Dicloberl 75 mg/3 ml

Package leaflet: Information for the patient

Dicloberl 75 mg/3 ml
75 mg/3 ml, solution for injection
Diclofenacum natricum
Please read carefully the entire leaflet before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any doubts, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

1. What Dicloberl 75 mg/3 ml is and what it is used for
2. Important information before using Dicloberl 75 mg/3 ml
3. How to use Dicloberl 75 mg/3 ml
4. Possible side effects
5. How to store Dicloberl 75 mg/3 ml
6. Contents of the pack and other information

1. What Dicloberl 75 mg/3 ml is and what it is used for

Dicloberl 75 mg/3 ml is an anti-inflammatory and analgesic medicine (non-steroidal anti-inflammatory drug, NSAID).
Symptomatic treatment of acute pain in:

• acute joint inflammation, including gout attacks;
• chronic joint inflammation, particularly rheumatoid arthritis (chronic polyarthritis);
• ankylosing spondylitis (Bechterew's disease) and other rheumatic inflammatory conditions of the spine;
• exacerbations of degenerative joint disease of peripheral joints and degenerative spinal disease;
• inflammation of soft tissues in rheumatic disorders;
• painful traumatic swellings and inflammatory conditions.

Dicloberl 75 mg/3 ml is intended for use in adults.
Note:
The use of the solution for injection is indicated only when a very rapid onset of action is required or when oral administration or use in suppository form is not possible.
In such cases, treatment with a single injection should only initiate therapy.
If there is no improvement or the patient feels worse, contact the doctor.

2. Information before using Dicloberl 75 mg/3 ml

When not to use Dicloberl 75 mg/3 ml:

• if the patient is allergic to diclofenac or any of the other ingredients of this medicine (listed in section 6);
• if the patient has previously experienced breathing problems (bronchospasm), asthma attacks, chest pain, nasal mucosal swelling, or skin reactions after taking acetylsalicylic acid or another non-steroidal anti-inflammatory drug (NSAID);
• if the patient currently has non-specific blood disorders;
• if the patient currently has gastric or intestinal ulcers, bleeding, or perforations (may present as bloody vomiting, bleeding during defecation, fresh blood in stool, or black-coloured stool, tarry stools);
• if the patient has active or recurrent gastric and/or duodenal ulcer disease or bleeding (two or more separate episodes of ulcers or bleeding confirmed);
• if the patient has a history of gastrointestinal bleeding or perforation related to previous use of NSAIDs;
• if the patient has cerebral haemorrhage or any other active bleeding;
• if the patient has severe renal or hepatic insufficiency;
• if the patient has heart disease and/or cerebrovascular disease, e.g. after myocardial infarction, stroke, transient ischaemic attack (TIA), or embolism in the heart or brain, or after a procedure to unblock or bypass obstructed blood vessels;
• if the patient has peripheral vascular disease (circulatory disorders), present or in the past;
• during the last three months of pregnancy;
• in children and adolescents under 18 years of age due to the high content of active substance.

Warnings and precautions
The following situations require special caution when using Dicloberl 75 mg/3 ml. The medicine should then be used only in a specific manner (e.g. with longer intervals between doses or lower doses under medical supervision). Consult a doctor.
This also applies to conditions that occurred in the past.
Before starting treatment with Dicloberl 75 mg/3 ml, discuss this with your doctor or pharmacist.

General
Using the lowest effective dose for the shortest duration necessary to relieve symptoms reduces the risk of adverse effects (see section 3 "How to use Dicloberl 75 mg/3 ml").
Avoid concomitant use of Dicloberl 75 mg/3 ml with other NSAIDs, including so-called COX-2 inhibitors (selective cyclooxygenase-2 inhibitors), due to lack of data confirming improved efficacy and the possibility of increased frequency and severity of adverse effects.

