Package leaflet: Information for the user

Dololibre 50 mg/ml oral suspension

Naproxen
Equivalent medicine
Please read all of this leaflet carefully before taking this medicine because it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask 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 may be harmful.
If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Dololibre is and what it is used for
What you need to know before taking Dololibre
How to take Dololibre
Possible side effects
How to store Dololibre
Contents of the pack and other information

1. What Dololibre is and what it is used for

Dololibre contains a medicine called naproxen, which is a "non-steroidal anti-inflammatory drug" (NSAID).
Dololibre is used in adults for the symptomatic treatment of:

pain and inflammation in:
rheumatoid arthritis, ankylosing spondylitis (pain and stiffness of the neck and back), acute attacks of osteoarthritis and spondyloarthritis
acute gout
inflammatory rheumatic diseases of soft tissues
painful swelling or inflammation following musculoskeletal injuries
menstrual pain

It may also be used in children from the age of 2 years and in adolescents affected by juvenile idiopathic arthritis.

2. What you should know before taking Dololibre

Do not take Dololibre:

if you are allergic to naproxen or to any of the other ingredients of this medicine (listed in section 6).
if you have a history of asthma attacks, angioedema, skin reactions, or acute rhinitis after taking acetylsalicylic acid or any other NSAID.
if you have blood formation disorders.
if you currently have a stomach or intestinal ulcer or bleeding.
if you have a history of duodenal or gastric ulcer (peptic ulcers) or recurrent bleeding (at least two distinct episodes of ulcer or confirmed bleeding).
if in the past you experienced perforation or bleeding in the stomach or intestine while taking NSAIDs.
if you have severe renal, hepatic, or cardiac insufficiency.
if you are experiencing cerebral haemorrhage.
if you currently have any other form of acute bleeding.
if you are in the last three months of pregnancy (see "Pregnancy, breastfeeding and fertility").

Warnings and precautions
Adverse effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.
Medicines such as Dololibre may be associated with a small increased risk of heart attack ("myocardial infarction") or stroke. The risk is more likely with high-dose treatment and prolonged use. Do not exceed the recommended dose or duration of treatment.
If you have heart problems, have had a stroke, or think you may be at higher risk of these conditions (for example, high blood pressure, diabetes, high cholesterol levels, or if you smoke), discuss this treatment with your doctor or pharmacist.
Consult your doctor or pharmacist before taking Dololibre:

if you have asthma, allergies (such as hay fever), or chronic obstructive airway disease, or if you previously experienced swelling of the face, lips, eyes, or tongue.
if you have nasal polyps or sneeze frequently, or have a runny, blocked, or itchy nose (rhinitis).
if you feel weak (possibly due to illness) or if you are elderly.
if you have kidney or liver problems.
if you have blood clotting disorders.
if you are taking medicines such as corticosteroids, anticoagulants, selective serotonin re-uptake inhibitors (SSRIs), acetylsalicylic acid, or NSAIDs, including cyclooxygenase-2 (COX-2) inhibitors.
if you have previously had stomach ulcers or bleeding. You will be asked to report any unusual stomach symptoms to your doctor.
if you have an autoimmune disease, such as systemic lupus erythematosus (SLE; causing joint pain, skin rashes, and fever), mixed connective tissue disease, ulcerative colitis, or Crohn's disease (conditions causing intestinal inflammation and pain, diarrhoea, vomiting, and weight loss).
if you have vision or hearing problems.
if you recently underwent major surgery before starting treatment with Dololibre.
if you have heavy menstrual periods.
if you have a disorder of red pigment biosynthesis that gives blood its colour (porphyria).

Treatment with this medicine must be stopped immediately in case of gastrointestinal bleeding, visual disturbances, or hearing impairment.
Severe skin reactions (including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis) have been very rarely reported in association with NSAID administration. These reactions usually occur early in treatment (within the first month). If you develop a skin rash (including mucosal lesions such as in the mouth, throat, nose, eyes, genitals) or other signs of hypersensitivity, stop using Dololibre immediately and seek immediate medical advice.

General information
Pain relief and underlying disease
If you do not feel better during treatment with naproxen, or if your pain, fever, or other signs of illness persist, consult your doctor. Painkillers may mask symptoms of an underlying condition.
Medication-overuse headache
Prolonged use of high doses of painkillers may cause headache, which should not be treated by taking higher doses of painkillers.
Kidney damage from painkillers
Regular, long-term use of certain painkillers may lead to permanent kidney damage and risk of kidney failure.

