Last Updated on eMC 03-11-2015 View medicine  | Aspen Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Reasons for adding or updating:

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 5.3 - Preclinical safety data
  • Change to section 9 - Date of first authorisation/renewal of the authorisation
  • Change to section 10 - Date of revision of the text
  • Correction of spelling/typing errors

Date of revision of text on the SPC:31-03-2015

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Text in red = new text
Text strikethrough = deleted text

2        QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Each tablet contains 2 mg of the active ingredient chlorambucil.

 

Excipient(s) with known effect:

4.2 Posology and method of administration

 

Posology

 

Paediatric population


Older people

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

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


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).

Skin and subcutaneous tissue
disorders Uncommon Rash.
Rare


Stevens-Johnson syndrome, toxic epidermal necrolysis.4 (see Immune system disorders)
On rare occasions skin rash has been reported to progress to serious conditions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
Renal and urinary disorders Very rare Sterile cystitis.
Reproductive system and breast
disorders Not known Amenorrhoea, azoospermia.


Reproductive system and breast
disorders Not known Amenorrhoea, azoospermia.

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. Healthcare
professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at
www.mhra.gov.uk/yellowcard.


5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group
: Antineoplastic and immunomodulating agents,
antineoplastic agents, alkylating agents, nitrogen mustard analogues
ATC code: L01AA02

5.3 Preclinical safety data
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.

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

22 June 2006


10. DATE OF REVISION OF THE TEXT


03/2015

Reasons for adding or updating:

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:01-11-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Text in red = new
Text strikethrough = deleted


7.         MARKETING AUTHORISATION HOLDER


Aspen Pharma Trading Limited

12/13 Exchange Place,

I.F.S.C,

Dublin 1, Ireland

3016 Lake Drive

Citywest Business Campus

Dublin 24

Ireland

 



10.              DATE OF REVISION OF THE TEXT

 

November 2012 November 2013

Reasons for adding or updating:

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.1 - Therapeutic indications
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.3 - Contraindications
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.7 - Effects on ability to drive and use machines
  • Change to section 4.8 - Undesirable effects
  • Change to section 4.9 - Overdose
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 5.3 - Preclinical safety data
  • Change to section 6.1 - List of excipients
  • Change to section 6.3 - Shelf life
  • Change to section 6.4 - Special precautions for storage
  • Change to section 6.5 - Nature and contents of container
  • Change to section 6.6 - Special precautions for disposal and other handling
  • Change to section 7 - Marketing authorisation holder
  • Change to section 8 - Marketing authorisation number(s)
  • Change to section 9 - Date of first authorisation/renewal of the authorisation
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:01-11-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Type II variation to incorporate Global Data Sheet v 16

SUMMARY OF PRODUCT CHARACTERISTICS

 

Product Summary

 

 

1          Name of the Medicinal Product

 

Chlorambucil 2 mg tablets

 

 

2          Qualitative and Quantitative Composition

2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Each tablet contains 2 mg of the active ingredient chlorambucil.

 

 

3          Pharmaceutical Form

 

Film-coated tablet

 

 

4        Clinical Particulars

 

Each tablet also contains 67.65 mg of lactose.

For the full list of excipients, see section 6.1.

 

 

3        PHARMACEUTICAL FORM

 

Brown, film-coated, round, biconvex tablets engraved ‘GX EG 3’ on one side and ‘L’ on the other.

 

 

4.      CLINICAL PARTICULARS

 

4.1       Therapeutic Indicationsindications

 

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 Methodmethod of Administrationadministration

 

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

 

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).

 

HODGKIN’S DISEASE

Adults:  Hodgkin's Disease

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.

 

Children:Non-Hodgkin's Lymphoma

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.

 

Chronic Lymphocytic Leukaemia:   Children:

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 per cent.  %.

 

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.

 

Waldenstrom's MacroglobulinaemiaWALDENDSTROM’S MACROGLOBULINAEMIA

Adults:

Chlorambucil is the treatment of choice in this indication. 

Starting doses of 6-12 mg daily until leucopenia 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.

Children:  Chlorambucil may be used in the management of Hodgkin's disease and non-Hodgkin's lymphomas in children.  The dosage regimes are similar to those used in adults.

 

Use in the Elderly:  No specific studies have been carried out in the elderly, however, it may be advisable to monitor renal or hepatic function and if there is serious impairment then caution should be exercised.

 

 

4.3       Contraindications

 

Hypersensitivity to chlorambucil or to any of the excipients.

 

 

4.4       Special Warningswarnings and Precautionsprecautions for Useuse

 

Continued treatment with chlorambucil should be assessed if a rash develops since there have been reports of Stevens-Johnson Syndrome in patients receiving chlorambucil (see section 4.8 Undesirable effects).

