post-title portfolio-title Carmustine powder and solvent for concentrate for solution for infusion IP 100mg Taj Pharma 2020-02-24 11:29:06 no no

Carmustine powder and solvent for concentrate for solution for infusion IP 100mg Taj Pharma

Carmustine? powder and solvent for concentrate for solution for infusion IP 100mg Taj Pharma

Overview

INTRODUCTION

Carmustine 100mg Injection is used to treat cancer of lymphatic system, brain and certain types of cancers of bone marrow. It may also be used to treat other types of cancer. It can be used alone, or together with certain other medicines as part of combination chemotherapy.

Carmustine 100mg Injection is given as an injection into veins by the healthcare provider. This will depend on what you are being treated for and may change from time to time. You should take it exactly as your doctor has advised. Taking it in the wrong way or taking too much can cause very serious side effects. It may take several weeks or months for you to see or feel the benefits but do not stop taking it unless your doctor tells you to.

The most common side effects of this medicine include nausea, vomiting, infection, confusion, and rash. Other than this some patients might notice anemia (low number of red blood cells), decreased white blood cell count. It is very strong medicine and some people may develop serious side effects while taking it. This medicine may lower your ability to fight infections and lead to problems with your blood, lungs, liver or kidneys. Your doctor will advise you regular blood tests to check for these.

Before taking it, tell your doctor if you have liver, lungs, or kidney problems or are taking any medicines to treat infections. Many other medicines can affect, or be affected by, this medicine so let your doctor know all medications you are using. This medicine is not recommended during pregnancy or while breastfeeding. It may harm your baby. You and your partner should avoid becoming pregnant or fathering a child for several months after your treatment with it has stopped.

USES OF CARMUSTINE INJECTION

  • Brain tumor

SIDE EFFECTS OF CARMUSTINE INJECTION

Common

  • Headache
  • Weakness
  • Vomiting
  • Infection
  • Confusion
  • Constipation
  • Rash
  • Hair loss
  • Fever
  • Convulsion
  • Depression
  • Speech disorder
  • Brain swelling
  • Thrombophlebitis
  • Hemiplegia (paralysis of one side of the body)
  • Sleepiness

HOW TO USE CARMUSTINE INJECTION

Your doctor or nurse will give you this medicine. Kindly do not self administer.

HOW CARMUSTINE INJECTION WORKS

Carmustine 100mg Injection is an anti-cancer medication. It works by damaging the genetic material (DNA and RNA) of the cancer cells. This stops their growth and multiplication.

SAFETY ADVICE

warningsAlcohol

CONSULT YOUR DOCTOR

It is not known whether it is safe to consume alcohol with Carmustine 100mg Injection. Please consult your doctor.

warningsPregnancy

CONSULT YOUR DOCTOR

Carmustine 100mg Injection is unsafe to use during pregnancy as there is definite evidence of risk to the developing baby. However, the doctor may rarely prescribe it in some life-threatening situations if the benefits are more than the potential risks. Please consult your doctor.

warningsBreastfeeding

UNSAFE

Carmustine 100mg Injection is unsafe to use during breastfeeding. Data suggests that the drug may cause toxicity to the baby.

warningsDriving

UNSAFE

Carmustine 100mg Injection may cause side effects which could affect your ability to drive.

warningsKidney

CONSULT YOUR DOCTOR

There is limited information available on the use of Carmustine 100mg Injection in patients with kidney disease. Please consult your doctor.
However, the use of Carmustine 100mg Injection is not recommended in patients with severe kidney disease.

warningsLiver

CONSULT YOUR DOCTOR

There is limited information available on the use of Carmustine 100mg Injection in patients with liver disease. Please consult your doctor.

WHAT IF YOU FORGET TO TAKE CARMUSTINE INJECTION?

If you miss a dose of Carmustine 100mg Injection, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular schedule. Do not double the dose.

Carmustine? powder and solvent for concentrate for solution for infusion IP 100mg Taj Pharma

1. NAME OF THE MEDICINAL PRODUCT

Carmustine? powder and solvent for concentrate for solution for infusion IP 100mg Taj Pharma

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

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

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 dosePercentage of prior dose to be given
Leucocytes/mm3Platelets/mm3
>4,000>100,000100%
3,000 ? 3,99975,000 – 99,999100%
2,000 ? 2,99925,000 – 74,99970%
<2,000<25,00050%

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.

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.

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.

Hepatic and renal function should also be checked prior to treatment and regularly monitored during therapy (see section 4.8).

Carmustine is carcinogenic in rats and mice at doses less than the recommended human dose based on body surface area.

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 to 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.

