Israel - English - Ministry of Health
Patient package insert in accordance with the Pharmacists’ Regulations
(Preparations) – 1986
The medicine is dispensed according to a physician's prescription only
Name of preparation and form:
Active ingredients and quantity:
Tramadol Hydrochloride 37.5 mg
Paracetamol 325 mg
Inactive and allergic ingredients in the medicinal product – see section 6 and also
"Important information about some ingredients of the medicine" in section 2.
Read the entire leaflet carefully before using the medicine.
This leaflet contains concise information about the medicine. If you have any further
questions, refer to the physician or the pharmacist.
This medicine has been prescribed to treat your illness. Do not pass it on to others. It
may harm them, even if it seems like their disease is similar to yours.
WHAT IS THE MEDICINE INTENDED FOR?
Zaldiar is a combination of two analgesics, tramadol and paracetamol, which work
together to relieve pain.
Zaldiar is intended for use only by adults and children over the age of 14.
The preparation contains a combination of tramadol – a pain reliever from the
opioids group and paracetamol – a pain reliever and fever reducer from the anilide
group and is intended to treat moderate to severe pain.
BEFORE USING THE MEDICINE:
Do not use the medicine if:
You are sensitive (allergic) to the active ingredients or to any of the additional
ingredients contained in the medicine (listed in section 6).
In cases of acute alcohol poisoning.
You are taking sleeping pills, pain relievers or medicines that affect mood and
You are also taking medicines called monoamine oxidase inhibitors (MAOIs)
or have taken MAOIs in the last 14 days before treatment with Zaldiar. MAOIs
are used in the treatment of depression or Parkinson’s disease.
You have a severe liver disorder.
You have epilepsy that is not adequately controlled by your current medicine.
In children under the age of 14.
You are pregnant or breastfeeding (see Pregnancy, breastfeeding and fertility
Special warnings regarding use of the medicine:
If you developed skin reactions in the past as a result of taking preparations
containing paracetamol, do not use preparations containing paracetamol, so that
severe skin reactions will not recur.
Before beginning Zaldiar treatment, inform your physician if:
You take medicines containing paracetamol or tramadol.
You have liver problems or disease, or your eyes and skin may turn yellow,
which may suggest jaundice.
You have kidney problems.
You have severe difficulties in breathing, for example asthma or severe lung
You have epilepsy or have already experienced fits or seizures.
You have recently suffered from a head injury, shock or severe headaches
associated with vomiting (being sick).
You are dependent on any medicine for example morphine.
You take other medicines to treat pain that contain buprenorphine,
nalbuphine or pentazocine.
You are going to have an anaesthetic (tell your physician or dentist that you
are taking Zaldiar).
If any of the above-mentioned points applied to you in the past or applies to you while
you are taking Zaldiar, please make sure your physician knows. He can then decide
whether you should continue to use this medicine.
Other Medicines and Zaldiar
If you are taking or have recently taken other medicines including non-
prescription medicines and food supplements, tell the physician or the
Do not exceed the maximum daily doses of paracetamol or tramadol from this or
Do not take Zaldiar with MAOIs (see the section ‘Before using the medicine’).
Zaldiar is not recommended to be taken with the following:
carbamazepine (a medicine used to treat epilepsy or
some types of pain).
buprenorphine, nalbuphine or pentazocine (opioid-type
The risk of side effects increases:
if you are taking triptans (used for migraine) or selective serotonin re-uptake
inhibitors (SSRIs, used for depression). Check with your physician if you
experience confusion, restlessness, fever, sweating, uncoordinated movement of
limbs or eyes, uncontrollable jerking of muscles or diarrhea.
if you are taking tranquilizers, sleeping pills, other pain relievers such as
morphine and codeine (also as cough medicine), baclofen (a muscle relaxant),
medicines used to lower blood pressure or medicines to treat allergies. Check
with your physician if you feel drowsy or feel faint.
if you are taking medicines which may cause convulsions (fits), such as certain
antidepressants or antipsychotics. The risk having a fit may increase if you take
Zaldiar at the same time. Your physician will tell you whether Zaldiar is suitable
if you are taking certain antidepressants. Zaldiar may interact with these
medicines and you may experience symptoms such as involuntary, rhythmic
contractions of muscles, including the muscles that control movement of the eye,
agitation, excessive sweating, tremor, exaggeration of reflexes, increased muscle
tension and body temperature above 38°C.
if you are taking warfarin or phenprocoumon (for blood thinning). The
effectiveness of such medicines may be altered and bleeding may occur (see
The effectiveness of Zaldiar may be altered if you also take:
Metoclopramide, domperidone or ondansetron (medicines used to treat
nausea and vomiting/being sick).
Cholestyramine (medicine used to reduce cholesterol in the blood).
Your physician will advise you which medicines are safe to use with Zaldiar.
Zaldiar with food and alcohol:
Do not drink alcohol while you are taking Zaldiar, as you may feel drowsier.
Zaldiar may be taken with or without food.
Pregnancy, breastfeeding and fertility:
Do not take Zaldiar while you are pregnant or breastfeeding.
Check with your physician if you become pregnant during treatment with Zaldiar and
before taking any further tablets. Tramadol is excreted into breast milk. For this
reason, you should not take Zaldiar more than once during breastfeeding, or
alternatively, if you take Zaldiar more than once, you should stop breastfeeding.
Based on human experience, tramadol is suggested not to influence female or male
fertility. No data on the influence of the combination of tramadol and paracetamol on
fertility are available.
Ask your physician or pharmacist for advice before taking the medicine.
Driving and using machines:
If you feel drowsy while taking Zaldiar, do not drive, use tools or use machinery.
The medicine can affect your ability to drive as it may make you sleepy or dizzy.
Do not drive while taking this medicine until you know how it affects you.
Talk to your physician or pharmacist if you are not sure whether it is safe for you to
drive while taking this medicine.
Important information about some ingredients of the medicine:
Zaldiar contains lactose
If you have been told by your physician that you have an intolerance to some sugars,
contact your physician before taking this medicinal product.
3. HOW SHOULD YOU USE THE MEDICINE?
Always use this medicine according to the physician’s instructions. You should check
with the physician or pharmacist if you are not sure.
The dosage should be adjusted to the intensity of your pain and your individual pain
sensitivity. In general the lowest pain-relieving dose should be taken.
Take Zaldiar for as short a time as possible, and no longer than your physician has
The dosage and treatment will be determined only by the physician.
The usual dose is an initial dosage of up to 2 tablets. If required, further tablets may
be taken, as instructed by your physician. The shortest time between doses must be
at least 6 hours.
Do not take more than 8 tablets per day (300 mg tramadol, 2600 mg
paracetamol). Do not use Zaldiar more often than your physician has told you.
