Consumer medicine information

Mabcampath

Alemtuzumab

BRAND INFORMATION

Brand name

MabCampath

Active ingredient

Alemtuzumab

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Mabcampath.

SUMMARY CMI

Mabcampath

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I receiving Mabcampath?

Mabcampath contains the active ingredient alemtuzumab. Mabcampath is used to treat a form of leukaemia known as B cell chronic lymphocytic leukaemia (B-CLL). This is a cancer of the type of white blood cells called lymphocytes.

For more information, see Section 1. Why am I receiving Mabcampath? in the full CMI.

2. What should I know before I receive Mabcampath?

Do not use if you have ever had an allergic reaction to alemtuzumab, other murine proteins or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I receive Mabcampath? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Mabcampath and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I receive Mabcampath?

  • Mabcampath is given via infusion into the blood. Each time you are given Mabcampath it will take about 2 hours.
  • During the first week, 3 mg of Mabcampath is given on Day 1, then 10 mg on Day 2 and 30 mg on Day 3
  • Mabcampath will continue to be given at 30 mg doses on 3 alternate days each week

More instructions can be found in Section 4. How do I receive Mabcampath? in the full CMI.

5. What should I know while receiving Mabcampath?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are receiving Mabcampath.
  • If you are a fertile male or female of childbearing potential, ensure that you are using reliable birth control during treatment and for at least 6 months after treatment.
Driving or using machines
  • Be careful driving or operating machinery until you know how Mabcampath affects you
  • Confusion and sleepiness have been reported with this medicine
Looking after your medicine
  • Mabcampath will be stored by your doctor or pharmacist

For more information, see Section 5. What should I know while receiving Mabcampath? in the full CMI.

6. Are there any side effects?

Common side effects include bleeding or bruising more easily than normal, tiredness, headaches, weight loss, loss of appetite, fainting, dizziness, tremor, pins and needles, headache, nausea, vomiting, fever, aching muscles, diarrhoea, constipation.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Mabcampath

Active ingredient(s): alemtuzumab

Consumer Medicine Information (CMI)

This leaflet provides important information about using Mabcampath. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Mabcampath.

Where to find information in this leaflet:

1. Why am I receiving Mabcampath?
2. What should I know before I receive Mabcampath?
3. What if I am taking other medicines?
4. How do I receive Mabcampath?
5. What should I know while receiving Mabcampath?
6. Are there any side effects?
7. Product details

1. Why am I receiving Mabcampath?

Mabcampath contains the active ingredient alemtuzumab. Mabcampath is a monoclonal antibody that specifically recognises and binds to a unique protein located on the surface of abnormal lymphocytes.

Mabcampath is an anti-cancer drug used to treat a form of leukaemia known as B cell chronic lymphocytic leukaemia (B-CLL). This is a cancer of the type of white blood cells called lymphocytes.

Patients with B-CLL have too many abnormal lymphocytes, which displace healthy cells in the bone marrow (where most new blood cells are formed) in addition to the blood stream and other organs. Without enough healthy blood cells, infections, anaemia, bruising, excessive bleeding or organ failure can result.

2. What should I know before I receive Mabcampath?

Warnings

Do not use Mabcampath if:

  • you are allergic to to alemtuzumab or murine proteins, or any of the ingredients listed at the end of this leaflet.
  • Always check the ingredients to make sure you can use this medicine.

Check with your doctor if you:

  • have any other medical conditions including:
    - an active infection which is spread around the body
    - HIV
    - an active secondary cancer
    - heart disease or condition - your doctor will monitor you carefully as Mabcampath may make these conditions worse

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Do not receive treatment with Mabcampath if you are pregnant. It may affect your developing baby if you receive this medicine whilst pregnant. Ensure you are using reliable contraception during treatment and for 6 months after treatment.

If you become pregnant whilst receiving this medicine inform your doctor immediately.

Do not breastfeed if you are receiving Mabcampath. Do not begin to breastfeed until at least 4 weeks after you have finished your treatment with Mabcampath and have consulted your doctor. It is possible that your baby might be affected if you breastfeed.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with Mabcampath and affect how it works. These include

  • anti-cancer medicines. It is recommended that Mabcampath is not given within 3 weeks of other chemotherapeutic medicines
  • live viral vaccines. It is recommended that patients do not receive live viral vaccines for at least 12 months following Mabcampath therapy

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Mabcampath.

