Chlorambucil Tablets 2mg USP Taj Pharma

1.NAME OF THE MEDICINAL PRODUCT

Chlorambucil Tablets 2mg USP Taj Pharma
Chlorambucil Tablets 5mg USP Taj Pharma

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

a)Chlorambucil Tablets 2mg USP Taj Pharma
Each film-coated tablet contains:
Chlorambucil USP                                  2mg
Excipients                                                q.s.
Colours: Titanium Dioxide USP

b) Chlorambucil Tablets 5mg USP Taj Pharma
Each film-coated tablet contains:
Chlorambucil USP                                  5mg
Excipients                                                q.s.
Colours: Titanium Dioxide USP

For the full list of excipients, see section 6.1.

  1. PHARMACEUTICAL FORM

Film-coated tablets.

  1. CLINICAL PARTICULARS

4.1 Therapeutic indications
Chlorambucil is indicated in the treatment of Hodgkin’s disease, certain forms of non-Hodgkin’s lymphoma, chronic lymphocytic leukaemia, and Waldenstrom’s macroglobulinaemia.
4.2  Posology and method of administration

The relevant literature should be consulted for full details of the treatment schedules used.

Chlorambucil is an active cytotoxic agent for use only under the direction of physicians experienced in the administration of such agents.

Posology

HODGKIN’S DISEASE

Adults

Used as a single agent in the palliative treatment of advanced disease a typical dosage is 0.2 mg/kg/day for 4-8 weeks. Chlorambucil is usually included in combination therapy and a number of regimes have been used. Chlorambucil has been used as an alternative to nitrogen mustard with a reduction in toxicity but similar therapeutic results.

Paediatric population

Chlorambucil may be used in the management of Hodgkin’s disease in children. The dosage regimes are similar to those used in adults.

NON-HODGKIN’S LYMPHOMA

Adults

Used as a single agent the usual dosage is 0.1-0.2 mg/kg/day for 4-8 weeks initially, maintenance therapy is then given either by a reduced daily dosage or intermittent courses of treatment.

Chlorambucil is useful in the management of patients with advanced diffuse lymphocytic lymphoma and those who have relapsed after radiotherapy. There is no significant difference in the overall response rate obtained with chlorambucil as a single agent and combination chemotherapy in patients with advanced non-Hodgkin’s lymphocytic lymphoma.

Paediatric population

Chlorambucil may be used in the management of non Hodgkin’s disease in children. The dosage regimes are similar to those used in adults.

CHRONIC LYMPHOCYTIC LEUKAEMIA

Adults

Treatment with Chlorambucil is usually started after the patient has developed symptoms or when there is evidence of impaired bone marrow function (but not bone marrow failure) as indicated by the peripheral blood count. Initially Chlorambucil is given at a dosage of 0.15 mg/kg/day until the total leucocyte count has fallen to 10,000 per µL. Treatment may be resumed 4 weeks after the end of the first course and continued at a dosage of 0.1 mg/kg/day.

In a proportion of patients, usually after about 2 years of treatment, the blood leucocyte count is reduced to the normal range, enlarged spleen and lymph nodes become impalpable and the proportion of lymphocytes in the bone marrow is reduced to less than 20%.

Patients with evidence of bone marrow failure should first be treated with prednisolone and evidence of marrow regeneration should be obtained before commencing treatment with Chlorambucil. Intermittent high dose therapy has been compared with daily Chlorambucil but no significant difference in therapeutic response or frequency of side effects was observed between the two treatment groups.

WALDENDSTROM’S MACROGLOBULINAEMIA

Adults

Chlorambucil is one of the treatment choices in this indication.

Starting doses of 6-12 mg daily until leukopenia occurs are recommended followed by 2-8 mg daily indefinitely.

SPECIAL POPULATIONS

Renal impairment

Dose adjustment is not considered necessary in renal impaired patients.

