Adverse reactions : תופעות לוואי

4.8. Undesirable effects

The most commonly reported adverse reactions are nausea and dizziness, both occurring in more than 10 % of patients.

The frequencies are defined as follows:
Very common:        ≥1/10
Common:             ≥1/100, <1/10
Uncommon:           ≥1/1000, <1/100
Rare:               ≥1/10000, <1/1000
Very rare:          <1/10000
Not known           cannot be estimated from the available data 
Immune system disorders:
Uncommon: toxic epidermal necrolysis (TEN) and Stevens-Johnson-syndrome (SJS), and cross reactivity with non-steroidal anti-inflammatory drugs 
Cardiovascular disorders:

Common: hot flushes, vasodilation
Uncommon: cardiovascular regulation (palpitation, tachycardia, postural hypotension or cardiovascular collapse). These adverse reactions may occur especially on intravenous administration and in patients who are physically stressed. Myocardial infarction, peripheral ischemia, hypertension, hypertension aggravated.

Rare: bradycardia

Nervous system disorders:
Very common: dizziness/vertigo

Common: headache, drowsiness, somnolence, hypoesthesia

Uncommon: sedation, disturbance in attention, dizziness aggravated 
Rare: changes in appetite, paraesthesia, tremor, respiratory depression, epileptiform convulsions, involuntary muscle contractions, abnormal coordination, syncope, hypertonia and dysgeusia. If the recommended doses are considerably exceeded and other centrally depressant substances are administered concomitantly (see section 4.5), respiratory depression may occur. Epileptiform convulsions occurred mainly after administration of high doses of tramadol or after concomitant treatment with medicinal products which can lower the seizure threshold (see sections 4.4 and 4.5).

Not known: speech disorders, abnormal gait, amnesia, difficulty in concentration, movement disorder, euphoria, emotional lability, delirium, paresthesia 
Psychiatric disorders:

Common: depression, restlessness
Uncommon: irritability, libido decreased, disorientation, abnormal dreams 
Rare: hallucinations, confusion, sleep disturbance, anxiety and nightmares. Psychic adverse reactions may occur following administration of Tramadex which vary individually in intensity and nature (depending on personality and duration of treatment). These include changes in mood (usually elation, occasionally dysphoria), changes in activity (usually suppression, occasionally increase) and changes in cognitive and sensorial capacity (e.g. decision behaviour, perception disorders).
Dependence may occur. Suicidal ideation, drug abuse and addiction.

Eye disorders:

Common: miosis, visual disturbance
Rare: blurred vision
Not known: mydriasis

Respiratory disorders:

Common: sneezing, cough, rhinorrhea, nasal congestion, sinus congestion 
Uncommon: yawning
Rare: dyspnoea. Worsening of asthma has been reported, though a causal relationship has not been established.

Gastrointestinal disorders:

Very common: nausea
Common: constipation, dry mouth, vomiting, dyspepsia, abdominal pain 
Uncommon: anorexia, retching; gastrointestinal irritation (a feeling of pressure in the stomach, bloating), diarrhea, flatulence, toothache, constipation aggravated, appendicitis, pancreatitis

Not known: sore throat

Skin and subcutaneous tissue disorders:
Common: sweating, dermatitis

Uncommon: dermal reactions (e.g. pruritus, rash, urticaria), contusion, piloerection, clamminess, night sweats

Not known: Vesicles

Musculo-skeletal disorders:
Common: arthralgia, back pain, pain in limb, neck pain

Uncommon: muscle cramps, muscle spasms, joint stiffness, muscle twitching, myalgia, osteoarthritis aggravated

Rare: motorial weakness

Hepatobiliary disorders:
Uncommon: cholelithiasis, cholecystitis

Very rare: In a few isolated cases an increase in liver enzyme values has been reported in a temporal connection with the therapeutic use of tramadol.

Renal and urinary disorders:

Common: Urinary frequency
Uncommon: hematuria

Rare: micturition disorders (difficulty in passing urine, dysuria and urinary retention) 
Reproductive system and breast disorders:

Common: menopausal symptoms
Rare: menstrual disorders
Infections and infestations:

Common: nasopharyngitis, upper respiratory tract infection, sinusitis, influenza, gastroenteritis viral, urinary tract infection, bronchitis

Uncommon: cellulitis, ear infection, gastroenteritis, pneumonia, viral infection 

General disorders:
Common: fatigue, asthenia, malaise, weakness, pain, feeling hot, influenza like illness, fall, rigors, lethargy, pyrexia, chest pain, blood creatine phosphokinase increased, appetite decrease

Uncommon: feeling jittery, edema lower limb, shivering, joint swelling, drug withdrawal syndrome, peripheral swelling, joint sprain, muscle injury, alanine aminotransferase increased, blood pressure increased, aspartate aminotransferase increased, heart rate increased, blood glucose increase, liver function tests abnormal

Rare: weight loss, allergic reactions (e.g. dyspnoea, bronchospasm, wheezing, angioneurotic oedema) and anaphylaxis; Symptoms of withdrawal reactions, 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 with tramadol discontinuation include: panic attacks, severe anxiety, hallucinations, paraesthesias, tinnitus and unusual CNS symptoms (i.e. confusion, delusions, depersonalization, derealization, paranoia)

Not known: accidental injury, death, serotonin syndrome, flushing, hypoglycaemia 
Other adverse experiences, causal relationship unknown: A variety of other adverse events were reported infrequently in patients taking tramadol during clinical trials and/or reported in post-marketing experience. A causal relationship between Tramadol and these events has not been determined.
Aabnormal ECG, hypotension, myocardial ischemia, pulmonary edema, pulmonary embolism, migraine, gastrointestinal bleeding, liver failure, proteinuria, hepatitis, stomatitis, Creatinine increase, hemoglobin decrease, cataracts, deafness