Lomustine Capsule 40mg Taj Pharma

1. Name of the medicinal product

Lomustine Capsule 10mg Taj Pharma
Lomustine Capsule 40mg Taj Pharma
Lomustine Capsule 100mg Taj Pharma

2. Qualitative and quantitative composition

a) Lomustine Capsule 10mg Taj Pharma
Each Hard-gelatin capsule contains:
Lomustine 10mg
Excipients: q.s.
Colours: Approved colours used in capsule shells

b) Lomustine Capsule 40mg Taj Pharma
Each Hard-gelatin capsule contains:
Lomustine 40mg
Excipients: q.s.
Colours: Approved colours used in capsule shells

c) Lomustine Capsule 100mg Taj Pharma
Each Hard-gelatin capsule contains:
Lomustine 100mg
Excipient: q.s.
Colours: Approved colours used in capsule shells

For the full list of excipients, see section 6.1

3. Pharmaceutical form

Hard-gelatin capsule.

4. Clinical particulars

4.1 Therapeutic indications

As palliative or supplementary treatment, usually in combination with radiotherapy and/or surgery as part of multiple drug regimens in:

• brain tumours (primary or metastatic)
• lung tumours (especially oat-cell carcinoma)

Hodgkin’s disease (resistant to conventional combination chemotherapy)

• malignant melanoma (metastatic)

Lomustine Taj Pharma may also be of value as second-line treatment in Non-Hodgkin’s lymphoma, myelomatosis, gastrointestinal tumours, carcinoma of the kidney, the testis, the ovary, the cervix uteri and the breast.

4.2 Posology and method of administration

Posology

Adults

Lomustine Taj Pharma is given by mouth. The recommended dose in patients with normally functioning bone marrow receiving Lomustine Taj Pharma as their only chemotherapy is 120 – 130mg/m² as a single dose every six to eight weeks (or as a divided dose over 3 days, e.g. 40mg/m²/day).

Dosage is reduced

• if Lomustine Taj Pharma is given as part of a drug regimen which includes other marrow-depressant medicinal products.
• in the presence of leucopenia below 3,000/mm³ or thrombocytopenia below 75,000/mm³.

Marrow depression after Lomustine Taj Pharma is sustained longer than after nitrogen mustards and recovery of white cell and platelet counts may not occur for six weeks or more. Blood elements depressed below the above levels should be allowed to recover to 4,000/mm³ (WBC) and 100,000/mm³ (platelets) before repeating Lomustine Taj Pharma dosage.

Paediatric population

Until further data is available, administration of Lomustine Taj Pharma to children with malignancies other than brain tumours should be restricted to specialised centres and exceptional situations. Dosage in children, like that in adults, is based on body surface area (120 – 130mg/m² every six to eight weeks, with the same qualifications as apply to adults).

Method of administration

Lomustine Taj Pharma is given by mouth.

4.3 Contraindications

Lomustine Taj Pharma can cause birth defects. Men and women are recommended to take contraceptive precautions during therapy with Lomustine Taj Pharma and for 6 months after treatment. Men should be informed about the risk for an irreversible infertility due to treatment with Lomustine Taj Pharma (see section 4.6).

Lomustine Taj Pharma should not be administered to patients who are pregnant or to mothers who are breastfeeding.

Other contraindications are:

– Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1;

– Previous hypersensitivity to nitrosoureas;

– Previous failure of the tumour to respond to other nitrosoureas;

– Severe bone marrow depression;

– Severe renal impairment;

– Coeliac disease or wheat allergy;

– Concomitant use of yellow fever vaccine or other live vaccines is contraindicated in immunosuppressed patients (see section 4.5).

4.4 Special warnings and precautions for use

Patients receiving Lomustine Taj Pharma chemotherapy should be under the care of doctors experienced in cancer treatment. Delayed bone marrow suppression, notably thrombocytopenia and leukopenia, which may contribute to bleeding and overwhelming infections in an already compromised patient, is the most common and severe of the toxic effects of Lomustine Taj Pharma.

Therefore, blood counts should be carried out before starting the medicinal product and at frequent intervals (preferably weekly for at least 6 weeks after a dose; see section 4.8) during treatment. Treatment and dosage is governed principally by the haemoglobin, white cell count and platelet count. Liver and kidney function should also be assessed periodically.

