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TARGINACT 10MG/5MG PROLONGED RELEASE TABLETS

Active substance(s): NALOXONE HYDROCHLORIDE DIHYDRATE / OXYCODONE HYDROCHLORIDE / NALOXONE HYDROCHLORIDE DIHYDRATE / OXYCODONE HYDROCHLORIDE / NALOXONE HYDROCHLORIDE DIHYDRATE / OXYCODONE HYDROCHLORIDE

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Package leaflet: Information for the user

Targinact® 10 mg/5 mg prolonged-release tablets
(oxycodone hydrochloride and naloxone hydrochloride)
Read all of this leaflet carefully before you start
taking this medicine because it contains important
information for you.





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.








®

The name of your medicine is Targinact 10 mg/5 mg
prolonged-release tablets but will be referred to as
Targinact or Targinact tablets throughout this leaflet.
Please note that this leaflet also contains information
about the other strengths such as Targinact 5 mg/2.5 mg,
20 mg/10 mg and 40 mg/20 mg prolonged-release tablets.
What is in this leaflet:
1. What Targinact tablets are and what they are used
for
2. What you need to know before you take Targinact
tablets
3. How to take Targinact tablets
4. Possible side effects
5. How to store Targinact tablets
6. Contents of the pack and other information

1. What Targinact tablets are and what they
are used for
Targinact is a prolonged-release tablet, which means
that its active substances are released over an
extended period. Their action lasts for 12 hours.
These tablets are only for use in adults.
Pain relief
You have been prescribed Targinact tablets for the
treatment of severe pain, which can be adequately
managed only with opioid analgesics. Naloxone is
added to counteract constipation.
How these tablets work in pain relief
These tablets contain oxycodone hydrochloride and
naloxone hydrochloride as active substances.
Oxycodone is responsible for the painkilling effect of the
tablets. It is a strong analgesic (‘painkiller’) that belongs
to a group of medicines called opioids. Naloxone is
intended to bring relief from constipation. Constipation is
a typical side effect of treatment with strong painkillers.
Restless legs syndrome
You have been prescribed Targinact tablets for the
second line symptomatic treatment of severe to very
severe restless legs syndrome in people who can’t be
treated with dopamine medicines. People with restless
legs syndrome have unpleasant sensations in their
limbs. This can start as soon as they sit or lie down and
is only relieved by an irresistible urge to move the legs,
sometimes the arms and other parts of the body. It
makes sitting still and sleeping very difficult. Naloxone
hydrochloride is added to counteract constipation.
How these tablets work in restless legs syndrome
These tablets help to relieve the unpleasant sensations
and so reduces the urge to move the limbs. Naloxone is
intended to bring relief from constipation. Constipation is
a typical side effect of treatment with strong painkillers.

2. What you need to know before you take
Targinact tablets
Do not take Targinact tablets
● if you are allergic (hypersensitive) to oxycodone or
naloxone, or any of the other ingredients of the
tablets (listed in section 6);



if you have breathing problems, such as breathing
more slowly or weakly than expected (respiratory
depression);
if you suffer from a severe lung disease associated
with narrowing of the airways (chronic obstructive
pulmonary disease or COPD);
if you suffer from a condition known as cor
pulmonale. In this condition, the right side of the
heart becomes enlarged, due to increased pressure
inside blood vessels in the lung etc. (e.g. as a result
of COPD – see above);
if you suffer from severe bronchial asthma;
if you have a type of bowel obstruction
(paralytic ileus) not caused by opioids;
if you have moderate to severe liver problems.