Gastrointestinal bleeding, ulcer disease, and perforation:
Gastrointestinal bleeding, gastric and/or duodenal ulcer disease, and perforations with fatal outcomes have been reported during treatment with all NSAIDs, occurring at various times during therapy, with or without warning symptoms, and with or without prior severe gastrointestinal adverse effects.
The risk of gastrointestinal bleeding, gastric and/or duodenal ulcer disease, and perforation increases with higher NSAID doses, is greater in patients with a history of gastric and/or duodenal ulcers, especially if complicated by bleeding or perforation, and in elderly patients. In such patients, treatment should be initiated and maintained using the lowest possible doses.
In such patients and in patients requiring concomitant administration of low-dose acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal disorders, the doctor may consider concomitant use of gastroprotective agents (e.g. misoprostol or proton pump inhibitors).
Patients who have experienced gastrointestinal adverse effects, especially elderly patients, should report any abnormal abdominal symptoms (particularly gastrointestinal bleeding), especially at the beginning of treatment.
Caution is advised in patients receiving concomitant medications that may increase the risk of gastric and/or duodenal ulcer disease or bleeding, such as systemic corticosteroids, anticoagulants like warfarin, selective serotonin reuptake inhibitors (SSRIs) used, among others, in depression treatment, or antiplatelet agents such as acetylsalicylic acid (see section 2: Dicloberl 75 mg/3 ml and other medicines).
If gastrointestinal bleeding or gastric and/or duodenal ulcer disease occurs in a patient taking Dicloberl 75 mg/3 ml, the medicine should be discontinued.
Discontinue use of Dicloberl 75 mg/3 ml and contact a doctor immediately if the patient experiences severe upper abdominal pain, tarry stools, or bloody vomiting (see section 4 "Possible side effects").
NSAIDs should be administered cautiously and under strict medical supervision to patients with symptoms indicating gastrointestinal disorders, patients with a history of gastric and/or duodenal ulcer disease, bleeding or perforation, or with gastrointestinal diseases (ulcerative colitis, Crohn's disease) in the past, as disease exacerbation may occur (see section 4 "Possible side effects").
Before using Dicloberl 75 mg/3 ml, inform the doctor if the patient has recently undergone or plans to undergo surgery of the stomach or gastrointestinal tract, as Dicloberl 75 mg/3 ml may sometimes impair intestinal wound healing after surgery.

Effect on the circulatory system
Taking medicines such as Dicloberl 75 mg/3 ml may be associated with an increased risk of heart attack ("myocardial infarction") or stroke.
Before taking Dicloberl 75 mg/3 ml, inform the doctor:

• if the patient smokes;
• if the patient has diabetes;
• if the patient has: angina pectoris, reduced cardiac output, heart disease characterised by reduced blood supply to the heart, conditions affecting blood supply to the brain, narrowing of arteries other than those supplying blood to the heart or brain, thrombosis, hypertension, elevated cholesterol levels, or elevated triglyceride levels.

The occurrence of adverse effects can be minimized by using the medicine at the lowest effective dose and for no longer than necessary.
If the patient has heart problems or has had a stroke, discuss treatment options with a doctor or pharmacist.

Skin reactions
Very rarely, severe skin reactions with redness and blistering, some with fatal outcomes, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis (Lyell’s syndrome), have been reported in connection with NSAID use (see section 4 "Possible side effects"). The highest risk of these reactions appears to occur early in treatment: in most cases, onset occurs within the first month of treatment.
Before using Dicloberl 75 mg/3 ml, inform the doctor if the patient has ever experienced severe skin rash, skin peeling, blistering, and/or oral mucosal ulcers after taking Dicloberl 75 mg/3 ml or other painkillers.
If the first signs of skin rash, mucosal changes (oral or nasal mucosa), or other hypersensitivity symptoms occur, discontinue Dicloberl 75 mg/3 ml and contact a doctor.

