Carmustine Obvius

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
  



2 

 
1. NAME OF THE MEDICINAL PRODUCT 
 
Carmustine Obvius 100 mg powder and solvent for concentrate for solution for infusion 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each vial of powder for concentrate for solution for infusion contains 100 mg carmustine. 

 
After reconstitution and dilution (se section 6.6), one mL of solution contains 3.3 mg carmustine. 
 
Excipient with known effect 
Each ampoule of solvent contains 3 ml ethanol anhydrous (that is equivalent to 2.37 g). 

 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for concentrate for solution for infusion. 

 
Powder: white to almost white powder or lyophilisate.  

 
Solvent: colourless clear liquid. 

 
The pH and osmolarity of ready-to-use solutions for infusion are: 
pH 4.0 to 5.0 and 385-397mOsm/l (if diluted in glucose 50 mg/ml [5%] solution for injection), and  
pH 4.0 to 6.8 and 370-378mOsm/l (if diluted in sodium chloride 9 mg/ml [0.9%] solution for 
injection). 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Carmustine is effective in the following malignant neoplasms as a single agent or in combination with 
other antineoplastic agents and/or other therapeutic measures (radiotherapy, surgery): 
 

- Brain tumours (glioblastoma, Brain-stem gliomas, medulloblastoma, astrocytoma and 
ependymoma), brain metastases 
 

- Secondary therapy in non-Hodgkin’s lymphoma and Hodgkin’s disease 
 

- as conditioning treatment prior to autologous haematopoietic progenitor cell transplantation 
(HPCT) in malignant haematological diseases (Hodgkin’s disease / Non-hodgkin’s 
lymphoma). 

 
4.2 Posology and method of administration 
 
Carmustine Obvius must be administered only by specialists experienced in the field of chemotherapy 
and under appropriate medical supervision 
 



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Posology 
 
Initial doses 
The recommended dose of Carmustine Obvius as a single agent in previously untreated patients is 
150 to 200 mg/m2 intravenously every 6 weeks. This may be given as a single dose or divided into 
daily infusions such as 75 to 100 mg/m2 on two successive days. 

 
When Carmustine Obvius is used in combination with other myelosuppressive medicinal products or 
in patients in whom bone marrow reserve is depleted, the doses should be adjusted according to the 
haematologic profile of the patient as shown below. 

 
Monitoring and subsequent doses 
A repeat course of Carmustine Obvius should not be given until circulating blood elements have 
returned to acceptable levels (platelets above 100,000/mm3, leukocytes above 4,000/mm3), and this is 
usually in six weeks. Blood counts should be monitored frequently and repeat courses should not be 
given before six weeks because of delayed haematologic toxicity. 

 
Doses subsequent to the initial dose should be adjusted according to the haematologic response of the 
patient to the preceding dose, in both monotherapy as well as in combination therapy with other 
myelosuppressive medicinal products. The following schedule is suggested as a guide to dosage 
adjustment: 
 
Table 1 

Nadir after prior dose Percentage of prior dose 
to be given Leucocytes/mm3 Platelets/mm3 

>4,000 >100,000 100% 
3,000 – 3,999 75,000 - 99,999 100% 
2,000 – 2,999 25,000 - 74,999 70% 
<2,000 <25,000 50% 

 
In cases where the nadir after initial dose does not fall in the same row for leucocytes and platelets 
(e.g. leucocytes >4,000 and platelets <25,000) the value given the lowest percentage of prior dose 
should be used (e.g. platelets <25,000 then a maximum of 50% of prior dose should be given). 

 
There are no limits for the period of application of carmustine therapy. In case the tumor remains 
incurable or some serious or intolerable adverse reactions appear, the carmustine therapy must be 
terminated. 
 
Conditioning treatment prior to HPCT 
 
Carmustine is given in combination with other chemotherapeutic agents in patients with malignant 
haematological diseases before HPCT at a dose of 300 - 600 mg/m2 intravenously. 
 
Special populations 

 
Paediatric population 
Carmustine is contraindicated in children and adolescents aged <18 years (see section 4.3) 
 
Elderly 
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of 
the dose range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and 
take into consideration concomitant disease or therapy with other medicinal products. Because elderly 
patients are more likely to have decreased renal function, care should be taken in dose selection, and 
the glomerular filtration rate should be monitored and the dose reduced according to this.  
 



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Renal impairment 
For patients with renal impairment the dose of Carmustine Obvius should be reduced if the glomerular 
filtration rate is reduced. 
 
Method of administration 
Carmustine Obvius is for intravenous use after reconstitution and further dilution. 
 
By reconstituting the powder with the solvent provided, a solution has to be prepared by adding 
additional 27 ml water for injections. Reconstitution and dilution, as recommended, results in a clear, 
colourless to light yellow stock solution which has to be further diluted with 500 ml sodium chloride 
9 mg/ml (0.9%) solution for injection, or glucose 50 mg/ml (5%) solution for injection. 

 
The resulting ready-to-use solution for infusion should then be administered immediately by 
intravenous drip over a one- to two-hour period protected from light. The duration of infusion should 
not be less than one hour, otherwise it leads to burning and pain in the injected area. The injected area 
should be monitored during the administration.  

 
For instructions on reconstitution and dilution of the medicinal product before administration, see 
section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance, to other nitrosoureas or to any of the excipients listed in 
section 6.1. 
Severe bone marrow depression. 
Severe (end-stage) renal impairment. 
Children and adolescents  
Breast-feeding. 
 