This medicinal product contains 0.57 vol% ethanol (alcohol), i.e. up to 7.62 g per dose, equivalent to 11.2 ml beer or 4.65 ml wine per dose. Harmful for those suffering from alcoholism. To be taken into account in high-risk groups such as patients with liver disease or epilepsy. The amount of alcohol in this medicinal product may alter the effects of other medicines, and may impair your ability to drive or use machines.

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.

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. 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 classFrequencyAdverse reactions
Neoplasms benign, malignant and unspecified (including cysts and polyps)CommonAcute leukaemia, bone marrow dysplasia – following long-term use.
Blood and lymphatic system disordersVery commonMyelosuppression.
CommonAnaemia.
Nervous system disordersVery commonAtaxia, dizziness, headache.
CommonEncephalopathy (high-dose therapy and dose-limiting).
Not knownMuscular pain, status epilepticus, seizure, grand mal seizure.
Eye disordersVery commonOcular toxicities, transient conjunctival flushing and blurred vision due to retinal haemorrhages.
Cardiac disordersVery commonHypotension, due to the alcohol content of the solvent (high-dose therapy).
Vascular disordersVery commonPhlebitis.
RareVeno-occlusive disease (high-dose therapy).
Respiratory, thoracic and mediastinal disordersVery commonPulmonary toxicity, interstitial fibrosis (with prolonged therapy and cumulative dose)

Pneumonitis.

RareInterstitial fibrosis (with lower doses).
Gastrointestinal disordersVery commonEmetogenic potential.

Nausea and vomiting – severe

CommonAnorexia, constipation, diarrhoea, stomatitis.
Hepatobiliary disordersCommonHepatotoxicity, 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 disordersVery commonDermatitis with topical use improves with reduced concentration of compounded product, hyperpigmentation, transient, with accidental skin contact.
CommonAlopecia, flushing (due to alcohol content of solvent; increased with administration times <1-2 h), injection site reaction.
Not knownExtravasation hazard: vesicant
Renal and urinary disordersRareRenal toxicity.
Reproductive system and breast disordersRareGynecomastia.
Not knownInfertility, teratogenesis.

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.

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.

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 1 hour, the carmustine-plasma level drops in a biphasic manner. The half-life ? is 1-4 minutes and the half-life ? 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

2 years.

After reconstitution and dilution

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.

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.

7. Manufactured in India By:
TAJ PHARMACEUTICALS LIMITED
Mumbai, India
Survey No.188/1 to 189/1,190/1 to 4,
Athiyawad, Dabhel,
Daman- 396210 (INDIA)

Carmustine? powder and solvent for concentrate for solution for infusion IP 100mg Taj Pharma
Package leaflet: Information for the patient

Carmustine

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 itagain.
  • If you have any further questions, ask your doctor orpharmacist.
  • This medicine has been prescribed for you only. Do not pass it on to others. It may harmthem, even if their signs of illness are the same asyours.
  • If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section4.

What is in this leaflet:

  1. What Carmustine is and what it is usedfor
  2. What you need to know before you take Carmustine
  3. How to take Carmustine
  4. Possible sideeffects
  5. How to store Carmustine
  6. Contents of the pack and otherinformation
1 WHAT CARMUSTINE IS AND WHAT IT IS USED FOR

Carmustine 100 mg-Powder and solvent for solution for infusion is a medicine which contains carmustine. Carmustine belongs to a group of anticancer substances known as nitrosourea that act by slowing the growth of cancer cells.
Carmustine is used as palliative therapy (relieving and preventing the suffering of patients) as a single agent or in established combination therapy with other approved anticancer substances in certain types of cancers, like:
? Brain tumors- glioblastoma, medulloblastoma, astrocytoma and metastatic brain tumors
? Multiple myeloma (malignant tumor developing from bone marrow)
? Hodgkin’s disease (lymphoid tumor)
? Non-Hodgkin’s lymphomas (lymphoid tumor)

2 WHAT YOU NEED TO KNOW BEFORE YOU TAKE CARMUSTINE

Do not use Carmustine
– if you are allergic to carmustine, other nitrosourea medicines or any of the other ingredients of this medicine (listed in section 6).

Carmustine should not be used in patients who have reduced number of blood platelets (thrombocytes), white blood cells (leucocytes) or red blood cells (erythrocytes), either as a result of chemotherapy or from other causes.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Carmustine.
Since the major side effect of this medicine is delayed bone marrow suppression, your doctor will monitor blood counts weekly for at least 6 weeks after a dose. At the recommended dosage, courses of Carmustine would not be given more frequently than every 6 weeks. The dosage will be confirmed with the blood count.
Before treatment, your liver and kidney function will be tested and observed regularly during the treatment.
Since the use of Carmustine can lead to lung damage, an X-ray of the chest region and the lung function tests will be conducted (Please also see the section ?Possible side effects?).
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).