Patients with evidence of impaired renal function should be carefully monitored as they are prone to additional myelosuppression associated with azotaemia.

Hepatic impairment

Patients with hepatic impairment should be closely monitored for signs and symptoms of toxicity.

Since chlorambucil is primarily metabolized in the liver, dose reduction should be considered in patients with severe hepatic impairment. However, there are insufficient data in patients with hepatic impairment to provide a specific dosing recommendation.

Older people

No specific studies have been carried out in older people, however, it may be advisable to monitor renalor hepatic function and if there is impairment then caution should be exercised.

While clinical experience has not revealed age-related differences in response, drug dosage generally should be titrated carefully in older patients, usually initiating therapy at the low end of the dosage range.

Method of administration

Chlorambucil tablets are administered orally and should be taken daily on an empty stomach (at least one hour before meals or three hours after meals).

4.3 Contraindications

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

4.4 Special Warnings and precautions for use

Continued treatment with chlorambucil should be assessed if a rash develops since there have been reports of Stevens-Johnson Syndrome in patients receiving chlorambucil.

Safe Handling of Chlorambucil tablets:

Immunisation using a live organism vaccine has the potential to cause infection in immunocompromised hosts. Therefore, immunisations with live organism vaccines are not recommended.

Patients who will potentially have autologous stem cell transplantation should not be treated with chlorambucil long term.

Monitoring

Since Chlorambucil is capable of producing irreversible bone marrow suppression, blood counts should be closely monitored in patients under treatment.

At therapeutic dosage Chlorambucil depresses lymphocytes and has less effect on neutrophil and platelet counts and on haemoglobin levels. Discontinuation of Chlorambucil is not necessary at the first sign of a fall in neutrophils but it must be remembered that the fall may continue for 10 days or more after the last dose.

Chlorambucil should not be given to patients who have recently undergone radiotherapy or received other cytotoxic agents.

When lymphocytic infiltration of the bone marrow is present or the bone marrow is hypoplastic, the daily dose should not exceed 0.1 mg/kg body weight.

Children with nephrotic syndrome, patients prescribed high pulse dosing regimens and patients with a history of seizure disorder, should be closely monitored following administration of Chlorambucil, as they may have an increased risk of seizures.

Mutagenicity and Carcinogenicity

Chlorambucil has been shown to cause chromatid or chromosome damage in man.

Secondary malignancies, most commonly acute secondary haematologic malignancies (especially leukaemia and myelodysplastic syndrome) have been reported, particularly after long term treatment.

A comparison of patients with ovarian cancer who received alkylating agents with those who did not, showed that the use of alkylating agents, including Chlorambucil, significantly increased the incidence of acute leukaemia.

Acute myelogenous leukaemia has been reported in a small proportion of patients receiving Chlorambucil as long term adjuvant therapy for breast cancer.

The leukaemogenic risk must be balanced against the potential therapeutic benefit when considering the use of Chlorambucil.

Sugar intolerances

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medication.

4.5 Interaction with other medicinal products and other forms of interaction

Vaccinations with live organism vaccines are not recommended in immunocompromised individuals.

Purine nucleoside analogues (such as fludarabine, pentostatin and cladribine) increased the cytotoxicity of chlorambucil ex vivo; however, the clinical significance of this finding is unknown.

4.6 Fertility, pregnancy and lactation

Pregnancy

As with all cytotoxic therapy chemotherapy, adequate contraceptive precautions should be advised when either partner is receiving Chlorambucil.

The use of Chlorambucil should be avoided whenever possible during pregnancy, particularly during the first trimester. In any individual case, the potential hazard to the foetus must be balanced against the expected benefit to the mother.

Breast-feeding

Mothers receiving Chlorambucil should not breast feed.

Fertility:

Chlorambucil may cause suppression of ovarian function and amenorrhoea has been reported following chlorambucil therapy.

