Subutex Drug Uses, Dosage, Side Effects, Precautions & Warnings

subutex generic name

subutex Generic drug of the therapeutic class: Neurology–psychiatry
active ingredients: Buprenorphine

what is subutex?

This medication is exclusively reserved for substitution treatment of major opioid dependence, as part of a medical and psycho-social monitoring, based on an agreement between the patient and his doctor.

This treatment is reserved for adults and children over 15 who are volunteers to receive substitution treatment.

what is subutex used for and indication?

• Substitution treatment for opioid dependence as part of a global treatment of medical, social and psychological care.
• The treatment is reserved for adults and adolescents over the age of 15 who are volunteers to receive opioid dependence treatment.

subutex dosage

The treatment is reserved for adults and adolescents over 15 years old, volunteers to receive substitution treatment.

When initiating treatment with buprenorphine, the physician should take into account the partial agonist profile of the molecule at the opioid receptors, which may induce a withdrawal syndrome in opioid-dependent patients.

The result of the treatment depends, on the one hand, on the prescribed dosage and, on the other hand, the associated medico-psychological and socio-educational measures for monitoring patients.

Sublingual administration : to prevent patients that the sublingual route is the only effective and well tolerated route for the administration of this product.

The tablet should be kept under the tongue until dissolved, which usually occurs in 5 to 10 minutes.

Implementation of the treatment:

1. The initial dose is 0.8 to 4 mg once daily.
2. · In non-weaned opioid addicts: at the time of induction of treatment, buprenorphine should be taken at least 4 hours after the last narcotic intake or at the onset of the first signs of withdrawal.
3. · In patients receiving methadone: first reduce the methadone dose to a maximum of 30 mg / day; however, withdrawal syndrome precipitated by buprenorphine may occur.

Dosage adjustment up to a maintenance dose:

1. The dosage should be individually adapted to each patient. The maintenance dosage is variable among individuals and should be adjusted by gradually increasing the doses to the lowest effective dose. The average maintenance dose is 8 mg / d, but in some patients an increase of up to 16 mg / d will be required. The maximum dosage is 16 mg / day. Dose changes are then determined after reassessment of the clinical status and accompanying measures.
2. Daily delivery of buprenorphine is recommended, especially during the initiation period of treatment. Thereafter and after stabilization of its state, quantities of drug for several days of treatment can be given to the patient. It is recommended, however, to limit the quantity of the drug delivered in one go to 7 days maximum.

Reduction of doses and cessation of treatment:

1. After a period of stabilization deemed satisfactory, the doctor may propose to the patient to gradually reduce his dose of buprenorphine, until a complete cessation of substitution treatment in favorable cases.
2. The provision of sublingual tablets dosed at 0.4 mg, 2 mg and 8 mg, respectively, allows a gradual reduction of the dosage. During the period of discontinuation of treatment, special attention will be paid to the risk of relapse.

Contraindications

Hypersensitivity to buprenorphine or any other component of the product.

Children under 15.

Severe respiratory failure.

Severe hepatic impairment.

Acute alcohol poisoning or delirium tremens .

 Combination with methadone, or level III opioid analgesics.

how subutex works?

Pharmacotherapeutic group: drug used in opioid dependence, ATC code: N07BC01.

Buprenorphine is a morphine agonist-antagonist and binds to the brain receptors m and k . His activity in the opioid substitution treatment is attributed to its slowly reversible receptor  meters that would minimize the need for prolonged periods of drug addicts.

The partial agonist activity of buprenorphine confers on the product a high therapeutic index by limiting its depressant effects, especially on the cardio-respiratory functions. The therapeutic margin of buprenorphine may be reduced when combined with benzodiazepines or misuse of buprenorphine.

subutex side effects

The occurrence of adverse effects depends on the tolerance threshold, which is higher for drug users than for the general population.

The following table includes adverse reactions reported in clinical studies.

Treatment-related side effects reported by organ system Very common (≥ 1/10) frequent (≥ 1/100 to <1/10); uncommon (≥1 / 1,000 to <1/100); rare (≥ 1 / 10,000 to <1 / 1,000); very rare (<1 / 10,000) (CIOMS III)
Psychiatric disorders
Rare:	Hallucination.
Nervous system disorders
Frequent	Insomnia, headache, fainting, dizziness.
Vascular disorders
Frequent	Orthostatic hypotension.
Respiratory, thoracic and mediastinal disorders
Rare:	Respiratory depression (see sections 4.4 and Interactions with other medicinal products and other forms of interaction ).
Gastrointestinal disorders
Frequent	Constipation, nausea, vomiting.
General disorders and administration site conditions
Frequent	Asthenia, drowsiness, sweat.

