Indications:

Tramadol is indicated for the treatment of moderate to intense pain, particularly postoperative pain for the injectable form.
Available in the form of capsules with prolonged release or not, in drinkable form and in injectable form.

Dosage and method of administration:

The dosage of tramadol must be adapted to the level of pain and to the person, tolerance and effectiveness being highly variable depending on the patient.

Capsule:

Tramadol 50 mg capsule, is not suitable for the treatment of children under 15 years of age.
Under no circumstances should this medicinal product be administered for longer than absolutely necessary. If long-term treatment of pain with this drug is necessary, given the nature and severity of the disease, careful and regular monitoring should be carried out (interposing therapeutic breaks if necessary) in order to check whether and to what extent further processing is necessary.

Sharp pains:

The starting dose is 100 mg (2 capsules) followed by 50 or 100 mg (1 or 2 capsules) every 4-6 hours without exceeding 400 mg/24 h (8 capsules).

Chronic pain:

The starting dose is 50 or 100 mg (1 or 2 capsules) followed by 50 or 100 mg (1 or 2 capsules) every 4-6 hours without exceeding 400 mg/24 h (8 capsules).
In the event of association with a prolonged-release form (interdose in the event of a painful sting), the dose of 400 mg per day should not be exceeded.

LP tablets:

The usual starting dose is 50 to 100 mg of tramadol hydrochloride twice a day, morning and evening. If the level of analgesia is insufficient, the dose may be increased to 150 mg or 200 mg tramadol hydrochloride twice daily. This form is in no way intended for children under 15 years of age. Do not exceed the dose of 400 mg/d.

Drinkable solution :

Reserved for children from 3 years old and teenagers. The dose depends on the weight of the patient. Cases of accidental overdose and cases of rapid metabolisers have been reported in children (see Warnings/Precautions for use: “Children and rapid metabolisers” and Overdose).
The usual dosage per intake is 1 mg/kg of tramadol, i.e.:

• 0.4 × Weight (kg) = Number of drops per dose.
• To be renewed if necessary 3 to 4 times a day (6 to 8 hour interval between doses).

The maximum dosage per intake is 2 mg/kg of tramadol, i.e.:

• 0.8 × Weight (kg) = Number of drops per dose.
• Do not exceed 40 drops per dose (i.e. 100 mg of tramadol hydrochloride).
• To be renewed if necessary 3 to 4 times a day (6 to 8 hour interval between doses).

When prescribing, indicate the dose in number of drops per dose. Round down to the nearest unit (in case of decimals).

Solution for injection:

Tramadol can be injected intravenously slowly (2-3 minutes) or brought into solution for administration by infusion or by a patient-controlled analgesia device.
Severe pain: The starting dose is 100 mg. During the first hour after the loading dose, additional doses of 50 mg may be given every 10-20 minutes without exceeding a total dose of 250 mg (including the loading dose). Subsequently, administer 50 or 100 mg every 4-6 hours without exceeding a total daily dose of 600 mg.
Moderate pain: Administer 50 or 100 mg during the 1st hour.

Hepatic and renal impairment:

The elimination of tramadol in these situations is delayed. The interval between doses of tramadol may need to be increased. Similarly in the elderly, as renal function may be impaired, increased vigilance will be necessary regarding the frequency of treatment doses.

Contraindications:

– Hypersensitivity to the active substance or to any of the excipients listed under Composition;
– During acute intoxication by alcohol, hypnotics, analgesics, opioids or other psychotropic drugs;
– In patients who are being treated concurrently or who have been treated within the previous 14 days with MAO inhibitors, especially with linezolid and methylene blue (see Interactions);
– In case of severe respiratory failure;
– In children under 15 years of age (capsule and solution for injection);
– In children under 3 years old (oral solution);
– In case of epilepsy not controlled by treatment (see Warnings and Precautions for use);
– In the withdrawal treatment of drug addicts.
– This medication should generally not be used during pregnancy.