4.4 Special warnings and precautions for use 
 
Pulmonary toxicity characterised by pulmonary infiltrates and/or fibrosis has been reported to occur 
with a frequency ranging up to 30%. This may occur within 3 years of therapy and appears to be dose 
related with cumulative doses of 1,200-1,500 mg/m2 being associated with increased likelihood of lung 
fibrosis. Risk factors include smoking, the presence of a respiratory condition, pre-existing 
radiographic abnormalities, sequential or concomitant thoracic irradiation and association with other 
agents that cause lung damage. Baseline pulmonary function studies and chest X-ray should be 
conducted along with frequent pulmonary function tests during treatment. Patients with a baseline 
below 70% of the predicted forced vital capacity (FVC) or carbon monoxide diffusing capacity 
(DLCO) are particularly at risk. 
 
An increased risk for pulmonary toxicities upon treatment with conditioning regimes and HPCT for 
females has been reported. So far, this increased risk is described for the treatment itself including 
conditioning regimes without carmustine (e.g. TBI or busulfan-cyclophosphamide) or with carmustine 
(BEAM: carmustine, etopside, cytarabine and melphalan or CBV: cyclophosphamide, carmustine and 
etoposide). 
 
High-dose therapy with carmustine (especially with 600 mg/m2) prior to haematopoietic stem cell 
transplantation has been shown to increase the risk for incidence and severity of pulmonary toxicities. 
Therefore, in patients with other risks for pulmonary toxicities, use of carmustine needs to be weighed 
against the risks.  
 
Upon high-dose therapy with carmustine, the risk and severity for infections, cardiac, hepatic, 
gastrointestinal, and renal toxicity, diseases of the nervous system and electrolyte abnormalities 
(hypokalemia, hypomagnesemia and hypophosphatemia) rises. 
 



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Patients with comorbidities and worse disease status have a higher risk for adverse events. This needs 
to be respected especially for elderly patients. 
 
Hepatic and renal function should also be checked prior to treatment and regularly monitored during 
therapy (see section 4.8). 
 
Neutropenic enterocolitis can occur as therapy-related adverse event upon treatment with 
chemotherapeutic agents. 
 
Carmustine is carcinogenic in rats and mice at doses less than the recommended human dose based on 
body surface area (see section 5.3). 
 
Bone marrow toxicity is a common and severe toxic adverse reaction of carmustine. Complete blood 
count should be monitored frequently for at least six weeks after a dose. In case of a decreased number 
of circulating platelets, leucocytes or erythrocytes either from previous chemotherapy or other cause 
the dose should be adjusted, see Table 1, section 4.2. Liver, kidney and lung function should be 
checked and monitored regularly during therapy (see section 4.8). Repeat doses of Carmustine Obvius 
should not be given more frequently than every six weeks. The bone marrow toxicity of carmustine is 
cumulative and therefore the dosage adjustment must be considered on the basis of nadir blood counts 
from prior doses (see section 4.2).  
 
Direct administration of carmustine into the carotid artery is regarded as experimental and has been 
associated with ocular toxicity. 
 
A dose of 600 mg/mg2 of this medicine administered to an adult weighing 70 kg would result in 
exposure to 370 mg/kg of ethanol which may cause a rise in blood alcohol concentration (BAC) of 
about 61.7 mg/100 ml. For comparison, for an adult drinking a glass of wine or 500 ml of beer, the 
BAC is likely to be about 50 mg/100 ml. Co-administration with medicines containing e.g. propylene 
glycol or ethanol may lead to accumulation of ethanol and induce adverse effects. Because this 
medicine is usually given slowly over 6 hours, the effects of alcohol may be reduced. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Phenytoin and dexamethasone 
In combination with chemotherapeutic medicinal products reduced activity of antiepileptic medicinal 
products must be anticipated.  
 
Cimetidine 
Concomitant use with cimetidine leads to delayed, major, suspected, increased carmustine toxic effect 
(due to the inhibition of carmustine metabolism).  
 
Digoxin 
Concomitant use with digoxin leads to delayed, moderate, suspected, decreased effect of digoxin (due 
to the decreased digoxin absorption).  
 
Melphalan 
Concomitant use with melphalan leads to increased risk of pulmonary toxicity. 
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential/contraception in males and females 
Women should use effective contraception to avoid becoming pregnant while on treatment and for at 
least 6 months after treatment.  
 
Male patients should be advised to use adequate contraceptive measures while on treatment with 
carmustine and for at least 6 months after treatment. 
 



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Pregnancy 
Carmustine should not be administered to patients who are pregnant. Safe use in pregnancy has not 
been established and therefore the benefit must be carefully weighed against the risk of toxicity. 
Carmustine is embryotoxic in rats and rabbits and teratogenic in rats when given in doses equivalent to 
the human dose (see section 5.3). If Carmustine Obvius is used during pregnancy, or if the patient 
becomes pregnant while taking (receiving) Carmustine Obvius, the patient should be apprised of the 
potential hazard to the foetus. 
 
Breast-feeding 
It is unknown whether carmustine/metabolites are excreted in human milk. A risk to the 
newborns/infants cannot be excluded. Carmustine Obvius is contraindicated during breast-feeding and 
up to seven days post-treatment (see section 4.3). 
 
Fertility 
Carmustine may impair male fertility. Males should be advised of potential risk of infertility and to 
seek fertility/family planning counselling prior to therapy with carmustine . 
 
4.7 Effects on ability to drive and use machines 
 
Carmustine Obvius has no or negligible influence on the ability to drive and use machines. However, 
the possibility will have to be taken into consideration, that the alcohol quantity in these 
pharmaceutical medicines can impair the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
The table includes adverse reactions that were presented during treatment with this medicinal product 
but may not necessarily have a causal relationship with the medicinal product. Because clinical trials 
are conducted under very specific conditions, the adverse reaction rates observed may not reflect the 
rates observed in clinical practice. Adverse reactions are generally included if they were reported in 
more than 1% of patients in the product monograph or pivotal trials, and/or determined to be clinically 
important. When placebo-controlled trials are available, adverse reactions are included if the incidence 
is ≥ 5% higher in the treatment group. 