 

Chlorambucil is an active cytotoxic agent for useand should only be administrated under the direction of physicians experienced ina specialist oncology service having the administrationfacilities for regular monitoring of such agentsclinical biochemical and haematological effects during and after the treatment.

 

Safe Handling of Chlorambucil tablets: 

See section 6.6 InstructionsSpecial precautions for Use/Handlingdisposal

 

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

 

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.

 

Renal impairment:

 

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

 

Hepatic impairment:

 

The metabolism of Chlorambucil is still under investigation and consideration should be given to dose reduction in patients with gross hepatic dysfunction.

 

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 (see Sectionsection 4.8 Undesirable effects).  

 

 

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 glucose intolerance, the Lapp lactase

deficiency or glucose-galactose malabsorption should not take this medication.  Each Chlorambucil 2mg tablet contains 68mg of lactose.

 

 

4.5       InteractionInteractions with other medicinal products and other forms of interaction

 

Vaccinations with live organism vaccines are not recommended in immunocompromised individuals (see Sectionsection 4.4 Special Warningswarnings and Precautionsprecautions for use).

 

Patients receiving phenylbutazone may require a reduced dose of Chlorambucil.

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

 

 

4.6       Fertility, pregnancy, and lactation

 

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 400-2600 mg.

 

 

Teratogenicity:

As with other cytotoxic agents Chlorambucil is potentially teratogenic. 

 

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.

 

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

 

Lactation:

Mothers receiving Chlorambucil should not breast feed.

 

 

4.7       Effects on Abilityability to Drivedrive and Use Machinesuse machines

 

None known

No data.

 

 

4.8       Undesirable Effectseffects

 

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 (³1/10), common (³1/100 and <1/10), uncommon (³1/1000 and <1/100), rare (³1/10,000 and <1/1000) and very rare (<1/10,000).

 

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:     Leucopenia, neutropenia, thrombocytopenia, pancytopenia or bone marrow suppression.

Common:                     Anaemia.

 

Very rare:             Irreversible bone marrow failure.

 

 

Although bone marrow suppression frequently occurs, it is usually reversible if Chlorambucil is withdrawn early enough.

 

Immune system disorders

 

Uncommon:         Rash.

Rare:                    Allergic reactions such as urticaria and angioneurotic oedema following initial or subsequent dosing. Stevens-Johnson syndrome and toxic epidermal necrolysis.

 

(See Skin and subcutaneous tissue disorders)

 

On rare occasions skin rash has been reported to progress to serious conditions including Stevens-Johnson Syndrome and toxic epidermal necrolysis.

 

Nervous system disorders

 

Common:             Seizures in children with nephrotic syndrome.

Rare:                    Seizures#, focal and/or generalised in children and adults receiving therapeutic daily doses or high pulse dosing regimens of chlorambucil.

Very rare:             Movement disorders including tremor, twitching and myoclonia in the absence of convulsions.  Peripheral neuropathy.

 

#Patients with a history of seizure disorder may be particularly susceptible.

 

Respiratory, thoracic and mediastinal disorders

 

Very rare:            Interstitial pulmonary fibrosis, interstitial pneumonia.

 

 

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.

 

Gastrointestinal disorders

 

Common:                   Gastro-intestinal disturbances such as nausea and vomiting, diarrhoea and oral ulceration.

 

Hepatobiliary disorders

 

Rare:                    Hepatoxicity, jaundice.

 

Skin and subcutaneous tissue disorders

 

Uncommon:         Rash.

Rare:                    Allergic reactions such as urticaria and angioneurotic oedema following initial or subsequent dosing.  Stevens-Johnson syndrome and toxic epidermal necrolysis.

 

(See Immune system disorders)

 

On rare occasions skin rash has been reported to progress to serious conditions including Stevens-Johnson syndrome and toxic epidermal necrolysis.

 

Renal and urinary disorders

 

Very rare:            Sterile cystitis.

 

General disorders and administration site conditions

 

Rare:                    Drug fever.

 

 

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.

 

 

5        Pharmacological Properties

 

5.      PHARMACOLOGICAL PROPERTIES

 

5.1       Pharmacodynamic Propertiesproperties

 

 

Pharmacotherapeutic group: Alkylating agents, nitrogen mustard analogues

ATC code: L01AA02

 

Mechanism of action:

Chlorambucil is an aromatic nitrogen mustard derivative which acts as a bifunctional alkylating agent.  Alkylation takes place through the formation of a highly reactive ethylenimonium radical.  A probable mode of action involves cross-linkage of the ethylenimonium derivative between 2 strands of helical DNA and subsequent interference with replication.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 chlomrambucil is due to both

5.2       Pharmacokinetic Properties

 

In a study of 12 patients administered chlorambucil and its major metabolite phenylacetic acid mustard (see Pharmacokinectics; metabolism).