If any of the above situations apply to you or if you have any doubts,
consult your doctor or pharmacist before taking Dololibre.
Laboratory test results
If your doctor recommends monitoring of blood counts, blood coagulation tests, and/or kidney and liver function tests and/or other tests (e.g., measuring blood levels of certain medicines), it is essential that you undergo them. This particularly applies to patients with impaired liver function, heart failure, high blood pressure, or kidney damage.
If you need to undergo an adrenal function test, you should stop (temporarily) taking Dololibre at least 3 days before the test to avoid interference with test results.

Children and adolescents
Dololibre is not recommended for children under 2 years of age due to insufficient experience.
Dololibre is not recommended for use in conditions other than juvenile idiopathic arthritis in children and adolescents under 18 years of age.

Other medicines and Dololibre
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including over-the-counter medicines or herbal remedies. In particular, inform your doctor or pharmacist if you are taking:

Other NSAIDs, including salicylates (such as acetylsalicylic acid) and COX-2 inhibitors.
Aspirin/acetylsalicylic acid for prevention of blood clots.
Glucocorticoids (for swelling and inflammation), such as hydrocortisone, prednisolone, and dexamethasone.
Medicines to prevent blood clotting, such as warfarin, heparin, or clopidogrel.
Phenytoin (used to treat epilepsy).
Sulphonamide medicines, such as hydrochlorothiazide, acetazolamide, indapamide, and including sulphonamide antibiotics (for infections).
Oral medicines for diabetes, such as glimepiride or glipizide.
An ACE inhibitor or any other medicine for high blood pressure, such as cilazapril, enalapril, or propranolol.
An angiotensin II receptor antagonist, such as candesartan, eprosartan, or losartan.
A diuretic (medicine to increase urine excretion) (for high blood pressure), such as furosemide or triamterene.
A cardiac glycoside (for heart problems), such as digoxin.
A quinolone antibiotic (for infections), such as ciprofloxacin or moxifloxacin.
Certain medicines for mental health conditions, such as lithium or selective serotonin re-uptake inhibitors (SSRIs), such as fluoxetine or citalopram.
Probenecid and sulfinpyrazone (for gout).
Methotrexate (used in the treatment of skin conditions, arthritis, or cancer).
Cyclosporine or tacrolimus (for skin conditions or after organ transplant).
Zidovudine (used in the treatment of AIDS and HIV infections).
Mifepristone (used to terminate a pregnancy or induce labour in case of intrauterine fetal death).
Antacids (to neutralize excess stomach acidity).

If any of the above situations apply to you or if you have any doubts, consult your doctor or pharmacist before taking Dololibre.

Dololibre with food, drinks, and alcohol
Consuming alcoholic beverages during treatment with Dololibre increases the risk of gastrointestinal bleeding (in the stomach and intestine) and should therefore be avoided.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Dololibre should be avoided during the first 6 months of pregnancy unless specifically prescribed by your doctor.
Do not take Dololibre during the last trimester of pregnancy, as it may have harmful effects on you and your baby.
Do not take Dololibre after childbirth, as it may delay the process of uterine involution (reduction of the uterus to its normal size and shape).
Breastfeeding
You should avoid taking Dololibre while breastfeeding, as the medicine may be excreted in breast milk in small amounts.
Fertility
Dololibre may make it more difficult to conceive. Inform your doctor if you are planning a pregnancy or if you have fertility problems.

Driving and using machines
Dololibre may cause fatigue, dizziness, visual disturbances, or other central nervous system disorders. If you experience any of these symptoms, consult your doctor and do not drive or operate machinery.

Dololibre contains sucrose, sorbitol (E 420), sodium, and methyl parahydroxybenzoate (E 218)
Sucrose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine. One ml contains 300 mg of sucrose (sugar). This should be considered in people with diabetes mellitus. It may be harmful to teeth.
Sorbitol (E 420)
This medicine contains 90 mg of sorbitol (E 420) per ml. Sorbitol (E 420) is a source of fructose. If your doctor has told you that you (or your child) have an intolerance to certain sugars, or if you have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which patients cannot metabolize fructose, consult your doctor before you (or your child) take this medicine.
Sodium
This medicine contains 9.2 mg of sodium (the main component of table salt) per ml. This corresponds to 0.46% of the maximum daily dietary intake recommended for an adult.
Methyl parahydroxybenzoate (E 218)
This medicine contains methyl parahydroxybenzoate (E 218) as a preservative. It may cause allergic reactions (including delayed-type reactions).

