Gexiro

Package leaflet: Information for the patient

Gexiro, (10 mg + 3 mg)/mL, infusion solution
Paracetamolum + Ibuprofenum
Please read this leaflet carefully before using the medicine, as it contains important information for you.

• Keep this leaflet so that you can read it again if necessary.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.
• Do not use this medicine for longer than 2 days.

Table of contents

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

1. What Gexiro is and what it is used for

Gexiro contains paracetamol and ibuprofen as active substances. Ibuprofen belongs to a group of medicines called non-steroidal anti-inflammatory drugs (or NSAIDs). Paracetamol works differently from ibuprofen, but together both substances act to reduce pain.
Gexiro is used in adults for short-term symptomatic treatment of acute moderate pain when intravenous administration is necessary and/or other routes of administration are not feasible.

2. Important information before using Gexiro

When not to use Gexiro:

• if the patient is allergic to the active substances, other NSAIDs, or any of the other ingredients of this medicine (listed in section 6);
• if the patient has severe heart, liver, or kidney failure;
• if the patient regularly consumes large amounts of alcohol;
• if the patient has asthma, urticaria, or allergic-type reactions after taking acetylsalicylic acid or other NSAIDs;
• if the patient has a history of gastrointestinal bleeding or perforation related to previous treatment with NSAIDs;
• if the patient has or has had active or recurrent peptic ulcer disease (e.g. gastric or duodenal ulcer) or bleeding (two or more distinct episodes of confirmed ulceration or bleeding);
• if the patient has bleeding within the brain (cerebral haemorrhage) or any other active bleeding;
• if the patient has blood clotting disorders or increased tendency to bleed;
• if the patient is severely dehydrated (due to vomiting, diarrhoea, or insufficient fluid intake);
• during the third trimester of pregnancy;
• if the patient is under 18 years of age.

Warnings and precautions
To avoid the risk of overdose, you should:

• check whether other medicines being taken contain paracetamol;
• not exceed the maximum recommended doses (see section 3).

Adverse effects can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms. Do not use Gexiro for longer than 2 days.
If the patient has severe medical conditions while being treated with Gexiro, including severe renal impairment, sepsis (when bacteria and their toxins circulate in the blood, leading to organ damage), malnutrition, chronic alcoholism, or if the patient is also taking flucloxacillin (an antibiotic), severe metabolic acidosis (an abnormality in blood and body fluids) has been reported. This condition may occur when paracetamol is taken regularly over a prolonged period or when paracetamol is taken together with flucloxacillin.
Symptoms of metabolic acidosis may include: severe breathing difficulties, including rapid deep breathing, drowsiness, nausea, and vomiting.
Before starting treatment with Gexiro, discuss this with your doctor or nurse if:

• the patient is taking any other medicines containing paracetamol, ibuprofen, or other non-steroidal anti-inflammatory painkillers (NSAIDs) (to avoid the risk of overdose);
• the patient has heart disease, such as heart failure, angina (chest pain), previous heart attack, bypass surgery, peripheral arterial disease (poor circulation in legs or feet due to narrowed or blocked arteries), or any history of stroke [including "mini-stroke" or transient ischemic attack (TIA)];
• the patient has high blood pressure, diabetes, elevated cholesterol levels, a family history of heart disease or stroke, or is a smoker;
• the patient has liver disease, hepatitis, kidney disease, or difficulty passing urine;
• the patient currently has an infection; Gexiro may mask signs or symptoms of infection (fever, pain, swelling);
• the patient has or has previously had heartburn, indigestion, stomach ulcers, or any other stomach problems;
• the patient has recently had or is planning to undergo surgery;
• the patient has an infection (see section "Infections" below);
• the patient has asthma;
• the patient is dehydrated or has diarrhoea;
• the patient has intestinal disorders such as ulcerative colitis or Crohn's disease;
• the patient has inherited or acquired enzyme deficiencies presenting with neurological or skin disorders, or sometimes both, e.g. porphyria;
• the patient has an autoimmune disease such as systemic lupus erythematosus or other connective tissue disorders, as this may increase the risk of aseptic meningitis (inflammation of the protective membranes covering the brain);
• the patient has hay fever, nasal polyps, or chronic obstructive pulmonary disease (COPD), as this may increase the risk of allergic reactions;
• the patient is pregnant or planning to become pregnant (see section "Pregnancy, breastfeeding and fertility").

