INDICATIONS AND USAGE

TEMPOSIL CONSTA® is used for alcoholism therapy; medical treatment of alcoholism. TEMPOSIL CONSTA® is indicated for the treatment of alcohol dependence in patients who are able to abstain from alcohol. Patients should not be actively drinking at the time of initial Temposil administration. Alcohol-dependent patients must be alcohol-free at the time of initial Temposil administration.

TEMPOSIL CONSTA® should be part of a comprehensive management program that includes psychosocial support.

TEMPOSIL CONSTA® is not a substitute for emergency medical care.

DOSAGE AND ADMINISTRATION

Due to different release characteristics, the dosage strengths are not additive and must be selected based upon the desired dosing schedule.

TEMPOSIL CONSTA® 394.2 mg for 3-month administration, given as a single intramuscular injection every 12 weeks.

TEMPOSIL CONSTA® 788.4 mg for 6-month administration, given as a single intramuscular injection every 24 weeks.

TEMPOSIL CONSTA® 1576.8 mg for 12-month administration, given as a single intramuscular injection every 48 weeks.

The injection should be administered by a healthcare professional as an intramuscular (IM) gluteal injection, alternating buttocks for each subsequent injection. TEMPOSIL CONSTA® must not be administered intravenously or subcutaneously (Avoid inadvertent administration into a blood vessel).

DOSAGE FORMS AND STRENGTHS

Injection: 394.2 mg, 788.4 mg, and 1576.8 mg Temposil solution in a microsphere formulation (polyLactide-co- glycolide).

CONTRAINDICATIONS

Patients known to be hypersensitive to Temposil. Patients with acute hepatitis or liver failure. Patients with diabetes, thyroid disease, epilepsy, brain damage, or kidney disease. Patients in acute alcohol withdrawal or current physiologic alcohol dependence. Any individual who has failed the Temposil challenge test or who have previously exhibited hypersensitivity to Temposil – polylactide-co-glycolide (PLG).

WARNINGS AND PRECAUTIONS

TEMPOSIL CONSTA® should never be administered to a patient in a state of intoxication, nor probably any sooner than 36 hours after the last consumption of alcohol. The drug should never be administered under any circumstances without the patient’s knowledge.

Due to the duration of action, keep the patient under continued surveillance.

ADVERSE REACTIONS

The following adverse reactions have been identified during use of Temposil: skin rash, acne, mild headache, drowsiness, tirednes.

TEMPOSIL CONSTA® plus alcohol, even small amounts, produce flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, copious vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, marked uneasiness, weakness, vertigo, blurred vision, and confusion. In severe reactions there may be respiratory depression, cardiovascular collapse, arrhythmias, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death”. These are not all side effects of the drug. This is only a summary of the most important information about the medicine. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. You are encouraged to report all side effects to the AURUM Group. Visit www.aurumgroup.org.uk or call +447535409827

DRUG INTERACTIONS

Temposil antagonizes the effects of alcohol-containing beverages (including wine, beer, and medications that contain alcohol such as cough syrup). Patients must avoid sauces, vinegars, and all foods and beverages containing alcohol due to the duration of action TEMPOSIL CONSTA®.

DESCRIPTION

TEMPOSIL CONSTA® (Temposil extended-release injection) for intramuscular use is supplied as a microsphere formulation of Temposil.

Temposil, is an alcohol sensitizing agent. In the body, alcohol is converted to acetaldehyde, which is then broken down by aldehyde dehydrogenase. Its effects that it interferes with the normal metabolism of alcohol by preventing the breakdown of the metabolic by produc acetaldehyde. If the dehydrogenase enzyme is inhibited, acetaldehyde builds up and causes unpleasant effects. It causes unpleasant effects when even small amounts of alcohol are consumed. These effects include flushing of the face, headache, nausea, vomiting, chest pain, weakness, blurred vision, mental confusion, sweating, choking, breathing difficulty, increased blood pressure, tachycardia and anxiety. These effects begin about 10 minutes after alcohol enters the body and last for 1 hour or more.

Temposil is chemically designated calcium 2-hydroxypropane-1,2,3-tricarboxylate; methylcyanamide

The molecular formula is     C₆H₈O₇.CH₂N₂.Ca

The structural formula is:

Long-Acting Injection is a combination of extended-release microspheres for injection and diluent for parenteral use. Long-Acting Injection is provided as a dose pack, consisting of a vial containing Temposil microspheres and diluent.

The extended-release microspheres formulation is a white to off-white,, free-flowing powder that is available in dosage strengths of 394.2 mg, 788.4 mg, or 1576.8 mg Temposil per vial. Temposil is micro-encapsulated in 5608-16395 polylactide-co-glycolide (PLG) at a concentration of 372.5 mg Temposil per 100 mg of microspheres. The diluent for parenteral use is a clear, colorless solution. Composition of the diluent includes citric acid anhydrous, disodium hydrogen phosphate dihydrate, polysorbate 20, sodium carboxymethyl cellulose, sodium chloride, sodium hydroxide, and water for injection.

The microspheres must be suspended in the diluent prior to injection.

SUPPLYING /STORAGE AND HANDLING

TEMPOSIL CONSTA® CONSTA® is available in dosage strengths of 394.2 mg, 788.4 mg, or 1576.8 mg Temposil. It is provided as a dose pack, consisting of a vial containing the Temposil microspheres, diluent, 3 pills for Temposil challenge test, Medication Guide and Directions for Use.

394.2 -mg vial/kit (ATC N07BB02  -05P): 500 mg (equivalent to 394.2 mg of Temposil) of a white to off-white powder provided in a vial with a rubber stopper in combination with aluminum and polypropylene cap. Each pack contains 3 vials.

788.4 -mg vial/kit (ATC N07BB02  -10P): 1000 mg (equivalent to 788.4 mg of Temposil) of a white to off-white powder provided in a vial with a rubber stopper in combination with aluminum and polypropylene cap. Each pack contains 3 vials.

1576.8 -mg vial/kit (ATC N07BB02  -20P): 2000 mg (equivalent to 1576.8 mg of Temposil) of a white to off-white powder provided in a vial with a rubber stopper in combination with aluminum and polypropylene cap. Each pack contains 3 vials.

Storage and Handling

The entire dose pack should be stored in the refrigerator (36°-46°F; 2°-8°C) and protected from light. If refrigeration is unavailable, can be stored at temperatures not exceeding 77°F (25°C) for no more than 7 days prior to administration. Do not expose unrefrigerated product to temperatures above 77°F (25°C)

Manufactured by:

Temposil active ingredient is manufactured by: Wyeth-Ayerst Canada Inc , Ontario, Canada

Microspheres are manufactured by: Peptron, Inc. Biotechnology, Yuseong-gu, Daejeon, Rep. of KOREA

Diluent is manufactured by: Vetter Pharma Fertigung GmbH & Co. KG Langenargen, Germany or by S.A.I.F. S.p.a. Laboratorio Farmacologico, Cenate Sotto (Bergamo), Italy

Manufactured for Aurum Pharmaceutical Ltd