Patients must be strictly instructed not to use higher doses of Lomustine Taj Pharma than recommended by a physician and should be told that Lomustine Taj Pharma is taken as a single oral dose and will not be repeated for at least 6 weeks.

The bone marrow toxicity of Lomustine Taj Pharma is cumulative and therefore dose adjustments must be considered on the basis of nadir blood counts from prior dose.

Caution should be used in administering Lomustine Taj Pharma to patients with decreased circulating platelets, leukocytes, or erythrocytes.

Pulmonary toxicity from Lomustine Taj Pharma appears to be dose-related (see section 4.8). Baseline pulmonary function studies should be conducted along with frequent pulmonary function tests during treatment. Patients with a baseline below 70 % of the predicted Forced Vital Capacity (FVC) or Carbon Monoxide Diffusing Capacity (DLco) are particularly at risk.

Since Lomustine Taj Pharma may cause liver dysfunction, it is recommended that liver function tests be monitored periodically (see section 4.8).

Renal function tests should also be monitored periodically (see section 4.8).

Long term use of nitrosoureas has been reported to be possibly associated with the development of secondary malignancies.

Care must be taken whenever handling anticancer products. Steps should be taken to avoid exposure. This includes appropriate equipment, such as wearing gloves, and washing hands with soap and water after handling such products.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

Lomustine Taj Pharma use in combination with theophylline or with the H₂ receptor antagonist cimetidine may potentiate bone marrow toxicity. Cross-resistance with other nitrosoureas is usual, but cross-resistance with conventional alkylating agents is unusual.

Pretreatment with phenobarbital can lead to a reduced antitumour effect of Lomustine Taj Pharma due to an accelerated elimination caused by induction of microsomal liver enzymes.

There is increased risk of fatal systemic vaccinal disease with the use of yellow fever vaccine. Live vaccines are contraindicated in immunosuppressed patients (see section 4.3)

Co-administration of antiepileptic medicinal products and chemotherapeutic medicinal products including Lomustine Taj Pharma can lead to complications secondary to pharmacokinetic interaction between the medicinal products.

4.6 Fertility, pregnancy and lactation

Pregnancy

Lomustine Taj Pharma is contraindicated during pregnancy (see section 4.3). Safe use in pregnancy has not been established. Animal studies have shown reproductive toxicity (see section 5.3). If this medicinal product is used during pregnancy, or if the patient becomes pregnant while taking (receiving) this medicinal product, the patient should be apprised of the potential hazard to the foetus. Women of childbearing potential should be advised to avoid becoming pregnant.

Breastfeeding

Lomustine Taj Pharma is contraindicated during breastfeeding (see section 4.3). Due to the lipophilic nature of Lomustine Taj Pharma, it is likely to be excreted in human milk. As a risk to the nursing child potentially exists, a decision must be made whether to discontinue breastfeeding or to discontinue/abstain from Lomustine Taj Pharma therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

Fertility

Lomustine Taj Pharma can have a mutagenic effect. Men treated with Lomustine Taj Pharma are therefore advised not to father children during treatment and for up to 6 months afterwards, and to seek advice regarding sperm conservation before the start of treatment given the possibility of irreversible infertility caused by Lomustine Taj Pharma therapy.

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.

Lomustine Taj Pharma capsules can impair the ability to drive and use machines, e.g. because of nausea and vomiting.

4.8 Undesirable effects

The list is presented by system organ class and frequency

• Very common (≥1/10)
• Common (≥1/100 to <1/10)
• Uncommon (≥1/1,000 to <1/100)
• Rare (≥1/10,000 to <1/1,000)
• Very rare (<1/10,000)
• Not known (cannot be estimated from the available data).

Blood and lymphatic system disorders

The principal adverse effect is marrow toxicity of a delayed or prolonged nature. It usually occurs four to six weeks after administration of the medicinal product and is dose-related. Thrombocytopenia appears about four weeks after a dose of Lomustine Taj Pharma and lasts one or two weeks at a level around 80 – 100,000/mm³. Leucopenia appears after five to six weeks and persists for one or two weeks at about 4 – 5,000/mm³.

The haematological toxicity may be cumulative, leading to successively lower white cell and platelet counts with successive doses of the medicinal product. Approximately 65 % of patients receiving 130mg/m² develop white blood cell counts below 5,000 WBC/mm³. Thirty-six percent developed white blood cell counts below 3,000/mm³. Thrombocytopenia is generally more severe than leukopenia. However, both may be dose-limiting toxicities.

