DOXORUBICINA 2 мг/мл Концентрат для инфузионного раствора

Содержание инструкции

1. Doxorubicina Teva 2 mg/ml concentrate for solution for infusion
   1. What Doxorubicina Teva is and what it is used for
   2. What you need to know before using Doxorubicina Teva
   3. How to use Doxorubicina Teva
   4. Possible side effects
   5. How to store Doxorubicina Teva
   6. Contents of the pack and other information

Doxorubicina Teva 2 mg/ml concentrate for solution for infusion

Generic medicine

Read this leaflet carefully before using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

• 1. What Doxorubicina Teva is and what it is used for
• 2. What you need to know before you use Doxorubicina Teva
• 3. How to use Doxorubicina Teva
• 4. Possible side effects
• 5. How to store Doxorubicina Teva
• 6. Contents of the pack and other information

1. What Doxorubicina Teva is and what it is used for

The active substance of this medicine is doxorubicin hydrochloride. Doxorubicin belongs to a
group of anti-cancer drugs (anti-neoplastic agents) called anthracyclines. Doxorubicin damages cancer
cells and prevents their growth.
Doxorubicin is used for the treatment of:
breast cancer
bone cancer (osteosarcoma), with administration before and after surgery
soft tissue cancer (advanced soft tissue sarcoma in adults)
lung cancer (small cell lung carcinoma)
lymphatic tissue cancer (Hodgkin's and non-Hodgkin's lymphoma)
some blood cancers (acute lymphoblastic or myeloblastic leukemias)
bone marrow cancer (multiple myeloma)
cancer of the uterine lining (advanced or recurrent endometrial carcinoma)
thyroid cancers (advanced papillary/follicular thyroid carcinoma, anaplastic thyroid
carcinoma)
some bladder cancers (locally advanced or metastatic). It is also used
intravesically (into the bladder) for early-stage (superficial) bladder cancer to
prevent a recurrence of bladder cancer after surgery.
recurrent ovarian cancer
a particular pediatric kidney cancer (Wilms' tumor)
a pediatric nervous tissue tumor (advanced neuroblastoma).
Doxorubicin is also used in combination with other anti-cancer medicines.
Because Doxorubicina Teva is an anti-cancer medicine, it will be administered within a
specialized unit and under the supervision of a doctor qualified in the use of anti-cancer
medicines. The unit staff will explain what special attention you need to pay during and after
treatment. This leaflet will help you remember what you need to do.

2. What you need to know before using Doxorubicina Teva

Do not use Doxorubicina Teva if

• you are allergic to doxorubicin hydrochloride, to other similar medicines called anthracyclines or anthracenediones, or to any of the excipients of this medicine (listed in section 6)
• you are breastfeeding.

Doxorubicina Teva must not be administered intravenously (into a vein) if

• you have a decrease in the production of blood cells, a decrease in bone marrow function (myelosuppression) or inflammation of the mouth (stomatitis) due to previous treatment with anticancer medicines and/or radiotherapy.
• you have an infectious disease.
• your liver function is severely impaired.
• you have heart problems (severe disturbances of the heart rhythm, reduced heart function, [previous] heart attack, inflammation of the heart). These problems can occur rapidly and have a short but serious course.
• you have been previously treated with doxorubicin or similar anticancer drugs such as daunorubicin, epirubicin, idarubicin and/or with other medicines belonging to the anthracycline and anthracenedione group (see “Other medicines and Doxorubicina Teva”) and you have received the maximum dose of these drugs.

Doxorubicina Teva must not be administered intravesically (into the bladder) if

• the tumor has spread to the bladder wall.
• you have a urinary tract infection.
• you have inflammation of the bladder.
• you have problems with the use of the catheter (a tube inserted into the bladder for draining urine).
• you have blood in your urine (hematuria).

Warnings and precautions
Talk to your doctor before using Doxorubicina Teva.
Take special precautions with Doxorubicina Teva and inform your doctor before treatment if

• you are elderly or overweight.
• you have or have had a heart condition.
• you have received or are to receive vaccinations with live or live attenuated vaccines.
• you have liver or kidney problems.
• you have had bone marrow damage.
• you have been treated with radiotherapy in the chest cavity (mediastinum).
• you have been treated with similar anticancer products (other anthracyclines or anthracenediones).

