Package leaflet: Information for the user

Dicloratio, (75 mg + 20 mg)/2 ml solution for injection
Diclofenacum natricum + Lidocaini hydrochloridum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

Keep this leaflet, as you may need to read it again.
If you have any further questions, please ask your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents:

What Dicloratio is and what it is used for
Important information before using Dicloratio
How to use Dicloratio
Possible side effects
How to store Dicloratio
Contents of the pack and other information

1. WHAT DICLORATIO IS AND WHAT IT IS USED FOR

Dicloratio contains diclofenac, which is a derivative of aminophenylacetic acid. It belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs). It also has analgesic properties. Due to the presence of lidocaine hydrochloride, Dicloratio has a local anaesthetic effect, which reduces the pain of injection.
Dicloratio is used in the treatment of:

acute flare-ups of inflammatory or degenerative rheumatic diseases:
rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, soft tissue rheumatism (inflammation of muscles, ligaments, fasciae, bursae, tendon sheaths)
acute gout attacks
pain caused by traumatic and postoperative inflammatory conditions and oedema.

2. IMPORTANT INFORMATION BEFORE USING DICLORATIO

When not to use Dicloratio

if the patient is allergic to diclofenac, lidocaine hydrochloride, or any of the other ingredients of this medicine (listed in section 6.)
if the patient has hypersensitivity to other nonsteroidal anti-inflammatory drugs (NSAIDs)
if the patient has hypersensitivity to acetylsalicylic acid, manifested by bronchospasm, asthma attacks, chest pain, skin reactions, or allergic rhinitis
if the patient has disorders of blood-forming and coagulation systems of unknown etiology
if the patient has active or recurrent gastric or duodenal ulcer
if the patient is in the third trimester of pregnancy
if the patient has severe liver, kidney, or heart failure
if the patient has previously experienced gastrointestinal bleeding or perforation after using NSAIDs
if the patient has been diagnosed with heart disease and/or cerebrovascular disease, e.g. after myocardial infarction, stroke, transient ischemic attack (TIA), or arterial embolism in the heart or brain, or after revascularization or bypass surgery
if the patient has current or past circulatory disorders (peripheral vascular disease)
if the patient has active bleeding from cerebral or other blood vessels

Due to the presence of lidocaine, Dicloratio is contraindicated if:

the patient has severe disorders of the cardiac conduction system
the patient has cardiogenic or hypovolemic shock
the patient has severe congestive heart failure
the patient has first- or second-degree atrioventricular block
the patient has bradycardia
the patient has hypersensitivity to lidocaine or to amide-type local anesthetics.

Do not use in patients under 18 years of age.
Warnings and precautions
Before starting Dicloratio, discuss this with your doctor or pharmacist:

if the patient is in the first or second trimester of pregnancy
if the patient is breastfeeding
if the patient has hepatic porphyria
if the patient has systemic lupus erythematosus (SLE) or mixed connective tissue diseases (collagenoses)
if the patient has a history of gastrointestinal disorders, intestinal ulcers, or inflammatory bowel disease (ulcerative colitis, Crohn’s disease)
if the patient has hypertension and/or cardiac dysfunction
if the patient has renal impairment
if the patient has hepatic impairment
if the patient has recently undergone major surgery
if the patient has hay fever, nasal polyps, or chronic obstructive pulmonary disease, which constitute a group at increased risk of allergic reactions. These may manifest as asthma attacks, angioedema, or urticaria
if the patient has hypersensitivity to other substances. In such patients, use of the drug is associated with an increased risk of hypersensitivity reactions
if the patient is elderly.

Before taking the medicine, inform the doctor:

if the patient smokes
if the patient has diabetes
if the patient has angina pectoris, thrombosis, hypertension, elevated cholesterol, or elevated triglycerides.