Effect on the liver
Caution should be exercised before initiating diclofenac treatment in patients with liver function disorders (consult a doctor or pharmacist), as disease exacerbation may occur. During treatment with NSAIDs, including diclofenac, increased activity of one or more liver enzymes may occur. If diclofenac is to be used long-term or repeatedly, regular monitoring of liver function parameters is recommended as a precaution. Dicloberl 75 mg/3 ml should be discontinued immediately if symptoms of liver dysfunction occur.
Hepatitis without preceding warning symptoms may occur during diclofenac treatment.
Caution is advised when using Dicloberl 75 mg/3 ml in patients with hepatic porphyria (a blood disorder), as it may trigger disease exacerbation.

Effect on the kidneys
Due to reported cases of fluid retention and oedema associated with NSAID treatment, including diclofenac, particular caution is required in patients with impaired renal function, a history of hypertension, elderly patients, patients receiving diuretics or other drugs that significantly reduce renal function, and patients with substantial extracellular fluid volume depletion for any reason (e.g. before or after major surgical procedures). In such cases, as a precaution, monitoring of renal function is recommended during diclofenac treatment.
Discontinuation of treatment usually leads to recovery to the pre-treatment state.

Other
Dicloberl 75 mg/3 ml should only be used after careful consideration of benefit-risk ratio:

• in certain inherited blood disorders (e.g. acute intermittent porphyria);
• in certain autoimmune diseases (systemic lupus erythematosus, mixed connective tissue disease).

Dicloberl 75 mg/3 ml should only be used under strict medical supervision:

• in patients with allergies (e.g. skin reactions to other drugs, asthma, hay fever), chronic nasal mucosal oedema, or chronic respiratory disease with airway narrowing or chronic respiratory infections, as such patients have an increased risk of allergic reactions.

Particular caution is advised during parenteral administration of diclofenac in patients with bronchial asthma, as symptoms may worsen.
Do not inject Dicloberl 75 mg/3 ml into areas affected by inflammation or infection.
Severe, acute hypersensitivity reactions (e.g. anaphylactic shock) may rarely occur. If the first symptoms of hypersensitivity occur after administration of Dicloberl 75 mg/3 ml, discontinue the medicine. Healthcare professionals should initiate appropriate symptomatic treatment.
Diclofenac may temporarily inhibit platelet aggregation. Therefore, the doctor will closely monitor patients with coagulation disorders.
Like other NSAIDs, diclofenac may mask signs of infection. If signs of infection (e.g. redness, swelling, warmth, pain, fever) appear or worsen during treatment with Dicloberl 75 mg/3 ml, the patient should contact a doctor immediately.
If the patient is taking concomitant drugs that inhibit blood coagulation or lower blood glucose levels, coagulation or blood glucose levels should be monitored preventively.
During prolonged administration of Dicloberl 75 mg/3 ml, regular monitoring of liver function, renal function, and blood morphology is required.
Inform the doctor or dentist about taking Dicloberl 75 mg/3 ml before surgical procedures.
Prolonged use of analgesics may lead to headache, which should not be treated by increasing the dose of these medicines. Consult a doctor if the patient frequently experiences headaches despite using Dicloberl 75 mg/3 ml.
Chronic use of analgesics, especially combinations of multiple active substances with analgesic effects, may cause irreversible kidney damage, associated with the risk of renal failure (analgesic nephropathy).

Children and adolescents
Do not use Dicloberl 75 mg/3 ml in children and adolescents under 18 years of age (see section 2 "When not to use Dicloberl 75 mg/3 ml").

Elderly patients
Due to the risk of adverse effects, elderly patients should be monitored particularly closely. Caution is advised in elderly patients due to coexisting diseases.
In particular, in frail elderly patients or those with low body weight, the lowest effective dose should be used. The frequency of adverse effects during NSAID treatment, especially gastrointestinal bleeding, ulcers, and perforations, is higher in elderly patients. These gastrointestinal reactions usually have more serious consequences in the elderly and may lead to death.

Dicloberl 75 mg/3 ml and other medicines
Inform the doctor or pharmacist about all medicines currently or recently taken by the patient, as well as any medicines the patient plans to take.