Other adverse reactions reported since marketing:

Immune system disorders:

• Hypersensitivity reactions such as rash, urticaria, pruritus, bronchospasm, angioedema, anaphylactic shock.

Hepatobiliary disorders (see section Warnings and precautions for use ):

• Under normal conditions of use: rare elevations of transaminases and hepatitis with jaundice of generally favorable evolution.
• In cases of intravenous diversion, local, sometimes septic, potentially serious acute hepatitis reactions and endocarditis due to unsafe injection practices have been reported (see Warnings and Precautions).
• In patients with marked opioid dependence, a first administration of buprenorphine may produce a withdrawal effect of the same type as that of naloxone.

SUBUTEX Interactions

Associations contraindicated

+ Methadone:

• Decrease in the effect of methadone by competitive receptor blockade, with the risk of a withdrawal syndrome.

+ Step III morphine analgesics:

• In patients using level III analgesics, a decrease in the analgesic effect of morphine can be observed, by competitive blocking of the receptors, with the risk of appearance of a withdrawal syndrome.

Associations advised against

+ Naltrexone:

• Risk of appearance of withdrawal syndrome.

+ Level II Analgesics:

• In patients using Tier II analgesics, a decrease in the analgesic effect of morphine can be observed, by competitive blocking of the receptors, with the risk of appearance of a withdrawal syndrome.

+ Codeine, ethylmorphine:

• In patients using codeine or ethylmorphine, a decrease in the analgesic effect of morphine can be observed, by competitive blocking of the receptors, with the risk of appearance of a withdrawal syndrome.

Other associations advised against

Alcohol:

• Alcohol enhancement of the sedative effect of buprenorphine. Impairment of alertness can make driving and using machines dangerous.
• Avoid taking alcoholic drinks and drugs containing alcohol.

Associations to consider

+ Combination with benzodiazepines is at risk of death from respiratory depression of central origin. Dosage should be limited and this combination avoided if there is a risk of misuse (see Warnings and Precautions and Adverse Reactions sections ). An appropriate medical evaluation of the benefit / risk ratio must be initiated before the prescription of this combination.

+ Other central nervous system depressants: other morphine derivatives (analgesics and antitussives), certain antidepressants, sedative H1 antihistamines, benzodiazepines, anxiolytics other than benzodiazepines, neuroleptics, clonidine and related drugs:

Increased depression of the central nervous system. Impairment of alertness can make driving and using machines dangerous.

+ Barbiturates

• Increased risk of respiratory depression.

+ CYP3A4 inhibitors

• An interaction study between buprenorphine and ketoconazole (a potent inhibitor of CYP3A4) showed an increase in buprenorphine Cmax and AUC (approximately 70% and 50%, respectively) and, to a lesser extent, norbuprenorphine.
• Therefore, patients treated with SUBUTEX should be closely monitored for co-administration of strong CYP3A4 inhibitors such as azole antifungals (ketoconazole, itraconazole, voriconazole or posaconazole), and a decrease in the dosage of SUBUTEX may be indicated. necessary (see section Warnings and precautions for use ).

+ Protease inhibitors

• There is a risk of increased or decreased effects of buprenorphine, both because of inhibition and induction of its metabolism by protease inhibitors (eg ritonavir, nelfinavir or indinavir). The resulting effect may be either signs of withdrawal or overdose. Patients receiving SUBUTEX in combination with protease inhibitors should be closely monitored and, if necessary, dosage adjustment should be considered (see Warnings and Precautions ).

+ Inductors of CYP3A4

• The interactions between buprenorphine and inducers of CYP3A4 have not been studied. Therefore, close monitoring is recommended in patients who are co-administered with CYP3A4 inducers (such as phenobarbital, carbamazepine, phenytoin, and rifampicin).
• To date, no significant interaction of buprenorphine has been observed with cocaine, the most frequently narcotic drug associated with opioids in polydrug use.

Warnings and Precautions

SUBUTEX Warnings

• This medication is exclusively for the treatment of opioid dependence.
• Use in adolescents: Due to the lack of data in adolescents (aged 15 to 17 years), patients belonging to this age range should be more closely monitored during treatment.
• It is recommended that this treatment be prescribed by physicians providing comprehensive therapeutic management of opioid dependence (see section “Conditions of Prescription and Delivery”).