Cardiovascular risk
The use of anti-inflammatory and/or pain-relieving medicines such as ibuprofen may cause a small increase in the risk of heart attack or stroke, especially when used at high doses. Do not exceed the recommended dose or duration of treatment.
Gastrointestinal symptoms
Serious gastrointestinal adverse effects (affecting the stomach and intestines) have been reported with the use of NSAIDs, including ibuprofen. These may occur with or without warning symptoms. The risk of such adverse effects is higher in patients with a history of stomach or intestinal ulcers, particularly if there was also bleeding or perforation. Elderly patients are more susceptible to gastrointestinal adverse effects. Discuss any past gastrointestinal disorders with your doctor and remain vigilant for any unusual abdominal symptoms, including nausea, vomiting, diarrhoea, constipation, indigestion, abdominal pain, tarry stools, or bloody vomit.
For elderly patients, treatment should be discussed with a doctor before starting. Elderly patients have a higher risk of adverse effects, especially gastrointestinal bleeding and perforation.
Skin reactions
Severe skin reactions associated with ibuprofen treatment have been reported. Immediately consult a doctor or nurse if the patient develops a skin rash, mucosal lesions, blisters on the skin, or other allergic symptoms, as these may be early signs of a very serious skin reaction. See section 4.
Infections
Gexiro may mask symptoms of infection such as fever and pain. Therefore, using Gexiro may delay the start of appropriate treatment for infection, increasing the risk of complications. This has been observed in cases of bacterial pneumonia and bacterial skin infections during chickenpox. If the patient has an infection and symptoms persist or worsen, seek immediate medical advice.
Long-term use of painkillers
Long-term use of painkillers may cause headaches, which should not be treated by increasing the dose of these medicines. If the patient experiences such symptoms, they should consult a doctor or pharmacist.
Vision disturbances
If the patient experiences any visual disturbances after taking Gexiro, treatment should be stopped immediately and the doctor informed.

Children and adolescents
Gexiro is not indicated for use in children and adolescents under 18 years of age.

Gexiro and other medicines
Tell your doctor or nurse about all medicines the patient is currently taking or has recently taken, as well as any medicines they plan to take.
Always inform your doctor if the patient is taking other medicines containing paracetamol, ibuprofen, or other NSAID painkillers, including those available without a prescription, to avoid the risk of overdose.
Gexiro may affect other medicines, or other medicines may affect Gexiro. For example:

• acetylsalicylic acid, salicylates, or other NSAIDs (including COX-2 inhibitors such as celecoxib or etoricoxib);
• medicines used to treat heart conditions (e.g. digoxin or beta-blockers (beta-adrenolytics));
• corticosteroids such as prednisone or cortisone;
• anticoagulants (i.e. blood thinners/agents preventing blood clotting, e.g. acetylsalicylic acid, warfarin, ticlopidine);
• medicines that lower high blood pressure (angiotensin-converting enzyme inhibitors such as captopril, beta-adrenolytics such as atenolol, angiotensin II receptor antagonists such as losartan);
• medicines used to treat epilepsy or seizures (e.g. phenytoin, phenobarbital, carbamazepine);
• medicines used to treat mania (e.g. lithium);
• medicines used to treat depression, e.g. selective serotonin reuptake inhibitors;
• probenecid, a medicine used to treat gout;
• diuretics, medicines used to increase urine output;
• methotrexate, a medicine used to treat rheumatoid arthritis and certain types of cancer;
• tacrolimus or cyclosporine, immunosuppressive medicines used after organ transplantation;
• zidovudine, a medicine used to treat HIV infection (AIDS virus);
• sulfonylurea derivatives, medicines used to treat diabetes;
• certain antibiotics known as quinolone antibiotics (e.g. ciprofloxacin);
• certain antibiotics known as aminoglycosides (e.g. gentamicin, streptomycin);
• chloramphenicol, an antibiotic used to treat ear and eye infections;
• antifungal medicines such as voriconazole or fluconazole;
• medicines used to treat tuberculosis, such as isoniazid and rifampicin;
• mifepristone, a medicine used for medical termination of pregnancy;
• certain herbal medicines such as Ginkgo biloba (sometimes used to treat dementia) or Hypericum perforatum (St. John's wort, sometimes used for mild depression);
• flucloxacillin (an antibiotic), due to the serious risk of a blood and body fluid disorder (called high anion gap metabolic acidosis), which requires urgent treatment (see section 2).

