ciproxin

Main use	Active ingredient	Manufacturer
Bacterial infections	Ciprofloxacin	Bayer

How does it work?

Ciproxin tablets, suspension and infusion all contain the active ingredient ciprofloxacin, which is a type of medicine called a quinolone antibiotic. Antibiotics are used to treat infections caused by bacteria. (NB. Ciprofloxacin is also available without a brand name, ie as the generic medicine.)
Ciprofloxacin works by killing the bacteria that are causing an infection. It does this by entering the bacterial cells and inhibiting a bacterial enzyme called DNA-gyrase. This enzyme is involved in replicating and repairing the genetic material (DNA) of the bacteria. If this enzyme doesn't work, the bacteria cannot reproduce or repair themselves and this kills the bacteria.
Ciprofloxacin is effective against a large number of bacteria, some of which tend to be resistant to other commonly used antibiotics. It is particularly useful against a sub-group of bacteria called Gram-negative bacteria, including salmonella, shigella, campylobacter, neisseria, and pseudomonas. It is used to treat a wide range of infections, including infections of the chest, urinary tract and of the gastrointestinal system. It is also used as a single dose treatment for gonorrhoea.
To make sure the bacteria causing an infection are susceptible to ciprofloxacin your doctor may take a tissue sample, for example a swab from the throat or skin, or a urine or blood sample.

What is it used for?

In adults, ciprofloxacin can be used to treat the infections below, when caused by susceptible bacteria.

• Bacterial infections of the lungs and airways (respiratory tract), such as pneumonia (but not 1st line treatment of pneumococcal pneumonia), acute bronchitis, bronchiectasis and lung infections in cystic fibrosis or chronic bronchitis.
• Bacterial ear, nose and throat infections such as sinusitis, otitis media and otitis externa.
• Bacterial eye infections such as bacterial conjunctivitis.
• Bacterial infections of the urinary tract, such as cystitis, kidney infections (pyelonephritis), urethritis.
• Bacterial infection of the prostate gland (prostatitis) or testicles (epididymitis).
• Bacterial infections of the skin and soft tissue, such as infected ulcers, wounds or burns, abscesses, cellulitis, erysipelas.
• Bacterial infections of bones and joints, such as osteomyelitis and septic arthritis.
• Abdominal bacterial infections, such as peritonitis or abdominal abscesses.
• Bacterial infections of the stomach and intestines, such as typhoid fever or infective diarrhoea.
• Bacterial infections of the biliary tract or gall bladder.
• Bacterial infections in the pelvis, such as pelvic inflammatory disease or infections in the uterus (endometritis) or uterine tube (salpingitis).
• Gonorrhoea.
• Bacterial infection of the blood (septicaemia or blood poisoning).
• Preventing infections in people having stomach or intestinal surgery or endoscopic procedures, where there is an increased risk of infection.
• Preventing or treating anthrax affecting the lungs, following exposure to anthrax spores.

In children, ciprofloxacin can be used to treat the infections below, when caused by susceptible bacteria.

• 2nd and 3rd line treatment of complicated urinary tract infections and kidney infections (pyelonephritis) in children and adolescents aged 1 to 17 years.
• Lung infections caused by a type of bacteria called Pseudomonas aeruginosa in children and adolescents aged 5 to 17 years with cystic fibrosis.
• Preventing or treating anthrax affecting the lungs, following exposure to anthrax spores.

How do I take it?

• The dose of this medicine and how long it needs to be taken for depends on your kidney function and the type of infection you have. Follow the instructions given by your doctor. These will be printed on the dispensing label that your pharmacist has put on the packet of medicine.
• Ciprofloxacin is usually taken twice a day (every 12 hours).
• Ciprofloxacin tablets should be swallowed whole and not chewed.
• Bottles of suspension should be shaken before measuring out a dose. Only use the measuring spoon provided with the suspension. You should not use a regular teaspoon or tablespoon to take the medicine, as this will not give an accurate dose.
• Ciprofloxacin can be taken either with or without food.
• You should not take milk, yoghurt, antacids for indigestion or heartburn, or medicines containing calcium, iron, zinc, magnesium or aluminium at the same time as ciprofloxacin. This is because these can reduce the absorption of the antibiotic from the gut. (See end of factsheet for more information.)
• Unless your doctor tells you otherwise, it is important that you finish the prescribed course of this antibiotic medicine, even if you feel better or it seems the infection has cleared up. Stopping the course early increases the chance that the infection will come back and that the bacteria will grow resistant to the antibiotic.

Warning!

• This medicine may reduce your ability to drive or operate machinery safely. This effect may be enhanced by drinking alcohol. Do not drive or operate machinery until you know how this medicine affects you and you are sure it won't affect your performance.
• You should make sure you drink plenty of fluid while taking this medicine. This is to reduce the risk of crystals of the medicine forming in the urine.
• Avoid exposing your skin to excessive sunlight, sunlamps or sunbeds while taking ciprofloxacin, as it may increase the sensitivity of your skin to UV light. If you get a rash or other skin reaction on exposure to sunlight you should stop taking this medicine and consult your doctor.
• Treatment with antibiotics can sometimes cause overgrowth of other organisms that are not susceptible to the antibiotic, for example fungi or yeasts such as Candida. This may sometimes cause infections such as thrush. Tell your doctor if you think you have developed a new infection during or after taking this antibiotic.
• Broad-spectrum antibiotics can sometimes cause inflammation of the bowel (colitis). For this reason, if you get diarrhoea either during or after taking this medicine, particularly if it becomes severe or persistent, or contains blood or mucus, you should consult your doctor immediately.
• Quinolone antibiotics may rarely cause tendon inflammation (tendinitis) and tendon rupture. People aged over 60, people who have had a kidney, heart, or lung transplant and those taking corticosteroid medication are most at risk of this. You should stop taking this medicine immediately if you experience any pain or inflammation in your joints during treatment. Rest the affected limb(s) and consult a doctor immediately.

Use with caution in

• Children and adolescents.
• People over 60 years of age.
• People using corticosteroid medicines.
• People who have had a kidney, heart, or lung transplant.
• Decreased kidney function.
• History of convulsions (fits), eg epilepsy.
• People with conditions that increase the risk of seizures.
• Abnormal muscle weakness (myasthenia gravis).
• History of psychiatric illness.
• People who a lack an enzyme called G6PD in their blood, or who have a family history of this disorder (G6PD deficiency).
• Heart disease.
• People with a personal or family history of an abnormal heart rhythm seen on a heart monitoring trace (ECG) as a 'prolonged QT interval'.

Not to be used in

• History of tendon disorders caused by previous treatment with a quinolone-type antibiotic.
• Allergy to other quinolone-type antibiotics, eg norfloxacin, ofloxacin.

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy. If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

• This medicine is not recommended for use in pregnancy. This is because ciprofloxacin has been shown to cause joint disease in immature animals and may therefore have this effect in humans. There are usually safer alternative antibiotics available. Seek medical advice from your doctor.
• Ciprofloxacin passes into breast milk. It is not recommended for use during breastfeeding, as there are usually safer alternative antibiotics available. Seek medical advice from your doctor.

Side effects

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here does not mean that all people using this medicine will experience that or any side effect.

Common (affect between 1 in 10 and 1 in 100 people)

• Nausea.
• Diarrhoea.

Uncommon (affect between 1 in 100 and 1 in 1000 people)

• Rash.
• Itching.
• Loss of appetite.
• Headache.
• Dizziness.
• Feeling weak or tired (asthenia).
• Sleep disturbances.
• Hyperactivity or agitation.
• Taste disturbances.
• Abdominal pain, flatulence (wind) or indigestion.
• Vomiting.
• Joint or back pain.
• Fungal infections.