Other NSAIDs (including acetylsalicylic acid) and glucocorticosteroids
Concomitant use of Dicloberl 75 mg/3 ml with other anti-inflammatory and analgesic NSAIDs or glucocorticosteroids (anti-inflammatory drugs or those used in hormone replacement therapy) increases the risk of gastric and/or duodenal ulcer disease and gastrointestinal bleeding. Do not take diclofenac with other NSAIDs.

Digoxin, phenytoin, lithium
Concomitant use of Dicloberl 75 mg/3 ml with digoxin (used in cardiac arrhythmia treatment), phenytoin (used in seizure treatment), or lithium (used in psychiatric disorders) may increase blood levels of these drugs. Monitoring of lithium blood levels is necessary. Monitoring of digoxin and phenytoin serum levels is recommended.

Diuretics, beta-adrenergic receptor blockers, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II antagonists
Dicloberl 75 mg/3 ml may reduce the effect of diuretics and antihypertensive drugs (diuretics and antihypertensives, e.g. beta-adrenergic receptor blockers, ACE inhibitors, and angiotensin II antagonists). Therefore, blood pressure should be monitored periodically.
Dicloberl 75 mg/3 ml may reduce the effect of ACE inhibitors and angiotensin II antagonists (drugs used in heart disease and blood pressure-lowering drugs). Concomitant use of these drugs with Dicloberl 75 mg/3 ml may increase the risk of renal function disorders. Patients should be adequately hydrated, and renal function should be monitored periodically.
Concomitant use of Dicloberl 75 mg/3 ml with potassium-sparing drugs (such as potassium-sparing diuretics) and other drugs such as tacrolimus or trimethoprim may lead to increased blood potassium levels. Therefore, regular monitoring of potassium levels is recommended.

Selective serotonin reuptake inhibitors (SSRIs)
Some antidepressants (selective serotonin reuptake inhibitors [SSRIs]) may increase the risk of gastric and/or duodenal ulcer disease or gastrointestinal bleeding.

Methotrexate
Taking Dicloberl 75 mg/3 ml within 24 hours before or after methotrexate (used in inflammatory diseases and treatment of certain cancers) may increase methotrexate blood levels and increase adverse effects.

Cyclosporine
Non-steroidal anti-inflammatory drugs (including diclofenac) may increase the nephrotoxic effects of cyclosporine (used to prevent transplant rejection and in treatment of rheumatic diseases). The patient should use a lower dose of diclofenac.

Anticoagulants and antiplatelet agents
Non-steroidal anti-inflammatory drugs may enhance the effects of antiplatelet and anticoagulant drugs (used to prevent blood clotting), such as warfarin, leading to increased risk of bleeding. Regular visits to the doctor are recommended.

Probenecid
Drugs containing probenecid (used in gout treatment) may slow down diclofenac elimination. This may intensify adverse effects.

Antidiabetic drugs
During use of blood glucose-lowering drugs (antidiabetic drugs, e.g. sulfonylurea derivatives), isolated cases of diclofenac affecting blood glucose levels have been reported, necessitating adjustment of antidiabetic drug doses. Therefore, as a precaution, blood glucose monitoring is recommended during concomitant use of these drugs.

Quinolone antibiotics
Quinolones (certain types of antibiotics) may cause seizures during concomitant use with NSAIDs.

Cholestyramine and colestipol
These drugs (used to lower blood cholesterol levels) may delay or reduce diclofenac absorption. Therefore, diclofenac should be taken at least one hour before or 4 to 6 hours after cholestyramine or colestipol.

Strong CYP2C9 inhibitors
Voriconazole (used in treatment of severe fungal infections) and sulfinpyrazone (used in gout treatment) may increase diclofenac blood levels during concomitant use. This may lead to diclofenac accumulation in the body and intensify adverse effects.

Tenofovir
Concomitant use of tenofovir (used in treatment of hepatitis B virus and in prevention and treatment of HIV/AIDS) with NSAIDs (such as diclofenac) may increase blood urea nitrogen and creatinine levels (renal function parameters). Renal function should therefore be monitored to detect possible increases in these parameters.