The occurrence of acute leukaemia and bone marrow dysplasia have been reported in patients following long-term nitrosourea therapy.

Anaemia also occurs, but is less frequent and less severe than thrombocytopenia or leukopenia.

Gastrointestinal disorders

Nausea and vomiting usually occur four to six hours after a full single dose of Lomustine Taj Pharma and last for 24 – 48 hours, followed by anorexia for two or three days. The effects are less troublesome if the 6-weekly dose is divided into three doses given on each of the first three days of the six week period. Gastrointestinal tolerance is usually good, however, if prophylactic antiemetics are given (e.g. metoclopramide or chlorpromazine). Disorders of liver function have been reported commonly. They are mild in most cases. In rare cases a cholestatic jaundice occurs. Transient elevation of liver enzymes (SGOT, SGPT, LDH or alkaline phosphatase) are occasionally observed.

More rarely patients are troubled by stomatitis and diarrhoea.

Nervous system disorders

Mild neurological symptoms, like e.g. apathy, disorientation, confusion and stuttering can occur uncommonly in combination therapy with other antineoplastic medicinal products or radiation.

Respiratory, thoracic and mediastinal disorders

Interstitial pneumonia or lung fibrosis have been reported rarely.

Renal and urinary disorders

Renal failure, decrease in kidney size, and progressive azotaemia have been reported in single cases after prolonged treatment with Lomustine Taj Pharma and related nitrosoureas reaching a high cumulative total dose. Therefore it is recommended not to exceed a maximum cumulative total Lomustine Taj Pharma dose of 1,000mg/m².

Kidney damage has also been reported occasionally in patients receiving lower total doses.

Other side effects

Loss of scalp hair has been reported rarely.

In single cases an irreversible vision loss has been reported after a combined therapy of Lomustine Taj Pharma with radiation.

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

Accidental overdose with Lomustine Taj Pharma has been reported, including fatal cases. Symptoms of overdose with Lomustine Taj Pharma will probably include bone marrow toxicity, haematological toxicity, abdominal pain, nausea and vomiting, diarrhoea, anorexia, lethargy, dizziness, abnormal hepatic function, cough, and shortness of breath.

Emergency procedures

Overdose should be treated immediately by gastric lavage.

Antidote

There is no specific antidote to overdose with Lomustine Taj Pharma. Treatment should be symptomatic and supportive. Appropriate blood product replacement should be given as clinically required.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: cytostatics, alkylating agents.

The mode of action is believed to be partly as an alkylating agent and partly by inhibition of several steps in the synthesis of nucleic acid and inhibition of the repair of single strand breaks in DNA chains.

5.2 Pharmacokinetic properties

Lomustine Taj Pharma is readily absorbed from the intestinal tract. A maximum plasma concentration of 0.5 – 2 ng/ml is reached after 3 hours following an oral dose of 30 – 100mg/m².

The plasma disappearance of the chloroethyl-group follows by a single phased course with a half-life of 72 hours. The cyclohexyl-group disappears according to a twofold plasma disappearance with half-lives of 4 hours (t ½ α) and 50 hours (t ½ β). After oral application of radioactive marked Lomustine Taj Pharma the blood-brain-barrier is passed. Approximately 15 to 30 % of the measured radioactivity in the plasma can be detected in the cerebrospinal fluid.

Lomustine Taj Pharma is rapidly metabolised and metabolites are excreted mainly via the kidneys. Lomustine Taj Pharma cannot be detected in its active form in the urine at any time.

5.3 Preclinical safety data

Lomustine Taj Pharma is embryotoxic and teratogenic in rats and embryotoxic in rabbits at dose levels equivalent to the human dose.

6. Pharmaceutical particulars

6.1 List of excipients

Lactose, Wheat Starch, Talc, Magnesium Stearate, Gelatine, Indigo carmine and Titanium Dioxide

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Do not store above 25 °C.

Store in the original container in order to protect from light and moisture.

6.5 Nature and contents of container

Each capsule contains Lomustine Taj Pharma as an active substance

Pack size:

Each pack contains 5, 10, 15, 20, 30, 40, 50, 60, or 100 capsules

Each box containing 20, 30, 40, 50, 60, 100, 150, 240, 360 and 500 capsules.

6.6 Special precautions for disposal and other handling

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

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

 Lomustine Capsule 40mg Taj Pharma

Package leaflet: Information for the user

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.