In elderly patients (above 75 years) the excretion of tramadol may be delayed. If this
applies to you, your physician may recommend prolonging the dosage interval.
Severe liver or kidney disease (insufficiency)/dialysis patients:
Patients with severe liver and/or kidney insufficiency should not take Zaldiar. If in
your case the insufficiency is mild or moderate, your physician may recommend
prolonging the dosage interval.
Do not exceed the recommended dose.
Method of administration:
The tablets are for oral use.
Swallow the whole tablet with sufficient liquid.
Do not chew, divide, or crush the tablets!
If you think that the effect of Zaldiar is too strong (you feel very drowsy or have
difficulty breathing) or too weak (you do not have enough pain relief), contact your
If you take more Zaldiar than you should
If you mistakenly took more Zaldiar than instructed, contact your physician or
pharmacist immediately, even if you feel well. This is because too much paracetamol
can cause delayed, serious liver damage.
In case of overdose, or if a child accidently swallowed the medicine, immediately
refer to the emergency room of a hospital, and bring the medicine package with you.
Do not induce vomiting without a physician’s specific instruction!
If you forget to take Zaldiar
If you forget to take Zaldiar, pain is likely to return.
Do not take a double dose to make up for forgotten individual doses; simply continue
taking the tablets as before.
If you stop taking Zaldiar
Generally, there will be no side effects when treatment with Zaldiar is stopped.
Rarely, people who have been using a medicine containing tramadol may become
dependent on it, making it hard to stop taking it. If you have been taking Zaldiar for
some time and want to stop, contact your physician because your body may have
become used to Zaldiar.
feel agitated, anxious, nervous or shaky
be over active
have difficulty sleeping
have stomach or bowel disorders.
Very few people may also get:
hallucinations, unusual perceptions such as itching, tingling and numbness
ringing in the ears.
If you experience any of these effects after stopping this medicine, please contact
Other side effect information is listed in section 4.
Do not take medicines in the dark!
Check the label and dose each time you take the medicine. Wear glasses, if you
If you have any other questions regarding the use of the medicine, consult the
physician or the pharmacist.
4. SIDE EFFECTS
As with all medicines, this medicine may cause side effects in some users. Do not be
alarmed when reading the list of side effects. You may not experience any of them.
Some side effects could be serious. Contact your physician immediately if any
of the following occur:
rarely cases of skin rash, indicating an allergic reaction, may develop with
sudden swelling of the face and neck, difficulties breathing or drop of blood
pressure and fainting. If this happens to you, stop treatment. Do not take the
prolonged or unexpected bleeding, from the use of Zaldiar with medicines
used to thin the blood (e.g. warfarin, phenprocoumon).
Paracetamol may, in rare cases, cause severe skin diseases. The possible
signs are: skin redness, rashes, blisters, extensive dermal injury. Severe
dermal side effects may also appear even if you have previously taken
preparations that contain the active agent paracetamol without any problem.
Additional Side Effects:
Additionally, if any of the following side effects get serious, contact your physician or
Very common: may affect more than 1 in 10 people
Common: may affect up to 1 in 10 people
vomiting (being sick), digestion problems (constipation, flatulence, diarrhoea),
stomach pain, dry mouth
itching, sweating (hyperhidrosis)
confusional state, sleep disorders, mood changes (anxiety, nervousness,
feeling of high spirits).
Uncommon: may affect up to 1 in 100 people
increase in pulse or blood pressure, heart rate or heart rhythm disorders
tingling, numbness or feeling of pins and needles in the limbs, ringing in the
ears, involuntary muscle twitching
depression, nightmares, hallucinations (hearing, seeing or sensing things that
are not really there), memory lapses
difficulty swallowing, blood in the stools
skin reactions (for example rashes, hives)
increase in liver enzyme values
presence of albumin in urine, difficulties or pain on passing urine
shivering, hot flushes, pain in the chest.
Rare: may affect up to 1 in 1,000 people
fits, uncoordinated movements, transient loss of consciousness (syncope)
vision blurred, constriction of the pupil (miosis)
excessive dilation of the pupils (mydriasis).
decrease in blood sugar level (hypoglycaemia).
In addition, the following side effects have been reported by people using medicines
that contain only tramadol or only paracetamol:
feeling faint when getting up from a lying or sitting position, slow heart rate,
changes in appetite
muscle weakness, slower or weaker breathing
mood changes, changes in activity, changes in perception
worsening of existing asthma
nose bleeds or bleeding gums, which may result from a low blood platelet
very rare cases of serious skin reactions have been reported with
rare cases of respiratory depression have been reported with tramadol.
If a side effect has appeared, if any of the side effects gets worse, or if you suffer
from any side effect that has not been mentioned in the leaflet, you should consult
Side effects may be reported to the Ministry of Health by clicking on the link “Report
Side Effects of Drug Treatment” found on the Ministry of Health homepage
(www.health.gov.il) which refers you to the online form for reporting side effects, or
by entering the link:
5. HOW SHOULD THE MEDICINE BE STORED?
This medicine, like all medicines, must be stored in a closed place out of the sight
and reach of children and/or infants, to avoid poisoning. Do not induce vomiting
without a physician’s specific instruction.
Do not use this medicine after the expiry date (exp. date), which is printed on the box
and on the blister. The expiry date refers to the last day of the indicated month.
The medicine is to be stored at a temperature not higher than 30°C.
6. ADDITIONAL INFORMATION
In addition to the active ingredients, the medicine also contains:
Powdered cellulose, Maize starch, Pregelatinized starch, Sodium starch glycolate,
Hypromellose, Lactose monohydrate, Titanium dioxide, Macrogol 6000, Yellow iron
oxide, Propylene glycol, Talc.
Each tablet contains 1.878 mg Lactose monohydrate.
What the medicine looks like and contents of the pack:
Zaldiar tablets are pale yellow film-coated tablets, marked with the manufacturer’s
logo on one side and “T5” on the other. Zaldiar is packed in blister packs of 10
Zaldiar comes in packages of 10 and 20 film-coated tablets.
Not all pack sizes may be marketed.
Registration Owner: Tec-O-Pharm Libra Ltd., POB 45054 Jerusalem.
Manufacturer: Grunenthal GmbH, Aachen, Germany.
Registration number of the medicine in the National Drug Registry of the Ministry of
This leaflet was checked and approved by the Ministry of Health on 06.2016 and
updated according to the guidelines of the Ministry of Health in 12.2017.
SUMMARY OF PRODUCT CHARACTERISTICS
NAME OF THE MEDICINAL PRODUCT
37.5 mg/325 mg, film coated-tablets
QUALITATIVE AND QUANTITATIVE COMPOSITION
One film-coated tablet contains 37.5 mg tramadol hydrochloride and 325 mg paracetamol.