 
Tabulated list of adverse reactions 
The following table includes adverse reactions of carmustine listed by MedDRA system organ class 
and frequency convention presented in order of decreasing seriousness: 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), not known (frequency cannot be estimated from the available data). Within each 
frequency grouping, adverse reactions are presented in order of decreasing seriousness: 
 
MedDRA system organ 
class 

Frequency Adverse reactions 

Neoplasms benign, 
malignant and unspecified 
(including cysts and polyps) 

Common Acute leukaemia, bone marrow 
dysplasia - following long-term use. 

Blood and lymphatic 
system disorders 

  

Very 
common 

Myelosuppression. 



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Common Anaemia. 

Nervous system disorders Very 
common 

Ataxia, dizziness, headache. 

Common Encephalopathy (high-dose therapy and 
dose-limiting). 

Not known Muscular pain, status epilepticus, seizure, 
grand mal seizure. 

Eye disorders Very 
common 

Ocular toxicities, transient conjunctival 
flushing and blurred vision due to retinal 
haemorrhages. 

Cardiac disorders Very common Hypotension, due to the alcohol content of the 
solvent (high-dose therapy). 

Not known Tachycardia 

Vascular disorders Very 
common 

Phlebitis. 

Rare Veno-occlusive disease (high-dose 
therapy). 

Respiratory, thoracic and 
mediastinal disorders 

Very 
common 

Pulmonary toxicity, interstitial fibrosis 
(with prolonged therapy and cumulative 
dose)* 
Pneumonitis. 

Rare Interstitial fibrosis (with lower doses). 
Gastrointestinal disorders Very 

common 
 

Emetogenic potential. 
Nausea and vomiting - severe 

Common Anorexia, constipation, diarrhoea, 
stomatitis. 

Hepatobiliary disorders Common Hepatotoxicity, reversible, delayed up to 
60 days after administration (high-dose 
therapy and dose-limiting), manifested by: 

- bilirubin, reversible increase 
- alkaline phosphatase, reversible 

increase 
- SGOT, reversible increase. 

Skin and subcutaneous 
tissue disorders 

 
Very 
common 

 
Dermatitis with topical use improves with 
reduced concentration of compounded 
product, hyperpigmentation, transient, with 
accidental skin contact. 

Common Alopecia, flushing (due to alcohol content of 
solvent; increased with administration times 
<1-2 h), injection site reaction. 



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Not known Extravasation hazard: vesicant 

Renal and urinary 
disorders 

Rare Renal toxicity.  
 

Reproductive system and 
breast disorders 

Rare Gynecomastia. 

Not known Infertility, teratogenesis. 

Metabolism and nutrition 
disorders 

Not known Electrolyte abnormalities (hypokalemia, 
hypomagnesemia and hypophosphatemia) 

* An increased risk for pulmonary toxicities upon treatment with conditioning regimes and HPCT for 
females has been reported. So far, this increased risk is described for the treatment itself including 
conditioning regimes without carmustine (e.g. TBI or busulfan-cyclophosphamide) or with carmustine 
(BEAM: carmustine, etopside, cytarabine and melphalan or CBV: cyclophosphamide, carmustine and 
etoposide). 

 
Description of selected adverse reactions 
 
Myelosuppression 
Myelosuppression is very common and begins 7-14 days of administration with recovery 42-56 days 
of administration. The myelosuppression is dose and cumulative dose related, and often biphasic. 
 
Respiratory, thoracic and mediastinal disorders  
Pulmonary fibrosis (with fatal outcome), pulmonary infiltration  
Pulmonary toxicity has been observed in up to 30% of patients. In cases where pulmonary toxicity 
started early (within 3 years of treatment), pulmonary infiltrates and/or pulmonary fibrosis occurred, 
some of which were fatal. The patients were between 22 months and 72 years old. Risk factors include 
smoking, respiratory disease, existing radiographic abnormalities, sequential or concomitant thoracic 
radiation, as well as combination with other active substances that can cause lung damage. The 
incidence of adverse reactions is probably dose-related; cumulative doses of 1200-1500 mg/m2 have 
been associated with an increased likelihood of pulmonary fibrosis. During treatment, lung function 
tests (FVC, DLCO) should be performed regularly. Patients showing a baseline value of <70% of 
expected forced vital capacity or carbon monoxide diffusion capacity in these tests are at particular 
risk.  
In patients having received carmustine in childhood or adolescence, cases of extremely delayed-onset 
pulmonary fibrosis (up to 17 years after treatment) have been described.  
Long-term follow-up observation of 17 patients who survived brain tumours in childhood showed that 
8 of them succumbed to pulmonary fibrosis. Two of these 8 fatalities occurred within the first 3 years 
of treatment and 6 of them occurred 8-13 years after treatment. The median age of patients who died 
on treatment was 2.5 years (1-12 years), the median age of long-term survivors on treatment was 10 
years (5-16 years). All patients younger than 5 years of age at the time of treatment died from 
pulmonary fibrosis; neither the carmustine dose nor an additional vincristine dose or spinal radiation 
had any influence on the fatal outcome.  
All remaining survivors available for follow-up were diagnosed with pulmonary fibrosis. Use of 
carmustine in children and adolescents < 18 years is contraindicated, see section 4.3. 

 
Pulmonary toxicity also manifested in the post-marketing phase as pneumonitis and interstitial lung 
disease. Pneumonitis is seen for doses >450 mg/m2 and interstitial lung disease is seen with prolonged 
therapy and cumulative dose > 1,400 mg/m2. 
 
Emetogenic potential  
The emetogenic potential is high at doses >250 mg/m2 and high to moderate in doses ≤250 mg/m2. 
Nausea and vomiting are severe and begins within 2-4 h of administration and lasts for 4-6 h. 
 