What is in this leaflet

1. What Lomustine Taj Pharma is and what it is used for
2. What you need to know before you take Lomustine Taj Pharma
3. How to take Lomustine Taj Pharma
4. Possible side effects
5. How to store Lomustine Taj Pharma
6. Contents of the pack and other information

1.What Lomustine Taj Pharma is and what it is used for

This medicine contains an active ingredient called Lomustine Taj Pharma.

Lomustine Taj Pharma belongs to a group of medicines called antineoplastic or cytotoxic agents. These medicines affect growth and proliferation of cancer cells.

Lomustine Taj Pharma capsules are used to treat tumours and other malignant growths or diseases, for example, cancer of the lung or skin.

2. What you need to know before you take Lomustine Taj Pharma

Do not take Lomustine Taj Pharma

• if you are allergic to Lomustine Taj Pharma or any of the other ingredients of this medicine (listed in section6).
• if you have had a similar medicine before which you had to stop taking because of side effects or because it was ineffective.
• if you have any blood disorder.
• if you have severe kidney problems.
• if you have coeliac disease (your body cannot digest gluten) or wheat allergy.
• if you have had a vaccination against yellow fever or another live vaccine vaccination and suffer from immunosuppression.
• if you are pregnant or breastfeeding.

You and your partner should avoid becoming pregnant or fathering a child during treatment and for at least 6 months after your treatment with Lomustine Taj Pharma has stopped.

Warnings and precautions

Talk to your doctor or pharmacist before taking Lomustine Taj Pharma

• Do not take a higher dose of Lomustine Taj Pharma as prescribed by your doctor and do not repeat treatment before the end of 6 weeks.
• Your doctor will check your blood weekly during your therapy and up to 6 weeks afterwards.
• Lomustine Taj Pharma might impair the function of your blood-building system, and increase the risk of bleeding and infections. This effect might occur after a certain time of therapy.
• As the toxic effects of Lomustine Taj Pharma to your blood-building system are cumulative your doctor might decide to adjust the dosage of your therapy.
• Tell your doctor if you have any liver problems. Before you start with Lomustine Taj Pharma, your doctor will check the function of your liver and additionally

of your lung and kidneys. These tests will be repeated during the time of your therapy.

• Long term use of nitrosoureas has been reported to be possibly associated with the development of secondary cancers.

Other medicines and Lomustine Taj Pharma

No special studies regarding interactions between Lomustine Taj Pharma and other medicines have been performed, but tell your doctor if you are taking any of the following medicines:

• theophylline – medicine used in the treatment of respiratory tract diseases, e.g. asthma
• cimetidine – medicine largely used in the treatment of heartburn and peptic ulcers
• other chemotherapeutic medicines, because co-administration can lead to complications due to interactions between the medicines.

Tell your doctor if you have ever taken phenobarbital – an anticonvulsant, or any other antiepileptic medicine.

You should also inform your doctor if you have recently been vaccinated.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

Pregnant women should not take this medicine. It is important to tell your doctor if you are pregnant or think you might be pregnant, because safe use in pregnancy has not been established. If you become pregnant while you are treated with Lomustine Taj Pharma tell your doctor immediately, as taking Lomustine Taj Pharma might affect your unborn baby detrimentally. If you areof childbearing age you should avoid becoming pregnant.

Breastfeeding

You should not breast-feed your baby while being treated with this medicine, because Lomustine Taj Pharma might pass into your breast milk. As a risk to the nursing child potentially exists, a decision should be made whether to discontinue breast-feeding or to discontinue Lomustine Taj Pharma therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the mother.

Fertility

Men who are treated with Lomustine Taj Pharma should not father a child during their therapy and up to 6 month afterwards. As Lomustine Taj Pharma may affect your fertility, ask your doctor to inform you about possible precautions like sperm conservation before you start with the treatment.

Driving and using machines

No special studies have been performed, but Lomustine Taj Pharma capsules can impair your ability to drive and use machines, e.g. because of nausea and vomiting.

Lomustine Taj Pharma contains lactose and wheat starch This medicine contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

This medicine also contains wheat starch. Patients with wheat allergy or coeliac disease should

not take this medicine (see above “Do not take Lomustine Taj Pharma”).