Excipients: One film coated tablet contains 1.878 mg lactose monohydrate (= 1.784 mg lactose).
For the full list of excipients, see section 6.1.
Pale yellow film-coated tablet, marked with the manufacturer‘s logo
on one side and ‘T5’ on the
Zaldiar tablets are indicated for the symptomatic treatment of moderate to severe pain.
The use of Zaldiar should be restricted to patients whose moderate to severe pain is considered to
require a combination of tramadol and paracetamol (see also Section 5.1).
Posology and method of administration
The use of Zaldiar should be restricted to patients whose moderate to severe pain is considered
to require a combination of tramadol and paracetamol.
The dose should be individually adjusted according to intensity of pain and response of the patient.
The lowest effective dose for analgesia should generally be selected. The total dose of 8 tablets
(equivalent to 300 mg tramadol hydrochloride and 2600 mg paracetamol) per day should not be
exceeded. The dosing interval should not be less than six hours.
Adults and Adolescents (14 years and older).
An initial dose of two tablets of Zaldiar is recommended Additional doses can be taken as needed,
not exceeding 8 tablets (equivalent to 300 mg tramadol and 2600 mg paracetamol) per day.
The dosing interval should not be less than six hours.
Zaldiar should under no circumstances be administered for longer than is strictly necessary (see
also section 4.4 - Special warnings and precautions for use). If repeated use or long term treatment
with Zaldiar is required as a result of the nature and severity of the illness, then careful, regular
monitoring should take place (with breaks in the treatment, where possible), to assess whether
continuation of the treatment is necessary.
The effective and safe use of Zaldiar has not been established in children below the age of 14
years. Treatment is therefore not recommended in this population.
A dose adjustment is not usually necessary in patients up to 75 years without clinically manifest
hepatic or renal insufficiency. In elderly patients over 75 years elimination may be prolonged.
Therefore, if necessary the dosage interval is to be extended according to the patient's requirements.
In patients with renal insufficiency the elimination of tramadol is delayed. In these patients
prolongation of the dosage intervals should be carefully considered according to the patient's
In patients with hepatic impairment the elimination of tramadol is delayed. In these patients
prolongation of the dosage intervals should be carefully considered according to the patient’s
requirements (see section 4.4). Because of the presence of paracetamol Zaldiar should not be used
in patients with severe hepatic impairment (see Section 4.3).
Method of administration
Tablets must be swallowed whole, with a sufficient quantity of liquid. They must not be broken or
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1
acute intoxication with alcohol, hypnotic drugs, centrally-acting analgesics, opioids or
Zaldiar should not be administered to patients who are receiving monoamine oxidase
inhibitors or within two weeks of their withdrawal (see 4.5. Interactions with other
medicinal products and other forms of interaction),
severe hepatic impairment,
epilepsy not controlled by treatment (see. 4.4. Special Warnings).
Special warnings and precautions for use
In adults and adolescents 14 years and older. The maximum dose of 8 tablets of Zaldiar
should not be exceeded. In order to avoid inadvertent overdose, patients should be advised
not to exceed the recommended dose and not to use any other paracetamol (including over
the counter) or tramadol hydrochloride containing products concurrently without the advice
of a physician.
In severe renal insufficiency (creatinine clearance <10 ml/mm), Zaldiar is not
In patients with severe hepatic impairment Zaldiar should not be used ( See Section 4.3). The
hazards of paracetamol overdose are greater in patients with non- cirrhotic alcoholic liver
disease. In moderate cases prolongation of dosage interval should be carefully considered.
In severe respiratory insufficiency, Zaldiar is not recommended.
Tramadol is not suitable as a substitute in opioid-dependent patients. Although it is an opioid
agonist, tramadol cannot suppress morphine withdrawal symptoms.
Convulsions have been reported in tramadol-treated patients susceptible to seizures or taking
other medications that lower the seizure threshold, especially selective serotonin re-uptake
inhibitors, tricyclic antidepressants, antipsychotics, centrally acting analgesics or local
anaesthesia. Epileptic patients controlled by a treatment or patients susceptible to seizures
should be treated with Zaldiar only if there are compelling circumstances. Convulsions have
been reported in patients receiving tramadol at the recommended dose levels. The risk may be
increased when doses of tramadol exceed the recommended upper dose limit
Concomitant use of opioid agonists-antagonists (nalbuphine, buprenorphine, pentazocine) is not
recommended (see section 4.5).
Paracetamol has been associated with a risk of rare but serious skin reactions. These skin
reactions, known as Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and
acute generalized exanthematous pustulosis (AGEP), can be fatal.
Reddening of the skin, rash, blisters, and detachment of the upper surface of the skin can occur
with the use of drug products that contain paracetamol. These reactions can occur with first-time
use of paracetamol or at any time while it is being taken.
Anyone who develops a skin rash or reaction while using paracetamol should stop the drug and seek
medical attention right away. Anyone who has experienced a serious skin reaction with paracetamol
should not take the drug again and should contact their health care professional to discuss alternative
pain relievers/fever reducers.
Health care professionals should be aware of this rare risk and consider paracetamol along with
other drugs already known to have such an association, when assessing patients with potentially
drug induced skin reactions.
Sleep-related breathing disorders
Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-
related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who
present with CSA, consider decreasing the total opioid dosage.
Precautions for use
Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs
Concomitant use of Tramadol hydrochloride/Paracetamol and sedative medicines such as
benzodiazepines or related drugs may result in sedation, respiratory depression, coma and death.
Because of these risks, concomitant prescribing with these sedative drugs should be reserved for
patients for whom alternative treatment options are not possible. If a decision is made to prescribe
Tramadol hydrochloride/Paracetamol concomitantly with sedative medicines, the lowest effective dose
should be used, and the duration of the concomitant treatment should be as short as possible.
The patients should be followed closely for signs and symptoms of respiratory depression and
sedation. In this respect, it is strongly recommended to inform patients and their caregivers to be aware
of these symptoms (see section 4.5).
Tolerance and physical and/or psychological dependence may develop, even at therapeutic doses. The
clinical need for analgesic treatment should be reviewed regularly (see 4.2). In opioid-dependent
patients and patients with a history of drug abuse or dependence, treatment should only be for short
period and under medical supervision. Zaldiar should be used with caution in patients with cranial
trauma, in patients prone to convulsive disorder, biliary tract disorders, in a state of shock, in an
altered state of consciousness for unknown reasons, with problems affecting the respiratory center or
the respiratory function, or with an increased intracranial pressure.
Paracetamol in overdose may cause hepatic toxicity in some patients.
Symptoms of withdrawal reaction, similar to those occurring during opiate withdrawal, may occur
even at therapeutic doses and for short term treatment (see section 4.8). Withdrawal symptoms may
be avoided by taper it at the time of discontinuation especially after long treatment periods. Rarely,
cases of dependence and abuse have been reported (see section 4.8).
