Diclofenac Ratiopharm: detailed information

Package leaflet: information for the patient

Diclofenac ratiopharm 50 mg gastro-resistant tablets

sodium diclofenac
Equivalent medicine
Read this entire leaflet carefully before using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, consult your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it could be harmful.
If you experience any adverse reaction, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Diclofenac ratiopharm is and what it is used for
What you need to know before using Diclofenac ratiopharm
How to use Diclofenac ratiopharm
Possible adverse effects
How to store Diclofenac ratiopharm
Contents of the pack and other information

1. What Diclofenac ratiopharm is and what it is used for

Diclofenac ratiopharm contains sodium diclofenac, a substance that belongs to a group of
medicines called NSAIDs ( non-steroidal anti-inflammatory drugs ), used for its pain-relieving and anti-inflammatory properties.
Diclofenac ratiopharm 50 mg gastro-resistant tablets are indicated for the treatment of:

inflammatory and degenerative rheumatic diseases such as rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, and extra-articular rheumatism;
painful conditions caused by inflammation of non-rheumatic origin, or following trauma;
pain associated with menstrual cycle (primary dysmenorrhea). Consult your doctor if you do not feel better or if you feel worse.

2. What you need to know before using Diclofenac ratiopharm

Do not use Diclofenac ratiopharm

if you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);
if you are allergic to other analgesics, antipyretics, or anti-inflammatory drugs, particularly acetylsalicylic acid;
if you have a stomach or intestinal ulcer, bleeding, perforation, or serious disorders affecting the stomach and intestines (even if these conditions occurred after taking other NSAIDs);
if you have severe impairment of liver or kidney function (severe hepatic or renal insufficiency);
if you are regularly taking diuretic medicines, unless your doctor considers it strictly necessary;
if you currently have bleeding (haemorrhage) or are prone to developing it;
if you have a blood cell production disorder (disturbances in haematopoiesis);
if in the past you experienced asthma attacks, swelling of the face, lips, tongue, throat and/or extremities (signs of angioedema), urticaria, chest pain, or acute rhinitis after taking acetylsalicylic acid (aspirin), ibuprofen, or other NSAIDs such as diclofenac;
if you have serious heart problems (severe heart failure, congestive heart failure, myocardial ischaemia, peripheral arterial disease, cerebrovascular disease), unless your doctor considers it strictly necessary;
to treat a child or adolescent under 14 years of age;
during the first and second trimesters of pregnancy, unless your doctor considers it strictly necessary;
during the third trimester of pregnancy and while breastfeeding.

Inform your doctor if you have recently undergone or are about to undergo surgery on the stomach or intestinal tract before taking Diclofenac ratiopharm, as Diclofenac ratiopharm may sometimes impair wound healing in the intestine following surgical intervention.

Warnings and precautions
Talk to your doctor or pharmacist before using Diclofenac ratiopharm.
The use of diclofenac in gastro-resistant tablets is recommended for short-term treatment.
However, your doctor may prescribe this medicine for longer periods. Always follow your doctor's instructions.
To reduce the risk of adverse effects associated with the use of this medicine, it is recommended to use the lowest effective dose for the shortest possible duration. Always follow your doctor's advice.
Avoid taking other NSAIDs (including COX-2 inhibitors) during treatment with diclofenac, as this may increase the risk of serious adverse reactions.

You must stop treatment and contact your doctor immediately if you experience:

skin rashes, itching, breathing difficulties (bronchospasm), or difficulty swallowing, swelling of the face, hands and feet, eyes, lips, tongue and/or face (angioedema). These may be signs of allergic reactions, even severe ones (anaphylactic shock). See also section "Possible side effects";
mild abdominal pain and cramps at the beginning of treatment with diclofenac, followed by rectal bleeding or bloody diarrhoea usually within 24 hours after onset of abdominal pain (frequency of these symptoms is unknown, cannot be estimated from available data);
other abdominal symptoms and disturbances, especially at the beginning of treatment, particularly if you are elderly or have previously experienced side effects on the stomach or intestines due to medications. These could be symptoms of bleeding, perforations, or ulcerations in the stomach or intestine;
worsening or persistent abnormalities in liver function blood tests, or other signs of liver disease, such as elevated white blood cell count (eosinophilia) or skin rash. These could indicate liver inflammation, even severe forms;
chest pain, shortness of breath, weakness, or speech difficulties. These may be symptoms of serious thrombotic events (problems due to blood clot formation);
excessive fluid accumulation in your body (oedema); this condition is reversible upon discontinuation of treatment.

