DOLL-P Tablet

For the symptomatic treatment of moderate to severe pain.

The use of DOLL-P should be restricted to patents whose moderate to severe pain is considered to require a combination of tramadol and acetaminophen.

Dosage and Direction For Use

ADULTS AND ADOLESCENTS (12 years and older)

The use of DOLL-P should be restricted to patients whose moderate to severe pain is considered to require a combination of tramadol and Acetaminophen.

The dose should be individually adjusted according to intensity of pain and response of the patient.

An initial dose of 2 tablets of DOLL-P is recommended. Additional doses can be taken as needed, not exceeding 8 tablets/day (equivalent to 300mg tradmadol and 2600mg Acetaminophen) per day.

The dosing interval should not be less than 6 hours.

DOLL-P should under no circumstances be administered for longer than is strictly necessary. If repeated use or long term treatment with DOLL-P 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.

Method of administration: oral use.

Tablets must be swallowed whole, with a sufficient quantity of liquid. They must not be broken or chewed.

(Please see the package insert about the details below.)

Children

Elderly patients

Renal insufficiency

Hepatic insufficiency

- Hypersensitivity to tramadol, acetaminophen or to any of the excipients used.

- Acute intoxication with alcohol, hypnotic drugs, centrally-acting analgesics, opioids or psychotropic drugs.

- Patients who are receiving monoamine oxidase inhibitors or within 2 weeks of their withdrawal.

- Severe hepatic impairment.

- Epilepsy not controlled by treatment.

The most commonly reported undesirable effects during the clinical trials performed with the Acetaminophen/tramadol combination were nausea, dizziness and somnolence, observed in more than 10% of patients.

Cardiovascular system disorders

Uncommon: hypertension, palpitations, tachycardia, arrhythmia.

Central and peripheral nervous system disorders:

Very common: dizziness, somnolence

Common: headache trembling

Uncommon: involuntary muscular contractions, paresthesia, tinnitus

Rare: ataxia, convulsions, syncope

Psychiatric disorders:

Common: confusion, mood changes (anxiety, nervousness, euphoria), sleep disorders

Uncommon: depression, hallucinations, nightmares, amnesia

Rare: drug dependence

Concomitant use is contraindicated with:

- Non-selective MAO inhibitors: risk of serotoninergic syndrome (diarrhea, tachycardia, sweating, trembling, confusion, even coma).

- Selective-A MAO inhibitors: extrapolation from non-selective MAO inhibitors, risk of serotoninergic syndrome (diarrhoea, tachycardia, sweating, trembling, confusion, even coma).

- Selective-B MAO inhibitors: central excitation symptoms evocative of a serotoninergic syndrome (diarrhoea, tachycardia, sweating, trembling, confusion, even coma).

In case of recent treatment with MAO inhibitors, a delay of 2 weeks should occur before treatment with tramadol.

Tolerance and physical and/or psychological dependence may develop, even at therapeutic doses. The clinical need for analgesic treatment should be reviewed regularly. 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. DOLL-P 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 or the respiratory function, or with an increased intracranial pressure.

Acetaminophen in overdosage 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. Withdrawal symptoms may be avoided by tapering it at the time of discontinuation especially after long treatment periods. Rarely, cases of dependence and abuse have been reported.

Symptoms of withdrawal reactions, similar to those occurring during opiate withdrawal may occur.

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.

DOLL-P 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.

Tramadol is an opioid analgesic that acts on the central nervous system. Tramadol is a pure non selective agonists of the µ, δ and κ opioid receptors with a higher affinity for theµ 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 the one-tenth to one-sixth that of morphine.

The precise mechanism of the analgesic properties of Acetaminophen is unknown and may involve central and peripheral effects.