3. How to take Lomustine Taj Pharma

Care must be taken whenever handling anticancer products. Caution! Do not break open the Lomustine Taj Pharma capsules. If you accidentally get the powder on your skin or in your mouth, wash it off with plenty of water. Wash your hands with soap and water after handling this product.

Always take this medicine exactly as your doctor has told you, and in an interval of no less than

6 weeks. Check with your doctor or pharmacist if you are not sure.

Lomustine Taj Pharma capsules are taken by mouth. Swallow the capsules whole, do not chew or break them.

Use in adults

Your doctor will decide the exact dose to give you and how often to give it. Usually the dose depends on your height and weight. You may expect to receive 200 – 240mg Lomustine Taj Pharma. Lomustine Taj Pharma capsules are usually taken once every 6 to 8 weeks either as a single dose or as a divided dose over 3 days, e.g. 80mg/day.

The dose you take may be reduced if you are taking other medicines to treat your condition or if you have a blood disorder.

Use in children

Lomustine Taj Pharma capsules may be used in children with certain types of tumours. You must only use Lomustine Taj Pharma for children as prescribed by the doctor. Lomustine Taj Pharma capsules are usually taken once every

6 to 8 weeks either as a single dose or as a divided dose over 3 days, e.g. 40mg/day.

If you take more Lomustine Taj Pharma than you should Accidental overdose with Lomustine Taj Pharma has been reported, including fatal cases.

If you have taken too much medication please consult your doctor or local casualty department immediately.

An overdose might show in abdominal pain, diarrhoea, regurgitation, lack of appetite, lethargy, a feeling of dizziness, cough or shortness of breath.

If you forget to take Lomustine Taj Pharma

It is important to complete the course of medication exactly as prescribed by your doctor. If you think you have missed a dose for any reason please tell your doctor or nurse immediately. Your doctor will decide how to proceed with the intake of Lomustine Taj Pharma.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Please tell your doctor immediately if any of the following side effects occur:

Not known (frequency cannot be estimated from the available data)

• Various types of effects on the blood, such as too little red and white blood cells and/or platelets. This can manifest itself either in the fact that you bruise more easily than usual or you suffer repeated infections, e.g. sore throat or cough. You should contact your doctor immediately if this occurs.
• Nausea, vomiting and loss of appetite. Nausea and vomiting usually occur approximately

3 – 6 hours after you have taken your dose and can last for 24 – 48 hours, possibly followed by reduced appetite for 2 – 3 days. Your doctor may prescribe other medicines (anti-emetics) which you can take concurrently to relieve this. It might also help to take Lomustine Taj Pharma on an empty stomach.

• Stomatitis (inflammation inside the mouth) and diarrhoea
• Apathy, difficulties in orientation, confusion and stuttering
• Hair loss

Other possible side effects:

Very common (may affect more than 1 in 10 people) • Decrease in white blood cells

Not known(frequency cannot be estimated from the available data)

• Acute leukaemia (blood cancer) and myelodysplastic syndrome (blood disorder associated with insufficient production of blood cells in the bone marrow)
• Pneumonia
• Acute and chronic lung reactions with changes in lung tissue seen in x-ray, shortness of breath and dry cough
• Lasting visual impairment (in combination with radiation treatment)
• Kidney failure, decrease in kidney size and kidney damage
• Abnormal coordination
• Sleepiness, sluggishness
• Difficulty speaking, unclear speech
• Increase in liver enzymes and bilirubin (break-down product of the red blood pigment)

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

5. How to store Lomustine Taj Pharma

Keep this medicine out of the sight and reach of children.

Do not store above 25 °C.

Keep the box in the outer carton in order to protect from light and moisture.

Do not use this medicine after the expiry date which is stated on the carton. The expiry date refers to the last day of that month.

Do not throw away any medicines via wastewater or household waste. At the end of treatment return any leftover medicine to your hospital or pharmacist.

6. Contents of the pack and other information

What Lomustine Taj Pharma contains

• The active substance is Lomustine Taj Pharma. Each capsule contains 10 or 40mg or 100 Lomustine Taj Pharma. The other ingredients are lactose, wheat starch, talc and magnesium stearate.
• The capsule is made of gelatine and the colouring agents titanium dioxide and indigotine.

What Lomustine Taj Pharma capsules and their contents of the pack

Lomustine Taj Pharma are hard capsules. Lomustine Taj Pharma capsules are packed in a plastic box.

There are 10, 20 and 30 capsules in each pack.

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