolism

Unchanged stavudine was the major drug-related component in total plasma radioactivity circulating 
after an oral 80 mg dose of 14C-stavudine in healthy subjects. The AUC(inf) for stavudine was 61% of 
the AUC(inf) of the total circulating radioactivity. Metabolites include oxidised stavudine, glucuronide 
conjugates of stavudine and its oxidised metabolite, and an N-acetylcysteine conjugate of the ribose 
after glycosidic cleavage, suggesting that thymine is also a metabolite of stavudine. 

Elimination

Following an oral 80-mg dose of 14C-stavudine to healthy subjects, approximately 95% and 3% of the 
total radioactivity was recovered in urine and faeces, respectively.  Approximately 70% of the orally 

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administered stavudine dose was excreted as an unchanged drug in urine. Mean renal clearance of the 
parent compound is approximately 272 ml/min, accounting for approximately 67% of the apparent 
oral clearance, indicating active tubular secretion in addition to glomerular filtration.  

In HIV-infected patients, total clearance of stavudine is 594±164 ml/min, and renal clearance 
is 237±98 ml/min. The total clearance of stavudine appears to be higher in HIV-infected patients, 
while the renal clearance is similar between healthy subjects and HIV-infected patients.  The 
mechanism and clinical significance of this difference are unknown. After intravenous 
administration, 42% (range: 13% to 87%) of dose is excreted unchanged in the urine. The 
corresponding values after oral single and multiple dose administration are 35% (range: 8% to 72%) 
and 40% (range: 12% to 82%), respectively. The mean terminal elimination half-life of stavudine 
is 1.3 to 2.3 hours following single or multiple doses, and is independent of dose.  In vitro, stavudine 
triphosphate has an intracellular half-life of 3.5 hours in CEM T-cells (a human T-lymphoblastoid cell 
line) and peripheral blood mononuclear cells, supporting twice daily dosing. 
The pharmacokinetics of stavudine was independent of time, since the ratio between AUC(ss) at steady 
state and the AUC(0-t) after the first dose was approximately 1. Intra-and interindividual variation in 
pharmacokinetic characteristics of stavudine is low, approximately 15% and 25%, respectively, after 
oral administration. 

Special Populations 

Renal impairment: the clearance of stavudine decreases as creatinine clearance decreases; therefore, it 
is recommended that the dosage of Zerit be adjusted in patients with reduced renal function (see 
section 4.2). 

Hepatic impairment: stavudine pharmacokinetics in patients with hepatic impairment were similar to 
those in patients with normal hepatic function.

Paediatric population 

Adolescents, children and infants: total exposure to stavudine was comparable between adolescents, 
children and infants ≥ 14 days receiving the 2 mg/kg/day dose and adults receiving 1 mg/kg/day. 
Apparent oral clearance was approximately 14 ml/min/kg for infants ages 5 weeks 
to 15 years, 12 ml/min/kg for infants ages 14 to 28 days, and 5 ml/min/kg for infants on the day of 
birth. Two to three hours post-dose, CSF/plasma ratios of stavudine ranged from 16% to 125% (mean 
of 59%±35%). 

5.3 Preclinical safety data 

Animal data showed embryo-foetal toxicity at very high exposure levels. An ex vivo study using a 
term human placenta model demonstrated that stavudine reaches the foetal circulation by simple 
diffusion. A rat study also showed placental transfer of stavudine, with the foetal tissue concentration 
approximately 50% of the maternal plasma concentration. 
Stavudine was genotoxic in in vitro tests in human lymphocytes possessing triphosphorylating activity 
(in which no no-effect level was established), in mouse fibroblasts, and in an in vivo test for 
chromosomal aberrations. Similar effects have been observed with other nucleoside analogues. 
Stavudine was carcinogenic in mice (liver tumours) and rats (liver tumours: cholangiocellular, 
hepatocellular, mixed hepatocholangiocellular, and/or vascular; and urinary bladder carcinomas) at 
very high exposure levels. No carcinogenicity was noted at doses of 400 mg/kg/day in mice 
and 600 mg/kg/day in rats, corresponding to exposures ~ 39 and 168 times the expected human 
exposure, respectively, suggesting an insignificant carcinogenic potential of stavudine in clinical 
therapy. 

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6. PHARMACEUTICAL PARTICULARS 

6.1 List of excipients 

Cherry flavour 
Methylhydroxybenzoate (E218) 
Propylhydroxybenzoate (E216) 
Silicon dioxide 
Simethicone 
Sodium carmellose 
Sorbic acid 
Stearate emulsifiers 
Sucrose 

6.2 Incompatibilities  

Not applicable. 

6.3 Shelf life 

2 years. 
After reconstitution, store the prepared oral solution in a refrigerator (2°C - 8°C) for 30 days. 

6.4 Special precautions for storage 

Do not store the dry powder above 30°C.  
Store in the original package. 
Keep the bottle tightly closed in order to protect from excessive moisture. 
For storage conditions of the reconstituted medicinal product, see section 6.3. 

6.5 Nature and contents of container 

HDPE bottle with child resistant screw cap, fill mark (200 ml of solution after reconstitution) and 
measuring cup. 

6.6 Special precautions for disposal and other handling 

Instructions for preparation 

Zerit should be reconstituted with water to a 200 ml deliverable volume solution (stavudine 
concentration of 1 mg/ml). 
To reconsistute Zerit, add 202 ml of water to the original bottle (when the patient makes up the 
solution, they should be instructed to fill to the top edge of the bottle label, indicated by the arrow 
marks). Replace the cap. 
The bottle should be shaken well, until the powder dissolves completely. The solution appears as a 
colourless to slightly pink, hazy solution. 
The solution should be dispensed with the measuring cup provided, or for doses less than 10 ml, 
dispense with a syringe. The patient should be instructed to shake the bottle well prior to measuring 
each dose. 

Disposal 

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 

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7. MARKETING AUTHORISATION HOLDER 

Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland 

8. MARKETING AUTHORISATION NUMBER(S) 

EU/1/96/009/009 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

Date of first authorisation: 08 May 1996 
Date of last renewal: 20 April 2011 

10. DATE OF REVISION OF THE TEXT 

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu/. 

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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 

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A MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

Name and address of the manufacturer(s) responsible for batch release 

Bristol-Myers Squibb S.r.l., Contrada Fontana del Ceraso, 03012 Anagni (FR), Italy 

Aesica Queenborough Limited, North Road, Queenborough, Kent, ME11 5EL, United Kingdom 

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 requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal. 

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

• Risk Management Plan (RMP) 

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. 

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ANNEX III 

LABELLING AND PACKAGE LEAFLET 

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34

A. LABELLING 

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35

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

OUTER CARTON TEXT (BLISTER) 

1. NAME OF THE MEDICINAL PRODUCT 

Zerit 15 mg hard capsules 
Stavudine 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

Each hard capsule contains 15 mg stavudine. 

3. LIST OF EXCIPIENTS 

Lactose 

4. PHARMACEUTICAL FORM AND CONTENTS 

56 hard capsules 

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 REACH AND SIGHT 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 

Store below 25°C.  
Store in the original package. 

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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 

Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/96/009/002 

13. BATCH NUMBER 

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY 

15. INSTRUCTIONS ON USE 

16. INFORMATION IN BRAILLE 

Zerit 15 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE 

2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

PC: 
SN: 
<NN:>  

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

BLISTER TEXT 

1. NAME OF THE MEDICINAL PRODUCT 

Zerit 15 mg hard capsules 
Stavudine 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

BRISTOL-MYERS SQUIBB PHARMA EEIG 

3. EXPIRY DATE 

EXP 

4. BATCH NUMBER 

Lot 

5. OTHER 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 

OUTER CARTON TEXT AND BOTTLE LABEL TEXT (BOTTLE PRESENTATION) 

1. NAME OF THE MEDICINAL PRODUCT 

Zerit 15 mg hard capsules 
Stavudine 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

Each hard capsule contains 15 mg stavudine. 

3. LIST OF EXCIPIENTS 

Lactose 

4. PHARMACEUTICAL FORM AND CONTENTS 

60 hard capsules 

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 REACH AND SIGHT 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 

Do not store above 30°C. 
Store in the original package. 

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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 

Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/96/009/001 

13. BATCH NUMBER 

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY 

15. INSTRUCTIONS ON USE 

16. INFORMATION IN BRAILLE 

Outer carton: Zerit 15 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE 

Outer carton: 2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

Outer carton 
PC: 
SN: 
<NN:>  

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40

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

OUTER CARTON TEXT (BLISTER) 

1. NAME OF THE MEDICINAL PRODUCT 

Zerit 20 mg hard capsules 
Stavudine 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

Each hard capsule contains 20 mg stavudine. 

3. LIST OF EXCIPIENTS 

Lactose 

4. PHARMACEUTICAL FORM AND CONTENTS 

56 hard capsules 

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 REACH AND SIGHT 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 

Store below 25°C.  
Store in the original package. 

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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 

Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/96/009/004 

13. BATCH NUMBER 

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY 

15. INSTRUCTIONS ON USE 

16. INFORMATION IN BRAILLE 

Zerit 20 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE 

2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

PC: 
SN: 
<NN:>  

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

BLISTER TEXT 

1. NAME OF THE MEDICINAL PRODUCT 

Zerit 20 mg hard capsules 
Stavudine 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

BRISTOL-MYERS SQUIBB PHARMA EEIG 

3. EXPIRY DATE 

EXP 

4. BATCH NUMBER 

Lot 

5. OTHER 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 

OUTER CARTON TEXT AND BOTTLE LABEL TEXT (BOTTLE PRESENTATION) 

1. NAME OF THE MEDICINAL PRODUCT 

Zerit 20 mg hard capsules 
Stavudine 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

Each hard capsule contains 20 mg stavudine. 