Exercise particular caution and consult your doctor before taking Diclofenac ratiopharm if:

you are elderly;
you suffer from gastrointestinal disorders or have previously had gastric or intestinal ulcers, bleeding, or perforations (see also “Gastrointestinal effects”);
you are already taking medicines that may increase the risk of ulcers or bleeding (e.g., systemic corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors, or antiplatelet agents such as aspirin);
you suffer from ulcerative colitis or have Crohn’s disease;
your liver or kidney function is impaired;
you suffer from a rare disease characterised by enzyme deficiency in the liver (hepatic porphyria);
your heart function is impaired, for example, if you have heart failure or mild to moderate congestive heart failure, confirmed myocardial ischaemia, or cerebrovascular disease;
you suffer from or have suffered from high blood pressure (hypertension or uncontrolled hypertension);
you are being treated with diuretic medicines;
you are already taking medicines that may affect kidney function; your doctor will inform you if any of your current medications fall into this category;
your extracellular fluid volume is reduced;
you suffer from peripheral arterial disease (formation of fatty deposits on artery walls causing narrowing and blockage);
you are exposed to multiple risk factors for cardiovascular events (such as smoking, diabetes mellitus, high blood pressure, or high blood lipid levels);
you have problems stopping bleeding after injury (problems with haemostasis);
you suffer from asthma, seasonal allergic rhinitis, nasal mucosa swelling, chronic obstructive pulmonary diseases, or chronic respiratory tract infections;
you are prone to allergies;
if you are a woman experiencing fertility problems.

Gastrointestinal effects
Given the serious gastrointestinal consequences that may occur with diclofenac use, to reduce the risk—especially in patients who have previously suffered from ulcers (particularly when complicated by haemorrhage or perforation) and in elderly patients—treatment should be initiated and maintained at the lowest effective dose. The risk of gastrointestinal bleeding is higher in these patient groups, especially when high doses of NSAIDs or other medicines such as corticosteroids, anticoagulants, antiplatelet agents, or selective serotonin reuptake inhibitors are taken. For these patients and for those taking low-dose acetylsalicylic acid (ASA/aspirin), concomitant use of gastroprotective agents (such as misoprostol or proton pump inhibitors) during diclofenac treatment is also recommended. Always follow your doctor's instructions.

Laboratory tests
Depending on your health status and response to the medicine, your doctor may periodically prescribe certain checks and blood tests to monitor the function of your heart, liver, and kidneys, thus evaluating your response to diclofenac therapy and improvement in your health condition.
In particular, you should undergo regular monitoring if:

you need to take diclofenac for prolonged periods;
you have liver or kidney problems; especially if your kidney function is impaired (elderly or dehydrated patients), and you are being treated with ACE inhibitors or angiotensin II antagonists and diclofenac, which may increase the risk of developing renal toxicity—in this case, your doctor will recommend drinking plenty of fluids;
you suffer from high blood pressure (hypertension) and are already taking blood pressure-lowering medicines;
you are diabetic.

Children and adolescents
This medicine must not be used to treat a child or adolescent under 14 years of age.

Elderly patients
Elderly patients have a higher likelihood of experiencing adverse reactions, particularly bleeding and perforations in the stomach or intestine, which are generally more severe and may even be fatal. If you are elderly, especially if you are frail and underweight, your doctor will prescribe the lowest effective dose. Inform your doctor of any unusual stomach or intestinal symptoms, particularly at the beginning of treatment with this medicine.

Other medicines and Diclofenac ratiopharm
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Pay particular attention and inform your doctor if you are taking any of the following medicines:

lithium, used to treat certain mental disorders, or digoxin, used to treat certain heart conditions, because concomitant use with diclofenac increases their plasma concentrations and may lead to possible toxicity;
diuretics and other antihypertensive medicines (such as beta-blockers, ACE inhibitors, angiotensin II antagonists, and potassium-sparing agents) used to treat high blood pressure, because diclofenac may reduce the therapeutic effect of these drug classes;
NSAIDs (non-steroidal anti-inflammatory drugs) and corticosteroids, used to treat certain allergic conditions, because concomitant use with diclofenac increases the risk of gastrointestinal side effects;
anticoagulants and antiplatelet agents, used to thin the blood, because concomitant use with diclofenac may increase the risk of bleeding and haemorrhage;
selective serotonin reuptake inhibitors (SSRIs), used to treat depression, because concomitant use with diclofenac may increase the risk of gastrointestinal bleeding;
antidiabetic agents, because concomitant use with diclofenac may cause an increase or decrease in the therapeutic effect of these medicines;
methotrexate, used to treat certain cancers and autoimmune diseases, because diclofenac may increase the toxicity of this medicine. Your doctor will carefully assess whether diclofenac should be administered within 24 hours before or after methotrexate;
cyclosporine and tacrolimus, immunosuppressants used to modify the body's immune response. Concomitant use of diclofenac and cyclosporine may increase renal toxicity;
trimethoprim (an antibiotic);
quinolone antibacterial agents, antibiotic medicines, because cases of convulsions have been reported during concomitant use with diclofenac;
phenytoin, used to treat epilepsy, because diclofenac increases phenytoin blood levels, increasing the risk of toxicity;
colestipol and cholestyramine, used to treat cholesterol, because they may delay or reduce diclofenac absorption and thus its therapeutic effect;
potent CYP2C9 inhibitors (such as sulfinpyrazone and voriconazole), because medicines in this class may increase diclofenac toxicity;
rifampicin (an antibiotic used to treat bacterial infections), because it may reduce diclofenac absorption.