Rare (affect between 1 in 1000 and 1 in 10,000 people)

• Disturbances in the numbers of blood cells in the blood.
• Increased blood sugar levels (hyperglycaemia).
• Confusion.
• Anxiety.
• Depression. Tell your doctor straight away if you notice any change in your mood, feelings or thoughts while taking this medicine.
• Hallucinations.
• Abnormal dreams.
• Tremor.
• Convulsions.
• Pins and needles, burning or numb sensations. Tell your doctor straight away if you notice any strange sensations while taking this medicine.
• Visual disturbances.
• Hearing problems, including tinnitus.
• Increased heart rate.
• Low blood pressure or fainting.
• Sweating.
• Shortness of breath.
• Muscle pain or cramps.
• Increased sensitivity of the skin to sunlight (photosensitivity - see warning section above).
• Inflammation of the bowel lining (colitis - see warning section above).
• Liver or kidney disorders. Tell your doctor if you experience any of the following symptoms while taking this medicine, as they may suggest a problem with your liver: rapidly feeling weak or unwell, unexplained itching, loss of appetite, abdominal pain, yellowing of the skin or whites of the eyes (jaundice) or unusually dark urine.

Very rare (affect less than 1 in 10,000 people)

• Disturbances in smell.
• Tendon disorders (see warning section above).
• Psychotic reactions.
• Migraine.
• Inflammation of the pancreas (pancreatitis).
• Severe allergic skin reactions. Consult your doctor immediately if you get a severe rash, skin peeling, or painful blisters in the mouth/nose or genitals while taking this medicine.

The side effects listed above may not include all of the side effects reported by the medicine's manufacturer. For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines while taking this one, to ensure that the combination is safe.
You should not take any of the following medicines at the same time of day as your ciprofloxacin dose, as they can reduce the absorption of the ciprofloxacin from the gut and make it less effective. If you need to take any of these, the doses should be separated from your ciprofloxacin dose by at least four hours:

• antacids for indigestion or heartburn
• iron, calcium, magnesium or zinc supplements
• other medicines containing calcium, magnesium, aluminium, zinc or iron
• sevelamer
• sucralfate
• Videx chewable/dispersible tablets (these contain an antacid).

Strontium ranelate may also reduce the absorption of ciprofloxacin from the gut and could make it less effective. If you are taking strontium for osteoporosis its manufacturer recommends that you stop taking it temporarily while you are taking a course of ciprofloxacin.
If ciprofloxacin is used in combination with any of the following medicines there may be an increased risk of seizures (fits):

• theophylline (ciprofloxacin also increases the level of theophylline in the blood - see below)
• non-steroidal anti-inflammatory drugs (NSAIDs) such as indometacin, fenbufen, naproxen.

Ciprofloxacin can affect the blood level of phenytoin. As it can also increase the risk of seizures, it should generally be avoided in people with epilepsy.
Ciprofloxacin may enhance the anti-blood-clotting effect of anticoagulant medicines such as warfarin. As this may increase the risk of bleeding, your blood clotting time (INR) should be monitored more frequently if you are taking ciprofloxacin with an anticoagulant.
If ciprofloxacin is taken with the following medicines it may increase their blood levels, with the following effects:

• ciclosporin (increased risk of side effects on the kidneys)
• clozapine (possible increased risk of side effects)
• duloxetine (ciprofloxacin should not be taken by people taking duloxetine).
• glibenclamide (may rarely cause an excessive drop in blood sugar)
• methotrexate (may increase the risk of toxicity - people taking this combination should be monitored)
• ropinirole (possible increased risk of side effects)
• theophylline (ciprofloxacin should not be used in combination with theophylline unless the dose of theophylline is reduced and the theophylline level can be monitored with blood tests)
• tizanidine (increased risk of significant side effects - ciprofloxacin should not be taken by people taking tizanidine)
• zolmitriptan (increased risk of side effects - lower dose of zolmitriptan recommended).

Probenecid may increase the amount of ciprofloxacin in the blood.
Oral typhoid vaccine (Vivotif) should not be taken until at least three days after you have finished a course of this antibiotic, because the antibiotic could make the vaccine less effective.
In the past, women using hormonal contraception such as the pill or patch would be advised to use an extra method of contraception (eg condoms) while having treatment with an antibiotic like this one and for seven days after finishing the course. However, this advice has now changed. You no longer need to use an extra method of contraception with the pill, patch or vaginal ring while you have a course of antibiotics. This change in advice comes because to date there is no evidence to prove that antibiotics (other than rifampicin or rifabutin) affect these contraceptives. This is the latest guidance from the Faculty of Sexual & Reproductive Healthcare.
However, if you are taking the contraceptive pill and experience vomiting or diarrhoea as a result of treatment with this antibiotic, you should follow the instructions for vomiting and diarrho
 

bentelan

01.0 DENOMINAZIONE DEL MEDICINALE -Inizio Pagina

BENTELAN COMPRESSE EFFERVESCENTI

02.0 COMPOSIZIONE QUALITATIVA E QUANTITATIVA - Inizio Pagina

BENTELAN 0,5 mg compresse effervescenti

Una compressa da 0,5 mg contiene:

Betametasone disodio fosfato 0,6578 mg

pari a Betametasone 0,5 mg

BENTELAN 1 mg compresse effervescenti

Una compressa da 1 mg contiene:

Betametasone disodio fosfato 1,316 mg

pari a Betametasone 1 mg

Per gli eccipienti v. punto 6.1

03.0 FORMA FARMACEUTICA - Inizio Pagina

Compresse effervescenti.

04.0 INFORMAZIONI CLINICHE - Inizio Pagina

04.1 Indicazioni terapeutiche - Inizio Pagina

La terapia corticosteroidea può trovare indicazione in una vasta gamma di malattie.

Tra le principali vanno ricordate:

-asma bronchiale;

-allergopatie gravi;

-artrite reumatoide;

-collagenopatie;

-dermatosi infiammatorie;

-neoplasie specialmente a carico del tessuto linfatico (emolinfopatie maligne acute e croniche, morbo di Hodgkin).

Altre indicazioni sono: sindrome nefrosica, colite ulcerosa, ileite segmentaria (sindrome di Crohn), pemfigo, sarcoidosi (specialmente ipercalcemica), cardite reumatica, spondilite anchilosante e diverse emopatie discrasiche, quali certi casi di anemia emolitica, agranulocitosi e porpora trombocitopenica.

Pubblicità

04.2 Posologia e modo di somministrazione - Inizio Pagina

ADULTI:

Terapie di breve durata:

4-6 compresse al giorno di BENTELAN 0,5 mg compresse effervescenti o 2-3 compresse al giorno di BENTELAN 1 mg compresse effervescenti (pari a 2-3 mg), riducendo gradualmente tale dose in base all’evoluzione clinica.

Terapie di lunga durata

Nel trattamento di forme morbose croniche o subacute (collagenopatie, anemie emolitiche, asma bronchiale cronico, sindrome nefrosica, colite ulcerosa, pemfigo), dopo una terapia d’attacco in genere di 6-8 compresse al giorno di BENTELAN 0,5 mg compresse effervescenti o 2-3 compresse al giorno di BENTELAN 1 mg compresse effervescenti (pari a 3-4 mg) ridurre gradualmente la posologia fino alla dose di mantenimento mini–ma capace di tenere sotto controllo la sintomatologia.

Mantenimento:

La dose di mantenimento oscilla nell’adulto di peso medio fra 1-2 compresse al giorno.