Before using Dicloratio, tell your doctor if the patient has recently undergone or is scheduled for stomach or gastrointestinal surgery, as Dicloratio may sometimes impair intestinal wound healing after surgery.
Rarely (especially at the beginning of treatment), the use of this medicine may cause life-threatening skin reactions such as exfoliative dermatitis, Stevens-Johnson syndrome with widespread rash, high fever, and joint pain, or toxic epidermal necrolysis with skin and mucosal lesions, high fever, and severe general condition.
If the first signs of rash, mucosal lesions, or other symptoms of allergic reaction occur, discontinue the drug and contact a doctor immediately.
The medicine may mask symptoms of infection (e.g. headache, elevated body temperature) and may interfere with accurate diagnosis. Inform the doctor about using this medicine during medical examinations.
Avoid concomitant use of Dicloratio with systemic NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors, due to lack of evidence for benefits from combination therapy and potential increased risk of adverse effects.
Dicloratio should be used with caution in elderly patients. In elderly patients and those with low body weight, the lowest effective dose should be used.
Patients with asthma
In patients with asthma, seasonal allergic rhinitis, nasal mucosal edema (e.g. nasal polyps), chronic obstructive pulmonary disease, or chronic respiratory infections (especially with symptoms resembling allergic rhinitis), asthma exacerbations, Quincke’s edema, or urticaria occur more frequently after NSAID use (analgesic intolerance) than in other patients. Therefore, special caution is advised in these patients (ensure rapid access to medical help).
Particular caution should be exercised in patients with allergies to other substances, e.g. those with skin reactions, itching, or urticaria, and in patients with bronchial asthma, due to the possibility of worsening symptoms.
Effect on hematological parameters
Diclofenac may transiently inhibit platelet aggregation. Therefore, in patients with coagulation disorders, the doctor may recommend monitoring coagulation parameters.
If the medicine is used long-term, regular monitoring of liver and kidney function and blood counts should be performed.
Using the lowest effective dose for the shortest duration necessary to relieve symptoms reduces the risk of adverse effects.
Effect on the gastrointestinal tract
Use of the medicine may cause gastrointestinal bleeding, ulceration, or perforation (potentially fatal). This risk is particularly high when high doses are used, or in patients with a history of gastrointestinal ulcers or in the elderly. If any unusual abdominal symptoms (especially gastrointestinal bleeding) occur during treatment with Dicloratio, the medicine should be discontinued immediately and a doctor contacted. Patients with ulcerative colitis or Crohn’s disease should be under close medical supervision due to the risk of worsening overall condition.
Effect on liver function
In patients with impaired liver function, the medicine may exacerbate the course of the disease. Strict adherence to the doctor’s recommendations regarding regular liver function tests is essential. In patients with hepatic porphyria, the medicine may trigger an attack of porphyria.
Effect on kidney function
Fluid retention and edema have been reported with NSAID therapy. Therefore, particular caution is required in patients with impaired cardiac or renal function, history of hypertension, the elderly, patients receiving diuretics or drugs significantly affecting kidney function, and patients with excessive extracellular fluid loss due to various causes, e.g. in the peri- or postoperative phase after major surgery. In such cases, monitoring of kidney function is recommended as a precaution during Dicloratio treatment.
Discontinuation of Dicloratio treatment usually results in return to the pre-treatment state.
When administering intramuscular injections containing lidocaine, care must be taken to ensure the medicine does not enter blood vessels during injection.
Effect on the circulatory system and cerebral blood vessels
Use of medicines such as Dicloratio may be associated with an increased risk of heart attack (myocardial infarction) or stroke. This risk increases with long-term use of high doses. Do not use higher doses or longer treatment durations than recommended. If the patient has heart problems, a history of stroke, or suspected risk of these conditions (e.g. high blood pressure, diabetes, high cholesterol, smoking), discuss treatment options with a doctor or pharmacist.
Due to the presence of lidocaine, caution is required in cases of:

increased risk of seizures
ventricular conduction disorders and first-degree atrioventricular block
myasthenia gravis (rapid muscle fatigue and weakness)
injection into inflamed (infected) areas

