VINBLASTINE STADA 10 mg POWDER FOR INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

Vinblastine Stada 10 mg powder for injectable solution

Read all of this leaflet carefully before you start using 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.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the package leaflet

1. What is Vinblastine Stada and what is it used for
2. What you need to know before you use Vinblastine Stada
3. How to use Vinblastine Stada
4. Possible side effects
5. Storage of Vinblastine Stada
6. Contents of the pack and further information

1. What is Vinblastine Stada and what is it used for

Vinblastine Stada belongs to the group of cytostatics (cancer medicines). Vinblastine Stada works by stopping the growth of cancer cells, which results in their destruction.

Indications

• Generalized Hodgkin's disease (stages III and IV, Ann Arbor modification of the Rye classification system).
• Lymphocytic lymphoma (nodular and diffuse, poorly and well differentiated).
• Histiocytic lymphoma.
• Mycosis fungoides (advanced stages).
• Advanced testicular cancer.
• Kaposi's sarcoma.
• Letterer-Siwe disease (histiocytosis X)
• Choriocarcinoma resistant to other chemotherapeutic agents.
• Breast cancer that does not respond to endocrine surgery and adequate hormonal treatment.

2. What you need to know before you use Vinblastine Stada

Do not use Vinblastine Stada powder for injectable solution

• if you have a white blood cell deficiency(leucopenia not related to the disease)
• if you have an uncontrolled infection, first the infection must be treated with disinfectants (antiseptics) or antibiotics.
• if you are allergic (hypersensitive) to vinblastine, to other products of the so-called vinca alkaloids group(e.g. vincristine) or to any of the other components of this medicine (listed in section 6).
• if you are breast-feeding(see the section "Pregnancy, breast-feeding and fertility")

Tell your doctor if you have any of the above contraindications or if you have had them before.

Warnings and precautions

Consult your doctor before starting to use Vinblastine Stada.

Vinblastine Stada should only be administered under the strict supervision of doctors who have experience with regard to treatment with cytostatics (cancer medicines).

Vinblastine Stada must be administered exclusively by the intravenous route (in the vein) and in no case by any other route. Administration by other routes can be fatal.

You should avoid contact of Vinblastine Stada with the eyes. If Vinblastine Stada comes into contact with the eyes, rinse them immediately with plenty of water and consult your doctor if irritation persists.

Be particularly careful with Vinblastine Stada:

• If after administration of the dose of Vinblastine Stada a decrease in white blood cells(leucopenia) appears; you should be closely monitored until your white blood cell count increases to a safe value, as otherwise, an infection may occur.
• If you have cancer cells in the bone marrow; blood production in the bone marrow may sometimes decrease significantly during treatment with Vinblastine Stada.
• In the case of women of childbearing age, Vinblastine Stada may affect fertility. Both men and women of childbearing age should use effective contraceptive methods during treatment and for at least 3 months, and preferably 6 months, after treatment with vinblastine.
• If your liver is not functioning properly, the elimination of Vinblastine Stada may be delayed. In these cases, your doctor will adjust the dose of Vinblastine Stada.
• In case of concomitant prescription with mitomycin C. In these cases, there is a higher risk of dyspnea and sudden apneas (see also "Administration of Vinblastine Stada with other medicines").
• During treatment with Vinblastine Stada, avoid intense sun exposure.
• If during treatment with Vinblastine Stada you need to be vaccinated, vaccination with a specific type of vaccine (so-called live vaccines) may cause a serious illness. Your doctor will prescribe an inactivated vaccine or postpone vaccination.
• In case you get up after a prolonged rest, a sudden drop in blood pressure(orthostatic hypotension) may occur, especially in elderly patients.
• If you have heart diseases such as ischemic heart disease(heart and circulatory problems).

Other medicines and Vinblastine Stada

Tell your doctor or pharmacist if you are using or have recently used or may need to use any other medicine.

