- buprenorphine hydrochloride
POM: Prescription only medicine
This information is intended for use by health professionals
White to off-white, round, biplane tablet with facet (diameter: approximately 5.00 mm).
DosageThe dosage of Tephine should generally be adjusted to the intensity of the pain and the individual sensitivity of the patient.The recommended single dose in patients with a bodyweight greater than 45 kg is 1 2 sublingual tablets Tephine 200 microgram The onset of effects generally occurs within 30 minutes after sublingual administration.The average duration of effects is 6 8 hours.If necessary, 1 2 sublingual tablets Tephine 200 microgram may be administered every 6 8 hours.In severe chronic pain, the dose of Tephine should be adjusted to the intensity of the pain and administered regularly in accordance with a fixed schedule corresponding to the duration of effects.Patients with a bodyweight of 35 45 kg should be given a single dose of 1 sublingual tablet Tephine 200 microgram, if necessary, every 6 8 hours. This is equivalent to an average single dose of 5 micrograms/kg bodyweight.Patients with a bodyweight of 16 35 kg should be given a single dose of 100 microgram of buprenorphine, if necessary, every 6 8 hours. Tephine 200 microgram sublingual tablets are not divisible. Other buprenorphine containing products covering the 100 microgram dosage are available.Buprenorphine should not be used in children less than 2 years of age or in children weighing less than 16 kg.
Patients with hepatic insufficiency:Buprenorphine is metabolised in the liver. The degree and duration of its effects in patients with impaired hepatic function may therefore be altered. It is thus advisable to appropriately adjust the dose of Tephine in this patient group.
Method of administrationThe sublingual tablets are placed under the tongue, where they will dissolve within 5 10 minutes. In the presence of very dry oral mucosa, a few drops of liquid will accelerate the dissolution process.The sublingual tablets must not be sucked, chewed or swallowed.At the beginning of treatment, ambulatory patients should rest during and for 1 2 hours after administration of Tephine.
Duration of useTephine should not be used for longer than is absolutely necessary. If longer term pain management is required, it is advisable to reassess at regular and frequent intervals (with administration pauses, if applicable) whether and at what dosage Tephine should continue to be administered.There is currently insufficient clinical experience of longer term use of buprenorphine in children.
Risk from concomitant use of sedative medicinal products such as benzodiazepines or related medicinal products
Concomitant use of buprenorphine and sedative medicinal products such as benzodiazepines or related medicinal products may result in sedation, respiratory depression, coma and death. Because of these risks, concomitant prescribing with these sedative medicinal products should be reserved for patients for whom alternative treatment options are not possible. If a decision is made to prescribe buprenorphine concomitantly with sedative medicinal products the lowest effective dose should be used, and the duration of 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).Buprenorphine should be used only with particular caution:• in elderly and debilitated patients• in the presence of impaired renal function or renal insufficiency (e.g. Addison's disease)• in patients with myxoedema or hypothyroidism• in toxic psychosis, central nervous depression or coma• in acute alcoholism or delirium tremens• in kyphoscoliosis with restrictive disturbances of the airways• in patients who have recently been treated with narcoanalgesics.It has been demonstrated in controlled studies in humans and animals that buprenorphine has a lower dependency potential than pure opioid agonists. Minor euphoric effects of buprenorphine have been observed in humans. This could result in abuse of the substance to some extent. Caution should therefore be exercised if buprenorphine is prescribed for patients with a known or suspected history of drug abuse.In addition, buprenorphine should be used with particular caution and at a reduced dose in prostatic hypertrophy, constriction of the urinary tract and biliary tract disorders.As is the case with all opioids, chronic use of buprenorphine can result in development of physical dependence. Withdrawal symptoms (abstinence syndrome) should they occur at all tend to be mild, commence after 2 days and may persist for up to 2 weeks. Withdrawal symptoms include excitation, anxiety states, nervousness, insomnia, hyperkinesia, tremor and gastrointestinal complaints.Use of Tephine can lead to positive results in doping tests. Abuse of the medicinal product Tephine for doping purposes can endanger health.This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.Diversion of buprenorphine has been reported. Diversion refers to the introduction of buprenorphine into the illicit market either by patients or by individuals who obtain the medicinal product through theft from patients or pharmacies. This diversion may lead to new addicts using buprenorphine as the primary drug of abuse, with the risks of overdose, spread of blood borne viral infections and respiratory depression.