Azoospermia have been observed as a result of therapy with chlorambucil although it is estimated that a total dose of at least 400 mg is necessary.

Varying degrees of recovery of spermatogenesis have been reported in patients with lymphoma following treatment with Chlorambucil in total doses of 410-2600 mg.

Teratogenicity

As with other cytotoxic agents Chlorambucil is potentially teratogenic.

4.7 Effects on ability to drive and use machines

No information on the effects of Chlorambucil on the ability to drive and use machines is available.

 

4.8 Undesirable Effects

For this product there is no modern clinical documentation which can be used as support for determining the frequency of undesirable effects. Undesirable effects may vary in their incidence depending on the dose received and also when given in combination with other therapeutic agents.

The following convention has been utilised for the classification of frequency: Very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10,000 and <1/1000) and very rare (<1/10,000) , not known (cannot be estimated from the available data).

Body System Side effects
Neoplasms benign, malignant and unspecified (including cysts and polyps) Common Acute secondary haematologic malignancies (especially leukaemia and myelodysplastic syndrome), particularly after long term treatment.
Blood and lymphatic system disorders Very common Leukopenia, neutropenia, thrombocytopenia, pancytopenia or bone marrow suppression1.
Common Anaemia.
Very rare Irreversible bone marrow failure.
Immune system disorders Rare Hypersensitivity such as urticaria and angioneurotic oedema following initial or subsequent dosing.

(See Skin and subcutaneous tissue disorders)

Nervous system disorders Common Convulsions in children with nephrotic syndrome.
Rare Convulsions 2, partial and/or generalised in children and adults receiving therapeutic daily doses or high pulse dosing regimens of chlorambucil.
Very rare Movement disorders including tremor, muscle twitching and myoclonus in the absence of convulsions. Peripheral neuropathy.
Respiratory, thoracic and mediastinal disorders Very rare Interstitial pulmonary fibrosis3, interstitial pneumonia.
Gastrointestinal disorders Common Gastro-intestinal disorders such as nausea and vomiting, diarrhoea and mouth ulceration.
Hepatobiliary disorders Rare Hepatoxicity, jaundice.
Skin and subcutaneous tissue disorders Uncommon Rash.
Rare Stevens-Johnson syndrome, toxic epidermal necrolysis.(see Immune system disorders)
Renal and urinary disorders Very rare Sterile cystitis.
Reproductive system and breast disorders Not known Amenorrhoea, azoospermia.
General disorders and administration site conditions Rare Pyrexia.
  1. Although bone marrow suppression frequently occurs, it is usually reversible if Chlorambucil is withdrawn early enough.
  2. Patients with a history of seizure disorder may be particularly susceptible.
  3. Severe interstitial pulmonary fibrosis has occasionally been reported in patients with chronic lymphocytic leukaemia on long-term Chlorambucil therapy. However, this may be reversible on withdrawal of Chlorambucil.
  4. Skin rash has been reported to progress to serious conditions including Stevens-Johnson syndrome and toxic epidermal necrolysis.

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
Symptoms and signs

Reversible pancytopenia was the main finding of inadvertent overdoses of Chlorambucil. Neurological toxicity ranging from agitated behaviour and ataxia to multiple grand mal seizures has also occurred.

Treatment

As there is no known antidote the blood picture should be closely monitored and general supportive measures should be instituted, together with appropriate blood transfusion if necessary.

 

  1. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antineoplastic and immunomodulating agents, antineoplastic agents, alkylating agents, nitrogen mustard analogues

Mechanism of action

Chlorambucil is an aromatic nitrogen mustard derivative which acts as a bifunctional alkylating agent.

In addition to interference with DNA replication, chlorambucil induces cellular apoptosis via the accumulation of cytosolic p53 and subsequent activation of an apoptosis promoter (Bax).

Pharmacodynamic effects

The cytotoxic effect of chlorambucil is due to both chlorambucil and its major metabolite phenylacetic acid mustard (see section 5.2).

