Combogesic IV 10 mg/ml + 3 mg/ml [1000mg / 300mg in 100ml] solution for infusion

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.
• You should not use this medicine for longer than 2 days.

1. What Combogesic IV is and what it is used for
2. What you need to know before you are given Combogesic IV
3. How you are given Combogesic IV
4. Possible side effects
5. How to store Combogesic IV
6. Contents of the pack and other information

• if you are allergic to the active substances, other NSAIDs, or any of the other ingredients of this medicine (listed in section 6);
• if you have severe heart failure, liver failure or kidney failure;
• if you regularly drink large quantities of alcohol;
• if you have asthma, urticaria or allergic-type reactions after taking acetylsalicylic acid or other NSAIDs;
• if you have a history with gastrointestinal bleeding or perforation related to previous NSAID therapy;
• if you have an active or recurrent peptic ulcer (i.e. stomach or duodenal ulcer), or bleeding (two or more distinct episodes of proven ulceration or bleeding);
• if you have bleeding of the brain (cerebrovascular bleeding) or other active bleeding;
• if you have a blood clotting disorder or increased tendency to bleeding;
• if you have severe dehydration (caused by vomiting, diarrhoea or insufficient fluid intake);
• during the last three months of pregnancy;
• if you are under the age of 18 years.

Do not take anything else containing paracetamol while taking this medicine.

In order to avoid the risk of overdose,

• check that other medicines do not contain paracetamol,
• do not exceed the maximum recommended doses (see section 3).

During treatment with Combogesic IV, tell your doctor straight away if:

If you have severe illnesses, including severe renal impairment or sepsis (when bacteria and their toxins circulate in the blood leading to organ damage), or you suffer from malnutrition, chronic alcoholism or if you are also taking flucloxacillin (an antibiotic). A serious condition called metabolic acidosis (a blood and fluid abnormality) has been reported in patients in these situations when paracetamol is used at regular doses for a prolonged period or when paracetamol is taken together with flucloxacillin. Symptoms of metabolic acidosis may include: serious breathing difficulties with deep rapid breathing, drowsiness, feeling sick (nausea) and being sick (vomiting).

If you are taking Combogesic IV for longer than the recommended time or at higher than recommended doses you are at risk of serious harms. These include serious harms to the stomach/gut and kidneys, as well as very low levels of potassium in your blood. These can be fatal (see section 4)

Side effects may be minimised by using the minimum effective dose for the shortest duration necessary to control symptoms. Do not use Combogesic IV for more than 2 days.

Talk to your doctor or nurse before you are given Combogesic IV if:

• you are taking any other medicines containing paracetamol, ibuprofen, or any other anti-inflammatory (NSAID) painkillers (in order to avoid the risk of an overdose);
• you have heart problems including heart failure, angina pectoris (chest pain), or if you have had a heart attack, bypass surgery, peripheral artery disease (poor circulation in the legs or feet due to narrow or blocked arteries), or any kind of stroke (including ‘mini-stroke’ or transient ischaemic attack “TIA”).
• you have high blood pressure, diabetes, high cholesterol, have a family history of heart disease or stroke, or if you are a smoker;
• you have liver disease, hepatitis, kidney disease or difficulty urinating;
• you currently have an infection; Combogesic IV may hide the symptoms or signs of an infection (fever, pain and swelling);
• you have or had previously had heartburn, indigestion, stomach ulcer or any other stomach problems;
• you have recently had or plan to have surgery;
• you have an infection (see heading “Infections” below);
• you have asthma;
• you are dehydrated or have diarrhoea;
• you have bowel or intestinal problems such as ulcerative colitis or Crohn’s Disease;
• you have an inherited genetic or acquired disorder of certain enzymes that manifests with either neurological complications or skin problems or occasionally both, i.e. porphyria;
• you have an autoimmune disease such as Lupus erythematosus or other connective tissue disorders, as there may be an increased risk of aseptic meningitis (inflammation of the protective membrane surrounding the brain);
• you suffer from hay fever, nasal polyps or chronic obstructive respiratory disorders since there may be an increased risk of allergic reactions;
• you are pregnant or intend to become pregnant (see section Pregnancy, breast-feeding and fertility).

Cardiovascular risk

Anti-inflammatory/pain-killer medicines like ibuprofen may be associated with a small increased risk of heart attack or stroke, particularly when used at high doses. Do not exceed the recommended dose or duration of treatment.

Gastrointestinal symptoms

Serious gastrointestinal side effects (affecting the stomach and intestines) have been reported with the use of NSAIDs, including ibuprofen. These can occur with or without warning symptoms. The risk of these side effects is higher in patients with a history of ulcers of the stomach or intestines, particularly if bleeding or perforation was also involved. Elderly patients are at greater risk of gastrointestinal side effects. You should discuss any history of gastrointestinal problems with your doctor, and remain alert for any unusual abdominal symptoms, including nausea, vomiting, diarrhoea, constipation, indigestion, abdominal pain, tar-like stools, or vomiting blood.