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before using this medicine.

Pregnancy
Do not take Diclofenac ratiopharm during the last 3 months of pregnancy, as it may harm the fetus or cause problems during delivery. It may cause kidney and heart problems in the fetus. It may affect your and your baby's tendency to bleed and delay or prolong labour beyond expectations.
You should not take Diclofenac ratiopharm during the first 6 months of pregnancy unless absolutely necessary and under medical advice. If treatment is required during this period or during attempts to conceive, the lowest possible dose for the shortest possible time should be used.
From week 20 of pregnancy, Diclofenac ratiopharm may cause kidney problems in the fetus if taken for more than a few days, reducing the levels of amniotic fluid surrounding the baby (oligohydramnios) or causing narrowing of a blood vessel (ductus arteriosus) in the baby's heart.
If treatment for more than a few days is required, your doctor may recommend additional monitoring.

Breastfeeding
Do not take this medicine if you are breastfeeding, as diclofenac passes into breast milk.

Fertility
This medicine may affect female fertility. Therefore, it is recommended to discontinue treatment in women who are trying to conceive, those experiencing fertility difficulties, or those undergoing fertility investigations.

Driving and using machines
Diclofenac ratiopharm may affect your ability to drive and use machinery, as vision disturbances, dizziness, vertigo, drowsiness, or other central nervous system disorders may occur during treatment.

Diclofenac ratiopharm gastro-resistant tablets contain:

lactose: if your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
sodium: this medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially "sodium-free".

3. How to use Diclofenac ratiopharm

Use this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Dosage

Recommended initial dose	100 - 150 mg daily, taken in divided doses of 2 or 3 times a day
Recommended dose for initial therapy	1 tablet 3 times a day (150 mg daily)
Recommended dose for maintenance therapy	1 tablet 2 times a day (100 mg daily)

Treatment of pain associated with the menstrual cycle (primary dysmenorrhoea)
The recommended dose is 50 - 150 mg per day (initially take 50 - 100 mg and, if necessary, increase the dose up to a maximum of 150 mg per day during subsequent menstrual cycles).
Treatment should begin at the onset of the first symptoms and, if needed, continued for a few days. Always follow your doctor's instructions.
Special populations
If you belong to any of the categories listed below, you may not be able to take diclofenac or your doctor may prescribe lower doses than those indicated in this leaflet (see also “Warnings and precautions”):

elderly people;
people with heart or circulatory problems;
people with kidney dysfunction;
people with liver dysfunction.

Method of administration
Take the tablets preferably during or after meals. The tablets should be swallowed whole with some liquid and must not be crushed, split or chewed.

Use in children
Diclofenac ratiopharm 50 mg gastro-resistant tablets must not be used in children or adolescents under 14 years of age.
If you take more Diclofenac ratiopharm than you should
In case of accidental ingestion/overdose of this medicine, contact your doctor immediately or go to the nearest hospital.
Symptoms of overdose may include vomiting, gastrointestinal bleeding, diarrhoea, dizziness, unpleasant ringing in the ears (tinnitus), or seizures.
Taking an extremely high dose of diclofenac may lead to impaired kidney and liver function (acute renal failure).
If you forget to take Diclofenac ratiopharm
Do not take a double dose to make up for the missed dose.
If you stop treatment with Diclofenac ratiopharm
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
Some side effects may be serious.
Stop treatment and contact your doctor immediately if you experience:

skin rash, itching, difficulty breathing (bronchospasm) or swallowing, swelling of the face, hands and feet, eyes, lips, tongue and/or face (angioedema). These may be signs of allergic reactions, including severe ones (anaphylactic shock);
chest pain, which may indicate a potentially serious allergic reaction known as Kounis syndrome;
mild abdominal tenderness and cramps occurring shortly after starting diclofenac treatment, followed by rectal bleeding or hemorrhagic diarrhea usually within 24 hours of the onset of abdominal pain (the frequency of these symptoms is not known, i.e. cannot be estimated from available data);
other gastrointestinal symptoms and disturbances, especially at the beginning of treatment, particularly if you are elderly or have previously experienced stomach or intestinal side effects from medications. These could be symptoms of bleeding, perforation, or ulceration in the stomach or intestine;
worsening or persistent abnormalities in liver function blood tests, or other signs of liver disease, such as elevated white blood cell count (eosinophilia) or skin rash, if you have hepatic insufficiency;
chest pain, shortness of breath, weakness, and speech difficulties. These may be symptoms of serious thrombotic events (problems caused by blood clots);
excessive fluid accumulation in the body (edema); this condition is reversible upon discontinuation of treatment.

Other possible side effects include:

Common (may affect up to 1 in 10 people)

headache, dizziness, vertigo;
nausea, vomiting, diarrhea, indigestion (dyspepsia), abdominal pain, flatulence;
eating disorder leading to food refusal (anorexia);
increased levels of certain liver enzymes (transaminases);
skin rash.

