Prospect: information for the user

Megamilbedoce 10.000 micrograms Injectable Solution

Hidroxocobalamina

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

• Conserve this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only to you, and you should not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect.

1.What is Megamilbedoce and for what it is used

2.What you need to know before starting to use Megamilbedoce

3.How to use Megamilbedoce

4.Possible adverse effects

5.Conservation of Megamilbedoce

6.Contents of the package and additional information

Megamilbedoce contains a form of Vitamin B12ina very high dose, allowing for intense and prolonged administration. Vitamin B12 is involved in the body in many metabolic processes, including some related to the nervous system and the formation of blood cells.

Megamilbedoce is indicated in vitamin B12 deficiency states, such as:

-Pernicious anemia (a type of anemia), malabsorption syndromes (digestive absorption problems, such as inflammatory intestinal processes like sprue or Crohn's disease), gastrectomy (complete or partial removal of the stomach) or significant ileal resection (removal of a large portion of a part of the small intestine). In strict vegetarians.

-Metabolic disorders: patients with methylmalonic acidemia (a hereditary disorder in which a substance called methylmalonic acid accumulates in the blood) with or without homocystinuria.

No use Megamilbedoce:

-if you are allergic to the active ingredient, cobalamins (vitamin B12, other forms), cobalt, or any of the other components of this medication (listed in section 6).

Advertencias and precautions

Consult your doctor before starting to useMegamilbedoce.

• In case of anemia, the vitamin B12 deficiency must be confirmed before starting treatment, so it is likely that your doctor will instruct you to undergo blood and urine tests. During treatment, you will also be sent periodic tests to monitor your blood cells and vitamin B12 and other product levels.
• Before injectable treatment, you must monitor your blood potassium levels and, if necessary, administer this product to prevent the possibility of a severe reaction.

-Parenteral administration (intramuscular or intravenous) requires caution, as some sensitive patients may experience anaphylactic shock (generalized allergic reaction) and angioedema (rapid swelling of the skin, mucous membranes, and nearby tissues). Therefore, it is recommended to administer a test dose to patients who may be sensitive.

• If you are prone to gout, you should be cautious because hydroxocobalamin may precipitate a gout crisis.
• The effect of vitamin B12 treatment (active ingredient of this medication) decreases in situations such as uremia (increase of nitrogenous substances in the blood), infections, iron deficiency, or folic acid deficiency, and with the administration of bone marrow suppressor medications (e.g., chloramphenicol).
• This medication may mask the symptoms of polycythemia vera (blood disease).
• Intravenous administration (directly into a vein) may cause a rise in blood pressure.
• The administration of large amounts of hydroxocobalamin by intravenous route in a parenteral nutrition solution would result in almost total loss through urine (see the last section of the prospectus).

Interference withdiagnostic tests: If you are to undergo any diagnostic test (including blood, urine, skin tests using allergens, etc.), inform your doctor that you are taking this medication, as it may alter the results.

Children and adolescents

Although this medication should not be used in children under 3 years of age (see sectionMegamilbedoce contains benzyl alcohol and sodium), it may be used in this population if considered essential, administered under medical supervision.

Use ofMegamilbedocewith other medications

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

Megamilbedocemay interact with the following medications:

-Chloramphenicol (antibiotic).

-Oral contraceptives.

-Several medications may interfere with hydroxocobalamin (vitamin B12) and may decrease its absorption if taken orally, including: antibiotics aminoglycosides such as neomycin, colchicine (gout medication), mesalazine (for intestinal diseases),medications for ulcers (cimetidine, ranitidine, etc.), medications for epilepsy (phenytoin, phenobarbital, primidone, etc.), potassium preparations with sustained release, cobalt radiation, vitamin C supplements, and excessive alcohol intake.

Use ofMegamilbedocewith alcohol

Large alcohol intake decreases theabsorption of vitamin B12.

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.

At present, there are no well-controlled studies in pregnant women.

It is not recommended to use Megamilbedoce during pregnancy.

Vitamin B12is excreted in breast milk. Given the lack of information on safety, the use of Megamilbedoce is contraindicated during lactation.

Driving and operating machines

The influence of Megamilbedoceon the ability to drive and operate machines is insignificant. However,this medication may cause dizziness in some patients, who in this case should not drive or operate hazardous machines.

Megamilbedoce contains alcohol bencílico and sodio

This medication should not be administered to premature infants or newborns because it contains 4 mg per ampoule of benzyl alcohol. It may cause toxic reactions and allergic reactions in children under 3 years of age.

(See sectionChildren and adolescentsin section 2.What you need to know...).