Misuse, abuse and misuse

• Like other opioids, licit or illicit, buprenorphine can be misused or misused. Risks of misuse and abuse include overdose, the spread of viral infections or localized and systemic infections transmitted through the blood, respiratory depression and hepatic latteint. The misuse of buprenorphine by someone other than the patient for whom the product is intended may also create a new category of individuals primarily dependent on that substance; this type of use may also occur when the drug is dispensed directly by the patient for illicit use or when the drug is stolen, but not stored in a safe place.
• In case of intentional misuse of the drug intravenously, local reactions, sometimes septic (abscess, cellulitis), potentially serious acute hepatitis and other acute infections, such as pneumonia or endocarditis, have been reported.
• Suboptimal buprenorphine therapy may indicate misuse of the drug by the patient, which may result in overdose or discontinuation of treatment. A patient under-dosed with buprenorphine may continue to manage withdrawal symptoms and urge to consume opioids, alcohol, or other nonspecies (eg, benzodiazepines).
• In order to reduce the risk of misuse, abuse and misuse, physicians should take appropriate measures when prescribing and administering buprenorphine, for example, avoiding giving prescriptions for multiple renewals from the start of treatment; on the other hand, they must make follow-up visits to the patient while setting up a clinical control adapted to the needs of the patient.

Respiratory depression

• Cases of death from respiratory depression have been observed, particularly when buprenorphine was used in combination with benzodiazepines (see section 4.5) or when buprenorphine was not used according to the prescribing information. Deaths have also been reported after concomitant use of buprenorphine and other depressants such as alcohol or other opioids. Administration of buprenorphine to non-opioid-dependent individuals who are not opioid-tolerant may result in potentially life-threatening respiratory depression.
• This product should be used with caution in patients with asthma or respiratory insufficiency (such as chronic obstructive pulmonary disease, pulmonary curvature, decreased respiratory capacity, hypoxia, hypercapnia, pre-existing respiratory depression or kyphoscoliosis ( deformity of the spine that may lead to dyspnea).
• Patients with the above physical and / or pharmacological risk factors should be monitored and a dose reduction can be considered.
• Buprenorphine can cause severe life-threatening respiratory depression in children and non-dependent individuals who accidentally or deliberately linger. Patients should be warned to keep the platelets safe, never to take the tablets out of the pack, to keep the pads out of the reach of children and other family members, and not to take this medicine in front of children. . An emergency service must be immediately contacted in case of accidental ingestion or suspected ingestion.

CNS depression

• Buprenorphine may cause drowsiness, particularly when taken / concomitantly administered with alcohol or central nervous system depressants (such as benzodiazepines, tranquillizers, sedatives or hypnotics).

Addiction

• Animal studies, as well as clinical data, have shown that buprenorphine, a partial agonist for opioid μ receptors, may cause dependence on chronic administration, but this is less than that caused by a complete agonist (such as than morphine).
• Abrupt discontinuation of treatment may result in withdrawal syndrome, the first signs of which may appear later.

Hepatitis, liver injury

• Cases of severe acute hepatitis have been reported during misuse, including intravenous.
• These liver disorders have been observed mainly at high doses, and may be due to mitochondrial toxicity. In many cases, the presence of pre-existing mitochondrial dysfunction (genetic disease, liver enzyme abnormalities, hepatitis B virus or hepatitis C infection, alcohol abuse, anorexia, concomitant use of other potentially hepatotoxic drugs) and persistence of drug injections may occur. be responsible for liver injury or contribute to it.
• Patients with viral hepatitis, concomitant medical treatment (see section 4.5) and / or hepatic dysfunction have a higher risk of liver disease and these underlying factors should be taken into account before and during the buprenorphine regimen. treatment (see section 4.2).
• If there is suspicion of liver injury, a thorough biological and etiological assessment should be performed. Depending on the results obtained, treatment may be cautiously interrupted to prevent the onset of withdrawal symptoms and to prevent the return to illicit drug use. If treatment continues, hepatic function should be closely monitored.

Precipitation of opioid withdrawal syndrome

• When initiating buprenorphine therapy, the physician should consider the partial agonist profile of buprenorphine and be aware that the treatment may precipitate the onset of withdrawal syndrome in opioid-dependent patients, particularly if treatment is given.
• less than 6 hours after the last use of heroin or other short-acting opioid, or if it is administered less than 24 to 48 hours after the last methadone dose (consistent with the long half-life of methadone).
• Patients should be closely monitored during the transitionfrom methadone to buprenorphine because withdrawal symptoms have been reported. In order to avoid precipitating the onset of withdrawal syndrome, induction of buprenorphine therapy should be performed as soon as the objective signs of withdrawal appear .
• Withdrawal symptoms may also be associated with underdosing.

Allergic reactions

• Cases of acute and chronic hypersensitivity to buprenorphine have been reported in clinical studies and postmarketing. The most common signs and symptoms are: rash, hives and pruritus. Cases of bronchospasm, dangidema and anaphylactic shock have been reported.
• A history of hypersensitivity to buprenorphine is a contraindication to the use of buprenorphine.
• Subutex contains lactose monohydrate. Its use is not recommended in patients with galactose intolerance, Lapp lactase deficiency or glucose or galactose malabsorption syndrome (rare hereditary diseases).