Deferasirox
Concomitant use of deferasirox (used in patients undergoing repeated blood transfusions due to various types of anaemia) with NSAIDs (such as diclofenac) may increase the risk of gastrointestinal adverse effects. Therefore, the doctor should closely monitor patients receiving concomitant deferasirox and NSAIDs.

Mifepristone
Used to terminate pregnancy. Do not use NSAIDs for 8-12 days after mifepristone administration due to the theoretical risk that prostaglandin synthesis inhibitors may alter mifepristone efficacy.

Pemetrexed
Concomitant use of pemetrexed (used in cancer treatment) and NSAIDs may intensify pemetrexed effects; therefore, particular caution is required when administering higher NSAID doses.

Use of Dicloberl 75 mg/3 ml with alcohol
Do not consume alcohol during treatment with Dicloberl 75 mg/3 ml.

Pregnancy, breastfeeding, and effects on fertility
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor or pharmacist before using this medicine.

Pregnancy
Inform the doctor if pregnancy is confirmed during treatment with Dicloberl 75 mg/3 ml. Dicloberl 75 mg/3 ml may be used during the first and second trimesters of pregnancy after consultation with a doctor.
Do not use Dicloberl 75 mg/3 ml during the last three months of pregnancy, as it may harm the unborn child or cause complications during delivery.
Dicloberl 75 mg/3 ml may cause kidney and heart dysfunction in the unborn child. It may increase the tendency to bleeding in the mother and child and may delay or prolong labour. Dicloberl 75 mg/3 ml should not be used during the first 6 months of pregnancy unless the doctor considers its use absolutely necessary. If treatment is required during this period or when trying to conceive, the lowest possible dose should be used for the shortest possible duration.
From week 20 of pregnancy, Dicloberl 75 mg/3 ml, if taken for longer than a few days, may cause kidney dysfunction in the unborn child—this may lead to reduced amniotic fluid volume (oligohydramnios) or narrowing of blood vessels (ductus arteriosus) in the child's heart. If treatment is required for longer than a few days, the doctor may recommend additional monitoring.

Breastfeeding
Like other NSAIDs, diclofenac passes into breast milk in small amounts. To avoid adverse effects in the infant, diclofenac should not be used during breastfeeding.

Effect on fertility
Like other drugs inhibiting prostaglandin synthesis, Dicloberl 75 mg/3 ml may impair fertility. If the patient is planning pregnancy or has difficulty conceiving, she should inform the doctor.

Driving and operating machinery
When using high doses of Dicloberl 75 mg/3 ml, adverse effects on the central nervous system such as fatigue and dizziness may occur. In individual cases, the ability to drive or operate machinery may be impaired.
This is especially relevant when the medicine is taken concomitantly with alcohol. The patient may have reduced ability to react quickly and appropriately to unexpected or sudden events.
If the above symptoms occur, do not drive or operate machinery.

Note:
Propylene glycol contained in Dicloberl 75 mg/3 ml may cause symptoms similar to alcohol consumption.

Dicloberl 75 mg/3 ml contains benzyl alcohol, propylene glycol, and sodium

Benzyl alcohol
This medicine contains 105 mg of benzyl alcohol per ampoule. Benzyl alcohol may cause allergic reactions.
Pregnant or breastfeeding women should consult a doctor before using the medicine, as large amounts of benzyl alcohol may accumulate in their bodies and cause adverse effects (so-called metabolic acidosis).
Patients with liver or kidney disease should consult a doctor before using the medicine, as large amounts of benzyl alcohol may accumulate in their bodies and cause adverse effects (so-called metabolic acidosis).

Propylene glycol
This medicine contains 600 mg of propylene glycol per ampoule.

Sodium
This medicine contains less than 1 mmol (23 mg) of sodium per ampoule, meaning the medicine is considered "sodium-free".