Interactions:

Drugs causing serotonin syndrome:

Tramadol can cause seizures and increase the seizure potential of
– selective serotonin reuptake inhibitors (SSRIs),
– serotonin and adrenaline reuptake inhibitors (IRSA),
– tricyclic antidepressants,
– antipsychotics (neuroleptics such as phenothiazines and butyrophenones) and other drugs lowering the seizure threshold (such as bupropion, mirtazapine, tetrahydrocannabinol, mefloquine, chloroquine, fluoroquinolones).

Concomitant use of tramadol and serotonergic products, such as selective serotonin reuptake inhibitors (SSRIs), serotonin adrenaline reuptake inhibitors (IRSA), MAO inhibitors (see Contraindications), tricyclic antidepressants and mirtazapine can lead to serotonin syndrome:
diarrhea, tachycardia, sweating, tremors, confusion or even coma. Interruption of serotonergic products generally leads to rapid improvement. Treatment depends on the type and severity of symptoms.

Sedative drugs:

It must be taken into account that many drugs or substances can add to their depressant effects on the central nervous system and contribute to reducing alertness. These are morphine derivatives (analgesics, cough suppressants and substitution treatments), neuroleptics, barbiturates, benzodiazepines, anxiolytics other than benzodiazepines (for example, meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepin , mianserin, mirtazapine, trimipramine), sedating H1 antihistamines, central antihypertensives, baclofen and thalidomide.

Contraindicated :

Irreversible MAOIs (iproniazid): risk of onset of serotonin syndrome: diarrhea, tachycardia, sweating, tremors, confusion or even coma. Respect a period of two weeks between stopping the MAOI and starting treatment with tramadol, and at least one week between stopping treatment with tramadol and starting the MAOI.

Not recommended:

– Morphine agonists-antagonists (buprenorphine, nalbuphine, pentazocine): reduction of the analgesic effect by competitive blocking of the receptors, with risk of appearance of a withdrawal syndrome.
– Alcohol (drink or excipient): alcohol increases the sedative effect of morphine analgesics. Impaired alertness can make driving vehicles and using machines dangerous. Avoid taking alcoholic beverages and medications containing alcohol.
– Carbamazepine: may decrease tramadol plasma concentrations and may therefore reduce the analgesic effects and shorten the duration of action of tramadol.
– Reversible MAOIs A including linezolid and methylene blue: risk of onset of serotonin syndrome: diarrhea, tachycardia, sweating, tremors, confusion or even coma. If the association cannot be avoided, very close clinical monitoring. Start the combination at the minimum recommended dosages.
– Morphine partial antagonists: risk of reduced analgesic effect.
– Naltrexone: risk of reduced analgesic effect.
– Sodium Oxybate: increased central depression. Impaired alertness can make driving vehicles and using machines dangerous.

Requiring precautions for use:

Vitamin K antagonist: risk of increased effect of vitamin K antagonist and risk of bleeding. More frequent monitoring of INR. Possible adjustment of vitamin K antagonist dosage during tramadol treatment and after its discontinuation.

To consider :

– Other morphine agonist analgesics, morphine-like antitussives (dextromethorphan, noscapine, pholcodine), true morphine antitussives (codeine, ethylmorphine): increased risk of respiratory depression which can be fatal in the event of overdose.
– Other drugs lowering the seizure threshold: increased risk of seizures.
– Other sedative drugs: increased central depression. Impaired alertness can make driving vehicles and using machines dangerous.
– Benzodiazepines and related drugs: increased risk of respiratory depression which can be fatal in the event of overdose.
– Barbiturates: increased risk of respiratory depression which can be fatal in the event of overdose.
– MAOI-B: risk of onset of serotonin syndrome.
– Selective serotonin reuptake inhibitors (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline): risk of seizures and/or serotonin syndrome.
– Venlafaxine: risk of onset of seizures and/or serotonin syndrome.
– Bupropion: increased plasma concentrations of tramadol by decreasing its hepatic metabolism by bupropion. In addition, risk of convulsions by adding the effects of the two drugs.
– Ondansetron: decreased intensity and duration of the analgesic effect of tramadol and risk of decreased antiemetic effect of ondansetron.