3. LIST OF EXCIPIENTS 

Lactose 

4. PHARMACEUTICAL FORM AND CONTENTS 

60 hard capsules 

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 REACH AND SIGHT 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 

Do not store above 30°C. 
Store in the original package. 

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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 

Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/96/009/003 

13. BATCH NUMBER 

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY 

15. INSTRUCTIONS ON USE 

16. INFORMATION IN BRAILLE 

Outer carton: Zerit 20 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE 

Outer carton: 2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

Outer carton 
PC: 
SN: 
<NN:>  

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

OUTER CARTON TEXT (BLISTER) 

1. NAME OF THE MEDICINAL PRODUCT 

Zerit 30 mg hard capsules 
Stavudine 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

Each hard capsule contains 30 mg stavudine. 

3. LIST OF EXCIPIENTS 

Lactose 

4. PHARMACEUTICAL FORM AND CONTENTS 

56 hard capsules 

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 REACH AND SIGHT 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 

Store below 25°C.  
Store in the original package. 

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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 

Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/96/009/006 

13. BATCH NUMBER 

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY 

15. INSTRUCTIONS ON USE 

16. INFORMATION IN BRAILLE 

Zerit 30 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE 

2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

PC: 
SN: 
<NN:>  

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

BLISTER TEXT 

1. NAME OF THE MEDICINAL PRODUCT 

Zerit 30 mg hard capsules 
Stavudine 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

BRISTOL-MYERS SQUIBB PHARMA EEIG 

3. EXPIRY DATE 

EXP 

4. BATCH NUMBER 

Lot 

5. OTHER 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 

OUTER CARTON TEXT AND BOTTLE LABEL TEXT (BOTTLE PRESENTATION) 

1. NAME OF THE MEDICINAL PRODUCT 

Zerit 30 mg hard capsules 
Stavudine 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

Each hard capsule contains 30 mg stavudine. 

3. LIST OF EXCIPIENTS 

Lactose 

4. PHARMACEUTICAL FORM AND CONTENTS 

60 hard capsules 

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 REACH AND SIGHT 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 

Do not store above 30°C. 
Store in the original package. 

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49

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 

Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/96/009/005 

13. BATCH NUMBER 

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY 

15. INSTRUCTIONS ON USE 

16. INFORMATION IN BRAILLE 

Outer carton: Zerit 30 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE 

Outer carton: 2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

Outer carton 
PC: 
SN: 
<NN:>  

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50

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

OUTER CARTON TEXT (BLISTER) 

1. NAME OF THE MEDICINAL PRODUCT 

Zerit 40 mg hard capsules 
Stavudine 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

Each hard capsule contains 40 mg stavudine. 

3. LIST OF EXCIPIENTS 

Lactose 

4. PHARMACEUTICAL FORM AND CONTENTS 

56 hard capsules 

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 REACH AND SIGHT 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 

Store below 25°C.  
Store in the original package. 

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51

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 

Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/96/009/008 

13. BATCH NUMBER 

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY 

15. INSTRUCTIONS ON USE 

16. INFORMATION IN BRAILLE 

Zerit 40 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE 

2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

PC: 
SN: 
<NN:>  

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52

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

BLISTER TEXT 

1. NAME OF THE MEDICINAL PRODUCT 

Zerit 40 mg hard capsules 
Stavudine 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

BRISTOL-MYERS SQUIBB PHARMA EEIG 

3. EXPIRY DATE 

EXP 

4. BATCH NUMBER 

Lot 

5. OTHER 

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53

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING 

OUTER CARTON TEXT AND BOTTLE LABEL TEXT (BOTTLE PRESENTATION) 

1. NAME OF THE MEDICINAL PRODUCT 

Zerit 40 mg hard capsules 
Stavudine 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

Each hard capsule contains 40 mg stavudine. 

3. LIST OF EXCIPIENTS 

Lactose 

4. PHARMACEUTICAL FORM AND CONTENTS 

60 hard capsules 

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 REACH AND SIGHT 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 

Do not store above 30°C. 
Store in the original package. 

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54

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 

Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/96/009/007 

13. BATCH NUMBER 

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY 

15. INSTRUCTIONS ON USE 

16. INFORMATION IN BRAILLE 

Outer carton: Zerit 40 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE 

Outer carton: 2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

Outer carton 
PC: 
SN: 
<NN:>  

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55

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING  

OUTER CARTON TEXT AND BOTTLE LABEL TEXT 

1. NAME OF THE MEDICINAL PRODUCT 

Zerit 200 mg powder for oral solution 
Stavudine 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

Each bottle contains stavudine 200 mg 
The reconstituted solution contains 1 mg of stavudine per ml. 

3. LIST OF EXCIPIENTS 

Sucrose and preservatives (E218 and E216) 

4. PHARMACEUTICAL FORM AND CONTENTS 

Powder for oral solution, 200 mg 

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 REACH AND SIGHT OF CHILDREN 

Keep out of the sight and reach of children. 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

Shake well before use. 

8. EXPIRY DATE 

EXP 

9. SPECIAL STORAGE CONDITIONS 

Do not store above 30°C. 
Stable for 30 days after reconstitution, when stored in a refrigerator. 
Store in the original package in order to protect from excessive moisture. 

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56

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 

Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland 

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/96/009/009 

13. BATCH NUMBER 

Lot 

14. GENERAL CLASSIFICATION FOR SUPPLY 

15. INSTRUCTIONS ON USE 

16. INFORMATION IN BRAILLE 

Outer carton: Zerit 200 mg 

17. UNIQUE IDENTIFIER – 2D BARCODE 

Outer carton: 2D barcode carrying the unique identifier included. 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

Outer carton 
PC: 
SN: 
<NN:>  

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57

B. PACKAGE LEAFLET 

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58

Package leaflet: Information for the user 

Zerit 15 mg hard capsules 
Stavudine 

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 Zerit is and what it is used for 
2. What you need to know before you take Zerit 
3. How to take Zerit 
4. Possible side effects 
5. How to store Zerit 
6. Contents of the pack and other information 

1. What Zerit is and what it is used for 

Zerit belongs to a particular group of antiviral medicines, also known as antiretrovirals, called 
nucleoside reverse transcriptase inhibitors (NRTIs). 

These are used to treat Human Immunodeficiency Virus (HIV) infection. 

This medicinal product, in combination with other antiretrovirals, reduces the HIV viral load and 
keeps it at a low level. It also increases CD4 cell counts. These CD4 cells play an important role in 
maintaining a healthy immune system to help fight infection. Response to treatment with Zerit varies 
between patients. Your doctor will therefore be monitoring the effectiveness of your treatment. 

Zerit may improve your condition, but it is not a cure for your HIV infection. 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. 
During treatment, other infections linked to a weakened immunity (opportunistic infections) may arise. 
These will require specific and sometimes preventive treatment. 

2. What you need to know before you take Zerit 

Do not take Zerit 
 If you are allergic to stavudine or any of the other ingredients of this medicine (listed in section 

6). Contact your doctor or pharmacist for advice. 
 If you are taking didanosine, used to treat HIV infection. 

Warnings and precautions 
Talk to your doctor before taking Zerit. 
Before treatment with Zerit, you should have told your doctor: 
 if you suffer from kidney disease or liver disease (such as hepatitis) 
 if you have had peripheral neuropathy (persistent numbness, tingling, or pain in the feet and/or 

hands) 
 if you have suffered from pancreatitis (inflammation of the pancreas). 

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Zerit can cause a sometimes fatal condition called lactic acidosis, together with an enlarged liver. This 
condition usually does not occur until a few months after onset of treatment. This rare, but very serious 
side effect occurs more often in women, particularly if very overweight. In addition, rare cases of liver 
failure/renal failure or fatal hepatitis have been reported. 
Patients with chronic hepatitis B or C and treated with antiretroviral agents are at increased risk for 
severe and potentially fatal liver side effects and may require blood tests for control of liver function. 

If you develop one of the following, contact your doctor: 
 persistent numbness, tingling or pain in feet and/or hands (this may indicate the beginning of 

peripheral neuropathy, an adverse effect on the nerves), muscular weakness 
 abdominal pain, nausea or vomiting 
 rapid deep breathing, drowsiness (which may indicate pancreatitis, liver disturbance such as 

hepatitis, or lactic acidosis). 

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

During therapy with Zerit there is often a gradual loss of subcutaneous fat (fat found beneath the skin), 
which is most notable in the face and on the legs and arms. Contact your doctor if you notice such 
changes. 

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

Other medicines and Zerit 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 

Do not take Zerit if you are taking didanosine, used to treat HIV infection. 

Tell your doctor if you are taking any of the following medicines, as undesirable interactions may 
occur: 
 zidovudine, used to treat HIV infection 
 doxorubicin, used to treat cancer 
 ribavirin, used to treat hepatitis C infection. 

Zerit with food and drink 
For maximum effect, Zerit should be taken on an empty stomach, and preferably at least one hour 
before a meal. If this is not possible, the capsules may also be taken with a light meal. 

Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine. 

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60

Pregnancy 
You must contact your doctor to discuss the potential side effects and the benefits and risks of your 
antiretroviral therapy to you and your child. Lactic acidosis (sometimes fatal) has been reported in 
pregnant women who received Zerit in combination with other antiretroviral treatment. 
If you have taken Zerit during your pregnancy, your doctor may request regular blood tests and other 
diagnostic tests to monitor the development of your child. In children whose mothers took NRTIs 
during pregnancy, the benefit from the protection against HIV outweighed the risk of side effects. 

Breast-feeding 
Tell your doctor if you are breast-feeding. It is recommended that HIV-infected women should not 
breast-feed under any circumstances in order to avoid transmission of HIV to the baby. 

Driving and using machines 
Zerit may cause dizziness and drowsiness. 
If you are affected, do not drive and do not use any tools or machines. 

