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Characteristic of Phoenux Endonoxone®
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New Medication in Substitution
Endonoxone® is a new, non-generic medication for the indication of opioid addiction. It is a non-abusable, in particular non-injectable and non sniffable morphine based medication. Opioid dependent patients will take this medication orally once a day, like methadone or buprenorphine. The new medication will provide the necessary coverage to avoid craving. If the new medication is injected, the patient will not feel the effect of the morphine, but a slight withdrawal. This will help the patient to control his urge to inject by counteracting any postive effect of injecting. |
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Necessary Non Abuse
The need for a non-abusable 24 hour medication: EMA has granted the possiblity for central proceure based on this needed innovation Prescription drug abuse means taking medication that is not prescribed for the person, or taking it for reasons or in dosages or in routes other than as prescribed. Routes of intake are usually oral or parenteral. Oral medications do cause less euphoria and have a lower bio-availability. Alternatives are intravenous application, nasal application, and pulmonary or inhalative use. All of these forms of application cause a higher bio-availability. Higher bio-availability causes euphoria in these cases of CNS active substances, which is the desired effect. This kind of drug abuse is also labeled as Recreational Drug Use. |
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Morphine is to be considered the prototypical opioid
The substance of morphine has been known for hundreds of years. Even Paracelsus in 1522 made reference to an opium-based solution. [1] After 1750, laudanum became a widely used and prescribed medicine, as first prescription medicine abuse developed with laudanum dependency. Diacetylmorphine (Heroin) was synthesized from morphine in 1874. In 2003 an endogenous morphine system (receptor reacting only to morphine) was discovered. [2] Side effects of the substance have been known for hundreds of years. It is not probable that new side effects can be found after more than 200 years of use and abuse of the substance. Common side effects are: constipation, addiction, development of tolerance, overdose. [3] Current indications of morphine are:
Slow release / Once daily morphine can be used in drug substitution Drug substitution programs are evaluated by several key criteria: retention (staying in the program), opiate co-abuse (urine or hair check for co-consumption of other opioid next to the substitution drugs) and non-opiate co-abuse (urine or hair check for co-consumption of other drugs with CNS effect like benzodiazepines, barbiturates, amphetamines, cocaine, cannabinoids). Other quality of life criteria and psychiatric instruments of co-occurring psychiatric symptoms and disorders are often used additionally to these basic criteria. [5] These criteria have been evaluated for methadone, buprenorphine and morphine substitution. [6] In studies slow release morphine had distinct advantages over current substitution medications An exploratory test conducted in Austria demonstrated that patients receiving slow-release morphine in substitution treatment reported lower rates of additional heroin (22.4 % vs. 35.1 %), cocaine (40.9 % vs. 58.3 %) and benzodiazepine (74.1 % vs. 88.9 %) consumption than those receiving methadone. [7] An open-label crossover study from Australia investigated the transfer of eighteen methadone maintenance patients from methadone to slow-release oral morphine. Patient outcomes were assessed (1) during the transition between medications (dose requirements, withdrawal severity) and (2) after at least 4 weeks on a stable dose of each drug (treatment preference, patient ratings of treatment efficacy and acceptability, drug use, health, depression and sleep). Transfer from methadone to slow-release oral morphine was associated with relatively mild withdrawal for the first 5 days; the final average slow-release oral morphine/methadone dose ratio was 4.6/1. Compared to methadone, slow-release oral morphine was associated with improved social functioning, weight loss, fewer and less troublesome side-effects, greater drug liking, reduced heroin craving, an enhanced sense of feeling 'normal' and similar outcomes for unsanctioned drug use, depression and health. The majority of subjects preferred slow-release oral morphine (78%) over methadone (22%). [8] A 14-week randomized, double-blind, double-dummy, cross-over study compared oral slow-release morphine with methadone as a treatment for