Uncommon (may affect up to 1 in 100 people)

palpitations, chest pain, heart failure, myocardial infarction*. *These side effects have been reported as uncommon in patients treated with diclofenac over long periods and at high doses (150 mg daily). In these patients, the risk of such events is higher.

Rare (may affect up to 1 in 1,000 people)

drowsiness;
asthma and breathing difficulties (dyspnea);
gastritis, gastrointestinal bleeding, presence of blood in vomit (hematemesis), hemorrhagic diarrhea, passage of blood with stools (melena), gastrointestinal ulcer (with or without bleeding, stenosis, or perforation which may lead to peritonitis);
impaired liver function (hepatitis and liver disorders);
yellowing of the skin and whites of the eyes (jaundice);
urticaria;
fluid accumulation (edema).

Very rare (may affect up to 1 in 10,000 people)

reduced number of blood cells called platelets (thrombocytopenia), reduced white blood cell count (leukopenia), excessive reduction of red blood cells (anaemia), inadequate production in the bone marrow of all types of blood cells (aplastic anaemia), low haemoglobin concentration in the blood (haemolytic anaemia), reduced number of white blood cells called granulocytes (agranulocytosis);
disorientation, depression, insomnia, nightmares, irritability, psychotic reactions, anxiety;
altered sensation in limbs or other body parts (paraesthesia);
memory impairment, seizures, tremors;
central nervous system disorder characterized by inflammation of the meninges (aseptic meningitis);
taste disturbances;
stroke (cerebrovascular accidents);
visual disturbances, blurred vision, double vision (diplopia);
ringing in the ears (tinnitus), worsening of hearing;
high blood pressure (hypertension);
inflammation of blood vessels (vasculitis);
pneumonia;
severe intestinal inflammation characterized by episodes of severe diarrhea (colitis), including hemorrhagic enterocolitis, ischemic colitis, and worsening of ulcerative colitis or Crohn's disease;
constipation;
inflammation of the mouth mucosa (stomatitis) or tongue (glossitis), esophageal disorders, narrowing of certain intestinal segments (stenosis), inflammation of the pancreas (pancreatitis);
impaired liver function (liver failure, fulminant hepatitis, or death of liver cells leading to loss of liver function, known as hepatic necrosis);
blistering rashes;
skin changes such as urticaria, formation of red papules or widespread blisters and peeling, particularly on legs, arms, hands and feet, which may extend to the face and lips, occasionally accompanied by fever. These may be symptoms of serious skin diseases such as erythema, erythema multiforme, toxic epidermal necrolysis (Lyell's syndrome), or Stevens-Johnson syndrome;
itching, urticaria, skin rashes, skin irritation, blister formation on the skin and mucous membranes – symptoms of conditions such as eczema, bullous dermatitis, exfoliative dermatitis;
hair loss;
immune system reaction to sunlight manifesting as itchy skin rash (photosensitivity reaction);
small red or purple spots spread over the skin, with or without joint pain, muscle pain, weakness and fever – these may be symptoms of inflammation of blood vessel walls known as purpura (including Henoch-Schönlein purpura);
itching;
impaired kidney function (acute renal failure, nephrotic syndrome, interstitial nephritis, renal papillary necrosis);
presence of blood in urine (haematuria);
excretion of protein in urine (proteinuria).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please contact your doctor or pharmacist. You may also report side effects directly via the national reporting system at: www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Diclofenac ratiopharm

Keep this medicine out of the sight and reach of children.
Store in the original packaging to protect the medicine from moisture.
Do not use this medicine after the expiry date stated on the carton after "Exp". The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Diclofenac ratiopharm contains

The active substance is diclofenac. One gastro-resistant tablet contains 50 mg of sodium diclofenac.
The other ingredients are maize starch, lactose monohydrate, povidone, hydrated colloidal silica, sodium carboxymethylstarch (type A), methacrylic acid-ethyl acrylate copolymer (1:1) 30 percent dispersion, diethyl phthalate, magnesium stearate, microcrystalline cellulose, talc, polysorbate 80, iron oxide (E 172).

Description of the appearance of Diclofenac ratiopharm and package contents
Diclofenac ratiopharm 50 mg gastro-resistant tablets come in a box containing 30 tablets in blister packs.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
ratiopharm GmbH - Graf-Arco Strasse n. 3 - Ulm (Germany)
Manufacturer
Doppel Farmaceutici S.r.l. - Via Volturno, 48 - 20089 Quinto de’ Stampi - Rozzano (MI)

Patient information leaflet

Diclofenac ratiopharm 75 mg/3 ml solution for injection for intramuscular use

sodium diclofenac
Generic medicine
Please read this leaflet carefully before using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, consult your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
If any adverse reaction occurs, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Diclofenac ratiopharm is and what it is used for
What you need to know before using Diclofenac ratiopharm
How to use Diclofenac ratiopharm
Possible side effects
How to store Diclofenac ratiopharm
Contents of the pack and other information

1. What Diclofenac ratiopharm is and what it is used for

Diclofenac ratiopharm contains diclofenac sodium, a substance that belongs to a group of medicines called NSAIDs (non-steroidal anti-inflammatory drugs), used for its analgesic and anti-inflammatory properties.
Diclofenac ratiopharm is indicated for the treatment of:

acute pain episodes due to inflammation of muscles, joints, and bones;
sudden, involuntary contractions of smooth muscle (spasms).

