The active ingredients of OXA® B12 I.M. are sodium diclofenac, a drug which belongs to the non-steroidal anti-inflammatory drugs (NSAIDs); betamethasone, a corticosteroid, and hydro­xocobalamin (B₁₂ vitamin). OXA® B12 I.M. is indicated for pain relief and inflammation; it benefits nerve regeneration for the treatment of acule musculoskeletal conditions (bones, joints and muscles) such as low back pain, lumbosciatic pain and worsening of chronic rheumatic disorders such as rheumatoid arthritis, osteoarthritis (arthrosis), ankylosing spondylitis (a type of arthritis that affects the joints of the spine) and gout.

As it may occur with all medications, OXA® B12 I.M. may cause adverse events in sorne people.

The following adverse events have been reported during the treatment with the medication ingredients; but it does not mean that they are causally related with the medication.

Diclofenac

Incidence > 1 % of the treated cases - Probable causal relationship

General: abdominal pain or cramps, headache, fluid retention, abdominal enlargement.

Digestive system: diarrhea, digestive disorders, nausea, constipation, flatulence, modifications of hepatic laboratory tests, peptic ulcer with or without bleeding and perforation or hemorrhage without ulcer.

Nervous system: vertigo.

Skin and appendages: rash, itching.

Special senses: tinnitus.

Incidence < 1 % of the treated cases: general discomfort, allergic-type reactions, high blood pressure, congestive heart failure, vomiting, jaundice, melena, aphthous stomatitis, dried mouth and mucosae, melena, hepatitis, pancreatitis with or without concomitant hepatitis, decreased hemoglobin, leukopenia, thrombocytopenia, purpura, high levels of urea, insomnia, depression, fatigue, double vision, anxiety, irritability, epistaxis, asthma, laryngeal edemas, alopecia, hives, eczema, dermatitis, angioedema, blurred vision, alterations in taste, reversible loss of hearing, blind spots, proteinuria.

Betamethasone

The betamethasone used in the recommended doses during short periods (no more than 2 weeks) is generally well tolerated. The following adverse events may appear in high doses or during prolonged treatments.

Hydroelectrolytic disorders: sodium retention, fluid retention, congestive heart failure in susceptible patients, hypocalcemia in blood, high blood pressure.

Musculoskeletal: muscular weakness, loss of muscle mass, osteoporosis, vertebral fractures by compression, aseptic necrosis of humeral and hip heads, pathological fractures of long bones.

Gastrointestinal: peptic ulcer with or without perforation or hemorrhage, pancreatitis, abdominal enlargement, ulcerative esophagitis.

Skin: irregular healing of wounds, thin and fine skin, ecchymosis and petechia, facial erythema, increased sweating, may cause negative results in the skin-reactions tests. Neurological: convulsions, increased intracranial pressure with papillary stasis, vertigo, headache.

Endocrine: menstrual disorders, Cushing syndrome, decreased children`s growth, lack of adrenal and pituitary response, especially under stress situations (trauma, surgery, etc.), decreased tolerance to carbohydrates, increased insulin doses or oral hypoglycemic agents in patients with diabetes mellitus, occurrence of a subclinical diabetes mellitus.

Ophthalmologic: cataract (posterior subcapsular), increased intraocular pressure, glaucoma, exophthalmos (protruding eyes).

Metabolic: protein catabolism (protein degradation). With parenteral administration, hyperpigmentation or hypopigmentation, cutaneous and subcutaneous atrophy, and sterile abscess have been reported.

Hydroxocobalamin

Rare cases of allergic reactions, following injection, have been observed.

Local reactions due to intramuscular injections

The intramuscular administration of medications may cause reactions in the application site, which may be related with the administered medication, the application technique and/or patient`s individual factors. Undesirable local events in the application site have been reported such as post-injection pain, induration and, in rare cases, evident abscesses and necrosis. If redness, hardening or pain in the application site are observed, contact immediately your doctor.

5. Additional information

Do not administer by intravenous route.

Expiration date

DO NOT ADMINISTER THE MEDICATION AFTER THE EXPIRATION DATE PRINTED IN THE PACKAGE.

The expiration date corresponds to the last day of the mentioned month.

STORAGE CONDITIONS

Store at 15 to 30 ºC, protected from light, in the original packaging.

HOW SUPPLIED

Packages with 3 and 6 ampoules.

KEEP THIS MEDICINE OUT OF THE REACH OF CHILDREN.

Each ampoule contains:

Hydroxocobalamin ........................................................................... 10 mg

Betamethasone 21 sodium phosphate

(equivalent to 2 mg of betamethasone base) ...................................... 2,63 mg

Sodium diclofenac ............................................................................ 75 mg

Benzyl alcohol, sodium metabisulfite,

propylene glycol, disodium EDTA,

sodium hydroxide and water for injection, q.s ................................... 3 ml

Keep this leaflet. lt is possible that you may have to read it again. It you have any doubt, contact your doctor or pharmacist. This medication has been prescribed to you, and you should not give this drug product to others, although they have the same symptoms that you have. It may cause harm to them.

