ESPRANOR Oral lyophilisate Ref.[49987] Active ingredients: Buprenorphine

Treatment should be under the supervision of a clinician experienced in the management of opiate dependence/addiction.

Espranor is not interchangeable with other buprenorphine products. Different buprenorphine products have different bioavailability. Therefore, the dose in mg can differ between products. Once the appropriate dose has been identified for a patient with a certain product (brand), the product cannot readily be exchanged with another product.

The route of administration for Espranor is on the tongue, not under it.

Administration is oromucosal. The oral lyophilisate should be taken from the blister unit with dry fingers, and placed whole on the tongue until dispersed, which usually occurs within 15 seconds, and then absorbed through the oromucosa. Swallowing should be avoided for 2 minutes. The oral lyophilisate should be taken immediately after opening the blister. Patients should not consume food or drink for 5 minutes after administration.

Physicians must advise patients that the oromucosal route of administration is the only effective and safe route of administration for this medicinal product. If the oral lyophilisate, or saliva containing buprenorphine are swallowed, the buprenorphine will be metabolised and excreted and have minimal effect.

Adults and adolescents aged 15 years or over

Precautions to be taken before induction

Prior to treatment initiation, consideration should be given to the type of opioid dependence (i.e. long- or short-acting opioid), the time since last opioid use and the degree of opioid dependence. To avoid precipitating withdrawal, induction with buprenorphine should be undertaken when objective and clear signs of withdrawal are evident (demonstrated e.g. by a score indicating mild to moderate withdrawal on the validated Clinical Opioid Withdrawal Scale, COWS).

Opioid-dependent drug addicts who have not undergone withdrawal: When treatment starts, the first dose of Espranor should be taken when signs of withdrawal appear, but not less than 6 hours after the patient last used opioids (e.g. heroin; short acting opioids).

Patients receiving methadone: Before beginning Espranor therapy, the dose of methadone must be reduced to a maximum of 30 mg/day. The long half-life of methadone should be considered when starting buprenorphine therapy. The first dose of Espranor should be taken when signs of withdrawal appear, but not less than 24 hours after the patient last used methadone. Buprenorphine may precipitate symptoms of withdrawal in patients dependent upon methadone.

Because of the partial agonist profile of buprenorphine, the patient should be warned that the first 24 hours of buprenorphine substitution therapy may feel uncomfortable with some mild opiate withdrawal symptoms.

Initiation therapy (induction)

The recommended starting dose is 2 mg of Espranor (1 Espranor 2 mg oral lyophilisate). An additional one to two Espranor 2 mg oral lyophilisates may be administered on day one depending on the individual patient’s requirement.

During the initiation of treatment, daily supervision of dosing is recommended to ensure proper placement of the dose on the tongue and to observe patient response to treatment as a guide to effective dose titration according to clinical effect.

Dosage adjustment and maintenance

The dose of Espranor should then be adjusted according to clinical effect with the aim of quickly stabilising the patient. The dosage can be titrated up or down according to assessment of the clinical and psychological status of the patient in steps of 2-6 mg until the minimum effective maintenance dose is achieved, but should not exceed a maximum single daily dose of 18 mg. During the initiation of treatment, daily dispensing of buprenorphine is recommended. After stabilisation, a reliable patient may be given a supply of Espranor sufficient for several days of treatment. It is recommended that the amount of Espranor be limited to 7 days or according to local requirements.

Less than daily dosing

After satisfactory stabilisation has been achieved the frequency of Espranor dosing may be decreased to dosing every other day at twice the individually titrated daily dose. For example, a patient stabilised to receive a daily dose of 8 mg may be given 16 mg on alternate days, with no dose on the intervening days. In some patients, after a satisfactory stabilisation has been achieved, the frequency of Espranor dosing may be decreased to 3 times a week (for example on Monday, Wednesday and Friday). The dose on Monday and Wednesday should be twice the individually titrated daily dose, and the dose on Friday should be three times the individually titrated daily dose, with no dose on the intervening days. However, the dose given on any one day should not exceed 18 mg. Patients requiring a titrated daily dose >8 mg/day may not find this regimen adequate.