Consult your doctor if you do not feel better or if you feel worse.

2. What you need to know before using Diclofenac ratiopharm

Do not use Diclofenac ratiopharm

if you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);
if you are allergic to other analgesics, antipyretics, or anti-inflammatory drugs, particularly acetylsalicylic acid;
if you have a stomach or intestinal ulcer, bleeding, perforation, or serious disorders affecting the stomach and intestines (even if these conditions occurred after taking other NSAIDs);
if you have severe impairment of liver or kidney function (severe hepatic or renal insufficiency);
if you are regularly taking diuretic medicines, unless your doctor considers it strictly necessary;
if you currently have bleeding (haemorrhage) or are prone to developing it;
if you have a blood cell production disorder (haematopoietic disorders);
if in the past you experienced asthma attacks, swelling of the face, lips, tongue, throat, and/or extremities (signs of angioedema), urticaria, chest pain, or acute rhinitis after taking acetylsalicylic acid (aspirin), ibuprofen, or other NSAIDs such as diclofenac;
if you have severe heart problems (severe heart failure, congestive heart failure, myocardial ischaemia, peripheral arterial disease, cerebrovascular disease), unless your doctor considers it strictly necessary;
to treat a child or adolescent (use of this pharmaceutical form is restricted to adults only);
during the first and second trimester of pregnancy, unless your doctor considers it strictly necessary;
during the third trimester of pregnancy and while breastfeeding.
Inform your doctor if you have recently undergone or are about to undergo stomach or intestinal surgery before taking Diclofenac ratiopharm, as Diclofenac ratiopharm may sometimes impair intestinal wound healing following surgery.

Warnings and precautions
Talk to your doctor or pharmacist before using Diclofenac ratiopharm.
Use Diclofenac ratiopharm 75 mg/3 ml injectable solution only under strict medical supervision and for no more than 2 consecutive days (see also “How to use Diclofenac ratiopharm”).
To reduce the risk of adverse effects associated with the use of this medicine, it is recommended to use the lowest effective dose for the shortest possible duration. Always follow your doctor’s instructions.
Avoid taking other NSAIDs (including COX-2 inhibitors) during treatment with diclofenac, as this may increase the risk of serious adverse reactions.
You must stop treatment and contact your doctor immediately if you experience:

skin rashes, itching, breathing difficulties (bronchospasm), or difficulty swallowing, swelling of the face, hands and feet, eyes, lips, tongue, and/or face (angioedema). These may be signs of allergic reactions, even severe ones (anaphylactic shock). See also section “Possible side effects”;
mild abdominal discomfort and cramps at the beginning of treatment with diclofenac, followed by rectal bleeding or haemorrhagic diarrhoea usually within 24 hours of the onset of abdominal pain (the frequency of these symptoms is unknown, cannot be estimated from available data);
other gastrointestinal symptoms or disturbances, especially at the beginning of treatment, particularly if you are elderly or have previously experienced stomach or intestinal side effects from medications. These may be symptoms of gastrointestinal bleeding, perforation, or ulceration;
worsening or persistent abnormalities in liver function blood tests, or other signs of liver disease, such as elevated white blood cell count (eosinophilia) or skin rash. These may indicate liver inflammation, even severe;
chest pain, shortness of breath, weakness, or speech difficulties. These may be symptoms of serious arterial thrombotic events (problems due to blood clot formation);
excessive fluid accumulation in the body (oedema); this condition is reversible upon discontinuation of treatment.

Take special care and consult your doctor before using Diclofenac ratiopharm if:

you are elderly;
you suffer from gastrointestinal disorders or have previously had gastric or intestinal ulcers, bleeding, or perforations (see also “Gastrointestinal effects”);
you are already taking medicines that may increase the risk of ulceration or bleeding (e.g. systemic corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors, or antiplatelet agents such as aspirin);
you have ulcerative colitis or Crohn’s disease;
your liver or kidney function is impaired;
you suffer from a rare disease characterised by an enzyme deficiency in the liver (hepatic porphyria);
your heart function is impaired, for example if you have heart failure or mild to moderate congestive heart failure, confirmed myocardial ischaemia, or cerebrovascular disease;
you suffer from or have suffered from high blood pressure (hypertension or uncontrolled hypertension);
you are being treated with diuretic medicines;
you are already taking medicines that may affect kidney function; your doctor will inform you if any of your current medications fall into this category;
your extracellular fluid volume is reduced;
you suffer from peripheral arterial disease (formation of fatty deposits on artery walls causing narrowing and obstruction);
you are exposed to multiple risk factors for cardiovascular events (such as smoking, diabetes mellitus, high blood pressure, and high blood lipid levels);
you have problems stopping bleeding in case of injury (haemostasis disorders);
you suffer from asthma, seasonal allergic rhinitis, nasal mucosa swelling, chronic obstructive pulmonary disease, or chronic respiratory tract infections;
you are prone to allergies;
if you are a woman experiencing fertility problems.