Warnings and precautions for use:

Warnings :

Topalgic should be used with caution in patients with:
– Opioid addiction. If necessary, the treatment will be short and under strict medical supervision. Tramadol is not a replacement drug. Tramadol cannot correct opioid withdrawal symptoms.
– A predisposition to convulsions. tramadol may cause seizures in these patients.
– Head trauma.
– A state of shock.
– An alteration of consciousness without obvious cause.
– Central or peripheral respiratory function disorders. A risk of respiratory depression cannot be excluded in this situation.
– An increase in intracranial pressure.
Tolerance and physical and/or psychic dependence may develop even at therapeutic doses. The clinical need for analgesic treatment should be reassessed on a regular basis). Addiction and abuse have been reported. Withdrawal symptoms, similar to those that occur during opioid withdrawal, could occur even at therapeutic doses and for short courses of treatment. Withdrawal symptoms can be avoided by gradually reducing the doses when stopping treatment, especially after long periods of treatment.
The combination of tramadol with opioid agonists-antagonists (buprenorphine, nalbuphine, pentazocine) and carbamazepine are not recommended.
Drinking alcohol during treatment is not recommended.
This medication contains castor oil and may cause digestive disorders (mild laxative effect, diarrhea).
This medicinal product contains 0.0425 mg of sodium per drop. To be taken into account in people following a strict low-sodium diet.
This medicine contains sucrose. Its use is not recommended in patients with fructose intolerance, glucose-galactose malabsorption syndrome or sucrase/isomaltase deficiency.

Children and Rapid Metabolizers:

– The child’s entourage should be informed that the oral solution must be kept out of reach of children (locked up) in order to avoid any risk of accidental overdose which could have potentially fatal consequences (see Overdose).
– Cases of ultra-rapid metabolisers have been reported, particularly in children.
– The parents must be informed, particularly during the first administration, of the need to monitor their child, and to call a doctor or an emergency service in the event of any unusual sign, in particular disturbances of consciousness, miosis, vomiting, convulsions or respiratory depression (see Overdose).

Precautions for use:

Tramadol should only be used after careful assessment of the benefit/risk ratio, depending on the origin of the pain and the patient’s profile.
Tramadol should be used with caution in elderly patients, due to the risk of falling and loss of consciousness.

Side effects :

Immune system disorders:

Rare: allergic reactions (dyspnoea, bronchospasm, wheezing, angioedema) and anaphylaxis.

Psychiatric disorders:

Rare :
– Hallucinations, confusion, sleep disturbances, delirium, anxiety and nightmares.
– Psychic side effects whose intensity and nature vary from one patient to another (depending on individual reactivity and duration of treatment).
– Mood disturbances (usually elation, occasionally dysphoria), changes in activity (usually decreased activity, occasionally increased) and changes in cognitive and sensory abilities (for example, decision-making ability, perceptual disturbances).
– Cases of abuse and dependence have been reported as well as cases of withdrawal syndrome. Withdrawal symptoms, similar to those noted during opiate withdrawal, may occur such as: agitation, anxiety, nervousness, insomnia , hyperkinesia, tremors and gastrointestinal symptoms.
– Other withdrawal symptoms have been reported very rarely, including: panic attack, severe anxiety, hallucinations, paraesthesia, tinnitus, other CNS disorders (e.g. confusion, delirium, depersonalization, derealization, paranoia).

Nervous system disorders:

Very common: dizziness.
Common: headache, somnolence.
Rare: paraesthesia, tremors, convulsions, involuntary muscle contractions, coordination abnormal, syncope, slurred speech.
Convulsions have occurred mainly after administration of high doses of tramadol or after concomitant treatment with medicinal products which may lower the seizure threshold (see Warnings and Precautions for use, Interactions).
Not known: Fainting.