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Renal toxicity 
Renal toxicity is rare, but occurs for cumulative doses < 1,000 mg/m2. 
 
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 
 
The main symptom of intoxication is myelosuppression. In addition, the following serious adverse 
reactions may occur: liver necrosis, interstitial pneumonitis, encephalomyelitis. A specialized antidote 
is not available. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antineoplastic agents, alkylating agents, nitrosoureas,  
ATC code: L01AD01 
 
Mechanism of action 
Carmustine is a cell-cycle phase nonspecific antineoplastic agent of the nitrosourea type, which exerts 
tumor cytotoxicity via multiple mechanisms. As an alkylating agent, it can alkylate reactive sites on 
nucleoproteins, thus interfering with DNA and RNA synthesis and DNA repair. It is able to form 
interstrand crosslinks in DNA, which prevents DNA replication and transcription. In addition, 
carmustine is known to carbamoylate lysine residues on proteins causing irreversible inactivation of 
enzymes including glutathione reductase. The carbamoylating activity of carmustine is generally 
considered less significant than the alkylating activity in its action on tumors, but carbamoylation may 
serve to inhibit DNA repair. 
 
Pharmacodynamic effects 
The antineoplastic and toxic activities of carmustine may be due to its metabolites. Carmustine and 
related nitrosoureas are unstable in aqueous solutions and degrade spontaneously to reactive 
intermediates that are capable of alkylation and carbamoylation. The alkylating intermediates are 
believed to be responsible for the antitumor effect of carmustine. However, opinion is divided over the 
role of the carbamoylating intermediates as mediators of the biological effects of the nitrosoureas. On 
one hand, their carbamoylating activity was reported to contribute to the cytotoxic properties of their 
parent drugs by inhibiting DNA repair enzymes. On the other hand, it has been speculated that the 
carbamoylating species may mediate some of toxic effects of carmustine.  
 
Carmustine crosses the blood-brain barrier readily because of its lipophilic nature. 
 
Paediatric population 
Carmustine Obvius should not be used in children and adolescents due to high risk of pulmonary 
toxicity. 
 
5.2 Pharmacokinetic properties 
 
Distribution 
Intravenously administered carmustine is rapidly degraded, with no substance intact detectable after 
15 minutes. Because of the good lipid solubility and the lack of ionisation at the physiological pH, 
carmustine is very well transferred through the blood-brain barrier. Levels of radioactivity in the 
cerebrospinal fluid are at least 50% higher than those measured concurrently in plasma. The kinetic of 
carmustine in humans is characterised by a two-chamber model. After the intravenous infusion over 

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


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1 hour, the carmustine-plasma level drops in a biphasic manner. The half-life α is 1-4 minutes and the 
half-life β is 18-69 minutes. 
 
Biotransformation 
It is presumed that the metabolites of carmustine cause its antineoplastic and toxic activity. 
 
Elimination 
Approximately 60-70% of a total dose is excreted in the urine in 96 hours and about 10% as 
respiratory CO2. The fate of the remainder is undetermined. 
 
5.3 Preclinical safety data 
 
Carmustine was embryotoxic and teratogenic in rats and embryotoxic in rabbits at dose levels 
equivalent to the human dose. Carmustine affected the fertility of male rats at doses higher than the 
human dose. Carmustine, at clinically relevant dose levels, was carcinogenic in rats and mice. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Powder  
No excipients. 
 
Solvent 
Ethanol, anhydrous. 
 
6.2 Incompatibilities 
 
The intravenous solution is unstable in polyvinyl chloride containers. All plastic coming into contact 
with the carmustine solution for infusion (e.g. infusion set, etc.) should be PVC-free polyethylene 
plastic, otherwise glass ware should be used. 

 
This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6. 
 
6.3 Shelf life 
 
Unopened vial 
3 years. 
 
After reconstitution and dilution 
The solution should be administered within 3 hours after reconstitution and dilution of the product. 
The solution should be protected from light until end of administration. 
 
6.4 Special precautions for storage 
 
Store and transport refrigerated (2°C – 8°C). 
 
Keep the vial and ampoule in the outer carton in order to protect from light. 
 
For storage conditions after reconstitution and further dilution of the medicinal product, see section 
6.3. 
 



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6.5 Nature and contents of container  
 
Powder 
Brown type I hydrolytic glass vial (50 ml) with light grey 20 mm bromobutyl rubber stopper and 
sealed with a dark red aluminium flip-off cap. 
 
Solvent 
Clear type I glass ampoule (5 ml). 
 
One pack contains one vial with 100 mg of powder for concentrate for solution for infusion and one 
ampoule with 3 ml of solvent. 
 
6.6 Special precautions for disposal and other handling 
 
The carmustine powder for concentrate for solution for infusion contains no preservative and is not 
intended as a multiple dose vial. Reconstitution and further dilutions should be carried out under 
aseptic conditions. 
 
The dry frozen product does not contain any preservatives and is suitable only for one use. The 
lyophilisate can appear as a fine powder, however handling can cause it to appear as a more heavy and 
lumpy lyophilisate than as a powdery lyophilisate due to the mechanical instability of the freeze 
drying cake. The presence of an oily film can be an indication of melting of the medicinal product. 
Such products are not accepted for use due to the risk of temperature excursions to more than 
30°C.This medicinal product should not be used any further. When you are not clear about the fact 
whether the product is adequately cooled, then you should immediately inspect each and every vial in 
the carton. For verification, hold the vial in bright light. 
 
Reconstitution and dilution of the powder for concentrate for solution for infusion 
Dissolve the Carmustine (100 mg powder) with 3 ml of the supplied sterile refrigerated ethanol 
solvent in the primary packaging (brown glass vial). Carmustine must be completely dissolved in ethanol 
before sterile water for injections is added. 
Then aseptically add 27 ml of sterile water for injection to the alcohol solution. The 30 ml stock 
solution needs to be mixed thoroughly. Reconstitution, as recommended, results in a clear, colourless 
to light yellow stock solution. 
 
