Chlorpheniramine is an antihistamine,
prescribed for allergic conditions such as itchy and watery eyes,
sneezing, runny nose, hay fever and common cold. It may also be used to
relieve the itching from insect bites and bee stings.
Clemastine is an antihistamine and
anticholinergic agent, prescribed for allergic rhinitis. It is also used
for uricaria and angioedema. This medication inhibits the effect of
histamines in the body.
Epinephrine is a hormone, recommended for
cardiac arrest (to restart the heart beat), dilation of blood vessels,
increase of diastolic blood pressure, increasing the flow of blood to
heart and anaphylactic shock (allergic reactions). It is effective in
controlling superficial bleeding and re
This medicine helps relieve mild to moderate pain such as
headache, migraine, neuralgia, backache, toothache, period pain; and
rheumatic and muscle pain. It is helpful if the pain disturbs your
sleep. The main ingredients in this medicine are paracetamol and
diphenhydramine which work together to help relieve pain and aid a
restful sleep. Paracetamol is a pain killer and helps relieve pain and
fever. Diphenhydramine is an antihistamine which works by blocking the
effects of histamine and causes drowsiness.
This medicine is available in the form tablets that are taken by
mouth. You should take this medicine 20 minutes before going to bed.
This medicine contains paracetamol. If you are taking other
medicines that contain paracetamol you must make sure that you do not
take more than the recommended daily dose of paracetamol. You should
also avoid taking other medicines that make you drowsy.
Do not take this medicine continuously for more than seven nights.
Consult your doctor if you have a persistent headache or if your
symptoms do not improve after taking this medicine for seven days, or if
they get worse during treatment with this medicine.
Before using Panadol Night
This medicine may not be suitable for everyone and some people
must never have it. Check the leaflet that comes with your medicine to
make sure that the medicine is suitable before having it.
Always get advice from a healthcare professional before taking this medicine if:
you are allergic or sensitive to or have had a reaction to any of the ingredients in the medicine
this medicine is for a child under 12 years of age
you are elderly
you have liver problems
you have kidney problems
you have pyloroduodenal obstruction
you have porphyria
you have heart and circulation problems
you have asthma, bronchitis, COPD or lung problems
you have myasthenia gravis
you have epilepsy or another condition that makes you prone to seizures
you have closed-angle glaucoma
you have an enlarged prostate gland
you have urinary retention
you have galactose intolerance
you have Lapp lactase deficiency
you have glucose-galactose malabsorption
you are taking other medicines that contain paracetamol
Medicines interactions
If you are taking more than one medicine they may interact with
each other. Before taking this medicine consult your doctor or
pharmacist if you are taking or have recently taken any other medicines
including vitamins supplements and herbal or complementary preparations.
The following medicines may interact with this medicine:
other medicines that contain paracetamol
cough and cold medicines
other antihistamines including preparations that are applied on the skin
metoclopramide
domperidone
cholestyramine
anticoagulants such as warfarin or other coumarins
monoamine oxidase inhibitors - you should not use this
medicine within two weeks of stopping a monoamine oxidase inhibitor or
while you are taking one
central nervous system depressants such as tranquilisers, hypnotics and anxiolytics
antimuscarinic medicines such as atropine or tricyclic antidepressants
medicines that are metabolised by cytochrome p450 such as metoprolol and venlafaxine
Possible side effects of Panadol Night
Most medicines can cause some side-effects but not everyone having the same medicine will get the same side-effects.
The following side-effects have been associated with people taking this medicine:
hypersensitivity reactions including anaphylaxis, skin rashes,
angioedema, urticaria, breathing difficulties, Stevens-Johnson syndrome
and toxic epidermal necrolysis
bronchospasm
liver problems
tiredness
confusion
paradoxical excitation including feelings of increased energy, nervousness and restlessness
dizziness
concentration problems
unsteadiness
convulsions
headache
blood and bone marrow problems
drowsiness or sedation
blurred vision
faster heart rate
palpitations
thickening of bronchial secretions
dry mouth
gastrointestinal disturbances including nausea and vomiting
muscle twitching
urinary retention
urinary difficulties
difficulty in co-ordinating movement
pins and needles sensations
Pregnancy and breast-feeding
If you are trying to become pregnant or are pregnant you should
seek medical advice before taking this medicine. Do not take this
medicine if you are breast-feeding.
Other important information
Make sure that you read the leaflet that comes with your medicine
to check what dose you should take and if there is anything that you
need to do if you take more than the recommended dose. If you are in any
doubt about whether this medicine is suitable for you, speak to your
doctor or pharmacist.
Seek immediate medical advice if you accidentally take an extra dose of this medicine even if you feel well.
This medicine may affect your ability to drive or operate
machinery. If this medicine affects you, you should not drive or operate
machinery.
This medicine may interact with alcohol. It is best to avoid alcoholic drinks while you are taking this medicine.
Keep all medicines out of the sight and reach of children.
AVELOX (moxifloxacin) hydrochloride is a synthetic broad
spectrum antibacterial agent for oral and intravenous administration.
Moxifloxacin, a fluoroquinolone, is available as the monohydrochloride salt of
1-cyclopropyl-7-[(S,S)2,8-diazabicyclo[4.3.0]non-8-yl]-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3
quinoline carboxylic acid. It is a slightly yellow to yellow crystalline
substance with a molecular weight of 437.9. Its empirical formula is C21H24FN3O4*HCl
and its chemical structure is as follows:
AVELOX Tablets
AVELOX Tablets are available as film-coated tablets
containing moxifloxacin hydrochloride (equivalent to 400 mg moxifloxacin).
The inactive ingredients are microcrystalline cellulose,
lactose monohydrate, croscarmellose sodium, magnesium stearate, hypromellose,
titanium dioxide, polyethylene glycol and ferric oxide.
AVELOX IV
AVELOX IV is available in ready-to-use 250 mL latex-free
flexibags as a sterile, preservative free, 0.8% sodium chloride aqueous
solution of moxifloxacin hydrochloride (containing 400 mg moxifloxacin) with pH
ranging from 4.1 to 4.6.
The appearance of the intravenous solution is yellow. The
color does not affect, nor is it indicative of, product stability.
The inactive ingredients are sodium chloride, USP, Water
for Injection, USP, and may include hydrochloric acid and/or sodium hydroxide
for pH adjustment.
AVELOX IV contains approximately 34.2 mEq (787 mg) of
sodium in 250 mL.
What are the possible side effects of moxifloxacin (Avelox)?
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Stop using moxifloxacin and call your doctor at once if you have a serious side effect such as:
severe dizziness, fainting, fast or pounding heartbeats;
sudden pain, snapping or popping sound, bruising, swelling, tenderness, stiffness, or loss of movement in any of your joints;
diarrhea that is watery or bloody;
confusion, hallucinations, depression, insomnia or nightmares, unusual...
What are the precautions when taking moxifloxacin hcl (Avelox)?
See also Warning section.
Before taking moxifloxacin, tell your doctor or pharmacist if you
are allergic to it; or to other quinolone antibiotics (such as
ciprofloxacin, levofloxacin); 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: diabetes, heart problems (such as
recent heart attack), joint/tendon problems (such as tendonitis,
bursitis), liver disease, myasthenia gravis, nerve problems (such as
peripheral neuropathy), seizure disorder, conditions that increase your
risk of seizures (such as brain/head injury, brain tumors, cerebral...
Levofloxacin is used to treat certain infections such as pneumonia,
chronic bronchitis and sinus, urinary tract, kidney, prostate (a male
reproductive gland), and skin infections. Levofloxacin is also used to
prevent anthrax (a serious infection that may be spread on purpose as
part of a bioterror attack) in people who may have been exposed to
anthrax germs in the air. Levofloxacin is in a class of antibiotics
called fluoroquinolones. It works by killing bacteria that cause
infections. Antibiotics will not work for colds, flu, or other viral
infections.
How should this medicine be used?
Levofloxacin comes as a tablet and a solution (liquid) to take by
mouth. It is usually taken once a day. The length of your treatment
depends on the type of infection you have. Your doctor will tell you how
long to take levofloxacin. The tablet may be taken with or without
food. The solution should be taken 1 hour before or 2 hours after
eating. Take levofloxacin at around the same time every day. Follow the
directions on your prescription label carefully, and ask your doctor or
pharmacist to explain any part you do not understand. Take levofloxacin
exactly as directed. Do not take more or less of it or take it more
often than prescribed by your doctor.
You should begin to feel better during the first few days of
treatment with levofloxacin. If your symptoms do not improve or if they
get worse, call your doctor.
Take levofloxacin until you finish the prescription, even if you feel
better. Do not stop taking levofloxacin without talking to your doctor
unless you experience certain serious side effects listed in the
IMPORTANT WARNING or SIDE EFFECTS sections. If you stop taking
levofloxacin too soon or skip doses, your infection may not be
completely treated and the bacteria may become resistant to antibiotics.
Other uses for this medicine
Levofloxacin is also sometimes used to treat endocarditis (infection
of the heart lining and valves), certain sexually transmitted diseases,
and tuberculosis (TB). Levofloxacin is also sometimes used to prevent or
treat traveler's diarrhea and plague (a serious infection that may be
spread on purpose as part of a bioterror attack). Talk to your doctor
about the risks of using this medication for your condition.
