Leaflet: information for the user

Vinblastina Stada 10 mg powder for injectable solution

Read this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What isVinblastina Stadaand what is it used for

2. What you need to know before starting to useVinblastina Stada

3. How to useVinblastina Stada

4. Possible side effects

5. Storage ofVinblastina Stada

6. Contents of the pack and additional information

Vinblastina Stada belongs to the group of cytostatics (cancer medications). Vinblastina Stada acts so that cancer cells stop growing, resulting in their destruction.

Indications

• Generalized Hodgkin's disease (stages III and IV, modification of Ann Arbor 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 appropriate hormone treatment.

Do not use Vinblastina Stada powder for injectable solution

• if you have awhite blood cell deficiency(unrelated to the disease)
• if you have anuncontrolled infection, first the infection must be treated with disinfectants (antisetics) or antibiotics.
• if you areallergic (hypersensitive) to vinblastine, to other products in the group of compounds called vinca alkaloids(for example, vincristine) or to any of the other components of this medication (listed in section 6).
• if you arebreastfeeding(see the section "Pregnancy, lactation and fertility")

Inform your doctor if you have any of the contraindications mentioned above or if you have had them in the past.

Warnings and precautions

Consult your doctor before starting to use Vinblastina 10 mg.

Vinblastina Stada should only be administered under the strict supervision of doctors who have experience with the treatment of cytostatics (cancer medications).

Vinblastina Stada should be administeredexclusively by intravenous (in the vein) route and in no case by any other route. Administration by other routes may be fatal.

It should be avoided to have contact of Vinblastina Stada with the eyes. In case Vinblastina Stada enters into contact with the eyes, they should be rinsed immediately with plenty of water and consult your doctor if the irritation persists.

Be especially careful with Vinblastina Stada:

• If after the administration of the dose of Vinblastina Stada adecrease in white blood cells(leucopenia) appears; you should be closely monitored until your white blood cell count increases to a safe value, since otherwise, it is possible that an infection may appear.
• If you havecancer cells in the bone marrow; the production of blood in the bone marrow may sometimes decrease significantly during treatment with Vinblastina Stada.
• In the case ofwomen of childbearing age, Vinblastina Stada may affect fertility. Both men and women of childbearing age should use effective contraceptive methods during treatment and for at least 3 months, but preferably for 6 months after treatment with vinblastine.
• Ifyour liver does not function correctly, the elimination of Vinblastina Stada may be delayed. In these cases, your doctor will adjust the dose of Vinblastina Stada.
• In the case of concomitant prescription withmitomycin C. In these cases, there is a higher risk of dyspnea and sudden apneas (see also, “Administration of Vinblastina Stada with other medications”).
• During treatment with Vinblastina Stada, avoidintense exposure to the sun.
• If during treatment with Vinblastina Stadayou must undergo vaccination, vaccination with a specific type of vaccine (live vaccines) may cause a severe disease. Your doctor will prescribe an inactivated vaccine or postpone the vaccination.
• In the case that you get up after a prolonged rest, asudden drop in blood pressure(orthostatic hypotension) may occur, especially in elderly patients.
• If you have heart diseases such as, for example,ischemic cardiopathy(heart and circulatory problems).

Other medications and Vinblastina Stada

Inform your doctor or pharmacist if you are using or have used recently or may have to use any other medication.

The term “interaction” means that a medication administered concomitantly may influence the effect and/or side effects of another medication. An interaction may appear in the concomitant administration of this injectable solution with the following medications:

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

Pregnancy, lactation and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor before using this medication.

Pregnancy

You should not use Vinblastina 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 possible toxicity. However, based on the effect of the medication, it is possible that Vinblastina Stada may cause harmful effects on the fetus. In animal studies, harmful effects were observed.

Lactation

Breastfeeding should be avoided during treatment with Vinblastina Stada. Although it is not known whether vinblastine is excreted in breast milk, it 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, but preferably for 6 months after treatment with vinblastine. If you become pregnant during treatment, inform your doctor immediately. If you are already pregnant or become pregnant during treatment with vinblastine, it is recommended to seek genetic counseling.

In the case of men, it should be avoided to father a child during treatment with vinblastine and for at least 3 months, but preferably 6 months, after treatment.

Fertility

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

Driving and operating machinery

There is no information available on the effect of this medication on driving ability or on the ability to operate machinery. However, in some cases, this medication may cause dizziness or seizures (see the section, “4. Possible adverse effects”). If you experience any of these adverse effects, do not drive any vehicle and/or operate machinery that requires maximum attention.