4. How do I receive Mabcampath?

How much is given and when

  • Mabcampath is given under the supervision of your doctor
  • It is given in the form of a solution directly into the bloodstream through a vein, known as an intravenous infusion
  • Each time you receive Mabcampath the infusion will take about 2 hours
  • During the first week, 3 mg of Mabcampath will be given on Day 1, then 10 mg on Day 2 and 30 mg on Day 3. Mabcampath will continue to be given at 30 mg doses on 3 alternate days each week
  • You may experience early side effects and the initial smaller doses may be repeated until the side effects go away or reduce. The aim is to increase the amounts of Mabcampath you receive slowly in order to reduce the possibility of side effects and to enable your body to tolerate the medicine better
  • Your doctor will carefully monitor you and decide how much to give you throughout your treatment with Mabcampath

How long is Mabcampath given for?

  • Mabcampath treatment may continue for up to 12 weeks, depending on your progress.

Mabcampath causes suppression of the immune system, which affects the natural ability of the body to fight infection for up to 6 months after treatment. Therefore, you may require antibiotics or antivirals to provide you with extra protection until your immune system has recovered.

If you receive too much Mabcampath

If you think that you have been given too much Mabcampath, you may need urgent medical attention.

Your doctor will treat you as required if you have any ill effects from having received too much Mabcampath.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26)

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while receiving Mabcampath?

Things you should do

Remind any doctor or dentist you visit that you are receiving Mabcampath.

If you are going to have surgery, tell the surgeon and/or anaesthetist that you are receiving this medicine.

If you are about to have any blood tests, tell your doctor that you are receiving this medicine.

Keep all of your doctor's appointments so that your progress can be checked.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Mabcampath affects you.

Mabcampath may cause confusion and sleepiness in some people.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • discharge with itching of the eyes and crusty eyelids
  • bleeding or bruising more easily than normal
  • tiredness, headaches, being short of breath when exercising, dizziness, looking pale
  • weight loss, loss of appetite
  • anxiety, confusion, depression, drowsiness, trouble sleeping, being unusually overactive
  • fainting, dizziness
  • tremor, pins and needles, decreased feeing or sensitivity, headache, taste loss
  • bluish discoloration of skin, flushing
  • abnormal heart beat (fast or slow)
  • difficulty in breathing, pressure, chest tightness, coughing,
  • nausea, vomiting, stomach pain, diarrhoea, indigestion, constipation, wind
  • rash (itchy or not), excessive sweating, redness of the skin
  • aching muscles, muscle tenderness or weakness (not caused by exercise), back pain, joint pain, chest pain
  • fever, chills, tiredness, unusual weakness
  • feeling of tension or fullness in the nose, cheeks and behind your eyes, sometimes with a throbbing ache, fever, stuffy nose and loss of the sense of smell
  • sore throat and discomfort when swallowing
  • symptoms of low calcium levels in the blood which includes muscle spasm or twitching, numbness or tingling in fingers and toes
  • depression, irritability, confusion, disorientation
  • dehydration or excessive thirst
  • blisters and/or ulcers in the mouth or genitalia
  • symptoms of pneumonia such as fever, chills, shortness of breath, cough and phlegm that may be blood stained
  • flu-like symptoms, such as high temperature, sore throat, runny nose, cough and chills
  • burning or pain upon urination, increased frequency to urinate
  • sore, creamy-yellow, raised patches in the mouth
  • itching, burning and a thick, white, “cottage cheese” discharge
  • unexplained weight gain, feeling cold, worsening tiredness, new constipation
  • weight loss, excessive sweating, intolerance to heat, increased bowel movements
Speak to your doctor if you have any of these less serious side effects and they worry you.
If you believe the side effect is of a more severe nature, tell your doctor as soon as possible.

Serious side effects

Serious side effectsWhat to do
  • vomitting blood or material that looks like coffee grounds, bleeding from the back passage, black sticky bowel motions (stools) or bloody diarrhoea
  • unusually swollen glands in the neck, armpit or groin
  • loss of hearing
  • loss of control of your bladder or bowel
  • sudden signs of allergy such as rash, itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing
  • signs of heart attack such as central crushing chest pain, aching sensation in your chest or arms that may spread to your neck, jaw or back, pain in left arm, increased sweating
  • signs of a stroke such as drooping of the skin on your face or sudden weakness or numbness on one side of the body or sudden difficulty with speech or your vision
  • signs of tumour lysis syndrome such as pain in one side of the body under the rib cage, little or no urine, drowsiness, nausea, vomiting, breathlessness, irregular heart beat, loss of memory, loss of consciousness
  • signs of haemophagocytic lymphohistiocytosis (excessive activation of white blood cells) such as fever, swollen glands, bruising, or skin rash. Haemophagocytic lymphohistiocytosis can be fatal if not diagnosed and treated early
  • signs of glomerulonephritis such as pink or cola-coloured urine, or foam in the urine, or noticeable swelling face, hands, feet and abdomen
  • signs of Guillain-Barre syndrome, which is a temporary inflammation of the nerves, causing pain, weakness, and paralysis in the extremities and often progressing up to the chest and face
  • signs of hepatitis (associated with a viral infection called Epstein-Barr Virus) including fatigue, flu-like symptoms, dark urine, pale stool, abdominal pain, loss of appetite, unexplained weight loss, yellow skin and eyes
  • abnormally fast or irregular heart beat
  • extreme difficulty breathing, shortness of breath, sharp chest pains which are worse when breathing in, frequent fainting
  • severe bleeding or bruising more than usual (e.g. persistent nose bleeds)
  • signs of intracranial haemorrhage such as severe headache, nausea, vomiting, alertness changes, problems with speech, balance, coordination or focusing of the eyes
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or nurse if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What Mabcampath contains