3. How to take Dololibre

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Shake the bottle vigorously before use. Take Dololibre with a sufficient amount of liquid.
Dololibre starts to work more quickly if taken on an empty stomach. However, patients who have a sensitive stomach are advised to take Dololibre during meals.
Like all NSAIDs, you should take the lowest possible dose of Dololibre necessary to relieve pain, and for the shortest possible duration. This precaution helps minimize potential side effects.
The package contains an 8 ml oral dosing syringe graduated in 0.1 ml increments, which must be used to administer this medicine.

Instructions for using the oral dosing syringe:

Insert the tip of the oral dosing syringe into the medicine.
Holding the syringe in place, gently pull back the plunger to draw the medicine up to the correct mark on the syringe.
If air bubbles form, return the medicine to the bottle and draw it up again to the correct mark on the syringe.
Remove the syringe from the bottle.
Place the tip of the syringe into the patient’s mouth and gently and slowly push the plunger to release the medicine.
After use, close the bottle with the screw cap. Wash the syringe with water. Disassemble the two parts of the syringe and allow them to dry. Keep out of the reach of children.

Unless otherwise prescribed by the doctor, the recommended dose is:
Adults up to 65 years of age
The recommended dose is 10 to 20 ml of Dololibre (500 mg to 1,000 mg of naproxen) per day. The daily dose must not exceed 20 ml of Dololibre (1,000 mg of naproxen).
Dosage should be adjusted according to the individual patient’s clinical condition.

Symptomatic treatment of painful swelling or inflammation following musculoskeletal injuries
The initial dose is usually 10 ml of Dololibre (500 mg of naproxen). If needed, you may take an additional dose of 5 ml (250 mg of naproxen) every 6–8 hours. The daily dose must not exceed 20 ml of Dololibre (1,000 mg of naproxen).

Symptomatic treatment of pain and inflammation in rheumatoid arthritis, ankylosing spondylitis, acute attacks of osteoarthritis and spondyloarthritis, and inflammatory rheumatic diseases of soft tissues
The usual daily dose is 10–15 ml of Dololibre (500–750 mg of naproxen). At the beginning of treatment, during acute phases of inflammation, or when switching from another high-dose NSAID to Dololibre, the recommended dose is 15 ml of Dololibre (750 mg of naproxen), taken as two divided doses per day (10 ml in the morning and 5 ml in the evening, or vice versa) or as a single daily dose (in the morning or evening).
In individual cases, the doctor may increase the daily dose up to 20 ml of Dololibre (1,000 mg of naproxen).
The maintenance dose is 10 ml of Dololibre (500 mg of naproxen) per day, which may be taken as two divided doses (5 ml in the morning and 5 ml in the evening) or as a single daily dose (in the morning or evening).

Symptomatic treatment of pain and inflammation in acute gout
The initial dose is usually 15 ml of Dololibre (750 mg of naproxen); thereafter, take 5 ml of Dololibre (250 mg of naproxen) every 8 hours until the attack resolves. During acute gout attacks, the maximum daily dose of 20 ml (1,000 mg of naproxen) may be exceeded for a short period of time.

Symptomatic treatment of menstrual pain
The initial dose is usually 10 ml of Dololibre (500 mg of naproxen); thereafter, you may take 5 ml of Dololibre (250 mg of naproxen) every 6–8 hours. The daily dose must not exceed 20 ml of Dololibre (1,000 mg of naproxen).

Children from 2 years of age and adolescents for the treatment of juvenile idiopathic arthritis
The recommended dose is 10 mg/kg body weight of naproxen per day, corresponding to a daily dose of 0.2 ml of Dololibre per kilogram of body weight, administered as two divided doses (single dose of 0.1 ml of Dololibre (5 mg of naproxen) per kilogram of body weight). In adolescents, the daily dose must not exceed 20 ml (1,000 mg of naproxen).
Dololibre is not recommended in children under 2 years of age (see section “Warnings and precautions”, subsection “Children and adolescents”).

Special patient populations
Elderly (over 65 years of age)
Careful monitoring by the doctor is required. In elderly patients, it is particularly important to select the lowest effective dose of Dololibre for the shortest possible treatment duration (see section 2 “What you need to know before taking Dololibre”).

Patients with impaired liver function
Patients with impaired liver function are at risk of overdose when taking Dololibre. Therefore, the lowest effective dose of Dololibre should be selected. Careful monitoring by the doctor is required.
If your liver function is severely impaired, you must not take Dololibre (see section 2 “What you need to know before taking Dololibre”).

Patients with impaired kidney function
If you have impaired kidney function, your doctor may decide to reduce the dose of Dololibre.
If your kidney function is severely impaired, you must not take Dololibre (see section 2 “What you need to know before taking Dololibre”).