BAMBINI:

I bambini tollerano in genere dosi proporzionalmente superiori a quelle stabilite per gli adulti: si consigliano 0,1-0,2 mg/Kg di peso corporeo al giorno.

Le compresse di BENTELAN sono divisibili a metà per facilitare l’aggiustamento della posologia, inoltre la solubilità in acqua consente una pratica ed agevole somministrazione.

Aerosolterapia: 0,5-1 mg sciolti al momento dell’uso in 1-2 ml di acqua.

Links sponsorizzati

04.3 Controindicazioni - Inizio Pagina

Infezioni sistemiche, qualora non venga attuata specifica terapia antiinfettiva.

Immunizzazione con virus attenuati; altri procedimenti immunizzanti non vanno intrapresi in pazienti che ricevono glicocorticoidi, specialmente ad alte dosi, a causa di possibili rischi di complicazioni neurologiche e di insufficiente risposta anticorpale. Generalmente controindicato in gravidanza e durante l’allattamento (v. par. 4.6)

04.4 Speciali avvertenze e precauzioni per l'uso - Inizio Pagina

Nei pazienti in terapia con glicocorticoidi, sottoposti a particolari stress, è indispensabile un adattamento della dose in rapporto all’entità della condizione stressante.

I glicorticoidi possono mascherare alcuni segni di infezione e durante il loro impiego si possono verificare infezioni intercorrenti a causa delle difese immunitarie ridotte. In questi casi va sempre valutata l’opportunità di istituire un’adeguata terapia antibiotica.

L’uso nella tubercolosi attiva va limitato ai casi di malattia fulminante o disseminata, nei quali il glicocorticoide va usato con appropriata terapia antitubercolare.

Se i glicocorticoidi vengono somministrati nei pazienti con tubercolosi latente o con risposta positiva alla tubercolina, è necessaria una stretta sorveglianza in quanto si può verificare una riattivazione della malattia.

Nella terapia prolungata questi soggetti devono ricevere una chemioprofilassi.

Uno stato di insufficienza surrenale secondaria, indotta dal glicocorticoide, può essere minimizzato con una riduzione graduale del dosaggio. Questo tipo di relativa insufficienza può persistere fino ad un anno dopo la sospensione della terapia.

Quindi, in qualsiasi situazione di stress che si manifestasse in questo periodo, la terapia ormonale dovrebbe essere ripresa.

Poichè la secrezione mineralcorticoide può essere compromessa, bisognerebbe somministrare in concomitanza cloruro sodico e/o mineralcorticoide.

A causa della possibilità di una ritenzione di liquidi, bisogna porre attenzione nella somministrazione di corticosteroidi a pazienti con insufficienza cardiaca congestizia.

In corso di terapia prolungata e con dosi elevate, se si dovesse verificare un’alterazione del bilancio elettrolitico, è opportuno adeguare l’apporto di sodio e di potassio.

Tutti i glicocorticoidi aumentano l’escrezione di calcio.

La terapia corticosteroidea può peggiorare il diabete mellito, l’osteoporosi, l’ipertensione, il glaucoma e l’epilessia.

Durante la terapia possono manifestarsi alterazioni psichiche di vario genere: euforia, insonnia, mutamenti dell’umore o della personalità, depressione grave o sintomi di vere e proprie psicosi.

Una preesistente instabilità emotiva o tendenze psicotiche possono essere aggravate dal glicocorticoide.

La stessa attenzione deve essere posta nei casi di precedente miopatia steroido indotta o ulcera peptica.

Nei pazienti con insufficienza epatica i livelli ematici dei corticosteroidi possono essere aumentati, così come avviene con gli altri farmaci che vengono metabolizzati nel fegato.

Nei pazienti ipotiroidei o affetti da cirrosi epatica la risposta ai glicocorticoidi può essere aumentata.

Si consiglia cautela nei pazienti con herpes simplex oculare, perchè è possibile una perforazione corneale.

Nei pazienti con ipoprotrombinemia, si consiglia prudenza nell’associare l’acido acetilsalicilico ai glicocorticoidi.

I bambini e gli adolescenti sottoposti a prolungata terapia devono essere strettamente sorvegliati dal punto di vista della crescita e dello sviluppo.

Il trattamento dovrebbe essere limitato alle dosi minime ed al periodo di tempo più breve possibile. Al fine di ridurre al minimo la soppressione dell’asse ipotalamo-ipofisi-surrene ed i ritardi della crescita dovrebbe essere valutata la possibilità di effettuare una somministrazione singola a giorni alterni.

Nei pazienti anziani la terapia, in particolare se prolungata, deve essere pianificata in considerazione della maggiore incidenza degli effetti collaterali quali osteoporosi, peggioramento del diabete, dell’ipertensione, maggiore suscettibilità alle infezioni, assottigliamento cutaneo.

La posologia di mantenimento deve essere sempre la minima in grado di controllare la sintomatologia; una riduzione posologica va fatta sempre gradualmente durante un periodo di alcune settimane o mesi in rapporto alla dose precedentemente assunta ed alla durata della terapia.

I glicocorticoidi devono essere somministrati con cautela nei seguenti casi:

colite ulcerosa non specifica con pericolo di perforazione, ascessi e infezioni piogeniche in genere, diverticolite, anastomosi intestinali recenti, ulcera peptica attiva o latente, insufficienza renale, ipertensione, osteoporosi, miastenia grave.

Il prodotto deve essere usato sotto il personale controllo del medico.

Si possono presentare effetti sistemici con i corticosteroidi inalatori, in particolare quando prescritti ad alte dosi per periodi prolungati. Tali effetti si verificano con meno probabilità rispetto al trattamento con corticosteroidi orali. I possibili effetti sistemici includono la sindrome di Cushing, aspetto Cushingoide, soppressione surrenalica, ritardo della crescita in bambini e adolescenti, riduzione della densità minerale ossea, cataratta, glaucoma e, più raramente una serie di effetti psicologici o comportamentali che includono iperattività psicomotoria, disturbi del sonno, ansietà, depressione o aggressività (particolarmente nei bambini). È importante, quindi che la dose del corticosteroide per inalazione sia la più bassa dose possibile con cui viene mantenuto il controllo effettivo dell’asma.

 

KEPPRA

KEPPRA
(levetiracetam)

Share this Article:
Facebook Twitter Email Print
DRUG DESCRIPTION

KEPPRA is an antiepileptic drug available as 250 mg (blue), 500 mg (yellow), 750 mg (orange), and 1000 mg (white) tablets and as a clear, colorless, grape-flavored liquid (100 mg/mL) for oral administration.

The chemical name of levetiracetam, a single enantiomer, is (-)-(S)-α-ethyl-2-oxo-1-pyrrolidine acetamide, its molecular formula is C8H14N2O2 and its molecular weight is 170.21. Levetiracetam is chemically unrelated to existing antiepileptic drugs (AEDs). It has the following structural formula:

KEPPRA (levetiracetam) Structural Formula Illustration

Levetiracetam is a white to off-white crystalline powder with a faint odor and a bitter taste. It is very soluble in water (104.0 g/100 mL). It is freely soluble in chloroform (65.3 g/100 mL) and in methanol (53.6 g/100 mL), soluble in ethanol (16.5 g/100 mL), sparingly soluble in acetonitrile (5.7 g/100 mL) and practically insoluble in n-hexane. (Solubility limits are expressed as g/100 mL solvent.)