Additionally for restless legs syndrome
● if you have a history of opioid abuse
Warnings and Precautions
Talk to your doctor or pharmacist before taking these
tablets:
● in the case of elderly or debilitated (weak) patients;
● if you have a type of bowel obstruction (paralytic
ileus) caused by opioids;
● if you have kidney problems;
● if you have mild liver problems;
● if you have severe lung problems (i.e. reduced
breathing capacity);
● if you suffer with a condition characterised by
frequent breathing stops during the night which may
make you feel very sleepy during the daytime (sleep
apnoea);
● if you have myxoedema (a thyroid disorder, with
dryness, coldness and swelling [‘puffiness’] of the
skin, affecting the face and limbs);
● if your thyroid gland is not producing enough
hormones (underactive thyroid or hypothyroidism);
● if your adrenal glands are not producing enough
hormones (adrenal insufficiency or Addison’s
disease);
● if you have a mental disorder as a result of an
intoxication (toxic psychosis);
● if you suffer from gallstone problems;
● if your prostate gland is abnormally enlarged
(prostate hypertrophy);
● if you are or ever have been addicted to alcohol or
drugs, or have previously suffered from withdrawal
symptoms such as agitation, anxiety, shaking or
sweating upon stopping alcohol or drugs;
● if your pancreas is inflamed (pancreatitis);
● if you have low blood pressure (hypotension);
● if you have high blood pressure (hypertension);
● if you have heart problems;
● if you have a head injury (due to the risk of
increased brain pressure);
● if you suffer from epilepsy or are prone to fits;
● if you are also taking a type of medicine known as a
MAO inhibitor (used to treat depression or
Parkinson’s disease) e.g. medicines containing
tranylcypromine, phenelzine, isocarboxazid,
moclobemide and linezolid;
● if sleepiness or episodes of suddenly falling asleep
occur.
Tell your doctor if any of the above has ever applied to
you in the past. Also, please tell your doctor if you
develop any of them while you are taking these tablets.
The most serious result of opioid overdose is
respiratory depression (slow and shallow breathing).
This may also cause blood oxygen levels to fall,
resulting in possible fainting, etc.
You must swallow the tablet whole, so as not to affect
the slow release of oxycodone hydrochloride from the
tablet. Do not break, chew or crush the tablets. Taking
broken, chewed or crushed tablets may lead to the
absorption of a potentially lethal dose of oxycodone
hydrochloride (see section 3: "If you take more
Targinact than you should").

If you experience severe diarrhoea at the start of
treatment (within the first 3-5 days) this may be due to
the effect of naloxone. It may be a sign that your bowel
movements are returning to normal. If diarrhoea persists
after 3-5 days, or it gives you cause for concern, please
contact your doctor.
If you have been using another opioid, withdrawal
symptoms (such as restlessness, bouts of sweating
or muscle pain) may occur when you initially switch to
taking these tablets. If you experience withdrawal
symptoms, you may need to be specially monitored by
your doctor.
If you have been taking these tablets for a long time, you
may become tolerant. This means you may need a
higher dose to achieve the desired effect. Long-term use
of these tablets may also lead to addiction. Withdrawal
symptoms may occur if treatment is stopped too
suddenly. If you no longer need treatment, you should
reduce your daily dose gradually, in consultation with
your doctor.
As with other strong opioid painkillers, there is a risk that
you may develop a psychological dependence to
oxycodone.
Tell your doctor if you have advanced digestive or
pelvic cancers where bowel obstruction may be a
problem.
If you need to undergo surgery, please tell your doctor
that you are taking Targinact.
You may notice remains of the tablet in your stools.
Do not be alarmed, as the active ingredients will have
already been released in the stomach and gut, and
absorbed into your body.
Incorrect use of Targinact tablets
These tablets are not suitable for withdrawal treatment.
These tablets should never be abused, particularly if you
have a drug addiction. If you are addicted to drugs such
as heroin, morphine or methadone, severe withdrawal
symptoms are likely if you abuse these tablets because
they contain the ingredient naloxone. Pre-existing
withdrawal symptoms may be made worse.
You should never misuse the tablets by dissolving and
injecting them (e.g. into a blood vessel). They contain
talc, which can cause destruction of local tissue
(necrosis) and changes in lung tissue (lung granuloma).
Misuse can also have other serious consequences
which may be fatal.
The use of these tablets may produce positive results in
drugs tests.
Other medicines and Targinact tablets
Tell your doctor or pharmacist if you are taking, have
recently taken or might take any other medicines. If you
take these tablets at the same time as you take other
medicines, the effect of these tablets or the other
medicine may be changed. Tell your doctor if you are
taking:
● other strong painkillers (opioids);
● sleep medication and tranquillisers (sedatives,
hypnotics);
● medicines to treat depression;
● medicines used to treat allergies, travel sickness or
nausea (antihistamines or antiemetics);
● medicines to treat psychiatric or mental disorders
(phenothiazines, neuroleptics, antipsychotics);
● medicines that decrease the blood’s clotting ability
(coumarin derivatives), this clotting time may be
speeded up or slowed down;
● antibiotics of the macrolide type (such as
clarithromycin, erythromycin or telithromycin);
● antifungal medicines of the –azole type (such as
ketoconazole, voriconazole, itraconazole or
posaconazole);
● a specific type of medicine known as a protease
inhibitor used to treat HIV (examples include
ritonavir, indinavir, nelfinavir or saquinavir;
● cimetidine (a medicine for stomach ulcers,
indigestion or heartburn);
● rifampicin (used to treat tuberculosis);
● carbamazepine (used to treat seizures, fits or
convulsions and certain pain conditions);
● phenytoin (used to treat seizures, fits or
convulsions).