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before taking levofloxacin,
tell your doctor and pharmacist if you are allergic or have had a
severe reaction to levofloxacin; any other quinolone or fluoroquinolone
antibiotic such as ciprofloxacin (Cipro), gatifloxacin (Tequin) (not
available in the U.S.), gemifloxacin (Factive), lomefloxacin (Maxaquin)
(not available in the U.S.), moxifloxacin (Avelox), nalidixic acid
(NegGram), norfloxacin (Noroxin), ofloxacin (Floxin), and sparfloxacin
(Zagam) (not available in the U.S.): or any other medications, or if you
are allergic to any of the ingredients in levofloxacin tablets or
solution. Ask your pharmacist or check the Medication Guide for a list
of the ingredients.
tell your doctor and pharmacist what other prescription and
nonprescription medications, vitamins, nutritional supplements, and
herbal products you are taking or plan to take. Be sure to mention the
medications listed in the IMPORTANT WARNING section and any of the
following: anticoagulants ('blood thinners') such as warfarin (Coumadin,
Jantoven); certain antidepressants; antipsychotics (medications to
treat mental illness); cyclosporine (Gengraf, Neoral, Sandimmune);
diuretics ('water pills'); insulin; oral medications for diabetes such
as glyburide (DiaBeta, in Glucovance, Micronase, others); certain
medications for irregular heartbeat such as amiodarone (Cordarone),
procainamide (Procanbid), quinidine, and sotalol (Betapace, Betapace AF,
Sorine); nonsteroidal anti-inflammatory drugs (NSAIDs) such as
ibuprofen (Advil, Motrin, others) and naproxen (Aleve, Naprosyn,
others); tacrolimus (Prograf); or theophylline (Elixophyllin, Theo-24,
Uniphyl, others). Your doctor may need to change the doses of your
medications or monitor you carefully for side effects.
if you are taking antacids containing aluminum hydroxide or
magnesium hydroxide (Maalox, Mylanta, Tums, others), didanosine (Videx),
sucralfate (Carafate), or vitamin or mineral supplements that contain
iron or zinc, take these medications 2 hours before or after you take
levofloxacin.
tell your doctor if you or anyone in your family has or has ever had
a prolonged QT interval (a rare heart problem that may cause irregular
heartbeat, fainting, or sudden death) or an irregular heartbeat, and if
you have or have ever had nerve problems; a low level of potassium in
your blood; a slow heartbeat; cerebral arteriosclerosis (narrowing of
blood vessels in or near the brain that can lead to stroke or
mini-stroke); seizures; chest pain; or liver disease.
tell your doctor if you are pregnant, plan to become pregnant, or
are breast-feeding. If you become pregnant while taking levofloxacin,
call your doctor.
you should know that levofloxacin may cause confusion, dizziness,
lightheadedness, and tiredness. Do not drive a car, operate machinery,
or participate in activities requiring alertness or coordination until
you know how this medication affects you.
plan to avoid unnecessary or prolonged exposure to sunlight or
ultraviolet light (tanning beds and sunlamps) and to wear protective
clothing, sunglasses, and sunscreen. Levofloxacin may make your skin
sensitive to sunlight or ultraviolet light. If your skin becomes
reddened, swollen, or blistered, like a bad sunburn, call your doctor.
What special dietary instructions should I follow?
Make sure you drink plenty of water or other fluids every day while you are taking levofloxacin.
What should I do if I forget a dose?
Take the missed dose as soon as you remember it. However, if it is
almost time for the next dose, skip the missed dose and continue your
regular dosing schedule. Do not take a double dose to make up for a
missed one.
What side effects can this medication cause?
Levofloxacin may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
nausea
vomiting
diarrhea
stomach pain
constipation
heartburn
headache
vaginal itching and/or discharge
Some side effects can be serious. If you experience any of these
symptoms call your doctor immediately, but do not stop taking
levofloxacin without talking to your doctor:
severe diarrhea (watery or bloody stools) that may occur with or
without fever and stomach cramps (may occur up to 2 months or more after
your treatment)
dizziness
confusion
nervousness
restlessness
anxiety
not trusting others or feeling that others want to hurt you
difficulty falling asleep or staying asleep
nightmares or abnormal dreams
hallucinations (seeing things or hearing voices that do not exist)
depression
thoughts about dying or killing yourself
uncontrollable shaking of a part of the body
If you experience any of the following symptoms, or the symptoms of
tendinitis or tendon rupture described in the IMPORTANT WARNING section,
stop taking levofloxacin and call your doctor immediately or get
emergency medical help:
rash
hives
itching
peeling or blistering of the skin
fever
swelling of the eyes, face, mouth. lips, tongue, throat, hands, feet, ankles or lower legs
hoarseness
difficulty breathing or swallowing
fast heartbeat
fainting
loss of consciousness
yellowing of the skin or eyes
dark urine
decreased urination
seizures
unusual bruising or bleeding
joint or muscle pain
Levofloxacin may cause problems with bones, joints, and tissues
around joints in children. Levofloxacin should not normally be given to
children younger than 18 years of age unless they have been exposed to
anthrax in the air. If your doctor prescribes levofloxacin for your
child, be sure to tell the doctor if your child has or has ever had
joint-related problems. Call your doctor if your child develops joint
problems, such as pain or swelling, while taking levofloxacin or after
treatment with levofloxacin.
Levofloxacin may cause nerve damage that may not go away even after
you stop taking levofloxacin. This damage may occur soon after you begin
taking levofloxacin. If you experience any of the following symptoms,
call your doctor immediately: numbness, tingling, pain, or burning in
the arms or legs; or a change in your ability to feel light touch, pain,
heat, or cold. If you experience these symptoms, do not take any more
levofloxacin until you talk to your doctor. Your doctor may prescribe a
different antibiotic for you to take instead of levofloxacin.
Talk to your doctor about the risks of taking levofloxacin or giving levofloxacin to your child.
Levofloxacin may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your doctor may send a
report to the Food and Drug Administration's (FDA) MedWatch Adverse
Event Reporting program online
What should I know about storage and disposal of this medication?
Keep this medication in the container it came in, tightly closed, and
out of reach of children. Store it at room temperature and away from
excess heat and moisture (not in the bathroom). Throw away any
medication that is outdated or no longer needed. Talk to your pharmacist
about the proper disposal of your medication.
In case of emergency/overdose
In case of overdose, call your local poison control center at
1-800-222-1222. If the victim has collapsed or is not breathing, call
local emergency services at 911.
What other information should I know?
Keep all appointments with your doctor and the laboratory. Your
doctor may order certain lab tests to check your body's response to
levofloxacin.
Before having any laboratory test, tell your doctor and the laboratory personnel that you are taking levofloxacin.
Do not let anyone else take your medication. Your prescription is
probably not refillable. If you still have symptoms of infection after
you finish taking levofloxacin, call your doctor.
It is important for you to keep a written list of all of the
prescription and nonprescription (over-the-counter) medicines you are
taking, as well as any products such as vitamins, minerals, or other
dietary supplements. You should bring this list with you each time you
visit a doctor or if you are admitted to a hospital. It is also
important information to carry with you in case of emergencies.
Bacterial infections of the lungs (chest or lower respiratory tract infections), eg
bronchitis,
pneumonia.
Bacterial infections of the nasal passages, sinuses or throat
(upper respiratory tract infections) eg
sinusitis, pharyngitis.
Bacterial infections of the skin or soft tissue, eg cellulitis,
folliculitis or
erysipelas.
Bacterial infections of the middle ear (otitis
media).
Lyme disease.
Eradicating Helicobacter pylori bacteria from the gut in people
with
peptic
ulcers.
How do I take it?
The dose of this medicine and how long it needs to be taken for
depends on the type of infection you have and your age. 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.
Clarithromycin is usually taken twice a day (every 12 hours).
It can be taken either with or without food.
Klaricid adult sachets contain granules that should be mixed with a small amount of water before taking.
Bottles of Klaricid paediatric 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.
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!
Broad-spectrum antibiotics can sometimes cause inflammation of
the bowel (colitis). For this reason, if you get diarrhoea that becomes severe
or persistent or contains blood or mucus, either during or after taking this
medicine, you should consult your doctor immediately.
All antibiotics can sometimes result in overgrowth of organisms that
are not susceptible to the antibiotic, in particular fungi. You should
let your doctor know if you think you have developed any other
infections while you are taking this medicine, so that they can be
treated appropriately.
Klaricid paediatric suspension can be stored at room temperature
(below 30°C). Any suspension remaining after 14 days should be disposed
of, preferably by returning it to your pharmacist.
Use with caution in
Decreased kidney function.
Decreased liver function.
People with an abnormal heart rhythm seen on a
heart monitoring trace (ECG) as a 'prolonged QT
interval', or people at risk of this (your doctor will know).
Not to be used in
People allergic to other macrolide-type antibiotics, eg
erythromycin, azithromycin.
People taking astemizole, cisapride, pimozide, terfenadine or ergot
derivatives, eg ergotamine, dihydroergotamine.
Klaricid tablets and adult sachets are not suitable for children under 12 years of age.
Klaricid adult sachets and Klaricid paediatric suspensions contain
sucrose and are not suitable for people with rare hereditary problems of
fructose intolerance, glucose-galactose malabsorption or
sucrase-isomaltase insufficiency.
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 during pregnancy has not been
established. It should not be used in pregnant women unless the expected
benefit to the mother is greater than any possible risk to the developing baby. Seek
medical advice from your doctor.
This medicine passes into breast milk, but the effect on the
nursing infant is unknown. It should not be used in breastfeeding women unless
the expected benefit to the mother is greater than any possible risk to the
nursing infant. Seek medical advice from your doctor.
Label warnings
Take at regular intervals. Complete the prescribed course
unless otherwise directed.
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, it does not mean that all people using this medicine will experience that
or any side effect.
Disturbances of the gut such as diarrhoea, nausea, vomiting,
indigestion, abdominal pain.
Sore mouth or tongue.
Tongue or tooth discolouration.
Oral thrush (see warning section above).
Pins and needles sensations.
Headache.
Pain in the muscles or joints.
Disturbance of taste or smell.
Allergic skin reactions.
Dizziness.
Spinning sensation (vertigo).
Difficulty sleeping or bad dreams.
Confusion.
Reversible loss of hearing.
Inflammation of the large intestine (colitis) - see warning section above.
Low blood sugar (hypoglycaemia).
Liver or kidney disorders.
Abnormal heart beats (arrhythmias).
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.
Clarithromycin should not be taken by people who are taking any
of the following medicines, because clarithromycin can raise the blood levels of
these medicines, resulting in an increased risk of serious side effects:
astemizole
cisapride
dronedarone
eletriptan
eplerenone
ergot derivatives, eg ergotamine, dihydroergotamine or methysergide (used to treat
migraine)
everolimus
ivabradine
mizolastine
pimozide
ranolazine
saquinavir
simvastatin
terfenadine.
Clarithromycin may reduce the breakdown of the medicines listed
below. If the blood levels of these medicines are raised as a result, it
may lead to an increased risk of their side effects. If you are taking
one of these medicines and are prescribed clarithromycin you should let
your doctor or pharmacist know if you experience any new or increased
side effects:
alprazolam
aprepitant
bromocriptine
cabergoline
carbamazepine
ciclosporin
cilostazol
colchicine
digoxin
disopyramide
droperidol
etravirine
fesoterodine
itraconazole
maraviroc
methylprednisolone and possibly other corticosteroids
midazolam
nilotinib
pazopanib
phenytoin
quetiapine
reboxetine
repaglinide
rifabutin (increased risk of uveitis)
sildenafil
sirolimus
tacrolimus
tadalafil
theophylline
tolterodine
triazolam
vardenafil
verapamil
zopiclone.
Clarithromycin may also increase the blood levels and hence
anti-blood-clotting effects of the anticoagulants nicoumalone and warfarin. As
this may increase the risk of bleeding, people taking these combinations,
particularly elderly people, may need more frequent monitoring of their blood
clotting time (INR) so the dose of anticoagulant can be adjusted if necessary.
Clarithromycin may also increase the blood levels of
cholesterol-lowering medicines called statins, eg atorvastatin and simvastatin.