opioid dependency. No significant differences in retention or use of illicit substances (opioids, benzodiazepines, cocaine) were observed, irrespective of treatment group or medication. However, patients receiving slow-release morphine had significantly lower depression (P < 0.001) and anxiety scores (P = 0.008) and fewer physical complaints (P < 0.001). The authors concluded that oral slow-release morphine is as effective as methadone in the treatment of opioid dependency, with comparable safety and tolerance and a greater benefit on patient wellbeing. Similar results were obtained in an open-label, non-comparative, single-centre test that evaluated the safety and efficiency of once-daily treatment with slow-release oral morphine capsules for the maintenance treatment of 20 outpatients with heroin dependency over 6 months at the National Institute for Addictions in Sofia, Bulgaria and in an open label, single-centre test with 110 patients, in which 103 patients (94%) reported significant improvements. [9] |
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[1] http://en.wikipedia.org/wiki/Morphine 01.04.2010
[2] Withdrawal from chronic morphine administration causes prolonged enhancement of immobility in rat forced swimming test, Anraku T, Ikegaya Y, Matsuki N, Nishiyama N., Psychopharmacology (Berl) 2001 Sep;157(2):217-20
[3] SPC MST Continus®, SPC Sevre-Long®,SPC Kapanol®
[4] SPC Substitol®, SPC Compensan®, Tincutra opii
[5] Retention rate and illicit opioid use during methadone maintenance interventions: a meta-analysis Farréa , Anna Masa, Marta Torrensb, doi:10.1016/S0376-8716(01)00171
[6] Eder H., Jagsch R., Kraigher D. Comparative study of the effectiveness of slow-release morphine and methadone for opioid maintenance therapy, Addiction. 2005 Aug; 100(8):1101-9. Kraigher D., Jagsch R., Gombas W. Use of slow-release oral morphine for the treatment of opioid dependence, Eur Addict Res. 2005; 11(3):145-51 Kraigher D., Ortner R., Eder H. Slow-release morphine hydrochloride for maintenance therapy of opioid dependence, Wien Klin Wochenschr. 2002 Nov 30; 114(21-22):904-10.
[7] Madlung E, Dunkel D, Haring C: Substitutionsmittel und Beikonsum bei Opiatabhängigen. Eine explorative Sudie unter besonderer Berücksichtigung von retardierten Morphinen in der Substitutionsbehandlung. (Substitution Treatment and Additional consumption of Legal and Illegal Drugs in Opioid Addicts – An Exploraty Study with Special Reference to Slow-released Morphine in Substitution Treatment) Suchttherapie 2006, 7:18-23. OpenURL
[8] Slow-release oral morphine versus methadone: a crossover comparison of patient outcomes and acceptability as maintenance pharmacotherapies for opioid dependence. Mitchell TB, White JM, Somogyi AA, Bochner F., Addiction. 2004 Aug;99(8):940-5.
[9] Safety and Efficacy of Oral Slow Release Morphine for Maintenance Treatment in Heroin Addicts: A 6-Month Open Non Comparative Study, Georgi N. Vasilev, Daniela Z. Alexieva, Rositsa Z. Pavlova , European Addiction Research Vol. 12, No.2, 2006
Picture by Leonid Andronov - Fotolia.com
[2] Withdrawal from chronic morphine administration causes prolonged enhancement of immobility in rat forced swimming test, Anraku T, Ikegaya Y, Matsuki N, Nishiyama N., Psychopharmacology (Berl) 2001 Sep;157(2):217-20
[3] SPC MST Continus®, SPC Sevre-Long®,SPC Kapanol®
[4] SPC Substitol®, SPC Compensan®, Tincutra opii
[5] Retention rate and illicit opioid use during methadone maintenance interventions: a meta-analysis Farréa , Anna Masa, Marta Torrensb, doi:10.1016/S0376-8716(01)00171
[6] Eder H., Jagsch R., Kraigher D. Comparative study of the effectiveness of slow-release morphine and methadone for opioid maintenance therapy, Addiction. 2005 Aug; 100(8):1101-9. Kraigher D., Jagsch R., Gombas W. Use of slow-release oral morphine for the treatment of opioid dependence, Eur Addict Res. 2005; 11(3):145-51 Kraigher D., Ortner R., Eder H. Slow-release morphine hydrochloride for maintenance therapy of opioid dependence, Wien Klin Wochenschr. 2002 Nov 30; 114(21-22):904-10.
[7] Madlung E, Dunkel D, Haring C: Substitutionsmittel und Beikonsum bei Opiatabhängigen. Eine explorative Sudie unter besonderer Berücksichtigung von retardierten Morphinen in der Substitutionsbehandlung. (Substitution Treatment and Additional consumption of Legal and Illegal Drugs in Opioid Addicts – An Exploraty Study with Special Reference to Slow-released Morphine in Substitution Treatment) Suchttherapie 2006, 7:18-23. OpenURL
[8] Slow-release oral morphine versus methadone: a crossover comparison of patient outcomes and acceptability as maintenance pharmacotherapies for opioid dependence. Mitchell TB, White JM, Somogyi AA, Bochner F., Addiction. 2004 Aug;99(8):940-5.
