Currently Rusan Pharma Ltd. is the only Indian formulator licensed to manufacture & distribute ADDNOK (Buprenorphine) 2mg/ 0.4mg Sublingual Tablets. Rusan is providing Addnok sublingual tablets to the various NGOs for the treatment of Opioid addiction.
PRODUCT PROFILE
Addnok offers a valuable addition to the treatment choices available for transitioning patients from active drug use to abstinence from heroin. The unique mechanism of action of Addnok provides desirable properties in the treatment of opioid addiction and an additional element of safety for patients. These include low levels of traditional narcotic effects such as physical dependence, euphoria and withdrawal.
This is the latest addition to the pharmacological agents available to the physician for the detoxification of heroin addicts.
Buprenorphine was first introduced in France in 1988 (14). In 1990 a retrospective evaluation of these patients was done. In 1996 high dose sublingual Buprenorphine tablets were launched in France as Subutex (Schering Plough in France and Reckitt and Coleman in the U.K.)
COMPOSITION :
ADDNOK 2 mg - Each sublingual uncoated tablet contains :
Buprenorphine Hydrochloride I.P
Equivalent to Buprenorphine 2 mg
ADDNOK 0.4 mg - Each sublingual uncoated tablet contains :
Buprenorphine Hydrochloride I.P
Equivalent to Buprenorphine 0.4 mg
THERAPEUTIC INDICATIONS :
ADDNOK is indicated as a substitution treatment of opiate addiction along with medical, Social and psychlological support offered by specialists.
MODE OF ACTION IN THE TREATMENT OF ADDICTION :
Addnok is a partial agonist at the m receptors and an antagonist at the k receptors. (15)
It has a high affinity for the m receptors but a low intrinsic activity (efficacy) here.
This is an advantage because low efficacy k agonists like buprenorphine do not produce profound respiratory depression, (16) thus improving its safety profile.
Besides, a lack of agonist effect at k receptors implies that Buprenorphine would not cause dysphoria. This makes it an acceptable substitution drug in the treatment of addiction.
Addnok binds very tightly to the opioid receptors”. (11) This accounts for its long duration of action. Also the slow dissociation helps to maintain homeostasis and may help to counter the development of an overt withdrawal Syndrome. (18)
Addnok is well tolerated even at high doses. It has been observed that at high doses Addnok exhibits auto-antagonism, i.e. it antagonizes its own effects. The mechanism is not clear. However its auto-antagonism plus its low intrinsic activity at m receptors limits the toxicity of Addnok. (19)
It also limits its abuse liability and makes it useful for the treatment of opiate dependence. (19)
PHARMACOKINETICS
(20)
Peak blood levels of Buprenorphine were higher after I.M doses than after oral doses due to extensive first - pass metabolism.
After I. M. injection peak levels are achieved within 2 - 5 minutes after dosing. The systemic availability is 100% by both I.M and I.V. route.
The time to reach peak plasma levels after the sublingual route is 90 - 360 min.
Sublingual absorption of buprenorphine whether in tablet or solution is quite high
as 31-52%).
96% of Buprenorphine is protein bound.
Buprenorphine is excreted in the urine and faeces. The dose need not be adjusted in patients with compromised renal function.
The plasma 1/2 life is 1.2 - 7.2 hours, but there is no correlation between plasma levels and pharmacological activity. (21)
DOSE :
As mentioned in the Treatment guidelines
CONTRAINDICATIONS:
Hypersensitivity to Buprenorphine, in children below 15 years: severe respiratory deficiency: severe hepatic deficiency: acute alcoholic intoxication and delirium tremors.
SAFETY & PRECAUTIONS:
ADDNOK is to be used exclusively in the treatment of opioid addiction. This product can provoke an opioid withdrawal syndrome if it is administered to an addict less than 4 hours after the last narcotic dose.
DOSAGE AND MODE OF ADMINISTRATION: This product can induce a certain drowsiness, susceptible to being potential zed by other agents of central action such as alcohol, tranquilizers, sedatives and hypnotics (Medical Interaction); this product can provoke an orthostatic hypo-tension among ambulatory patients; the studies among animals and the clinical experience have shown that Buprenorphine exhibits all the same to a pharmaco-dependence but much less than morphine. Consequently it is important to honour the criteria of prescribing, of follow-ups and with regards to the dosage levels.
SAFETY:
This product is to be used with care among asthmatic and respiratory deficient patients (some cases of respiratory depression have been observed).
The renal elimination of Buprenorphine, which represents 20 % of an administered dose can be prolonged in this pathology.
Hepatic deficiency -the hepatic metabolism of Buprenorphine can be modified in this pathology.
DRUG INTERACTIONS:
Advice against combinations:
Alcohol: Excess of alcohol on the sedative effect of Buprenorphine; Blurred vision can be dangerous to drivers and to machine operators. Avoid the taking of alcoholic drinks and medications containing alcohol.
Combinations to take account of :- other depressants of the central nervous system; other morphine derivatives (analgesics anti tussives); certain antidepressants, antihistamines, sedatives, barbiturates, enzodiazepines, neuroleptics , clonidine and its related compounds:
Excess of CNS depression, blurred vision can be dangerous for drivers of vehicles and machine operators. IMAO- Possible overating of the opiate effects of Morphine.
Up to date no noticeable interaction of Buprenorphine has been noted as with cocaine, marijuana stupefying the more frequent association to opioids in the addicts.
Pregnancy & Nursing:
Pregnancy: In the absence of sufficient data on the effects of Buprenorphine on pregnant women, its use is not recommended during pregnancy.
Nursing: Among animals, Buprenorphine passes into the mother’s milk. At high doses, the product reduces the secretion of milk. Nursing is not advised in female addicts treated with Buprenorphine.
Effects on the efficiency of driver of a vehicle and utilisers of machines:
Attention is drawn notably to the drivers of vehicles and machine operators on the risk of drowsiness attached to the users of this medication, in particular if it is associated with Alcohol or to a medicament which depresses the central nervous system.( Of Medical Interaction).
ADVERSE EFECTS:
The occurrence of undesirable effects depends on the limit of tolerance more among addicts than general population. The most frequent manifestations observed with Buprenorphine are: Constipation, headache, insomnia, debility, drowsiness, nausea, vomiting and giddy sensations, hypertension, sweating although the other susceptible undesirable effects that have been observed are infrequent cardiac or respiratory depression, hallucinations. Among patients with a marked opioid dependence, an initial administration of Buprenorphine can produce a withdrawal effect similar to that of Naloxone.
OVERDOSE:
The partial agonistic morphine- like properties of Buprenorphine confer to it a margin of theoretically important security. In case of accidental over-dosage, the cardio-respiratory state of the patient must be strictly supervised. Some measures may be necessary in order to maintain the respiratory function and fight against a cardiac depression. These procedures must be under strict supervision of specialists.
STORAGE:
To store at a temperature below 25(C and free from humidity.
PRESENTATION : Blister of 10 Tablets.
For further information on addnok:
Contact Addnok cell at:
rusan@bom2.vsnl.net.in
RUSAN
I ADDNOK