In one study, use of tramadol during general anaesthesia with enflurane and nitrous oxide was reported
to enhance intra-operative recall. Until further information is available, use of tramadol during light
planes of anaesthesia should be avoided.
Zaldiar tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the
Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-
Interactions with other medicinal products and other forms of interaction
Concomitant use is contraindicated with:
Non-selective MAO Inhibitors
Risk of serotonergic syndrome: diarrhoea, tachycardia, hyperhidrosis, trembling, confusional state,
Selective-A MAO Inhibitors
Extrapolation from non-selective MAO inhibitors
Risk of serotonergic syndrome: diarrhoea, tachycardia, hyperhidrosis, trembling, confusional
state, even coma.
Selective-B MAO Inhibitors
Central excitation symptoms evocative of a serotoninergic syndrome: diarrhoea, tachycardia,
hyperhidrosis, trembling, confusional state, even coma
In case of recent treatment with MAO inhibitors, a delay of two weeks should occur before treatment
Concomitant use is not recommended with:
Alcohol increases the sedative effect of opioid analgesics.
The effect on alertness can make driving of vehicles and the use of machines dangerous. Avoid intake
of alcoholic drinks and of medicinal products containing alcohol.
Carbamazepine and other enzyme inducers
Risk of reduced efficacy and shorter duration due to decreased plasma concentrations of tramadol.
Opioid agonists-antagonists (buprenorphine, nalbuphine, pentazocine)
Decrease of the analgesic effect by competitive blocking effect at the receptors, with the risk of
occurrence of withdrawal syndrome.
Concomitant use which needs to be taken into consideration:
Tramadol can induce convulsions and increase the potential for selective serotonin reuptake
inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic
antidepressants, antipsychotics and seizure threshold-lowering medicinal products (such as
bupropion, mirtazapine, tetrahydrocannabinol) to cause convulsions.
Concomitant therapeutic use of tramadol and serotonergic drugs such as selective serotonin
re-uptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), MAO
inhibitors (see section 4.3), tricyclic antidepressants and mirtazapine may cause serotonin
toxicity. Serotonin syndrome is likely when one of the following is observed:
Inducible or ocular clonus with agitation or diaphoresis ,
Tremor and hyperreflexia
Hypertonia and body temperature > 38 °C and inducible or ocular clonus.
Withdrawal of the serotonergic drugs usually brings about a rapid improvement. Treatment
depends on the type and severity of the symptoms.
Other opioid derivatives (including antitussive drugs and substitutive treatments),
benzodiazepines and barbiturates.
Increased risk of respiratory depression which can be fatal in cases of overdose.
Other central nervous system depressants, such as other opioid derivatives (including
antitussive drugs and substitutive treatments), barbiturates, benzodiazepines, other
anxiolytics, hypnotics, sedative antidepressants, sedative antihistamines, neuroleptics,
centrally-acting antihypertensive drugs, thalidomide and baclofen.
These drugs can cause increased central depression. The effect on alertness can make driving of
vehicles and the use of machines dangerous.
Sedating medicinal products such as benzodiazepines or related substances:
The concomitant use of opioids with sedative medicines such as benzodiazepines or related drugs
increases the risk of sedation, respiratory depression, coma and death because of additive CNS
depressant effects. The dose and duration of the concomitant use should be limited (see section 4.4).
As medically appropriate, periodic evaluation of prothrombin time should be performed
when Zaldiar and warfarin like compounds are administered concurrently due to reports of
In a limited number of studies, the pre- or postoperative application of the antiemetic 5HT3
antagonist ondansetron increased the requirement of tramadol in patients with postoperative pain.
Fertility, pregnancy and lactation
Since Zaldiar is a fixed combination of active ingredients including tramadol, it should
not be used during pregnancy.
Data regarding paracetamol:
Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol used
in the recommended dosages.
Data regarding tramadol:
Tramadol should not be used during pregnancy as there is inadequate evidence available to
assess the safety of tramadol in pregnant women. Tramadol administered before or during birth
does not affect uterine contractility. In neonates it may induce changes in the respiratory rate
which are usually not clinically relevant. Long-term treatment during pregnancy may lead to
withdrawal symptoms in the newborn after birth, as a consequence of habituation.
Since Zaldiar is a fixed combination of active ingredients including tramadol, it
should not be ingested during breast feeding.
Data regarding paracetamol:
Paracetamol is excreted in breast milk but not in a clinically significant amount. Available
published data do not contraindicate breast feeding by women using single ingredient medicinal
products containing only paracetamol.
Data regarding tramadol:
Approximately 0.1% of the maternal dose of tramadol is excreted in breast milk. In the
immediate post-partum period, for maternal oral daily dosage up to 400 mg, this corresponds to a
mean amount of tramadol ingested by breast-fed infants of 3% of the maternal weightadjusted
dosage. For this reason tramadol should not be used during lactation or alternatively, breast-
feeding should be discontinued during treatment with tramadol. Discontinuation of breast-
feeding is generally not necessary following a single dose of tramadol.
Post marketing surveillance does not suggest an effect of tramadol on fertility.
Animal studies did not show an effect of tramadol on fertility. No study on fertility was
accomplished with the combination of tramadol and paracetamol
Effects on ability to drive and use machines
Tramadol may cause drowsiness or dizziness, which may be enhanced by alcohol or other CNS
depressants. If affected, the patient should not drive or operate machinery.
The most commonly reported undesirable effects during the clinical trials performed with the
paracetamol/tramadol hydrochloride combination were nausea, dizziness and somnolence,
observed in more than 10 % of the patients.
The frequencies are defined as follows:
≥1/100 to <1/10
≥1/1000 to <1/100
≥1/10 000 to <1/1000
Frequency cannot be estimated from the available data
Within each frequency grouping, undesirable effects are presented in order of decreasing
Uncommon: palpitations, tachycardia, arrythmia.
Rare: vision blurred, miosis, mydriasis.
Ear and labyrinth disorders:
Very common: nausea
Common: vomiting, constipation, dry mouth, diarrhea, abdominal pain, dyspepsia,
Uncommon: dysphagia, melaena.
General disorders and administration site conditions:
Uncommon: chills, chest pain.
Uncommon: transaminases increased.
Metabolism and nutrition disorders:
Nervous system disorders:
Very common: dizziness, somnolence
Common: headache, trembling
Uncommon: muscle contractions involuntary, paraesthesia, amnesia
Rare: ataxia, convulsions, syncope, speech disorders.
Common: confusional state, mood altered, anxiety, nervousness, euphoric mood, sleep
Uncommon: depression, hallucinations, nightmares
Rare: delirium, drug dependence.
Post marketing surveillance
Very rare: abuse.