Zerit contains lactose 
These capsules contain lactose. If you have been told by your doctor that you have an intolerance to 
some sugars, contact your doctor before taking this medicinal product. 

3. How to take Zerit 

Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure. Your doctor has defined your daily dose based on your weight and individual characteristics. 
Please follow these recommendations closely as they will give you the best chance to delay 
development of a resistance to the medicinal product. Do not change the dose on your own. Continue 
to take this medicine until your doctor tells you otherwise. 
For adults whose body weight is 30 kg or more, the usual starting dose is 30 or 40 mg given twice 
daily (with approximately 12 hours between each dose). 
To obtain optimal absorption, the capsules should be swallowed with a glass of water, preferentially at 
least one hour before a meal and on an empty stomach. If this is not possible, Zerit may also be taken 
with a light meal. 
If you have problems swallowing capsules you should ask your doctor about the possibility of 
changing to the solution form of this medicine or you could carefully open the capsule and mix its 
contents with some food. 

Use in children 
For children whose body weight is 30 kg or more, the usual starting dose is 30 or 40 mg given twice 
daily (with approximately 12 hours between each dose). 
Children older than 3 months, whose body weight is less than 30 kg, should receive 1 mg/kg twice 
daily. 

If you take more Zerit than you should 
If you have taken too many capsules or if someone accidentally swallows some, there is no immediate 
danger. However, you should contact your doctor or the nearest hospital for advice. 

If you forget to take Zerit 
If you accidentally miss a dose, then simply take your normal dose when the next one is due. Do not 
take a double dose to make up for a forgotten dose. 

If you stop taking Zerit 
The decision to stop using Zerit should be discussed with your doctor. 

If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 

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4. Possible side effects 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

When treating HIV infection, it is not always possible to differentiate between unwanted effects 
caused by Zerit, or those caused by any other medicines you may be taking at the same time, or by the 
complications of the infection. For this reason, it is important that you inform your doctor of any 
change in your health. 

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. 

Treatment with stavudine (Zerit) often causes a loss of fat from legs, arms and face (lipoatrophy). This 
loss of body fat has been shown to be not fully reversible after discontinuation of stavudine.  Your 
doctor should monitor for signs of lipoatrophy. Tell your doctor if you notice any loss of fat from your 
legs, arms, and face. When these signs occur, Zerit should be stopped and your HIV treatment 
changed. 

Patients treated with Zerit have reported the following side effects: 

Common (may affect up to 1 in 10 people)  
 asymptomatic hyperlactatemia (build up of acid in your blood)  
 lipoatrophy  
 depression  
 peripheral neurologic symptoms including peripheral neuropathy, paresthesia, and peripheral 

neuritis (numbness, weakness, tingling or pain in the arms and legs) 
 dizziness, abnormal dreams, headache  
 insomnia (difficulty sleeping), somnolence (sleepiness), abnormal thinking 
 diarrhoea, abdominal pain (stomach pain of discomfort) 
 nausea, dyspepsia (indigestion) 
 rash, pruritus (itching)  
 fatigue (extreme tiredness) 

Uncommon (may affect up to 1 in 100 people) 
 lactic acidosis (build up of acid in your blood) in some cases involving motor weakness 

(weakness in your arms, legs or hands) 
 gynaecomastia (breast enlargement in men) 
 anorexia (loss of appetite), anxiety, emotional lability 
 pancreatitis (inflammation of the pancreas), vomiting 
 hepatitis (inflamation of the liver), jaundice (yellow of the skin or eyes) 
 urticaria (itchy rash), arthralgia (joint pain) 
 myalgia (aching muscles), asthenia (unusual tiredness or weakness) 

Rare (may affect up to 1 in 1,000 people) 
 anemia 
 hyperglycaemia (high sugar levels in the blood) 
 hepatic steatosis (fat in the liver) 

Very rare (may affect up to 1 in 10,000 people) 
 thrombocytopenia, neutropenia (blood disorders)  
 diabetes mellitus 
 motor weakness (most often reported in the setting of symptomatic hyperlacetatemia or lactic 

acidosis syndrome) 
 liver failure 

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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 Zerit 

Keep this medicine out of the sight and reach of children. 

Do not use this medicine after the expiry date which is stated on the carton, the bottle label and/or the 
blister after EXP. The expiry date refers to the last day of that month. 

Store below 25°C (aclar/alu blisters). 
Do not store above 30°C (HDPE bottles). 
Store in the original package. 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 

6. Contents of the pack and other information 

What Zerit contains 
 The active substance is stavudine (15 mg). 
 The other ingredients of the powder contained in the hard capsule are: lactose (120 mg), 

magnesium stearate, microcrystalline cellulose and sodium starch glycolate. 
 The ingredients of the capsule shell are gelatine, iron oxide colorant (E172), silicon dioxide, 

sodium laurilsulphate and titanium dioxide colorant (E171). 
 The capsule shells are marked using edible black printing ink containing shellac, propylene 

glycol, purified water, potassium hydroxide and iron oxide (E172). 

What Zerit looks like and content of the pack 
Zerit 15 mg hard capsules are red and yellow and marked with “BMS 1964” on one side and “15” on 
the other side. 
Zerit 15 mg hard capsules are supplied in blister packs of 56 hard capsules or bottles of 60 hard 
capsules. To help protect the capsules from excessive moisture, the bottle includes a desiccant canister. 

Marketing Authorisation Holder and Manufacturer 
Marketing Authorisation Holder 
Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland 

Manufacturer 
Bristol-Myers Squibb S.r.l. 
Contrada Fontana del Ceraso 
03012 Anagni (FR) 
Italy 

Aesica Queenborough Limited 
North Road, Queenborough 
Kent, ME11 5EL 
United Kingdom 

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63

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 

Belgique/België/Belgien 
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 

Lietuva
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: +370 52 369140 

България 
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Teл.: + 359 800 12 400 

Luxembourg/Luxemburg
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 

Česká republika 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 420 221 016 111 

Magyarország 
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel.: + 36 1 301 9700 

Danmark 
Bristol-Myers Squibb 
Tlf: + 45 45 93 05 06 

Malta 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 

Deutschland
Bristol-Myers Squibb GmbH & Co. KGaA 
Tel: + 49 89 121 42-0 

Nederland
Bristol-Myers Squibb B.V. 
Tel: + 31 (0)30 300 2222 

Eesti
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: +372 640 1030

Norge 
Bristol-Myers Squibb Norway Ltd 
Tlf: + 47 67 55 53 50 

Ελλάδα
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 30 210 6074300 

Österreich
Bristol-Myers Squibb GesmbH 
Tel: + 43 1 60 14 30 

España
BRISTOL-MYERS SQUIBB, S.A. 
Tel: + 34 91 456 53 00 

Polska
BRISTOL-MYERS SQUIBB POLSKA SP. Z O.O. 
Tel.: + 48 22 5796666 

France
Bristol-Myers Squibb SARL 
Tél: +33 (0)1 58 83 84 96 

Portugal
Bristol-Myers Squibb Farmacêutica Portuguesa, 
S.A. 
Tel: + 351 21 440 70 00 

Hrvatska
Bristol-Myers Squibb spol. s r.o. 
TEL: +385 1 2078 508 

România 
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: + 40 (0)21 272 16 00 

Ireland
Bristol-Myers Squibb Pharmaceuticals Ltd 
Tel: + 353 (1 800) 749 749 

Slovenija
Bristol-Myers Squibb spol. s r.o. 
Tel: +386 1 2355 100 

Ísland
Vistor hf. 
Sími: + 354 535 7000 

Slovenská republika
Bristol-Myers Squibb spol. s r.o. 
Tel: + 421 2 59298411 

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64

Italia
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 

Suomi/Finland
Oy Bristol-Myers Squibb (Finland) Ab 
Puh/Tel: + 358 9 251 21 230 

Κύπρος
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 357 800 92666 

Sverige
Bristol-Myers Squibb AB 
Tel: + 46 8 704 71 00 

Latvija
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: +371 67708347 

United Kingdom
Bristol-Myers Squibb Pharmaceuticals Ltd 
Tel: + 44 (0800) 731 1736 

This leaflet was last revised in {MM/YYYY}. 

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/. 

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65

Package leaflet: Information for the user 

Zerit 20 mg hard capsules 
Stavudine 

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 Zerit is and what it is used for 
2. What you need to know before you take Zerit 
3. How to take Zerit 
4. Possible side effects 
5. How to store Zerit 
6. Contents of the pack and other information 

1. What Zerit is and what it is used for 

Zerit belongs to a particular group of antiviral medicines, also known as antiretrovirals, called 
nucleoside reverse transcriptase inhibitors (NRTIs). 

These are used to treat Human Immunodeficiency Virus (HIV) infection. 

This medicinal product, in combination with other antiretrovirals, reduces the HIV viral load and 
keeps it at a low level. It also increases CD4 cell counts. These CD4 cells play an important role in 
maintaining a healthy immune system to help fight infection. Response to treatment with Zerit varies 
between patients. Your doctor will therefore be monitoring the effectiveness of your treatment. 

Zerit may improve your condition, but it is not a cure for your HIV infection. 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. 
During treatment, other infections linked to a weakened immunity (opportunistic infections) may arise. 
These will require specific and sometimes preventive treatment. 

2. What you need to know before you take Zerit 

Do not take Zerit 
 If you are allergic to stavudine or any of the other ingredients of this medicine (listed in section 

6). Contact your doctor or pharmacist for advice.  
 If you are taking didanosine, used to treat HIV infection. 

Warnings and precautions 
Talk to your doctor before taking Zerit. 
Before treatment with Zerit, you should have told your doctor: 
 if you suffer from kidney disease or liver disease (such as hepatitis) 
 if you have had peripheral neuropathy (persistent numbness, tingling, or pain in the feet and/or 

hands) 
 if you have suffered from pancreatitis (inflammation of the pancreas). 