Hepatic insufficiency

• The effect of hepatic insufficiency on the pharmacokinetics of buprenorphine was evaluated in a single dose postmarketing study. Due to the extensive metabolism of buprenorphine,
• higher plasma buprenorphine levels are found in patients with moderate and severe hepatic insufficiency.
• Patients should be monitored to avoid the signs and symptoms of toxicity or overdose caused by high levels of buprenorphine.
• Subutex should be used with caution in patients with moderate hepatic insufficiency. In patients with severe hepatic impairment, the use of buprenorphine is contraindicated.

Renal failure

• Renal elimination may be prolonged as 30% of the administered dose is eliminated by the kidney.
• The metabolites of buprenorphine accumulate in patients with renal insufficiency.
• Caution is advised in patients with severe renal impairment (creatinine clearance <30 ml / min) .

General warnings for the class of opioids

• Opioids can cause orthostatic hypotension.
• Opioids can increase cerebrospinal fluid pressure, which can lead to epileptic seizures. As with other opioids, caution is advised in buprenorphine-treated patients with head trauma, intracranial lesions and increased intracranial pressure, or who have a history of epileptic seizures.
• Opioid-induced miosis, changes in the level of consciousness, or perception of pain as a symptom of the disease may interfere with patient evaluation or complicate the diagnosis or clinical treatment of a concomitant disease.
• Opioids should be used with caution in patients with myxedema, hypothyroidism or adrenocortical insufficiency (eg Addison’s disease).
• Opioids should be used with caution in patients with hypotension, prostatic hypertrophy or urethral stenosis.
• Opioids may be responsible for an increase in intra-choledeal pressure and should therefore be used with caution in patients with bile duct dysfunction.
• Opioids should be given with caution in elderly or debilitated patients.

Athletes’ attention should be drawn to the fact that this specialty contains buprenorphine and that this active ingredient is included in the list of doping substances.

The following combinations are not recommended with buprenorphine: Tier II analgesics, ethylmorphine and alcohol.

Drive and use machines

Attention is drawn to the risk of drowsiness associated with the use of this drug, particularly for vehicle drivers and machine users, especially if it is associated with alcohol or a depressant medicine in the system. central nervous system (see section Interactions with other medicinal products and other forms of interaction ).

PREGNANCY / BREAST FEEDING / FERTILITY

subutex and pregnancy

• Based on available data and maternal / fetal benefit, buprenorphine can be used during pregnancy. However, an adjustment of the daily dosage may be necessary in order to maintain the effectiveness of the treatment.
• Chronic intake of buprenorphine by the mother, at any dose, at the end of pregnancy, may result in withdrawal syndrome (acute cries, poor food intake, abnormal sleep, irritability, tremor, hypertonia, myoclonus, or convulsions). the newborn.
• This syndrome is usually delayed for several hours to several days after birth. Cases of respiratory disorders in newborns have also been reported.
• Therefore, if the mother is treated until the end of pregnancy, surveillance should be considered at birth and for several days afterwards.

subutex and feeding

• Very small amounts of buprenorphine and its metabolites pass into breast milk.
• These amounts are not sufficient to avoid the withdrawal syndrome that can be delayed in breastfed infants.
• After an assessment of individual risk factors, breastfeeding may be considered in patients treated with buprenorphine.

subutex and Fertility

• In a study conducted with pharmacological doses in the mouse, testicular atrophy with tubular calcification was demonstrated in the treated animals.
• No adverse effects on fertility were observed in the rat studies; however, calving difficulties have been noted .

What happens if I overdose from SUBUTEX ?

Overdose with buprenorphine requires medical supervision of the patient and possibly emergency treatment at the hospital. Immediately consult your doctor or pharmacist..

What is  Forms and Composition SUBUTEX ?

QUALITATIVE AND QUANTITATIVE COMPOSITION

Buprenorphine hydrochloride. 2.16 mg

Amount corresponding to buprenorphine base ………. 2.00 mg for one tablet.

Excipients: Lactose

For the full list of excipients,.

2. PHARMACEUTICAL FORM

Sublingual tablet.

White to cream, oval, flat tablet with beveled edges with “B2” engraving on one side.

NOT’s

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general information:

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Additional information:

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Special warnings:

• For pregnant and breastfeeding women, the elderly, boys and drivers, and use before surgery.

Side effects:

• It treats possible side effects and drug interactions that require attention and its effect on continuous use.
• The information contained in this medicine is based on medical literature, but it is not a substitute for consulting a doctor.