Important information about Doxorubicina Teva

• Doxorubicin can cause infertility, which may be permanent, in men and women (see also “Pregnancy, breastfeeding and fertility”).
• If you experience severe pain or a burning sensation at the injection site of doxorubicin, this may be due to leakage of doxorubicin from the vein. If this happens, inform your doctor immediately: they will start treatment in another vein and carefully monitor the affected area.
• Your urine may become reddish in color during treatment with Doxorubicina Teva.
• During treatment with Doxorubicina Teva, you may experience severe symptoms of nausea, vomiting and inflammation of the mucous membrane of the mouth or nose. If you experience any of these symptoms, tell your doctor immediately, who will provide you with the necessary treatment.
• Vaccinations are not recommended during treatment with Doxorubicina Teva. You should also avoid contact with people who have recently been vaccinated with the polio vaccine.

Before and during treatment with Doxorubicina Teva, your doctor:

• must check your blood count before each treatment cycle, as treatment with doxorubicin can damage the bone marrow, causing a decrease in white blood cells and making your body more susceptible to infections and bleeding. In case of severe bone marrow damage, the doctor may reduce, interrupt or postpone treatment.
• must check your lungs and chest to ensure that your lungs are functioning properly during treatment.
• must perform an electrocardiogram (ECG), an examination that records the activity of the heart, before starting treatment with doxorubicin and during the entire treatment, as doxorubicin can cause inflammation of the heart muscle (cardiomyopathy). This can happen especially if you have had a heart disease, are over 70 or under 15 years old, have been previously treated with doxorubicin (or with other related medicines of the anthracycline group) or with radiotherapy in the chest cavity. A cumulative dose of 450-550 mg/m must not be exceeded, as at higher doses the risk of developing heart failure increases considerably, especially in children and patients who have had previous heart disease. Generally, the maximum cumulative dose for children is calculated at 300 mg/m (under 12 years of age) and 450 mg/m (over 12 years of age). For newborns, the maximum cumulative dose may be even lower. The doctor may also perform other tests to monitor the functioning of your heart.
• must monitor the levels of uric acid in your blood and ensure that you drink enough fluids, as doxorubicin can increase the levels of uric acid in the blood (hyperuricemia).
• must regularly check your mouth and throat during treatment, as doxorubicin can cause changes in the lining of the mouth and throat.
• must monitor your kidney function. A dose reduction may be necessary.
• must monitor your liver function (through blood tests). A dose reduction may be necessary if liver function decreases.
• must check your overall health condition, as doxorubicin should not be used in the presence of inflammation, ulcers or diarrhea. Any existing infections must be treated by the doctor before you start taking Doxorubicina Teva.

Other medicines and Doxorubicina Teva
Tell your doctor or pharmacist if you are taking or have recently taken or may take any other
medicine.
Tell your doctor if

