Prospecto:Information for the Patient

Natulan 50 mg Hard Capsules

procarbazine

Read this prospect carefully before starting to take this medicine,because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult yourdoctororpharmacist.
• This medicine has been prescribedonlyto you, and you must not give it to other people even iftheyhavethe same symptomsas you,as it may harm them.
• If you experience any adverse effects,consult yourdoctororpharmacist,evenifthey are not listed in this prospect. See section 4.

1.What is Natulan and for what it is used

2.What you need to knowbeforestarting totake Natulan

3.How to take Natulan

4.Possible adverse effects

5Storage of Natulan

6.Contents of the package and additional information

Natulan contains the active ingredient procarbazine. Procarbazine is a medication for treating cancer (systemic cytotoxic drug). It acts by killing cancer cells. This is also known as "chemotherapy".

Adults
Natulan is indicated for combined chemotherapy for the treatment of Hodgkin's lymphoma. This medication is also indicated as part of a combined chemotherapy regimen for other advanced lymphomas and brain tumors.

Children and adolescents
Natulan, when combined with other antineoplastic treatments, is indicated for the treatment of Hodgkin's lymphoma in children aged 2 to 18 years.

Do not take Natulan

• if you are allergic to procarbazine or any of the other components of this medication (listed in section 6).
• if you have a severe bone marrow disorder (bone marrow depression) and severe alterations in the number of white blood cells and platelets in the blood.
• if your renal and/or hepatic function is severely impaired.
• during pregnancy or lactation.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Natulan.

• Procarbazine may affect your blood and immune system. Blood cells are produced in your bone marrow. These cells are of three types:
• • red blood cells, which transport oxygen in the body,
  • white blood cells, which fight infections, and
  • platelets, which allow blood to clot.
• After receiving this medication, your blood cell count will decrease. Therefore, your doctor will monitor your blood countsbefore and during the administration of this medication.
• Before treatment, your liver and kidney function will be evaluated and monitored periodically during treatment.
• During treatment with this medication, you may experience fever, bleeding, or superficial bleeding on the skin due to a decrease in blood cells. If this occurs, you must immediately inform your doctor.
• If you experience gastrointestinal discomfort with nausea and vomiting, consult your doctor immediately.

Children and adolescents

Natulan is always administered to children and adolescents at the same dose as for adults in combination with other cancer medications. Your doctor will determine the necessary dose for your child.

Other medications and Natulan

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

Some medications may alter the effect of Natulan, or Natulan may affect the efficacy of other medications administered at the same time.

Procarbazine potentiates the effect of the following medications:

• oral antidiabetic agents (diabetes medications taken orally) and insulin: since these can reduce your blood sugar level more than usual when used with this medication, they may cause low blood sugar levels.
• antihistamines (for the treatment of allergic symptoms)
• barbiturates (sleep inducers and narcotics)
• hypotensive medications (medications to lower blood pressure)
• narcotics
• phenothiazines (medications for the treatment of mental disorders, or tranquilizers)

As procarbazine is a weak monoamine oxidase inhibitor (MAO), interactions with medications that induce a nervous system reaction are possible, such as:

• sympathomimetics (to stimulate the autonomic nervous system)
• antiasmatics (for the treatment of asthma)
• nasal anti-inflammatory sprays/aerosols
• medications that increase blood pressure
• tricyclic antidepressants (amitriptyline, imipramine)
• serotonin reuptake inhibitors (SSRIs, for the treatment of depression, for example, sertraline)

The allopurinol may prolong the effect of procarbazine.

No studies have been conducted on interactions with medications such as ketoconazole or rifampicin, so caution should be exercised when using them in combination with procarbazine.

Taking Natulan with food, drinks, and alcohol

The simultaneous ingestion of procarbazine and foods high in tyramine may cause hypertensive crises. Therefore, cheese, cheese spread, yogurt, beverages containing methylxanthine (coffee, black tea, Coca-Cola), alcoholic beverages (beer, wine, vermouth, sherry, port), chocolate, dry sausages (salami), meat, liver, yeast or yeast extracts, beans, peas, overripe fruits, avocado, bananas, figs, herring, smoked or marinated meats or fish, as well as spoiled or smoked meats or fish.