This may increase the risk of side effects on the muscles (myopathy) from these
medicines. Combined use of simvastatin and clarithromycin should be avoided.
Clarithromycin may decrease the absorption of zidovudine from
the gut. If you are taking both these medicines the clarithromycin should be
taken at least two hours before or after the zidovudine to avoid the
interaction. Ask your pharmacist for further advice.
There may be an increased risk of abnormal heart beats if
clarithromycin is taken in combination with any of the following
medicines:
anti-arrhythmic medicines (for an irregular heartbeat), eg amiodarone, disopyramide, quinidine
certain antimalarials, eg chloroquine, quinine, mefloquine, halofantrine
certain antipsychotics, eg chlorpromazine, thioridazine, fluphenazine, haloperidol.
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 this 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 taking 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 take 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 taking this antibiotic, you should
follow the instructions for vomiting and diarrhoea described in the
leaflet provided with your pills.
Ritonavir may increase the blood level of clarithromycin. This
is not normally a problem, but if you have kidney problems and are taking
ritonavir your doctor may prescribe you a lower than normal dose of
clarithromycin.
Augmentin contains a combination of amoxicillin and clavulanate
potassium. Amoxicillin is an antibiotic in a group of drugs called
penicillins. Amoxicillin fights bacteria in the body.
Clavulanate potassium is a form of clavulanic acid, which is similar
to penicillin. Clavulanate potassium fights bacteria that is often
resistant to penicillins and other antibiotics.
Augmentin is used to treat many different infections caused by
bacteria, such as sinusitis, pneumonia, ear infections, bronchitis,
urinary tract infections, and infections of the skin.
Augmentin may also be used for purposes not listed in this medication guide.
Important information
Do not use Augmentin if you are allergic to amoxicillin or
clavulanate potassium, or if you have ever had liver problems caused by
this medication. Do not use if you are allergic to any other penicillin
antibiotic, such as amoxicillin (Amoxil, Augmentin, Dispermox, Moxatag),
ampicillin (Principen, Unasyn), dicloxacillin (Dycill, Dynapen),
oxacillin (Bactocill), or penicillin (Bicillin L-A, PC Pen VK,
Pfizerpen), and others.
Before taking Augmentin, tell your doctor if you have liver disease
(or a history of hepatitis or jaundice), kidney disease, or
mononucleosis, or if you are allergic to a cephalosporin antibiotic,
such as cefdinir (Omnicef), cefprozil (Cefzil), cefuroxime (Ceftin),
cephalexin (Keflex), and others.
If you switch from one tablet form to another (regular, chewable, or
extended-release tablet), take only the new tablet form and strength
prescribed for you. This medicine may not be as effective or could be
harmful if you do not use the exact tablet form your doctor has
prescribed.
Amoxicillin and clavulanate potassium can pass into breast milk and
may harm a nursing baby. Do not use this medication without telling your
doctor if you are breast-feeding a baby. Augmentin can make birth
control pills less effective. Ask your doctor about using a non-hormone
method of birth control (such as a condom, diaphragm, spermicide) to
prevent pregnancy while taking Augmentin.
Before taking this medicine
Do not use Augmentin if you are allergic to amoxicillin or
clavulanate potassium, or if you have ever had liver problems caused by
this medication. Do not use if you are allergic to any other penicillin
antibiotic, such as amoxicillin (Amoxil, Augmentin, Dispermox, Moxatag),
ampicillin (Principen, Unasyn), dicloxacillin (Dycill, Dynapen),
oxacillin (Bactocill), or penicillin (Bicillin L-A, PC Pen VK,
Pfizerpen)), and others.
To make sure you can safely take this medicine, tell your doctor if you have any of these other conditions:
liver disease (or a history of hepatitis or jaundice);
kidney disease;
mononucleosis; or
if you are allergic to a cephalosporin antibiotic, such as cefdinir
(Omnicef), cefprozil (Cefzil), cefuroxime (Ceftin), cephalexin (Keflex),
and others.
FDA pregnancy category B. Augmentin is not expected to be harmful to
an unborn baby. Tell your doctor if you are pregnant or plan to become
pregnant during treatment. Augmentin can make birth control pills less
effective. Ask your doctor about using a non-hormone method of birth
control (such as a condom, diaphragm, spermicide) to prevent pregnancy
while taking Augmentin. Amoxicillin and clavulanate potassium can pass
into breast milk and may harm a nursing baby. Do not use Augmentin
without telling your doctor if you are breast-feeding a baby. See also: Pregnancy and breastfeeding warnings (in more detail)
The liquid and chewable tablet forms of this medication may contain
phenylalanine. Talk to your doctor before using these forms of Augmentin
if you have phenylketonuria (PKU).
How should I take Augmentin?
Take Augmentin exactly as prescribed by your doctor. Do not take in
larger or smaller amounts or for longer than recommended. Follow the
directions on your prescription label.
If you switch from one tablet form to another (regular, chewable, or
extended-release tablet), take only the new tablet form and strength
prescribed for you. The strength of clavulanate potassium is not the
same among the different tablet forms, even though the amount of
amoxicillin may be the same as in the tablet you were using before. This
medicine may not be as effective or could be harmful if you do not use
the exact tablet form your doctor has prescribed. Take this medicine
with a full glass of water. Take the medicine at the start of a meal to
reduce stomach upset.
Take the medicine at the same time each day.
The Augmentin tablet should be swallowed whole.
The Augmentin Chewable tablet must be chewed before swallowing. Do not swallow a chewable tablet whole.
Do not crush or chew the Augmentin XR (extended-release) tablet.
Swallow the pill whole, or break the pill in half and take both halves
one at a time. If you have trouble swallowing a whole or half pill, talk
with your doctor about using another form of Augmentin. Shake the
liquid form of this medicine well just before you measure a dose. To be
sure you get the correct dose, measure the liquid with a marked
measuring spoon or medicine cup, not with a regular table spoon. If you
do not have a dose-measuring device, ask your pharmacist for one.
Take Augmentin for the full prescribed length of time. Your symptoms
may improve before the infection is completely cleared. Skipping doses
may also increase your risk of further infection that is resistant to
antibiotics. Augmentin will not treat a viral infection such as the
common cold or flu.
Augmentin can cause false results with certain lab tests for glucose
(sugar) in the urine. Tell any doctor who treats you that you are using
Augmentin.
Store Augmentin tablets at room temperature away from moisture and
heat. Store Augmentin liquid in the refrigerator. Throw away any unused
liquid after 10 days.
What happens if I miss a dose?
Take the missed dose as soon as you remember. Skip the missed dose if
it is almost time for your next scheduled dose. Do not take extra
medicine to make up the missed dose.
What happens if I overdose?
Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.
Overdose can cause nausea, vomiting, stomach pain, diarrhea, skin rash, drowsiness, and hyperactivity.
What should I avoid?
Antibiotic medicines can cause diarrhea, which may be a sign of a new
infection. If you have diarrhea that is watery or has blood in it, stop
taking Augmentin and call your doctor. Do not use any medicine to stop
the diarrhea unless your doctor has told you to.
Augmentin side effects
Get emergency medical help if you have any of these signs of an
allergic reaction to Augmentin: hives; difficulty breathing; swelling of
your face, lips, tongue, or throat. Stop using this medicine and call
your doctor at once if you have a serious side effect such as:
diarrhea that is watery or has blood in it;
pale or yellowed skin, dark colored urine, fever, confusion or weakness;
easy bruising or bleeding;
skin rash, bruising, severe tingling, numbness, pain, muscle weakness;
agitation, confusion, unusual thoughts or behavior, seizure (convulsions);
nausea, upper stomach pain, itching, loss of appetite, dark urine,
clay-colored stools, jaundice (yellowing of the skin or eyes); or
severe skin reaction -- fever, sore throat, swelling in your face or
tongue, burning in your eyes, skin pain, followed by a red or purple
skin rash that spreads (especially in the face or upper body) and causes
blistering and peeling.
Left Ventricular Dysfunction Following Myocardial Infarction
Carvedilol tablets, USP are indicated
to reduce cardiovascular mortality in clinically stable patients who
have survived the acute phase of a myocardial infarction and have a left
ventricular ejection fraction of ≤40% (with or without symptomatic
heart failure)
Hypertension
Carvedilol tablets, USP are indicated for the management of essential hypertension. It can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics
2. DOSAGE AND ADMINISTRATION
Carvedilol should be taken with food to slow the rate of absorption and reduce the incidence of orthostatic effects.
Left Ventricular Dysfunction Following Myocardial Infarction
DOSAGE MUST BE INDIVIDUALIZED AND
MONITORED DURING UP-TITRATION. Treatment with Carvedilol tablets may be
started as an inpatient or outpatient and should be started after the
patient is hemodynamically stable and fluid retention has been
minimized. It is recommended that Carvedilol tablets be started at 6.25
mg twice daily and increased after 3 to 10 days, based on tolerability,
to 12.5 mg twice daily, then again to the target dose of 25 mg twice
daily. A lower starting dose may be used (3.125 mg twice daily) and/or
the rate of up-titration may be slowed if clinically indicated (e.g.,
due to low blood pressure or heart rate, or fluid retention). Patients
should be maintained on lower doses if higher doses are not tolerated.
The recommended dosing regimen need not be altered in patients who
received treatment with an IV or oral β-blocker during the acute phase
of the myocardial infarction.
DOSAGE MUST BE INDIVIDUALIZED. The
recommended starting dose of Carvedilol tablets is 6.25 mg twice daily.
If this dose is tolerated, using standing systolic pressure measured
about 1 hour after dosing as a guide, the dose should be maintained for 7
to 14 days, and then increased to 12.5 mg twice daily if needed, based
on trough blood pressure, again using standing systolic pressure one
hour after dosing as a guide for tolerance. This dose should also be
maintained for 7 to 14 days and can then be adjusted upward to 25 mg
twice daily if tolerated and needed. The full antihypertensive effect of
Carvedilol tablet is seen within 7 to 14 days. Total daily dose should
not exceed 50 mg.
Concomitant administration with a diuretic can be expected to produce
additive effects and exaggerate the orthostatic component of Carvedilol
action.
Hepatic Impairment
Carvedilol tablets should not be given to patients with severe hepatic impairment
3. DOSAGE FORMS AND STRENGTHS
The white to off-white, round,
film-coated tablets are available in the following strengths: 3.125 mg–
debossed with Z and 1, 6.25 mg–debossed with ZC40, 12.5 mg–debossed with
ZC41 and 25 mg–debossed with ZC42.
4. CONTRAINDICATIONS
Carvedilol tablets are contraindicated in the following conditions:
Bronchial asthma or related bronchospastic conditions. Deaths from
status asthmaticus have been reported following single doses of
Carvedilol tablets.
