Posology : מינונים

5       DOSAGE AND ADMINISTRATION
5.1     Important Dosage and Administration Information
SUBOXONE film is administered sublingually or buccally as a single daily dose.
Medication should be prescribed in consideration of the frequency of visits. Provision of multiple refills is not advised early in treatment or without appropriate patient follow-up visits.

5.2       Induction
Prior to induction, consideration should be given to the type of opioid dependence (i.e., long- or short-acting opioid products), the time since last opioid use, and the degree or level of opioid dependence.
Patients dependent on heroin or other short-acting opioid products
Patients dependent on heroin or other short-acting opioid products may be inducted with either SUBOXONE film or with sublingual buprenorphine monotherapy. At treatment initiation, the first dose of SUBOXONE film should be administered when objective signs of moderate opioid withdrawal appear, not less than six hours after the patient last used opioids.
It is recommended that an adequate treatment dose, titrated to clinical effectiveness, be achieved as rapidly as possible. In some studies, a too-gradual induction over several days led to a high rate of drop-out of buprenorphine patients during the induction period.
On Day 1, an induction dosage of up to 8 mg/2 mg SUBOXONE film is recommended. Clinicians should start with an initial dose of 2 mg/0.5 mg or 4 mg/1 mg buprenorphine/naloxone and may titrate upwards in 2 or 4 mg increments of buprenorphine, at approximately 2-hour intervals, under supervision, to 8 mg/2 mg buprenorphine/naloxone based on the control of acute withdrawal symptoms.
On Day 2, a single daily dose of up to 16 mg/4 mg SUBOXONE film is recommended.
Because the exposure to naloxone is somewhat higher after buccal than after sublingual administration, it is recommended that the sublingual site of administration be used during induction to minimize exposure to naloxone, to reduce the risk of precipitated withdrawal.
Patients dependent on methadone or long-acting opioid products
Patients dependent upon methadone or long-acting opioid products may be more susceptible to precipitated and prolonged withdrawal during induction than those on short-acting opioid products.
Buprenorphine/naloxone combination products have not been evaluated in adequate and well-controlled studies for induction in patients who are physically dependent on long-acting opioid products, and the naloxone in these combination products is absorbed in small amounts by the sublingual route and could cause worse precipitated and prolonged withdrawal. For this reason, buprenorphine monotherapy is recommended in patients taking long-acting opioids when used according to approved administration instructions. Following induction, the patient may then be transitioned to once-daily SUBOXONE film.
5.3       Maintenance
•     For maintenance, SUBOXONE film may be administered buccally or sublingually.
•     The dosage of SUBOXONE film from Day 3 onwards should be progressively adjusted in increments/decrements of 2 mg/0.5 mg or 4 mg/1 mg buprenorphine/naloxone to a level that holds the patient in treatment and suppresses opioid withdrawal signs and symptoms.
•     After treatment induction and stabilization, the maintenance dose of SUBOXONE film is generally in the range of 4 mg/1 mg buprenorphine/naloxone to 24 mg/6 mg buprenorphine/naloxone per day depending on the individual patient and clinical response. The recommended target dosage of SUBOXONE film during maintenance is 16 mg/4 mg buprenorphine/naloxone/day as a single daily dose. Dosages higher than 24 mg/6 mg daily have not been demonstrated to provide a clinical advantage.
•     When determining the prescription quantity for unsupervised administration, consider the patient’s level of stability, the security of his or her home situation, and other factors likely to affect the ability to manage supplies of take-home medication.