The 30 ml stock solution is to be diluted immediately by adding the 30 ml stock solution to either 500 
ml 5% glucose or 500 ml sodium chloride 9 mg/ml (0.9%) solution for injection in glass containers. 
The 530 ml diluted solution (i.e. the ready-to-use solution) should be mixed for at least 10 seconds 
before administration. The Ready-to-Use solution should be administered over 1-2 hours and 
administration should be finalised within 3 hours from reconstitution of the product.  
 
Administration of the infusion should be performed using a PVC free PE infusion set. 
During administration of the medicinal product, the container shall be of suitable glass ware. Further, 
the ready-to-use solution solution needs to be protected from light (e.g. using alu-foil wrapped around 
the container of the ready-to-use solution) and preferably kept at temperatures below 20-22°C as 
Carmustine degrades faster at higher temperatures. 
 
Infusion of Carmustine Obvius in less than one hour may produce intense pain and burning at the site 
of injection (see section 4.2). 
 
Guidelines for the safe handling and disposal of antineoplastic agents must be observed. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements 
 
 



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7. MARKETING AUTHORISATION HOLDER 
 
Obvius Investment B.V. 
De Cuserstraat 93 
1081 CN Amsterdam 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1278/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 19.07.2018 
 
 
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 
 
  



13 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 
 
European Pharma Hub Ltd 
7000/9 hrsz, warehouse 15 and 16 
Gyál, 2360 
HUNGARY 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to restricted medical prescription. 
 
 
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. 

 
  



15 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Carmustine Obvius 100 mg powder and solvent for concentrate for solution for infusion 
 
carmustine  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial of powder for concentrate for solution for infusion contains 100 mg carmustine. 
After reconstitution and dilution, one mL of solution contains contains 3.3 mg carmustine. 
 
 
3. LIST OF EXCIPIENTS 
 
Ethanol. See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for concentrate for solution for infusion 
 
1 vial of 100 mg powder 
1 ampoule of 3 ml solvent 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For single use only. 
 
Read the package leaflet before use. 
 
Intravenous use after reconstitution and dilution. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Cytotoxic: Handle with caution. Avoid skin contact with concentrate for solution for infusion.  
May cause birth defects. 
 
 



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8. EXPIRY DATE 
 
EXP 
 
After reconstitution/dilution: See package leaflet for the shelf life of the reconstituted medicine. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store and transport refrigerated. 
Keep the vial and ampoule in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Guidelines for the safe disposal of antineoplastic agents must be observed. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Obvius Investment B.V. 
De Cuserstraat 93 
1081 CN Amsterdam 
The Netherlands  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1278/001  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



19 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



20 

 
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 
 
POWDER VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Carmustine Obvius 100 mg powder for concentrate for solution for infusion 
 
carmustine  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each vial of powder for concentrate for solution for infusion contains 100 mg carmustine. 
After reconstitution and dilution, one mL of solution contains contains 3.3 mg carmustine. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder for concentrate for solution for infusion 
100 mg 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For single use only. 
 
Read the package leaflet before use. 
 
Intravenous use after reconstitution and dilution. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
Cytotoxic: Handle with caution. Avoid skin contact with concentrate for solution for infusion.  
May cause birth defects. 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



21 

9. SPECIAL STORAGE CONDITIONS 
 
Store and transport refrigerated. 
 
Keep the vial in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Guidelines for the safe disposal of antineoplastic agents must be observed. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Obvius Investment B.V. 
De Cuserstraat 93 
1081 CN Amsterdam 
The Netherlands  
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1278/001  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
  



22 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SOLVENT AMPOULE  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Solvent for Carmustine Obvius 
ethanol anhydrous 
IV 
 
 
2. METHOD OF ADMINISTRATION 
 
For dissolving purposes only 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3 ml 
 
 
6. OTHER 
 
 
 
  



23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



24 

Package leaflet: Information for the user 
 

Carmustine Obvius 100 mg powder and solvent for concentrate for solution for infusion 
carmustine 

 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4. 
 
 
What is in this leaflet 
 
1. What Carmustine Obvius is and what it is used for  
2. What you need to know before Carmustine Obvius is given to you  
3. How to use Carmustine Obvius  
4. Possible side effects  
5. How to store Carmustine Obvius  
6. Contents of the pack and other information 
 
 
1. What Carmustine Obvius is and what it is used for 
 
Carmustine Obvius is a medicine which contains carmustine. Carmustine belongs to a group of 
anticancer medicines known as nitrosourea that act by slowing the growth of cancer cells. 

 
Carmustine is effective in the following malignant neoplasms as a single agent or in combination with 
other antineoplastic agents and/or other therapeutic measures (radiotherapy, surgery): 
 
- Brain tumours (glioblastoma, Brain-stem gliomas, medulloblastoma, astrocytoma and 

ependymoma), brain metastases 
- Secondary therapy in non-Hodgkin’s lymphoma and Hodgkin’s disease 
- as conditioning treatment prior to autologous haematopoietic progenitor cell transplantation 

(HPCT) in malignant haematological diseases (Hodgkin’s disease / Non-hodgkin’s lymphoma). 
 
 
2. What you need to know before you use Carmustine Obvius  
 
Do not use Carmustine Obvius: 
- if you are allergic to carmustine or any of the other ingredients of this medicine (listed in section 

6). 
- if you suffer from suppression of blood cell formation in the bone marrow and the number of 

your platelets, white blood cells (leucocytes), or red blood cells (erythrocytes) is therefore 
reduced, either as a result of chemotherapy or other causes. 