The term "interaction" means that a medicine administered together may influence the effect and/or side effects of another medicine. An interaction may occur when this injectable solution is administered together with the following medicines:

• Medicines that prevent the formation of blood clots (anticoagulants); in this case, close monitoring may be necessary.
• Medicines known to produce an inhibitory effect on the elimination of medicines in the liver; their concomitant administration may accelerate the onset of side effects and/or increase their severity.
• Phenytoin (a medicine for epilepsy); vinblastine may reduce the effect of phenytoin with the subsequent appearance of more epileptic seizures. If necessary, the dose of phenytoin should be adjusted according to blood levels.
• Mitomycin C (a cancer medicine); there is a higher risk of harmful effects on the lungs. See also the section "4. Possible side effects".
• Cisplatin (a cancer medicine) or interferon (a medicine for cancer, hepatitis C, or autoimmune diseases); the side effects of cisplatin or interferon on the nervous system may be more pronounced.
• Bleomycin (a cancer medicine); the combination may cause vascular manifestations, such as Raynaud's phenomenon (see the section "4. Possible side effects").
• Other medicines used against cancer (cytostatics) or that depress the immune system; side effects may be more pronounced.
• Radiation therapy; side effects on the bone marrow may be more pronounced.
• Digoxin (a product used to treat different heart diseases); the effect of digoxin may decrease.
• Erythromycin (a certain antibiotic); may increase the side effects of vinblastine.
• Vaccines; vinblastine depresses the immune system and may act on the body's ability to respond to the vaccine.
• Itraconazole (a medicine for fungal infections) may increase the risk of neurotoxicity or paralytic ileus (alteration of intestinal motility).

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before using this medicine.

Pregnancy

You should not use Vinblastine Stada during pregnancy unless your doctor has prescribed it. There is not enough information available on the administration of vinblastine during pregnancy to determine its potential toxicity. However, based on the effect of the medicine, it is possible that Vinblastine Stada may cause harmful effects on the fetus. In animal studies, harmful effects were observed.

Breast-feeding

Breast-feeding should be avoided during treatment with Vinblastine Stada. Although it is not known whether vinblastine is excreted in breast milk, this possibility cannot be ruled out.

Contraception in men and women

In cases of women of childbearing age, effective contraceptive methods should be used during treatment and for at least 3 months, and preferably 6 months, after treatment with vinblastine. If you become pregnant during treatment, you should inform your doctor immediately. If you are already pregnant or become pregnant during treatment with vinblastine, genetic counseling is recommended.

In the case of men, they should avoid fathering a child during treatment with vinblastine and for at least 3 months, and preferably 6 months, after treatment.

Fertility

There is a risk that vinblastine may cause male and female infertility. Before starting treatment, male patients should be informed about the possibility of preserving their sperm.

Driving and using machines

There is no data available on the effect of this medicine on the ability to drive or use machines. However, this medicine may sometimes cause dizziness or seizures (see the section "4. Possible side effects"). If you experience any of these side effects, do not drive or operate machinery that requires your full attention.

Vinblastine Stada contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per vial; it is essentially "sodium-free".

3. How to use Vinblastine Stada

Posology

Vinblastine Stada will be injected into your vein by your doctor, either by injection or infusion.

Although vinblastine is sometimes administered alone, it is usually used in combination with other cancer medicines.

Your doctor will determine the dose of Vinblastine Stada and the number of administrations, which may vary depending on the patient. The dose may be increased at weekly intervals until the desired effect on the cancer is achieved or until the white blood cell count decreases to a certain level (leucopenia). It is recommended to administer the medicine with a frequency not exceeding once every 7 days. In general, a dose, as high as possible, is administered once every 7 to 14 days, without causing a dangerous reduction in the number of white blood cells (leucopenia).

If at the beginning of treatment your liver is not functioning properly, your doctor may reduce the dose or suspend treatment.

Method of administration

This product is for intravenous use only and should be administered by personnel experienced in the administration of vinblastine.

Vinblastine Stada should only be administered in a vein by injection or infusion.

If during treatment a decrease in white blood cells (leucopenia) or an infection occurs, treatment with vinblastine will be suspended or an anti-infectious medicine (antibiotic) will be prescribed.

Direct contact of the medicine with the skin, eyes, and mucous membranes should be avoided. In case of accidental contact, the area should be rinsed immediately with plenty of water.

If you are given more Vinblastine Stada than you should

If you are given too much Vinblastine Stada, the side effects described in the section "4. Possible side effects", such as a decrease in white blood cells (causing a greater propensity to infections), symptoms of peripheral neuropathy (e.g. tingling, pinching, numbness of the skin) without physical reason, may occur more intensely.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, telephone: 91 562 04 20, indicating the medicine and the amount administered.

If you miss a dose of Vinblastine Stada

If you miss a dose of Vinblastine Stada, it should be administered as soon as possible. Contact your doctor immediately to consult when the missed dose can be administered.

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

If you stop treatment with Vinblastine Stada

Always consult your doctor before stopping treatment with Vinblastine Stada. If treatment is stopped, the symptoms that existed before may reappear.