Duration of treatment
The duration of treatment is determined by the treating physician.
For rheumatic diseases, long-term treatment with Dololibre may be necessary.
For menstrual pain, the duration of treatment depends on the individual symptoms. However, treatment with Dololibre should not exceed a few days.

If you take more Dololibre than you should
If you take more Dololibre than you should, contact your doctor immediately or go to hospital straight away. Take the medicine package with you.
For healthcare professionals: information on the management of naproxen poisoning is provided at the end of this leaflet.

If you forget to take Dololibre
Do not take a double dose to make up for the missed dose. Continue taking Dololibre as usual.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them. Medicines such as Dololibre may be associated with a modest increase in the risk of heart attack ("myocardial infarction") or stroke.
Important side effects to be aware of:
If you experience any of the following symptoms or combinations of symptoms, stop taking this medicine immediately and consult your doctor without delay. You may require urgent medical treatment.
Severe allergic reactions (may affect up to 1 in 10,000 people), signs include:

Shortness of breath
Severe drop in blood pressure
Swelling of the face or throat, difficulty swallowing
Skin rash (itchy), redness, small blisters

Severe stomach and intestinal problems (may affect up to 1 in 10 people), signs include:

Relatively severe abdominal (stomach) pain, especially if it occurs suddenly
Vomiting blood or coffee-ground-like vomit
Black or bloody stools
Ulcers, perforations (holes), and bleeding in the stomach or intestine, sometimes fatal, particularly in elderly patients
Heart attack, signs include:
Chest pain that may spread to the neck and shoulders and down the left arm

Liver problems (may affect up to 1 in 10,000 people), signs include:

Extreme tiredness associated with loss of appetite, with or without yellowing of the skin and whites of the eyes
Nausea or vomiting or pale-coloured stools

Sensory organ impairment, for example:

Sudden onset of visual disturbances (may affect up to 1 in 10,000 people) or hearing impairment (may affect up to 1 in 10 people)

Aseptic meningitis (may affect up to 1 in 10,000 people), signs include:

Severe headache, particularly if sudden
Stiff neck, fever, nausea or vomiting
Confusion, sensitivity to bright light

Patients with autoimmune disorders (SLE, mixed connective tissue disease) are at higher risk of developing meningitis.
Blood and lymphatic system disorders (may affect up to 1 in 10,000 people), signs include:

Flu-like symptoms, mouth ulcers, sore throat and nosebleeds

Dololibre may cause the following side effects:
Very common side effects (may affect up to 1 in 10 people):

Feeling unwell
Vomiting
Heartburn
Stomach pain
Fullness
Constipation or diarrhoea and minor rectal bleeding in the gastrointestinal tract which, in rare cases, may lead to anaemia

Common side effects (may affect up to 1 in 10 people):

Bleeding of the skin and mucous membranes
Depression
Changes in dream activity
Difficulty falling asleep or staying asleep (insomnia)
Headache
Dizziness
Restlessness
Irritability
Sleep disturbances
Fatigue
Disturbances in perception and cognitive dysfunction
Ringing in the ears
Vertigo (dizziness)
Sweating
Fluid retention in tissues (oedema), particularly in patients with high blood pressure
Thirst

Uncommon side effects (may affect up to 1 in 100 people):

Changes in blood count
Increase in number of certain types of white blood cells (eosinophilia)
Asthma attacks (with or without reduction in blood pressure)
Inflammation of the lungs (eosinophilic pneumonia)
Lower abdominal symptoms (e.g., inflammation of the large intestine with bleeding or worsening of Crohn's disease/ulcerative colitis)
Inflammation of the inner lining of the oral cavity (mouth)
Injury to the digestive tract
Changes in liver function with increased transaminases
Hair loss (usually temporary)
Skin inflammation caused by light (sunlight) (which may include rash with blisters)
Muscle pain
Muscle weakness
Acute kidney failure
Impaired kidney function (nephrotic syndrome)
Inflammation of one or both kidneys (interstitial nephritis)
Fever and chills, malaise
Inflammation of the inner lining of the stomach
Gas

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

Skin rash with blisters (reactions similar to bullous epidermolysis)