Gastrointestinal effects
Given the serious gastrointestinal consequences that may occur following diclofenac use, to reduce the risk—especially in patients with a history of ulcers (particularly when complicated by haemorrhage or perforation) and in the elderly—treatment should be initiated and maintained at the lowest effective dose. The risk of gastrointestinal bleeding is higher in these patient groups, especially when taking high doses of NSAIDs or other medicines such as corticosteroids, anticoagulants, antiplatelet agents, or selective serotonin reuptake inhibitors. For these patients, and for those taking low-dose acetylsalicylic acid (ASA/aspirin), concomitant use of gastroprotective agents (such as misoprostol or proton pump inhibitors) during diclofenac treatment is also recommended. Always follow your doctor’s advice.

Injection site reactions
Injection site reactions have been reported after intramuscular administration (a technique used to deliver the medicine deep into the muscle) of diclofenac, including pain at the injection site, redness, swelling/hardening, ulceration, sometimes with haematoma or pus collection, and damage to the skin and underlying tissue (particularly after accidental subcutaneous administration), a phenomenon known as Nicolau syndrome.

Laboratory tests
Depending on your health status and response to the medicine, your doctor may periodically prescribe blood tests to monitor the function of your heart, liver, and kidneys, and to assess your response to diclofenac therapy and improvement in your health condition.
You should undergo regular monitoring if:

you need to take diclofenac for prolonged periods;
you have liver or kidney problems; particularly if your renal function is impaired (elderly or dehydrated patients) and you are being treated with ACE inhibitors or angiotensin II antagonists; diclofenac may increase the risk of developing renal toxicity—in such cases, your doctor may recommend increased fluid intake;
you have high blood pressure (hypertension) and are already taking blood pressure-lowering medicines;
you are diabetic.

Children and adolescents
This medicine must not be used to treat children or adolescents. The use of Diclofenac ratiopharm 75 mg/3 ml injectable solution for intramuscular use is restricted to adult patients only.

Elderly patients
Elderly patients have a higher likelihood of experiencing adverse reactions, particularly gastrointestinal bleeding and perforation, which are generally more severe and may even be fatal. If you are elderly, especially if you are frail or underweight, your doctor will prescribe the lowest effective dose. Inform your doctor of any unusual stomach or intestinal symptoms, particularly at the beginning of treatment with this medicine.

Other medicines and Diclofenac ratiopharm
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Take particular care and inform your doctor if you are taking any of the following medicines:

lithium, used to treat certain mental disorders, or digoxin, used to treat certain heart conditions, as concomitant use with diclofenac increases their plasma concentrations and may lead to toxicity;
diuretics and other antihypertensive medicines (such as beta-blockers, ACE inhibitors, angiotensin II antagonists, and potassium-sparing agents) used to treat high blood pressure, as diclofenac may reduce the therapeutic effect of these medicines;
NSAIDs (non-steroidal anti-inflammatory drugs) and corticosteroids, used to treat certain allergic conditions, as concomitant use with diclofenac increases the risk of gastrointestinal side effects;
anticoagulants and antiplatelet agents, used to thin the blood, as concomitant use with diclofenac may increase the risk of bleeding and haemorrhage;
selective serotonin reuptake inhibitors (SSRIs), used to treat depression, as concomitant use with diclofenac may increase the risk of gastrointestinal bleeding;
antidiabetic medicines, as concomitant use with diclofenac may increase or decrease the therapeutic effect of these medicines;
methotrexate, used to treat certain cancers and autoimmune diseases, as diclofenac may increase its toxicity. Your doctor will carefully evaluate whether diclofenac should be administered within 24 hours before or after methotrexate;
cyclosporine and tacrolimus, immunosuppressants used to modify the body’s immune response. Concomitant use with diclofenac may increase renal toxicity;
trimethoprim (an antibiotic);
quinolone antibiotics, as cases of convulsions have been reported during concomitant use with diclofenac;
phenytoin, used to treat epilepsy, as diclofenac increases phenytoin blood levels, increasing the risk of toxicity;
cholestyramine and colestipol, used to treat cholesterol, as they may delay or reduce diclofenac absorption and thus its therapeutic effect;
potent CYP2C9 inhibitors (such as sulfinpyrazone and voriconazole), as these medicines may increase diclofenac toxicity;
rifampicin (an antibiotic used to treat bacterial infections), as it may reduce diclofenac absorption.

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.

Pregnancy
Do not take Diclofenac ratiopharm during the last three months of pregnancy, as it may harm the foetus or cause delivery complications. It may cause kidney and heart problems in the foetus. It may affect your and your baby’s tendency to bleed and may delay or prolong labour beyond normal. You should not take Diclofenac ratiopharm during the first six months of pregnancy unless absolutely necessary and under medical advice. If treatment is required during this period or during attempts to conceive, the lowest possible dose for the shortest possible time should be used. From week 20 of pregnancy, Diclofenac ratiopharm may cause kidney problems in the foetus if taken for more than a few days, leading to reduced levels of amniotic fluid surrounding the baby (oligohydramnios) or narrowing of a blood vessel (ductus arteriosus) in the baby’s heart. If treatment is needed for more than a few days, your doctor may recommend additional monitoring.