Some other medicines may also affect the action of Gexiro or this medicine may affect their action. Therefore, always consult a doctor, nurse, or pharmacist before taking any other medicine.
If blood or urine tests are required, inform the doctor that Gexiro is being taken, as it may affect test results.

Gexiro and alcohol
Do not drink alcoholic beverages while taking this medicine. Consuming alcohol during treatment with Gexiro may cause liver damage.

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

Pregnancy
Do not take this medicine if the patient is in the last three months of pregnancy, as it may harm the unborn child or cause delivery complications. The medicine may cause kidney and heart problems in the unborn child. It may also affect bleeding tendencies in both mother and child and may delay or prolong labour.
Do not use this medicine during the first six months of pregnancy unless absolutely necessary and recommended by a doctor. If treatment is required during this period or when trying to conceive, use the lowest possible dose for the shortest possible time.
Gexiro taken for longer than a few days starting from week 20 of pregnancy may cause kidney problems in the unborn child, leading to reduced amniotic fluid volume (oligohydramnios). Narrowing of a blood vessel (ductus arteriosus) in the child's heart has also been observed. If treatment lasts longer than a few days, the doctor may recommend additional monitoring.

Breastfeeding
Only small amounts of paracetamol and ibuprofen pass into human milk. This medicine may be used during breastfeeding if taken at the recommended dose and for as short a duration as possible.

Fertility
This medicine may impair fertility in women and is not recommended for women trying to conceive. This effect is reversible upon discontinuation of the medicine.

Driving and operating machinery
After taking NSAIDs, adverse effects such as dizziness, drowsiness, fatigue, and visual disturbances may occur. If such symptoms occur, do not drive or operate machinery.

Gexiro contains sodium
Gexiro contains 35 mg (1.52 mmol) of sodium (the main component of table salt) in each 100 mL of solution (0.35 mg [0.0152 mmol] per 1 mL). This corresponds to 1.75% of the maximum recommended daily sodium intake for an adult.

3. How to use Gexiro

Gexiro will be administered to the patient as an intravenous infusion by a healthcare professional.
The medicine should be given as a 15-minute infusion.
This medicine is intended for short-term use only, for a maximum of 2 days.
Recommended dose:
For adult patients weighing more than 50 kg: if necessary, one vial (100 mL) every 6 hours.
The maximum daily dose of the medicine is 4 vials (400 mL), corresponding to 4000 mg of paracetamol
and 1200 mg of ibuprofen.
For patients weighing 50 kg or less, elderly patients, or those with impaired liver or kidney function:
the physician may decide to reduce the dose or prolong the interval between doses due to increased risk of adverse reactions.
A dose higher than recommended does not enhance analgesic effect but may lead to serious risks (see also section "Overdose of Gexiro").
The lowest effective dose should be used for the shortest duration necessary to relieve symptoms.
If the patient has any infection, symptoms (such as fever and pain) persist or worsen, medical advice should be sought immediately (see section 2).