The occurrence of adverse effects can be minimized by using the lowest effective dose for the shortest duration necessary.
Dicloratio and other medicines
Tell your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines the patient plans to take.
Litium, digoxin, phenytoin
Concomitant use of diclofenac with medicines containing digoxin, phenytoin, or lithium may increase serum concentrations of these substances.
Diuretics, ACE inhibitors, angiotensin II antagonists
Diclofenac may reduce the effect of diuretic and antihypertensive medicines. Concomitant use of diclofenac and potassium-sparing diuretics may lead to hyperkalemia. Therefore, serum potassium levels should be monitored during diclofenac treatment. Due to increased risk of nephrotoxicity, patients should be adequately hydrated and kidney function periodically monitored after initiation and during combined treatment, especially when diuretics and angiotensin-converting enzyme inhibitors (ACE inhibitors) are used.
Angiotensin-converting enzyme (ACE) inhibitors
Concomitant administration of diclofenac with ACE inhibitors may reduce their effectiveness and increase the risk of renal dysfunction.
Antihypertensive medicines
Diclofenac may exhibit antagonistic effects against antihypertensive medicines.
Nonsteroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors, salicylates, and corticosteroids
Concomitant use of diclofenac with other NSAIDs, analgesics, or glucocorticoids increases the risk of gastrointestinal adverse effects.
Concomitant administration of acetylsalicylic acid reduces blood levels of diclofenac and diminishes its effect.
Methotrexate
Caution is advised when using NSAIDs within 24 hours before or after methotrexate treatment, as this may increase methotrexate blood levels and its toxicity.
Probenecid, sulfinpyrazone
Use of medicines containing probenecid or sulfinpyrazone may delay diclofenac elimination.
Anticoagulants and antiplatelet agents
Clinical studies have not shown interactions between diclofenac and anticoagulants, but concomitant use increases the risk of bleeding. Therefore, for safety, coagulation parameters should be monitored during combined therapy.
Selective serotonin reuptake inhibitors (SSRIs)
Concomitant use of NSAIDs and SSRIs may increase the risk of gastrointestinal bleeding.
Cyclosporine and tacrolimus
Diclofenac may enhance the nephrotoxic effects of cyclosporine and tacrolimus.
Sulfonylurea derivatives
Some reports suggest that diclofenac administration may affect blood glucose levels, requiring adjustment of antidiabetic drug dosage. Blood glucose monitoring is recommended.
Antibacterial quinolones
Concomitant administration of diclofenac and quinolone antibiotics may occasionally exacerbate adverse effects (seizures) of quinolones.
Colestipol and cholestyramine
These medicines may prolong or reduce diclofenac absorption. Therefore, diclofenac should be taken at least one hour before or 4–6 hours after colestipol or cholestyramine.
Strong CYP2C9 inhibitors
Caution is advised when prescribing diclofenac with strong CYP2C9 inhibitors (e.g. sulfinpyrazone, voriconazole) due to the potential for significantly increased diclofenac concentration and exposure resulting from inhibition of diclofenac metabolism.
Mifepristone
NSAIDs should not be administered within 8 to 12 days after discontinuation of mifepristone, as they may reduce its efficacy.
Phenytoin
During concomitant use of phenytoin and diclofenac, monitoring of plasma phenytoin levels is recommended due to the potential for increased exposure to phenytoin.
Alcohol
When NSAIDs and alcohol are used concomitantly, adverse effects related to drug administration (particularly gastrointestinal or central nervous system effects) may be intensified.
Additional notes regarding lidocaine content
Lidocaine, when combined with antiarrhythmic drugs, beta-blockers, or calcium antagonists, may additionally inhibit atrioventricular conduction, ventricular conduction, and contractile force.
Pregnancy, breastfeeding, and effect on fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult a doctor or pharmacist before using this medicine.
Pregnancy
Diclofenac use in pregnant women has not been studied. Therefore, Dicloratio should not be used during the first 6 months of pregnancy unless the benefit to the mother outweighs the risk to the fetus. When using diclofenac in women planning pregnancy or during the first and second trimesters, the lowest possible dose and shortest duration of treatment should be used. Dicloratio is contraindicated in the third trimester of pregnancy due to the risk of inhibiting uterine contractions and/or premature closure of the fetal ductus arteriosus (Botalli).
Diclofenac may cause difficulties in becoming pregnant. Consult a doctor if pregnancy is planned, if pregnancy occurs, or if there are problems conceiving while using the medicine.
Lidocaine may be administered to pregnant women only if absolutely necessary. Controlled studies in pregnant women have not been conducted. Data from a limited number of exposed pregnant women do not indicate teratogenic effects of lidocaine. Animal studies have shown toxic effects on fertility. Lidocaine rapidly crosses the placenta.
Breastfeeding
Diclofenac passes into breast milk in small amounts. Therefore, diclofenac should not be used during breastfeeding to avoid adverse effects in the infant.
Lidocaine is excreted in small amounts into breast milk. There is likely no risk to the infant when the medicine is used at therapeutic doses. Since adverse effects in infants are not known, short-term use of diclofenac with lidocaine usually does not require discontinuation of breastfeeding. However, in the case of long-term use of high doses for treating rheumatic diseases, discontinuation of breastfeeding should be considered.
Fertility
Dicloratio may impair fertility. Inform the doctor if the patient plans pregnancy or has difficulty conceiving.
Driving and operating machinery
Patients using Dicloratio who experience visual disturbances, drowsiness, dizziness, fatigue, or other central nervous system disorders should refrain from driving or operating machinery and inform their doctor or pharmacist. Use of Dicloratio may cause adverse effects such as fatigue and dizziness. In individual cases, the ability to drive or operate machinery may be impaired.
Important information about certain ingredients of the medicine:
The medicine contains 480 mg of propylene glycol in each 2 ml of injection solution.