Vinblastina Stada contains sodium

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

Dosage

Vinblastina Stada will be injected into a vein by your doctor, either as an injection or an infusion.

Although vinblastine is sometimes administered alone, it is common for it to be used in combination with other cancer medications.

Your doctor will establish the dosage of Vinblastina Stada and the number of administrations, which may vary depending on the patient. The dosage may be increased at weekly intervals until the desired effect on cancer is achieved or until the white blood cell count is reduced to a certain level (leucopenia). It is recommended to administer the medication at a frequency not exceeding once every seven days. Generally, a single dose, as high as possible, is administered once every 7 to 14 days, without causing a dangerous reduction in white blood cell count (leucopenia).

If your liver does not function correctly at the beginning of treatment, your doctor may reduce the dosage or suspend treatment.

Administration Form

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

Vinblastina Stada should only be administered through a vein by injection or infusion.

If a decrease in white blood cells (leucopenia) or an infection appears during treatment, treatment with vinblastine will be suspended or an antimicrobial medication (antibiotic) will be prescribed.

Direct contact of the medication with the skin, eyes, and mucous membranes should be avoided. In the event of accidental contact, the area should be immediately rinsed with abundant water.

If more Vinblastina Stada is administered than it should

If an excessive amount of Vinblastina Stada is administered, the side effects described in the section “4. Possible adverse effects” such as a decrease in white blood cells (causing an increased propensity to infections), symptoms of peripheral neuropathy (for example, tingling, pins and needles, skin numbness) without a physical reason for it, may manifest more intensely.

In the event of an overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20 indicating the medication and the amount administered.

If you forgot to use Vinblastina Stada

In the event of a missed dose of Vinblastina Stada, it should be administered as soon as possible. Contact your doctor immediately to consult when the missed dose can be administered.

Ask your doctor or pharmacist if you are unsure.

If you interrupt treatment with Vinblastina Stada

Always consult your doctor before suspending the administration of Vinblastina Stada. In the event of suspension, the symptoms that already existed previously may reappear.

Ask your doctor or pharmacist if you have any other doubts about the use of this product.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Among others, the following side effects may appear:

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

• Blood disorders (low white blood cell count), including an increased susceptibility to infections (leucopenia)
• Nausea, vomiting
• Hair loss, which is usually not complete and may recover during treatment
• Blistering in the mouth and on the skin

Common(may affect up to 1 in 10 people)

• Anemia, blood disorder (low platelet count), 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
• Itching, tingling, and pinching without a perceptible cause (paresthesia), decreased reflexes.
• Constipation, limited or absent intestinal transit (ileus), gastric or duodenal ulcer bleeding, intensely bleeding intestinal mucosa inflammation (enterocolitis hemorrágica), rectal bleeding, loss of appetite (anorexia), diarrhea. Constipation that may appear responds well to measures such as enemas or laxatives.

Uncommon(may affect up to 1 in 100 people)

• Depression
• In some cases, throat inflammation (pharyngitis) appears. Shortness of breath and sudden apneas may occur due to contraction of the respiratory tract muscles (bronchoconstriction). In the case of simultaneous or previous administration of mitomycin C, shortness of breath, wheezing, and respiratory function disorder may appear a short time after treatment or up to two weeks after treatment. In this case, the doctor must immediately suspend treatment with vinblastine and mitomycin C; see also the section, “Other medicines and Vinblastine Stada”
• Tumor site pain, discomfort sensation.

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

• Severe disease, in which an excess of fluid is retained as a result of an elevated secretion of a certain hormone from the adrenal glands (SIADH: Syndrome of inappropriate ADH secretion). Appears both with recommended doses and with higher doses
• Stroke in patients who have received treatment with a combination of bleomycin, cisplatin, and vinblastine; sensation of deafness, numbness, neuritis (inflammation of the nerves), including pain, emotional disorder, and, in some cases, inflammation of the peripheral nervous tissue in the extremities (peripheral neuritis) that manifests in the form of pain, tingling, pinching, numbness of the skin without a physical cause, headache, convulsions, and sensory weakness.
• Partial or total deafness, which 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), cardiac rhythm disorder

Frequency not known(cannot be estimated from available data)