phenytoin (used to treat seizures, fits or convulsions);
a herbal remedy called St John's Wort (also known as
Hypericum perforatum);
quinidine (a medicine to treat an irregular heartbeat).

Targinact tablets with food, drink and alcohol
Drinking alcohol whilst taking Targinact may make you feel
more sleepy or increase the risk of serious side effects such
as shallow breathing with a risk of stopping breathing, and
loss of consciousness. It is recommended not to drink alcohol
while you’re taking Targinact.
You should avoid drinking grapefruit juice while you are taking
these tablets.
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be
pregnant or are planning to have a baby, ask your doctor or
pharmacist for advice before taking this medicine.
Pregnancy
Use of these tablets during pregnancy should be avoided
unless your doctor thinks treatment with this medicine is
essential. If used over prolonged periods during pregnancy,
oxycodone may lead to withdrawal symptoms in the newborn
baby. If oxycodone is given during childbirth, the baby may
have breathing problems (respiratory depression).
Breastfeeding
Breastfeeding should be stopped during treatment with these
tablets as oxycodone (one of the active ingredients of your
medicine) passes into breast milk.
Driving and using machines
This medicine can affect your ability to drive as it may make
you sleepy or dizzy. This is most likely at the start of your
treatment, after a dose increase or after switching from a
different medication. These side effects should disappear
once you are on a stable dose.
This medicine has been associated with sleepiness and
episodes of suddenly falling asleep. If you experience these
side effects, you must not drive or operate machinery. You
should tell your doctor if this occurs.
● Do not drive while taking this medicine until you know how
it affects you.
● It is an offence to drive while you have this medicine in
your body over a specified limit unless you have a
defence (called the ‘statutory defence’).
● This defence applies when:
o The medicine has been prescribed to treat a
medical or dental problem; and
o You have taken it according to the instructions
given by the prescriber and in the information
provided with the medicine.
● Please note that it is still an offence to drive if you are unfit
because of the medicine (i.e. your ability to drive is being
affected).
Details regarding a new driving offence concerning driving
after drugs have been taken in the UK may be found
here: https://www.gov.uk/drug-driving-law.
Talk to your doctor or pharmacist if you are not sure whether it
is safe for you to drive while taking this medicine.
Targinact tablets contain lactose
These tablets contain lactose (milk sugar). If you have been
told that you have an intolerance to some sugars, contact your
doctor before taking these tablets.

3. How to take Targinact tablets
Always take these tablets exactly as your doctor has told you.
Check with your doctor or pharmacist if you are not sure.
Targinact is a prolonged-release tablet, which means that its
active substances are released over an extended period. Their
action lasts for 12 hours.
You must swallow these prolonged-release tablets whole
so as not to affect the slow release of oxycodone from the
tablets. Do not break, chew or crush these tablets. Taking
broken, chewed or crushed tablets may result in your body
absorbing a potentially fatal dose of oxycodone (see
section 3: ‘If you take more Targinact tablets than you
should’). Unless otherwise prescribed by your doctor, the
usual dose is:
To treat pain
Adults
The usual starting dose is 10 mg oxycodone hydrochloride / 5
mg naloxone hydrochloride every 12 hours.