Alcohol and alcoholic beverages combined with procarbazine may cause a reaction that includes hot flashes, including facial flushing (flushing), increased heart rate, sweating, decreased blood pressure, headache, and difficulty breathing (antabuse syndrome). Therefore, complete avoidance of alcohol during the entire therapy is recommended.

Pregnancy, lactation, and fertility

If you are pregnant or breastfeeding, consult your doctor or pharmacist.

Pregnancy

Procarbazine may cause genetic damage andmay harm the fetus.Do not use this medication during pregnancy unless your doctor considers it clearly necessary. If you receive this treatment, ask a doctor to explain the risk of possible adverse effects of the treatment for your child and genetic counseling is recommended.

Women should not become pregnant during procarbazine treatment.

If you become pregnant during treatment, genetic counseling is recommended.

Lactation

This medication should not be administered during lactation. If you need treatment with procarbazine during lactation, you should discontinue it.

Fertility

Before starting procarbazine treatment, both male and female patients should be informed about the risk of permanent infertility (sterility).

Male patients treated with procarbazine should use contraceptive methods during treatment and for 3 months after treatment. Due to the possibility of irreversible infertility after procarbazine treatment, consult your doctor about sperm conservation.

Women should not become pregnant during procarbazine treatment. They should use recognized contraceptive methods during treatment and for 6 months after treatment with this medication.

Driving and operating machinery

As procarbazine may cause nausea and vomiting, it may indirectly affect your ability to drive and operate machinery. If you feel dizzy or drowsy, do not drive or operate machinery until these effects have disappeared.

As a general rule, procarbazine should only be prescribed by doctors with sufficient medical oncological or hematological experience and in accordance with an appropriate chemotherapy protocol for their disease. This applies particularly to its use in children and adolescents.

Follow exactly the administration instructions for this medication indicated by your doctor.In case of doubt, consult your doctor again?or?pharmacist.

Dosage

Procarbazine dosage in combination with other chemotherapeutic agents:

The usual dose in most combinations is 100mg/m2/day for 10 to 14days of each cycle of 4 to 6weeks. The dose should be adjusted according to the chemotherapy protocol used.

Procarbazine dosage in monotherapy:

Adults

Start with 50mg on the first day, then increase progressively 50mg each day until reaching a dose of 250 to 300mg/day.

The treatment should be continued with a dose of 250 or 300mg per day until the most complete possible remission is achieved, after which a maintenance dose should be administered. A maintenance dose of 50 to 150mg per day should be administered. The treatment should be continued until a total dose of at least 6g has been administered.

Pediatric population (2 to 18years)

The dose used in most published clinical trials was analogous to that used in adults (100mg/m2/day for a maximum of 14days). Available data are limited. Dosing in children should be adapted individually and with strict clinical control.

The dose should be adjusted according to:

• The chemotherapy protocol used.
• The functional status of the bone marrow.
• Previous cycles of chemotherapy and radiation therapy.
• The myelosuppressive effect of other cytostatic agents used.
• The treatment should be temporarily interrupted if the white blood cell count is less than 3,000mm3and/or platelets are below 80,000mm3and it can be restarted when the levels recover. The patient's hematological status should be determined at least every 3 or 4 days.

Special populations

Patients with liver and kidney insufficiency:

Procarbazine should be used with caution in patients with liver or kidney insufficiency and is contraindicated in case of severe insufficiency (see section4.3). Liver and kidney function should be determined weekly.

Older patients:

It should be administeredwith caution in older patients. Patients in this group should be closely monitored to identify early signs of treatment failure or intolerance.

Administration form

Procarbazine capsules are for oral administration. Capsules should not be opened, broken, or chewed. Capsules should be taken whole, with a glass of water, with or without food.

If you take more Natulan than you should

If you, or anyone else, exceed the dose of this medication, inform your doctorimmediatelyor go to the nearest hospital emergency room. Please remember to bring this medication package or this leaflet with you.

Especially in patients with limited bone marrow reserve, procarbazine overdose can cause severe functional impairment or bone marrow deterioration.In this case, supportive treatment measures, such as antibiotic treatment and platelet replacement, may be required in a specialized intensive care unit for oncology medicine, according to the severity of symptoms.

The following events have been reported associated with procarbazine overdose: dizziness, nausea, vomiting, diarrhea, decreased blood pressure, palpitations, tremors, hallucinations, depression, bone marrow insufficiency, convulsions, coma, and muscle cramps.