Overdose of Gexiro
If an overdose of Gexiro is suspected, immediate contact with a doctor or nurse is required.
This should be done even if the patient feels well, because an excessive dose of paracetamol may cause delayed, severe liver damage, which can be fatal.
Even in the absence of discomfort or poisoning symptoms, urgent medical treatment may be necessary.
To prevent liver damage, prompt treatment is essential. The shorter the time (the fewer hours) between drug administration and initiation of antidote therapy, the greater the likelihood of preventing liver damage.
Other symptoms of overdose may include nausea, abdominal pain, vomiting (possibly with blood), headache, tinnitus, confusion, and nystagmus.
After large doses, drowsiness, chest pain, palpitations, loss of consciousness, seizures (mainly in children), weakness, dizziness, blood in urine, low blood potassium levels, feeling cold, and breathing difficulties may occur.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.
Stop taking the Gexiro medicine and immediately tell your doctor or go to
the nearest hospital emergency department if any of the following
adverse effects occur:
Not common

• vomiting blood or material resembling coffee grounds;
• bleeding from the rectum, black sticky stools or bloody diarrhoea;
• swelling of the face, lips or tongue, which may cause difficulty in swallowing or breathing.

Very rare

• asthma, wheezing, shortness of breath;
• sudden or severe itching, skin rash, urticaria;
• severe rash with blisters and bleeding around the lips, eyes, nose and genitals (Stevens-Johnson syndrome). Severe skin reactions have very rarely been reported;
• worsening of existing severe skin infections (rash, blisters and skin discolouration may occur, along with fever, drowsiness, diarrhoea and nausea) or worsening of other infections, including chickenpox or shingles, or severe infection with tissue necrosis (death) of the subcutaneous tissue and muscles, formation of blisters and skin peeling;
• fever, general malaise, nausea, abdominal pain, headache and neck stiffness (symptoms of aseptic meningitis, i.e. inflammation of the protective membranes covering the brain).

Frequency unknown (frequency cannot be estimated from the available data):

• a severe skin reaction known as DRESS syndrome (drug reaction with eosinophilia and systemic symptoms) may occur, characterised by skin rash, fever, swollen lymph nodes and increased eosinophil count (a type of white blood cell);
• red, scaly, widespread rash with subcutaneous nodules and blisters located mainly in skin folds, trunk and upper limbs, accompanied by fever at the beginning of treatment (acute generalised exanthematous pustulosis). See also section 2.

Other possible adverse effects
Common adverse effects (may affect fewer than 1 in 10 people):

• nausea or vomiting;
• loss of appetite;
• heartburn or pain in the upper stomach;
• stomach cramps, flatulence, constipation or diarrhoea, minor gastrointestinal bleeding;
• skin rashes, itching;
• headache;
• dizziness;
• feeling of nervousness;
• ringing or buzzing in the ears;
• unusual weight gain, swelling and fluid retention, swelling of ankles or legs.

Not common adverse effects (may affect fewer than 1 in 100 people):

• decrease in red blood cells, nosebleeds and heavy menstrual bleeding (menorrhagia);
• allergic reactions – skin rash, fatigue, joint pain (e.g. serum sickness, systemic lupus erythematosus, Henoch-Schönlein purpura, angioedema);
• breast enlargement in men;
• low blood sugar level;
• insomnia;
• mood changes, such as depression, disorientation, nervousness;
• eye problems such as blurred vision (reversible), eye pain and redness, itching;
• thickened mucus;
• severe pain or tenderness in the stomach; peptic ulcer and (or) gastrointestinal ulceration;
• inflammation of the intestines and worsening of inflammatory conditions of the colon (colitis) and gastrointestinal tract (Crohn's disease), as well as complications related to colonic diverticula (perforation or fistula);
• inability to completely empty the bladder (urinary retention);
• abnormal laboratory test results (concerning blood, liver and kidney enzymes).

Rare adverse effects (may affect fewer than 1 in 1,000 people):

• tingling in hands and feet;
• unusual dreams, seeing things that are not there (hallucinations);
• kidney tissue damage (especially during long-term use of the medicine);
• high levels of uric acid in the blood (hyperuricaemia).