• you have been treated with other anthracyclines or other medicines that can damage the heart, such as 5-fluorouracil, cyclophosphamide or paclitaxel (anticancer medicines) or other medicines that affect heart function (e.g. calcium antagonists such as verapamil).
• you have been treated with or are about to be treated with trastuzumab (an anticancer medicine), as your doctor must monitor your heart function.
• you have been treated with 6-mercaptopurine (an anticancer medicine) as you have a higher risk of adverse liver events.
• you have been treated with medicines that affect bone marrow function, such as cytostatic agents (e.g. cytarabine, cisplatin or cyclophosphamide), sulfonamides (for infections), chloramphenicol (for infections), phenytoin (for epilepsy), amidopyrine derivatives (for pain and inflammation), antiretroviral drugs (for AIDS). This can cause damage to the bone marrow causing a decrease in blood cells.
• you are taking cyclosporine (to suppress normal immune defenses) or cimetidine (for stomach ulcers), which can increase the amount of doxorubicin in the blood. Your doctor may consider a dose reduction.
• you are taking phenobarbital (for epilepsy) or rifampicin (an antibiotic), because the amount of doxorubicin in the blood may decrease and a reduced effect of Doxorubicina Teva may be obtained.
• you are currently undergoing or have previously undergone radiotherapy, as adverse effects may increase.
• you have taken cyclophosphamide (an anticancer medicine), as this increases the risk of adverse events to the bladder (hemorrhagic cystitis, an infection of the bladder that sometimes causes blood in the urine).
• you are currently treated or have been previously treated with paclitaxel (an anticancer medicine), as they may increase the effects or side effects of doxorubicin.
• you are taking medicines that lower uric acid. Dose adjustments of these medicines may be necessary, as doxorubicin can cause an increase in uric acid levels in the blood.
• you are taking digoxin (for the heart), as the effect of digoxin may decrease.
• you are taking medicines to control epilepsy, such as phenytoin, carbamazepine or valproate, as the effect of these medicines may decrease.
• you are taking medicines including St. John's wort.
• you are also taking heparin (used to prevent blood clotting) or 5-fluorouracil (an anticancer medicine). If administered with the same infusion, doxorubicin may bind to these medicines and cancel their effect.
• you are taking sorafenib (for inoperable liver cancer and advanced kidney cancer).

Pregnancy, breastfeeding and fertility
If you are a woman, you must avoid becoming pregnant during treatment with doxorubicin and up to 6
months after the end of treatment. Doxorubicin must not be taken during pregnancy.
If you are a man, you must take the necessary precautions to prevent your partner from becoming pregnant
during treatment with doxorubicin and up to 6 months after the end of treatment. Men and
women should therefore use an effective contraceptive method during and up to 6 months after
the end of treatment.
Because doxorubicin can cause permanent infertility, it is advisable to talk to your doctor about
the possibility of freezing sperm before starting treatment (cryopreservation or
cryoconservation).
Breastfeeding must be stopped for the duration of therapy with Doxorubicina Teva, as a
part may pass into breast milk and possibly cause harm to the newborn.

Driving and operating machinery
Do not drive vehicles and do not use tools or machinery if you do not feel well and have nausea, vomiting or dizziness.

Doxorubicina Teva contains sodium
This medicine contains 18 mg of sodium (the main component of table salt) per vial
of 5 ml. This is equivalent to 0.9% of the recommended daily intake of salt with the diet of an
adult.
This medicine contains 35 mg of sodium (the main component of table salt) per vial
of 10 ml. This is equivalent to 1.8% of the recommended daily intake of salt with the diet of an
adult.
This medicine contains 89 mg of sodium (the main component of table salt) per vial
of 25 ml. This is equivalent to 4.4% of the recommended daily intake of salt with the diet of an
adult.
This medicine contains 354 mg of sodium (the main component of table salt) per vial
of 100 ml. This is equivalent to 17.7% of the recommended daily intake of salt with the diet of
an adult.

3. How to use Doxorubicina Teva

Doxorubicina Teva will be administered to you by a doctor. Your doctor may subject you to some tests, such as
blood tests, ECG, etc., before starting or during treatment to establish
the dose of Doxorubicina Teva to be administered.
Doxorubicin is administered intravenously, via an intravenous infusion, or into the bladder.
The preparation and administration of the medicine must be carried out exclusively by a
qualified healthcare professional in hospital.
The dose will depend on your age (the dose may be reduced for children and elderly patients), your
build, your weight and your general health conditions. It will also depend on any other
treatments you may have received for cancer. The doctor will calculate your body surface area in square
meters (m²). The medicine will be administered to you every 3 weeks for a duration of 6-12 months. In case
of administration into the bladder, the dose may be repeated at intervals ranging from 1
week to 1 month. The exact duration of your treatment will depend on your condition.

Patients with kidney or liver problems
If you have impaired kidney or liver function, a dose reduction may be necessary.