KEPPRA tablets contain the labeled amount of levetiracetam. Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, polyethylene glycol 3350, polyethylene glycol 6000, polyvinyl alcohol, talc, titanium dioxide, and additional agents listed below:

250 mg tablets: FD&C Blue #2/indigo carmine aluminum lake

500 mg tablets: iron oxide yellow

750 mg tablets: FD&C yellow #6/sunset yellow FCF aluminum lake, iron oxide red

KEPPRA

 oral solution contains 100 mg of levetiracetam per mL. Inactive ingredients: ammonium glycyrrhizin ate, citric acid monohydrate, glycerin, maltitol solution, methylparaben, potassium acesulfame, propylparaben, purified water, sodium citrate dihydrate and natural and artificial flavor.
What are the possible side effects of levetiracetam (Keppra, Keppra XR)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any new or worsening symptoms such as: mood or behavior changes, depression, anxiety, or if you feel agitated, hostile, restless, hyperactive (mentally or physically), or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have any of these serious side effects:

    hallucinations;
    fever, chills, body aches, flu...

Read All Potential Side Effects and See Pictures of Keppra »
What are the precautions when taking levetiracetam (Keppra)?

Before using this medication, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease (including dialysis treatment), mental/mood disorders (such as depression).

This drug may make you dizzy or drowsy, especially during the first month of treatment. Do not drive, use machinery, ride a bicycle, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

Before having surgery, tell your doctor or dentist about...

Read All Potential Precautions of Keppra »

dicloreum

Dicloreum -

 General Information:
A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt. [PubChem]

Related offer from MedStore:
Voltaren    Generic Voltaren (Diclofenac) - 50mg 90 pills for $52.92
Diclofenac is in a group of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs). Diclofenac works by reducing hormones that cause inflammation and pain in the body. Diclofenac is used to treat pain or inflammation caused by arthritis or ankylosing spondylitis.

Pharmacology:
Dicloreum is an acetic acid nonsteroidal antiinflammatory drug (NSAID) with analgesic and antipyretic properties. Dicloreum is used to treat pain, dysmenorrhea, ocular inflammation, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and actinic keratosis

Buy Celebrex online
Brand and Generic. Professional and discreet delivery. The best offer.
http://www.rxstore.euAds by rivaclick
Dicloreum for patients

Diclofenac, like other drugs of its class, is not free of side effects. The side effects of these drugs can cause discomfort and rarely, more serious side effects, such as gastrointestinal bleeding, and more rarely, liver toxicity which may result in hospitalization and even fatal outcomes.

NSAIDs are often essential agents in the management of arthritis and have a major role in the management of pain, but they also may be commonly employed for conditions that are less serious.

Physicians may w.s. to discuss with their patients the potential risks and likely benefits of NSAID treatment, particularly when the drugs are used for less serious conditions where treatment without NSAIDs may represent an acceptable alternative to both the patient and physician.

Because serious G.I. tract ulceration and bleeding can occur without warning symptoms, physicians should follow chronically treated patients for the signs and symptoms of ulceration and bleeding and should inform them of the importance of this follow-up. If diclofenac is used chronically, patients should also be instructed to report any signs and symptoms that might be due to hepatotoxicity of dictofenac; these symptoms may become evident between visits when periodic liver laboratory tests are performed
Dicloreum Interactions

Aspirin: Concomitant administration of diclofenac and aspirin is not recommended because diclofenac is displaced from its binding sites during the concomitant administration of aspirin, resulting in lower plasma concentrations, peak plasma levels, and AUC values.

Anticoagulants: While studies have not shown diclofenac to interact with anticoagulants of the warfarin type, caution should be exercised, nonetheless, since interactions have been seen with other NSAIDs. Because prostaglandins play an important role in hemostasis, and NSAIDs affect platelet function as well, concurrent therapy with all NSAIDs, including diclofenac, and warfarin requires close monitoring of patients to be certain that no change in their anticoagulant dosage is required.

Digoxin, Methotrexate, Cyclosporine: Diclofenac, like other NSAIDs, may affect renal prostaglandins and increase the toxicity of certain drugs. Ingestion of diclofenac may increase serum concentrations of digoxin and methotrexate and increase cyclosporineís nephrotoxicity. Patients who begin taking diclofenac or who increase their diclofenac dose or any other NSAID while taking digoxin, methotrexate, or cyclosporine may develop toxicity characteristics for these drugs. They should be observed closely, particularly if renal function is impaired. In the case of digoxin, serum levels should be monitored.

Lithium: Diclofenac decreases lithium renal clearance and increases lithium plasma levels. In patients taking diclofenac and lithium concomitantly, lithium toxicity may develop.

Oral Hypoglycemics: Diclofenac does not alter glucose metabolism in normal subjects nor does it alter the effects of oral hypoglycemic agents. There are rare reports, however, from marketing experiences, of changes in effects of insulin or oral hypoglycemic agents in the presence of diclofenac that necessitated changes in the doses of such agents. Both hypo- and hyperglycemic effects have been reported. A direct causal relationship has not been established, but physicians should consider the possibility that diclofenac may alter a diabetic patientís response to insulin or oral hypoglycemic agents.

Diuretics: Diclofenac and other NSAIDs can inhibit the activity of diuretics. Concomitant treatment with potassium-sparing diuretics may be associated with increased serum potassium levels.

Other Drugs: In small groups of patients (7-10/interaction study), the concomitant administration of azathioprine, gold, chloroquine, D-penicillamine, prednisolone, doxycycline, or digitoxin did not significantly affect the peak levels and AUC values of diclofenac. Phenobarbital toxicity has been reported to have occurred in a patient on chronic phenobarbital treatment following the initiation of diclofenac therapy.

Protein Binding

In vitro, diclofenac interferes minimally or not at all with the protein binding of salicylic acid (20% decrease in binding), tolbutamide, prednisolone (10% decrease in binding), or warfarin. Benzylpenicillin, ampicillin, oxacillin, chlortetracycline, doxycycline, cephalothin, erythromycin, and sulfamethoxazole have no influence in vitro on the protein binding of diclofenac in human serum.

Drug/Laboratory Test Interactions

Effect on Blood Coagulation: Diclofenac increases platelet aggregation time but does not affect bleeding time, plasma thrombin clotting time, plasma fibrinogen, or factors V and VII to XII. Statistically significant changes in prothrombin and partial thromboplastin times have been reported in normal volunteers. The mean changes were observed to be less than 1 second in both instances, however, and are unlikely to be clinically important. Diclofenac is a prostaglandin synthetase inhibitor, however, and all drugs that inhibit prostaglandin synthesis interfere with platelet function to some degree; therefore, patients who may be adversely affected by such an action should be carefully observed.

Dicloreum Contraindications

Diclofenac in all formulations, Cataflam, Voltaren, and Voltaren-XR, is contraindicated in patients with known hypersensitivity to diclofenac and diclofenac-containing products. Diclofenac should not be given to patients who have experienced asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to diclofenac have been reported in such patients.