Very rare adverse effects (may affect fewer than 1 in 10,000 people):

• low potassium levels – weakness, fatigue, muscle cramps (hypokalaemia);
• symptoms of anaemia such as fatigue, headaches, shortness of breath and pale skin;
• easier than usual bleeding or bruising, red or purple spots under the skin;
• severe or persistent headache;
• sensation of spinning (dizziness);
• fast or irregular heartbeat, also known as palpitations;
• increased blood pressure and possible heart function disturbances;
• oesophagitis;
• yellowing of the skin and (or) eyes, also known as jaundice;
• liver damage (especially after long-term use);
• hair loss;
• increased sweating;
• symptoms of frequent or worrying infections, such as fever, severe chills, sore throat or mouth ulcers;
• various forms of nephrotoxicity, including interstitial nephritis, nephrotic syndrome, and acute or chronic kidney failure.

Frequency unknown (frequency cannot be estimated from the available data):
A serious condition that may cause the blood to become more acidic (so-called metabolic acidosis) in patients with severe disease taking paracetamol (see section 2).

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, tell your doctor or pharmacist. Adverse effects 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, telephone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps provide more information on the safety of the medicine.

5. How to store Gexiro

Keep the medicine out of sight and reach of children.
Store below 25°C. Do not store in the refrigerator or freeze.
Keep the vial in the outer packaging to protect from light.
Do not use this medicine after the expiry date stated on the cardboard box and on the vial after "EXP". The expiry date refers to the last day of the stated month.
Do not use this medicine if the packaging is damaged or shows signs of tampering. Do not use this medicine if visible particles or discoloration are present.
Gexiro is for single use only. The medicine should be used immediately after opening. Any unused solution leftovers must be discarded.
Any unused solution leftovers should be disposed of according to local regulations.

6. Contents of the pack and other information

What Gexiro contains
The active substances are: paracetamol 10 mg/mL and ibuprofen in the form of ibuprofen sodium
dihydrate 3 mg/mL.
The other components are: L-cysteine hydrochloride monohydrate, disodium phosphate dihydrate, mannitol
(E 421), hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), and water for injections.

What Gexiro looks like and contents of the pack
Gexiro is a clear, colourless infusion solution free from visible solid particles. It is available in 100 mL
flasks made of colourless Type II glass, closed with a grey bromobutyl rubber stopper and an aluminium
flip-off cap. The medicine is supplied in packs containing 10 flasks.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Medical Valley Invest AB
Brädgårdsvägen 28
236 32 Höllviken
Sweden
email: [email protected]

Manufacturer
S.M. Farmaceutici S.r.l.
Zona Industriale Tito Scalo Snc
85050 Tito
Italy

This medicinal product is authorised in the following European Economic Area countries under the following names:
Greece Combogesic
Ireland Combogesic 10mg/ml Paracetamol + 3mg/ml Ibuprofen solution for infusion
Poland Gexiro
Portugal Combogesic IV
Sweden Duofen

The following information is intended for healthcare professionals only:
Gexiro, (10 mg + 3 mg)/mL, infusion solution
Paracetamolum + Ibuprofenum

Gexiro should be inspected visually prior to administration, if possible, to ensure the solution contains no solid particles or discolouration, depending on the solution and container. The solution must not be used if particulate matter, discolouration, or any foreign particles are visible.

Due to lack of compatibility studies, this medicinal product must not be mixed with diluents. If less than a full flask (100 mL) is required for administration of a single dose, the appropriate volume should be administered and any unused portion discarded.

Gexiro should be used for only one patient on a single occasion only. This medicinal product does not contain antibacterial preservatives. Any unused portion of the solution must be discarded.

Method of administration
Gexiro must be administered as a 15-minute intravenous infusion.

To withdraw the solution from the 100 mL flask, use a 0.8 mm needle (21G) inserted vertically into the designated area of the stopper.

In patients with body weight below 50 kg, when a full flask (100 mL) is not required, the appropriate volume should be administered and any unused portion discarded.

As with all infusion solutions in glass flasks, close monitoring is essential, particularly towards the end of the infusion, regardless of the route of administration. This monitoring at the end of the infusion is especially important for intravenous infusions administered via central venous access to avoid the risk of air embolism.