• Anemia caused by abnormal destruction of red blood cells (hemolytic anemia)
• Painful facial and mandibular nerve, neuritis including pain, emotional disorder, and, in some cases, decreased effect on nerves in the extremities (peripheral neuropathy), vocal cord paralysis
• Severe mental illness in which behavior and personal actions are affected (psychosis)
• Severe corneal injury, accompanied by eyelid spasm, eyelid swelling, and preauricular lymph node swelling, following contact of vinblastine with the eyes
• Tinnitus (ringing in the ears)
• Myocardial infarction in people who have received treatment with a combination of bleomycin, cisplatin, and vinblastine
• Reduction of blood flow to the extremities (Raynaud's phenomenon) in patients treated with a combination of bleomycin, cisplatin, and vinblastine
• In some cases, high blood pressure (hypertension) or very low blood pressure (hypotension) may appear
• Orthostatic hypotension, including dizziness, caused by a rapid rise from a seated or lying position
• Mucosal inflammation of the mouth and stomach, abdominal pain, painful salivary glands
• Severe liver disease (hepatic fibrosis), characterized by permanent damage to the liver tissue
• Skin inflammation (dermatitis), hypersensitivity to light or sunlight (phototoxicity)
• Decreased muscle mass (muscular atrophy)
• Urinary retention due to altered bladder emptying
• Microangiopathic thrombotic disease with renal failure
• Decreased fertility (in both men and women), lack of semen (aspermia)
• Weakness, fever, pain, inflammation of veins, subcutaneous tissue, and skin, skin death in the event of accidental injection of vinblastine outside the veins, pain at the injection site.

Reporting of side effects

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

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

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

Vials of Vinblastina Stada must be stored in a refrigerator (between 2 and 8°C).

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

Medicines should not be thrown down the drains or in the trash. Ask your pharmacist how to dispose of the packaging and the medications that you no longer need. In this way, you will help protect the environment.

Composition of Vinblastina Stada

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

Appearance of the product and contents of the container

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

Marketing Authorization Holder

STADA, S.L.

Frederic Mompou, 5

08960 Sant Just Desvern

(Barcelona)

Spain

Responsible for manufacturing

STADA Arzneimittel AG

Stadastraße 2-18

61118 Bad Vilbel

Germany

Last review date of this leaflet:October 2017

The detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/

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This information is intended solely for healthcare professionals:

Administration

Vinblastine must 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 must be handled exclusively by trained personnel, familiar with the safe handling of the preparation. The reconstitution of the powder and transfer to syringes must be performed only in a designated area for this purpose.

The personnel performing these operations must be properly protected with protective clothing, gloves, and protective glasses.

Pregnant women must not come into contact with cytotoxic drugs.

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

Vinblastina Stada must not be mixed with other medications in the same container.

Contamination

In case of contact with the skin or eyes, the affected area must be rinsed with plenty of water or physiological serum. A refreshing cream may be used to treat the temporary sensation of burning on the skin. In case of ocular involvement, medical intervention is required.

In case of spills, personnel must 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. Introduce all solutions and sponges into a plastic bag intended for this purpose and seal it.

Stools and vomit must be cleaned carefully.

Disposal of waste

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

All unused material, damaged containers, or contaminated waste must be disposed of in accordance with local requirements in containers designed specifically for this purpose.

Compatibilities:

Sodium chloride 0.9%,

Benzyl alcohol 0.9%

The intrathecal administration of vinblastine may cause potentially fatal neurotoxicity

When vinblastine sulfate is administered accidentally by intrathecal route, the following treatment is recommended. In one case, the progressive paralysis in an adult who had received an alkaloid derived from vincristine, vincristine sulfate, by intrathecal route was inhibited with the following treatment. The treatment must be initiated immediately:

1. The largest possible amount of cerebrospinal fluid was removed through the lumbar access, without compromising safety.

1. A solution of Ringer lactate was irrigated through the subarachnoid space by continuous infusion through a catheter inserted into the lateral cerebral ventricle at a rate of 150 ml/hour. The liquid was removed through a lumbar access.

1. After performing the procedure in point 2, 25 ml of plasma, previously briefly frozen, was diluted in 1 liter of Ringer lactate solution and infused through a cerebral ventricular catheter at a rate of 75 ml/h. The liquid was removed 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 diluted plasma, previously briefly frozen.

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

1. A solution of folic acid was infused intravenously in a bolus of 100 mg, followed by a rate of 25 mg/h for 24 hours. Subsequently, injections of 25 mg every 6 hours for a week were administered. Pyridoxine was administered at a dose of 50 mg every 8 hours by intravenous infusion of 30 minutes' duration. The effect of these substances on the reduction of neurotoxicity is unclear.