Approved 1.0v



66

Zerit can cause a sometimes fatal condition called lactic acidosis, together with an enlarged liver. This 
condition usually does not occur until a few months after onset of treatment. This rare, but very serious 
side effect occurs more often in women, particularly if very overweight. In addition, rare cases of liver 
failure/renal failure or fatal hepatitis have been reported. 
Patients with chronic hepatitis B or C and treated with antiretroviral agents are at increased risk for 
severe and potentially fatal liver side effects and may require blood tests for control of liver function. 

If you develop one of the following, contact your doctor: 
 persistent numbness, tingling or pain in feet and/or hands (this may indicate the beginning of 

peripheral neuropathy, an adverse effect on the nerves), muscular weakness 
 abdominal pain, nausea or vomiting 
 rapid deep breathing, drowsiness (which may indicate pancreatitis, liver disturbance such as 

hepatitis, or lactic acidosis). 

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

During therapy with Zerit there is often a gradual loss of subcutaneous fat (fat found beneath the skin), 
which is most notable in the face and on the legs and arms. Contact your doctor if you notice such 
changes. 

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

Other medicines and Zerit 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 

Do not take Zerit if you are taking didanosine, used to treat HIV infection. 

Tell your doctor if you are taking any of the following medicines, as undesirable interactions may 
occur: 
 zidovudine, used to treat HIV infection 
 doxorubicin, used to treat cancer 
 ribavirin, used to treat hepatitis C infection 

Zerit with food and drink 
For maximum effect, Zerit should be taken on an empty stomach, and preferably at least one hour 
before a meal. If this is not possible, the capsules may also be taken with a light meal. 

Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine. 

Approved 1.0v



67

Pregnancy 
You must contact your doctor to discuss the potential side effects and the benefits and risks of your 
antiretroviral therapy to you and your child. Lactic acidosis (sometimes fatal) has been reported in 
pregnant women who received Zerit in combination with other antiretroviral treatment. 
If you have taken Zerit during your pregnancy, your doctor may request regular blood tests and other 
diagnostic tests to monitor the development of your child. In children whose mothers took NRTIs 
during pregnancy, the benefit from the protection against HIV outweighed the risk of side effects. 

Breast-feeding 
Tell your doctor if you are breast-feeding. It is recommended that HIV-infected women should not 
breast-feed under any circumstances in order to avoid transmission of HIV to the baby. 

Driving and using machines 
Zerit may cause dizziness and drowsiness. 
If you are affected, do not drive and do not use any tools or machines. 

Zerit contains lactose 
These capsules contain lactose. If you have been told by your doctor that you have an intolerance to 
some sugars, contact your doctor before taking this medicinal product. 

3. How to take Zerit 

Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure. Your doctor has defined your daily dose based on your weight and individual characteristics. 
Please follow these recommendations closely as they will give you the best chance to delay 
development of a resistance to the medicinal product. Do not change the dose on your own. Continue 
to take this medicine until your doctor tells you otherwise. 
For adults whose body weight is 30 kg or more, the usual starting dose is 30 or 40 mg given twice 
daily (with approximately 12 hours between each dose). 
To obtain optimal absorption, the capsules should be swallowed with a glass of water, preferentially at 
least one hour before a meal and on an empty stomach. If this is not possible, Zerit may also be taken 
with a light meal. 
If you have problems swallowing capsules you should ask your doctor about the possibility of 
changing to the solution form of this medicine or you could carefully open the capsule and mix its 
contents with some food. 

Use in children 
For children whose body weight is 30 kg or more, the usual starting dose is 30 or 40 mg given twice 
daily (with approximately 12 hours between each dose). 
Children older than 3 months, whose body weight is less than 30 kg, should receive 1 mg/kg twice 
daily. 

If you take more Zerit than you should 
If you have taken too many capsules or if someone accidentally swallows some, there is no immediate 
danger. However, you should contact your doctor or the nearest hospital for advice. 

If you forget to take Zerit 
If you accidentally miss a dose, then simply take your normal dose when the next one is due. Do not 
take a double dose to make up for a forgotten dose. 

If you stop taking Zerit 
The decision to stop using Zerit should be discussed with your doctor. 

If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 

Approved 1.0v



68

4. Possible side effects 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

When treating HIV infection, it is not always possible to differentiate between unwanted effects 
caused by Zerit, or those caused by any other medicines you may be taking at the same time, or by the 
complications of the infection. For this reason, it is important that you inform your doctor of any 
change in your health. 

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. 

Treatment with stavudine (Zerit) often causes a loss of fat from legs, arms and face (lipoatrophy). This 
loss of body fat has been shown to be not fully reversible after discontinuation of stavudine.  Your 
doctor should monitor for signs of lipoatrophy. Tell your doctor if you notice any loss of fat from your 
legs, arms, and face. When these signs occur, Zerit should be stopped and your HIV treatment 
changed. 

Patients treated with Zerit have reported the following side effects: 

Common (may affect up to 1 in 10 people)  
 asymptomatic hyperlactatemia (build up of acid in your blood)  
 lipoatrophy  
 depression  
 peripheral neurologic symptoms including peripheral neuropathy, paresthesia, and peripheral 

neuritis (numbness, weakness, tingling or pain in the arms and legs) 
 dizziness, abnormal dreams, headache  
 insomnia (difficulty sleeping), somnolence (sleepiness), abnormal thinking 
 diarrhoea, abdominal pain (stomach pain of discomfort) 
 nausea, dyspepsia (indigestion) 
 rash, pruritus (itching)  
 fatigue (extreme tiredness) 

Uncommon (may affect up to 1 in 100 people) 
 lactic acidosis (build up of acid in your blood) in some cases involving motor weakness 

(weakness in your arms, legs or hands) 
 gynaecomastia (breast enlargement in men) 
 anorexia (loss of appetite), anxiety, emotional lability 
 pancreatitis (inflammation of the pancreas), vomiting 
 hepatitis (inflamation of the liver), jaundice (yellow of the skin or eyes) 
 urticaria (itchy rash), arthralgia (joint pain) 
 myalgia (aching muscles), asthenia (unusual tiredness or weakness) 

Rare (may affect up to 1 in 1,000 people) 
 anemia 
 hyperglycaemia (high sugar levels in the blood) 
 hepatic steatosis (fat in the liver) 

Very rare (may affect up to 1 in 10,000 people) 
 thrombocytopenia, neutropenia (blood disorders)  
 diabetes mellitus 
 motor weakness (most often reported in the setting of symptomatic hyperlacetatemia or lactic 

acidosis syndrome) 
 liver failure 

Approved 1.0v



69

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 Zerit 

Keep this medicine out of the sight and reach of children. 

Do not use this medicine after the expiry date which is stated on the carton, the bottle label and/or the 
blister after EXP. The expiry date refers to the last day of that month. 

Store below 25°C (aclar/alu blisters). 
Do not store above 30°C (HDPE bottles). 
Store in the original package. 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 

6. Contents of the pack and other information 

What Zerit contains 
 The active substance is stavudine (20 mg). 
 The other ingredients of the powder contained in the hard capsule are: lactose (180 mg), 

magnesium stearate, microcrystalline cellulose and sodium starch glycolate. 
 The ingredients of the capsule shell are gelatine, iron oxide colorant (E172), silicon dioxide, 

sodium laurilsulphate and titanium dioxide colorant (E171). 
 The capsule shells are marked using edible black printing ink containing shellac, propylene 

glycol, purified water, potassium hydroxide and iron oxide (E172). 

What Zerit looks like and content of the pack 
Zerit 20 mg hard capsules are brown and marked with “BMS 1965” on one side and “20” on the other 
side. 
Zerit 20 mg hard capsules are supplied in blister packs of 56 hard capsules or bottles of 60 hard 
capsules. To help protect the capsules from excessive moisture, the bottle includes a desiccant canister. 

Marketing Authorisation Holder and Manufacturer 
Marketing Authorisation Holder 
Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland 

Manufacturer 
Bristol-Myers Squibb S.r.l. 
Contrada Fontana del Ceraso 
03012 Anagni (FR) 
Italy 

Aesica Queenborough Limited 
North Road, Queenborough 
Kent, ME11 5EL 
United Kingdom 

Approved 1.0v



70

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 

Belgique/België/Belgien 
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 

Lietuva
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: +370 52 369140 

България 
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Teл.: + 359 800 12 400 

Luxembourg/Luxemburg
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 

Česká republika 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 420 221 016 111 

Magyarország 
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel.: + 36 1 301 9700 

Danmark 
Bristol-Myers Squibb 
Tlf: + 45 45 93 05 06 

Malta 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 

Deutschland
Bristol-Myers Squibb GmbH & Co. KGaA 
Tel: + 49 89 121 42-0 

Nederland
Bristol-Myers Squibb B.V. 
Tel: + 31 (0)30 300 2222 

Eesti
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: +372 640 1030

Norge 
Bristol-Myers Squibb Norway Ltd 
Tlf: + 47 67 55 53 50 

Ελλάδα
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 30 210 6074300 

Österreich
Bristol-Myers Squibb GesmbH 
Tel: + 43 1 60 14 30 

España
BRISTOL-MYERS SQUIBB, S.A. 
Tel: + 34 91 456 53 00 

Polska
BRISTOL-MYERS SQUIBB POLSKA SP. Z O.O. 
Tel.: + 48 22 5796666 

France
Bristol-Myers Squibb SARL 
Tél: +33 (0)1 58 83 84 96 

Portugal
Bristol-Myers Squibb Farmacêutica Portuguesa, 
S.A. 
Tel: + 351 21 440 70 00 

Hrvatska
Bristol-Myers Squibb spol. s r.o. 
TEL: +385 1 2078 508 

România 
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: + 40 (0)21 272 16 00 

Ireland
Bristol-Myers Squibb Pharmaceuticals Ltd 
Tel: + 353 (1 800) 749 749 

Slovenija
Bristol-Myers Squibb spol. s r.o. 
Tel: +386 1 2355 100 

Ísland
Vistor hf. 
Sími: + 354 535 7000 

Slovenská republika
Bristol-Myers Squibb spol. s r.o. 
Tel: + 421 2 59298411 

Approved 1.0v



71

Italia
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 

Suomi/Finland
Oy Bristol-Myers Squibb (Finland) Ab 
Puh/Tel: + 358 9 251 21 230 

Κύπρος
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 357 800 92666 

Sverige
Bristol-Myers Squibb AB 
Tel: + 46 8 704 71 00 

Latvija
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: +371 67708347 

United Kingdom
Bristol-Myers Squibb Pharmaceuticals Ltd 
Tel: + 44 (0800) 731 1736 

This leaflet was last revised in {MM/YYYY}. 