Do not administer OXA® B12 I.M. if you do not talk previously to your doctor about the following conditions:

• If you are allergic (hypersensitive) to diclofenac, betamethasone or others corticosteroids, B₁₂ vitamin or any other ingredient of the medication.
• If you are allergic to aspirin or any other similar painkiller. The reactions may include shortness of breath, hives, nasal congestion or swelling of the face.
• If you have bleeding or perforation of the stomach or intestine.
• If you suffer from severe kidney or liver disease, asthma, bleeding disorders, hepatic porphyria or severe cardiac insufficiency.
• If you are pregnant.
• If you had clotting disorders.
• If you have cardiovascular problems or history of stroke, or if you have risk of developing these diseases (for example, if you have high blood pressure, increased levels of cholesterol, diabetes or if you smoke).
• If you have systemic fungal infections, viral infections, especially herpes, chickenpox or measles, tuberculosis or positiva reaction to tuberculin (Mantoux test), infestation by Strongyloides (strongyloidiasis) or if you have recently been vaccinated.
• If you develop ulcerative colitis, inflammation of diverticula, recent intestinal anastomosis, myasthenia gravis, osteoporosis, diabetes, glaucoma (high eye pressure) or family history of glaucoma, history of myopathy induced by corticosteroids or epilepsy.
• If you are emotionally unstable or have psychotic reactions.

Warnings

OXA® B12 I.M. should not be administered intravenously.

OXA® B12 I.M., as all the medications that contain non-steroidal anti-inflammatory agents, should be administered at the lowest effective doses and, if possible, during the shortest period in order to monitor the symptoms.

A long treatment with corticosteroids should not be discontinued abruptly; it is recommended to gradually reduce the dose. The treatment with OXA® B12 I.M. may mask sorne infection signs (for example, fever). The prolonged use of corticosteroids not only may decrease the resistance to infection but also may make it difficult to determine where they are.

Patients treated with corticosteroids especially with high doses should not be vaccinated due to possible neurological complications and reduced immune response.

Measles and chickenpox may severely evolve being fatal in patients treated with corticosteroids.

Similarly, corticosteroids should be used with caution in patients with known or suspected infestation produced by Strongyloides.

Patients with active tuberculosis should not receive OXA® B12 I.M. The use in patients with inactive tuberculosis or with a positive reaction to PPD test requires a careful monitoring, since a disease reactivation may occur.

Episodes of hypocalcemia together with risk of cardiac arrhythmias have been reported al the beginning of the treatment with hydroxocobalamin so that serum potassium concentration should be monitored.

Contact your doctor if you have nausea, fatigue, flu-like symptoms, if your skin and eyes look yellow, or if your pain is located in the upper quadrant, because it may be due to liver disorder associated or not with drug administration. You should also contact immediately your doctor if you have sharp and chronic abdominal pain, black stools or blood vomitus.

The non-steroidal anti-inflammatory agents such as diclofenac can be associated with an increased risk of suffering from myocardial infarction or strokes, especially when they are administered in high doses and during prolonged periods. Do not exceed the recommended dosage and the treatment duration. Besides, this kind of drugs may cause fluid retention, especially in patients with heart insufficiency or high blood pressure.

OXA® B12 I.M. should not be used alter surgery of coronary bypass.

lt is important that you use the lowest dose to relieve and monitor your pain; you should not take this medication for a period longer than the indicated one in order to relieve your symptoms.

Inform your doctor if you are taking or have recently taken any other drug product, including over-the-counter medicines.

Sorne drug products may interfere with OXA® B12 I.M.; in these cases, it may be necessary to change the dose or to discontinue one of the treatments.

It is important that you tell your doctor if you are taking or have recently taken any of the following medications:

• Aspirin or any other anti-inflammatory agent
• Anticoagulants
• Methotrexate
• Cyclosporine
• Lithium
• Diuretics
• Drugs to treat diabetes
• Drugs to treat high blood pressure
• Rifampin or rifabutin
• Carbamazepine
• Phenytoin
• Primidone
• Phenobarbitone
• Aminoglutethimide
• Ephedrine

Pregnancy and breast-feeding

OXA® B12 I.M. should be avoided during the first and second quarter of pregnancy, unless the doctor considers its administration strictly necessary. OXA® B12 I.M. should be avoided during the third quarter of pregnancy because it may cause severe cardiovascular disorders in the fetus, with potential fetal death.

OXA® B121.M. should be avoided during breast-feeding.

 Driving and operating machinery

Atl normal dose levels, OXA® B12 I.M. does not affect the capacity to drive or to operate machinery. However, if you have drowsiness, dizziness or visual disturbances, do not drive or operate machinery.

Follow strictly the instructions about administration that your doctor has already given to you. Do not administer OXA® 812 I.M. al higher doses or in longer periods than it has been prescribed.

Administer 1 or 2 ampoules per day, only by a slow and deep intramuscular injection (for example, in the upper external quadrant of the gluteus).

The maximum dose is 2 ampoules per day.

It is not recommended the use of OXA® B12 I.M. for more than 3 days, without a new prescription.

It is not recommended the administration of OXA® B12 I.M. in patients under 18 years old.

If you forget the administration of OXA® B12 I.M.

Do not administer the medication twice if you have forgotten the dose.

If you forget a dose, apply it as soon as possible, unless the time of the next dose is very near; then, return to the regular dosage schedule. If you forget several doses, contact your doctor.

If you have received a dose higher than the one prescribed, or in case of overdose or accidental ingestion, contact your doctor or go to the nearest hospital, indicating the medication and the administered amount.

Keep this leaflet. lt is possible that you may have to read it again. It you have any doubt, contact your doctor or pharmacist. This medication has been prescribed to you, and you should not give this drug product to others, although they have the same symptoms that you have. It may cause harm to them.