If you are given too much Doxorubicina Teva
Since the medicine is administered by a doctor, it is unlikely that you will experience an overdose.
However, if you have any concerns, report them immediatelyto your doctor or nurse.
The effects of administering an excessive dose of Doxorubicina Teva include: inflammation
of the stomach and intestines (especially the lining), heart problems and severe damage
to the bone marrow (myelosuppression). These effects may be accompanied by an increased risk
of bleeding and bruising and an increased risk of infections (leukopenia).
Treatment takes place in hospital and consists of the administration of antibiotics and blood transfusions
(especially white blood cells and platelets) and the treatment of any undesirable effects. It is possible
that you will be transferred to a sterile room. In case of heart problems, you will be visited by a specialist
(cardiologist). Heart problems may occur up to six months after the overdose.
If you have any doubts about the use of this medicine, consult your doctor or nurse.

4. Possible side effects

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

Tell your doctor or nurse immediately if

• you become dizzy, have a mild fever, have shortness of breath with a tight feeling in your chest or throat, or develop a itchy rash. This type of allergic reaction can be very serious.
• you feel tired and lethargic. These could be signs of anemia (low red blood cell count).
• you have a fever or other signs of infection. These can be signs of a reduced number of white blood cells (which fight infections).
• you bruise or bleed more easily. These could be signs of a reduced number of platelets in your blood (cells that help the blood to clot).

Very common:may affect more than 1 in 10 people

• Nausea, vomiting, digestive problems, diarrhea
• Hair loss (reversible)
• Reddish discoloration of urine
• Bone marrow damage (myelosuppression) with reduction of white blood cells and platelets, which increases the likelihood of contracting an infection and the risk of bleeding or bruising
• Anemia (a reduction in red blood cells, which can make the skin pale and cause weakness or shortness of breath)
• Heart muscle damage (cardiotoxicity). The risk increases if the patient is treated with radiotherapy or with other medicines toxic to the heart, if the patient is elderly or if the patient has high blood pressure. Effects can occur immediately after treatment or may manifest several years after treatment.
• Inflammation of the mucous membrane of the nose, mouth or vagina (mucositis)
• Inflammation or ulceration of the lining of the mouth (stomatitis), nose or throat (esophagitis), e.g. mouth ulcers and cold sores
• Inflammation of the colon (colitis)
• Skin sensitivity to artificial or natural light (photosensitivity), skin redness
• Fever, weakness (asthenia), chills
• Reduced appetite
• Infection
• Redness, swelling, numbness, pain and tingling in palms and soles (palmo-plantar erythrodysesthesia syndrome)
• Abnormalities in laboratory tests related to electrocardiogram (ECG) Abnormal levels of liver enzymes (transaminases)
• Weight gain in patients with early breast cancer

Common:may affect up to 1 in 10 people

• Blood poisoning (sepsis/septicemia)
• Heart rhythm disturbances (irregular heartbeat, increased heart rate, decreased heart rate), contraction of the heart ventricles, reduction in the amount of blood pumped to the body by the heart, deterioration of heart muscle function (cardiomyopathy) that can lead to death
• Inflammation of the outer part of the eye (conjunctivitis)
• Abdominal pain
• Bleeding problems (hemorrhage)
• Local allergic reactions at the sites treated with radiotherapy (the so-called radiation recall reaction)
• Itching
• Skin rash (exanthema), hives
• Darkening of areas of skin and nails (hyperpigmentation)

Following administration into the bladder, the following common side effects may be observed:

• Difficulty, pain or burning sensation during urination
• Reduced amount of urine
• Increased frequency of urination
• Bladder cramps
• Inflammation of the bladder sometimes causing blood in the urine
• Local side effects with administration into the bladder, such as inflammation of the bladder (chemical cystitis)

Uncommon:may affect up to 1 in 100 people

• When combined with other anticancer medicines, doxorubicin can cause certain forms of blood cancer (leukemia). These forms of cancer may appear many years after treatment.
• Bleeding in the stomach or intestine
• Ulcers and possible death of tissue cells (necrosis) of the large intestine with bleeding and infections in combination therapies with cytarabine (an anticancer medicine). Embolism (formation of a blood clot)
• Loss of water (dehydration) Rare:may affect up to 1 in 1,000
• Detachment of nails (onycholysis)
• Dizziness
• Reactions at the injection site, including itching, rash and pain, inflammation of the vein (phlebitis), thickening or hardening of the vein walls (phlebosclerosis)
• Severe allergic reaction causing difficulty breathing or dizziness (anaphylactic reaction)
• A stinging or burning sensation at the site of administration due to leakage of medicine from the vein. This can cause death of local tissue cells and requires appropriate treatment, in some cases surgical measures.