Active ingredient
(main ingredient)

alemtuzumab

Other ingredients
(inactive ingredients)

disodium edentate

phosphate buffered saline. This consists of polysorbate 80, potassium chloride, monobasic potassium phosphate, sodium chloride, dibasic sodium phosphate and water for injections

Do not take this medicine if you are allergic to any of these ingredients.

What Mabcampath looks like

Mabcampath is a colourless to slightly yellow concentrate. (AUST R 116622).

Mabcampath, when reconstituted, should be used immediately after dilution or within 8 hours after dilution, The solution should be stored between 15°C and 30°C or refrigerated. Preparation of the solution should occur under aseptic conditions and the solution should be protected from light.

Mabcampath contains no antimicrobial preservative.

Who distributes Mabcampath

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113
Freecall: 1800 818 806

This leaflet was prepared in January 2022.

mabcampath-ccdsv19-cmiv4-23dec21

Published by MIMS March 2022

BRAND INFORMATION

Brand name

MabCampath

Active ingredient

Alemtuzumab

Schedule

S4

 

1 Name of Medicine

Alemtuzumab (rch).

2 Qualitative and Quantitative Composition

Each vial contains 30 mg/mL alemtuzumab as a concentrated solution for infusion. See Section 6.1 List of Excipients.

3 Pharmaceutical Form

Alemtuzumab (rch) is a recombinant DNA-derived humanized monoclonal antibody directed against the 21-28 kD cell surface glycoprotein, CD52. Alemtuzumab (rch) is an IgG1 kappa antibody with human variable framework and constant regions, and complementarity-determining regions from a murine monoclonal antibody. The antibody has an approximate molecular weight of 150 kD. Alemtuzumab (rch) is produced in mammalian cell (Chinese hamster ovary) suspension culture in a nutrient medium.
Alemtuzumab (rch) is a sterile, clear, colourless to slightly yellow, injection concentrate. It is intended for dilution prior to infusion.

4 Clinical Particulars

4.1 Therapeutic Indications

MabCampath is indicated for the treatment of patients with B cell chronic lymphocytic leukaemia (B - CLL).

4.2 Dose and Method of Administration

General considerations.

MabCampath should be administered under the supervision of a physician experienced in the use of cancer therapy.
Medications for the treatment of hypersensitivity reactions as well as preparedness for institution of emergency measures is necessary.
MabCampath solution must be prepared according to the instructions provided under 'Instructions for reconstitution, handling and disposal'. All doses should be administered by intravenous infusion over approximately 2 hours.
Patients should be premedicated with an appropriate antihistamine and analgesic prior to the first dose at each escalation and prior to subsequent infusions, as clinically indicated (see Section 4.4 Special Warnings and Precautions for Use).
Antibiotics and antivirals should be administered routinely to all patients throughout and following treatment (see Section 4.4 Special Warnings and Precautions for Use).

Dose.