Renal and urinary disorders:
Uncommon: albuminuria, micturition disorders (dysuria and urinary retention).
Respiratory, thoracic and mediastinal disorders:
Skin and subcutaneous tissue disorders:
Common: hyperhidrosis, pruritus
Uncommon: dermal reactions (e.g. rash, urticaria).
Uncommon: hypertension, hot flush.
Although not observed during clinical trials, the occurrence of the following undesirable
effects known to be related to the administration of tramadol or paracetamol cannot be
Postural hypotension, bradycardia, collapse (tramadol).
Post-marketing surveillance of tramadol has revealed rare alterations of warfarin effect,
including elevation of prothrombin times.
Rare cases (10000 to < 1/1000) : allergic reactions with respiratory symptoms (e.g.
dyspnoea, bronchospasm, wheezing, angioneurotic oedema) and anaphylaxis
Rare cases (10000 to < 1/1000): changes in appetite, motor weakness, and respiratory
Psychic side-effects may occur following administration of tramadol which vary
individually in intensity and nature (depending on personality and duration of
medication). These include changes in mood, (usually euphoric mood occasionally
dysphoria), changes in activity (usually suppression occasionally increase) and changes
in cognitive and sensorial capacity (e.g. decision behaviour perception disorders).
Worsening of asthma has been reported though a causal relationship has not been
Symptoms of drug withdrawal syndrome, similar to those occurring during opiate
withdrawal may occur as follows: agitation, anxiety, nervousness, insomnia,
hyperkinesia, tremor and gastrointestinal symptoms. Other symptoms that have very
rarely been seen if tramadol hydrochloride is discontinued abruptly include: panic
attacks, severe anxiety, hallucinations, paraesthesia, tinnitus and unusual CNS
Adverse effects of paracetamol are rare but hypersensitivity including skin rash may
occur. There have been reports of blood dyscrasias including thrombocytopenia and
agranulocytosis, but these were not necessarily causally related to paracetamol.
There have been several reports that suggest that paracetamol may produce
hypoprothrombinemia when administered with warfarin-like compounds. In other
studies, prothrombin time did not change.
Very rare cases of serious skin reactions have been reported.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Any suspected adverse events should be reported to the Ministry of Health
according to the National Regulation by using an online form
fixed combination of active ingredients. In case of overdose, the symptoms
include the signs and symptoms of toxicity of tramadol or paracetamol
or of both these active
Symptoms of overdose from tramadol:
In principle, on intoxication with tramadol, symptoms similar to those of other centrally acting
analgesics (opioids) are to be expected. These include in particular, miosis, vomiting,
cardiovascular collapse, consciousness disorders up to coma, convulsions and respiratory
depression up to respiratory arrest.
Symptoms of overdose from paracetamol:
An overdose is of particular concern in young children. Symptoms of paracetamol overdosage
in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage
may become apparent 12 to 48 hours after ingestion.Abnormalities of glucose metabolism and
metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to
encephalophathy, coma and death. Acute renal failure with acute tubular necrosis may develop
even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been
reported.Liver damage is possible in adults who have taken 7.5-10 g or more of paracetamol. It
is considered that excess quantities of a toxic metabolite (usually adequately detoxified by
glutathione when normal doses of paracetamol are ingested), become irreversibly bound to
Transfer immediately to a specialised unit.
Maintain respiratory and circulatory functions
Prior to starting treatment, a blood sample should be taken as soon as possible after
overdose in order to measure the plasma concentration of paracetamol and tramadol and in
order to perform hepatic tests.
Perform hepatic tests at the start (of overdose) and repeat every 24 hours. An increase in
hepatic enzymes (ASAT, ALAT) is usually observed, which normalizes after one or two
Empty the stomach by causing the patient to vomit (when the patient is conscious) by
irritation or gastric lavage.
Supportive measures such as maintaining the patency of the airway and maintaining
cardiovascular function should be instituted; naloxone should be used to reverse
respiratory depression; fits can be controlled with diazepam.
minimally eliminated from
the serum by haemodialysis
haemofiltration. Therefore treatment
of acute intoxication with
or haemofiltration alone
suitable for detoxification.
Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of
significant early symptoms, patients should be referred to hospital urgently for immediate
medical attention and any adult or adolescent who had ingested around 7.5 g or more of
paracetamol in the preceding 4 hours or any child who has ingested
150 mg/kg of paracetamol
in the preceding 4 hours should undergo gastric lavage. Paracetamol concentrations in blood
should be measured later than 4 hours after overdose in order to be able to assess the risk of
developing liver damage (via the paracetamol overdose nomogram). Administration of oral
methionine or intravenous N-acetylcysteine (NAC) which may have a beneficial effect up to
at least 48 hours after the overdose, may be required. Administration of intravenous NAC is
most beneficial when initiated within 8 hours of overdose ingestion. However, NAC should
still be given if the time to presentation is greater than 8 hours after overdose and continued for
a full course of therapy. NAC treatment should be started immediately when massive
overdose is suspected. General supportive measures must be available.
Irrespective of the reported quantity of paracetamol ingested, the antidote for paracetamol,
NAC, should be administered orally or intravenously, as quickly as possible, if possible,
within 8 hours following the overdose.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Opioids in combination with non-opioid analgesics; tramadol and
ATC code: N02A J 13X02
Tramadol is an opioid analgesic that acts on the central nervous system. Tramadol is a pure non
selective agonists of the µ,
opioid receptors with a higher affinity for the µ receptors.
Other mechanisms which contribute to its analgesic effect are inhibition of neuronal reuptake of
noradrenaline and enhancement of serotonin release. Tramadol has an antitussive effect. Unlike
morphine, a broad range of analgesic doses of tramadol has no respiratory depressant effect.
Similarly, the gastro-intestinal motility is not modified. The cardiovascular effects are generally
slight. The potency of tramadol is considered to be one-tenth to one-sixth that of morphine.
The precise mechanism of the analgesic properties of paracetamol is unknown and may involve
central and peripheral effects.
step II analgesic
pain ladder and
accordingly by the physician.
5.2 Phamacokinetic properties
Tramadol is administered in racemic form and the [-] and [+] forms of tramadol and its metabolite
M1, are detected in the blood. Although tramadol is rapidly absorbed after administration, its
absorption is slower (and its half-life longer) than that of paracetamol.
(37.5 mg/325 mg) tablet, peak
plasma concentrations of
64.3/55.5 ng/ml [(+)-tramadol/(-)-tramadol] and 4.2 µg/ml
(paracetamol) are reached
[(+)-tramadol/(-)-tramadol] and 0.9
mean elimination half-lives
5.1/4.7 h [(+)-tramadol/(-)-tramadol]
and 2,5 h (paracetamol).