Other medicines and Carmustine
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
? Cimetidine, used for stomach problems like indigestion
? Digoxin, used if you have abnormal heart rhythm
? Melphalan, an anticancer drug

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 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 pregnancy, the patient must be aware of the potential risk to the unborn baby. Women of childbearing potential are advised to avoid becoming pregnant whilst being treated with this medicine. Male patients should use adequate contraceptives measures during treatment with Carmustine for at least 6 months to prevent their partners becoming pregnant.

Breast-feeding
You should not breast-feed while taking this medicine.

Driving and using machines
The effect of this medicine on your ability to drive and use machines is not known. 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 contains ethanol (alcohol)
This medicinal product contains 0.57 vol% ethanol (alcohol), which means 7.68 g per dose. This corresponds to 11.32 ml of beer or 4.72 ml wine, per dose. This may be harmful for those suffering from alcoholism, liver disease or epilepsy (fits)

3 HOW TO TAKE CARMUSTINE

Carmustine will always be given to you by a healthcare professional with experience in the use of anticancer agents.
This medication is for intravenous infusion.

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 as a single 2 agent in previously untreated patients is 150 to 200 mg/m intravenously every 6 weeks. This may be given as a single dose or divided into two daily injections such as? 75 to 100 mg/m on two successive days. Dosage will also depend on whether Carmustine is given with other anticancer drugs.
Doses will be adjusted according to how you respond to the treatment.
Your blood count will be monitored frequently to avoid toxicity in your bone marrow and the dose adjusted if necessary.

Route of administration
Carmustine is given into a vein by a drip over a one to two hour period. The time 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.

Use in children
Carmustine can be used with extreme caution in children due to high risk of lung toxicity.

Use in elderly
Carmustine can be used with caution in elderly patients. The kidney function will be carefully monitored.

If you use more Carmustine 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 your doctor or nurse if you have any concerns about the amount of medicine that you receive.
If you have any further questions on the use of this product, ask your doctor or pharmacist or nurse.

4 POSSIBLE SIDE EFFECTS

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

Tell yourdoctor ornurse 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 severe allergic reaction.

Carmustine 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);
? Ataxia (lack of voluntary coordination of muscle movements);
? Dizziness;
? Headache;
? Transient redness in the eye, blurred vision, retinal bleeding;
? Hypotension (fall in blood pressure) in high-dose therapy;
? Phlebitis (inflammation of the veins);
? Respiratory disorders (lung related disorders) with breathing problems;
? Severe nausea and vomiting; beginning within 2-4 hours of administration and lasting for 4-6 hours;
? 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 leukemias and bone marrow dysplasias (abnormal development of the bone marrow) following long term use;
? Anaemia (decrease in the amount of red blood cells in the blood);
? Encephalopathy (disorder of brain) in high-dose therapy;
? Anorexia;
? Constipation;
? Diarrhoea;
? Inflammation of the mouth and lips;
? Reversible liver toxicity in high-dose therapy, delayed up to 60 days after administration. 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) in high-dose therapy;
? Breathing problems caused by interstitial fibrosis (with lower doses);
? 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
? Any signs of infection
? Fast heart beat, chest pain

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. By reporting side effects you can help provide more information on the safety of this medicine.

5 HOW TO STORECARMUSTINE

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 statement ?can be used up to’. The expiry date refers to the last day of that month.
This medicine will be stored by your doctor or health care professional.
The unopened vial of the dry drug must be stored in a refrigerator (2?-8?C). After reconstitution as recommended, Carmustine is stable for 24 hours under refrigeration (2?-8?C) in a glass container and must be protected from light.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist or doctor 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 contains

The active substance is carmustine.

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 IP.
Each ampoule of solvent contains 3 ml ethanol anhydrous (that is equivalent to 2.37 g).

Contents of the pack

Powder and solvent for solution for infusion. Yellowish powder for reconstitution. Appearance of solution: colorless to light yellow

Powder: Type I amber glass vial (30 ml) sealed with a dark grey bromo butyl lyo rubber stopper and aluminium seal having polypropylene cap.

Diluent: Type I glass vial (5 ml) sealed with a grey bromo butyl rubber stopper with an aluminium seal having polypropylene cap.

7. Manufactured in India By:
TAJ PHARMACEUTICALS LIMITED
Mumbai, India
at SURVEY NO. 188/1, 190/1TO 4, ATHIYAWAD , DABHEL,
DAMAN- 396210 (INDIA)

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