Second- or third-degree AV block
Sick sinus syndrome
Severe bradycardia (unless a permanent pacemaker is in place)
Patients with cardiogenic shock or who have decompensated heart
failure requiring the use of intravenous inotropic therapy. Such
patients should first be weaned from intravenous therapy before
initiating Carvedilol tablets
Patients with severe hepatic impairment
Patients with a history of a serious hypersensitivity reaction
(e.g., Stevens-Johnson syndrome, anaphylactic reaction, angioedema) to
Carvedilol, any of the components of Carvedilol tablets.
5. WARNINGS AND PRECAUTIONS
Cessation of Therapy
Patients with
coronary artery disease, who are being treated with Carvedilol tablets,
should be advised against abrupt discontinuation of therapy. Severe
exacerbation of angina and the occurrence of myocardial infarction and
ventricular arrhythmias have been reported in angina patients following
the abrupt discontinuation of therapy with β-blockers. The last 2
complications may occur with or without preceding exacerbation of the
angina pectoris. As with other β-blockers, when discontinuation of
Carvedilol tablets is planned, the patients should be carefully observed
and advised to limit physical activity to a minimum. Carvedilol tablets
should be discontinued over 1 to 2 weeks whenever possible. If the
angina worsens or acute coronary insufficiency develops, it is
recommended that Carvedilol tablets be promptly reinstituted, at least
temporarily. Because coronary artery disease is common and may be
unrecognized, it may be prudent not to discontinue therapy with
Carvedilol abruptly even in patients treated only for hypertension or
heart failure.
Bradycardia
In clinical trials, Carvedilol
tablets caused bradycardia in about 2% of hypertensive patients, and
6.5% of myocardial infarction patients with left ventricular
dysfunction. If pulse rate drops below 55 beats/minute, the dosage
should be reduced.
Hypotension
Postural hypotension occurred in 1.8%
and syncope in 0.1% of hypertensive patients, primarily following the
initial dose or at the time of dose increase and was a cause for
discontinuation of therapy in 1% of patients.
In the CAPRICORN study of survivors of an acute myocardial
infarction, hypotension or postural hypotension occurred in 20.2% of
patients receiving Carvedilol tablets compared to 12.6% of placebo
patients. Syncope was reported in 3.9% and 1.9% of patients,
respectively. These events were a cause for discontinuation of therapy
in 2.5% of patients receiving Carvedilol tablets, compared to 0.2% of
placebo patients.
Starting with a low dose, administration with food, and gradual
up-titration should decrease the likelihood of syncope or excessive
hypotension.
During initiation of therapy, the patient should be cautioned to avoid
situations such as driving or hazardous tasks, where injury could result
should syncope occur.
Heart Failure/Fluid Retention
Worsening heart failure or fluid
retention may occur during up-titration of Carvedilol. If such symptoms
occur, diuretics should be increased and the Carvedilol dose should not
be advanced until clinical stability resumes [see DOSAGE AND ADMINISTRATION (2)].
Occasionally it is necessary to lower the Carvedilol dose or
temporarily discontinue it. Such episodes do not preclude subsequent
successful titration of, or a favorable response to, Carvedilol.
Non-allergic Bronchospasm
Patients with bronchospastic disease
(e.g., chronic bronchitis and emphysema) should, in general, not receive
β-blockers. Carvedilol tablets may be used with caution, however, in
patients who do not respond to, or cannot tolerate, other
antihypertensive agents. It is prudent, if Carvedilol tablets are used,
to use the smallest effective dose, so that inhibition of endogenous or
exogenous β-agonists is minimized.
In clinical trials, patients with bronchospastic disease were
enrolled if they did not require oral or inhaled medication to treat
their bronchospastic disease. In such patients, it is recommended that
Carvedilol be used with caution. The dosing recommendations should be
followed closely and the dose should be lowered if any evidence of
bronchospasm is observed during up-titration.
Glycemic Control in Type 2 Diabetes
In general, β-blockers may mask some
of the manifestations of hypoglycemia, particularly tachycardia.
Nonselective β-blockers may potentiate insulin-induced hypoglycemia and
delay recovery of serum glucose levels. Patients subject to spontaneous
hypoglycemia, or diabetic patients receiving insulin or oral
hypoglycemic agents, should be cautioned about these possibilities.
Studies designed to examine the effects of Carvedilol on glycemic
control in patients with diabetes and heart failure have not been
conducted.
In a study designed to examine the effects of Carvedilol on glycemic
control in a population with mild-to-moderate hypertension and
well-controlled type 2 diabetes mellitus, Carvedilol had no adverse
effect on glycemic control, based on HbA1c measurements [see CLINICAL STUDIES (14.4)].
Peripheral Vascular Disease
β-blockers can precipitate or
aggravate symptoms of arterial insufficiency in patients with peripheral
vascular disease. Caution should be exercised in such individuals.
Deterioration of Renal Function
Rarely, use of Carvedilol in patients
with heart failure has resulted in deterioration of renal function.
Patients at risk appear to be those with low blood pressure (systolic
blood pressure <100 mm Hg), ischemic heart disease and diffuse
vascular disease, and/or underlying renal insufficiency. Renal function
has returned to baseline when Carvedilol was stopped. In patients with
these risk factors it is recommended that renal function be monitored
during up-titration of Carvedilol and the drug discontinued or dosage
reduced if worsening of renal function occurs.
Major Surgery
Chronically
administered beta-blocking therapy should not be routinely withdrawn
prior to major surgery; however, the impaired ability of the heart to
respond to reflex adrenergic stimuli may augment the risks of general
anesthesia and surgical procedures.
Thyrotoxicosis
β-adrenergic blockade may mask
clinical signs of hyperthyroidism, such as tachycardia. Abrupt
withdrawal of β-blockade may be followed by an exacerbation of the
symptoms of hyperthyroidism or may precipitate thyroid storm.
Pheochromocytoma
In patients with pheochromocytoma, an
α-blocking agent should be initiated prior to the use of any β-blocking
agent. Although Carvedilol has both α- and β-blocking pharmacologic
activities, there has been no experience with its use in this condition.
Therefore, caution should be taken in the administration of Carvedilol
to patients suspected of having pheochromocytoma.
Prinzmetal’s Variant Angina
Agents with non-selective β-blocking
activity may provoke chest pain in patients with Prinzmetal's variant
angina. There has been no clinical experience with Carvedilol in these
patients although the α-blocking activity may prevent such symptoms.
However, caution should be taken in the administration of Carvedilol to
patients suspected of having Prinzmetal's variant angina.
Risk of Anaphylactic Reaction
While taking β-blockers, patients
with a history of severe anaphylactic reaction to a variety of allergens
may be more reactive to repeated challenge, either accidental,
diagnostic, or therapeutic. Such patients may be unresponsive to the
usual doses of epinephrine used to treat allergic reaction.
Intraoperative Floppy Iris Syndrome
Intraoperative
Floppy Iris Syndrome (IFIS) has been observed during cataract surgery
in some patients treated with alpha-1 blockers (Carvedilol is an
alpha/beta blocker). This variant of small pupil syndrome is
characterized by the combination of a flaccid iris that billows in
response to intraoperative irrigation currents, progressive
intraoperative miosis despite preoperative dilation with standard
mydriatic drugs, and potential prolapse of the iris toward the
phacoemulsification incisions. The patient's ophthalmologist should be
prepared for possible modifications to the surgical technique, such as
utilization of iris hooks, iris dilator rings, or viscoelastic
substances. There does not appear to be a benefit of stopping alpha-1
blocker therapy prior to cataract surgery.
6. ADVERSE REACTIONS
Clinical Studies Experience
Carvedilol tablets have been
evaluated for safety in patients with left ventricular dysfunction
following myocardial infarction and in hypertensive patients. The
observed adverse event profile was consistent with the pharmacology of
the drug and the health status of the patients in the clinical trials.
Adverse events reported for each of these patient populations are
provided below. Excluded are adverse events considered too general to be
informative, and those not reasonably associated with the use of the
drug because they were associated with the condition being treated or
are very common in the treated population. Rates of adverse events were
generally similar across demographic subsets (men and women, elderly and
non-elderly, blacks and non-blacks).
Left Ventricular Dysfunction Following Myocardial Infarction:
Carvedilol tablets have been evaluated for safety in survivors of an
acute myocardial infarction with left ventricular dysfunction in the
CAPRICORN trial which involved 969 patients who received Carvedilol
tablets and 980 who received placebo. Approximately 75% of the patients
received Carvedilol tablets for at least 6 months and 53% received
Carvedilol tablets for at least 12 months. Patients were treated for an
average of 12.9 months and 12.8 months with Carvedilol tablets and
placebo, respectively.
The following adverse events were reported with a frequency of >1%
but ≤3% and more frequently with Carvedilol tablets: flu syndrome,
cerebrovascular accident, peripheral vascular disorder, hypotonia,
depression, gastrointestinal pain, arthritis, and gout. The overall
rates of discontinuations due to adverse events were similar in both
groups of patients. In this database, the only cause of discontinuation
>1%, and occurring more often on Carvedilol was hypotension (1.5% on
Carvedilol, 0.2% on placebo). Hypertension:
Carvedilol tablets have been evaluated for safety in hypertension in
more than 2,193 patients in US clinical trials and in 2,976 patients in
international clinical trials. Approximately 36% of the total treated
population received Carvedilol tablets for at least 6 months. Most
adverse events reported during therapy with Carvedilol tablets were of
mild to moderate severity. In US controlled clinical trials directly
comparing Carvedilol tablets in doses up to 50 mg (n = 1,142) to placebo
(n = 462), 4.9% of patients receiving Carvedilol tablets discontinued
for adverse events versus 5.2% of placebo patients. Although there was
no overall difference in discontinuation rates, discontinuations were
more common in the Carvedilol group for postural hypotension (1% versus
0). The overall incidence of adverse events in US placebo-controlled
trials increased with increasing dose of Carvedilol tablets. For
individual adverse events this could only be distinguished for
dizziness, which increased in frequency from 2% to 5% as total daily
dose increased from 6.25 mg to 50 mg.
Table 1 shows adverse events in US placebo-controlled clinical trials
for hypertension that occurred with an incidence of >1% regardless
of causality, and that were more frequent in drug-treated patients than
placebo-treated patients.
Table 1 Adverse Events (%) Occurring in US Placebo-Controlled Hypertension Trials (Incidence ≥1%, Regardless of Causality)
Shown are events with rate >1% rounded to nearest integer.
Cardiovascular
Bradycardia
2
-
Postural hypotension
2
-
Peripheral edema
1
-
Central Nervous System
Dizziness
6
5
Insomnia
2
1
Gastrointestinal
Diarrhea
2
1
Hematologic
Thrombocytopenia
1
-
Metabolic
Hypertriglyceridemia
1
-
Dyspnea and fatigue were also reported in these studies, but the rates were equal or greater in patients who received placebo.