Very rare:may affect up to 1 in 10,000

• Heart rhythm disturbances (non-specific changes in the ECG tracing)
• Isolated cases of life-threatening irregular heartbeat (arrhythmias), left heart failure, inflammation of the lining of the heart causing chest pain and fluid accumulation around the heart (pericarditis), inflammation of the heart muscle and the sac surrounding the heart (pericarditis-myocarditis syndrome), loss of nerve impulses to the heart (atrioventricular block, bundle branch block)
• Ulcers in the lining of the mouth, throat, esophagus, stomach or intestine, discoloration (pigmentation) of the lining of the mouth
• Swelling and numbness of hands and feet (acral erythema), blistering
• Condition in which the kidneys stop working properly (acute renal failure)
• Excessively high levels of uric acid in the blood (hyperuricemia), which can cause gout, kidney stones or kidney damage due to rapid tumor breakdown
• Cessation of menstruation (amenorrhea)
• Fertility problems in men (low or absent active sperm)
• Hot flashes on the face Not known:frequency cannot be estimated from the available data
• Shortness of breath due to spasms of the airway muscles (bronchospasm)
• Temporary increase in liver enzymes
• Severe liver damage that can sometimes culminate in permanent damage to normal liver tissue (cirrhosis)
• Inflammation of the cornea (keratitis), increased tear production
• Severe pain and swelling of the joints
• Damage due to radiation (to skin, lungs, throat, esophagus, lining of stomach and intestine), which is already healing but may recur with doxorubicin treatment
• Thick, scaly or crusty skin patches (actinic keratosis)
• Feeling unwell
• Shock

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through
the national system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Doxorubicina Teva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label or the package after
EXP. The expiry date refers to the last day of that month.

Storage conditions

Before opening: store in a refrigerator (2-8 °C). Do not freeze.

After opening:the product must be used immediately after opening the vial.

After dilution:
The chemical and physical stability in use after dilution to a concentration of 0.5 mg/ml (in sodium
chloride 9 mg/ml (0.9%) solution for infusion or in glucose 50 mg/ml (5%) solution for infusion)
has been demonstrated for 7 days protected from light at room temperature (15-25°C) and at 2-8 °C.
After dilution to a concentration of 0.05 mg/ml, the diluted solution must be used
immediately.
From a microbiological point of view, the medicine must be used immediately. If it is not
used immediately, the in-use storage times and conditions prior to use are the
responsibility of the user. The storage times of the diluted product generally do not
exceed 24 hours at 2-8 °C, unless the dilution has taken place under controlled and validated aseptic
conditions.
Do not dispose of any medicine in the wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Doxorubicina Teva contains

• The active ingredient is doxorubicin hydrochloride. Each ml of concentrate for solution for infusion contains 2 mg of doxorubicin hydrochloride. Each vial of 5 ml contains 10 mg of doxorubicin hydrochloride. Each vial of 10 ml contains 20 mg of doxorubicin hydrochloride. Each vial of 25 ml contains 50 mg of doxorubicin hydrochloride. Each vial of 100 ml contains 200 mg of doxorubicin hydrochloride.
• The excipients are sodium chloride, hydrochloric acid (E507), sodium hydroxide (E524) and water for injections.

Description of the appearance of Doxorubicina Teva and contents of the pack
Doxorubicina Teva 2 mg/ml concentrate for solution for infusion is a transparent solution of
red color. The solution is supplied in colorless glass vials, closed by a chlorobutyl rubber stopper and an aluminum seal, covered by a colored disc. Doxorubicina Teva 2 mg/ml is
available in vials of 5 ml, 10 ml, 25 ml and 100 ml. Each pack contains one vial for
injection.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Teva Italia S.r.l. – Piazzale Luigi Cadorna, 4 – 20123 Milano

Manufacturer
Pharmachemie B.V., Swensweg 5, 2031 GA Haarlem, Netherlands
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The following information is intended exclusively for doctors or healthcare professionals
Incompatibilities
Doxorubicin is incompatible with heparin, aminophylline, cephalothin, dexamethasone,
fluorouracil and hydrocortisone.
Doxorubicin must only be diluted with sodium chloride 0.9% w/v solution for infusion or with
glucose 5% w/v solution for infusion.