Pregnant or breastfeeding women should not take this medicine without a doctor’s recommendation. The doctor may decide to perform additional tests in such patients.
Patients with impaired liver or kidney function should not take this medicine without a doctor’s recommendation. The doctor may decide to perform additional tests in such patients.
Propylene glycol contained in this medicine may cause alcohol-like symptoms and increase the likelihood of adverse effects.
The medicine should only be used on a doctor’s prescription. The doctor may decide to perform additional tests in patients taking this medicine.

The medicine contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per 2 ml, meaning it is considered "sodium-free".

3. HOW TO USE DICLORATIO

Dicloratio must always be used as directed by the physician. If in doubt,
contact the physician or pharmacist again.
The physician will recommend using the medicine at the lowest effective dose, for the shortest period necessary to
relieve symptoms.
Adults
Dicloratio is usually administered at a dose of 75 mg (single injection) per day. In severe
cases, the dose may be increased to 150 mg per day (2 injections), with several hours between
administration and changing the injection site. Diclofenac in injection solution is indicated only
when rapid analgesic action is required or when treatment with oral or rectal formulations cannot be used.
Use of the medicine should be limited to a single injection. After acute pain subsides,
treatment should continue with other diclofenac formulations, such as: enteric-coated tablets, capsules,
suppositories. When using injections together with other formulations, the daily dose of diclofenac should not exceed 150 mg.
Lidocaine hydrochloride
Lidocaine hydrochloride contained in the medicine is used as an anesthetic agent. In
local anesthesia, the dose depends on the area to be anesthetized, tissue perfusion, number of
neural segments requiring blockade, individual drug tolerance, and the anesthetic technique used.
The smallest therapeutic anesthetic dose should be administered.
Method of administration
To avoid nerve damage or other tissue injury at the injection site, injection recommendations must be followed.
The solution should be injected deeply into the gluteus maximus muscle, in the upper outer quadrant. Due to the possibility of anaphylactic reactions, including anaphylactic shock, properly functioning emergency equipment must be available. The physician will observe the patient for at least 1 hour after administration of the medicinal product. The above procedure will be explained to the patient by the physician or nurse.
Use in children and adolescents
Dicloratio injection solution is not recommended for use in children and adolescents under 18 years of age.
Use of a higher than recommended dose of Dicloratio
If an overdose is accidentally taken, contact a physician, pharmacist, or go immediately to a hospital emergency department.
Overdose may manifest as: headache, dizziness, drowsiness, and loss of consciousness; seizures may occur in children.
Additionally, gastrointestinal symptoms may occur (abdominal pain, nausea, and vomiting). Cardiac rhythm disturbances,
arterial hypotension to the level observed in shock, bradycardia (low heart rate), gastrointestinal bleeding, and disturbances in liver and kidney function may also occur.
There is no specific antidote. Treatment of acute poisoning with non-steroidal anti-inflammatory drugs (NSAIDs)
generally involves supportive measures to maintain vital organ function and symptomatic treatment. The physician will monitor vital functions; control and correct water-electrolyte balance.
Supportive and symptomatic treatment should be applied in cases of complications such as significant
decrease in arterial pressure, renal failure, seizures, gastrointestinal disturbances, and
respiratory disorders.
Specific interventions such as forced diuresis, dialysis, or blood transfusion are not helpful in accelerating the elimination of non-steroidal anti-inflammatory drugs (NSAIDs), due to their high protein-binding capacity and extensive metabolism.
Missed dose of Dicloratio
Do not use a double dose to make up for a missed dose.
Discontinuation of Dicloratio
If there are any doubts regarding the use of the medicine, consult the physician or pharmacist.

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the adverse symptoms worsen or if any adverse symptoms not listed in this leaflet occur,
a doctor or pharmacist should be informed immediately.
Please tell your doctor without delay if any of the following symptoms occur:

chest pain, which may be a sign of a potentially serious allergic reaction known as Kounis syndrome

The following adverse reactions have been reported during the use of Dicloratio with the following frequency:
Very common: 1 in 10 patients; common: 1 to 10 in 100 patients; uncommon: 1 to 10 in 1,000 patients;
rare: 1 to 10 in 10,000 patients; very rare: less than 1 in 10,000 patients; frequency not known: frequency cannot be estimated from the available data.