The following adverse events not described above were reported as
possibly or probably related to Carvedilol tablets in worldwide open or
controlled trials with Carvedilol tablets in patients with hypertension. Incidence >0.1% to ≤1% Cardiovascular:
Peripheral ischemia, tachycardia. Central and Peripheral Nervous System:
Hypokinesia. Gastrointestinal:
Bilirubinemia, increased hepatic enzymes (0.2% of hypertension
patients were discontinued from therapy because of increases in hepatic
enzymes) Psychiatric:
Nervousness, sleep disorder, aggravated depression, impaired concentration, abnormal thinking, paroniria, emotional lability. Respiratory System:
Asthma Reproductive, male:
Decreased libido. Skin and Appendages:
Pruritus, rash erythematous, rash maculopapular, rash psoriaform, photosensitivity reaction. Special Senses:
Tinnitus. Urinary System:
Micturition frequency increased. Autonomic Nervous System:
Dry mouth, sweating increased. Metabolic and Nutritional:
Hypokalemia, hypertriglyceridemia. Hematologic:
Anemia, leukopenia.
The following events were reported in ≤0.1% of patients and are
potentially important: Complete AV block, bundle branch block,
myocardial ischemia, cerebrovascular disorder, convulsions, migraine,
neuralgia, paresis, anaphylactoid reaction, alopecia, exfoliative
dermatitis, amnesia, GI hemorrhage, bronchospasm, pulmonary edema,
decreased hearing, respiratory alkalosis, increased BUN, decreased HDL,
pancytopenia, and atypical lymphocytes.
Laboratory Abnormalities
Reversible elevations in serum
transaminases (ALT or AST) have been observed during treatment with
Carvedilol tablets. Rates of transaminase elevations (2- to 3-times the
upper limit of normal) observed during controlled clinical trials have
generally been similar between patients treated with Carvedilol tablets
and those treated with placebo. However, transaminase elevations,
confirmed by rechallenge, have been observed with Carvedilol tablets. In
a long-term, placebo-controlled trial in severe heart failure, patients
treated with Carvedilol tablets had lower values for hepatic
transaminases than patients treated with placebo, possibly because
improvements in cardiac function induced by Carvedilol led to less
hepatic congestion and/or improved hepatic blood flow.
Carvedilol tablets have not been associated with clinically
significant changes in serum potassium, total triglycerides, total
cholesterol, HDL cholesterol, uric acid, blood urea nitrogen, or
creatinine. No clinically relevant changes were noted in fasting serum
glucose in hypertensive patients.
Postmarketing Experience
The following adverse reactions have
been identified during post-approval use of Carvedilol tablets. Because
these reactions are reported voluntarily from a population of uncertain
size, it is not always possible to reliably estimate their frequency or
establish a causal relationship to drug exposure.
Blood and Lymphatic System Disorders
Aplastic anemia. Immune System Disorders
Hypersensitivity (e.g., anaphylactic reactions, angioedema, urticaria). Renal and Urinary Disorders
Urinary incontinence. Respiratory, Thoracic and Mediastinal Disorders
Interstitial pneumonitis. Skin and Subcutaneous Tissue Disorders
Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.
7. DRUG INTERACTIONS
CYP2D6 Inhibitors and Poor Metabolizers
Interactions of Carvedilol with
potent inhibitors of CYP2D6 isoenzyme (such as quinidine, fluoxetine,
paroxetine, and propafenone) have not been studied, but these drugs
would be expected to increase blood levels of the R(+) enantiomer of
Carvedilol.
Retrospective analysis of side effects in clinical trials showed that
poor 2D6 metabolizers had a higher rate of dizziness during
up-titration, presumably resulting from vasodilating effects of the
higher concentrations of the α-blocking R(+) enantiomer.
Hypotensive Agents
Patients taking both agents with
β-blocking properties and a drug that can deplete catecholamines (e.g.,
reserpine and monoamine oxidase inhibitors) should be observed closely
for signs of hypotension and/or severe bradycardia. Concomitant
administration of clonidine with agents with β-blocking properties may
potentiate blood-pressure and heart-rate-lowering effects. When
concomitant treatment with agents with β-blocking properties and
clonidine is to be terminated, the β-blocking agent should be
discontinued first. Clonidine therapy can then be discontinued several
days later by gradually decreasing the dosage.
Cyclosporine
Modest increases in mean trough
cyclosporine concentrations were observed following initiation of
Carvedilol treatment in 21 renal transplant patients suffering from
chronic vascular rejection. In about 30% of patients, the dose of
cyclosporine had to be reduced in order to maintain cyclosporine
concentrations within the therapeutic range, while in the remainder no
adjustment was needed. On the average for the group, the dose of
cyclosporine was reduced about 20% in these patients. Due to wide
interindividual variability in the dose adjustment required, it is
recommended that cyclosporine concentrations be monitored closely after
initiation of Carvedilol therapy and that the dose of cyclosporine be
adjusted as appropriate.
Digitalis Glycosides
Both digitalis glycosides and
β-blockers slow atrioventricular conduction and decrease heart rate.
Concomitant use can increase the risk of bradycardia. Digoxin
concentrations are increased by about 15% when digoxin and Carvedilol
are administered concomitantly. Therefore, increased monitoring of
digoxin is recommended when initiating, adjusting, or discontinuing
Carvedilol tablets
Inducers/Inhibitors of Hepatic Metabolism
Rifampin reduced plasma concentrations of Carvedilol by about 70% Cimetidine increased AUC by about 30% but caused no change in Cmax.
Amiodarone
Amiodarone, and its metabolite
desethyl amiodarone, inhibitors of CYP2C9 and P385 glycoprotein,
increased concentrations of the S(-) enantiomer of Carvedilol by at
least 2-fold
The concomitant administration of amiodarone or other CYP2C9 inhibitors
such as fluconazole with Carvedilol may enhance the β-blocking
properties of Carvedilol resulting in further slowing of the heart rate
or cardiac conduction. Patients should be observed for signs of
bradycardia or heart block, particularly when one agent is added to
pre-existing treatment with the other.
Calcium Channel Blockers
Conduction disturbance (rarely with
hemodynamic compromise) has been observed when Carvedilol tablet is
co-administered with diltiazem. As with other agents with β-blocking
properties, if Carvedilol tablet is to be administered with calcium
channel blockers of the verapamil or diltiazem type, it is recommended
that ECG and blood pressure be monitored.
Insulin or Oral Hypoglycemics
Agents with β-blocking properties may
enhance the blood-sugar-reducing effect of insulin and oral
hypoglycemics. Therefore, in patients taking insulin or oral
hypoglycemics, regular monitoring of blood glucose is recommended
Anesthesia
If treatment with Carvedilol
extended-release capsules is to be continued perioperatively, particular
care should be taken when anesthetic agents which depress myocardial
function, such as ether, cyclopropane, and trichloroethylene, are used
[see OVERDOSAGE (10)].
8. USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category C. Studies
performed in pregnant rats and rabbits given Carvedilol revealed
increased post-implantation loss in rats at doses of 300 mg/kg/day (50
times the maximum recommended human dose [MRHD] as mg/m2) and in rabbits at doses of 75 mg/kg/day (25 times the MRHD as mg/m2).
In the rats, there was also a decrease in fetal body weight at the
maternally toxic dose of 300 mg/kg/day (50 times the MRHD as mg/m2),
which was accompanied by an elevation in the frequency of fetuses with
delayed skeletal development (missing or stunted 13th rib). In rats the
no-observed-effect level for developmental toxicity was 60 mg/kg/day (10
times the MRHD as mg/m2); in rabbits it was 15 mg/kg/day (5 times the MRHD as mg/m2).
There are no adequate and well-controlled studies in pregnant women.
Carvedilol tablets should be used during pregnancy only if the potential
benefit justifies the potential risk to the fetus.
Nursing Mothers
It is not known whether this drug is
excreted in human milk. Studies in rats have shown that Carvedilol
and/or its metabolites (as well as other β-blockers) cross the placental
barrier and are excreted in breast milk. There was increased mortality
at one week post-partum in neonates from rats treated with 60 mg/kg/day
(10 times the MRHD as mg/m2) and above during
the last trimester through day 22 of lactation. Because many drugs are
excreted in human milk and because of the potential for serious adverse
reactions in nursing infants from β-blockers, especially bradycardia, a
decision should be made whether to discontinue nursing or to discontinue
the drug, taking into account the importance of the drug to the mother.
The effects of other α- and β-blocking agents have included perinatal
and neonatal distress.
Pediatric Use
Effectiveness of Carvedilol tablets in patients younger than 18 years of age has not been established.
In a double-blind trial, 161 children (mean age 6 years, range 2
months to 17 years; 45% less than 2 years old) with chronic heart
failure [NYHA class II-IV, left ventricular ejection fraction <40%
for children with a systemic left ventricle (LV), and moderate-severe
ventricular dysfunction qualitatively by echo for those with a systemic
ventricle that was not an LV] who were receiving standard background
treatment were randomized to placebo or to 2 dose levels of Carvedilol.
These dose levels produced placebo-corrected heart rate reduction of 4-6
heart beats per minute, indicative of β-blockade activity. Exposure
appeared to be lower in pediatric subjects than adults. After 8 months
of follow-up, there was no significant effect of treatment on clinical
outcomes. Adverse reactions in this trial that occurred in greater than
10% of patients treated with Carvedilol and at twice the rate of
placebo-treated patients included chest pain (17% versus 6%), dizziness
(13% versus 2%), and dyspnea (11% versus 0%).
Geriatric Use
Of the 975 myocardial infarction
patients randomized to Carvedilol tablets in the CAPRICORN trial, 48%
(468) were 65 years of age or older, and 11% (111) were 75 years of age
or older.
Of the 2,065 hypertensive patients in US clinical trials of efficacy
or safety who were treated with Carvedilol tablets, 21% (436) were 65
years of age or older. Of 3,722 patients receiving Carvedilol tablets in
hypertension clinical trials conducted worldwide, 24% were 65 years of
age or older.
With the exception of dizziness in hypertensive patients (incidence
8.8% in the elderly versus 6% in younger patients), no overall
differences in the safety or effectiveness (see Figure 2)
were observed between the older subjects and younger subjects in each
of these populations. Similarly, other reported clinical experience has
not identified differences in responses between the elderly and younger
subjects, but greater sensitivity of some older individuals cannot be
ruled out.
10. OVERDOSAGE
Overdosage may cause severe
hypotension, bradycardia, cardiac insufficiency, cardiogenic shock, and
cardiac arrest. Respiratory problems, bronchospasms, vomiting, lapses of
consciousness, and generalized seizures may also occur.