•     There is no maximum recommended duration of maintenance treatment. Patients may require treatment indefinitely and should continue for as long as patients are benefiting and the use of SUBOXONE film contributes to the intended treatment goals.
5.4      Method of Administration
SUBOXONE film must be administered whole. Do not cut, chew, or swallow SUBOXONE film. Advise patients not to eat or drink anything until the film is completely dissolved.
Sublingual Administration
Place one film under the tongue, close to the base on the left or right side. If an additional film is necessary to achieve the prescribed dose, place an additional film sublingually on the opposite side from the first film. Place the film in a manner to minimize overlapping as much as possible. The film must be kept under the tongue until the film is completely dissolved. If a third film is necessary to achieve the prescribed dose, place it under the tongue on either side after the first 2 films have dissolved.
Buccal Administration
Place one film on the inside of the right or left cheek. If an additional film is necessary to achieve the prescribed dose, place an additional film on the inside of the opposite cheek. The film must be kept on the inside of the cheek until the film is completely dissolved. If a third film is necessary to achieve the prescribed dose, place it on the inside of the right or left cheek after the first two films have dissolved.
SUBOXONE film should NOT be moved after placement.
To ensure consistency in bioavailability, patients should follow the same manner of dosing with continued use of the product. Proper administration technique should be demonstrated to the patient.
5.5      Clinical Supervision
Treatment should be initiated with supervised administration, progressing to unsupervised administration as the patient’s clinical stability permits. SUBOXONE film is subject to diversion and abuse. When determining the prescription quantity for unsupervised administration, consider the patient’s level of stability, the security of his or her home situation, and other factors likely to affect the ability to manage supplies of take-home medication.
Ideally patients should be seen at reasonable intervals (e.g., at least weekly during the first month of treatment) based upon the individual circumstances of the patient. Medication should be prescribed in consideration of the frequency of visits. Provision of multiple refills is not advised early in treatment or without appropriate patient follow-up visits. Periodic assessment is necessary to determine compliance with the dosing regimen, effectiveness of the treatment plan, and overall patient progress.
Once a stable dosage has been achieved and patient assessment (e.g., urine drug screening) does not indicate illicit drug use, less frequent follow-up visits may be appropriate. A once-monthly visit schedule may be reasonable for patients on a stable dosage of medication who are making progress toward their treatment objectives. Continuation or modification of pharmacotherapy should be based on the healthcare provider’s evaluation of treatment outcomes and objectives such as:
1. Absence of medication toxicity.
2. Absence of medical or behavioral adverse effects.
3. Responsible handling of medications by the patient.
4. Patient’s compliance with all elements of the treatment plan (including recovery-oriented activities,
psychotherapy, and/or other psychosocial modalities).
5. Abstinence from illicit drug use (including problematic alcohol and/or benzodiazepine use).
If treatment goals are not being achieved, the healthcare provider should re-evaluate the appropriateness of continuing the current treatment.
5.6     Unstable Patients
Healthcare providers will need to decide when they cannot appropriately provide further management for particular patients. For example, some patients may be abusing or dependent on various drugs, or unresponsive to psychosocial intervention such that the healthcare provider does not feel that he/she has the expertise to manage the patient. In such cases, the healthcare provider may want to assess whether to refer the patient to a specialist or more intensive behavioral treatment environment. Decisions should be based on a treatment plan established and agreed upon with the patient at the beginning of treatment.
Patients who continue to misuse, abuse, or divert buprenorphine products or other opioids should be provided with, or referred to, more intensive and structured treatment.
5.7     Discontinuing Treatment
The decision to discontinue therapy with SUBOXONE sublingual film after a period of maintenance should be made as part of a comprehensive treatment plan. Advise patients of the potential to relapse to illicit drug use following discontinuation of opioid agonist/partial agonist medication-assisted treatment. Taper patients to reduce the occurrence of opioid withdrawal signs and symptoms [See Warnings and Precautions (7.6)].
5.8     Switching Between Buprenorphine or Buprenorphine and Naloxone Sublingual Tablets and SUBOXONE Sublingual Film
Patients being switched between buprenorphine and naloxone or buprenorphine only sublingual tablets and SUBOXONE film should be started on the same dosage of the previously administered product. However, dosage adjustments may be necessary when switching between buprenorphine products. Not all strengths and combinations of the SUBOXONE films are bioequivalent to SUBOXONE sublingual tablets as observed in pharmacokinetic studies [see Clinical Pharmacology (14.3)]. Therefore, systemic exposures of buprenorphine and naloxone may be different when patients are switched from tablets to film or vice-versa. Patients should be monitored for symptoms related to over-dosing or under-dosing.
5.9     Switching Between SUBOXONE Sublingual Film Strengths
As indicated in Table 1, the sizes and the compositions of the four units of SUBOXONE films, i.e., 2 mg/0.5 mg, 4 mg/1 mg, 8 mg/2 mg and the 12 mg/3 mg units, are different from one another. If patients switch between various combinations of lower and higher strength units of SUBOXONE films to obtain the same total dose, (e.g., from three 4 mg/1 mg units to a single 12 mg/3 mg unit, or vice-versa), systemic exposures of buprenorphine and naloxone may be different and patients should be monitored for over-dosing or under-dosing. For this reason, pharmacist should not substitute one or more film strengths for another without approval of the prescriber.
Table 1. Comparison of Available SUBOXONE Sublingual Film Strengths by Dimensions and Drug Concentrations.

SUBOXONE film unit strength                     SUBOXONE film unit       Buprenorphine         Naloxone (buprenorphine/naloxone)                        dimensions               Concentration         Concentration % (w/w)               % (w/w)

2 mg/0.5 mg                                     22.0 mm x 12.8 mm        5.4                   1.53



    4 mg/1 mg                                      22.0 mm x 25.6 mm     5.4                   1.53
(2 times the length of the 2 mg/0.5 mg unit)
8 mg/2 mg                                      22.0 mm x 12.8 mm     17.2                  4.88 

12 mg/3 mg                                     22.0 mm X 19.2 mm     17.2                  4.88 (1.5 times the length of the 8 mg/2 mg unit)

5.10      Switching Between Sublingual and Buccal Sites of Administration The systemic exposure of buprenorphine between buccal and sublingual administration of SUBOXONE film is similar. Therefore, once induction is complete, patients can switch between buccal and sublingual administration without significant risk of under or overdosing.