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

Decrease in the number of red blood cells and/or white blood cells and/or platelets in the blood (aplastic or haemolytic anaemia, thrombocytopenia, leucopenia, pancytopenia, agranulocytosis)
Convulsions (seizures)
Inflammation of nerves
High blood pressure
Increased heart rate
Palpitations (sensation of a pounding heartbeat)
Heart failure
Inflammation of blood vessels
Worsening of infection-related inflammation (e.g., development of necrotizing fasciitis, i.e., acute inflammation and necrosis [tissue death] of fatty tissues beneath the skin and muscles)
Anaphylactic or anaphylactoid systemic reactions
Liver inflammation (hepatitis), liver damage, particularly after long-term therapy
Hypersensitivity reactions such as skin rashes, erythema multiforme; in isolated cases, severe cutaneous adverse reactions (including Stevens-Johnson syndrome or toxic epidermal necrolysis)
Kidney damage (renal papillary necrosis) (particularly after long-term therapy)
Increased level of uric acid in the blood

Not known (frequency cannot be estimated from the available data):

Increased potassium levels
Decreased number of white blood cells (neutropenia)
Swelling of the lens and optic nerve head
Corneal opacity
Inflammation of the optic nerve head
Tingling or numbness of hands and feet
Pulmonary oedema
Inflammation of the pancreas (a large gland behind the stomach)
Erythema nodosum (a skin inflammation causing painful reddish bumps)
Lichen planus (an itchy, non-infectious skin rash that may appear in many areas of the body)
Systemic lupus erythematosus (SLE, an autoimmune disease causing inflammatory processes that may affect various parts of the body)
Pustular reaction
Fixed drug eruption (FDE, an allergic skin rash in patches that reappears in the same location each time the drug is taken)
Blood in the urine (haematuria)
Inflammation of certain parts of the kidneys (glomerulonephritis)
Female infertility
Oedema

Naproxen may interfere with laboratory test results; therefore, inform your doctors (if applicable) that you are taking Dololibre (see section 2 "What you need to know before taking Dololibre").
Methyl parahydroxybenzoate (E 218) may cause allergic reactions (including delayed reactions).
Additional side effects in children and adolescents
The frequency, type, and severity of side effects in children and adolescents are similar to those reported in adults.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You may also report side effects directly via the national reporting system at https://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 Dololibre

Keep in the original packaging to protect the medicine from light.
After first opening, this medicine is stable for 3 months. Store in the original packaging
to protect the medicine from light.
This medicine does not require any special storage temperature.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and on the carton after
"Exp". The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater. 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 Dololibre contains

The active substance is naproxen. 1 ml of Dololibre contains 50 mg of naproxen.
The other components are: sucrose (sugar), sodium saccharin (E 954), sodium cyclamate (E 952), sodium chloride, methyl parahydroxybenzoate (E 218), potassium sorbate (E 202), tragacanth gum (E 413), citric acid (E 330), liquid sorbitol (crystallizable) (E 420), water.

Description of the appearance of Dololibre and contents of the pack
Dololibre is an oral suspension, white or slightly yellowish-white in colour.
Amber glass bottle with a child-resistant screw cap.
Graduated oral dosing syringe of 8 ml, with 0.1 ml increments.
Pack size: 100 ml

Marketing Authorization Holder and Manufacturer
INFECTOPHARM Arzneimittel und Consilium GmbH
Von-Humboldt-Strasse 1
64646 Heppenheim
Germany

This medicinal product is authorized in the European Economic Area Member States under the following names:
Austria: Naproxen Infectopharm 50 mg/ml Suspension zum Einnehmen
Italy: Dololibre
Poland: Dololibre
Portugal: Dololibre
Spain: Naproxeno Infectopharm, 50 mg/ml suspensión oral

The following information is intended exclusively for physicians or healthcare professionals:

In case of naproxen overdose:

Symptoms of overdose
Symptoms of overdose may include central nervous system (CNS) disturbances such as headache, dizziness, and mental confusion, as well as epigastric pain, abdominal discomfort, indigestion, nausea, vomiting, transient alterations in liver function, hypoprothrombinemia, renal dysfunction, metabolic acidosis, apnea, and disorientation. Naproxen may be rapidly absorbed. High and early blood concentrations of the drug should be expected. Some patients have experienced convulsions, although it was not clearly established whether these were caused by naproxen treatment. Gastrointestinal bleeding may also occur. Hypertension, acute renal failure, respiratory depression, and coma may manifest, although rarely. Anaphylactic reactions have been reported following treatment with non-steroidal anti-inflammatory drugs and may also occur in cases of overdose.

Management of overdose
Patients should be treated symptomatically. There are no specific antidotes. Preventive measures to reduce further absorption (e.g., administration of activated charcoal) may be considered in patients within four hours after ingestion or following a significant overdose. Forced diuresis, alkalinization of urine, hemodialysis, or hemoperfusion are unlikely to be beneficial due to naproxen's high protein binding.