During pharmacokinetic studies
after single and repeated oral
of each active ingredient
active ingredients used alone.
Racemic tramadol is rapidly and almost completely absorbed after oral administration. The mean
absolute bioavailability of a single 100 mg dose is approximately 75 %. After repeated
administration, the bioavailability is increased and reaches approximately 90 %.
After administration of Zaldiar , the oral absorption of paracetamol is rapid and nearly complete
and takes place mainly in the small intestine. Peak plasma concentrations of paracetamol are
reached in one hour and are not modified by concomitant administration of tramadol.
The oral administration of Zaldiar with food has no significant effect on the peak plasma
concentration or extent of absorption of either tramadol or paracetamol so that Zaldiar can be
taken independently of meal times.
Tramadol has a high tissue affinity (V
40 l). It has a plasma protein binding of about
Paracetamol appears to be widely distributed throughout most body tissues except fat. Its
apparent volume of distribution is about 0.9 l/kg. A relative small portion (~20%) of paracetamol
is bound to plasma proteins.
Tramadol is extensively metabolized after oral administration. About 30 % of the dose is excreted
in urine as unchanged drug, whereas 60% of the dose is excreted as metabolites.
Tramadol is metabolised through O-demethylation (catalysed by the enzyme CYP2D6) to the
metabolite M1, and through N-demethylation (catalysed by CYP3A) to the metabolite M2. M1 is
further metabolised through N-demethylation and by conjugation with glucuronic acid. The plasma
elimination half-life of M1 is 7 hours. The metabolite M1 has analgesic properties and is more potent
than the parent drug. The plasma concentrations of M1 are several-fold lower than those of tramadol
and the contribution to the clinical effect is unlikely to change on multiple dosing.
Paracetamol is principally metabolized in the liver through two major hepatic routes:
glucuronidation and sulphation. The latter route can be rapidly saturated at doses above the
therapeutic doses. A small fraction (less than 4%) is metabolized by cytochrome P 450 to an
active intermediate (the N-acetyl benzoquinoneimine) which, under normal conditions of use, is
rapidly detoxified by reduced glutathione and excreted in urine after conjugation to cysteine and
mercapturic acid. However, during massive overdose, the quantity of this metabolite is increased.
Tramadol and its metabolites are eliminated mainly by the kidneys. The half-life of paracetamol is
approximately 2 to 3 hours in adults. It is shorter in children and slightly longer in the newborn
and in cirrhotic patients. Paracetamol is mainly eliminated by dose-dependent formation of
glucuro- and sulpho-conjugate derivatives. Less than 9 % of paracetamol is excreted unchanged
in urine. In renal insufficiency, the half-life of both compounds is prolonged.
5.3 Preclinical safety data
No preclinical study has been performed with the fixed combination (tramadol and paracetamol)
to evaluate its carcinogenic or mutagenic effects or its effects on fertility.
No teratogenic effect that can be attributed to the medicine has been observed in the progeny of
rats treated orally with the combination tramadol/paracetamol.
The combination tramadol/paracetamol has proven to be embryotoxic and foetotoxic in the rat at
materno-toxic dose (50/434 mg/kg tramadol/paracetamol), i.e., 8.3 times the maximum therapeutic
dose in man. No teratogenic effect has been observed at this dose. The toxicity to the embryo and
the foetus results in a decreased foetal weight and an increase in supernumerary ribs. Lower doses,
causing less severe materno-toxic effect (10/87 and 25/217 mg/kg tramadol/paracetamol) did not
result in toxic effects in the embryo or the foetus.
Results of standard mutagenicity tests did not reveal a potential genotoxic risk for tramadol in
Results of carcinogenicity tests do not suggest a potential risk of tramadol for man.
Animal studies with tramadol revealed, at very high doses, effects on organ development,
ossification and neonatal mortality, associated with maternotoxicity. Fertility reproductive
performance and development of offspring were unaffected. Tramadol crosses the placenta. Male
and female fertility was not affected.
Extensive investigations showed no evidence of a relevant genotoxic risk of paracetamol at
therapeutic (i.e. non-toxic) doses.
Long-term studies in rats and mice yielded no evidence of relevant tumorigenic effects at
nonhepatotoxic dosages of paracetamol.
Animal studies and extensive human experience to date yield no evidence of reproductive
List of excipients
powdered cellulose, maize starch, pregelatinised starch, sodium starch glycolate,
Film-coating: hypromellose, lactose monohydrate,titanium dioxide, macrogol 6000, yellow
iron oxide, propylene glycol, talc.
The expiry date of the product is indicated on the packaging materials
Special precautions for storage
Do not store above 30ºC
Nature and contents of container
Zaldiar tablets are packed in.paper/PET/aluminium-PVC blisters.
Box of 10 or 20 tablets
Not all packaging sizes may be marketed.
Special precautions for disposal and other handlings
No special requirements.