Elderly patients should first discuss treatment with a doctor. Elderly patients are at greater risk of side effects, especially bleeding and perforation in the digestive tract.

Skin reactions

Serious skin reactions have been reported in association with ibuprofen treatment. You should tell your doctor or nurse immediately if you develop any skin rash, lesions of the mucous membranes, blisters or other signs of allergy since these can be the first signs of a very serious skin reaction. See section 4.

Infections

Combogesic IV may hide signs of infections such as fever and pain. It is therefore possible that Combogesic IV may delay appropriate treatment of infection, which may lead to an increased risk of complications. This has been observed in pneumonia caused by bacteria and bacterial skin infections related to chickenpox. If you are given this medicine while you have an infection and your symptoms of the infection persist or worsen, consult a doctor without delay.

Prolonged use of painkillers

If you use painkillers for a long time, this can cause headaches, which should not be treated with more painkillers. If you think this applies to you, talk to your doctor or pharmacist.

Vision problems

If you notice any problems with your vision after using Combogesic IV, stop using the medicine and see a doctor.

Combogesic IV is not for use in children and adolescents under 18 years.

Tell your doctor or nurse if you are taking, have recently taken, or might take any other medicines.

Always tell the doctor if you are taking other medicines containing paracetamol, ibuprofen or other NSAID painkillers, including those you can buy without a prescription. This is to avoid the risk of overdose.

Combogesic IV may affect or be affected by some other medicines. For example:

• acetylsalicylic acid, salicylates or other NSAID medicines (including COX-2 inhibitors such as celecoxib or etoricoxib);
• medicines to treat heart conditions (e.g. digoxin or beta blockers);
• corticosteroids, such as prednisone, cortisone;
• medicines that are anti-coagulants (i.e. thin blood/prevent clotting e.g. acetylsalicylic acid, warfarin, ticlopidine);
• medicines that reduce high blood pressure (ACE-inhibitors such as captopril, beta-blockers such as atenolol, angiotensin-II receptor antagonists such as losartan);
• medicines to treat epilepsy or fits (e.g. phenytoin, phenobarbital, carbamazepine);
• medicines used to treat mania (e.g. lithium);
• medicines used to treat depression e.g. SSRIs (selective serotonin-reuptake inhibitors);
• probenecid, a medicine used to treat gout;
• diuretics, medicines used to increase urine output;
• methotrexate, a medicine used to treat arthritis and some types of cancer;
• tacrolimus or ciclosporin, immunosuppressive drugs used after organ transplant;
• zidovudine, a medicine used to treat HIV (the virus that causes AIDS);
• sulphonylureas, a medicine used to treat diabetes;
• a type of antibiotic known as quinolone antibiotics (e.g. ciprofloxacin);
• a type of antibiotic 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 a pregnancy;
• some herbal remedies, such as ginkgo biloba (sometimes used for dementia), or St John’s wort (Hypericum, sometimes used for mild depression);
• flucloxacillin (antibiotic), due to a serious risk of blood and fluid abnormality (called metabolic acidosis) that must have urgent treatment (see section 2).

Some other medicines may also affect or be affected by the treatment of Combogesic IV. You should therefore always seek the advice of your doctor, nurse or pharmacist before you take any other medicines.

If you need to leave a blood or urine sample for analysis, you need to tell your doctor that you are taking this medicine as it may interfere with the test results.

Do not drink alcoholic beverages when treated with this medicine. Combining alcohol with Combogesic IV may lead to liver damage.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or nurse for advice before this medicine is given to you.

Pregnancy

Do not take Combogesic IV if you are in the last 3 months of pregnancy as it could harm your unborn child or cause problems at delivery. It can cause kidney and heart problems in your unborn baby. It may affect your and your baby’s tendency to bleed and cause labour to be later or longer than expected. You should not take Combogesic IV during the first 6 months of pregnancy unless absolutely necessary and advised by your doctor. If you need treatment during this period or while you are trying to get pregnant, the lowest dose for the shortest time possible should be used. If taken for more than a few days from 20 weeks of pregnancy onward, Combogesic IV can cause kidney problems in your unborn baby that may lead to low levels of amniotic fluid that surrounds the baby (oligohydramnios) or narrowing of a blood vessel (ductus arteriosus) in the heart of the baby. If you need treatment for longer than a few days, your doctor may recommend additional monitoring.

Breast-feeding

Only small amounts of paracetamol and ibuprofen pass into breast milk. This medicine may be given during breast-feeding, if it is used at the recommended dose and for the shortest possible time.