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/. 

Approved 1.0v



72

Package leaflet: Information for the user 

Zerit 30 mg hard capsules 
Stavudine 

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 Zerit is and what it is used for 
2. What you need to know before you take Zerit 
3. How to take Zerit 
4. Possible side effects 
5. How to store Zerit 
6. Contents of the pack and other information 

1. What Zerit is and what it is used for 

Zerit belongs to a particular group of antiviral medicines, also known as antiretrovirals, called 
nucleoside reverse transcriptase inhibitors (NRTIs). 

These are used to treat Human Immunodeficiency Virus (HIV) infection. 

This medicinal product, in combination with other antiretrovirals, reduces the HIV viral load and 
keeps it at a low level. It also increases CD4 cell counts. These CD4 cells play an important role in 
maintaining a healthy immune system to help fight infection. Response to treatment with Zerit varies 
between patients. Your doctor will therefore be monitoring the effectiveness of your treatment. 

Zerit may improve your condition, but it is not a cure for your HIV infection. 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. 
During treatment, other infections linked to a weakened immunity (opportunistic infections) may arise. 
These will require specific and sometimes preventive treatment. 

2. What you need to know before you take Zerit 

Do not take Zerit 
 If you are allergic to stavudine or any of the other ingredients of this medicine (listed in section 

6). Contact your doctor or pharmacist for advice. 
 If you are taking didanosine, used to treat HIV infection. 

Warnings and precautions 
Talk to your doctor before taking Zerit. 
Before treatment with Zerit, you should have told your doctor: 
 if you suffer from kidney disease or liver disease (such as hepatitis) 
 if you have had peripheral neuropathy (persistent numbness, tingling, or pain in the feet and/or 

hands) 
 if you have suffered from pancreatitis (inflammation of the pancreas). 

Approved 1.0v



73

Zerit can cause a sometimes fatal condition called lactic acidosis, together with an enlarged liver. This 
condition usually does not occur until a few months after onset of treatment. This rare, but very serious 
side effect occurs more often in women, particularly if very overweight. In addition, rare cases of liver 
failure/renal failure or fatal hepatitis have been reported. 
Patients with chronic hepatitis B or C and treated with antiretroviral agents are at increased risk for 
severe and potentially fatal liver side effects and may require blood tests for control of liver function. 

If you develop one of the following, contact your doctor: 
 persistent numbness, tingling or pain in feet and/or hands (this may indicate the beginning of 

peripheral neuropathy, an adverse effect on the nerves), muscular weakness 
 abdominal pain, nausea or vomiting 
 rapid deep breathing, drowsiness (which may indicate pancreatitis, liver disturbance such as 

hepatitis, or lactic acidosis). 

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

During therapy with Zerit there is often a gradual loss of subcutaneous fat (fat found beneath the skin), 
which is most notable in the face and on the legs and arms. Contact your doctor if you notice such 
changes. 

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

Other medicines and Zerit 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 

Do not take Zerit if you are taking didanosine, used to treat HIV infection. 

Tell your doctor if you are taking any of the following medicines, as undesirable interactions may 
occur: 
 zidovudine, used to treat HIV infection 
 doxorubicin, used to treat cancer 
 ribavirin, used to treat hepatitis C infection. 

Zerit with food and drink 
For maximum effect, Zerit should be taken on an empty stomach, and preferably at least one hour 
before a meal. If this is not possible, the capsules may also be taken with a light meal. 

Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine. 

Approved 1.0v



74

Pregnancy 
You must contact your doctor to discuss the potential side effects and the benefits and risks of your 
antiretroviral therapy to you and your child. Lactic acidosis (sometimes fatal) has been reported in 
pregnant women who received Zerit in combination with other antiretroviral treatment. 
If you have taken Zerit during your pregnancy, your doctor may request regular blood tests and other 
diagnostic tests to monitor the development of your child. In children whose mothers took NRTIs 
during pregnancy, the benefit from the protection against HIV outweighed the risk of side effects. 

Breast-feeding 
Tell your doctor if you are breast-feeding. It is recommended that HIV-infected women should not 
breast-feed under any circumstances in order to avoid transmission of HIV to the baby. 

Driving and using machines 
Zerit may cause dizziness and drowsiness. 
If you are affected, do not drive and do not use any tools or machines. 

Zerit contains lactose 
These capsules contain lactose. If you have been told by your doctor that you have an intolerance to 
some sugars, contact your doctor before taking this medicinal product. 

3. How to take Zerit 

Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure. Your doctor has defined your daily dose based on your weight and individual characteristics. 
Please follow these recommendations closely as they will give you the best chance to delay 
development of a resistance to the medicinal product. Do not change the dose on your own. Continue 
to take this medicine until your doctor tells you otherwise. 
For adults whose body weight is 30 kg or more, the usual starting dose is 30 or 40 mg given twice 
daily (with approximately 12 hours between each dose). 
To obtain optimal absorption, the capsules should be swallowed with a glass of water, preferentially at 
least one hour before a meal and on an empty stomach. If this is not possible, Zerit may also be taken 
with a light meal. 
If you have problems swallowing capsules you should ask your doctor about the possibility of 
changing to the solution form of this medicine or you could carefully open the capsule and mix its 
contents with some food. 

Use in children 
For children whose body weight is 30 kg or more, the usual starting dose is 30 or 40 mg given twice 
daily (with approximately 12 hours between each dose). 
Children older than 3 months, whose body weight is less than 30 kg, should receive 1 mg/kg twice 
daily. 

If you take more Zerit than you should 
If you have taken too many capsules or if someone accidentally swallows some, there is no immediate 
danger. However, you should contact your doctor or the nearest hospital for advice. 

If you forget to take Zerit 
If you accidentally miss a dose, then simply take your normal dose when the next one is due. Do not 
take a double dose to make up for a forgotten dose. 

If you stop taking Zerit 
The decision to stop using Zerit should be discussed with your doctor. 

If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 

Approved 1.0v



75

4. Possible side effects 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

When treating HIV infection, it is not always possible to differentiate between unwanted effects 
caused by Zerit, or those caused by any other medicines you may be taking at the same time, or by the 
complications of the infection. For this reason, it is important that you inform your doctor of any 
change in your health. 

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. 

Treatment with stavudine (Zerit) often causes a loss of fat from legs, arms and face (lipoatrophy). This 
loss of body fat has been shown to be not fully reversible after discontinuation of stavudine.  Your 
doctor should monitor for signs of lipoatrophy. Tell your doctor if you notice any loss of fat from your 
legs, arms, and face. When these signs occur, Zerit should be stopped and your HIV treatment 
changed. 

Patients treated with Zerit have reported the following side effects: 

Common (may affect up to 1 in 10 people)  
 asymptomatic hyperlactatemia (build up of acid in your blood)  
 lipoatrophy  
 depression  
 peripheral neurologic symptoms including peripheral neuropathy, paresthesia, and peripheral 

neuritis (numbness, weakness, tingling or pain in the arms and legs) 
 dizziness, abnormal dreams, headache  
 insomnia (difficulty sleeping), somnolence (sleepiness), abnormal thinking 
 diarrhoea, abdominal pain (stomach pain of discomfort) 
 nausea, dyspepsia (indigestion) 
 rash, pruritus (itching)  
 fatigue (extreme tiredness) 

Uncommon (may affect up to 1 in 100 people) 
 lactic acidosis (build up of acid in your blood) in some cases involving motor weakness 

(weakness in your arms, legs or hands) 
 gynaecomastia (breast enlargement in men) 
 anorexia (loss of appetite), anxiety, emotional lability 
 pancreatitis (inflammation of the pancreas), vomiting 
 hepatitis (inflamation of the liver), jaundice (yellow of the skin or eyes) 
 urticaria (itchy rash), arthralgia (joint pain) 
 myalgia (aching muscles), asthenia (unusual tiredness or weakness) 

Rare (may affect up to 1 in 1,000 people) 
 anemia 
 hyperglycaemia (high sugar levels in the blood) 
 hepatic steatosis (fat in the liver) 

Very rare (may affect up to 1 in 10,000 people) 
 thrombocytopenia, neutropenia (blood disorders)  
 diabetes mellitus 
 motor weakness (most often reported in the setting of symptomatic hyperlacetatemia or lactic 

acidosis syndrome) 
 liver failure 

Approved 1.0v



76

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 Zerit 

Keep this medicine out of the sight and reach of children. 

Do not use this medicine after the expiry date which is stated on the carton, the bottle label and/or the 
blister after EXP. The expiry date refers to the last day of that month. 

Store below 25°C (aclar/alu blisters). 
Do not store above 30°C (HDPE bottles). 
Store in the original package. 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 

6. Contents of the pack and other information 

What Zerit contains 
 The active substance is stavudine (30 mg). 
 The other ingredients of the powder contained in the hard capsule are: lactose (180 mg), 

magnesium stearate, microcrystalline cellulose and sodium starch glycolate. 
 The ingredients of the capsule shell are gelatine, iron oxide colorant (E172), silicon dioxide, 

sodium laurilsulphate and titanium dioxide colorant (E171). 
 The capsule shells are marked using edible black printing ink containing shellac, propylene 

glycol, purified water, potassium hydroxide and iron oxide (E172). 