Breastfeeding
Do not take this medicine if you are breastfeeding, as diclofenac passes into breast milk.

Fertility
This medicine may affect female fertility. Therefore, it is recommended to discontinue treatment in women who are trying to conceive, those experiencing fertility problems, or those undergoing fertility investigations.

Driving and using machines
Diclofenac ratiopharm may affect your ability to drive or operate machinery, as vision disturbances, dizziness, vertigo, drowsiness, or other central nervous system disorders may occur during treatment.

Diclofenac ratiopharm injectable solution contains

sodium: this medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e., essentially “sodium-free”;
benzyl alcohol: this medicine contains 120 mg of benzyl alcohol per 3 ml vial. Benzyl alcohol may cause allergic reactions. Consult your doctor or pharmacist if you have liver or kidney disease, as large amounts of benzyl alcohol may accumulate in the body and cause adverse effects (such as metabolic acidosis);
propylene glycol: this medicine contains 600 mg of propylene glycol per vial.

3. How to use Diclofenac ratiopharm

Use this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Dosage

Recommended dose	1 vial per day
Recommended dose in severe cases (colic)	2 vials per day, separated by an interval of several hours (according to physician's instructions), or 1 vial combined with other diclofenac pharmaceutical forms, up to a maximum daily dose of 150 mg.

Use Diclofenac ratiopharm 75 mg/3 ml injectable solution only under strict medical supervision and for no more than 2 consecutive days. After 2 days of treatment, it is necessary to switch to other pharmaceutical forms in order to reduce the risk of developing serious adverse reactions. Prolonged use of Diclofenac ratiopharm 75 mg/3 ml injectable solution is therefore permitted only in hospitals or nursing homes.

Special populations
If you belong to one of the categories listed below, you may not be able to take diclofenac or your doctor may prescribe lower doses than those indicated in this leaflet (see also "Warnings and precautions"):

elderly people;
people with heart or circulatory dysfunction;
people with kidney dysfunction;
people with liver dysfunction.

Method of administration
Diclofenac injections must be administered following standard sterilization and aseptic procedures. Diclofenac must be injected intramuscularly: inject the contents of one vial deeply into the upper outer quadrant of the buttock. An appropriately long needle should be selected (taking into account the thickness of the patient's gluteal adipose tissue), and an appropriate injection technique must be used to avoid unintentional subcutaneous administration of the drug. If you need to use two vials of diclofenac, do not inject the contents of both vials into the same buttock (inject one vial into each buttock).

Use in children
Diclofenac must not be used in children or adolescents; use of this medicinal product is restricted to adults.

If you use more Diclofenac ratiopharm than you should
In case of accidental ingestion/overdose of this medicine, contact your doctor immediately or go to the nearest hospital.
Symptoms of overdose may include vomiting, gastrointestinal bleeding, diarrhoea, dizziness, unpleasant sensation of ringing in the ears (tinnitus), or seizures.
Ingestion of an extremely high dose of diclofenac may lead to impaired kidney function (acute renal failure) and liver function.

If you forget to use Diclofenac ratiopharm
Do not take a double dose to make up for the missed dose.

If you stop treatment with Diclofenac ratiopharm
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them.
Some side effects may be serious.
Stop taking this medicine and contact your doctor immediately if you experience:

skin rash, itching, difficulty breathing (bronchospasm) or swallowing, swelling of the face, hands and feet, eyes, lips, tongue and/or face (angioedema). These may be signs of allergic reactions, including severe (anaphylactic shock);
chest pain, which may be a sign of a potentially serious allergic reaction called Kounis syndrome;
mild abdominal pain and cramps occurring shortly after starting treatment with diclofenac, followed by rectal bleeding or bloody diarrhoea usually within 24 hours of the onset of abdominal pain (the frequency of these symptoms is not known, i.e. cannot be estimated from available data);
other gastrointestinal symptoms, especially at the beginning of treatment, particularly if you are elderly or have previously experienced stomach or intestinal side effects from medicines. These may be symptoms of bleeding, perforation or ulceration of the stomach or intestine;
worsening or persistent abnormalities in blood tests assessing liver function, or other signs of liver disease, such as elevated levels of white blood cells in the blood (eosinophilia) or skin rash, if you suffer from liver impairment;
chest pain, shortness of breath, weakness, and speech difficulties. These may be symptoms of serious thrombotic events (problems due to blood clot formation);
excessive fluid accumulation in the body (oedema); this condition is reversible upon discontinuation of treatment;
injection site reactions, including pain, redness, swelling, hard nodule, ulcers, and bruising. These reactions may worsen with darkening and death of the skin and underlying tissues surrounding the injection site, which then heal with scarring; this condition is known as Nicolau syndrome.