The patient should be placed in a supine position and, where
necessary, kept under observation and treated under intensive-care
conditions. Gastric lavage or pharmacologically induced emesis may be
used shortly after ingestion. The following agents may be administered: for excessive bradycardia: Atropine, 2 mg IV. to support cardiovascular function:
Glucagon, 5 to 10 mg IV rapidly over 30 seconds, followed by a
continuous infusion of 5 mg/hour; sympathomimetics (dobutamine,
isoprenaline, adrenaline) at doses according to body weight and effect.
If peripheral vasodilation dominates, it may be necessary to
administer adrenaline or noradrenaline with continuous monitoring of
circulatory conditions. For therapy-resistant bradycardia, pacemaker
therapy should be performed. For bronchospasm, β-sympathomimetics (as
aerosol or IV) or aminophylline IV should be given. In the event of
seizures, slow IV injection of diazepam or clonazepam is recommended.
NOTE: In the event of severe intoxication where there are symptoms of
shock, treatment with antidotes must be continued for a sufficiently
long period of time consistent with the 7- to 10-hour half-life of
Carvedilol.
Cases of overdosage with Carvedilol tablets alone or in combination
with other drugs have been reported. Quantities ingested in some cases
exceeded 1,000 milligrams. Symptoms experienced included low blood
pressure and heart rate. Standard supportive treatment was provided and
individuals recovered.
11. DESCRIPTION
Carvedilol is a nonselective β-adrenergic blocking agent with α1-blocking
activity. It is
(±)-1-(Carbazol-4-yloxy)-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol.
Carvedilol is a racemic mixture with the following structure:
Carvedilol, USP is a white to almost white crystalline powder with a molecular weight of 406.5 and a molecular formula of C24H26N2O4.
It is freely soluble in dimethylsulfoxide; soluble in methylene
chloride and methanol; sparingly soluble in 95% ethanol and isopropanol;
slightly soluble in ethyl ether; and practically insoluble in water,
gastric fluid (simulated, TS, pH 1.1), and intestinal fluid (simulated,
TS without pancreatin, pH 7.5).
Each Carvedilol tablet, USP intended for oral administration contains
3.125 mg or 6.25 mg or 12.5 mg or 25 mg of Carvedilol. In addition,
each tablet contains the following inactive ingredients: colloidal
silicon dioxide, crospovidone, hypromellose, lactose monohydrate,
magnesium stearate, polyethylene glycol, povidone, talc, and titanium
dioxide.
The product meets USP Dissolution Test 3.
12. CLINICAL PHARMACOLOGY
Mechanism of Action
Carvedilol is a racemic mixture in which nonselective β-adrenoreceptor blocking activity is present in the S(-) enantiomer and α1-adrenergic
blocking activity is present in both R(+) and S(-) enantiomers at equal
potency. Carvedilol has no intrinsic sympathomimetic activity.
Pharmacodynamics
Left Ventricular Dysfunction Following Myocardial Infarction:
The basis for the beneficial effects of Carvedilol tablets in
patients with left ventricular dysfunction following an acute myocardial
infarction is not established. Hypertension:
The mechanism by which β-blockade produces an antihypertensive effect has not been established.
β-adrenoreceptor blocking activity has been demonstrated in animal
and human studies showing that Carvedilol (1) reduces cardiac output in
normal subjects; (2) reduces exercise- and/or isoproterenol-induced
tachycardia; and (3) reduces reflex orthostatic tachycardia. Significant
β-adrenoreceptor blocking effect is usually seen within 1 hour of drug
administration.
α1-adrenoreceptor blocking activity has been
demonstrated in human and animal studies, showing that Carvedilol (1)
attenuates the pressor effects of phenylephrine; (2) causes
vasodilation; and (3) reduces peripheral vascular resistance. These
effects contribute to the reduction of blood pressure and usually are
seen within 30 minutes of drug administration.
Due to the α1-receptor blocking activity of
Carvedilol, blood pressure is lowered more in the standing than in the
supine position, and symptoms of postural hypotension (1.8%), including
rare instances of syncope, can occur. Following oral administration,
when postural hypotension has occurred, it has been transient and is
uncommon when Carvedilol tablets is administered with food at the
recommended starting dose and titration increments are closely followed
In hypertensive patients with normal renal function, therapeutic
doses of Carvedilol tablets decreased renal vascular resistance with no
change in glomerular filtration rate or renal plasma flow. Changes in
excretion of sodium, potassium, uric acid, and phosphorus in
hypertensive patients with normal renal function were similar after
Carvedilol tablets and placebo.
Carvedilol tablets have little effect on plasma catecholamines,
plasma aldosterone, or electrolyte levels, but it does significantly
reduce plasma renin activity when given for at least 4 weeks. It also
increases levels of atrial natriuretic peptide.
Pharmacokinetics
Carvedilol is rapidly and extensively
absorbed following oral administration, with absolute bioavailability
of approximately 25% to 35% due to a significant degree of first-pass
metabolism. Following oral administration, the apparent mean terminal
elimination half-life of Carvedilol generally ranges from 7 to 10 hours.
Plasma concentrations achieved are proportional to the oral dose
administered. When administered with food, the rate of absorption is
slowed, as evidenced by a delay in the time to reach peak plasma levels,
with no significant difference in extent of bioavailability. Taking
Carvedilol tablets with food should minimize the risk of orthostatic
hypotension.
Carvedilol is extensively metabolized. Following oral administration
of radiolabelled Carvedilol to healthy volunteers, Carvedilol accounted
for only about 7% of the total radioactivity in plasma as measured by
area under the curve (AUC). Less than 2% of the dose was excreted
unchanged in the urine. Carvedilol is metabolized primarily by aromatic
ring oxidation and glucuronidation. The oxidative metabolites are
further metabolized by conjugation via glucuronidation and sulfation.
The metabolites of Carvedilol are excreted primarily via the bile into
the feces. Demethylation and hydroxylation at the phenol ring produce 3
active metabolites with β-receptor blocking activity. Based on
preclinical studies, the 4'-hydroxyphenyl metabolite is approximately 13
times more potent than Carvedilol for β-blockade.
Compared to Carvedilol, the 3 active metabolites exhibit weak
vasodilating activity. Plasma concentrations of the active metabolites
are about one-tenth of those observed for Carvedilol and have
pharmacokinetics similar to the parent.
Carvedilol undergoes stereoselective first-pass metabolism with
plasma levels of R(+)-Carvedilol approximately 2 to 3 times higher than
S(-)-Carvedilol following oral administration in healthy subjects. The
mean apparent terminal elimination half-lives for R(+)-Carvedilol range
from 5 to 9 hours compared with 7 to 11 hours for the S(-)-enantiomer.
The primary P450 enzymes responsible for the metabolism of both R(+)
and S(-)-Carvedilol in human liver microsomes were CYP2D6 and CYP2C9 and
to a lesser extent CYP3A4, 2C19, 1A2, and 2E1. CYP2D6 is thought to be
the major enzyme in the 4'- and 5'-hydroxylation of Carvedilol, with a
potential contribution from 3A4. CYP2C9 is thought to be of primary
importance in the O-methylation pathway of S(-)-Carvedilol.
Carvedilol is subject to the effects of genetic polymorphism with
poor metabolizers of debrisoquin (a marker for cytochrome P450 2D6)
exhibiting 2- to 3-fold higher plasma concentrations of R(+)-Carvedilol
compared to extensive metabolizers. In contrast, plasma levels of
S(-)-Carvedilol are increased only about 20% to 25% in poor
metabolizers, indicating this enantiomer is metabolized to a lesser
extent by cytochrome P450 2D6 than R(+)-Carvedilol. The pharmacokinetics
of Carvedilol do not appear to be different in poor metabolizers of
S-mephenytoin (patients deficient in cytochrome P450 2C19).
Carvedilol is more than 98% bound to plasma proteins, primarily with
albumin. The plasma-protein binding is independent of concentration over
the therapeutic range. Carvedilol is a basic, lipophilic compound with a
steady-state volume of distribution of approximately 115 L, indicating
substantial distribution into extravascular tissues. Plasma clearance
ranges from 500 to 700 mL/min.
Specific Populations
Geriatric:
Plasma levels of Carvedilol average about 50% higher in the elderly compared to young subjects. Hepatic Impairment:
Compared to healthy subjects, patients with severe liver impairment
(cirrhosis) exhibit a 4- to 7-fold increase in Carvedilol levels.
Carvedilol is contraindicated in patients with severe liver impairment. Renal Impairment:
Although Carvedilol is metabolized primarily by the liver, plasma
concentrations of Carvedilol have been reported to be increased in
patients with renal impairment. Based on mean AUC data, approximately
40% to 50% higher plasma concentrations of Carvedilol were observed in
hypertensive patients with moderate to severe renal impairment compared
to a control group of hypertensive patients with normal renal function.
However, the ranges of AUC values were similar for both groups. Changes
in mean peak plasma levels were less pronounced, approximately 12% to
26% higher in patients with impaired renal function.
Consistent with its high degree of plasma protein-binding, Carvedilol
does not appear to be cleared significantly by hemodialysis.
Drug-Drug Interactions
Since Carvedilol undergoes
substantial oxidative metabolism, the metabolism and pharmacokinetics of
Carvedilol may be affected by induction or inhibition of cytochrome
P450 enzymes.
Amiodarone:
In a pharmacokinetic study conducted in 106 Japanese patients with
heart failure, coadministration of small loading and maintenance doses
of amiodarone with Carvedilol resulted in at least a 2-fold increase in
the steady-state trough concentrations of S(-) Carvedilol Cimetidine:
In a pharmacokinetic study conducted in 10 healthy male subjects,
cimetidine (1,000 mg/day) increased the steady-state AUC of Carvedilol
by 30% with no change in Cmax Digoxin:
Following concomitant administration of Carvedilol (25 mg once daily)
and digoxin (0.25 mg once daily) for 14 days, steady-state AUC and
trough concentrations of digoxin were increased by 14% and 16%,
respectively, in 12 hypertensive patients Glyburide:
In 12 healthy subjects, combined administration of Carvedilol (25 mg
once daily) and a single dose of glyburide did not result in a
clinically relevant pharmacokinetic interaction for either compound. Hydrochlorothiazide:
A single oral dose of Carvedilol 25 mg did not alter the
pharmacokinetics of a single oral dose of hydrochlorothiazide 25 mg in
12 patients with hypertension. Likewise, hydrochlorothiazide had no
effect on the pharmacokinetics of Carvedilol. Rifampin:
In a pharmacokinetic study conducted in 8 healthy male subjects, rifampin (600 mg daily for 12 days) decreased the AUC and Cmax of Carvedilol by about 70% Torsemide:
In a study of 12 healthy subjects, combined oral administration of
Carvedilol 25 mg once daily and torsemide 5 mg once daily for 5 days did
not result in any significant differences in their pharmacokinetics
compared with administration of the drugs alone. Warfarin:
Carvedilol (12.5 mg twice daily) did not have an effect on the
steady-state prothrombin time ratios and did not alter the
pharmacokinetics of R(+)- and S(-)-warfarin following concomitant
administration with warfarin in 9 healthy volunteers.