Your doctor will decide how much you should take every day
and how to divide your total daily dosage into morning and
evening doses. Your doctor will also decide on any necessary
dose adjustments during treatment depending on your level of
pain and individual sensitivity. You should be given the lowest
dose needed for pain relief. If you have already been treated
with opioids, your treatment with these tablets may be started
at a higher dose.
The maximum daily dose is 160 mg oxycodone hydrochloride
and 80 mg naloxone hydrochloride. If you need a higher dose,
your doctor may give you additional oxycodone without
naloxone. However, the maximum daily dose of oxycodone
should not exceed 400 mg. The beneficial effect of naloxone
on bowel movements may be affected if additional oxycodone
is given without additional naloxone
If you are switched from these tablets to another opioid pain
medication your bowel function will probably worsen.
If you experience pain between doses, you may need to take
an additional fast-acting painkiller. These tablets are not
suitable for this. Please talk to your doctor.
If you feel that these tablets are too strong or too weak, please
talk to your doctor or pharmacist.
To treat restless legs syndrome
Adults
The usual starting dose is 5 mg oxycodone hydrochloride/ 2.5
mg naloxone hydrochloride as prolonged-release tablet(s)
every 12 hours.
Your doctor will decide how much you should take every day
and how to divide your total daily dosage into morning and
evening doses. They will also decide on any necessary dose
adjustments during treatment. Your dose will be adjusted
according to your individual sensitivity. You should be given the
lowest dose needed to relieve your restless legs syndrome
symptoms.
If you feel that these tablets are too strong or too weak, please
talk to your doctor or pharmacist.
The maximum daily dose is 60 mg oxycodone hydrochloride
and 30 mg naloxone hydrochloride.
To treat pain or restless legs syndrome
Elderly patients
In general, no dose adjustment is necessary for elderly patients
with normal kidney and/or liver function.
Liver or kidney problems
If you have kidney or mild liver problems your doctor may
prescribe a lower dose. You must not take these tablets if you
have moderate or severe liver problems,
(see also Section 2 ‘Do not take Targinact tablets’ and ‘Take
special care with Targinact tablets’ and ‘Warnings and
Precautions’).
Children and adolescents below 18 years of age
No studies have been carried out to show that these tablets
work properly in children and adolescents, or are safe for them
to take. They are therefore not recommended for use in
patients under 18 years of age.
Method of administration
Swallow your tablets whole with a glass of water. You can take
these tablets with or without food. Take them every 12 hours.
For instance, if you take a tablet at 8 o’clock in the morning,
you should take your next tablet at 8 o’clock in the evening. Do
not break, chew or crush the tablets (see section 2 'Warnings
and precautions').
Duration of use
You should not take these tablets for any longer than you need
to. If you have been taking them for a long time your doctor
should regularly check that you still need them.
If you take more Targinact tablets than you should If you
have taken more than the prescribed dose, you must inform
your doctor immediately.
An overdose may result in:







a reduction in size of pupils in the eye;
breathing more slowly or weakly than expected
(respiratory depression);
drowsiness up to loss of consciousness;
low muscle tone (hypotonia);
reduced pulse rate;
a fall in blood pressure.

In severe cases, loss of consciousness (coma), fluid on
the lungs and circulatory collapse may occur, which may
be fatal.
You should avoid situations which require you to be alert,
e.g. driving.
If you forget to take Targinact tablets,
or if you take a lower dose than the one prescribed, you
may not feel any effect.
If you should forget to take your dose, please follow the
instructions below:
● If your next usual dose is due in 8 hours or more: Take
the forgotten dose immediately and continue with your
normal dosing routine.
● If your next usual dose is due in less than 8 hours:
Take the forgotten dose, then, wait another 8 hours
before taking your next dose. Try to get back in your
normal dosing routine (e.g. 8 o’clock in the morning
and 8 o’clock in the evening).
Do not take more than one dose within any 8 hour period.
Do not take a double dose to make up for a forgotten
dose.
If you stop taking Targinact tablets
Do not stop taking these tablets without first speaking with
your doctor. If you do not require any further treatment,
your doctor will advise you how to reduce the daily dose
gradually. In this way, you will avoid withdrawal
symptoms, such as restlessness, bouts of sweating and
muscle pain.
If you have any further questions on the use of these
tablets, ask your doctor or pharmacist.