Handling and precautions for disposal
Care must be taken when handling Doxorubicina Teva solution. Any contact with the solution must be
avoided. During preparation, a strictly aseptic technique must be adopted; protective measures must include the use of gloves, mask, safety glasses and protective clothing. The use of a vertical laminar flow (LAF) hood is recommended.
Personnel must be trained in good handling techniques for cytotoxic drugs. Pregnant personnel should be excluded from working with this drug.
If Doxorubicina Teva comes into contact with skin or mucous membranes, the exposed area should be
washed thoroughly with soap and water. If the substance comes into contact with the eyes, rinse
with water or sterile saline solution, then consult an ophthalmologist.
After use, vials and materials used for the injection, including gloves, must be destroyed
in accordance with the rules for cytotoxic agents. Unused medicinal product and waste derived from
such medicinal product must be disposed of in accordance with local regulations.
Inactivation of spills or leaks of the drug is achieved with a 1% or more sodium hypochlorite solution
or more simply with a phosphate buffer (pH>8) until the solution is eliminated.
All materials used for cleaning must be disposed of as indicated above.

Dosage and administration
Treatment with doxorubicin must be initiated by a doctor or after consulting a doctor
with extensive experience in cytotoxic therapy. Patients must be monitored frequently and
carefully during treatment.
Doxorubicin must NOT be administered intramuscularly, subcutaneously, orally or
intrathecally.
Intravenous (i.v.) administration of doxorubicin must be carried out with extreme care; it is
advisable to administer the medicinal product by infusion of a freely flowing physiological saline i.v. solution or 5% glucose over 3-5 minutes. This method minimizes the
risk of thrombosis and perivenous extravasation, which causes severe cellulitis, blistering and
tissue necrosis. Doxorubicin can be administered intravenously as a bolus over a few minutes, as a short infusion over a maximum of one hour or as a continuous infusion
for up to 96 hours. Direct intravenous injection is not recommended due to the risk of extravasation,
which can occur even with adequate blood return by needle aspiration.
Doxorubicin can be diluted in the concentration range between 0.05 mg/ml and 0.5
mg/ml in sodium chloride 9 mg/ml (0.9%) solution for infusion or in glucose 50 mg/ml (5%)
solution for infusion using non-PVC infusion bags.

Intravenous administration
The dose is usually calculated based on the body surface area (mg/m²). The dosage
of doxorubicin may vary depending on the indication (solid tumors or acute leukemia
and according to its use in the specific therapeutic regimen (monotherapy or in combination with other
cytotoxic agents or as part of multidisciplinary procedures including a combination of
chemotherapy, surgery, radiotherapy and hormonal treatment).

Monotherapy
The recommended dose is 60-75 mg/m² of body surface area i.v. as a single dose or in divided doses
over 2-3 consecutive days, with intravenous administration at intervals of 21 days. The dosage and
doses may be adjusted according to the protocol. For precise information on dosage,
consult current protocols.

Combination therapy
If Doxorubicina Teva is administered in combination with other cytostatic agents, the dose should
be reduced to 30-60 mg/m² every 3-4 weeks.

Maximum cumulative dose
In order to avoid cardiomyopathy, the total cumulative dose of doxorubicin
over a lifetime (including use with related drugs, such as daunorubicin) should not exceed 450-550
mg/m² of body surface area. Extreme caution is required when exceeding a cumulative dose of
400 mg/m² in cases of previous mediastinal irradiation, previous or concomitant treatment
with potentially cardiotoxic agents and high-risk patients (i.e. patients with hypertension
for more than 5 years; with pre-existing coronary, valvular or myocardial damage or over 70 years of age). Cardiac function of these patients must be
monitored.

Special populations

Immunocompromised patients
The dose should be reduced in case of immunosuppression; an alternative dose is 15-20 mg/m² of
surface area per week.