13. NONCLINICAL TOXICOLOGY
Carcinogenesis, Mutagenesis, Impairment Of Fertility
In 2-year studies conducted in rats given Carvedilol at doses up to 75 mg/kg/day (12 times the MRHD when compared on a mg/m2 basis) or in mice given up to 200 mg/kg/day (16 times the MRHD on a mg/m2 basis), Carvedilol had no carcinogenic effect.
Carvedilol was negative when tested in a battery of genotoxicity
assays, including the Ames and the CHO/HGPRT assays for mutagenicity and
the in vitro hamster micronucleus and in vivo human lymphocyte cell tests for clastogenicity.
At doses ≥200 mg/kg/day (≥32 times the MRHD as mg/m2)
Carvedilol was toxic to adult rats (sedation, reduced weight gain) and
was associated with a reduced number of successful matings, prolonged
mating time, significantly fewer corpora lutea and implants per dam, and
complete resorption of 18% of the litters. The no-observed-effect dose
level for overt toxicity and impairment of fertility was 60 mg/kg/day
(10 times the MRHD as mg/m2).
14. CLINICAL STUDIES
Left Ventricular Dysfunction Following Myocardial Infarction
CAPRICORN was a double-blind study
comparing Carvedilol and placebo in 1,959 patients with a recent
myocardial infarction (within 21 days) and left ventricular ejection
fraction of ≤40%, with (47%) or without symptoms of heart failure.
Patients given Carvedilol received 6.25 mg twice daily, titrated as
tolerated to 25 mg twice daily. Patients had to have a systolic blood
pressure >90 mm Hg, a sitting heart rate >60 beats/minute, and no
contraindication to β-blocker use. Treatment of the index infarction
included aspirin (85%), IV or oral β-blockers (37%), nitrates (73%),
heparin (64%), thrombolytics (40%), and acute angioplasty (12%).
Background treatment included ACE inhibitors or angiotensin receptor
blockers (97%), anticoagulants (20%), lipid-lowering agents (23%), and
diuretics (34%). Baseline population characteristics included an average
age of 63 years, 74% male, 95% Caucasian, mean blood pressure 121/74 mm
Hg, 22% with diabetes, and 54% with a history of hypertension. Mean
dosage achieved of Carvedilol was 20 mg twice daily; mean duration of
follow-up was 15 months.
All-cause mortality was 15% in the placebo group and 12% in the
Carvedilol group, indicating a 23% risk reduction in patients treated
with Carvedilol (95% CI 2-40%, p = 0.03), as shown in Figure 1. The
effects on mortality in various subgroups are shown in Figure 2. Nearly
all deaths were cardiovascular (which were reduced by 25% by
Carvedilol), and most of these deaths were sudden or related to pump
failure (both types of death were reduced by Carvedilol). Another study
end point, total mortality and all-cause hospitalization, did not show a
significant improvement.
There was also a significant 40% reduction in fatal or non-fatal
myocardial infarction observed in the group treated with Carvedilol (95%
CI 11% to 60%, p = 0.01). A similar reduction in the risk of myocardial
infarction was also observed in a meta-analysis of placebo-controlled
trials of Carvedilol in heart failure.
Figure 1 Survival Analysis for CAPRICORN (intent-to-treat)
Figure 2. Effects on Mortality for Subgroups in CAPRICORN
Hypertension
Carvedilol tablets were studied in 2
placebo-controlled trials that utilized twice-daily dosing, at total
daily doses of 12.5 to 50 mg. In these and other studies, the starting
dose did not exceed 12.5 mg. At 50 mg/day, Carvedilol tablets reduced
sitting trough (12-hour) blood pressure by about 9/5.5 mm Hg; at 25
mg/day the effect was about 7.5/3.5 mm Hg. Comparisons of trough to peak
blood pressure showed a trough to peak ratio for blood pressure
response of about 65%. Heart rate fell by about 7.5 beats/minute at 50
mg/day. In general, as is true for other β-blockers, responses were
smaller in black than non-black patients. There were no age- or
gender-related differences in response.
The peak antihypertensive effect occurred 1 to 2 hours after a dose.
The dose-related blood pressure response was accompanied by a
dose-related increase in adverse effects [see ADVERSE REACTIONS (6)].
Hypertension With Type 2 Diabetes Mellitus
In a double-blind study (GEMINI),
Carvedilol, added to an ACE inhibitor or angiotensin receptor blocker,
was evaluated in a population with mild-to-moderate hypertension and
well controlled type 2 diabetes mellitus. The mean HbA1c at baseline was
7.2%. Carvedilol was titrated to a mean dose of 17.5 mg twice daily
and maintained for 5 months. Carvedilol had no adverse effect on
glycemic control, based on HbA1c measurements (mean change from baseline
of 0.02%, 95% CI -0.06 to 0.10, p = NS) [see WARNINGS AND PRECAUTIONS (5.6)].
16. HOW SUPPLIED/STORAGE AND HANDLING
Carvedilol Tablets USP, 3.125 mg are
white to off-white, round, biconvex, film-coated tablets debossed with
'Z' on one side and '1' on other side and are supplied as follows:
NDC-68382-092-17 in bottles of 28 tablets
NDC-68382-092-01 in bottles of 100 tablets
NDC-68382-092-05 in bottles of 500 tablets
Carvedilol Tablets USP, 6.25 mg are white to off-white, round,
biconvex, beveled edge, film-coated tablets debossed with 'ZC40' on one
side and plain on other side and are supplied as follows:
NDC-68382-093-17 in bottles of 28 tablets
NDC-68382-093-01 in bottles of 100 tablets
NDC-68382-093-05 in bottles of 500 tablets
Carvedilol Tablets USP, 12.5 mg are white to off-white, round,
biconvex, beveled edge, film-coated tablets debossed with 'ZC41' on one
side and plain on other side and are supplied as follows:
NDC-68382-094-17 in bottles of 28 tablets
NDC-68382-094-01 in bottles of 100 tablets
NDC-68382-094-05 in bottles of 500 tablets
Carvedilol Tablets USP, 25 mg are white to off-white, round,
biconvex, beveled edge, film-coated tablets debossed with 'ZC42' on one
side and plain on other side and are supplied as follows:
NDC-68382-095-17 in bottles of 28 tablets
NDC-68382-095-01 in bottles of 100 tablets
NDC-68382-095-05 in bottles of 500 tablets Storage:
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Protect from moisture. Dispense in a tight, light-resistant container.
Patients taking Carvedilol tablets should be advised of the following:
Patients should take Carvedilol tablets with food.
Patients should not interrupt or discontinue using Carvedilol tablets without a physician’s advice.
Patients should consult their physician if they experience signs or
symptoms of worsening heart failure such as weight gain or increasing
shortness of breath.
Patients may experience a drop in blood pressure when standing,
resulting in dizziness and, rarely, fainting. Patients should sit or lie
down when these symptoms of lowered blood pressure occur.
If experiencing dizziness or fatigue, patients should avoid driving or hazardous tasks.
Patients should consult a physician if they experience dizziness or faintness, in case the dosage should be adjusted.
Diabetic patients should report any changes in blood sugar levels to their physician.
Contact lens wearers may experience decreased lacrimation.
FDA-Approved Patient Labeling
Patient labeling is provided separately.
Manufactured by:
Cadila Healthcare Ltd.
India Distributed by: Zydus Pharmaceuticals USA Inc.
Pennington, NJ 08534
Rev.: 04/14
Revision Date: 2014/04/17
PHARMACIST-DETACH HERE AND GIVE INSTRUCTIONS TO PATIENT
- - - - - - - - - - - - - - - - - - - - - - -
- - - - - - - - - - - - - - - - - - - - - - - -
- - - - - - - - - - - - - - - - - - - - - - - -
- - - - - - - - - - - - - - - - - - - - - - - -
- - - - - - - - - - - - - PATIENT INFORMATION Carvedilol TABLETS, USP
Read the Patient Information that comes with Carvedilol tablets
before you start taking it and each time you get a refill. There may be
new information. This information does not take the place of talking
with your doctor about your medical condition or your treatment. If you
have any questions about Carvedilol tablets, ask your doctor or
pharmacist. WHAT IS Carvedilol?
Carvedilol is a prescription medicine that belongs to a group of
medicines called "beta-blockers". Carvedilol tablets are used, often
with other medicines, for the following conditions:
To treat patients with high blood pressure (hypertension)
To treat patients who had a heart attack that worsened how well the heart pumps
Carvedilol tablets are not approved for use in children under 18 years of age. WHO SHOULD NOT TAKE Carvedilol TABLETS?
Do not take Carvedilol tablet if you:
Have severe heart failure and are hospitalized in the intensive care
unit or require certain intravenous medications that help support
circulation (inotropic medications)
Are prone to asthma or other breathing problems
Have a slow heartbeat or a heart that skips a beat (irregular heartbeat)
Have liver problems
Are allergic to any of the ingredients in Carvedilol tablets. The
active ingredient is Carvedilol. See the end of this leaflet for a list
of all the ingredients in Carvedilol tablets.
WHAT SHOULD I TELL MY DOCTOR BEFORE TAKING Carvedilol TABLETS?
Tell your doctor about all of your medical conditions, including if you:
Have asthma or other lung problems (such as bronchitis or emphysema)
Have problems with blood flow in your feet and legs (peripheral
vascular disease) Carvedilol tablets can make some of your symptoms
worse.
Have diabetes
Have thyroid problems
Have a condition called pheochromocytoma
Have had severe allergic reactions
Are pregnant or trying to become pregnant. It is not known if
Carvedilol tablets are safe for your unborn baby. You and your doctor
should talk about the best way to control your high blood pressure
during pregnancy.
Are breastfeeding. It is not known if Carvedilol passes into your
breast milk. You should not breastfeed while using Carvedilol tablets.
Are scheduled for surgery and will be given anesthetic agents
Are taking prescription or non-prescription medicines, vitamins, and
herbal supplements. Carvedilol tablets and certain other medicines can
affect each other and cause serious side effects. Carvedilol tablets may
affect the way other medicines work. Also, other medicines may affect
how well Carvedilol tablets works
Keep a list of all the medicines you take. Show this list to your doctor and pharmacist before you start a new medicine. HOW SHOULD I TAKE Carvedilol TABLETS? It is important for you to take your medicine
every day as directed by your doctor. If you stop taking Carvedilol
tablets suddenly, you could have chest pain and/or a heart attack. If
your doctor decides that you should stop taking Carvedilol tablets, your
doctor may slowly lower your dose over a period of time before stopping
it completely.