|General disorders and administration site conditions|
|Immune system disorders|
|Uncommon: Very rare:||Generalised (systemic) hypersensitivity reactions Anaphylactic shock|
|Uncommon:||Confusion, disorientation, nervousness, depression, psychosis, hallucinations, depersonalisation, euphoria, dysphoria, agitation (restlessness)|
|Nervous system disorders|
|Very common: Common: Uncommon:||Tiredness, sleep disturbances, drowsiness Dizziness, headache Exhaustion, dry mouth, slurred speech, coma, tremor (shaking), seizures, lack of muscle coordination|
|Common: Uncommon:||Miosis Double vision, visual disturbances, conjunctivitis|
|Ear and labyrinth disorders|
|Uncommon:||Tachycardia, bradycardia, cyanosis, AV block|
|Common: Uncommon:||Orthostatic hypotension Hypertension|
|Respiratory, thoracic and mediastinal disorders|
|Common: Uncommon: Very rare:||Respiratory depression Dyspnoea (respiratory distress), apnoea (respiratory arrest) Bronchospasm|
|Common: Uncommon:||Nausea, vomiting Constipation, dyspepsia, loss of appetite, diarrhoea|
|Skin and subcutaneous tissue disorders|
|Common: Uncommon: Very rare:||Sweating Paraesthesia, pruritus (itching), skin rash, pallor, urticaria Angioneurotic oedema (Quincke's oedema)|
|Renal and urinary disorders|
|Uncommon:||Micturition disorders, urinary retention|
Treatment:In case of overdose, the cardiac and respiratory status of the patient must be closely monitored and appropriate supportive measures should be initiated. A specific opioid antagonist, such as naloxone, can counteract the effects of buprenorphine. Higher doses are generally required for this purpose than with other opioids. It must be borne in mind that the duration of effects of opioids can exceed that of naloxone, so that there is a risk of recurrence of respiratory depression.Gastric lavage should be considered if larger doses of Tephine have been ingested.
AbsorptionThe absorption of buprenorphine after sublingual administration is good. The onset of analgesic effects commences approximately 30 minutes after sublingual administration. The effects peak after 60 120 minutes and persist for 6 8 hours.Peak plasma concentrations are reached within approximately 200 minutes after sublingual administration. Following intravenous injection of buprenorphine, plasma concentrations fall rapidly in the initial phase with a half-life of 2 5 minutes (distribution phase). Terminal half-life is approximately 3 hours. The concentrations of the active substance 10 minutes after i.m. injection are equivalent to those after i.v. injection. Terminal half-life after i.m. administration is also 3 hours. Because of the persistent receptor binding, pharmacodynamic effects do not correlate with blood concentrations or the elimination half-life of buprenorphine.In human plasma, 96% of a buprenorphine dose is bound to plasma proteins, mainly to α- and β-globulins. An influence on the protein binding of anticoagulants (bound to albumin) is therefore unlikely.
Metabolism and eliminationBuprenorphine is metabolised in the liver. It is subject to a phase 1 (N-dealkylation) and a phase 2 (O- and/or N-glucuronidation) metabolism.Unchanged buprenorphine and its metabolites are also excreted by the biliary route.Elimination occurs within 7 days, mainly via the faeces but 27% of a dose is eliminated in the urine. While predominantly unchanged buprenorphine has been detected in faeces, glucuronide derivatives of buprenorphine and N-dealkylbuprenorphine are mainly found in the urine. The slow rate of faecal excretion indicates the presence of an enterohepatic circulation.
Passage into cerebrospinal fluidBuprenorphine crosses the blood-brain barrier and is detectable in all sections of the brain. The concentration is highest in the pituitary gland and lower in the cerebellum and spinal marrow.
Placental passageStudies conducted in gestating rats have shown that buprenorphine crosses the placental barrier. The concentrations of buprenorphine in foetal tissue in the early phase of pregnancy are equivalent to maternal plasma levels. With progression of the pregnancy, buprenorphine can also be detected in the gastrointestinal tract of the foetus in some cases.Only immediately prior to birth is the foetal liver capable of metabolising buprenorphine and the substance is then found in the form of derivatives in the gastrointestinal tract of the foetus.
Passage into breast milkStudies conducted in rats have demonstrated that buprenorphine passes into breast milk.
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