What Zerit looks like and content of the pack 
Zerit 30 mg hard capsules are light and dark orange and marked with “BMS 1966” on one side and 
“30” on the other side. 
Zerit 30 mg hard capsules are supplied in blister packs of 56 hard capsules or bottles of 60 hard 
capsules. To help protect the capsules from excessive moisture, the bottle includes a desiccant canister. 

Marketing Authorisation Holder and Manufacturer 
Marketing Authorisation Holder 
Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland 

Manufacturer 
Bristol-Myers Squibb S.r.l. 
Contrada Fontana del Ceraso 
03012 Anagni (FR) 
Italy 

Aesica Queenborough Limited 
North Road, Queenborough 
Kent, ME11 5EL 
United Kingdom 

Approved 1.0v



77

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 

Belgique/België/Belgien 
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 

Lietuva
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: +370 52 369140 

България 
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Teл.: + 359 800 12 400 

Luxembourg/Luxemburg
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 

Česká republika 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 420 221 016 111 

Magyarország 
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel.: + 36 1 301 9700 

Danmark 
Bristol-Myers Squibb 
Tlf: + 45 45 93 05 06 

Malta 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 

Deutschland
Bristol-Myers Squibb GmbH & Co. KGaA 
Tel: + 49 89 121 42-0 

Nederland
Bristol-Myers Squibb B.V. 
Tel: + 31 (0)30 300 2222 

Eesti
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: +372 640 1030

Norge 
Bristol-Myers Squibb Norway Ltd 
Tlf: + 47 67 55 53 50 

Ελλάδα
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 30 210 6074300 

Österreich
Bristol-Myers Squibb GesmbH 
Tel: + 43 1 60 14 30 

España
BRISTOL-MYERS SQUIBB, S.A. 
Tel: + 34 91 456 53 00 

Polska
BRISTOL-MYERS SQUIBB POLSKA SP. Z O.O. 
Tel.: + 48 22 5796666 

France
Bristol-Myers Squibb SARL 
Tél: +33 (0)1 58 83 84 96 

Portugal
Bristol-Myers Squibb Farmacêutica Portuguesa, 
S.A. 
Tel: + 351 21 440 70 00 

Hrvatska
Bristol-Myers Squibb spol. s r.o. 
TEL: +385 1 2078 508 

România 
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: + 40 (0)21 272 16 00 

Ireland
Bristol-Myers Squibb Pharmaceuticals Ltd 
Tel: + 353 (1 800) 749 749 

Slovenija
Bristol-Myers Squibb spol. s r.o. 
Tel: +386 1 2355 100 

Ísland
Vistor hf. 
Sími: + 354 535 7000 

Slovenská republika
Bristol-Myers Squibb spol. s r.o. 
Tel: + 421 2 59298411 

Approved 1.0v



78

Italia
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 

Suomi/Finland
Oy Bristol-Myers Squibb (Finland) Ab 
Puh/Tel: + 358 9 251 21 230 

Κύπρος
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 357 800 92666 

Sverige
Bristol-Myers Squibb AB 
Tel: + 46 8 704 71 00 

Latvija
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: +371 67708347 

United Kingdom
Bristol-Myers Squibb Pharmaceuticals Ltd 
Tel: + 44 (0800) 731 1736 

This leaflet was last revised in {MM/YYYY}. 

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/. 

Approved 1.0v



79

Package leaflet: Information for the user 

Zerit 40 mg hard capsules 
Stavudine 

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 Zerit is and what it is used for 
2. What you need to know before you take Zerit 
3. How to take Zerit 
4. Possible side effects 
5. How to store Zerit 
6. Contents of the pack and other information 

1. What Zerit is and what it is used for 

Zerit belongs to a particular group of antiviral medicines, also known as antiretrovirals, called 
nucleoside reverse transcriptase inhibitors (NRTIs). 

These are used to treat Human Immunodeficiency Virus (HIV) infection. 

This medicinal product, in combination with other antiretrovirals, reduces the HIV viral load and 
keeps it at a low level. It also increases CD4 cell counts. These CD4 cells play an important role in 
maintaining a healthy immune system to help fight infection. Response to treatment with Zerit varies 
between patients. Your doctor will therefore be monitoring the effectiveness of your treatment. 

Zerit may improve your condition, but it is not a cure for your HIV infection. 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. 
During treatment, other infections linked to a weakened immunity (opportunistic infections) may arise. 
These will require specific and sometimes preventive treatment. 

2. What you need to know before you take Zerit 

Do not take Zerit 
 If you are allergic to stavudine or any of the other ingredients of this medicine (listed in section 

6). Contact your doctor or pharmacist for advice. 
 If you are taking didanosine, used to treat HIV infection. 

Warnings and precautions 
Talk to your doctor before taking Zerit. 
Before treatment with Zerit, you should have told your doctor: 
 if you suffer from kidney disease or liver disease (such as hepatitis) 
 if you have had peripheral neuropathy (persistent numbness, tingling, or pain in the feet and/or 

hands) 
 if you have suffered from pancreatitis (inflammation of the pancreas). 

Approved 1.0v



80

Zerit can cause a sometimes fatal condition called lactic acidosis, together with an enlarged liver. This 
condition usually does not occur until a few months after onset of treatment. This rare, but very serious 
side effect occurs more often in women, particularly if very overweight. In addition, rare cases of liver 
failure/renal failure or fatal hepatitis have been reported. 
Patients with chronic hepatitis B or C and treated with antiretroviral agents are at increased risk for 
severe and potentially fatal liver side effects and may require blood tests for control of liver function. 

If you develop one of the following, contact your doctor: 
 persistent numbness, tingling or pain in feet and/or hands (this may indicate the beginning of 

peripheral neuropathy, an adverse effect on the nerves), muscular weakness 
 abdominal pain, nausea or vomiting 
 rapid deep breathing, drowsiness (which may indicate pancreatitis, liver disturbance such as 

hepatitis, or lactic acidosis). 

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

During therapy with Zerit there is often a gradual loss of subcutaneous fat (fat found beneath the skin), 
which is most notable in the face and on the legs and arms. Contact your doctor if you notice such 
changes. 

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

Other medicines and Zerit 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines. 

Do not take Zerit if you are taking didanosine, used to treat HIV infection. 

Tell your doctor if you are taking any of the following medicines, as undesirable interactions may 
occur: 
 zidovudine, used to treat HIV infection 
 doxorubicin, used to treat cancer 
 ribavirin, used to treat hepatitis C infection. 

Zerit with food and drink 
For maximum effect, Zerit should be taken on an empty stomach, and preferably at least one hour 
before a meal. If this is not possible, the capsules may also be taken with a light meal. 

Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine. 

Approved 1.0v



81

Pregnancy 
You must contact your doctor to discuss the potential side effects and the benefits and risks of your 
antiretroviral therapy to you and your child. Lactic acidosis (sometimes fatal) has been reported in 
pregnant women who received Zerit in combination with other antiretroviral treatment. 
If you have taken Zerit during your pregnancy, your doctor may request regular blood tests and other 
diagnostic tests to monitor the development of your child. In children whose mothers took NRTIs 
during pregnancy, the benefit from the protection against HIV outweighed the risk of side effects. 

Breast-feeding 
Tell your doctor if you are breast-feeding. It is recommended that HIV-infected women should not 
breast-feed under any circumstances in order to avoid transmission of HIV to the baby. 

Driving and using machines 
Zerit may cause dizziness and drowsiness. 
If you are affected, do not drive and do not use any tools or machines. 

Zerit contains lactose 
These capsules contain lactose. If you have been told by your doctor that you have an intolerance to 
some sugars, contact your doctor before taking this medicinal product. 

3. How to take Zerit 

Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure. Your doctor has defined your daily dose based on your weight and individual characteristics. 
Please follow these recommendations closely as they will give you the best chance to delay 
development of a resistance to the medicinal product. Do not change the dose on your own. Continue 
to take this medicine until your doctor tells you otherwise. 
For adults whose body weight is 30 kg or more, the usual starting dose is 30 or 40 mg given twice 
daily (with approximately 12 hours between each dose). 
To obtain optimal absorption, the capsules should be swallowed with a glass of water, preferentially at 
least one hour before a meal and on an empty stomach. If this is not possible, Zerit may also be taken 
with a light meal. 
If you have problems swallowing capsules you should ask your doctor about the possibility of 
changing to the solution form of this medicine or you could carefully open the capsule and mix its 
contents with some food. 

Use in children 
For children whose body weight is 30 kg or more, the usual starting dose is 30 or 40 mg given twice 
daily (with approximately 12 hours between each dose). 
Children older than 3 months, whose body weight is less than 30 kg, should receive 1 mg/kg twice 
daily. 

If you take more Zerit than you should 
If you have taken too many capsules or if someone accidentally swallows some, there is no immediate 
danger. However, you should contact your doctor or the nearest hospital for advice. 

If you forget to take Zerit 
If you accidentally miss a dose, then simply take your normal dose when the next one is due. Do not 
take a double dose to make up for a forgotten dose. 

If you stop taking Zerit 
The decision to stop using Zerit should be discussed with your doctor. 

If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 

Approved 1.0v



82

4. Possible side effects 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

When treating HIV infection, it is not always possible to differentiate between unwanted effects 
caused by Zerit, or those caused by any other medicines you may be taking at the same time, or by the 
complications of the infection. For this reason, it is important that you inform your doctor of any 
change in your health. 

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. 