Additional information about Dicloreum
Dicloreum Indication: For the acute and chronic treatment of signs and symptoms of osteoarthritis and rheumatoid arthritis.
Mechanism Of Action: The antiinflammatory effects of diclofenac are believed to be due to inhibition of both leukocyte migration and the enzyme cylooxygenase (COX-1 and COX-2), leading to the peripheral inhibition of prostaglandin synthesis. As prostaglandins sensitize pain receptors, inhibition of their synthesis is responsible for the analgesic effects of ketoprofen. Antipyretic effects may be due to action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat dissipation.
Drug Interactions: Alendronate Increased risk of gastric toxicity
Anisindione The NSAID increases the anticoagulant effect
Cyclosporine Monitor for nephrotoxicity
Dicumarol The NSAID increases the anticoagulant effect
Warfarin The NSAID increases the anticoagulant effect
Rifampin Decreased levels/effect of the NSAID
Food Interactions: Take with food to reduce irritation.
Avoid alcohol.
Generic Name: Diclofenac
Synonyms: Diclofenac Sodium; Diclofenac Potassium; Diclofenac Acid
Drug Category: Nonsteroidal Antiinflammatory Agents (NSAIDs); Cyclooxygenase Inhibitors
Drug Type: Small Molecule; Approved; Investigational
Other Brand Names containing Diclofenac: Allvoran; Apo-Diclo; Assaren; Benfofen; Cataflam; Delphimix; Dichlofenac; Dichronic; Diclo-Phlogont; Diclo-Puren; Diclobenin; Diclord; Dicloreum; Dolobasan; Duravolten; Ecofenac; Effekton; Kriplex; Neriodin; Novapirina; Novo-Difenac; Novo-Difenac SR; Nu-Diclo; Pennsaid; Primofenac; Prophenatin; Rhumalgan; Solaraze; Solaraze T; Tsudohmin; Valetan; Voldal; Voltaren; Voltaren Ophtha; Voltaren Ophthalmic; Voltaren Rapide; Voltaren SR; Voltaren-XR; Voltarol; Xenid; Dyloject;
Absorption: Completely absorbed from the gastrointestinal tract.
Toxicity (Overdose): Symptoms of overdose include loss of consciousness, increased intracranial pressure, and aspiration pneumonitis. LD50=390mg/kg (orally in mice)
Protein Binding: More than 99%
Biotransformation: Hepatic
Half Life: 2 hours
Dosage Forms of Dicloreum: Tablet Oral
Tablet, extended release Oral
Solution Topical
Tablet, coated Oral
Solution Ophthalmic
Suppository Rectal
Chemical IUPAC Name: 2-[2-[(2,6-dichlorophenyl)amino]phenyl]acetic acid
Chemical Formula: C14H11Cl2NO2
Diclofenac on Wikipedia: http://en.wikipedia.org/wiki/Diclofenac
Organisms Affected: Humans and other mammals

cefixoral

Cefixoral 

- General Information:
Cefixoral, an antibiotic, is a third-generation cephalosporin like ceftriaxone and cefotaxime. Cefixoral is highly stable in the presence of beta-lactamase enzymes. As a result, many organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamases, may be susceptible to cefixime. The antibacterial effect of cefixime results from inhibition of mucopeptide synthesis in the bacterial cell wall.

Related offer from MedStore:
Suprax    Generic Suprax (Cefixime) - 100mg 30 pills for $72.00
Suprax (Cefixime) is a cephalosporin antibiotic used to treat infections caused by bacteria such as pneumonia; bronchitis; gonorrhea; and ear, lung, throat, and urinary tract infections. Antibiotics will not work for colds, flu, or other viral infections.

Pharmacology:
Cefixoral, an antibiotic, is a third-generation cephalosporin like ceftriaxone and cefotaxime. Cefixoral is highly stable in the presence of beta-lactamase enzymes. As a result, many organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamases, may be susceptible to cefixime. The antibacterial effect of cefixime results from inhibition of mucopeptide synthesis in the bacterial cell wall.

VALIUM Rocher -No prescrip- VISA Amx ech
FDA Approved brand and generic Valium - no RX required! Easy to buy! Secure transaction. We accept Visa, AMEX & eCheck! FedEx shipping VALIUM, XAMAX AMBIEN ATIVAN KLONOPIN CODEINE
http://www.rxpharma24hs.comAds by rivaclick
Cefixoral for patients

Cefixime is a cephalosporin antibiotic used to treat bacterial infections. Take at regular intervals and complete the entire course of therapy. Do not take this medication if you are allergic to any type of penicillin or cephalosporin. Notify your physician if you are pregnant or nursing. This antibiotic may decrease the effectiveness of birth control pills; use another form of birth control while taking this medication. Shake the suspension well before each use and store it in the refrigerator. May cause nausea, vomiting or diarrhea; notify your physician if these occur. Take with food or milk to avoid stomach upset. Cefixime may cause a false-positive reaction for nonspecific urine glucose tests in patients with diabetes. This medication does not interfere with enzyme-based urine glucose tests.
Cefixoral Interactions

Carbamazepine: Elevated carbamazepine levels have been reported in postmarketing experience when SUPRAX is administered concomitantly. Drug monitoring may be of assistance in detecting alterations in carbamazepine plasma concentrations.

Warfarin and Anticoagulants: Increased prothrombin time, with or without clinical bleeding, has been reported when cefixime is administered concomitantly.

Drug/Laboratory Test Interactions

A false-positive reaction for ketones in the urine may occur with tests using nitroprusside but not with those using nitroferricyanide.

The administration of SUPRAX may result in a false-positive reaction for glucose in the urine using ClinitestÒ**, Benedictís solution, or Fehlingís solution. It is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix®** or Tes-TapeÒ**) be used. A false-positive direct Coombs test has been reported during treatment with other cephalosporin antibiotics; therefore, it should be recognized that a positive Coombs test may be due to the drug.

Cefixoral Contraindications

SUPRAXÒ is contraindicated in patients with known allergy to the cephalosporin group of antibiotics.

Additional information about Cefixoral
Cefixoral Indication: For use in the treatment of the following infections when caused by susceptible strains of the designated microorganisms: (1) uncomplicated urinary tract infections caused by Escherichia coli and Proteus mirabilis, (2) otitis media caused by Haemophilus influenzae (beta-lactamase positive and negative strains), Moraxella catarrhalis (most of which are beta-lactamase positive), and S. pyogenes, (3) pharyngitis and tonsillitis caused by S. pyogenes, (4) acute bronchitis and acute exacerbations of chronic bronchitis caused by Streptococcus pneumoniae and Haemophilus influenzae (beta-lactamase positive and negative strains), and (5) uncomplicated gonorrhea (cervical/urethral) caused by Neisseria gonorrhoeae (penicillinase- and non-penicillinase-producing strains).
Mechanism Of Action: Like all beta-lactam antibiotics, cefixime binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, causing the inhibition of the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefixime interferes with an autolysin inhibitor.
Drug Interactions: Probenecid Probenecid increases the antibiotic's level
Food Interactions: Preferably on an empty stomach, rate of absorption is decreased but extenet of absorption remains the same: not really problematic.
Generic Name: Cefixime
Synonyms: Cefixima [Spanish]; Cefixime Anhydrous; Cefiximum [Latin]; Cefixim
Drug Category: Anti-Bacterial Agents; Cephalosporins
Drug Type: Small Molecule; Approved
Other Brand Names containing Cefixime: CFIX; Cefixoral; Cefspan; Cephoral; Oroken; Suprax; Unixime;
Absorption: About 40%-50% absorbed orally whether administered with or without food, however, time to maximal absorption is increased approximately 0.8 hours when administered with food.
Toxicity (Overdose): Symptoms of overdose include blood in the urine, diarrhea, nausea, upper abdominal pain, and vomiting.
Protein Binding: 65% (concentration independent)
Biotransformation: Hepatic. Approximately 50% of the absorbed dose is excreted unchanged in the urine in 24 hours.
Half Life: 3-4 hours (may range up to 9 hours). In severe renal impairment (5 to 20 mL/min creatinine clearance), the half-life increased to an average of 11.5 hours.
Dosage Forms of Cefixoral: Tablet Oral
Powder, for suspension Oral
Chemical IUPAC Name: (6R,7R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-(carboxymethyloxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Chemical Formula: C16H15N5O7S2
Cefixime on Wikipedia: http://en.wikipedia.org/wiki/Cefixime
Organisms Affected: Enteric bacteria and other eubacteria

clexane

How does it work?