4. Possible side effects
Like all medicines, these tablets can cause side effects,
although not everybody gets them.
Important side effects or signs to look out for, and
what to do if you are affected:
The most serious side effect is a condition where you
breathe more slowly or weakly than expected
(respiratory depression). It mostly occurs in elderly and
weak patients. Opioids can also cause a severe drop in
blood pressure in susceptible patients. If you are affected
by these important side effects, consult a doctor
immediately.
The following side effects have been seen in
patients being treated for pain
Common (may effect up to 1 in 10 people)
● abdominal pain
● constipation
● diarrhoea
● dry mouth
● indigestion
● vomit (be sick)
● feel sick
● flatulence (wind)
● decreased appetite up to loss of appetite
● a feeling of dizziness or ‘spinning’
● headache
● hot flushes
● a feeling of unusual weakness
● tiredness or exhaustion
● itchy skin
● skin reactions/rash
● sweating
● vertigo
● difficulty in sleeping
● drowsiness

Uncommon (may affect up to 1 in 100 people)
● abdominal bloating
● abnormal thoughts
● anxiety
● confusion
● depression
● nervousness
● chest tightness, especially if you already have
coronary heart disease
● drop in blood pressure
● withdrawal symptoms such as agitation































fainting
lack of energy
thirst
altered taste
palpitations
biliary colic
chest pain
generally feeling unwell
pain
swelling of the hands, ankles or feet
difficulties to concentrate
impaired speaking
shaking
difficulties breathing
restlessness
chills
hepatic enzymes increased
rise in blood pressure
reduced sexual drive
runny nose
cough
hypersensitivity/allergic reactions
weight loss
injuries from accidents
increased urge to urinate
muscle cramps
muscle twitches
muscle pain
vision impairment
epileptic seizures (especially in persons with
epileptic disorder or predisposition to seizures)

Rare (may affect up to 1 in 1,000 people)
● increase in pulse rate
● dental changes
● weight gain
● yawning
Not known (frequency cannot be estimated from
available data)
● euphoric mood
● severe drowsiness
● erectile dysfunction
● nightmares
● hallucinations
● shallow breathing
● difficulty in passing urine
● tingling skin (pins and needles)
● belching
The active ingredient oxycodone hydrochloride, if not
combined with naloxone hydrochloride, is known to have
the following differing side effects: Breathing problems,
such as breathing more slowly or weakly than expected
(respiratory depression), reduction in size of the pupils in the
eye, muscle cramps and decreased cough reflex.
Common (may affect up to 1 in 10 people)
● altered mood and personality changes (e.g.
depression, feeling of extreme happiness)
● decreased activity
● increased activity
● difficulties in passing urine
● hiccups

Uncommon (may affect up to 1 in 100 people)
● impaired concentration
● migraines
● increased muscle tension
● involuntary muscle contractions
● drug dependence
● a condition where the bowel stops working properly
(ileus)
● dry skin
● drug tolerance
● reduced sensitivity to pain or touch
● abnormal coordination
● vocal changes (dysphonia)
● water retention
● difficulty in hearing
● mouth ulcers
● difficulties in swallowing
● sore gums
● perception disturbances (e.g. hallucination,
derealisation)
● flushing of skin
● dehydration
● agitation
● a decrease in sex hormone levels which may affect
sperm production in men or the menstrual cycle in
females
Rare (may affect up to 1 in 1,000 people)
● itching rash (urticaria)
● infections such as cold sores or herpes (which may cause
blisters around the mouth or genital area)
● increased appetite
● black (tarry) stools
● bleeding gums
Not known (frequency cannot be estimated from the
available data)
● acute generalized allergic reactions (anaphylactic
reactions)
● an increase in sensitivity to pain
● absence of menstrual periods
● withdrawal symptoms in the newborn
● aggression
● problems with bile flow
● tooth decay
The following side effects have been seen in patients
being treated for restless legs syndrome
Very common (may affect 1 in 10 people or more)
● headache
● drowsiness
● constipation
● feel sick
● sweating
● tiredness or exhaustion
Common (may affect up to 1 in 10 people)
● decreased appetite to loss of appetite
● difficulty in sleeping
● depression
● a feeling of dizziness or ‘spinning’
● difficulty in concentrating
● shaking
● tingling in hands or feet
● vision impairment
● vertigo
● hot flushes
● drop in blood pressure
● rise in blood pressure
● abdominal pain
● dry mouth
● vomit (be sick)
● hepatic enzymes increased (alanine
aminotransferase increased, gammaglutamyltransferase increased)
● itchy skin
● skin reactions/rash
● chest pain
● chills
● pain
● thirst