Mechanism of resistance

Chlorambucil is an aromatic nitrogen mustard derivative and resistance to nitrogen mustards has been reported to be secondary to: alterations in the transport of these agents and their metabolites via various multi-resistant proteins, alterations in the kinetics of the DNA cross-links formed by these agents and changes in apoptosis and altered DNA repair activity. Chlorambucil is not a substrate of multi-resistant protein 1 (MRP1 or ABCC1), but its glutathione conjugates are substrates of MRP1 (ABCC1) and MRP2 (ABCC2).


5.2 Pharmacokinetic properties

Absorption

Chlorambucil is well absorbed by passive diffusion from the gastrointestinal tract and is measurable within 15-30 minutes of administration. The bioavailability of oral chlorambucil is approximately 70% to 100% following administration of single doses of 10-200 mg.

In a study of 12 patients administered approximately 0.2 mg/kg of oral chlorambucil, the mean dose adjusted maximum plasma concentration (492 ± 160 nanograms/ml) occurred between 0.25 and 2 hours after administration.

Consistent with the rapid, predictable absorption of chlorambucil, the inter-individual variability in the plasma pharmacokinetics of chlorambucil has been shown to be relatively small following oral dosages of between 15 and 70 mg (2-fold intra-patient variability, and a 2-4 fold interpatient variability in AUC).

The absorption of chlorambucil is reduced when taken after food. In a study of ten patients, food intake increased the median time to reach Cmax by greater than 100%, reduced the peak plasma concentration by greater than 50% and reduced mean AUC (0-∞) by approximately 27% (see section 4.2).

Distribution

Chlorambucil has a volume of distribution of approximately 0.14-0.24 L/kg. Chlorambucil covalently binds to plasma proteins, primarily to albumin (98%), and covalently binds to red blood cells.

Biotransformation

Chlorambucil is extensively metabolised in the liver by monodichloroethylation and β-oxidation, forming phenylacetic acid mustard (PAAM) as the major metabolite, which possesses alkylating activity in animals. Chlorambucil and PAAM degrade in vivo forming monohydroxy and dihydroxy derivatives. In addition, chlorambucil reacts with glutathione to form mono- and diglutathionyl conjugates of chlorambucil.

Following the administration of approximately 0.2 mg/kg of oral chlorambucil, PAAM was detected in the plasma of some patients as early as 15 minutes and mean dose adjusted plasma concentration (Cmax) of 306 ± 73 nanograms/ml occurred within 1 to 3 hours.

Elimination

The terminal phase elimination half-life ranges from 1.3-1.5 hours for chlorambucil and is approximately 1.8 hours for PAAM. The extent of renal excretion of unchanged chlorambucil or PAAM is very low; less than 1% of the administered dose of each of these is excreted in the urine in 24 hours, with the rest of the dose eliminated mainly as monohydroxy and dihydroxy derivatives.

5.3 Preclinical safety data

Mutagenicity and Carcinogenicity

As with other cytotoxic agents chlorambucil is mutagenic in in vitro and in vivo genotoxicity tests and carcinogenic in animals and humans.

Reproductive toxicology

In rats, chlorambucil has been shown to damage spermatogenesis and cause testicular atrophy.

Teratogenicity

Chlorambucil has been shown to induce developmental abnormalities, such as short or kinky tail, microcephaly and exencephaly, digital abnormalities including ectro-, brachy-, syn- and polydactyly and long-bone abnormalities such as reduction in length, absence of one or more components, total absence of ossification sites in the embryo of mice and rats following a single oral administration of 4 to 20 mg/kg.

Chlorambucil has also been shown to induce renal abnormalities in the offspring of rats following a single intraperitoneal injection of 3 to 6 mg/kg.

