Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Indivior Europe Limited, 27 Windsor Place, Dublin 2, D02 DK44, Ireland
Substitution treatment for opioid drug dependence, within a framework of medical, social and psychological treatment. The intention of the naloxone component is to deter intravenous misuse. Suboxone is indicated in adults and adolescents over 15 years of age who have agreed to be treated for addiction.
Treatment must be under the supervision of a physician experienced in the management of opiate dependence/addiction.
Prior to treatment initiation, consideration should be given to the type of opioid dependence (i.e. longor short-acting opioid), the time since last opioid use and the degree of opioid dependence. To avoid precipitating withdrawal, induction with buprenorphine/naloxone or buprenorphine only 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).
The recommended starting dose in adults and adolescents over 15 years of age is 4 mg/1 mg and can be repeated up to a maximum dose of 12 mg/ 3 mg on day 1 to minimise undue withdrawal symptoms and retain the patient in treatment. During the initiation of treatment, daily supervision of dosing is recommended to ensure proper sublingual placement of the dose and to observe patient response to treatment as a guide to effective dose titration according to clinical effect.
Following treatment induction on day 1, the patient must be rapidly stabilised on an adequate maintenance dose by titrating to achieve a dose that holds the patient in treatment and suppresses opioid withdrawal effects and is guided by reassessment of the clinical and psychological status of the patient. The maximum single daily dose should not exceed 24 mg buprenorphine.
During maintenance therapy, it may be necessary to periodically restabilise the patient on a new maintenance dose in response to changing patient needs.
After a satisfactory stabilisation has been achieved the frequency of Suboxone 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/2 mg may be given 16 mg/4 mg on alternate days, with no dose on the intervening days. In some patients, after a satisfactory stabilisation has been achieved, the frequency of Suboxone 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 24 mg. Patients requiring a titrated daily dose> 8 mg /day may not find this regimen adequate.
After a satisfactory stabilisation has been achieved, if the patient agrees, the dose may be reduced gradually to a lower maintenance dose; in some favourable cases, treatment may be discontinued. The availability of the sublingual tablet in doses of 2 mg/0.5 mg and 8 mg/2 mg allows for a downward titration of dose. For patients who may require a lower buprenorphine dose, buprenorphine 0.4 mg sublingual tablet may be used. Patients should be monitored following medical withdrawal because of the potential for relapse.
When used sublingually, buprenorphine/naloxone and buprenorphine have similar clinical effects and are interchangeable; however, before switching between buprenorphine/naloxone and buprenorphine, the prescriber and patient should agree to the change, and the patient should be monitored in case a need to readjust the dose occurs.
Patients being switched between Suboxone sublingual tablets and Suboxone film should be started on the same dose as the previously administered medicinal product. However, dose adjustments may be necessary when switching between medicinal products. Due to the potentially greater relative bioavailability of Suboxone film compared to Suboxone sublingual tablets, patients switching from sublingual tablets to film should be monitored for overdose. Those switching from film to sublingual tablets should be monitored for withdrawal or other indications of underdosing. In clinical studies, the pharmacokinetics of Suboxone film were not consistently shown to be similar to the respective dosage strengths of Suboxone sublingual tablets, as well as to the combinations (see section 5.2). If switching between Suboxone film and Suboxone sublingual tablets, the patient should be monitored in case a need to readjust the dose occurs. Combining different formulations or alternating between film and sublingual tablet formulations is not advised.
The safety and efficacy of buprenorphine/naloxone in elderly patients over 65 years of age have not been established. No recommendation on posology can be made.
As buprenorphine/naloxone 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. Buprenorphine/naloxone is contraindicated in patients with severe hepatic impairment (see sections 4.3 and 5.2).
Modification of the buprenorphine/naloxone dose is not required in patients with renal impairment. Caution is recommended when dosing patients with severe renal impairment (creatinine clearance <30 mL/min) (see sections 4.4 and 5.2).
The safety and efficacy of buprenorphine/naloxone in children below the age of 15 years have not been established. No data are available.
Physicians must warn patients that the sublingual route is the only effective and safe route of administration for this medicinal product (see section 4.4). The tablet is to be placed under the tongue until completely dissolved. Patients should not swallow or consume food or drink until the tablet is completely dissolved.
The dose can be made up from multiple Suboxone tablets of different strengths, which may be taken all at the same time or in two divided portions; the second portion to be taken directly after the first portion has dissolved.
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.
General supportive measures should be instituted, including close monitoring of respiratory and cardiac status of the patient. Symptomatic treatment of respiratory depression, and standard intensive care measures, should be implemented. 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 (i.e., 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.
If naloxone is used, the long duration of action of buprenorphine should be taken into consideration when determining the length of treatment and medical surveillance 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, repeated dosing with naloxone may be required. Ongoing intravenous infusion rates should be titrated to patient response.
3 years.
This medicinal product does not require any special storage conditions.
7 tablets in blister packs Paper/Aluminium/Nylon/Aluminium/PVC.
28 tablets in blister packs Paper/Aluminium/Nylon/Aluminium/PVC.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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