If you have any other questions about the use of this product, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Among others, the following adverse effects may appear:

Very Common(may affect more than 1 in 10 people)

• Blood disease (lack of white blood cells), including an increased propensity to infections (leukopenia)
• Nausea, vomiting
• Hair loss, which is usually not complete and can be restored during treatment
• Blister formation in the mouth and skin

Common(may affect up to 1 in 10 people)

• Anemia, blood disease (lack of platelets), including bruising and a tendency to bleeding (thrombocytopenia); bone marrow depression, which manifests in symptoms such as fatigue and frequent infections due to reduced immunity
• Tingling, itching, and pinching without apparent reason (paresthesia), decreased reflexes.
• Constipation, limited or absent transit in the small intestine (ileus), bleeding from a gastric or duodenal ulcer, intensely bleeding inflammation of the small intestine mucosa (hemorrhagic enterocolitis), blood loss through the anus, loss of appetite (anorexia), diarrhea. The constipation that may appear responds well to measures such as enemas or laxatives.

Uncommon(may affect up to 1 in 100 people)

• Depression
• Pharyngitis may occasionally appear. Shortness of breath and sudden apneas due to muscle contraction of the airways (bronchospasm) may occur. If mitomycin C is administered simultaneously or previously, shortness of breath, wheezing, which can be heard when breathing (rhonchus), and pulmonary function disorder may appear shortly after treatment or up to two weeks after it. In this case, the doctor should immediately discontinue treatment with vinblastine and mitomycin C; see also the section "Other Medicines and Vinblastina Stada"
• Pain in the tumor area, feeling of discomfort.

Rare(may affect up to 1 in 1,000 people)

• Severe disease, in which excess fluid is retained as a consequence of elevated secretion of a certain hormone from the adrenal glands (SIADH: Syndrome of Inappropriate Antidiuretic Hormone Secretion). It appears with both recommended doses and higher doses
• Stroke in patients who have received treatment with a combination of bleomycin, cisplatin, and vinblastine; feeling of deafness, feeling of numbness, neuritis (inflammation of the nerves), including pain, emotional disorder, and occasionally inflammation of the nerve tissue in the limbs (peripheral neuritis) that manifests as pain, tingling, pinching, numbness of the skin without physical reason, headache, convulsions, and sensory weakness.
• Partial or total deafness that may be temporary or permanent (ototoxicity) and may manifest as balance disorder, dizziness, or involuntary eye movements
• Increased heart rate (tachycardia), chest pain caused by insufficient blood supply to the heart muscle (angina pectoris), heart rhythm disorder

Frequency Not Known(cannot be estimated from available data)

• Anemia caused by abnormal destruction of red blood cells (hemolytic anemia)
• Nerve pain in the face and jaw, neuritis including pain, emotional disorder, and occasionally decreased effect on the nerves in the limbs (peripheral neuropathy), vocal cord paralysis
• Severe mental illness affecting control over behavior and personal actions (psychosis)
• After contact of vinblastine with the eyes; severe corneal injury, accompanied by eyelid contraction (blepharospasm), swelling of the eyelids and lymph nodes in front of the ears (preauricular lymph nodes)
• Ringing in the ears (tinnitus)
• Myocardial infarction in people who have received treatment with a combination of bleomycin, cisplatin, and vinblastine
• Reduced blood flow to the limbs (Raynaud's phenomenon) in patients treated with a combination of bleomycin, cisplatin, and vinblastine
• High blood pressure (hypertension) or very low blood pressure (hypotension) may occasionally appear
• Drop in blood pressure caused by rapid standing up from a sitting or lying position, including dizziness (orthostatic hypotension)
• Inflammation of the mouth and stomach mucosa, abdominal pain, painful salivary glands
• Severe liver disease (hepatic fibrosis), characterized by permanent liver tissue damage
• Skin inflammation (dermatitis), hypersensitivity to light or sunlight (phototoxicity)
• Decreased muscle size (muscle atrophy)
• Retention of urine in the urinary bladder due to a disorder in bladder emptying (urinary retention), blood vessel disease (thrombotic microangiopathy) with kidney failure
• Decreased fertility (in both men and women), lack of semen (aspermia)
• Weakness, fever, pain, inflammation of the veins, subcutaneous tissue, and skin, skin death in case vinblastine is accidentally injected outside the veins, pain at the injection site.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Vinblastina Stada

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Vinblastina Stada vials should be stored in a refrigerator (between 2 and 8 °C).

Stability after reconstitution:after reconstituting the powder in the vial and extracting a portion of the reconstituted solution, the remaining solution can be stored in a refrigerator (between 2°C and 8°C) for 28 days, without significant loss of potency.