Treatment with stavudine (Zerit) often causes a loss of fat from legs, arms and face (lipoatrophy). This 
loss of body fat has been shown to be not fully reversible after discontinuation of stavudine.  Your 
doctor should monitor for signs of lipoatrophy. Tell your doctor if you notice any loss of fat from your 
legs, arms, and face. When these signs occur, Zerit should be stopped and your HIV treatment 
changed. 

Patients treated with Zerit have reported the following side effects: 

Common (may affect up to 1 in 10 people)  
 asymptomatic hyperlactatemia (build up of acid in your blood)  
 lipoatrophy  
 depression  
 peripheral neurologic symptoms including peripheral neuropathy, paresthesia, and peripheral 

neuritis (numbness, weakness, tingling or pain in the arms and legs) 
 dizziness, abnormal dreams, headache  
 insomnia (difficulty sleeping), somnolence (sleepiness), abnormal thinking 
 diarrhoea, abdominal pain (stomach pain of discomfort) 
 nausea, dyspepsia (indigestion) 
 rash, pruritus (itching)  
 fatigue (extreme tiredness) 

Uncommon (may affect up to 1 in 100 people) 
 lactic acidosis (build up of acid in your blood) in some cases involving motor weakness 

(weakness in your arms, legs or hands) 
 gynaecomastia (breast enlargement in men) 
 anorexia (loss of appetite), anxiety, emotional lability 
 pancreatitis (inflammation of the pancreas), vomiting 
 hepatitis (inflamation of the liver), jaundice (yellow of the skin or eyes) 
 urticaria (itchy rash), arthralgia (joint pain) 
 myalgia (aching muscles), asthenia (unusual tiredness or weakness) 

Rare (may affect up to 1 in 1,000 people) 
 anemia 
 hyperglycaemia (high sugar levels in the blood) 
 hepatic steatosis (fat in the liver) 

Very rare (may affect up to 1 in 10,000 people) 
 thrombocytopenia, neutropenia (blood disorders)  
 diabetes mellitus 
 motor weakness (most often reported in the setting of symptomatic hyperlacetatemia or lactic 

acidosis syndrome) 
 liver failure 

Approved 1.0v



83

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 Zerit 

Keep this medicine out of the sight and reach of children. 

Do not use this medicine after the expiry date which is stated on the carton, the bottle label and/or the 
blister after EXP. The expiry date refers to the last day of that month. 

Store below 25°C (aclar/alu blisters). 
Do not store above 30°C (HDPE bottles). 
Store in the original package. 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 

6. Contents of the pack and other information 

What Zerit contains 
 The active substance is stavudine (40 mg). 
 The other ingredients of the powder contained in the hard capsule are: lactose (240 mg), 

magnesium stearate, microcrystalline cellulose and sodium starch glycolate. 
 The ingredients of the capsule shell are gelatine, iron oxide colorant (E172), silicon dioxide, 

sodium laurilsulphate and titanium dioxide colorant (E171). 
 The capsule shells are marked using edible black printing ink containing shellac, propylene 

glycol, purified water, potassium hydroxide and iron oxide (E172). 

What Zerit looks like and content of the pack 
Zerit 40 mg hard capsules are dark orange and marked with “BMS 1967” on one side and “40” on the 
other side. 
Zerit 40 mg hard capsules are supplied in blister packs of 56 hard capsules or bottles of 60 hard 
capsules. To help protect the capsules from excessive moisture, the bottle includes a desiccant canister. 

Marketing Authorisation Holder and Manufacturer 
Marketing Authorisation Holder 
Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland 

Manufacturer 
Bristol-Myers Squibb S.r.l. 
Contrada Fontana del Ceraso  
03012 Anagni (FR) 
Italy 

Aesica Queenborough Limited 
North Road, Queenborough 
Kent, ME11 5EL 
United Kingdom 

Approved 1.0v



84

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 

Belgique/België/Belgien 
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 

Lietuva
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: +370 52 369140 

България 
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Teл.: + 359 800 12 400 

Luxembourg/Luxemburg
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 

Česká republika 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 420 221 016 111 

Magyarország 
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel.: + 36 1 301 9700 

Danmark 
Bristol-Myers Squibb 
Tlf: + 45 45 93 05 06 

Malta 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 

Deutschland
Bristol-Myers Squibb GmbH & Co. KGaA 
Tel: + 49 89 121 42-0 

Nederland
Bristol-Myers Squibb B.V. 
Tel: + 31 (0)30 300 2222 

Eesti
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: +372 640 1030

Norge 
Bristol-Myers Squibb Norway Ltd 
Tlf: + 47 67 55 53 50 

Ελλάδα
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 30 210 6074300 

Österreich
Bristol-Myers Squibb GesmbH 
Tel: + 43 1 60 14 30 

España
BRISTOL-MYERS SQUIBB, S.A. 
Tel: + 34 91 456 53 00 

Polska
BRISTOL-MYERS SQUIBB POLSKA SP. Z O.O. 
Tel.: + 48 22 5796666 

France
Bristol-Myers Squibb SARL 
Tél: +33 (0)1 58 83 84 96 

Portugal
Bristol-Myers Squibb Farmacêutica Portuguesa, 
S.A. 
Tel: + 351 21 440 70 00 

Hrvatska
Bristol-Myers Squibb spol. s r.o. 
TEL: +385 1 2078 508 

România 
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: + 40 (0)21 272 16 00 

Ireland
Bristol-Myers Squibb Pharmaceuticals Ltd 
Tel: + 353 (1 800) 749 749 

Slovenija
Bristol-Myers Squibb spol. s r.o. 
Tel: +386 1 2355 100 

Ísland
Vistor hf. 
Sími: + 354 535 7000 

Slovenská republika
Bristol-Myers Squibb spol. s r.o. 
Tel: + 421 2 59298411 

Approved 1.0v



85

Italia
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 

Suomi/Finland
Oy Bristol-Myers Squibb (Finland) Ab 
Puh/Tel: + 358 9 251 21 230 

Κύπρος
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 357 800 92666 

Sverige
Bristol-Myers Squibb AB 
Tel: + 46 8 704 71 00 

Latvija
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: +371 67708347 

United Kingdom
Bristol-Myers Squibb Pharmaceuticals Ltd 
Tel: + 44 (0800) 731 1736 

This leaflet was last revised in {MM/YYYY}. 

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/. 

Approved 1.0v



86

Package leaflet: Information for the user 

Zerit 200 mg powder for oral solution 
Stavudine 

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 Zerit is and what it is used for 
2. What you need to know before you take Zerit 
3. How to take Zerit 
4. Possible side effects 
5. How to store Zerit 
6. Contents of the pack and other information 

1. What Zerit is and what it is used for 

Zerit belongs to a particular group of antiviral medicines, also known as antiretrovirals, called 
nucleoside reverse transcriptase inhibitors (NRTIs). 

These are used to treat Human Immunodeficiency Virus (HIV) infection. 

This medicinal product, in combination with other antiretrovirals, reduces the HIV viral load and 
keeps it at a low level. It also increases CD4 cell counts. These CD4 cells play an important role in 
maintaining a healthy immune system to help fight infection. Response to treatment with Zerit varies 
between patients. Your doctor will therefore be monitoring the effectiveness of your treatment. 

Zerit may improve your condition, but it is not a cure for your HIV infection. 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. 
During treatment, other infections, linked to a weakened immunity (opportunistic infections) may 
arise. These will require specific and sometimes preventive treatment. 

2. What you need to know before you take Zerit 

Do not take Zerit 
 If you are allergic to stavudine or any of the other ingredients of this medicine (listed in section 

6). Contact your doctor or pharmacist for advice. 
 If you are taking didanosine, used to treat HIV infection 

Warnings and precautions 
Talk to your doctor before taking Zerit. 
Before treatment with Zerit, you should have told your doctor: 
 if you suffer from kidney disease or liver disease (such as hepatitis) 
 if you have had peripheral neuropathy (persistent numbness, tingling, or pain in the feet and/or 

hands) 
 if you have suffered from pancreatitis (inflammation of the pancreas). 

Approved 1.0v



87

Zerit can cause a sometimes fatal condition called lactic acidosis, together with an enlarged liver. This 
condition usually does not occur until a few months after onset of treatment. This rare, but very serious 
side effect occurs more often in women, particularly if very overweight. In addition, rare cases of liver 
failure/renal failure or fatal hepatitis have been reported. 
Patients with chronic hepatitis B or C and treated with antiretroviral agents are at increased risk for 
severe and potentially fatal liver side effects and may require blood tests for control of liver function. 

If you develop one of the following, contact your doctor: 
 persistent numbness, tingling or pain in feet and/or hands (this may indicate the beginning of 

peripheral neuropathy, an adverse effect on the nerves), muscular weakness 
 abdominal pain, nausea or vomiting 
 rapid deep breathing, drowsiness (which may indicate pancreatitis, liver disturbance such as 

hepatitis, or lactic acidosis). 

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

During therapy with Zerit there is often a gradual loss of subcutaneous fat (fat found beneath the skin), 
which is most notable in the face and on the legs and arms. Contact your doctor if you notice such 
changes. 

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

Other medicines and Zerit 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines.  

Do not take Zerit if you are taking didanosine, used to treat HIV infection. 

Tell your doctor if you are taking any of the following medicines, as undesirable interactions may 
occur: 
 zidovudine, used to treat HIV infection 
 doxorubicin, used to treat cancer 
 ribavirin, used to treat hepatitis C infection. 

Zerit with food and drink 
For maximum effect, Zerit should be taken on an empty stomach, and preferably at least one hour 
before a meal. If this is not possible, Zerit may also be taken with a light meal. 

Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine.

Approved 1.0v



88

Pregnancy 
You must contact your doctor to discuss the potential side effects and the benefits and risks of your 
antiretroviral therapy to you and your child. Lactic acidosis (sometimes fatal) has been reported in 
pregnant women who received Zerit in combination with other antiretroviral treatment. 
If you have taken Zerit during your pregnancy, your doctor may request regular blood tests and other 
diagnostic tests to monitor the development of your child. In children whose mothers took NRTIs 
during pregnancy, the benefit from the protection against HIV outweighed the risk of side effects. 