This medication contains less than 23 mg (1 mmol) of sodium per ampoule, making it essentially “sodium-free”.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor again.

The recommended doses are:

The doses vary according to the indications.

Route of administrationor, in the case of patients who have undergone gastrectomy (complete or partial removal of the stomach) byintramuscular route or deep subcutaneous route.

Adults

• Deficiency of vitamin B12 inuncomplicated pernicious anemia or malabsorption of vitamin B12:

?The initial recommended dose is 100 micrograms of hydroxocobalamin (0.02 ml of solution) per day for 5-10 days, followed by 100-200 micrograms (0.02-0.04 ml of solution) per month until improvement. After remission, a maintenance dose of 100 micrograms per month is recommended.

?Another alternative treatment regimen with higher doses may be necessary: between 250 and 1,000 micrograms (0.05-0.2 ml of solution) intramuscularly on alternate days for 1 or 2 weeks, followed by 250 micrograms (0.05 ml) per week until remission; maintenance doses of 1,000 micrograms every 2 or 3 months.

• Pernicious anemia complicated or malabsorption of vitamin B12 with neurological complications (in the nervous system): the most common administration regimen is 1,000 micrograms of hydroxocobalamin (0.2 ml of injectable solution) per day for the first week of treatment, continuing with a dose of 1,000 micrograms (0.2 ml) per week for a month and then 1,000 micrograms (0.2 ml) per month as a maintenance dose until the cause is cured.

Patients with pernicious anemia or vitamin B12 deficiency due to another irreversible defect in absorption require lifelong maintenance treatment.

-Prophylaxis of anemia in gastrectomized patients:1,000 micrograms(0.2 ml) every 2 or 3 months,byintramuscular route or deep subcutaneous route.

-Vitamin B12 deficiency of dietary origin, such as in strict vegetarians: a dose of 100 micrograms (0.02 ml) per month by IM may be administered, with periodic blood tests.

-Metabolic disorders:

• Methylmalonic acidemias with homocystinuria: The minimum dose to be administered is 1,000 micrograms(0.2 ml)per day by intramuscular route, a dose that can be replaced by the administration of 1,000 micrograms (0.2 ml) intramuscularly on alternate days. In case of need, these doses could reach double (up to 2,000 micrograms per administration, that is, 0.4 ml of Megamilbedoce).
• Methylmalonic acidemia without homocystinuria: Some of them improve with hydroxocobalamin, at a dose of 1,000 micrograms(0.2 ml)per week, by intramuscular route. If no improvement is observed, your doctor will discontinue treatment.

Use in children

Although Megamilbedoce should not be used in children under 3 years old whenever possible due to its content of benzyl alcohol (seeMegamilbedoce contains benzyl alcohol ...,in section 2), it may be used if your doctor considers it necessary, under their supervision.

The requirements vary with age.

-In children with uncomplicated pernicious anemia or malabsorption of vitamin B12, the recommended dose is 30 to 50 micrograms per day (between 0.006 and 0.01 ml) for 2 or more weeks, until a total dose of 1,000 to 5,000 micrograms of hydroxocobalamin (between 0.2 and 1 ml) is reached; maintenance dose of 100 micrograms per month (0.02 ml) is recommended.

-In pernicious anemia or vitamin B12 deficiency due to another irreversible cause, the recommended dose is 1,000 micrograms (0.2 ml) intramuscularly every 2 or 3 days, until a total of 5 doses is reached; the maintenance dose is 1,000 micrograms every 3 months.

-Metabolic disorders:

• Methylmalonic acidemias with homocistinuria: The minimum dose to be administered is 1,000 micrograms(0.2 ml)per day by intramuscular route, a dose that can be replaced by the administration of 1,000 micrograms (0.2 ml) intramuscularly on alternate days. In case of need, these doses could reach double (up to 2,000 micrograms per administration, that is, 0.4 ml of Megamilbedoce). In smaller children, a dose of 200 micrograms/kg of body weight (0.04 ml/kg) per day is proposed.
• Methylmalonic acidemia without homocystinuria: Some of them improve with hydroxocobalamin, at a dose of 1,000 micrograms(0.2 ml)per week, by intramuscular route. If no improvement is observed, your doctor will discontinue treatment.

In other enzymatic deficiencies of vitamin B12 metabolism, patients may be treated with similar doses to those mentioned above, according to their response.

In metabolic disorders, if theoral routehad to be used, a dose of 10,000 micrograms (1 vial) is recommended for both adults and children, but due to poor absorption by this route, blood tests should be performed one week after administration.