MARKETING AUTHORISATION HOLDER
POB 45054, JERUSALEM 91450
Grünenthal GmbH, Zieglerstraße 6, 52078 Aachen, Germany
MARKETING AUTHORISATION NUMBER(S)
The content of this leaflet was approved by the Ministry of Health in October 2013 and and
updated according to the guidelines of the Ministry of Health in March 2020
ןכרצל ןולעב )תוחיטב עדימ ( הרמחה לע העדוה :ךיראת
םושירה רפסמו תילגנאב רישכת םש
:םושירה לעב םש מ"עב הרביל-םראפ-וא-קט תושקובמה תורמחהה ןולעב קרפ יחכונ טסקט שדח טסקט שמתשהל ןיא יתמ רישכתב .טסקט תנזהל ןאכ ץחל .טסקט תנזהל ןאכ ץחל שמתשהל ןיא ילבמ הפורתב ינפל אפורב ץעוויהל לופיטה תלחתה תלחממ ת/לבוס ךנה םייעמ וא תוילכ ,דבכ
אפורל חוודל ךילע ךנה םא וז הפורת לטונ ךנהש וא חותינ רובעל דמוע .המדרה דבכ תלחממ לבוס ךנה
םא וא וא ךלש םייניעה עבצש תנחבה רבד ,םיבוהצל וכפה ךלש רועה היעב וא תבהצ לע עיבצהל לוכיה הרמה יכרדב .הילכ תייעבמ לבוס ךנה םא וא חותינ רובעל דמוע ךנה וא אפורל ךכ לע רפס המדרה םייניש אפור
יאוול תועפות רבעב תחתיפ םא תליטנמ האצותכ תוירוע לומאטצרפ םיליכמה םירישכת םיליכמה םירישכת לוטיל ןיא בוש ומרגי אלש ידכ ,לומאטצרפ תורומח תוירוע תועפות
ןיב תובוגת תויתפורת
לופיטל , לוכי םירידנ םירקמב ,)ןואכידב לטונ ךנה םא םינטפירט - וא )הנרגימל(
"ןינוטורסה םורדניס" םרגיהל םייונישב אטבתהל לוכיה תונבצע :ןוגכ( ישפנה בצמב ,)תמדרת ,תויזה ,רתי :ןוגכ( תימונוטוא תוביצי-יא יתלב םד ץחל ,ריהמ בל בצק םייוקיל ,)הימרתרפיה ,ביצי :ןוגכ( םירלוקסומ-וריונ רסוח ,היסקלפ-רפיה םינימסת וא/ו )היצנידרואוק :ןוגכ( לוכיעה תכרעמ לש )רידנ( )לושלש ,האקה ,הליחב לע תועיפשמה תופורת תיזכרמה םיבצעה תכרעמ וא שוטשטל םרגל תויושע ולא תופורת .ןופליע תשוחת ,העגרהל תופורת תוללוכ ,ןוסניקרפב לופיטל ,הנישל דגנ ,היספליפאב לופיטל םימידרמ םירמוח ,תויגרלא םיבאכ יככשמו חותינל דגנ םיפוריסב םג( םייטוקרנ .לוהוכלאו )לועיש םד תשירק דגנ תופורת לש העפשהב הדירי ןכתת תוחקלנ ןהו הדימב ראידלאז :תואבה תופורתה םע דחי לופיטל( ןיפזאמברק - .)היספליפא יפקתהב םידיאויפוא םיבאכ יככשמ - :ומכ( םימייוסמ
לופיטל( ןורטסנדנוא -
serotonin re-uptake inhibitors
םא .)ןואכידב לופיטל , ,רתי תונבצע ,לובלב שיגרמ ךנה ,םוח תועזה היצנידרואוק רסוח , תוינוצר אל םירירש תועונתו – לושלש וא םייניעב וא םייפגב .אפורל הנפ ,העגרהל תופורת לטונ ךנה םא - ןוגכ םיבאכ יככשמ וא ,הנישל דגנ םיפוריסב םג( ןיאדוקו ןיפרומ ,)לועיש תייפרהל הפורת( ןפולקב ץחל תדרוהל תופורת ,)םירירש ,םד .תויגרלא דגנ תופורת ינונשי שיגרתו ןכתי ולא םירקמב ןופלע תשוחת וא הלא םירקמב . .אפורל רפס תומיוסמ תופורת לטונ ךנה םא הווחתו ןכתי .ןואכד דגנ םירירש יצוויכ לש םימוטפמיס ,ןיעה ירירש ללוכ ,םיינוצר אל ,דער ,רתי תעזה, תונבצע סונוט ,םימזגומ םיסקלפר לעמ םוחו הובג םירירש
לטונ ךנה םא - דגנ תופורת םד תשירק לש תויביטקפאה . ונכתיו תונתשהל הלוכי תופורתה תידימ אפורל חוודל שי .םימומיד ךשוממ םומיד לש הרקמ לכ לע יופצ אל וא
לש העפשהב יוניש ןכתת דחי תוחקלנ ןהו הדימב ראידלאז :תואבה תופורתה םע ןודירפמוד וא דימארפולקוטמ תוליחב דגנ( ןורטסנדנוא )תואקהו לופיטל( ןימאריטסלוכ םדב לורטסלוכ רתיב
:הקנהו ןוירה .)תוליחבב הנמ תליטנב ,תאז םע דחי ךרדב ןיא ראידלאז לש תדדוב תא קיספהל ךרוצ ללכ .הקנהה ןיצימורתיראו לוזנוקוטק )םימוהיזב לופיטל(
)הלטוב וז הלקה( יאוול תועפות )החירפ( תוירוע תובוגת ,הליל יטויס תורידנ םיתיעל יביטינגוק דוקפתב הדירי תויועטל םורגל הלולעה ,ןובאיתב יוניש ,טופישב ,היצנידרואוק תוערפה ץחלב הילע ,היאר תוערפה ,םירירש תיווע ,יטיא קפוד ,םד ,דוריג( תוליגר אל תושוחת תבחרה )המודכו ץוצקע םינושיא
החירפ המגודל תוירוע תובוגת (תויחופלשו "ףיעס האר תורהזא שומישב תועגונה תודחוימ הפורתב
םיפקתה :תורידנ םיתיעל תוערפה ,םייטפליפא ,תורכמתה ,היצנידרואוק שוטשט היאר
תבחרה .הפוקניס ,םינושיא תוצווכתה וא שמתשת דציכ ?הפורתב
קרפל ראידלאז לוטיל שי ,ןורקעב .שרדנה רתויב רצקה ןמזה
ןונימה תא לוטיל שי יללכ ןפואב תעינמל ירשפאה רתויב ךומנה .באכ הרומח דבכ הלחמ
לש הרקמב ראידלאז לוטיל ןיא תקיפס יא
לבוס ךנה תינוניב וא הלק דבכ תקיפס יאמ
ץילמהל יושע אפורה לע
.ןונימה תוילכ תלחמ
ץילמהל יושע אפורה לע תכראה
.ןונימה תעפשהש בשוח התא םא ךנה( ידמ הקזח איה ראידלאזה יישק ךל שי וא שטשוטמ שיגרמ ךוכיש( ידמ השלח וא )המישנ םע רשק רוצ ,)קפסמ וניא באכה ךלש אפורה
ראידלאז רתוי תלטנ םא אפורל תונפל שי ,תויחנההמ התא םא םג ,תידיימ חקורל וא ןוכיס םייקו תויה ,בוט שיגרמ עיפוהל לוכיש דבכל קזנ לש רתוי רחואמ
,תורידנ יאוול תועפות אפורל הנפ הבוגת חתפמ ךנה םא תאטבתמ .תיגרלא ,ןושלה ,םינפה תוחפנתהב החירפ ,העילבב ישוק ,עולה םלהו המישנב ישוק ,רועב .)קוש( יטקליפנא )החירפ( תוירוע תובוגת )תופסונ יאוול תועפות ףיעסב(
תובוגת קרפב קר תוסחייתה שי .תויתפורת ןיב ,תיגרלא הבוגת חתפמ ךניה םא םינפה תוחפנתהב תאטבתמה ראווצהו ישוק ,עולה ,ןושלה
ישוק ,רועב החירפ ,העילבב ,המישנב הדירי
םד ץחלב ןופליעו .)קוש( יטקליפנא םלהו , םירקמב םורגל לוכי לומטצרפ רוע תולחמ תעפוהל ,םירידנ םילוכי םהלש םינמיסהש תופירח ,תויחופלש ,החירפ ,םדוא :תויהל תועפות .תבחרנ תירוע העיגפ תולולע תופירח תוירוע יאוול תלטנ רבעב םא םג עיפוהל ביכרמה תא םיליכמה םירישכת .היעב אלל לומטצרפ ליעפה יאוול תועפות תועיפומ םא לופיטה קיספהל שי ,תוירוע ידיימ ןפואב אפורל תונפלו
םיאבה םירכומה יאוולה תועפות וחווד
םישמתשמה םישנא תופורתב