Very common:

nausea, vomiting, diarrhoea, minor gastrointestinal bleeding, in special cases leading to anaemia

Common:

hypersensitivity reactions, e.g. rash and itching
headache, dizziness, drowsiness, restlessness, irritability or fatigue
dyspepsia, flatulence, abdominal cramps, abdominal pain, loss of appetite and gastric ulcers (sometimes with bleeding and perforation)
increased aminotransferase activity
rash
irritation, pain, hardening at the injection site

Uncommon:

urticaria
gastritis, haematemesis, melaena or bloody diarrhoea
liver damage, particularly with long-term treatment, acute hepatitis with or without jaundice. For this reason, liver function tests should be performed regularly
alopecia
oedema, particularly in patients with hypertension or renal insufficiency

Rare:

asthma, bronchospasm (shortness of breath)
hepatitis, liver function disorders

Very rare:

abscesses at the injection site, symptoms of aseptic meningitis with neck stiffness, headache, nausea, vomiting, fever and confusion
reduction in platelet count (thrombocytopenia), reduction in white blood cell count (leukopenia), anaemia (including haemolytic anaemia), reduction in neutrophil count (agranulocytosis), pancytopenia. Initial symptoms may include: fever, sore throat, superficial oral ulcers, flu-like symptoms, severe exhaustion, nosebleeds and petechiae
depression, insomnia, nightmares, anxiety, psychotic disorders
angioedema (including facial swelling, tongue swelling, laryngeal oedema with airway narrowing, shortness of breath, tachycardia, hypotension to shock levels), vasculitis and hypersensitivity-related lung inflammation
psychotic reactions, depression, anxiety, nightmares
tremor, sensory disturbances, taste disturbances, memory impairment, disorientation, seizures
visual disturbances, blurred vision, double vision
tinnitus, temporary hearing loss
palpitations, chest pain, heart failure, myocardial infarction, hypertension
pneumonia
colitis (including haemorrhagic colitis, exacerbation of ulcerative colitis or Crohn’s disease), constipation, oral mucositis (including ulcerative stomatitis), glossitis, oesophageal disorders, membranous intestinal stricture, pancreatitis, discomfort in the lower abdomen
fulminant hepatitis without premonitory symptoms, liver necrosis, liver failure
rash, bullous rash, exanthema, erythema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), exfoliative dermatitis, photosensitivity reactions, purpura, Schönlein-Henoch disease, pruritus
haematuria, proteinuria, nephrotic syndrome, kidney tissue damage (interstitial nephritis, renal papillary necrosis), which may be associated with acute renal failure. Reduced urine output, oedema and general malaise may indicate kidney disease, including renal failure. If such symptoms occur or worsen, treatment with the medicine should be discontinued.

Frequency not known:

ischaemic colitis
necrosis at the injection site

Intramuscular administration may frequently cause local adverse reactions at the injection site (burning sensation) or tissue damage such as sterile abscess, fatty tissue or skin necrosis (Nicolau syndrome).

Additional effects of lidocaine:
Hypersensitivity reactions such as urticaria, oedema, bronchospasm or respiratory failure syndrome, and cardiovascular reactions have been reported rarely.
Due to the presence of lidocaine, rapid administration of the medicine (unintentional intravenous injection, injection into well-perfused tissue) or overdose may cause systemic reactions such as dizziness, drowsiness, seizures, confusion, nausea, vomiting, bradycardia, cardiac arrhythmias, hypotension to shock levels.

Due to NSAID treatment, oedema, hypertension and heart failure have been reported.

Clinical trials and epidemiological data indicate that the use of diclofenac, particularly at high doses (150 mg per day) over a prolonged period, may be associated with a small increased risk of arterial thromboembolic events (e.g. myocardial infarction or stroke).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, 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 to provide more information on the safety of the medicine.

5. HOW TO STORE DICLORATIO

Keep in the original packaging to protect from light.
Store in a place inaccessible and out of sight of children.
Do not use this medicine after the expiry date stated on the packaging.
The expiry date refers to the last day of the specified month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. This will help protect the environment.

6. CONTENTS OF THE PACKAGE AND OTHER INFORMATION

What Dicloratio contains

The active substances in this medicine are sodium diclofenac and lidocaine hydrochloride.
The other components are: disodium edetate, N-acetylcysteine, sodium hydroxide, Macrogol 400, propylene glycol, water for injections.

What Dicloratio looks like and contents of the pack
Ampoules with a capacity of 2 ml made of brown hydrolytic class I glass, OPC with a white spot, containing an injection solution, clear, colourless to pale yellow, free from visible particulate matter.
Pack sizes
3 or 30 ampoules in a cardboard box.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
ratiopharm GmbH, Graf-Arco-Strasse 3, 89079 Ulm, Germany
Manufacturer:
Merckle GmbH, Ludwig-Merckle-Strasse 3, 89143 Blaubeuren, Germany
For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder.
Teva Pharmaceuticals Polska Sp. z o.o.,
Emilii Plater 53 Street,
00-113 Warsaw,
tel. +48 22 345 93 00