Fertility

This product may impair female fertility and is not recommended in women attempting to conceive. This effect is reversible on stopping the medicine.

Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected you should not drive or operate machinery.

Combogesic IV contains 35 mg sodium (main component of cooking/table salt) in each 100 ml. This is equivalent to 1.75% of the recommended maximum daily dietary intake of sodium for an adult.

For adults who weigh more than 50 kg: 1 vial every 6 hours, as required.

The maximum daily dose is four vials which equals 4000 mg (4 g) paracetamol and 1200 mg ibuprofen.

If you weigh 50 kg or less, are elderly or if you have liver or kidney problems: Your doctor may decide to reduce your dose or increase the time between doses because of the increased risk of side effects.

Do not take more medicine than the label tells you to. If you do not get better, talk to your doctor.

A higher dose than the recommended does not increase pain relief; instead it can lead to serious risks (see also section “If you are given more Combogesic IV than you should”). The lowest effective dose should be given for the shortest duration necessary to relieve symptoms. If you have an infection, consult a doctor without delay if symptoms (such as fever and pain) persist or worsen (see section 2).

Immediately contact a doctor or nurse if you think that you accidentally may have been given too much of this medicine. Do this even if you feel well. This is because too much paracetamol can cause delayed, serious liver damage, which may be fatal. Even if there are no signs of discomfort or poisoning, you may need urgent medical attention.

In order to avoid liver damage it is essential to get medical treatment as early as possible. The shorter the interval between intake and initiation of treatment with antidote (as few hours as possible), the greater the likelihood that hepatic injury can be prevented.

Further symptoms can include nausea, stomach pain, vomiting (may be blood streaked), headache, ringing in the ears, confusion and shaky eye movement. At high doses, drowsiness, chest pain, palpitations, loss of consciousness, convulsions (mainly in children), weakness and dizziness, blood in urine, cold body feeling, and breathing problems have been reported.

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

• nausea or vomiting;
• loss of appetite;
• heartburn or pain the upper part of your stomach;
• stomach cramps, wind, constipation or diarrhoea, slight gastrointestinal blood loss;
• skin rashes, itching of the skin;
• headache;
• dizziness;
• feeling of being nervous;
• ringing or buzzing in the ears;
• unusual weight gain, swelling and fluid retention, swelling of ankles or legs (oedema).

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

• decrease in red blood cells, nose bleed and heavier periods (menstrual bleeding);
• allergic reactions – skin rash, tiredness, joint pain (e.g. serum sickness, lupus erythematosus syndrome, Henoch-Schönlein vasculitis, angioedema);
• enlargement of breast tissue in men; low blood sugar levels;
• sleeplessness;
• change in mood, for example depression, confusion, nervousness;
• eye problems such as blurred vision (reversible), sore red eyes, itching;
• thickened mucus;
• severe pain or tenderness in the stomach; peptic/gastrointestinal ulcer;
• Bowel inflammation and worsening of inflammation of the colon (colitis) and digestive tract (Crohn's disease) and complications of diverticula of the large bowel (perforation or fistula);
• inability to completely empty the bladder (urinary retention);
• abnormal laboratory test results (blood, liver and kidney enzyme test results).

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

• tingling of the hands and feet;
• abnormal dreams, seeing things (hallucinations);
• damage of the kidney tissue (particularly in long-term use);
• high level of uric acid in your blood (hyperuricemia).

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

• low potassium levels – weakness, fatigue, muscle cramps (hypokalaemia);
• signs of anaemia, such as tiredness, headaches, being short of breath, and looking pale;
• bleeding or bruising more easily than normal, reddish or purplish blotches under the skin;
• severe or persistent headache;
• spinning sensation (vertigo);
• fast or irregular heartbeats, also called palpitations;
• increase in blood pressure and possible heart problems;
• inflammation of the oesophagus;
• yellowing of the skin and /or eyes, also called jaundice;
• liver damage (particularly in long term use);
• loss of hair;
• increase in sweating;
• signs of frequent or worrying infections such as fever, severe chills, sore throat or mouth ulcers;
• nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome, and acute and chronic renal failure.

If you get any side effects talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provided more information on the safety of this medicine.

The active substances are 10 mg/ml paracetamol and 3 mg/ml ibuprofen (as sodium dihydrate).

The other ingredients are cysteine hydrochloride monohydrate, disodium phosphate dihydrate, mannitol, hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), and water for injections.

Combogesic IV is a clear, colourless solution for infusion, free from visible particles. It is supplied in 100 ml clear glass vials, closed with a grey bromobutyl rubber stopper and an aluminium flip-off cap. It comes in a pack size of 10 vials.

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