During the first week of treatment, MabCampath should be administered in escalating doses: 3 mg on day 1, 10 mg on day 2 and 30 mg on day 3 assuming that each dose is well tolerated. Thereafter, the recommended dose is 30 mg daily administered 3 times weekly on alternate days up to a maximum of 12 weeks.
In most patients, dose escalation to 30 mg can be accomplished in 3-7 days. However, if acute moderate to severe adverse reactions due to cytokine release (hypotension, rigors, fever, shortness of breath, chills, rashes and bronchospasm) occur at either the 3 mg or 10 mg dose levels, then those doses should be repeated daily until they are well tolerated before further dose escalation is attempted (see Section 4.4 Special Warnings and Precautions for Use).
Median duration of treatment was 11.7 weeks for first line patients and 9.0 weeks for previously treated patients. Once a patient meets all laboratory and clinical criteria for a complete response, MabCampath should be discontinued and the patient monitored. If a patient improves (i.e. achieves a partial response or stable disease) and then reaches a plateau without further improvement for 4 weeks or more, then MabCampath should be discontinued and the patient monitored. Therapy should be discontinued if there is evidence of disease progression.
In the event of serious infection or severe haematological toxicity, MabCampath should be interrupted until the event resolves. It is recommended that MabCampath should be interrupted in patients whose platelet count falls to < 25,000/microL or whose absolute neutrophil count (ANC) drops to < 250/microL. MabCampath may be reinstituted after the infection or toxicity has resolved. MabCampath should be permanently discontinued if autoimmune anaemia or autoimmune thrombocytopenia appears. Table 1 outlines the recommended procedure for dose modification following the occurrence of haematological toxicity while on therapy.
There are no dose modifications recommended for severe lymphopenia given the mechanism of action of MabCampath.

Instructions for reconstitution, handling and disposal.

 The vial contents should be inspected for particulate matter and discolouration prior to administration. If particulate matter is present or the concentrate is coloured, then the vial must not be used.
MabCampath contains no antimicrobial preservatives, therefore, it is recommended that it should be prepared using aseptic techniques and that the diluted solution for infusion should be administered within 8 hours after preparation. The required amount of the vial contents should be added to 100 mL of 0.9% sodium chloride solution or 5% glucose solution. The bag should be inverted gently to mix the solution.
This medicinal product should not be reconstituted with solvents other than those mentioned above.
There are no known incompatibilities with other medicinal products. However, other medicinal products should not be added to the MabCampath infusion solution or simultaneously infused though the same intravenous line.
Women who are pregnant or planning pregnancy should not handle MabCampath.
Caution should be exercised in the handling and preparation of the MabCampath solution. The use of latex gloves and safety glasses is recommended to avoid exposure in case of breakage of the vial or other accidental spillage.
Procedures for proper handling and disposal should be observed. Any spillage or waste material should be disposed of by incineration.

Patients with renal impairment.

No studies have been conducted in patients with renal impairment.

Patients with hepatic impairment.

No studies have been conducted in patients with hepatic impairment.

Elderly patients (over 65 years of age).

Recommendations are as stated above for adults. Patients should be monitored carefully (see Section 4.4 Special Warnings and Precautions for Use).

4.3 Contraindications

MabCampath is contraindicated in:
Hypersensitivity or anaphylactic reactions to alemtuzumab, to murine proteins or to any of the excipients.
In patients with active systemic infections.
In patients infected with HIV.
In patients with active secondary malignancies.
Pregnancy.
Breastfeeding.

4.4 Special Warnings and Precautions for Use

Infusion related reactions.

MabCampath can result in serious and, in some instances, fatal, infusion reactions. Patients should be carefully monitored during infusions and MabCampath discontinued if indicated. Gradual escalation to the recommended maintenance dose is required at the initiation of therapy and after interruption of therapy for 7 or more days (see Section 4.2 Dose and Method of Administration).
Patients may have allergic or hypersensitivity reactions to MabCampath and to murine or chimeric monoclonal antibodies (see Section 4.3 Contraindications). If any of these occur medications for the treatment of hypersensitivity reactions as well as preparedness for institution of emergency measures is necessary.
Acute adverse reactions, which may occur during initial dose escalation due to the release of cytokines, include hypotension, chills/ rigors, fever, shortness of breath and rashes. Additional reactions include nausea, urticaria, vomiting, fatigue, dyspnoea, headache, pruritus, diarrhoea and bronchospasm. The frequency of acute infusion related reactions was highest in the first week of therapy and declined in the second or third week of treatment in patients treated with MabCampath both as first line therapy and in previously treated patients. Grade 3 or 4 (according to Common Terminology Criteria for Adverse Events-CTCAE) infusion related reactions are uncommon after the first week of therapy.
If these events are moderate to severe, then dosing should continue at the same level prior to each dose escalation, with appropriate premedication, until each dose is well tolerated. If therapy is withheld for more than 7 days, MabCampath should be reinstituted with gradual dose escalation.
It is recommended that patients be premedicated with oral or intravenous steroids 30-60 minutes prior to each MabCampath infusion during dose escalation and as clinically indicated. Steroids may be discontinued as appropriate once dose escalation has been achieved. In addition, an oral antihistamine, e.g. diphenhydramine 50 mg, and an analgesic, e.g. paracetamol 500 mg, may be given. In the event that acute infusion reactions persist, the infusion time may be extended up to 8 hours from the time of reconstitution of MabCampath in solution for infusion.
Transient hypotension has occurred in patients receiving MabCampath. Careful monitoring of blood pressure and hypotensive symptoms is recommended especially in patients with ischaemic heart disease, angina and/or in patients receiving antihypertensive medication. Myocardial infarction and cardiac arrest have been observed in association with MabCampath infusion in this patient population.
Assessment and ongoing monitoring of cardiac function (e.g. echocardiography, heart rate and body weight) should be considered in patients previously treated with potentially cardiotoxic agents.
Therapy should be discontinued if there is evidence of disease progression (see Section 4.2 Dose and Method of Administration).