In methylmalonic acidemias with homocistinuria, this route of administration should not be used, as adequate levels of hydroxocobalamin are not reached.

Administration form:

(See also the last section of the prospectus).

Megamilbedoce is administered mainly byintramuscular routeand in the case of patients who have undergone gastrectomy (complete or partial removal of the stomach) byintramuscular route or deep subcutaneous route.

It may also be possible, in certain cases, to administer by the following routes:

• Oral route: it can be administered orally in patients who do not tolerate the intramuscular route, provided they do not have serious alterations in the digestive tract that affect absorption. Theabsorption of hydroxocobalamin by the oral route is irregular, so blood tests should be performed.

If administered orally, it can be taken directly or dissolved in liquid.

• Intravenous route: hydroxocobalamin could be administered intravenously in very specific cases and only when a doctor indicates it, as it presents a risk of anaphylactic reactions (exaggerated allergic reactions). It will be administered by direct intravenous infusion.

If you use more Megamilbedoce than you should

Even in accidental overdoses, there are no known cases of intoxication. In rare cases, a severe allergic reaction may occur.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or go to a medical center or call the Toxicology Information Service, Tel. 91 562 04 20, indicating the medication and the amount ingested.

If you forgot to use Megamilbedoce

Do not use a double dose to compensate for the missed doses.

If you forget to administer yourcorresponding dose, administer it as soon as possible.

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

Like all medications, Megamilbedoce may cause side effects, although not everyone will experience them.

These are generally infrequent but moderately important.

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

The following side effects may occur; the frequency of some of them is not known with precision:

-Frequently, reduction in the number of lymphocytes (a type of white blood cell).

- Possible masking of apolycythemia (blood disorder).

- Infrequently,pain at the injection site.

- Allergic reactions, with chest tightness, angioedema (rapid swelling of the skin, mucous membranes, and nearby tissues),urticaria (red, itchy hives),itching, difficulty breathing; frequently, skin redness, rashes (especially, acne-like); photosensitivity (sensitivity to sunlight).

- Rarely, anaphylactic reaction (generalized allergic reaction).

- Decrease in the amount of potassium in the blood, after the medication injection.

- Very frequently, headache.

- Restlessness, dizziness, swelling, irritation, and redness of the eyes.

- Rarely, arrhythmias (irregular heartbeats).

- It is possible congestive heart failure at the beginning of treatment.

- Hot flashes, peripheral edema (swelling of ankles, feet, and legs);peripheral vascular thrombosis (formation of a clot that blocks blood flow in a vessel outside the heart, usually in the legs or feet).

- With intravenous administration, hypervolemia (increase in total blood volume) and

very frequently, increased blood pressure;frequently, reaction at the injection site.

- Difficulty breathing or "choking" fatal in premature children, due to the content of benzyl alcohol (see sectionsMegamilbedoce contains benzyl alcohol and sodiumin section 2 andUse in childrenin section 3).Rarely, pulmonary edema (infiltration of fluid in the lungs).

- Frequently, nausea.

- Digestive discomfort, transient diarrhea.

- Very frequently, reddish discoloration of urine.

If you experience side effects, consult your doctor or pharmacist,even if they are side effects that do not appear in this prospectus.

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.

Medications should not be disposed of through drains or in the trash. Dispose of the packaging and medications you no longer need atthe SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medications you no longer need. By doing so, you will help protect the environment.

Composition ofMegamilbedoce 10.000 micrograms Injectable Solution

-The active ingredient ishydroxocobalamin (vitamin B12).

A 2 ml ampoule contains 10,000 micrograms ofhydroxocobalamin.

1 ml of solution contains 5,000 micrograms ofhydroxocobalamin.

-The other components (excipients) are: benzyl alcohol (4 mg per ampoule), sodium chloride and water for injection preparations.

Appearance of the product and contents of the packaging

The medicine is a solution that is presented in amber-colored ampoules containing a clear red liquid.

Box with 10 ampoules of 2 ml.

Holder of the marketing authorization

Aristo Pharma Iberia, S.L.

C/ Solana, 26

28850, Torrejón de Ardoz

Madrid. Spain

Responsible for manufacturing

Laboratorios Medicamentos Internacionales, S.A. (MEDINSA)

C/ Solana, 26

28850 – Torrejón de Ardoz. (Madrid)

Date of the last review of this leaflet:November 2012

Other sources of information

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

This information is intended solely for doctors or healthcare professionals:

The intramuscular injection will be performed in a wide muscle mass.

The intravenous administration will be performed by including small amounts of hydroxocobalamin in a parenteral nutrition solution.