Brain and plasma pharmacokinetics

After oral administration of 14C-marked chlorambucil to rats, the highest concentrations of radioactive marked material were found in the plasma, in the liver and in the kidneys. Only small concentrations were measured in the cerebral tissue of rats after intravenous administration of chlorambucil.

  1. PHARMACEUTICAL PARTICULARS

    6.1 List of excipients
    Microcrystalline cellulose , Anhydrous lactose, Colloidal anhydrous silica, Stearic acid Hypromellose, Titanium dioxide, Synthetic yellow iron oxide, Synthetic red iron oxide, Macrogol.

 6.2 Incompatibilities
None known.

6.3  Shelf life

3 years.

6.4 Special precautions for storage
Store in a refrigerator (2°C-8°C)

6.5 Nature and contents of container

Chlorambucil tablets are brown, round, biconvex, film-coated tablets, supplied in amber glass bottles with a child resistant closure containing 25 tablets..

6.6 Special precautions for disposal and other handling

Chlorambucil is an active cytotoxic agent for use only under the direction of physicians experienced in the administration of such agents.

The handling of Chlorambucil Tablets should follow guidelines for the handling of cytotoxic drugs according to prevailing local recommendations and/or regulations (for example, Royal Pharmaceutical Society of Great Britain Working Party on the Handling of Cytotoxic Drugs).

Provided that the outer coating of the tablet is intact, there is no risk in handling Chlorambucil Tablets.

Chlorambucil Tablets should not be divided.

7. Manufactured in India By:
TAJ PHARMACEUTICALS LIMITED
at SURVEY NO.188/1 TO 189/1,190/1 TO 4,
ATHIYAWAD, DABHEL, DAMAN- 396210 (INDIA).

Chlorambucil Tablets 2mg USP Taj Pharma
Chlorambucil Tablets 5mg USP Taj Pharma
(Chlorambucil)

Package leaflet:Information for the patient

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.
– Keep this leaflet. You may need to read it again.
 – If you have any further questions, ask your doctor or pharmacist.
– This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
– If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet (see section 4).
-The full name of the product is Chlorambucil 2 mg Film-coated Tablets but within the leaflet it will be referred to as Chlorambucil tablets.

What is in this leaflet

1. What Chlorambucil tablets are and what they are used for
2. What you need to know before you take Chlorambucil tablets
3. How to take Chlorambucil tablets
4. Possible side effects
5. How to store Chlorambucil tablets
6. Contents of the pack and other information

1.WHAT CHLORAMBUCIL TABLETS ARE AND WHAT THEY ARE USED FOR

Chlorambucil contains a medicine called chlorambucil. This belongs to a group of medicines called cytotoxics (also called chemotherapy). Chlorambucil is used to treat some types of cancer and certain blood problems. It works by reducing the number of abnormal cells your body makes.
Chlorambucil is used for:
Hodgkin’s disease and Non-Hodgkin’s Lymphoma. Together, these form a group of diseases called lymphomas. They are cancers formed from cells of the lymphatic system.
Chronic lymphocytic leukaemia. A type of white blood cell cancer where the bone marrow produces a large number of abnormal white cells.
Waldenstrom’s macroglobulinaemia A rare lymphoma associated with an uncontrolled increase of B-cells, a type of white blood cell, resulting in the release of an abnormal protein into the blood. Ask your doctor if you would like more explanation about these diseases.
You must talk to a doctor if you do not feel better or if you feel worse.

  1. WHAT YOU NEED TO KNOW BEFORE YOU TAKE CHLORAMBUCIL TABLETS

Do not take Chlorambucil :
– If you are allergic (hypersensitive) to chlorambucil or any of the other ingredients of Chlorambucil tablets (See section 6).

If you are not sure, talk to your doctor or nurse before taking Chlorambucil.