Immunosuppression.

Profound lymphocyte depletion, an expected pharmacological effect of MabCampath, inevitably occurs and may be prolonged. CD4 and CD8 T cell counts begin to rise from weeks 8-12 during treatment and continue to recover for several months following the discontinuation of treatment. In patients receiving MabCampath as first line therapy, the median time to recovery of CD4+ counts to ≥ 200 cells/microL occurred by 6 months post-treatment, however, at 2 months post-treatment the median was 183 cells/microL. In previously treated patients receiving MabCampath, the median time to reach a level of 200 cells/microL is 2 months following last infusion with MabCampath but may take more than 12 months to approximate pretreatment levels. This may predispose patients to opportunistic infections.
Serious, sometimes fatal bacterial, viral, fungal and protozoan infections have been reported in patients receiving MabCampath therapy. Prophylaxis directed against Pneumocystis jirovecii pneumonia and herpes virus infections has been shown to decrease, but not to eliminate, the occurrence of these infections.
It is highly recommended that anti-infective prophylaxis (e.g. (trimethoprim/ sulfamethoxazole 1 tablet twice daily, 3 times weekly or other prophylaxis against Pneumocystis jirovecii pneumonia (PCP) and an effective oral antiherpes agent, such as famciclovir 500 mg twice daily) should be initiated while on therapy and for a minimum of 2 months following completion of treatment with MabCampath or until the CD4+ count has recovered to 200 cells/microL or greater, whichever is the later.
Because of the potential of transfusion associated graft versus host disease (TAGVHD), it is recommended that patients who have been treated with MabCampath should receive irradiated blood products.
Asymptomatic laboratory positive cytomegalovirus (CMV) should not necessarily be considered a serious infection requiring interruption of therapy. Ongoing clinical assessment should be performed for symptomatic CMV infection during MabCampath treatment and for at least 2 months following completion of treatment.
Epstein-Barr virus (EBV) infection, including severe and sometimes fatal EBV associated hepatitis, has been reported in MabCampath-treated patients.

Haemophagocytic lymphohistiocytosis (HLH).

During post-marketing use, HLH has been reported in patients treated with MabCampath. HLH is a life-threatening syndrome of pathologic immune activation characterized by clinical signs and symptoms of extreme systemic inflammation. It is associated with high mortality rates if not recognized early and treated. Symptoms have been reported to occur within a few months following the initiation of treatment, commonly observed in association with infections. Patients who develop early manifestations of pathologic immune activation should be evaluated immediately, and a diagnosis of HLH should be considered.

Haematological toxicity.

Serious and in rare instances fatal, pancytopenia, autoimmune idiopathic thrombocytopenia and autoimmune haemolytic anaemia have occurred in patients receiving MabCampath. Single doses of MabCampath greater than 30 mg or cumulative doses greater than 90 mg per week should not be administered because these doses are associated with a higher incidence of pancytopenia.
Transient grade 3 or 4 neutropenia occurs very commonly by weeks 5-8 following initiation of treatment. Transient grade 3 or 4 thrombocytopenia occurs very commonly during the first 2 weeks of therapy and then begins to improve in most patients. Therefore, haematological monitoring of patients is indicated. If a severe haematological toxicity develops, MabCampath treatment should be interrupted until the event resolves. MabCampath treatment may be reinstituted following resolution of the haematological toxicity (see Section 4.2 Dose and Method of Administration). MabCampath should be permanently discontinued if autoimmune anaemia or autoimmune thrombocytopenia appears.
Complete blood counts and platelet counts should be obtained at regular intervals during MabCampath therapy and more frequently in patients who develop cytopenias.

CD52 expression.

It is not proposed that regular and systematic monitoring of CD52 expression should be carried out as routine clinical practice. However, if retreatment is considered, it may be prudent to confirm the presence of CD52 expression. In data available from patients in both treatment arms of the first line study, loss of CD52 expression was not observed around the time of progression or death.

Use in hepatic impairment.

No studies have been conducted in patients with hepatic impairment.

Use in renal impairment.

No studies have been conducted in patients with renal impairment.