3. How to use Dicloberl 75 mg/3 ml

This medicine should always be used as directed by a physician or pharmacist. If in doubt,
consult your doctor or pharmacist.
Recommended dose
Adults
Treatment with Dicloberl 75 mg/3 ml should be administered as a single injection.
In severe cases, the medicine may be given at a volume of 2 ampoules per day.
Parenteral administration should be limited to 2 days. The duration of treatment will be determined
by the attending physician.
If further treatment appears necessary, it should be continued using oral dosage forms or suppositories. The total daily dose of 150 mg must not be exceeded, even on the day of injection.
Method of administration
Dicloberl 75 mg/3 ml should be injected deeply into the gluteal muscle. Due to the
possibility of anaphylactic reactions (severe allergic reactions), the patient should be
observed for at least 1 hour.
If the effect of Dicloberl 75 mg/3 ml seems too strong or too weak, consult your doctor.
After first opening the ampoule, the medicine should be used immediately.
Warning: Handling OPC-type ampoules (one-point-cut)
It is not necessary to score the ampoule!

Hold the ampoule so that the Hold the ampoule so that the
colored dot is facing upwards colored dot is facing upwards
Tap or shake the ampoule to move the Tap or shake the ampoule to move the
entire solution from the upper part to solution to the lower part of the
the lower part of the ampoule. ampoule.
Break off the neck from the lower part of the ampoule.

Use of a higher than recommended dose of Dicloberl 75 mg/3 ml
There are no characteristic clinical symptoms specifically associated with overdose. Symptoms of overdose affecting the central nervous system may include: headache, dizziness, feeling of faintness, and loss of consciousness (in children, seizures may also occur), as well as abdominal pain, nausea, and vomiting. Additionally, gastrointestinal bleeding and disturbances in liver and kidney function may occur. A sudden drop in blood pressure, breathing difficulties (respiratory depression), and blue-red discoloration of the skin and mucous membranes (cyanosis) may also occur.
There is no specific antidote.
In case of suspected overdose, inform a doctor immediately.
Depending on the severity of poisoning, the doctor will decide on appropriate treatment.
If you have any further questions regarding the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Some adverse reactions may be serious. If any adverse reactions occur,
you should inform your doctor, who will decide on further management.
The occurrence of the following adverse reactions of the medicine primarily depends on the dose used and varies individually.
The adverse reactions presented below also include those reported
during the use of other forms of diclofenac, administered either short-term or long-term.
Gastrointestinal disturbances have been observed. Nausea, vomiting, diarrhoea, bloating, indigestion, and abdominal pain have been reported after administration of the medicine (see section 2 “Warnings and precautions”). Tarry stools, bloody vomiting, gastric and (or) duodenal ulceration, perforation or gastrointestinal bleeding, sometimes leading to death, particularly in elderly patients, may occur (see section 2 “Warnings and precautions”). The risk of gastrointestinal bleeding particularly depends on the dose administered and the duration of treatment.
Constipation, gastritis, oral ulcerative mucositis, and worsening of symptoms of colitis and Crohn’s disease have also been reported after administration of the medicine (see also section 2 “Warnings and precautions”).

Dicloberl 75 mg/3 ml should be discontinued and medical advice should be sought immediately if the patient notices:

• mild painful cramps and abdominal tenderness occurring soon after starting Dicloberl 75 mg/3 ml, followed by rectal bleeding or bloody diarrhoea, usually within 24 hours of the onset of abdominal pain (frequency unknown - cannot be estimated from available data),
• severe allergic skin reaction, which may manifest as widespread red and (or) dark spots, skin swelling, blisters, and itching (generalized fixed bullous eruption).

Seek immediate medical advice if any of the following symptoms occur:

• reactions at the injection site, including pain, redness, swelling, hard nodule, ulceration, and bruising. This may lead to necrosis and death of the skin and surrounding tissues at the injection site, healing with scarring, presenting as what is also known as Nicolau syndrome;
• chest pain, which may be a sign of a potentially serious allergic reaction called Kounis syndrome.

