Suboxone

/ NSE

Initiation Therapy (induction): The recommended starting dose in adults and adolescents over 15 years of age is one to two Suboxone 2 mg/0.5 mg. An additional one to two Suboxone 2 mg/0.5 mg 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 sublingual placement of the dose and to observe patient response to treatment as a guide to effective dose titration according to clinical effect.
Dosage adjustment and maintenance therapy: Following treatment induction on day one, the patient should be stabilized to a maintenance dose during the next few days by progressively adjusting the dose according to the clinical effect of the individual patient. Dose titration in steps of 2-8 mg is guided by reassessment of the clinical and psychological status of the patient, and should not exceed a maximum single daily dose of 24 mg.
Less than daily dosing: After a satisfactory stabilisation has been achieved the frequency of 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 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.
Medical withdrawal: 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 doses of 2 mg/0.5 mg and 8 mg/2 mg allows for a downward titration of dosage. For patients who may require a lower buprenorphine dose, buprenorphine 0.4 mg may be used. Patients should be monitored following medical withdrawal because of the potential for relapse.
For full details see prescribing information.

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.
Treatment is intended for use in adults and adolescents over 15 years of age who have agreed to be treated for addiction.

Hypersensitivity to the active substances or to any of the excipients, Severe respiratory insufficiency Severe hepatic impairment, Acute alcoholism or delirium tremens.

General warnings relevant to the administration of opioids: Buprenorphine/naloxone may produce orthostatic hypotension in ambulatory patients. Caution is requested in patients using buprenorphine and having head injury, increased intracranial pressure, hypotension, prostatic hypertrophy or urethral stenosis. As buprenorphine is an opioid, pain as a symptom of a disease may be attenuated. The concomitant use of monoamine oxidase inhibitors (MAOI) might produce exaggeration of the effects of opioids, based on experience with morphine.
Misuse, abuse and diversion Buprenorphine can be misused or abused in a manner similar to other opioids, legal or illicit. Some risks of misuse and abuse include overdose, spread of blood borne viral infections, respiratory depression and hepatic injury. Buprenorphine misuse by someone other than the intended patient poses the additional risk of new drug dependent individuals using buprenorphine as the primary drug of abuse, and may occur if the medicine is distributed for illicit use directly by the intended patient or if the medicine is not safeguarded against theft.
Sub-optimal treatment with buprenorphine/naloxone may prompt medication misuse by the patient, leading to overdose or treatment dropout. A patient who is under-dosed with buprenorphine/naloxone may continue responding to uncontrolled withdrawal symptoms by self-medicating with opioids, alcohol or other sedative-hypnotics such as benzodiazepines.
Hepatic metabolism of buprenorphine may be altered in patients with hepatic impairment, which may give rise to increased plasma concentrations of buprenorphine. A reduction of the buprenorphine/naloxone dose may be needed.
Renal Impairment: Renal elimination may be prolonged since 30 % of the administered dose is eliminated by the renal route.
CYP 3A inhibitors: Medicines that inhibit the enzyme CYP3A4 may give rise to increased concentrations of buprenorphine. A reduction of the buprenorphine/naloxone dose may be needed. Patients already treated with CYP3A4 inhibitors should have their dose of buprenorphine/naloxone titrated carefully since a reduced dose may be sufficient in these patients.
May cause CNS depression and respiratory depression.
For full details see prescribing information.

Constipation and symptoms commonly associated with drug withdrawal (i.e. Insomnia, headache, nausea, and hyperhidrosis). Some reports of seizure, vomiting, diarrhoea, and elevated liver function tests were considered serious.
For full details see prescribing information.

This drug should not be taken together with: alcoholic drinks or medicines containing alcohol, as alcohol increases the sedative effect of buprenorphine. Suboxone should be used cautiously when co-administered with:
benzodiazepines: This combination may result in death due to respiratory depression of central origin. Therefore, dosages must be limited and this combination must be avoided in cases where there is a risk of misuse. Patients should be warned that it is extremely dangerous to selfadminister non-prescribed benzodiazepines while taking this product, and should also be cautioned to use benzodiazepines concurrently with this product only as directed by their physician.
Other central nervous system depressants, other opioid derivatives (e.g. methadone, analgesics and antitussives), certain antidepressants, sedative H1-receptor antagonists, barbiturates, anxiolytics other than benzodiazepines, neuroleptics, clonidine and related substances: these combinations increase central nervous system depression. The reduced level of alertness can make driving and using machines hazardous.
CYP3A4 inhibitors: an interaction study of buprenorphine with ketoconazole (a potent inhibitor of CYP3A4) resulted in increased Cmax and AUC (area under the curve) of buprenorphine (approximately 70 % and 50 % respectively) and, to a lesser extent, of norbuprenorphine.
Patients receiving Suboxone should be closely monitored, and may require dose-reduction if combined with potent CYP3A4 inhibitors (e.g. protease inhibitors like ritonavir, nelfinavir or indinavir or azole antifungals such as ketoconazole or itraconazole).
CYP3A4 inducers: the interaction of buprenorphine with CYP3A4 inducers has not been investigated. Therefore it is recommended that patients receiving Suboxone should be closely monitored if inducers (e.g. phenobarbital, carbamazepine, phenytoin, rifampicin) are coadministered. The concomitant use of monoamine oxidase inhibitors (MAOI) might produce exaggeration of the effects of opioids, based on experience with morphine. To date, no notable interaction has been observed with cocaine, the agent most frequently used by multi-drug abusers in association with opioids.
For full details see prescribing information.

Pregnancy: There are no adequate data from the use of this drug in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown.
Towards the end of pregnancy high doses of buprenorphine may induce respiratory depression in the newborn infant even after a short period of administration. Long-term administration of buprenorphine during the last three months of pregnancy may cause a withdrawal syndrome in the neonate. In case pregnancy occurs while on buprenorphine/naloxone treatment, the mother and the unborn child should be closely monitored and a switch to treatment with buprenorphine alone should be considered if further treatment is required.
Breastfeeding: It is unknown whether naloxone is excreted in human breast milk. Buprenorphine and its metabolites are excreted in human breast milk. In rats buprenorphine has been found to inhibit lactation. Therefore, breastfeeding should be discontinued during treatment with this drug.
Fertility: Animal studies have shown a reduction in female fertility at high doses (systemic exposure > 2.4 times the human exposure at the maximum recommended dose of 24 mg buprenorphine, based on AUC).

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 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, 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.
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.

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