Clexane injection contains the active ingredient enoxaparin, which is a type of medicine called a low molecular weight heparin. It is used to stop blood clots forming within the blood vessels.

Blood clots normally only form to stop bleeding that has occurred as a result of injury to the tissues. The clotting process is complicated and begins when blood cells called platelets clump together and produce chemicals that activate the clotting process. The final part of this process involves a substance called thrombin being activated to produce a protein called fibrin. Fibrin binds the platelets together, forming a blood clot. This is the body’s natural way of repairing itself.

Sometimes, however, a blood clot can form abnormally within the blood vessels. This is known as a thrombus. It can be dangerous because the clot may detach and travel in the bloodstream, where it becomes known as an embolus. The embolus may eventually get lodged in a blood vessel, thereby blocking the blood supply to a vital organ such as the heart, brain or lungs. This is known as a thromboembolism.

Some people have an increased tendency for blood clots to form within the blood vessels. This is usually due to a disturbance in the blood flow within the blood vessels. For example, in coronary artery disease, fatty deposits (atherosclerosis) on the walls of the coronary arteries can disrupt the blood flow, giving a tendency for platelets to clump together and start off the clotting process. When a clot has formed in a coronary artery this reduces the flow of blood to the heart and causes chest pain (angina). It can also result in a heart attack.

Slow blood flow in the leg and pelvic veins can also result in clots forming in these veins (deep vein thrombosis). These clots can break off and travel to the lungs (pulmonary embolism). Being immobile for long periods of time, for example due to a severe medical condition or following surgery, can increase the risk of these types of blood clot.

Enoxaparin is used to prevent and treat these types of abnormal blood clots. It works by inactivating thrombin in the clotting process described above. This stops the formation of fibrin, the essential component of blood clots. The medicine is administered by injection under the skin (subcutaneous injection).

Enoxaparin can also be used to prevent blood clotting when it is filtered through a kidney dialysis machine.
What is it used for?

    Treatment of blood clots in the veins of the leg (deep vein thrombosis).
    Treatment of blood clots that travel to the lungs (pulmonary embolism).
    Preventing these types of blood clots (thromboembolic disorders), particularly following general surgery or surgery on the bones (orthopaedic surgery), or in people bedridden due to illness.
    Treating blood clots in the coronary arteries in unstable angina and heart attack (myocardial infarction).
    Preventing blood from clotting when it is filtered through an 'artificial kidney' (haemodialysis) machine as part of the management of kidney failure.

Warning!

    During treatment with this medicine you should have regular blood tests to monitor the numbers of blood cells called platelets in your blood.
    Your doctor may also want to monitor the level of potassium in your blood while you are having this medicine, particularly if treatment lasts for longer than 7 days.

Use with caution in

    People over 80 years of age.
    People who are underweight or overweight.
    Decreased kidney function.
    Chronic kidney failure.
    Decreased liver function.
    People who have previously developed a reduced platelet count in the blood due to treatment with heparin or low molecular weight heparin (heparin-associated thrombocytopenia).
    People with problems stopping bleeding.
    History of peptic ulcer.
    Recent stroke caused by a blood clot in the brain (ischaemic stroke).
    Severe uncontrolled high blood pressure (hypertension).
    Diabetes.
    Diabetes affecting the eyes (diabetic retinopathy).
    People who have recently had eye surgery.
    People who have recently had surgery on the brain or spinal cord (neurosurgery).
    People having spinal or epidural anaesthesia.
    High level of potassium in the blood (hyperkalaemia).
    Increase in the acidity of the blood (metabolic acidosis).

Not to be used in

    Allergy to heparin or other low molecular weight heparins.
    Bacterial infection of the heart valves and the lining surrounding the heart (bacterial endocarditis).
    Active major bleeding.
    Conditions with a high risk of uncontrolled bleeding, for example the blood clotting disorder haemophilia, or the conditions listed below.
    Active peptic ulcer.
    Recent stroke caused by bleeding in the brain (haemorrhagic stroke).
    Reduced platelet count in the blood (thrombocytopenia).
    This medicine is not recommended for use in children.

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.

If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.
Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

    The safety of this medicine for use during pregnancy has not been established. It is not recommended for use in pregnancy unless considered essential by your doctor. It is not recommended for preventing blood clots in pregnant women with artificial heart valves. Seek medical advice from your doctor.
    It is not known if this medicine passes into breast milk. Mothers who need treatment with this medicine should avoid breastfeeding their infants during the treatment. Seek further medical advice from your doctor.

Side effects

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here does not mean that all people using this medicine will experience that or any side effect.

    Bleeding.
    Pain and irritation at the injection site.
    Blood clots which form a solid swelling at the injection site (haematoma).
    Decrease in the number of platelets in the blood (thrombocytopenia).
    Major bleeding (haemorrhage), for example in the abdomen or inside the skull.
    Alteration in results of liver function tests.
    High blood potassium level (hyperkalaemia).
    Death of skin cells (necrosis) at the site of injection.
    Blood clots in the spinal cord (intraspinal haematoma) in people also having spinal or epidural anaesthesia.
    Osteoporosis (a reduction in bone density leading to bones which may fracture easily) has occurred after long-term treatment with a similar medicine called heparin. It is possible that this could happen with Clexane.

The side effects listed above may not include all of the side effects reported by the drug's manufacturer.

For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.
How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines while having treatment with this one, to ensure that the combination is safe.

There may be an increased risk of bleeding or increased time taken to stop bleeding, if this medicine is used in combination with medicines that affect blood clotting, such as the following:

    antiplatelet ('blood-thinning') medicines, such as aspirin, dipyridamole, clopidogrel
    clot-busting medicines (fibrinolytics) such as streptokinase, alteplase
    non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, diclofenac, naproxen
    oral anticoagulants, such as warfarin, nicoumalone, phenindione.

There may be an increased risk of a rise in the amount of potassium in your blood if this medicine is used in combination with any of the following:

    ACE inhibitors, eg captopril, lisinopril
    ciclosporin
    potassium-sparing diuretics, eg spironolactone, triamterene, amiloride
    potassium supplements
    potassium-containing salt substitutes.

The amount of potassium in your blood should be regularly monitored if you are taking any of these during treatment with this medicine.
Other medicines containing the same active ingredient

There are currently no other medicines available in the UK that contain enoxaparin as the active ingredient.

Read more: http://www.netdoctor.co.uk/heart-and-blood/medicines/clexane.html#ixzz2TY65NrGp
Follow us: @NetDoctor on Twitter | NetDoctorUK on Facebook

Oxycodone

Evidence snapshot icon Evidence snapshot
What is known about this drug

Oxycodone-with-naloxone controlled-release (CR) tablets provide equivalent analgesia to that of oxycodone CR tablets of the same oxycodone dose, with a similar adverse-effect profile.

Adding the naloxone component reduces, but does not eliminate, the prevalence of constipation. Compared with oxycodone CR, the number needed to treat (NNT) (for one person using opioids continuously to avoid constipation) was about 4 for people with existing opioid-induced constipation (after 4 weeks), and about 14 for people not selected for constipation symptoms (after 12 weeks).
  
Areas of uncertainty

Efficacy data regarding analgesia and constipation are from 12-week randomised controlled trials. Longer-term data (up to 52 weeks) are from uncontrolled trials. The tablets have not been compared with a regimen of oxycodone and prophylactic laxatives.

There are insufficient data from randomised controlled trials to characterise rare adverse events.
  
What does NPS say?