Medicines should not be thrown away through wastewater or household waste. Ask your pharmacist how to dispose of packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Vinblastina Stada Composition

• The active ingredient is vinblastine sulfate. A vial with a perforable stopper contains 10 mg of vinblastine sulfate lyophilized.
• The other components are sodium hydroxide solution, a mixture of sulfuric acid and water.

Product Appearance and Package Contents

Each package contains 10 mg of vinblastine sulfate in the form of lyophilized substance in a colorless glass vial (type I) with a bromobutyl rubber stopper and a "flip-off" polypropylene cap sealed with aluminum. Each package contains a vial with a perforable stopper.

Marketing Authorization Holder

Laboratorio STADA, S.L.

Frederic Mompou, 5

08960 Sant Just Desvern

(Barcelona)

Spain

Manufacturer

STADA Arzneimittel AG

Stadastraße 2-18

61118 Bad Vilbel

Germany

Date of Last Revision of this Prospectus:October 2017

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

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This information is intended only for healthcare professionals:

Administration

Vinblastine should be administered exclusively by a qualified doctor or under the supervision of a qualified doctor, with experience in the management of cytostatics.

Preparation

Cytostatics intended for administration should be handled exclusively by professional personnel, trained in the safe handling of preparation. The reconstitution of the powder and transfer to syringes should only be performed in a designated area.

Personnel performing these operations should be properly protected with protective clothing, gloves, and protective glasses.

Pregnant women should not come into contact with cytotoxic medicines.

To obtain a vinblastine solution at a concentration of 1 mg/ml, 10 ml of physiological saline solution should be added to the vial containing 10 mg of Vinblastina. The substance dissolves immediately in a clear form. The use of other solvents is not recommended. When further dilution is desired, it should be taken into account that amounts of solvents greater than 100 ml or infusion periods greater than 30 minutes increase the risk of venous irritation and extravasation.

Vinblastina Stada should not be mixed with other medicines in the same container.

Contamination

In case of contact with the skin or eyes, the affected area should be rinsed with plenty of water or physiological serum. A refreshing cream can be used to treat the transient burning sensation on the skin. In case of eye involvement, medical intervention is necessary.

In case of spills, personnel should wear protective gloves and absorb the spilled material with a sponge that will be kept in a designated area for this purpose. Rinse the area twice with water. Place all solutions and sponges in a plastic bag intended for this purpose and seal it.

Excrements and vomits should be cleaned carefully.

Waste Disposal

Syringes, containers, absorbent materials, solutions, and any other contaminated material should be disposed of in a thick plastic bag or another type of impermeable container and incinerated.

All unused material, damaged vials, or contaminated waste material should be eliminated, in accordance with local requirements, in waste containers specifically designed for this purpose.

Compatibilities:

Sodium chloride 0.9%,

Benzyl alcohol 0.9%

Intrathecal administration of vinblastine causes potentially fatal neurotoxicity

When vinblastine sulfate is administered accidentally by the intrathecal route, the following treatment is recommended. In one case, progressive paralysis was inhibited in an adult who had received a vinca alkaloid, vincristine sulfate, by the intrathecal route with the following treatment. Treatment should be started immediately:

1. As much cerebrospinal fluid as possible was removed through the lumbar access, without compromising safety.

1. The subarachnoid space was irrigated with a lactated Ringer's solution by continuous infusion through a catheter inserted into the lateral cerebral ventricle at a rate of 150 ml per hour. The fluid was extracted through a lumbar access.

1. After performing the procedure in point 2, 25 ml of previously frozen plasma was diluted in 1 liter of lactated Ringer's solution and infused through a cerebral ventricular catheter at a rate of 75 ml/h. The fluid was extracted again through the lumbar access. The infusion rate was adjusted to maintain a protein level of 150 mg/ml in the cerebrospinal fluid. The treatment in point 3 was repeated with 1 liter of previously frozen plasma diluted.

1. 10 g of glutamic acid was administered intravenously, followed by 500 mg orally three times a day for a month or until stabilization of neurological dysfunction. The function of glutamic acid in this treatment is not clear. Glutamic acid may not be necessary.

1. Folic acid was infused intravenously in a bolus of 100 mg and then infused at a rate of 25 mg/h for 24 hours. Subsequently, bolus injections of 25 mg were administered every 6 hours for a week. Pyridoxine was administered at a dose of 50 mg every 8 hours by intravenous infusion of 30 minutes duration. The effect of these substances in reducing neurotoxicity is not clear.