 

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 0.2 mg/kg body weight orallyproperties

 

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 ngnanograms/ml) occurred between 0.25 and 2 hours after administration.  The mean (± SD) terminal plasma elimination half-life was 1.3 ± 0.5 hours.

 

After oral administration of [14C]-chlorambucil, maximum plasma radioactivity occurs between 40 and 70 minutes later.  Studies have shown that chlorambucil disappears from the plasma with a mean terminal phase life of 1.5 hours and that its urinary excretion is low.  A high level of urinary radioactivity after oral or intravenous administration of [14C]-chlorambucil indicates that the drug is well absorbed after oral dosage.

 

The metabolism of chlorambucil in man appears to be similar to that in laboratory animals and involves S-oxidation of the butyric acid side chain.   Bis-2-chlorethyl-2(4-aminophenyl) acetic acid [phenylacetic acid mustard (PAAM)] is a major metabolite of chlorambucil. 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 12ten patients administered chlorambucil 0.2 mg/kg body weight orally,, food intake increased the mean dose adjusted-median time to reach Cmax by greater than 100%, reduced the peak plasma concentration of PAAM (306 ± 73 ng/ml) was reached within 1 - 3 hours.  The mean terminal elimination plasma half-life was 1.8 ± 0.4 hours.  The significant contribution of PAAM to the by greater than 50% and reduced mean AUC (0-¥)by approximately 27% (see Dosage & Administration)

 

 

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.

 

Metabolism

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 of the drug was evident as the mean area underin 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 time curve (AUC(Cmax) of PAAM was approximately 1.33 times greater than the AUC 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 Datasafety 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

 

See information under 'Pregnancy and Lactation' section.

Chlorambucil has been shown to induce skeletaldevelopmental 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 embryosembryo 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.

 

Effects on fertility

 

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

 

Azoospermia has 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 400-2600 mg.

 

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

 

 

6        Pharmaceutical Particulars

 

6.         PHARMACEUTICAL PARTICULARS

 

6.1       List of Excipientsexcipients

 

Tablet Core:

Microcrystalline cellulose (E460)

Anhydrous lactose

Colloidal anhydrous silica

Stearic acid (E570)

 

Tablet Film Coating:

Hypromellose

Titanium dioxide (E171)

Synthetic yellow iron oxide (E172)

Synthetic red iron oxide (E172)

Macrogol

 

 

6.2       Incompatibilities

 

None known.

 

 

6.3       Shelf Lifelife

 

3 years.

 

 

6.4       Special Precautionsprecautions for Storagestorage

 

Store at in a refrigerator (2 °C - 8 °C.)

 

 

6.5       Nature and Contentscontents of Containercontainer

 

Chlorambucil are brown film-coated, round, biconvex tablets engraved “GX EG3” on one side and “L” on the other,are supplied in amber glass bottles with a child resistant closure containing 25 tablets.

 

 

6.6       InstructionsSpecial precautions for Use/Handlingdisposal

 

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

 

Safe handling of Chlorambucil Tablets:  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          Marketing Authorisation Holder

7.       MARKETING AUTHORISATION HOLDER

 

Aspen Pharma Trading Limited

12/13 Exchange Place,

I.F.S.C,

Dublin 1, Ireland

 

 

8          Marketing Authorization Number

 

 

8.       MARKETING AUTHORISATION NUMBER

 

PL  39699/ 0041

9          Date of First Authorisation/Renewal of the Authorisation

 

 

9.       DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

 

22.06.2006

 

10        Date of (Partial) Revision of the Text

 

 

10.            DATE OF REVISION OF THE TEXT

 

      November 2012

 

11.     LEGAL CATEGORY

 

POM

 

Reasons for adding or updating:

  • Change to section 1 - Name of the medicinal product
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:13-11-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Change Brand name from Leukeran to generic name chlorambucil
Change revision of text to 13-Nov-2012

Reasons for adding or updating:

  • Change to section 7 - Marketing Authorisation Holder
  • Change to section 8 - MARKETING AUTHORISATION NUMBER(S)
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:01-05-2012

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



7.         Marketing Authorisation Holder changed from ALKOPHARMA SARL, 45-47, rte d’Arlon, L – 1140 Luxembourg  to

Aspen Pharma Trading Limited, 12/13 Exchange Place, I.F.S.C, Dublin 1, Ireland

 

8.         Marketing Authorisation Number changed from PL 36637/0007 to PL 39699/ 0041

 

 

10.       Date of (Partial) Revision of Text changed from September 2010 to May 2012

Reasons for adding or updating:

  • New SPC for eMC ie an SPC for an existing product, but one that is new for the eMC

Date of revision of text on the SPC:01-01-0001

Legal Category:POM

Black Triangle (CHM): NO