Switching to the fixed-dose combination tablets may benefit people who experience constipation while taking low to medium doses of oxycodone long term. Everyone taking regular opioids should increase their fluid and fibre intake and exercise levels to reduce the risk of opioid-induced constipation.

Among people without existing constipation, a small proportion will experience a benefit over oxycodone alone.
PBS listing

Restricted benefit

Chronic, severe disabling pain not responding to non-opioid analgesics.

Authorities for increased maximum quantities will be available for patients meeting the criteria listed in the note in the Schedule of Pharmaceutical Benefits.1

Oxycodone is a Controlled Drug (Schedule 8) and so must be prescribed in accordance with State or Territory regulations.
May be prescribed by nurse practitioners (shared care model)

Authorised nurse practitioners may prescribe this medicine as part of a formal care plan with a medical practitioner. See the PBS website for more information on nurse practitioner PBS prescribing.
What is it?

Oxycodone-with-naloxone controlled-release (CR) tablets (Targin) contain a combination of a strong opioid and an opioid antagonist in a controlled-release formulation. The tablets are bioequivalent to oxycodone CR (OxyContin) with regard to their oxycodone content and provide the same duration of action (i.e. approximately 12 hours). The available strengths are oxycodone/naloxone: 5 mg/2.5 mg, 10 mg/5 mg, 20 mg/10 mg and 40 mg/20 mg.

Injected naloxone has long been used to reverse systemic opioid effects, whereas oral naloxone is unsuited for this purpose because it undergoes extensive first-pass metabolism and has low systemic bioavailability. The controlled-release tablets deliver a naloxone dose that blocks opioid receptors in the gut, but not elsewhere (e.g. central nervous system), and therefore reduces gastrointestinal effects with a minimal effect on analgesia.2

See an assessment of oxycodone-with-naloxone CR tablets using a checklist of questions about fixed-dose combination preparations.Web extra: Child–Pugh classification of liver disease
Who is it for?

Oxycodone-with-naloxone CR tablets are indicated for severe chronic cancer or non-cancer pain unresponsive to non-opioid analgesia.* The naloxone component reduces opioid-induced constipation.1,2 Oxycodone, as with all strong opioids, should be offered to people with chronic non-cancer pain only when:

    non-opioid methods of analgesia have been tried and failed
    pain has a significant effect on the patient's quality of life
    there is no psychological contraindication, drug-seeking behaviour or history of drug or alcohol misuse
    prescribing is part of an agreed pain management plan that includes non-drug measures.2,3

See NPS Prescribing Practice Review 51 for information about developing a pain management plan.

Oxycodone-with-naloxone CR tablets are not indicated for acute pain.

* The tablets are also indicated but not PBS listed for moderate pain unresponsive to non-opioid analgesia.

Where does it fit?
An option for people with opioid-induced constipation

Oxycodone-with-naloxone CR tablets cause less constipation than conventional oxycodone CR tablets, but not all patients will benefit (see Less constipation than with oxycodone CR tablets). Switching from low-to-medium doses of oxycodone CR tablets to the fixed-dose combination tablets appears useful for people who suffer from constipation despite an adequate laxative regimen.

For palliative care patients experiencing opioid-induced constipation, adding methylnaltrexone (Relistor) to the existing opioid regimen is an option if laxatives fail (see the NPS RADAR review Methylnaltrexone injection (Relistor) for opioid-induced constipation in palliative care).

Among people without established opioid-induced constipation, a smaller proportion benefit (see Small benefit among people who do not already have opioid-induced constipation).
Laxatives may be required

As for oxycodone alone, advise people starting oxycodone-with-naloxone CR tablets to increase their fluid and fibre intake and exercise levels to reduce the risk of constipation. Recommend or prescribe regular laxatives as necessary (i.e. combined stool softener with stimulant laxative, such as docusate with senna [Coloxyl with Senna; Soflax], or an osmotic laxative, namely, sorbitol or lactulose).4,5

In trials, people taking oxycodone-with-naloxone CR tablets used laxatives only on demand, and 27–49% experienced some degree of constipation (see Less constipation than with oxycodone CR tablets).
Limited usefulness for people who need high doses of opioids

The maximum recommended daily dose of oxycodone-with-naloxone CR tablets is oxycodone 80 mg/naloxone 40 mg; higher doses have not been evaluated. People requiring a daily dose totalling more than oxycodone 80 mg can take additional oxycodone CR tablets 12 hourly, but a beneficial effect on constipation may be lessened.2
Long-term efficacy data regarding effect on constipation are lacking

There are no comparative data to demonstrate that oxycodone-with-naloxone CR tablets continue to prevent constipation for longer than 12 weeks, the length of the three key randomised controlled trials. However, average patient-reported constipation symptoms did not worsen over 52 weeks in open-label uncontrolled extension trials.6
Naloxone may deter intranasal or injected use

Oxycodone-with-naloxone CR tablets contain a dose of naloxone that will antagonise the acute central nervous system effect of oxycodone if used intranasally or injected. In theory, this will reduce the pleasurable effects and provoke unpleasant withdrawal symptoms for people who are opioid tolerant. The tablets may therefore be less appealing for unsanctioned (problematic or illicit) administration, but there is currently no direct evidence to confirm this. The tablets do not deter unsanctioned oral use.

As with other oxycodone preparations, oxycodone-with-naloxone CR tablets are not recommended for treating opioid withdrawal, and should be prescribed with caution and under close supervision for people who are known or suspected to misuse prescription medicines, alcohol or other substances.2
How does it compare?
Similar analgesia to that of oxycodone CR tablets

A pooled analysis of two 12-week randomised controlled trials found that oxycodone-with-naloxone CR tablets provided analgesia that was no worse than that of conventional oxycodone CR tablets. Participants in the trials had chronic non-cancer pain, mostly of musculoskeletal origin (e.g. osteoarthritis), and the average age was 58 years. The average difference in pain intensity score at 12 weeks was –0.01 (95% CI –0.15 to 0.13) on a pain scale from 0 to 10. There was no statistically significant difference in the amount of supplemental oxycodone used, and average daily oxycodone doses were similar in the two groups.7,8
Efficacy compared with prophylactic laxatives is not known

None of the clinical trials of oxycodone-with-naloxone CR tablets compared them with the combination of oxycodone or another strong opioid and a prophylactic laxative. Prophylactic laxative use is the standard of care when strong opioids are used regularly in chronic pain.4,9
Less constipation than with oxycodone CR tablets

In three comparative trials, oxycodone-with-naloxone CR tablets caused less constipation than oxycodone CR tablets, after 4 weeks and 12 weeks of therapy.10–12 Constipation was measured using the Bowel Function Index (BFI).*

As a secondary outcome, all three trials reported the number of participants with fewer than three complete spontaneous bowel movements per week, a common definition for constipation (see Table 1). Using these results it is possible to estimate for each trial the proportion of patients who avoided constipation by using oxycodone-with-naloxone CR tablets rather than oxycodone CR tablets (responder data are not available for BFI).

* The Bowel Function Index (BFI) is a patient-assessed score on a scale of 0 to 100 (0 = no symptoms). As well as frequency of bowel movements, the BFI incorporates other constipation-related symptoms such as straining and bloating. It was accepted by regulators as an outcome measure in oxycodone-with-naloxone trials but has not been used by other investigators.
Table 1. Proportion of trial participants with fewer than three complete spontaneous bowel movements per week

Trial
  

Oxycodone-with-naloxone CR
  

Oxycodone CR

Patients with existing opioid-induced constipation (OIC)*

OXN3001†11
  

35% (50/144)
  

61% (83/137)

OXN3006†10
  

49% (64/130)
  

74% (100/135)

Patients not selected for existing OIC

OXN3401‡7,12
  

27% (41/154)
  

34% (51/151)

* All trial participants had fewer than three complete spontaneous bowel movements per week at recruitment.