Dosage reduction and termination of treatment: After a satisfactory stabilisation has been achieved, if the patient agrees, the dosage may be reduced gradually to a lower maintenance dose; in some favourable cases, treatment may be discontinued. The availability of Espranor in doses of 2 mg and 8 mg allows for a downward titration of dosage. For patients who may require a lower buprenorphine dose, buprenorphine 1 mg or 0.4 mg sublingual tablets may be used. Patients should be monitored following termination of treatment because of the potential for relapse.

Elderly

The safety and efficacy of buprenorphine in the elderly over 65 years of age have not been established. No recommendation on posology can be made.

Paediatrics

The safety and efficacy of buprenorphine in children below the age of 15 years have not been established. No data are available.

Patients with impaired hepatic function

Baseline liver function tests and documentation of viral hepatitis status is recommended prior to commencing therapy. Patients who are positive for viral hepatitis, on concomitant medication (see section 4.5) and/or have existing liver dysfunction are at risk of accelerated liver injury. Regular monitoring of liver function is recommended (see section 4.4).

The effect of hepatic impairment on the pharmacokinetics of buprenorphine is unknown. Since buprenorphine is extensively metabolised in the liver, the plasma levels will be expected to be higher in patients with moderate or severe hepatic impairment.

As Espranor pharmacokinetics may be altered in patients with hepatic impairment, lower initial doses and careful dose titration in patients with mild to moderate hepatic impairment are recommended (see section 5.2). Buprenorphine is contraindicated in patients with severe hepatic insufficiency (see section 4.3).

Patients with impaired renal function

Modification of the Espranor dose is not generally required in patients with renal impairment. Caution is recommended when dosing patients with severe renal impairment (Creatinine Clearance <30 ml/min) (see section 4.4 and 5.2).

Method of administration

Physicians must warn patients that the route of administration is the only effective and safe route for this medicinal product (see section 4.4). The oral lyophilisate is to be placed on the tongue until completely dissolved. Patients should not swallow or consume food or drink until the lyophilisate is completely dissolved. For further information, see the national guidelines for buprenorphine treatment.

Symptoms: respiratory depression as a result of central nervous system depression is the primary symptom requiring intervention in the case of overdose because it may lead to respiratory arrest and death. Signs of overdose may also include somnolence, amblyopia, miosis, hypotension, nausea, vomiting and/or speech disorders.

Treatment: general supportive measures should be instituted, including close monitoring of respiratory and cardiac status of the patient. Symptomatic treatment of respiratory depression, following standard intensive care measures, should be instituted. A patent airway and assisted or controlled ventilation must be assured. The patient should be transferred to an environment within which full resuscitation facilities are available.

If the patient vomits, care must be taken to prevent aspiration of the vomitus.

Use of an opioid antagonist (e.g. naloxone) is recommended, despite the modest effect it may have in reversing the respiratory symptoms of buprenorphine compared with its effects on full agonist opioid agents. The long duration of action of Espranor should be taken into consideration when determining length of treatment needed to reverse the effects of an overdose. Naloxone can be cleared more rapidly than buprenorphine, allowing for a return of previously controlled buprenorphine overdose symptoms, so a continuing infusion may be necessary. If infusion is not possible, repeat dosing with naloxone may be required. The naloxone dose may range up to 2 mg and be repeated every 2-3 minutes until a satisfactory response is achieved, but should not exceed a 10 mg starting dose. Ongoing IV infusion rates should be titrated to patient response.

3 years.

This medicinal product does not require any special temperature storage conditions. Store in the original package (blister) to protect from light and moisture.

Unit dose blisters composed of PVC/OPA/Al/OPA/PVC film with Al/PET/paper lidding with 7 × 1 or 28 × 1 oral lyophilisates, in a cardboard carton.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.