תוליכמה לודמרט קר קר וא
תליטנ תעב ראידלאז ךכ לע חוודל שי , :אפורל
בצממ המיקב ןופלע תשוחת בל בצק ,הבישי וא הביכש יטיא ,תויופלעתה , ייוניש ןובאית ,םירירש תשלוח , המישנ רתוי תיטיא
חור בצמ ייוניש םייוניש , תוליעפב םייוניש , ,הסיפתב המתסא לש הרמחה
.תמייק םירידנ םירקמב
לע העיבצמש תיגרלא הבוגת ףיעס האר(
תונפל שי" , דימ .)"םא ,אפורל םיגירח םירקמב ת ןכתי הריפס לש הכומנ
אטבתתש ףאהמ םימומידב
םייכינח .תוממדמ דחי ראידלאזב שומיש םדה לולידל תופורת םע לוכי שי .םימומידל ןוכיסה תא לידגהל םומיד לכ לע חוודל
וא ךשוממ יופצ יתלב
ידימ ןפואב אפורל
םע יאוול תועפות לופיטה תקספה לופיט תקספהל ,יללכ ןפואב .יאוול תועפות הנייהת אל םיטעמ םילפוטמ לצא ,םלוא תפוקת ךשמב ולפוטש דאמ וקיספהשו ,הכורא ןמז הפורתה תליטנ תא תימואתפ יאוול תועפות עיפוהל תויושע ,הדרח ,טקש יא :ןוגכ תומיוסמ וא םדריהל ישוק ,תונבצע םירקמב .םייעמו הביק תויעב ,הקינאפ יפקתה ונכתי םירידנ תוליגר אל תושוחתו ,תויזה םיינזואב שער ,ץוצקע ומכ ( תוגירח תועפות .)המודכו ,לובלב ומכ םיבצעה תכרעמב .רתויב תורידנ ןניה היונראפו תועפותמ תחא העיפומ םא תקספה רחאל הלאה יאוולה םע ץעייתהל אנ – לופיטה .ךלש אפורה אל לופיט תקספהל ,יללכ ןפואב ,םלוא .יאוול תועפות הנייהת דאמ םיטעמ םילפוטמ לצא ןמז תפוקת ךשמב ולפוטש תא תימואתפ וקיספהשו ,הכורא עיפוהל תולולע הפורתה תליטנ האר( תומיוסמ יאוול תועפות ףיעס
םא .)"יאוול תועפות" ךנה תכשוממ הפוקתל ראידלאז לטונ ץעייתהל אנ ,קיספהל ךנוצרבו ךפוגו ןכתיו תויה ךלש אפורה םע הפורתל לגרתה
:)יאוול תועפות( ולטנש םישנא םירידנ םירקמב לודמרט םילולע ןמז ךרואל שוחל ערב
לופיטה תא וקיספי .תוימואתפב
ונכתי ולא םירקמב ,תונבצע ,הדרח לש תושוחת תיביטקארפיה ,דער
םישנא דואמ טעמ
ולבס ,הקינאפ יפקתהמ
ץוצקעו דרג ו לומינ , שער םיינזואב
.)ןוטניט שוחתו הדימב ולא תועפות
תקספה רחאל ראידלאזב לופיטה אנא , הנפ ךלש אפורל
אפורל ןולעב )תוחיטב עדימ ( הרמחה לע העדוה :ךיראת
:םושירה רפסמו תילגנאב רישכת םש
:םושירה לעב םש הרביל םראפ-וא-קט תושקובמה תורמחהה ןולעב קרפ יחכונ טסקט שדח טסקט
The dose should be individually
adjusted according to intensity of pain
and response of the patient.
The usual dosages may be used
although it should be noted that in
volunteers aged over 75 years the
elimination half life of tramadol was
increased by 17% following oral
administration. In patients over 75
years old, it is recommended that
the minimum interval between doses
should be not less than 6 hours, due
to the presence of tramadol
The dose should be individually adjusted
according to intensity of pain and response
of the patient. The lowest effective dose for
analgesia should generally be selected.
A dose adjustment is not usually
necessary in patients up to 75 years
without clinically manifest hepatic or renal
insufficiency. In elderly patients over 75
years elimination may be prolonged.
Therefore, if necessary the dosage interval
is to be extended according to the patient's
Special Warnings and
Interaction with Other
Other Forms of
In isolated cases there have been
reports of Serotonin Syndrome in a
temporal connection with the
therapeutic use of tramadol in
combination with other
serotoninergic medicines such as
selective serotonin re-uptake
inhibitors )SSRIs( and triptans.
Signs of Serotonin Syndrome may
be for example, confusion, agitation,
fever, sweating, ataxia,
hyperreflexia, myoclonus and
Concomitant therapeutic use of
tramadol and serotoninergic drugs
such as selective serotonin re-uptake
inhibitors )SSRIs(, serotonin-
norephnepherine reuptake inhibitors
)SNRIs(, MAO inhibitors )see section
4.3(, tricyclic antidepressants and
mirtazapine may cause serotonin
toxicty. Serotonin Syndrome is likely
when one of the following is observed:
Spontaneous clonus, Inducible or
ocular clonus with, agitation, or
diaphoresis, Tremor and
hyperreflexia,Hypertonia and body
temperature > 38°C and inducible or
oclurar clonus .Withdrawal of the
serotonergic drugs usually brings
about a rapid improvement.
Treatment depends on type and
severity of symptoms
Medicinal products reducing
the seizure threshold, such as
bupropion, serotonin reuptake
tricyclic antidepressants and
neuroleptics. Concomitant use
of tramadol with these drugs
can increase the risk of
Tramadol can induce convulsions and
increase the potential for selective
serotonin reuptake inhibitors )SSRIs(,
inhibitors )SNRIs(, tricyclic antidepressants
antipsychotics and other seizure
threashold-lowering medicinal products
)such as bupropion, mirtazapine,
tetrahydrocannabinol( to cause
Long-term treatment during pregnancy may
lead to withdrawal symptoms in the newborn
after birth, as a consequence of habituation
Central and peripheral nervous system
Rare )≥ 1/10000 to < 1/1000(: ataxia,
Rare )<0.1 %(: blurred vision
Central and peripheral nervous system
Rare )≥ 1/10000 to < 1/1000(: ataxia,
convulsions, speech disorder, syncope.
Rare )≥ 1/10000 to < 1/1000(: vision blurred
, miosis, mydriasis