† After 4 weeks of double-blind therapy

‡ After 12 weeks of double-blind therapy. Bowel function variables were secondary outcomes in this study.

Small benefit among people who do not already have opioid-induced constipation

One of the three key trials of oxycodone-with-naloxone CR tablets did not actively select participants with pre-existing opioid-induced constipation. In this trial, 80% of participants had no or mild constipation at randomisation (i.e. a BFI < 50), despite using an opioid analgesic for 2 or more weeks before enrolling in the study.12

In this population, there was a 7-percentage-point difference in constipation rates after 12 weeks of treatment between participants receiving oxycodone-with-naloxone CR tablets and participants receiving oxycodone CR tablets (see Table 1). People receiving oxycodone-with-naloxone CR tablets used laxatives on 7.9% of days, while people receiving oxycodone CR tablets used them on 10.4% of days (statistical significance of comparison not reported).7,12

There are few reliable data regarding the typical incidence of opioid-induced constipation, but the median rate of constipation was 30% in a meta-analysis of opioids for chronic non-cancer pain in older adults.13
No comparison with methylnaltrexone in palliative care population

Methylnaltrexone is an option for treating opioid-induced constipation in people receiving palliative care who have not responded to adequately titrated laxatives [see the NPS RADAR review Methylnaltrexone injection (Relistor) for opioid-induced constipation in palliative care]. A reduction in constipation with oxycodone-with-naloxone CR tablets has been demonstrated with a mean daily oxycodone dose of up to about 70 mg7,10–12; patients with cancer pain or in palliative care may require higher oxycodone doses.
Safety issues

Oxycodone-with-naloxone CR tablets appear to have a similar safety profile to that of oxycodone CR tablets; however, there are insufficient data from randomised controlled trials to characterise rare adverse events.

Report suspected adverse reactions to the Therapeutic Goods Administration (TGA) online or by using the 'Blue Card' distributed three times a year with Australian Prescriber. For information about reporting adverse reactions, see the TGA website.
Diarrhoea may occur

In the three key trials, the incidence of diarrhoea was about 5% with either oxycodone-with-naloxone CR tablets or with oxycodone CR tablets. When switching from long-term higher-dose opioid treatment to oxycodone-with-naloxone CR tablets, people may initially experience diarrhoea.2
Contraindicated in moderate or severe hepatic impairment

People with hepatic impairment experience higher systemic exposure to naloxone, which can antagonise the central nervous system effects of oxycodone.2 This could result in reduced analgesia, and opioid withdrawal symptoms in people who are opioid tolerant.

If prescribing to people with renal impairment or mild hepatic impairment, titrate the dose cautiously and monitor carefully. As with conventional oxycodone CR tablets, renal or hepatic impairment may increase oxycodone plasma concentrations (see Reduce the dose for people with mild hepatic impairment or creatinine clearance < 60 mL per min). Do not prescribe in moderate or severe hepatic impairment.2
Low incidence of withdrawal symptoms in trials

People receiving long-term higher-dose opioid treatment can initially experience opioid withdrawal symptoms when switching to oxycodone-with-naloxone CR tablets.2 In key trials the incidence of withdrawal symptoms was low and similar for oxycodone-with-naloxone CR tablets and oxycodone CR tablets.7
Few data about rare adverse events

Naloxone has been used as a parenteral opioid antagonist for several decades, and appears to cause few adverse effects except for those associated with acute opioid withdrawal.4

There is less experience with long-term oral use of naloxone and insufficient data from randomised controlled trials to characterise rare adverse events with oxycodone-with-naloxone CR tablets. However, oxycodone-with-naloxone CR tablets were first registered in Germany in 2006, and the Australian TGA-approved product information lists adverse events from European postmarketing data.7
Reason for PBS listing

In July 2010, the Pharmaceutical Benefits Advisory Committee (PBAC) rejected a submission requesting the PBS listing of oxycodone-with-naloxone CR tablets because of uncertain cost-effectiveness. The PBAC observed that the benefits appeared modest, especially in the population of patients who were not constipated before starting oxycodone with naloxone.14

A subsequent submission in November 2010 amended the price and also addressed uncertainties identified by the PBAC, including efficacy in the non-constipated population, the use of prophylactic laxatives, and the likely average daily dose of oxycodone. The PBAC recommended listing on the basis that the revised cost-effectiveness estimates were acceptable, relative to oxycodone CR tablets without prophylactic laxatives.

The PBAC accepted that oxycodone-with-naloxone CR tablets are efficacious in both constipated and non-constipated patients. They considered that availability of the tablets would improve the management of opioid-induced constipation, and may reduce diversion. They noted data indicating that GPs co-prescribed laxatives at a low rate for people receiving opioids, but also noted that many people purchase over-the-counter laxatives.15
Dosing issues

Initiate and dose oxycodone-with-naloxone CR tablets as for oxycodone CR tablets. People already receiving single-ingredient oral oxycodone preparations (immediate or controlled release) may switch to the combination tablets at the same total daily oxycodone dosage, equally divided into two 12-hourly doses.2

If switching from oral morphine, the Targin product information states that oxycodone 10 mg is equivalent to oral morphine 20 mg. Note that guidelines recommend starting with a lower dose than that calculated (e.g. 50% to 75% of the equianalgesic dose) then titrating to response. This is recommended to cater for differences in how people tolerate different opioids.2,4,9

The tablets are registered for use by children and adolescents from 12 years of age2, but oral opioids generally have a very limited role in treating chronic non-cancer pain in children.
Maximum strength is oxycodone 40 mg/naloxone 20 mg

There is no tablet strength corresponding to existing oxycodone CR 80 mg tablets. The maximum recommended dose is one oxycodone 40 mg/naloxone 20 mg tablet 12 hourly, but supplementary oxycodone CR tablets can be added (see Limited usefulness for people who need high doses of opioids).2
Reduce the dose for people with mild hepatic impairment or creatinine clearance < 60 mL per min

For people with mild hepatic impairment or renal impairment and creatinine clearance < 60 mL/min, reduce the dose to one-third to one-half of the usual. Titrate cautiously with careful monitoring. The tablets are contraindicated in moderate or severe hepatic impairment. 2
Advise people to take the tablets whole

Breaking, dissolving, chewing or crushing the tablets can lead to the rapid release of oxycodone and naloxone, and a potential overdose of oxycodone. The tablets are for oral use only.2
Information for patients

Advise patients as follows.

    Swallow the tablets whole with a full glass of water; do not chew, crush, break or dissolve the tablets.
    Take every 12 hours, with or without food.
    Do not take any other pain reliever or opioid, sleeping tablets or muscle relaxants without speaking with a doctor or pharmacist.
    Avoid drinking alcohol.
    The tablets can cause constipation, diarrhoea, nausea, vomiting, dizziness, drowsiness, headache, itching and other side effects.
    Laxatives may still be required — follow the course recommended by your doctor.
    Note carefully which of their existing medicines are being replaced by the combination tablets and return the unneeded medicines to a pharmacy.

Discuss the Targin consumer medicine information (CMI) leaflet with the patient.

Advise patients to reduce the chance of constipation by drinking water regularly throughout the day, increasing their fibre intake and keeping as mobile as they can. Consider recommending or prescribing regular laxatives (e.g. combined stool softener with stimulant laxative, such as docusate with senna [Coloxyl with Senna; Soflax]).4,5

Patients switching from another opioid preparation may need to reduce their laxative intake.