- if you suffer from higher-grade kidney dysfunction. 
- in children and adolescents 
- if you are breast-feeding. 
 
Warnings and precautions  
Talk to your doctor, pharmacist or nurse before using Carmustine Obvius. 
 
The major side effect of this medicine is delayed bone marrow suppression, which may show as 
tiredness, bleeding from the skin and mucous membranes as well as infections and fever due to 
changes in the blood. Therefore your doctor will monitor blood counts weekly for at least 6 weeks 



25 

after a dose. At the recommended dosage, courses of Carmustine Obvius would not be given more 
frequently than every 6 weeks. The dosage will be confirmed with the blood count. 
 
Before treatment, your liver, lung and kidney function will be tested and observed regularly during 
treatment.  
 
Since the use of Carmustine Obvius can lead to lung damage, an X-ray of the chest region and lung 
function tests will be conducted before treatment is started (please also see the section “Possible side 
effects”). 
 
High-dose treatment with Carmustine Obvius (up to 600 mg/m2) is only performed in combination 
with subsequent stem cell transplanation. Such a higher dose can increase frequency or severity of 
lung, kidney, liver, heart, and gastrointestinal toxicities as well as infections and disturbances in the 
electrolyte balance (low blood levels of potassium, magnesium, phosphate). 
 
Stomach pain (neutropenic enterocolitis) can occur as therapy-related adverse event upon treatment 
with chemotherapeutic agents. 
 
Your doctor will talk to you about the possibility of lung damage and allergic reactions and their 
symptoms. If such symptoms occur, you should contact your doctor immediately (see section 4). 
 
Children and adolescents 
Carmustine Obvius must not be used in children and adolescents aged <18 years. 
 
Other medicines and Carmustine Obvius 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 
medicines, including medicines obtained without prescription, such as: 
- Phenytoin, used in epilepsy 
- Dexamethasone, used as an anti-inflammatory and immunosuppressive agent 
- Cimetidine, used for stomach problems like indigestion 
- Digoxin, used if you have abnormal heart rhythm 
- Melphalan, an anticancer medicine 
 
Carmustine Obvius with alcohol 
The amount of alcohol in this medicine may alter the effects of other medicines. 
 
Pregnancy, breast-feeding and fertility 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or pharmacist for advice before taking this medicine. 
 
Pregnancy and fertility 
Carmustine Obvius should not be used during pregnancy because it may harm your unborn baby. 
Therefore this medicine should not normally be administered to pregnant women. If used during 
pregancy, the patient must be aware of the potential risk to the unborn baby. Women of childbearing 
potential are advised to use effective contraception to avoid becoming pregnant whilst being treated 
with this medicine and for at least 6 months after treatment. 
 
Male patients should use adequate contraceptive measures while on treatment with Carmustine Obvius 
and for at least 6 months after treatment to prevent their partners becoming pregnant. 
 
Breast-feeding 
You must not breast-feed while taking this medicine and up to 7 days after treatment. A risk to the 
newborn/infant cannot be excluded. 
 



26 

Driving and using machines 
Carmustine Obvius has no or negligible influence on the ability to drive and use machines. You must 
check with your doctor before driving or operating any tools or machines because the amount of 
alcohol in this medicine may impair your ability to drive or use machines.  
 
Carmustine Obvius contains ethanol (alcohol) 
This medicine contains 2.4 g of alcohol (ethanol) per vial, which isequivalent to 25.92 g per maximal 
dose (10vol%). The amount in maximal dose (600 mg/m2 in 70 kg patient) of this medicine is 
equivalent to 648 ml beer or 259 ml wine. 
 
The amount of alcohol in this medicine can affect your ability to drive or use machines. This is 
because it may affect your judgement and how fast you react.  
 
If you have epilepsy or liver problems, talk to your doctor or pharmacist before taking this medicine.  
 
The amount of alcohol in this medicine may alter the effects of other medicines. Talk to your doctor or 
pharmacist if you are taking other medicines.  
 
If you are pregnant, talk to your doctor or pharmacist before taking this medicine.  
 
If you are addicted to alcohol, talk to your doctor or pharmacist before taking this medicine. 
 
 
3. How to use Carmustine Obvius 
 
Carmustine Obvius will always be given to you by a healthcare professional with experience in the use 
of anticancer medicines. 
 
Adults 
Dosage is based on your medical condition, body size and response to treatment. It is usually given at 
least every 6 weeks. The recommended dose of Carmustine Obvius as a single agent in previously 
untreated patients is 150 to 200 mg/m2 intravenously every 6 weeks. This may be given as a single 
dose or divided into daily infusions such as 75 to 100 mg/m2 on two successive days. Dosage will also 
depend on whether Carmustine Obvius is given with other anti-cancer medicines. 
 
Doses will be adjusted according to how you respond to the treatment. 
 
The recommended dose of Carmustine Obvius given in combination with other chemotherapeutic 
agents before haematopoietic progenitor cell transplantation is 300 – 600 mg/m2 intravenously. 
 
Your blood count will be monitored frequently to avoid toxicity in your bone marrow and the dose 
adjusted if necessary. 
 
Route of administration 
Following reconstitution and dilution Carmustine Obvius is given into a vein by a drip (intravenously) 
over a one- to two-hour period protected from light. The duration of infusion should not be less than 
one hour to avoid burning and pain at the injected area. The injected area will be monitored during the 
administration. 
 
The duration of the treatment is determined by the doctor and may vary for each patient. 
 
If you use more Carmustine Obvius than you should 
As a doctor or nurse will be giving you this medicine, it is unlikely that you will receive an incorrect 
dose. Tell you doctor or nurse if you have any concern about the amount of medicine that you 
received. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist or nurse. 