Use in the elderly.

No studies have been conducted which specifically address the effect of age on MabCampath disposition and toxicity. In general, older patients (over 65 years of age) tolerate cytotoxic therapy less well than younger individuals. Since CLL occurs commonly in this older age group, these patients should be monitored carefully (see Section 4.2 Dose and Method of Administration). In the studies in first line and previously treated patients no substantial differences in safety and efficacy related to age were observed; however the sizes of the databases are limited.

Paediatric use.

No studies have been conducted to investigate the safety and efficacy of MabCampath in children.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No formal drug interaction studies have been performed with MabCampath. There are no known clinically significant interactions of MabCampath with other medicinal products. However, it is recommended that MabCampath should not be given within 3 weeks of other chemotherapeutic agents.
Although it has not been studied, it is recommended that patients should not receive live viral vaccines in at least the 12 months following MabCampath therapy. The ability to generate a primary or anamnestic humoral response to any vaccine has not been studied.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

The potential effects on fertility have not been investigated in animal studies. CD52 is expressed on sperm and epithelial cells of the epididymis and seminal vesicle. It is not known whether MabCampath can affect the reproductive capacity of men or women.
(Category B2)
MabCampath is contraindicated during pregnancy. Human IgG is known to cross the placental barrier; MabCampath is likely to cross the placental barrier as well and thus potentially cause foetal B and T cell lymphocyte depletion. Animal reproduction studies have not been conducted with MabCampath. Males and females of childbearing potential should use effective contraceptive measures during treatment and for 6 months following MabCampath therapy (see Section 4.6 Fertility, Pregnancy and Lactation).
 MabCampath is contraindicated during breastfeeding. It is not known whether MabCampath is excreted in human milk. Breastfeeding should be discontinued during treatment and for at least 4 weeks following MabCampath therapy. No studies have been performed in lactating animals.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects on the ability to drive and use machines have been performed. However, caution should be exercised as confusion and somnolence have been reported.

4.8 Adverse Effects (Undesirable Effects)

The frequencies of the adverse reactions by system organ classes and in descending order of severity in Tables 2 and 3, are based on clinical trial data.

Undesirable effects in previously treated patients.

Safety data in previously treated B-CLL patients are based on 149 patients enrolled in single arm studies of MabCampath (studies 1, 2 and 3). More than 80% of previously treated patients may be expected to experience adverse reactions; the most commonly reported reactions usually occur during the first week of therapy.

Undesirable effects in first line patients.

Safety data in first line - B-CLL patients are based on 147 patients enrolled in a randomised, controlled study of MabCampath as a single agent administered at a dose of 30 mg intravenously three times weekly for up to 12 weeks, inclusive of dose escalation period. Approximately 97% of first line patients experienced adverse reactions; the most commonly reported reactions in first line patients usually occurred during the first week of therapy.
Acute infusion reactions including fever, chills, nausea, vomiting, hypotension, fatigue, rash, urticaria, dyspnoea, headache, pruritus and diarrhoea have been reported. The majority of these reactions are mild to moderate in severity. Acute infusion reactions usually occur during the first week of therapy and substantially decline thereafter. Grade 3 or 4 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 3.0) infusion reactions are uncommon after the first week of therapy.

Post marketing data.

The reactions presented in this section were identified mainly from post marketing experience in previously treated patients. As these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to MabCampath exposure. Decisions to include these reactions in labelling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) reported frequency of the reaction, or (3) strength of causal connection to MabCampath. Events previously identified in clinical studies are not listed in this section.

Blood and lymphatic system disorders.

Severe bleeding reactions have been reported.

Cardiac disorders.

Cardiomyopathy, congestive heart failure and decreased ejection fraction have been reported in patients previously treated with potentially cardiotoxic agents.

Hepatobiliary disorders.

Hepatitis (associated with EBV infection) has been reported.

Immune system disorders.

Serious and sometimes fatal autoimmune phenomena including autoimmune haemolytic anaemia, autoimmune thrombocytopenia, aplastic anaemia, Graves' disease, Guillian-Barré syndrome and its chronic form, chronic inflammatory demyelinating polyradiculoneuropathy, serum sickness have been reported. A positive Coombs' test has also been observed. Fatal transfusion associated graft versus host disease has also been reported. Haemophagocytic lymphohistiocytosis (HLH).

Infusion reactions.

Serious and sometimes fatal reactions including bronchospasm, hypoxia, syncope, pulmonary infiltrates, ARDS, respiratory arrest, myocardial infarction, arrhythmias, acute cardiac insufficiency and cardiac arrest have been observed. Severe anaphylactic and other hypersensitivity reactions, including anaphylactic shock and angioedema, have been reported following MabCampath administration. These symptoms can be ameliorated or avoided if premedication and dose escalation are utilised (see Section 4.4 Special Warnings and Precautions for Use; Section 4.2 Dose and Method of Administration).