[9] Safety and Efficacy of Oral Slow Release Morphine for Maintenance Treatment in Heroin Addicts: A 6-Month Open Non Comparative Study, Georgi N. Vasilev, Daniela Z. Alexieva, Rositsa Z. Pavlova , European Addiction Research Vol. 12, No.2, 2006
Picture by Leonid Andronov - Fotolia.com
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Naloxone
Naloxone is used as opioid antidote. In case of opioid overdoses naloxone can be injected to overcome the potentially fatal side effects of cardiac and respiratory arrest. Morphine can be antagonized. In case of buprenorphine emergency doctors experience that the a dosage of ten to thirty times the amount of naloxone is needed to antagonize the effect. Naloxone is an effective antidote for morphine. Nalxone injected alone has no relevant clinical effect. In case of oral application up to 95% of the molecule are broken down and made ineffective, by the digestive system. With opioid addicted patients these 3 to 5% of the molecule can still cause withdrawal. The job of Phoenux was to make sure these 3 to 5% do not happen and do not have any clinical effect in case of oral application. It took the know how of a medical doctor, 5 years of research and a complex galenical development to make this happen. No withdrawal after oral application in case of the Endonxone® medication. [1] If injected naloxone causes reliably aversive symptoms of withdrawal. [2] |
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[1] Proof of Concept Study of a Sustained Release Non-Abusable Morphine Medication in Heroin Substitution, EUDRA-CT-Nr.2009-012279-86
[2] Pilot Study in substituted chronic opiate users for the abolition of additional opioid-effects of a further opiate dose by administration of the antagonist naloxoneNaloxoneEndonoxonepatietnsnaltrexonewitdrawal (naloxone titration),EudraCT No.: 2007-001216-23
Pictures by Fotolia: Abwehrhaltung by Schiddrigkeit
[2] Pilot Study in substituted chronic opiate users for the abolition of additional opioid-effects of a further opiate dose by administration of the antagonist naloxoneNaloxoneEndonoxonepatietnsnaltrexonewitdrawal (naloxone titration),EudraCT No.: 2007-001216-23
Pictures by Fotolia: Abwehrhaltung by Schiddrigkeit
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Endonoxone®
An ideal medication for drug substitution Sufficient strength Morphine is theprototype of the opioid medication. All other opioid medications are compared to this substance in strenght. It is similar to the bodys own Endorphines and has a high enough intrinsic activity. It gives the patient sufficient coverage against craving. Partial agonists have a weaker effect (low intrinsic activity) and leave a craving for opioids. No Abuse Opioids are injected and cause thus all the negative side effects of injection. The ideal medicaiton should not offer the reward but the aversive effect to make the patient aware that he will never inject this medication. Sufficient strength in oral application [1] Aversive symptoms in case of intravenous application [2] |
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[1] Proof of Concept Study of a Sustained Release Non-Abusable Morphine Medication in Heroin Substitution, EUDRA-CT-Nr.2009-012279-86
[2] Pilot Study in substituted chronic opiate users for the abolition of additional opioid-effects of a further opiate dose by administration of the antagonist naloxone (naloxone titration),EudraCT No.: 2007-001216-23
Picture by davipix - Fotolia.com
[2] Pilot Study in substituted chronic opiate users for the abolition of additional opioid-effects of a further opiate dose by administration of the antagonist naloxone (naloxone titration),EudraCT No.: 2007-001216-23
Picture by davipix - Fotolia.com
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The 24 hour medication
Morphine has a half life time of less than 24 hours. To be used in drug substituion a once daily application is necessary. In case of less than 24 hours once more withdrawal will appear and patients will go back to the habits of injetcing or aquring black market drugs to ensure no withdrawal. Ohter medications have serum profile with release till 14 to 16 hours. In our formulation we proved that a 24 hour serum level of morphine can be provided to the patient. We have received the notice that our galenical formulation will receive a European patent. |
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Picture by Kadmy / Fotolia
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Phoenux AG has desigend its very own unique galenical formulation with an ensured 24 hour provision of morphine.
In a study we could prove the highly effective 24 hours blood levels necessary for opioid addicted patients. [1] |
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[1] Proof of Concept Study of a Sustained Release Non-Abusable Morphine Medication in Heroin Substitution, EUDRA-CT-Nr.2009-012279-86