Other possible side effects include:

Common (may affect up to 1 in 10 people)

headache, dizziness, vertigo;
nausea, vomiting, diarrhoea, indigestion (dyspepsia), abdominal pain, flatulence;
eating disorder leading to food refusal (anorexia);
increased levels of certain liver enzymes (transaminases);
skin rash;
reaction, pain or hardening at the injection site.

Uncommon (may affect up to 1 in 100 people)

palpitations, chest pain, heart failure, myocardial infarction*. *These side effects have been reported as uncommon in patients treated with diclofenac over long periods and at high doses (150 mg daily). In these patients, the risk of such effects is higher.

Rare (may affect up to 1 in 1,000 people)

somnolence;
asthma and breathing difficulties (dyspnoea);
gastritis, gastrointestinal bleeding, presence of blood in vomit (haematemesis), bloody diarrhoea, passage of blood with stools (melena), gastrointestinal ulcer (with or without bleeding, stenosis or perforation which may lead to peritonitis);
altered liver function (hepatitis and liver disorders);
yellowing of the skin and whites of the eyes (jaundice);
urticaria;
fluid accumulation (oedema);
tissue damage at injection site.

Very rare (may affect up to 1 in 10,000 people)

reduced number of blood cells called platelets (thrombocytopenia), reduced white blood cells in the blood (leucopenia), excessive reduction in red blood cells (anaemia), inadequate production in the bone marrow of all types of blood cells (aplastic anaemia), low concentration of haemoglobin in the blood (haemolytic anaemia), reduced number of white blood cells called granulocytes (agranulocytosis);
disorientation, depression, insomnia, nightmares, irritability, psychotic reactions, anxiety;
altered sensation in limbs or other body parts (paraesthesia);
memory impairment, seizures, tremors;
central nervous system disorder characterised by inflammation of the meninges (aseptic meningitis);
taste disturbances;
stroke (cerebrovascular accidents);
visual disturbances, blurred vision, double vision (diplopia);
ringing in the ears (tinnitus), hearing loss;
high blood pressure (hypertension);
inflammation of blood vessels (vasculitis);
pneumonia;
severe intestinal inflammation characterised by episodes of severe diarrhoea (colitis), including haemorrhagic enterocolitis, ischaemic colitis, and worsening of ulcerative colitis or Crohn's disease;
constipation;
inflammation of the mucous membrane of the mouth (stomatitis) or tongue (glossitis), disorders affecting the oesophagus, narrowing of certain intestinal segments (stenosis), inflammation of the pancreas (pancreatitis);
altered liver function (liver failure, fulminant hepatitis, or death of liver cells leading to loss of liver function known as hepatic necrosis);
blistering rash;
skin changes such as urticaria, formation of red papules or widespread blisters and peeling, particularly on legs, arms, hands and feet, which may extend to the face and lips, occasionally accompanied by fever. These may be symptoms of serious skin diseases such as erythema, erythema multiforme, toxic epidermal necrolysis (Lyell's syndrome) or Stevens-Johnson syndrome;
itching, urticaria, skin rashes, skin irritation, blister formation on the skin and mucous membranes – symptoms of conditions such as eczema, bullous dermatitis, exfoliative dermatitis;
hair loss;
immune system reaction to sunlight manifesting as itchy skin rash (photosensitivity reaction);
small red or purple spots on the skin, with or without joint pain, muscle pain, weakness and fever; these may be symptoms of inflammation of blood vessel walls known as purpura (including Henoch-Schönlein purpura);
itching;
impaired kidney function (acute renal failure, nephrotic syndrome, interstitial nephritis, renal papillary necrosis);
presence of blood in urine (haematuria);
excretion of protein in urine (proteinuria);
inflammatory reaction at injection site (abscess).

Not known (frequency cannot be estimated from available data)

chest pain, which may be a sign of a potentially serious allergic reaction called Kounis syndrome;
Nicolau syndrome, which manifests as an immediate, intense painful sensation at the injection site, followed by redness, swelling, and nodule formation, possibly due to blockage of blood vessels leading to damage of the skin and underlying tissue.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at: www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Diclofenac ratiopharm

Keep this medicine out of the sight and reach of children.
Do not store above 30°C.
Store the ampoules in the original packaging to protect the medicine from light.
Do not use this medicine after the expiry date stated on the carton after Exp. The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Diclofenac ratiopharm contains

The active substance is diclofenac. One vial contains 75 mg of sodium diclofenac.
The other ingredients are acetylcysteine, disodium edetate, mannitol, benzyl alcohol, propylene glycol, sodium hydroxide, water for injections.

Description of the appearance of Diclofenac ratiopharm and contents of the pack
Diclofenac ratiopharm 75 mg/3 ml solution for injection for intramuscular use is presented in a box containing 5 glass vials.
Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
ratiopharm GmbH - Graf-Arco Strasse n. 3 - Ulm (Germany)
Manufacturer
Merckle GmbH - Graf-Arco Strasse, 3 - Ulm (Germany)