Infections and infestations.

Serious and sometimes fatal viral (e.g. adenovirus, parainfluenza, hepatitis B, progressive multifocal leukoencephalopathy [PML], bacterial (including tuberculosis and atypical mycobacteriosis, nocardiosis), protozoan (e.g. Toxoplasma gondii) and fungal (e.g. rhinocerebral mucormycosis) infections, including those due to reactivation of latent infections, have been observed during post marketing surveillance. The recommended anti-infective prophylaxis appears to be effective in reducing the risk of Pneumocystis jirovecii pneumonia (PCP) and herpes infections (see Section 4.4 Special Warnings and Precautions for Use). Epstein Barr virus (EBV) infection and Epstein Barr virus (EBV)-associated lymphoproliferative disorder has been reported.

Metabolism and nutrition disorders.

Tumour lysis syndrome with fatal outcome has been reported.

Nervous system disorders.

Intracranial haemorrhage has occurred with fatal outcome in patients with thrombocytopenia. Stroke, including haemorrhagic and ischaemic stroke.

Renal and urinary disorders.

Glomerulonephritis.

Post marketing experience with Lemtrada.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to alemtuzumab exposure.
The following adverse reactions were identified during post-approval use of alemtuzumab for the treatment of relapsing forms of multiple sclerosis (MS):

Nervous system disorders.

Stroke, including haemorrhagic and ischaemic stroke, cervicocephalic arterial dissection, and autoimmune encephalitis.

Endocrine disorders.

Hypothyroidism, hyperthyroidism, and thyroiditis.
Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

Patients have received repeated unit doses of up to 240 mg of MabCampath. The frequency of grade 3 or 4 adverse events, such as fever, hypotension and anaemia, may be higher in these patients. There is no known specific antidote for MabCampath. Treatment consists of discontinuation of MabCampath and supportive therapy.
For information on the management of overdose, contact the Poisons Information Centre, on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Alemtuzumab is a genetically engineered humanised IgG1 kappa monoclonal antibody specific for a 21-28 kD lymphocyte cell surface glycoprotein (CD52) antigen. It was generated by the insertion of six complementary determining regions from an IgG2a rat monoclonal antibody into a human IgG1 immunoglobulin molecule.
Alemtuzumab causes the lysis of lymphocytes by binding to CD52 antigen, which is expressed on the surface of essentially all B and T lymphocytes (benign and malignant) as well as monocytes, thymocytes and macrophages, sperm and epithelial cells of epididymis and seminal vesicle. The antigen has also been found on a small percentage (< 5%) of granulocytes, but not on erythrocytes or platelets.
The antibody mediates the lysis of lymphocytes via complement fixation and antibody dependent cell mediated cytotoxicity. Alemtuzumab does not appear to damage haematopoietic stem cells or progenitor cells.

Clinical trials.

Previously treated B-CLL patients.

Determination of the efficacy of MabCampath is based on overall response and survival rates. Data available from three uncontrolled B-CLL studies are summarised in Table 4.

First line B-CLL patients.

The safety and efficacy of MabCampath were evaluated in a phase 3, open label, randomised comparative trial of first line (previously untreated) Rai stage I-IV B-CLL patients requiring therapy (study 4). MabCampath was shown to be superior to chlorambucil as measured by the primary endpoint progression free survival (PFS) (see Figure 1).
The secondary objectives included complete response (CR) and overall response (CR or partial response (PR)) rates using the 1996 NCIWG criteria, the duration of response, time to alternative treatment and safety of the two treatment arms. See Table 5.
There are no data on the safety and efficacy of retreatment with alemtuzumab in patients who received the drug as first line therapy.

Cytogenetic analyses in first line B-CLL patients.

The cytogenetic profile of B-CLL has been increasingly recognised as providing important prognostic information and may predict response to certain therapies. Of the first line patients (n = 282) in whom baseline cytogenetic (FISH) data were available in study 4, chromosomal aberrations were detected in 82%, while normal karyotype was detected in 18%. Chromosomal aberrations were categorized according to Dohner's hierarchical model. In first line patients, treated with either MabCampath or chlorambucil, there were 21 patients with the 17p deletion, 54 patients with 11q deletion, 34 patients with trisomy 12, 51 patients with normal karyotype and 67 patients with sole 13q deletion.
Overall response rate (ORR) was superior in patients with any 11q deletion (87% v 29%; p < 0.0001) or sole deletion 13q (91% v 62%; p = 0.0087) treated with MabCampath compared to chlorambucil. A trend toward improved ORR was observed in patients with 17p deletion treated with MabCampath (64% v 20%; p = 0.0805). Complete remissions were also superior in patients with sole 13q deletion treated with MabCampath (27% v 0%; p = 0.0009). Median PFS was superior in patients with sole 13q deletion treated with MabCampath (24.4 v 13.0 months; p = 0.0170 stratified by Rai stage). A trend towards improved PFS was observed in patients with 17p deletion, trisomy 12 and normal karyotype, which did not reach significance due to small sample size.