Uncommon (may affect up to 1 in 100 people)
● reduced sexual drive
● episodes of suddenly falling asleep
● altered taste
● difficulties breathing
● wind
● erectile dysfunction
● withdrawal symptoms such as agitation
● swelling of hands, ankles or feet
● injuries from accidents
Not known (frequency cannot be estimated from
available data)
● hypersensitivity/ allergic reactions
● abnormal thoughts
● anxiety
● confusion
● nervousness
● restlessness
● euphoric mood
● hallucinations
● nightmares
● epileptic seizures (especially in persons with
epileptic disorder or predisposition to seizures)
● severe drowsiness
● impaired speaking
● fainting
● chest tightness especially if you already have
coronary heart disease
● palpitations
● increase in pulse rate
● shallow breathing
● cough
● runny nose
● yawning
● abdominal bloating
● diarrhoea
● indigestion
● belching
● dental changes
● biliary colic
● muscle cramps
● muscle twitches
● muscle pain
● difficulties in passing urine
● increased urge to urinate
● generally feeling unwell
● weight loss
● weight increase
● a feeling of unusual weakness
● lack of energy
Reporting of side effects
If you get any side effects, talk to your doctor,
pharmacist or nurse. This includes any possible side
effects not listed in this leaflet. You can also report side
effects directly via the Yellow Card Scheme at:
www.mhra.gov.uk/yellowcard. By reporting of side
effects, you can help provide more information on the
safety of this medicine.

5. How to store Targinact tablets
Keep all medicines out of the sight and reach of children.
Do not use any tablets after the expiry date which is stated
on the carton and blister, after ‘Exp...’. The expiry date refers
to the last day of the month.
Do not store above 25°C. Store in the original package in
order to protect from light.
Do not throw away any medicines via wastewater or
household waste. Ask your pharmacist how to throw away
medicines you no longer use. These measures will help to
protect the environment.
If your tablets become discoloured or show any signs of
deterioration, seek the advice of your pharmacist.

6. Contents of the pack and other information
What Targinact contains
The active ingredients in Targinact are oxycodone
hydrochloride and naloxone hydrochloride.
Each 10 mg/5 mg tablet contains 10 mg of oxycodone
hydrochloride (equivalent to 9 mg oxycodone), and 5.45
mg naloxone hydrochloride dihydrate (equivalent to 5 mg
naloxone hydrochloride and 4.5 mg naloxone).
The other ingredients are:
Tablet core: povidone K30, ethyl cellulose, stearyl alcohol,
lactose monohydrate, talc, magnesium stearate.
Tablet coat: polyvinyl alcohol, titanium dioxide (E171),
macrogol 3350, talc.
What Targinact looks like and contents of the pack
Targinact 10 mg/5 mg tablets are white, oblong, film coated
tablets, marked ‘OXN’ on one side and ‘10’ on the other.
Targinact tablets are available in pack sizes of 28 tablets.
Who makes and repackages your medicine?
Your medicine is manufactured by Bard Pharmaceuticals
Limited, Cambridge Science Park, Milton Road, Cambridge
CB4 0GW, UK. Procured from within the EU and repackaged
by Product Licence Holder: Primecrown Ltd., 4/5 Northolt
Trading Estate, Belvue Road, Northolt, Middlesex, UB5 5QS.
PL 10383/1997 Targinact 10 mg/5 mg prolonged-release
tablets

Leaflet date: 10.05.2017
Targinact is a registered trademark of Mundipharma AG
Basel, Switzerland.

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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