Warnings and precautions
Before you take Chlorambucil, tell your doctor or nurse if:
– you have been recently vaccinated, or planning to be vaccinated with a live vaccine (see Other medicines and Chlorambucil). Chlorambucil can make your body less able to fight infections.
– you are a potential candidate for bone marrow transplantation (autologous stem cell transplantation) as the long term use of Chlorambucil may reduce the amount of stem cells.
– you have had radiotherapy or chemotherapy, now or recently
– you have a liver or kidney problems
– you have a kidney problem (nephrotic syndrome) , had high pulse dosing regimen or ever had a fit or convulsion. If you had ever had fits or convulsions, you might be more at risk of having fits or convulsions when taking Chlorambucil.
It is possible that the use of Chlorambucil, particularly long term use, may increase the risk of developing a secondary blood cancer. In many cases, patients who develop this have also received another type of chemotherapy or some form of radiation therapy. Symptoms of a secondary blood cancer include tiredness, fever, infection and bruising. Tell your doctor as soon as possible if you have any of these symptoms.

Other medicines and Chlorambucil
Please tell your doctor if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription. This includes herbal medicines. In particular, tell your doctor if you are taking or have recently taken any of the following:
– Vaccines which contain live organisms (such as oral polio vaccine, measles, mumps, rubella). – Phenylbutazone (a medicine used to treat fever, pain, and inflammation in the body) – you may require a lower dose of Chlorambucil.
– Fludarabine, Pentostatin or Cladribine, which are other chemotherapy medicines that may be used for the treatment of haematological malignancies (types of cancer that affect blood, bone marrow and lymph nodes).

Chlorambucil with food
Chlorambucil should be taken on an empty stomach..

Pregnancy, breast-feeding and fertility Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. Do not take Chlorambucil if you are planning to have a baby. This applies to both men and women. Treatment with Chlorambucil is not recommended during pregnancy because it may cause permanent damage to a foetus. Your doctor will consider the risks and benefits to you and your baby of taking Chlorambucil. Do not breast-feed while taking Chlorambucil. There have been reports indicating that Chlorambucil and its ingredients can be passed into breast-milk. Ask your doctor or midwife for advice.

Fertility
 Chlorambucil can affect ovaries or sperm, which may cause infertility (inability to have a baby). In woman menstruation can stop (amenorrhoea) and in men, a complete lack of sperm can be observed (azoospermia). Use a reliable form of contraception to avoid pregnancy if either you or your partner is taking Chlorambucil. Ask your doctor for advice.

Driving and using machines
No information on the effects of Chlorambucil on the ability to drive and use machines is available.

Chlorambucil contains lactose
Chlorambucil tablets contain lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before you take Chlorambucil tablets.

 3. HOW TO TAKE CHLORAMBUCIL TABLETS

Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not sure. Chlorambucil should only be given to you by a specialist doctor who is experienced in treating cancer. The duration of the treatment will be decided by your doctor based on your disease.
– Chlorambucil is administrated orally and should be taken daily on an empty stomach (at least one hour before meals or three hours after meals).
– Swallow your tablets whole with a glass of water.
– Do not break, crush or chew the tablets.

The dose of Chlorambucil depends on the type of your blood problem or cancer .
– Your doctor may change your dose during your treatment depending on your needs. The dose can sometimes be changed if you are an older person or have liver problems. Your kidney or liver functions may be monitored during treatment, if you are an elderly person.
– When you take Chlorambucil your doctor will take regular blood tests to check the number of cells in your blood and your drug dose may be adjusted as a result.

Hodgkin’s Disease
The usual dose is 0.2 mg per kilogram of your body weight each day for adults and children.
Non-Hodgkin’s Lymphoma
– The usual dose is 0.1 to 0.2 mg per kilogram of your body weight each day for adults and children.
Chronic Lymphocytic Leukaemia
 – The usual starting dose is 0.15 mg per kilogram of your body weight each day. Waldenstrom’s macroglobulinaemia
– The usual starting dose is 6 to 12 mg each day. Some people have to take Chlorambucil long term. If you have to take it long term, the usual dose is 2 to 8 mg each day. Follow your doctor’s instructions carefully.