Take Carvedilol tablets exactly as prescribed. Your doctor will tell
you how many tablets to take and how often. In order to minimize
possible side effects, your doctor might begin with a low dose and then
slowly increase the dose.
Do not stop taking Carvedilol tablets and do not
change the amount of Carvedilol tablets you take without talking to your
doctor.
Tell your doctor if you gain weight or have trouble breathing while taking Carvedilol tablets.
Take Carvedilol tablets with food.
If you miss a dose of Carvedilol tablets, take your dose as soon as
you remember, unless it is time to take your next dose. Take your next
dose at the usual time. Do not take 2 doses at the same time.
If you take too much Carvedilol tablets, call your doctor or poison control center right away.
WHAT SHOULD I AVOID WHILE TAKING Carvedilol TABLETS?
Carvedilol tablets can cause you to feel dizzy, tired, or faint. Do
not drive a car, use machinery, or do anything that needs you to be
alert if you have these symptoms. WHAT ARE POSSIBLE SIDE EFFECTS OF Carvedilol TABLETS?
Low blood pressure (which may cause dizziness or fainting when you stand up). If these happen, sit or lie down right away and tell your doctor.
Tiredness. If you feel tired or dizzy you should not drive, use machinery, or do anything that needs you to be alert.
Slow heartbeat
Changes in your blood sugar. If you have diabetes, tell your doctor if you have any changes in your blood sugar levels.
Carvedilol tablets may hide some of the symptoms of low blood sugar, especially a fast heartbeat.
Carvedilol tablets may mask the symptoms of hyperthyroidism (overactive thyroid).
Worsening of severe allergic reactions.
Rare but serious allergic reactions (including hives or swelling of
the face, lips, tongue, and/or throat that may cause difficulty in
breathing or swallowing) have happened in patients who were on
Carvedilol. These reactions can be life-threatening.
Other side effects of Carvedilol tablets include
shortness of breath, weight gain, diarrhea, and fewer tears or dry eyes
that become bothersome if you wear contact lenses. Rare serious allergic
reactions have happened in patients who were on Carvedilol.
Call your doctor if you have any side effects that bother you or don't go away. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store Carvedilol tablets?
Store Carvedilol tablets at 20º to 25 º C (68 º to 77 ºF). Keep the tablets dry.
Safely, throw away Carvedilol tablets that are out of date or no longer needed.
Keep Carvedilol tablets and all medicines out of the reach of children.
GENERAL INFORMATION ABOUT Carvedilol TABLETS
Medicines are sometimes prescribed for conditions other than those
described in patient information leaflets. Do not use Carvedilol
tablets for a condition for which it was not prescribed. Do not give
Carvedilol tablets to other people, even if they have the same symptoms
you have. It may harm them.
This leaflet summarizes the most important information about
Carvedilol tablets. If you would like more information, talk with your
doctor. You can ask your doctor or pharmacist for information about
Carvedilol tablets that is written for healthcare professionals. Please
address medical inquiries to, (MedicalAffairs@zydususa.com) Tel.:
1-877-993-8779.
WHAT ARE THE INGREDIENTS IN Carvedilol TABLETS, USP?
Active Ingredient: Carvedilol, USP
Inactive Ingredients: Colloidal silicon dioxide, crospovidone,
hypromellose, lactose monohydrate, magnesium stearate, polyethylene
glycol, povidone, talc, and titanium dioxide.
Carvedilol tablets come in the following strengths: 3.125 mg, 6.25 mg, 12.5 mg and 25 mg What is high blood pressure (hypertension)?
Blood pressure is the force of blood in your blood vessels when your
heart beats and when your heart rests. You have high blood pressure when
the force is too much. High blood pressure makes the heart work harder
to pump blood through the body and causes damage to blood vessels.
Carvedilol can help your blood vessels relax so your blood pressure is
lower. Medicines that lower blood pressure may lower your chance of
having a stroke or heart attack.
Manufactured by:
Cadila Healthcare Ltd.
India Distributed by: Zydus Pharmaceuticals USA Inc.
Pennington, NJ 08534
Rev.: 06/13
Revision Date: 2013/06/08
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 68382-092-01 in bottle of 100 Tablets
Carvedilol Tablets USP, 3.125 mg
Rx only
100 Tablets
ZYDUS
NDC 68382-093-01 in bottle of 100 Tablets
Carvedilol Tablets USP, 6.25 mg
Rx only
100 Tablets
ZYDUS
NDC 68382-094-01 in bottle of 100 Tablets
Carvedilol Tablets USP, 12.5 mg
Rx only
100 Tablets
ZYDUS
NDC 68382-095-01 in bottle of 100 Tablets
Carvedilol Tablets USP, 25 mg
Rx only
100 Tablets
ZYDUS
Carvedilol Carvedilol tablet, film coated
Product Information
Product Type
HUMAN PRESCRIPTION DRUG LABEL
Item Code (Source)
NDC:68382-092
Route of Administration
ORAL
DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name
Basis of Strength
Strength
Carvedilol (Carvedilol)
Carvedilol
3.125 mg
Inactive Ingredients
Ingredient Name
Strength
AMINOLEVULINIC ACID HYDROCHLORIDE
AMINOMETRADINE
AMINOPENTAMIDE SULFATE
AMINOPHYLLINE
AMINOPROMAZINE
AMINOPROPAZINE FUMARATE
AMINOPTERIN SODIUM
AMMI VISNAGA FRUIT
AMOPROXAN
CROSPOVIDONE
HYPROMELLOSES
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
POLYETHYLENE GLYCOLS
COLLOIDAL SILICON DIOXIDE
POVIDONE
TALC
TITANIUM DIOXIDE
Product Characteristics
Color
WHITE (WHITE TO OFF- WHITE)
Score
no score
Shape
ROUND (ROUND)
Size
4mm
Flavor
Imprint Code
Z;1
Contains
Packaging
#
Item Code
Package Description
1
NDC:68382-092-17
28 TABLET, FILM COATED in 1 BOTTLE
2
NDC:68382-092-01
100 TABLET, FILM COATED in 1 BOTTLE
3
NDC:68382-092-05
500 TABLET, FILM COATED in 1 BOTTLE
Marketing Information
Marketing Category
Application Number or Monograph Citation
Marketing Start Date
Marketing End Date
ANDA
ANDA077614
09/05/2007
Carvedilol Carvedilol tablet, film coated
Product Information
Product Type
HUMAN PRESCRIPTION DRUG LABEL
Item Code (Source)
NDC:68382-093
Route of Administration
ORAL
DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name
Basis of Strength
Strength
Carvedilol (Carvedilol)
Carvedilol
6.25 mg
Inactive Ingredients
Ingredient Name
Strength
AMINOLEVULINIC ACID HYDROCHLORIDE
AMINOMETRADINE
AMINOPENTAMIDE SULFATE
AMINOPHYLLINE
AMINOPROMAZINE
AMINOPROPAZINE FUMARATE
AMINOPTERIN SODIUM
AMMI VISNAGA FRUIT
AMOPROXAN
CROSPOVIDONE
HYPROMELLOSES
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
POLYETHYLENE GLYCOLS
COLLOIDAL SILICON DIOXIDE
POVIDONE
TALC
TITANIUM DIOXIDE
Product Characteristics
Color
WHITE (WHITE TO OFF- WHITE)
Score
no score
Shape
ROUND (ROUND)
Size
6mm
Flavor
Imprint Code
ZC40
Contains
Packaging
#
Item Code
Package Description
1
NDC:68382-093-17
28 TABLET, FILM COATED in 1 BOTTLE
2
NDC:68382-093-01
100 TABLET, FILM COATED in 1 BOTTLE
3
NDC:68382-093-05
500 TABLET, FILM COATED in 1 BOTTLE
Marketing Information
Marketing Category
Application Number or Monograph Citation
Marketing Start Date
Marketing End Date
ANDA
ANDA077614
09/05/2007
Carvedilol Carvedilol tablet, film coated
Product Information
Product Type
HUMAN PRESCRIPTION DRUG LABEL
Item Code (Source)
NDC:68382-094
Route of Administration
ORAL
DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name
Basis of Strength
Strength
Carvedilol (Carvedilol)
Carvedilol
12.5 mg
Inactive Ingredients
Ingredient Name
Strength
CROSPOVIDONE
HYPROMELLOSES
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
POLYETHYLENE GLYCOLS
COLLOIDAL SILICON DIOXIDE
POVIDONE
TALC
TITANIUM DIOXIDE
Product Characteristics
Color
WHITE (WHITE TO OFF-WHITE)
Score
no score
Shape
ROUND (ROUND)
Size
8mm
Flavor
Imprint Code
ZC41
Contains
Packaging
#
Item Code
Package Description
1
NDC:68382-094-17
28 TABLET, FILM COATED in 1 BOTTLE
2
NDC:68382-094-01
100 TABLET, FILM COATED in 1 BOTTLE
3
NDC:68382-094-05
500 TABLET, FILM COATED in 1 BOTTLE
Marketing Information
Marketing Category
Application Number or Monograph Citation
Marketing Start Date
Marketing End Date
ANDA
ANDA077614
09/05/2007
Carvedilol Carvedilol tablet, film coated
Product Information
Product Type
HUMAN PRESCRIPTION DRUG LABEL
Item Code (Source)
NDC:68382-095
Route of Administration
ORAL
DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name
Basis of Strength
Strength
Carvedilol (Carvedilol)
Carvedilol
25 mg
Inactive Ingredients
Ingredient Name
Strength
CROSPOVIDONE
HYPROMELLOSES
LACTOSE MONOHYDRATE
MAGNESIUM STEARATE
POLYETHYLENE GLYCOLS
COLLOIDAL SILICON DIOXIDE
POVIDONE
TALC
TITANIUM DIOXIDE
Product Characteristics
Color
WHITE (WHITE TO OFF-WHITE)
Score
no score
Shape
ROUND
Size
10mm
Flavor
Imprint Code
ZC42
Contains
Packaging
#
Item Code
Package Description
1
NDC:68382-095-17
28 TABLET, FILM COATED in 1 BOTTLE
2
NDC:68382-095-01
100 TABLET, FILM COATED in 1 BOTTLE
3
NDC:68382-095-05
500 TABLET, FILM COATED in 1 BOTTLE
Marketing Information
Marketing Category
Application Number or Monograph Citation
Marketing Start Date
Marketing End Date
ANDA
ANDA077614
09/05/2007
Labeler - Zydus Pharmaceuticals (USA) Inc. (156861945)
Registrant - Zydus Pharmaceuticals (USA) Inc. (156861945)