During recovery and for at least two weeks thereafter, both the hemogram and liver function should be monitored regularly. Prophylaxis of infections should be considered. Additionally, the decision to continue specific treatment should be made based on blood values.

In case of 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 ingested).

If you forget to take Natulan

Do not take a double dose to compensate for the missed doses. If you forget to take this medication once, continue taking it as described in the dosing instructions without taking an additional dose.

However, you should talk to your doctor, especially if you have forgotten to take several doses. Your doctor will decide how to proceed with taking the medication.

If you interrupt treatment with Natulan

Procarbazine often causes nausea and vomiting. Do not interrupt treatment with Natulan, even if you start feeling unwell. If this occurs, inform your doctor immediately. You will take the necessary measures to make the unwanted side effects accompanying therapy more tolerable.

Inform your doctor if you vomited shortly after taking Natulan. They will then decide whether to take an additional dose or wait until the next regular dose.

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

The following list of adverse reactions includes all known adverse reactions during treatment with procarbazine. Natulan is a medicine that can kill cancer cells but also attacks normal cells, so it may have a series of side effects.

Your doctor will not administer Natulan unless he is convinced that your cancer has a greater risk for you than the possible side effects of treatment. Your doctor will examine you regularly and treat any adverse effect when possible.

Inform your doctor immediately if you notice any of the following severe side effects:

The most frequent severe reactions of procarbazine are hair loss (alopecia), gastrointestinal alterations such as weight loss (anorexia), nausea and vomiting, and bone marrow depression (reduction of the number of blood cells).

Due to its effects on different types of white blood cells, many cancer treatment medications, including procarbazine, cause a deep suppression of normal immunity, and patients may have a much greater risk of presenting severe and diverse infections.

The evaluation of side effects is based on the following frequencies:

Frequent: affects less than 1 in 10 treated patients

- infections;

- decrease in blood cell count (red blood cells, platelets, white blood cells);

- anorexia (loss of appetite);

- nausea;

- vomiting;

- alopecia;

Rare: affects more than 1 in 1000 patients

- hypersensitivity (including anaphylaxis, angioedema)

Unknown frequency (cannot be estimated from available data)

- sepsis, herpes zoster, pneumonia, urinary tract infection, nasopharyngitis;

- acute myeloid leukemia, myelodysplastic syndrome, primary secondary neoplasms;

- bone marrow insufficiency. abnormal blood cell count (decrease or increase) of red blood cells, white blood cells, platelets;

- depression, confusion;

- seizures, peripheral neuropathy, paresthesia, headaches;

- visual disturbances (including blurred vision and visual deterioration);

- hemorrhages;

- pulmonary diseases, dyspnea, cough;

- stomatitis, constipation, diarrhea, abdominal pain;

- hepatotoxicity. hepatitis, jaundice (increase in bilirubin);

-Stevens-Johnson syndrome, toxic epidermal necrolysis, skin rash, urticaria;

-osteonecrosis, myalgia;

- azoospermia (sometimes permanent), sterility;

- pain, fever, fatigue, general malaise, feeling of lack of energy or vitality.

Reporting of side effects

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

Keepthis medicationout 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.

Do not store above 25°C.

Store in the original packaging to protect it from moisture.

Medications should not be disposed of through drains or trash. Dispose of packaging and medications you no longer need at the SIGRE drop-off point at the pharmacy. Ask your pharmacist how to dispose of packaging and medications you no longer need. This will help protect the environment.

Natulan Composition

The active ingredient is: procarbazine

Each hard capsule contains 58.3 mg of hydrochloride of procarbazine (corresponding to 50 mg of procarbazine).

The other components are:

Capsule content: mannitol (E 421), talc, cornstarch, magnesium stearate.

Capsule coating: gelatin, titanium dioxide (E 171),yellow iron oxide (E172).

Product appearance and packaging contents

Natulan are hard, beige-yellow capsules available in brown glass bottles with HDPE screw cap with desiccant containing 50 hard capsules.

Marketing authorization holder and manufacturer responsible

Leadiant GmbH

Liebherrstasse 22

80538 Munich

Germany

For more information about this medication, please contact the local representative of the marketing authorization holder:

Medicare Pharma, S.L.,

Ctra. Fuencarral, 22,

28108, Alcobendas,

Madrid

Last review date of thisleaflet:August 2024

Detailed information about 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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