27 

 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Tell your doctor or nurse immediately if you notice any of the following: 
Any sudden wheeziness, difficulty in breathing, swelling of the eyelids, face or lips, rash or itching 
(especially affecting your whole body), and feeling you are going to faint. These may be signs of a 
severe allergic reaction. 
 
Carmustine Obvius may cause the following side effects: 
 
Very common (may affect more than 1 in 10 people) 
- Delayed myelosuppression (decrease in blood cells in bone marrow) which can increase the 

chance of infections if white blood cells are decreased 
- Ataxia (lack of voluntary coordination of muscle movements); 
- Dizziness; 
- Headache; 
- Transient redness in the eye, blurred vision due to retinal bleeding; 
- Hypotension (fall in blood pressure); 
- Phlebitis (inflammation of the veins) associated with pain, swelling, redness, tenderness; 
- Respiratory disorders (lung related disorders) with breathing problems; 

This medicine may cause severe (possibly fatal) lung damage. Lung damage may occur years 
after treatment. Tell your doctor immediately if you experience any of the following symptoms: 
shortness of breath, persistent cough, chest pain, persistent weakness/tiredness. 

- Severe nausea and vomiting 
- When used on the skin, inflammation of the skin (dermatitis); 
- Accidental contact with skin may cause transient hyperpigmentation (darkening of an area of 

skin or nails) 
 
Common (may affect up to 1 in 10 people) 
- Acute leukaemias and bone marrow dysplasias (abnormal development of the bone 

marrow).Symptoms may include bleeding from the gums, bone pain, fever, frequent infections, 
frequent or severe nosebleed, lumps caused by swollen lymph nodes in and around the neck, 
underarm, abdomen or groin, pale skin, shortness of breath, weakness, fatigue or a general 
decrease in energy;  

- Anaemia (decrease in the amount of red blood cells in the blood); 
- Encephalopathy (disorder of brain). Symptoms may include muscle weakness in one area, poor 

decision-making or concentration, involuntary twitching, trembling, difficulty speaking or 
swallowing, seizures; 

- Anorexia; 
- Constipation; 
- Diarrhoea; 
- Inflammation of the mouth and lips; 
- Reversible liver toxicity in high-dose therapy. This can result in increased liver enzymes and 

bilirubin (detected by blood tests); 
- Alopecia (loss of hair); 
- Flushing of the skin; 
- Reactions on the injection site 
 
Rare (may affect up to 1 in 1,000 people) 
- Veno-occlusive disease (progressive blockage of the veins) where very small (microscopic) 

veins in the liver are blocked. Symptoms may include: fluid accumulation in the abdomen, 
enlargement of spleen, severe bleeding of the oesophagus, yellow-colouring of skin and whites 
of the eyes;  

- Breathing problems caused by interstitial fibrosis (with lower doses); 

https://www.medicinenet.com/pain_surprising_reasons_pictures_slideshow/article.htm
https://www.healthline.com/symptom/muscle-weakness
https://www.healthline.com/symptom/unable-to-concentrate
https://www.healthline.com/symptom/speech-impairment
https://www.healthline.com/health/difficulty-in-swallowing
https://www.healthline.com/symptom/seizures


28 

- Kidney problems; 
- Gynecomastia (breast growth in males) 

 
Not known (frequency cannot be estimated from the available data) 
- Muscular pain; 
- Seizures (fits) including status epilepticus; 
- Tissue damage due to leakage in injection area; 
- Infertility; 
- Carmustine has been shown to adversely affect the development of unborn babies 
- Electrolyte abnormalities (and disturbances in the electrolyte balance (low blood levels of 

potassium, magnesium, phosphate)) 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store Carmustine Obvius 
 
This medicine will be stored by your doctor or health care professional. 
 
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 label and carton after EXP. The 
expiry date refers to the last day of that month. 
 
Store and transport refrigerated (2°C – 8°C). 
Keep the vial and ampoule in the outer carton in order to protect from light. 
 
After reconstitution and dilution 
After reconstitution Carmustine Obvius is stable for 3 hours, stored in a glass container and protected 
from light. 
 
The solution should be administered within 3 hours after reconstitution and dilution of the product. 
The solution should be protected from light until the end of administration.  
 
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 Carmustine Obvius contains  
- The active substance is carmustine. 

Each vial of powder for concentrate for solution for infusion contains 100 mg carmustine.  
After reconstitution and dilution, one mL of solution contains 3.3 mg carmustine.  

- Excipients:  
- Powder: No excipients. 
- Solvent: Ethanol, anhydrous. 
 
What Carmustine Obvius looks like and contents of the pack 
Carmustine Obvius is a powder and solvent for concentrate for solution for infusion.  
 
The powder is white to almost white powder supplied in a brown glass vial. 
The solvent is a colourless clear liquid supplied in a clear glass ampule. 

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


29 

 
One pack of Carmustine Obvius contains one vial with 100 mg of powder and one ampoule with 3 ml 
of solvent. 
 
Marketing Authorisation Holder 
Obvius Investment B.V. 
De Cuserstraat 93 
1081 CN Amsterdam 
The Netherlands 
 
Manufacturer 
European Pharma Hub Ltd. 
2360 Gyál, 7000/9 hrsz. 
Hungary 
 
This leaflet was last revised in 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site:  
http://www.ema.europa.eu/ema/.  
 
------------------------------------------------------------------------------------------------------------------------ 
 
The following information is intended for healthcare professionals only: 
 
This information is a short description of preparation and/or handling, incompatibilities, posology of 
the medicine, overdose or monitoring measures and laboratory investigations based on the current 
SmPC. 
 
The Carmustine Obvius powder for concentrate for solution for infusion contains no preservative and 
is not intended as multiple dose vial. Reconstitution and further dilutions should be carried out under 
aseptic conditions. 
 
By following the recommended storage conditions it is possible to avoid any decomposition of the 
unopened vial until the date of expiry mentioned on the packaging. 
 