Cases of fluid retention (oedema), high blood pressure, and heart failure associated with NSAID therapy have been reported.
The use of medicines such as Dicloberl 75 mg/3 ml may be associated with an increased risk of arterial thrombotic events, e.g. heart attack (myocardial infarction) or stroke (see section 2 “When not to use Dicloberl 75 mg/3 ml” and “Warnings and precautions”).

Common: may affect up to 1 in 10 patients

• gastrointestinal disorders such as nausea, vomiting, diarrhoea, as well as minor gastrointestinal blood loss, which in rare cases may lead to a deficiency in red blood cells (anaemia);
• hypersensitivity reactions such as skin rash and itching;
• central nervous system disorders such as headache, dizziness, feeling of emptiness in the head, anxiety (agitation), irritability, drowsiness;
• digestive disorders (dyspepsia), bloating, stomach cramps (abdominal pain), loss of appetite, as well as gastric or duodenal ulceration (with risk of bleeding or perforation);
• increased liver enzyme activity in blood;
• labyrinthine dizziness;
• adverse reactions at the injection site, pain and induration at the injection site;

Uncommon: may affect up to 1 in 100 patients

• urticaria; in such a case, the medicine should be discontinued immediately and medical advice should be sought;
• bloody vomiting, blood in stool or bloody diarrhoea;
• liver damage (particularly during long-term treatment), hepatitis with or without jaundice (in individual cases with fulminant course, even without preceding symptoms);
• alopecia;
• oedema formation (fluid retention), particularly in patients with high blood pressure or impaired kidney function;

Rare: may affect up to 1 in 1,000 patients

• hypersensitivity, anaphylactic and pseudoanaphylactic reactions (may manifest as airway constriction, breathlessness (respiratory failure), rapid heartbeat, low blood pressure (hypotension), and shock);
• gastritis, gastrointestinal bleeding;
• liver function disorders;
• asthma, including breathing difficulties (dyspnoea);
• hypersensitivity reactions to benzyl alcohol;
• swelling at the injection site;

Very rare: may affect up to 1 in 10,000 patients

• worsening of infection-related inflammation (e.g. development of necrotizing fasciitis) associated with the use of anti-inflammatory medicines (non-steroidal anti-inflammatory drugs, including Dicloberl 75 mg/3 ml); if signs of infection (e.g. redness, swelling, warmth, pain, fever) or their worsening occur during treatment with Dicloberl 75 mg/3 ml, the patient should seek immediate medical advice. The doctor will determine whether treatment with infection-fighting medicines or antibiotics is indicated;

• symptoms of meningitis (aseptic meningitis), such as headache, nausea, vomiting, fever, neck stiffness or altered consciousness, have occurred during diclofenac use. Patients with concomitant
  autoimmune diseases (systemic lupus erythematosus, mixed connective tissue diseases) appear to be more susceptible to the above-mentioned adverse reactions;

• blood disorders [anaemia, leukopenia (reduced white blood cell count), thrombocytopenia (reduced platelet count), pancytopenia (reduced red and white blood cells and platelets), agranulocytosis (acute condition associated with severe, life-threatening drop in neutrophil count), haemolytic and aplastic anaemia (lack of red blood cells due to accelerated breakdown)]. Initial symptoms of these disorders may include fever, sore throat, mouth ulcers, flu-like symptoms, severe fatigue, nosebleeds, and skin bleeding. In such cases, the medicine should be discontinued immediately and medical advice should be sought. Do not self-medicate with antipyretics or painkillers. Blood morphology parameters should be monitored regularly during prolonged treatment;

• angioedema (swelling of the face, tongue and larynx); if any of these symptoms occur, which may happen even after a single dose, diclofenac should be discontinued and immediate medical help should be sought;

• allergic vasculitis and lung inflammation;

• psychotic disorders, depression, anxiety, insomnia, nightmares;