Patients with impaired hepatic function
In case of impaired hepatic function, the dose should be reduced according to the following scheme.

Patients with impaired renal function
In patients with renal insufficiency (GFR less than 10 ml/min), only 75% of the planned dose should be administered.

Patients at risk of heart failure
For patients with an increased risk of cardiotoxicity, treatment with a 24-hour continuous infusion of a single dose should be considered instead of an injection. This can
reduce the frequency of cardiotoxicity without reducing therapeutic efficacy. In these patients, the ejection fraction should be measured before each cycle.

Patients with limited bone marrow reserve not related to bone marrow involvement by

the disease
Doses may be reduced in patients previously treated with myelosuppressive agents. The
bone marrow reserve of these patients may be insufficient.

Elderly
The dose may be reduced in elderly patients.

Paediatric population
Due to the concrete risk of doxorubicin-induced cardiotoxicity in childhood, certain maximum cumulative dosages dependent on the age of the patients must be applied. Generally, in
children (under 12 years of age) the maximum cumulative dose is calculated at 300 mg/m², while in
adolescents (over 12 years of age) the maximum cumulative dose is fixed at 450 mg/m². For newborns, the
maximum cumulative dosages have not yet been defined, but a further lower tolerability is presumed.
In children, the dose must be reduced, as they have a greater risk of cardiotoxicity, especially in the long term. Myelotoxicity with nadir at 10-14 days after
the start of treatment should be expected. Consult treatment protocols and specialist literature.

Obese patients
A reduced initial dose or a prolonged dose interval may be considered in obese patients.

Endovesical administration:
Doxorubicina Teva can be administered by endovesical instillation for the treatment
of superficial bladder carcinoma and to prevent recurrence after transurethral resection
(TUR). The recommended dose for endovesical treatment of superficial bladder carcinoma
is 30-50 mg in 25-50 ml of physiological saline for instillation. The optimal concentration is
approximately 1 mg/ml. The solution should remain in the bladder for 1-2 hours. During this period, the patient
should be rotated 90° every 15 minutes. To avoid undesirable dilution with urine, the patient

should be informed of the prohibition of drinking any liquids in the 12 hours before instillation (this
should reduce urine production to approximately 50 ml/h). The instillation can be repeated at an
interval between 1 week and 1 month, depending on the type of treatment, therapeutic or
prophylactic.
Note: Doxorubicina Teva cannot be replaced with a liposomal formulation of doxorubicin
hydrochloride.

Treatment monitoring
The following monitoring tests are recommended before or during treatment with doxorubicin (the
frequency of performing these tests depends on the patient's general condition, the dose and the
concomitant medications taken):

• chest X-rays and ECG
• regular monitoring of cardiac function (LVEF measured, for example, with ECG, echocardiogram and cardiac scintigraphy)
• inspection of the oral cavity and pharynx for changes in the mucous membranes
• blood tests: hematocrit, platelets, white blood cell count, SGPT, SGOT, LDH, bilirubin, uric acid, AST, ALT, ALP.

Left ventricular function monitoring
An analysis of the left ventricular ejection fraction (LVEF) by
echography or cardiac scintigraphy should be performed to optimize the patient's cardiac condition. This
monitoring should be carried out before the start of treatment and after each cumulative dose of approximately 100 mg/m².

Storage conditions after dilution
Chemical and physical stability in use has been demonstrated after dilution to a concentration of 0.5
mg/ml in sodium chloride 9 mg/ml (0.9%) solution for infusion or in glucose 50 mg/ml (5%)
solution for infusion for 7 days protected from light at room temperature (15-25°C) and at 2-8 °C.
After dilution to the concentration of 0.05 mg/ml, the diluted solution must be used
immediately.
From a microbiological point of view, the medicinal product must be used immediately. If it is not
used immediately, the storage times in use and the conditions prior to use are the responsibility of the user and normally do not exceed 24 hours at 2-8 °C, unless the
dilution has taken place under controlled and validated aseptic conditions.

Disposal
Disposal procedures in water must take into account the cytotoxic nature of this substance.