The dry frozen product does not contain any preservatives and is suitable only for one use. The 
lyophilisate can appear as a fine powder, however handling can cause it to appear as a more heavy and 
lumpy lyophilisate than as a powdery lyophilisate due to the mechanical instability of the freeze 
drying cake. The presence of an oily film can be an indication of melting of the medicinal product. 
Such products are not accepted for use due to the risk of temperature excursions to more than 30°C. 
This medicinal product should not be used any further. When you are not clear about the fact whether 
the product is adequately cooled, then you should immediately inspect each and every vial in the 
carton. For verification, hold the vial in bright light. 
 
Reconstitution and dilution of the powder for concentrate for solution for infusion: 
Dissolve the 100 mg Carmustine powder for concentrate for solution for infusion with 3 ml of the 
supplied sterile refrigerated ethanol solvent in the primary packaging (brown glass vial). Carmustine 
must be completely dissolved in ethanol before sterile water for injections is added. Then aseptically 
add 27 ml of sterile water for injections to the alcohol solution. The 30 ml stock solution needs to be 
mixed thoroughly. Reconstitution, as recommended, results in a clear, colourless to light yellow stock 
solution. 
The 30 ml stock solution is to be diluted immediately by adding the 30 ml stock solution to either 
500 ml glucose 50 mg/ml (5%) solution for injection or 500 ml sodium chloride 9 mg/ml (0.9%) 
solution for injection in glass containers. The 530 ml diluted solution (i.e. the ready-to-use solution) 
should be mixed for at least 10 seconds before administration.  



30 

 
The pH and osmolarity of ready-to-use solutions for infusion: 
pH 4.0 to 5.0 and 385-397 mOsm/l (if diluted in glucose 50 mg/ml [5%] solution for injection) and  
pH 4.0 to 6.8 and 370-378 mOsm/l (if diluted in sodium chloride 9 mg/ml [0.9%] solution for 
injection). 
 
Method of administration 
The reconstituted and diluted solution (i.e. ready-to-use solution) must be given intravenously and 
should be administered by intravenous drip over a one- to two-hour period and administration should 
be finalised within 3 hours from reconstitution/dilution of the medicinal product. Administration of the 
infusion should be performed using a PVC free PE infusion set. 
During administration of the medicinal product, the container shall be of suitable glass ware. Further, 
the ready-to-use solutions needs to be protected from light (e.g. using alu-foil wrapped around the 
container of the Ready-to-Use solution) and preferably kept at temperatures below 20-22°C as 
carmustine degrades faster at higher temperatures.  
Administration of the infusion should be performed using a PVC free PE infusion set. 
 
Infusion of Carmustine Obvius over shorter periods of time may produce intense pain and burning at 
the site of injection. The injected area should be monitored during the administration.  
 
Guidelines for the safe handling and disposal of antineoplastic agents must be observed. 
 
Posology and laboratory investigations 
Initial doses 
The recommended dose of Carmustine Obvius as a single agent in previously untreated patients is 
150 to 200 mg/m2 intravenously every 6 weeks. This may be given as a single dose or divided into 
daily infusions such as 75 to 100 mg/m2 on two successive days. 
 
When Carmustine Obvius is used in combination with other myelosuppressive medicinal products or 
in patients in whom bone marrow reserve is depleted, the doses should be adjusted according to the 
haematologic profile of the patient as shown below. 
 
Monitoring and subsequent doses 
A repeat course of Carmustine Obvius should not be given until circulating blood elements have 
returned to acceptable levels (platelets above 100,000/mm3, leukocytes above 4,000/mm3), and this is 
usually in six weeks. Blood counts should be monitored frequently and repeat courses should not be 
given before six weeks because of delayed haematologic toxicity. 
Doses subsequent to the initial dose should be adjusted according to the haematologic response of the 
patient to the preceding dose in both monotherapy as well as in combination therapy with other 
myelosuppressive medicinal products. The following schedule is suggested as a guide to dosage 
adjustment: 
 

Nadir after prior dose Percentage of prior dose 
to be given Leucocytes/mm3 Platelets/mm3 

>4,000 >100,000 100% 
3,000 – 3,999 75,000 - 99,999 100% 
2,000 – 2,999 25,000 - 74,999 70% 
<2,000 <25,000 50% 

 
In cases where the nadir after initial dose does not fall in the same row for leucocytes and platelets 
(e.g. leucocytes >4,000 and platelets <25,000) the value given the lowest percentage of prior dose 
should be used (e.g. platelets <25,000 then a maximum of 50% of prior dose should be given). 
 
There are no limits for the period of application of carmustine therapy. In case the tumor remains 
incurable or some serious or intolerable adverse reactions appear, the carmustine therapy must be 
terminated. 
 



31 

Conditioning treatment prior to HPCT 
Carmustine is given in combination with other chemotherapeutic agents in patients with malignant 
haematological diseases before HPCT at a dose of 300 - 600 mg/m2 intravenously. 
 
Special populations 
 
Paediatric population 
Carmustine must not be used in children aged <18 years because of safety concerns. 
 
Elderly 
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of 
the dose range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of 
concomitant disease or therapy with other medicinal products. Because elderly patients are more likely 
to have decreased renal function, care should be taken in dose selection, and the glomerular filtration 
rate should be monitored and dose reduced according to this.  
 
Renal impairment 
For patients with renal impairment the dose of Carmustine Obvius should be reduced if the glomerular 
filtration rate is reduced. 
 
Compatibility/Incompatibility with containers 
The intravenous solution is unstable in polyvinyl chloride containers. All plastic coming into contact 
with the carmustine solution for infusion (e.g. infusion set etc.) should be PVC free polyethylene 
plastic, otherwise glass ware should be used. 


	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