• sensory disturbances, taste disturbances, memory disorders, disorientation, seizures, tremor, stroke;

• visual disturbances (blurred and double vision);

• tinnitus, transient hearing disturbances;

• palpitations, chest pain, reduced heart function (heart failure), myocardial infarction;

• high blood pressure (hypertension);

• inflammation of the oral mucosa, including ulcerative conditions (oral ulcerative mucositis), glossitis, oesophageal damage, constipation, lower abdominal complaints such as colitis including bloody colitis or exacerbations of Crohn’s disease or ulcerative colitis (inflammation of the large intestine with associated ulceration), pancreatitis, intestinal stricture. If acute upper abdominal pain, bloody vomiting, black stools or blood in stool occur, Dicloberl 75 mg/3 ml should be discontinued and the doctor should be informed;

• liver necrosis, liver failure. Liver parameters should be monitored at regular intervals during long-term treatment;

• severe skin reactions such as skin rash with redness (rash, exanthema, erythema, erythema multiforme) and skin rash with epidermal detachment (e.g. Stevens-Johnson syndrome and toxic epidermal necrolysis - Lyell’s syndrome) or epidermal necrosis (exfoliative dermatitis), photosensitivity (photosensitivity reactions), local skin bleeding (purpura), which may be of allergic nature;

• kidney damage (interstitial nephritis, papillary necrosis), which may be accompanied by acute kidney failure, proteinuria and (or) haematuria, nephrotic syndrome (oedema and presence of protein in urine). Kidney function should be monitored regularly. Reduced urine output, fluid retention (oedema), as well as general malaise may be symptoms of kidney dysfunction, including kidney failure. If these symptoms occur or worsen, Dicloberl 75 mg/3 ml should be discontinued and immediate medical advice should be sought;

• abscess at the injection site.

Frequency not known (frequency cannot be estimated from available data)

• allergic skin reaction, which may manifest as round or oval redness and swelling of the skin, blisters and itching (erythema multiforme). The skin in affected areas may also have a darker colour, which may persist after healing. Upon re-administration of the medicine, erythema multiforme usually reappears in the same locations;
• tissue damage at the injection site;
• ischaemic colitis.

Follow the instructions given above regarding certain adverse reactions!
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Dicloberl 75 mg/3 ml

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the ampoule and outer packaging
following the letters "EXP". The expiry date refers to the last day of the stated month.
Do not store above 30°C.
Store the ampoules in the outer packaging to protect from light.
Do not store in the refrigerator or freeze.
Medicines should not be disposed of via the sewage system or household waste. Ask your
pharmacist how to dispose of medicines no longer required. Such measures help protect
the environment.

6. Contents of the package and other information

What Dicloberl 75 mg/3 ml contains
The active substance is sodium diclofenac.
One 3 ml ampoule of injection solution contains 75 mg of sodium diclofenac.
1 ml of injection solution contains 25 mg of sodium diclofenac.
Other ingredients are:
propylene glycol (600 mg/3 ml), benzyl alcohol (105 mg/3 ml), acetylcysteine, mannitol, sodium
hydroxide (1 N solution), water for injections.
Dicloberl 75 mg/3 ml has a pH of 8.0–9.0.

What Dicloberl 75 mg/3 ml looks like and contents of the pack
A clear, colourless solution in 3 ml ampoules made of colourless type I glass, packed in a cardboard
box.
Pack sizes: 1 or 5 ampoules.
Hospital pack sizes: 30, 150, 300, 600, 1200 ampoules.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
BERLIN-CHEMIE AG
Glienicker Weg 125
12489 Berlin, Germany

Manufacturer
A. Menarini Manufacturing Logistics and Services S.r.l.
Via Sette Santi, 3
50131 Florence, Italy
Alfasigma S.p.A.
Via Enrico Fermi, 1
65020 Alanno (Pescara)
Italy

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Berlin-Chemie/Menarini Polska Sp. z o.o.
Tel. + 48 22 566 21 00
Fax: + 48 22 566 21 01