Assessment of cytomegalovirus (CMV) by PCR.

In the randomised controlled trial in first line patients (study 4), patients in the MabCampath arm were tested weekly for CMV using a PCR (polymerase chain reaction) assay from initiation through completion of therapy, and every 2 weeks for the first 2 months following therapy. In this study, asymptomatic positive PCR only for CMV was reported in 77/147 (52.4%) of MabCampath treated patients; symptomatic CMV infection was reported less commonly in 23/147 MabCampath treated patients (16%). In the MabCampath arm 36/77 (46.8%) of patients with asymptomatic PCR positive CMV received antiviral therapy and 47/77 (61%) of these patients had MabCampath therapy interrupted. The presence of asymptomatic positive PCR for CMV or symptomatic PCR positive CMV infection during treatment with MabCampath had no measurable impact on progression free survival (PFS).

5.2 Pharmacokinetic Properties

Pharmacokinetics were characterised in alemtuzumab naive patients with B cell chronic lymphocytic leukaemia (B-CLL) who had failed previous therapy with purine analogues. Alemtuzumab was administered as a 2 hour intravenous infusion at the recommended dosing schedule, starting at 3 mg and increasing to 30 mg, 3 times weekly for up to 12 weeks. Alemtuzumab pharmacokinetics followed a 2 compartment model and displayed nonlinear elimination kinetics. After the last 30 mg dose, the median volume of distribution at steady state was 0.15 L/kg (range: 0.1-0.4 L/kg), indicating that distribution was primarily to the extracellular fluid and plasma compartments. Systemic clearance decreased with repeated administration due to decreased receptor mediated clearance (i.e. loss of CD52 receptors in the periphery). With repeated administration and consequent plasma concentration accumulation, the rate of elimination approached zero order kinetics. As such, half-life was 8 hours (range 2-32 hours) after the first 30 mg dose and was 6 days (range 1-14 days) after the last 30 mg dose. Steady-state concentrations were reached after about 6 weeks of dosing. No apparent difference in pharmacokinetics between males and females was observed nor was any apparent age effect observed.

5.3 Preclinical Safety Data

Genotoxicity.

No in vitro or animal studies have been conducted with MabCampath to assess the mutagenic potential.

Carcinogenicity.

No in vitro or animal studies have been conducted with MabCampath to assess the carcinogenic potential.

6 Pharmaceutical Particulars

6.1 List of Excipients

0.0187 mg disodium edetate, 0.1 mg polysorbate 80, 0.2 mg potassium chloride, 0.2 mg monobasic potassium phosphate, 8 mg sodium chloride, 1.15 mg dibasic sodium phosphate heptahydrate, and water for injections.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

MabCampath vials should be stored at 2 - 8°C (in a refrigerator).
Do not freeze. Protect from light.

Reconstituted solution.

MabCampath contains no antimicrobial preservative. To reduce microbiological hazard, use as soon as practicable after reconstitution/ preparation. If storage is necessary, hold at 2°C to 8°C for not more than 8 hours. This can only be accepted if preparation of the solution takes place under strictly aseptic conditions and the solution is protected from light.

6.5 Nature and Contents of Container

Vials of 2 mL, clear, glass type I, containing 1 mL colourless to slightly yellow concentrate.
Pack size: 3 vials.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

The alemtuzumab molecule consists of two ~ 24 kD small polypeptide chains (light chains, 214 amino acids) and two larger ~ 49 kD polypeptide chains (heavy chains, 450 amino acids) linked together by two inter (light chain - heavy chain) disulphide bridges and two inter (heavy chain - heavy chain) disulphide bridges to form a Y-shaped molecule, typical for immunoglobulins of the IgG1 subclass.
Each molecule also contains a total of 12 intrachain disulphide bridges and an asparagine residue (301) in each heavy chain which is glycosylated.
The structure is provided below:

CAS number.

Not applicable.

7 Medicine Schedule (Poisons Standard)

Schedule 4 (Prescription Only Medicine).

Summary Table of Changes