If you take more Chlorambucil than you should
Tell your doctor immediately or go to a hospital straight away. Ensure to take the medicine pack with you.

 If you forget to take Chlorambucil
Tell your doctor. Do not take a double dose to make up for a forgotten dose.

If you stop taking Chlorambucil
If you have any further questions on the use of this medicine, ask your doctor or nurse.

  1. POSSIBLE SIDE EFFECTS

Like all medicines, Chlorambucil can cause side effects, although not everybody experiences them.

If you experience any of the following, talk to your specialist doctor or go to hospital straight away:

– any signs of fever or infection (sore throat, sore mouth or urinary problems),
– any unexpected bruising or bleeding, as this could mean that too few blood cells of a particular type are being produced,
– if you suddenly feel unwell (even with a normal temperature), 5
– if you start feeling extremely tired,
– if you notice numbness or weakness of your muscles,
– if you experience skin rashes, blisters on the skin, sore mouth or eyes and have a high temperature.
Talk to your doctor if you have any of the following side effects, which may also happen with this medicine:

Very Common (affects more than 1 in 10 people)

– a drop in the number of blood cells, or bone marrow suppression.

Common (affects less than 1 in 10 people)

– feeling sick (nausea), being sick (vomiting), diarrhoea or mouth ulcers (sores), – secondary blood cancers (acute secondary haematologic malignancies), – fits (convulsions) in children with a kidney problem known as nephrotic syndrome, – a drop on red blood cells or anaemia which may make you feel tired or weak or breathless.

Uncommon (affects less than 1 in 100 people)
– rash.

 Rare (affects less than 1 in 1,000 people)
– yellowing of the whites of the eyes or skin (jaundice),
– allergy symptoms such as skin lumps, hives (urticaria) or swelling of the tissues (oedema),
– skin rash has been reported to progress to serious conditions including Stevens-Johnson syndrome and toxic epidermal necrolysis. These two forms of the same serious skin disease cause rash, skin peeling and stores on the mucous membranes,
– fever,
– fit or convulsion.
– liver damage/injury (hepatotoxicity).

Very rare (affects less than 1 in 10,000 people)
– abnormal and repetitive shaking movement of the body or twitching, without fits or convulsions,
– inflammation of the bladder called cystitis,
– irreversible bone marrow failure – your body may stop producing blood cells transiently,
– scarring and thickening in the lungs with shortness of breath,
– lung disease,
– condition affecting nerves leading to impairment of sensation, movement and organ function (peripheral neuropathy).

Not known: frequency cannot be estimated from the available data
– absence of menstruation (amenorrhoea),
– absence of sperm (azoospermia).

If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.
 Reporting of side effects
 If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet.

5. HOW TO STORE CHLOMBUCILTABLETS

-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 pack after ‘Exp’.
– Store in a refrigerator (2 and 8°C).
– If your doctor tells you to stop taking the tablets, it is important to return any which are left over to your pharmacist, who will destroy them according to disposal of dangerous substance guidelines. Only keep the tablets if your doctor tells you to.
– 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 FURTHER INFORMATION

What Chlorambucil contains
 – The active substance is chlorambucil. Each Chlorambucil tablet contains 2 mg or 5mg of chlorambucil.
– The other ingredients are microcrystalline cellulose, anhydrous lactose, colloidal anhydrous silica, stearic acid, hypromellose, titanium dioxide, synthetic yellow iron oxide, synthetic red iron oxide and macrogol.

What Chlorambucil looks like and contents of the pack
Chlorambucil tablets are brown, round, biconvex, film-coated tablets.

7. Manufactured in India By:
TAJ PHARMACEUTICALS LIMITED
at SURVEY NO.188/1 TO 189/1,190/1 TO 4,
ATHIYAWAD, DABHEL, DAMAN- 396210 (INDIA).

 

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