Metabolism and nutrition disorders:

Rare: change in appetite.
Not known: hypoglycaemia.

Visual disorders:

Rare: Miosis, blurred vision, mydriasis.

Cardiac and vascular disorders:

Uncommon: effects on cardiovascular regulation (palpitations, tachycardia, orthostatic hypotension or cardiovascular collapse). These side effects may occur especially after intravenous administration and in patients under physical stress.
Rare: bradycardia.
Under investigation: some increase in blood pressure.

Respiratory, Thoracic and Mediastinal Conditions:

Rare: Respiratory depression, dyspnea. Respiratory depression may occur if the doses administered greatly exceed the recommended doses and if other central depressant drugs are administered concomitantly (see Interactions).
Worsening of asthma has also been reported, although a causal relationship has not been established.

Gastrointestinal and Hepatobiliary Disorders:

Very common: nausea.
Common: Constipation, dry mouth, vomiting.
Uncommon: retching, gastrointestinal discomfort (gastric heaviness, flatulence), diarrhoea.
In a few isolated cases, an increase in liver enzymes has been reported during the therapeutic use of tramadol.

Skin and Subcutaneous Tissue Disorders:

Common: hyperhidrosis.
Uncommon: skin reactions (e.g. pruritus, rash, urticaria).

Musculoskeletal and Systemic Conditions:

Urinary and Kidney Disorders:

General conditions and administration site conditions:

Common: asthenia.

Overdose:

Symptoms :

Treatment :

Take the usual general emergency measures. Ensure the freedom of the respiratory tract (suction), maintain ventilation and circulation according to the symptoms. The antidote for respiratory depression is naloxone. In animal experiments, naloxone had no effect on seizures. In such cases, diazepam should be administered intravenously.
In case of poisoning with oral forms, gastrointestinal elimination with activated charcoal or gastric lavage is recommended only within 2 hours after taking tramadol. After this time, gastrointestinal decontamination may be useful in the event of intoxication by exceptionally large quantities of tramadol or by prolonged-release forms.
Tramadol is very slightly cleared from serum by hemodialysis or by hemofiltration. Therefore, treatment of acute Topalgic poisoning with hemodialysis or hemofiltration alone is not appropriate for detoxification.

Drinkable solution :

Pregnancy :

There is insufficient evidence regarding the safety of use of tramadol during pregnancy in humans. Tramadol should therefore not be used in pregnant women. Administered before or during childbirth, tramadol does not modify uterine contractility. Tramadol may cause changes in respiratory rate in neonates which are generally without adverse clinical consequences. Prolonged use during pregnancy may cause withdrawal syndrome in the newborn.

Feeding with milk :

Approximately 0.1% of the maternal dose of tramadol is secreted into breast milk. Thus, after oral administration in the immediate postpartum of doses up to 400 mg, the breast-fed child receives approximately 3% of the weight-adjusted maternal dose. Therefore, tramadol should not be used during breast-feeding, or breast-feeding should be discontinued in case of treatment with tramadol. Stopping breast-feeding is generally not necessary in the case of a single dose of tramadol.

Pharmacodynamics:

Tramadol is a centrally acting opioid analgesic. It is a partial and non-selective opioid µ, δ, and κ receptor agonist with higher affinity for µ receptors. Other mechanisms that contribute to the analgesic effects of the product are the inhibition of neuronal reuptake of norepinephrine and the increase in the release of serotonin. Tramadol has an antitussive effect. Unlike morphine, a wide range of analgesic doses of tramadol has no respiratory depressant effect. Gastrointestinal motility is also not influenced. Effects on the cardiovascular system tend to be mild. The potency of tramadol is said to be 1/10 to 1/6 that of morphine..