Breast-feeding 
Tell your doctor if you are breast-feeding. It is recommended that HIV-infected women should not 
breast-feed under any circumstances in order to avoid transmission of HIV to the baby. 

Driving and using machines 
Zerit may cause dizziness and drowsiness. 
If you are affected, do not drive and do not use any tools or machines. 

Zerit contains sucrose and preservatives  
After reconstitution with water, the solution contains 50 mg of sucrose per ml of solution. This should 
be taken into account in patients with diabetes mellitus.  If you have been told by your doctor that you 
have an intolerance to some sugars, contact your doctor before taking this medicinal product.  May be 
harmful to the teeth.  
This product contains methylhydroxybenzoate (E218) and propylhydroxybenzoate (E216) that may 
cause allergic reactions (possibly delayed). 

3. How to take Zerit 

Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure. Your doctor has defined your daily dose based on your weight and individual characteristics. 
Please follow these recommendations closely as they will give you the best chance to delay 
development of a resistance to the medicinal product. Do not change the dose on your own. Continue 
to take this medicine until your doctor tells you otherwise. 
For adults whose body weight is 30 kg or more, the usual starting dose is 30 or 40 mg given twice 
daily (with approximately 12 hours between each dose). 

To obtain optimal absorption, Zerit should be taken at least one hour before a meal and on an empty 
stomach. If this is not possible, Zerit may also be taken with a light meal. 
Prepare the ready-to-use solution by mixing the powder with 202 ml of water or by slowly adding 
water up to the top edge of the bottle label shown by the arrow fill marks. Then screw the cap on 
tightly and shake the bottle well until the powder dissolves completely, and take or dispense the 
solution with the measuring cup provided. For infants who require a dose less than 10 ml, ask your 
pharmacist for a syringe to use to accurately measure the oral dose. Do not worry if the solution 
remains slightly hazy after mixing with water; this is normal. If needed, consult your pharmacist for 
help with this procedure. 

Use in children 

For children whose body weight is 30 kg or more, the usual starting dose is 30 or 40 mg given twice 
daily (with approximately 12 hours between each dose). 
Children from birth to 13 days old should receive 0.5 mg/kg twice daily. Children at least 14 days old 
whose body weight is less than 30 kg, should receive 1 mg/kg twice daily. 

If you take more Zerit than you should 
If you have taken too much of the solution, or if someone accidentally swallows some, there is no 
immediate danger. However, you should contact your doctor or the nearest hospital for advice. 

Approved 1.0v



89

If you forget to take Zerit 
If you accidentally miss a dose, then simply take your normal dose when the next one is due. Do not 
take a double dose to make up for a forgotten dose. 

If you stop taking Zerit 
The decision to stop using Zerit should be discussed with your doctor. 

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.  

4. Possible side effects 

Like all medicines, this medicine can cause side effects, although not everybody gets them.   

When treating HIV infection it is not always possible to differentiate between unwanted effects caused 
by Zerit or those caused by any other medicines you may be taking at the same time, or by the 
complications of the infection. For this reason, it is important that you inform your doctor of any 
change in your health.  

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. 

Treatment with stavudine (Zerit) often causes a loss of fat from legs, arms and face (lipoatrophy). This 
loss of body fat has been shown to be not fully reversible after discontinuation of stavudine.  Your 
doctor should monitor for signs of lipoatrophy. Tell your doctor if you notice any loss of fat from your 
legs, arms, and face. When these signs occur, Zerit should be stopped and your HIV treatment 
changed. 

Patients treated with Zerit have reported the following side effects: 

Common (may affect up to 1 in 10 people)  
 asymptomatic hyperlactatemia (build up of acid in your blood)  
 lipoatrophy  
 depression  
 peripheral neurologic symptoms including peripheral neuropathy, paresthesia, and peripheral 

neuritis (numbness, weakness, tingling or pain in the arms and legs) 
 dizziness, abnormal dreams, headache  
 insomnia (difficulty sleeping), somnolence (sleepiness), abnormal thinking 
 diarrhoea, abdominal pain (stomach pain of discomfort) 
 nausea, dyspepsia (indigestion) 
 rash, pruritus (itching)  
 fatigue (extreme tiredness) 

Uncommon (may affect up to 1 in 100 people) 
 lactic acidosis (build up of acid in your blood) in some cases involving motor weakness 

(weakness in your arms, legs or hands) 
 gynaecomastia (breast enlargement in men) 
 anorexia (loss of appetite), anxiety, emotional lability 
 pancreatitis (inflammation of the pancreas), vomiting 
 hepatitis (inflamation of the liver), jaundice (yellow of the skin or eyes) 
 urticaria (itchy rash), arthralgia (joint pain) 
 myalgia (aching muscles), asthenia (unusual tiredness or weakness) 

Rare (may affect up to 1 in 1,000 people) 
 anemia 
 hyperglycaemia (high sugar levels in the blood) 

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 hepatic steatosis (fat in the liver) 

Very rare (may affect up to 1 in 10,000 people) 
 thrombocytopenia, neutropenia (blood disorders)  
 diabetes mellitus 
 motor weakness (most often reported in the setting of symptomatic hyperlacetatemia or lactic 

acidosis syndrome) 
 liver failure 

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 Zerit 

Keep this medicine out of the sight and reach of children. 

Do not use this medicine after the expiry date which is stated on the bottle and on the carton after 
EXP. The expiry date refers to the last day of that month. 

Do not store the dry powder above 30°C. Store in the original package in order to protect from 
excessive moisture. 
The prepared oral solution is stable for 30 days in a refrigerator (2°C -8°C).  
Keep the bottle tightly closed. 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 

6. Contents of the pack and other information 

What Zerit contains 
 The active substance is stavudine (200 mg). 
 The other ingredients of the powder are: cherry flavour, methylhydroxybenzoate (E218), 

propylhydroxybenzoate (E216), silicon dioxide, simethicone, sodium carmellose, sorbic acid, 
stearate emulsifiers and sucrose. 

What Zerit looks like and content of the pack 
The powder contains 200 mg stavudine. The reconstituted solution contains 1 mg of stavudine per ml. 
Before reconstitution the Zerit powder appears as off-white to pale-pink, gritty powder. When 
reconstituted with 202 ml of water, produces 210  ml of a colorless to slightly pink, hazy solution. 
Zerit 200 mg powder for oral solution is supplied in a bottle containing 200 ml solution. 

Marketing Authorisation Holder and Manufacturer 
Marketing Authorisation Holder 
Bristol-Myers Squibb Pharma EEIG 
Plaza 254 
Blanchardstown Corporate Park 2 
Dublin 15, D15 T867 
Ireland 

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Manufacturer 
Bristol-Myers Squibb S.r.l. 
Contrada Fontana del Ceraso 
03012 Anagni (FR) 
Italy 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 

Belgique/België/Belgien 
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 

Lietuva
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: +370 52 369140 

България 
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Teл.: + 359 800 12 400 

Luxembourg/Luxemburg
N.V. Bristol-Myers Squibb Belgium S.A. 
Tél/Tel: + 32 2 352 76 11 

Česká republika 
Bristol-Myers Squibb spol. s r.o. 
Tel: + 420 221 016 111 

Magyarország 
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel.: + 36 1 301 9700 

Danmark 
Bristol-Myers Squibb 
Tlf: + 45 45 93 05 06 

Malta 
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 

Deutschland
Bristol-Myers Squibb GmbH & Co. KGaA 
Tel: + 49 89 121 42-0 

Nederland
Bristol-Myers Squibb B.V. 
Tel: + 31 (0)30 300 2222 

Eesti
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: +372 640 1030

Norge 
Bristol-Myers Squibb Norway Ltd 
Tlf: + 47 67 55 53 50 

Ελλάδα
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 30 210 6074300 

Österreich
Bristol-Myers Squibb GesmbH 
Tel: + 43 1 60 14 30 

España
BRISTOL-MYERS SQUIBB, S.A. 
Tel: + 34 91 456 53 00 

Polska
BRISTOL-MYERS SQUIBB POLSKA SP. Z O.O. 
Tel.: + 48 22 5796666 

France
Bristol-Myers Squibb SARL 
Tél: +33 (0)1 58 83 84 96 

Portugal
Bristol-Myers Squibb Farmacêutica Portuguesa, 
S.A. 
Tel: + 351 21 440 70 00 

Hrvatska
Bristol-Myers Squibb spol. s r.o. 
TEL: +385 1 2078 508 

România 
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: + 40 (0)21 272 16 00 

Ireland
Bristol-Myers Squibb Pharmaceuticals Ltd 
Tel: + 353 (1 800) 749 749 

Slovenija
Bristol-Myers Squibb spol. s r.o. 
Tel: +386 1 2355 100 

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Ísland
Vistor hf. 
Sími: + 354 535 7000 

Slovenská republika
Bristol-Myers Squibb spol. s r.o. 
Tel: + 421 2 59298411 

Italia
BRISTOL-MYERS SQUIBB S.R.L. 
Tel: + 39 06 50 39 61 

Suomi/Finland
Oy Bristol-Myers Squibb (Finland) Ab 
Puh/Tel: + 358 9 251 21 230 

Κύπρος
BRISTOL-MYERS SQUIBB A.E. 
Τηλ: + 357 800 92666 

Sverige
Bristol-Myers Squibb AB 
Tel: + 46 8 704 71 00 

Latvija
Bristol-Myers Squibb Gyógyszerkereskedelmi Kft.
Tel: +371 67708347 

United Kingdom
Bristol-Myers Squibb Pharmaceuticals Ltd 
Tel: + 44 (0800) 731 1736 

This leaflet was last revised in {MM/YYYY}. 

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/. 

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	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