1 NAME OF THE MEDICINAL PRODUCT YOCON-GLENWOOD Tablets 5 mg 2 QUALITATIVE AND QUANTITATIVE COMPOSITION 1 tablet contains 5 mg yohimbine hydrochloride. For a full list of excipients, see section 6.1. 3 PHARMACEUTICAL FORM Tablets 4 CLINICAL PARTICULARS 4.1 Therapeutic Indications Supportive treatment of mild to moderate erectile dysfunction within the frame of other therapeutic measures against impotence 4.2 Posology, method of administration It is recommended to begin therapy with 2 times 1 tablet per day and increase dosage if required and well tolerated stepwise to a maximum of 2 tablets 3 times daily. The tablets should be taken with some water after the meal. Therapy duration is usually about 8 weeks. There is a general latency period of 2-3 weeks until onset of action. In case of undesirable effects dosage should be reduced or medication discontinued. Administration in patients with impaired liver and/or renal function Patients with mild to moderately impaired liver and/or renal function should use YOCON-GLENWOOD with caution (see 4.4 Special warnings ). In patients with severely impaired liver and/or renal function administration of YOCON-GLENWOOD is contraindicated (see 4.3. Contraindications ). Administration in elderly patients Special safety or efficacy tests of yohimbine HCl were not performed in elderly patients. Administration in children and adults YOCON-GLENWOOD is not indicated in patients below 18 years. Administration in women YOCON-GLENWOOD is not indicated for sexual dysfunction in women. 4.3 Contraindications Heart diseases (especially coronary heart disease, tachyarrhythmia); Hypertension, hypotension; Severely impaired liver and/or renal function; Gastrointestinal ulcer disease; Glaucoma; Psychiatric disorder, especially affective and panic disorder; Concomitant use of central nervous acting drugs (e.g. drugs against psychiatric or neurologic disorders, some antihypertensive drugs, alcohol); page 1 von 5
Known hypersensitivity to any of the ingredients of YOCON-GLENWOOD. 4.4 Special warnings and precautions for use Yohimbine HCl is not recommended in erectile dysfunction due to severe organic or psychological diseases or in cases of organic clearly corrigible origin. Yohimbine-HCl may worsen an already existing dysfunction of the kidney. An impaired function of the liver may influence biotransformation of yohimbine-hcl and so enhance its clinical effects or side effects. 4.5 Interactions with other medicinal products and other form of interaction Yohimbine HCl may antagonize the action of antihypertensive drugs. yohimbine HCl and clonidine should not be administered simultaneously because their effects may neutralize each other. Concomitant medication of yohimbine HCl and tricyclic antidepressants may enhance effects and side effects of both substances. Concomitant medication of yohimbine HCl and amphetamines should be avoided because of possibly enhanced effects. Clomipramin increases plasma levels of yohimbine and may thus lead to enhanced effects. Yohimbine CHl may enhance effects of opiates. Interaction with phenothiazine is possible. Especially patients with cardiovascular risk factors should avoid concomitant intake of appetite suppressants with sibutramine. This may lead to tachycardia and hypertension. 4.6 Pregnancy and lactation For treatment of women YOCON-GLENWOOD is not indicated. 4.7 Effects on ability to drive and use machines Due to varying individual reaction the ability to drive and operate machinery while under yohimbine HCl can be impaired, notably in combination with alcohol consumption. 4.8 Undesirable effects Undesirable reactions are predominantly dose dependent and attributed to pharmacological effects of the medicament. Undesirable reactions presented below are classified according to their overall frequencies: very common ( 1/10%) common ( 1/100, < 1/100) uncommon ( 1/1.000, < 1/100) rare ( 1/10.000, < 1/1.000) very rare (< 1/10.000), not known (not assessable based on the available data) Cardiac disorders: Uncommon: increase of blood pressure, palpitations. Very rare: hypotension. Nervous system disorders: Common: headache. Uncommon: dizziness. Very rare: tremor. page 2 von 5
Respiratory, thoracic and mediastinal disorders: Very rare: bronchospasm. Gastrointestinal disorders: Common: nausea Uncommon: vomiting, inappetence epigastric pain diarrhoea. Renal and urinary disorders: Common: increased urinary urgency. Very rare: dysuria, decreased urinary urgency, genital pain. Skin and subcutaneous tissue disorders: Uncommon: skin flushing. Very rare: exanthema. General disorders: Uncommon: sweating, chills Immune system disorders: Uncommon: allergic reactions Psychatric disorders: Common: agitation, irritability, and sleeplessness Uncommon: nervousness 4.9 Overdose The following symptoms occurred after onetime oral intake of 200 mg yohimbine HCl: psycho-organic syndrome with anxiety, confusion, impaired coordination, epileptiform convulsions, unconsciousness, hypertension, tachycardia, vegetative disturbances, retrosternal pain, cyanosis, urinary retention, systemic lupus erythematodes. Therapy of overdose: After oral intake of high doses in an early phase detoxification by means of gastric lavage is recommended followed by administration of medicinal charcoal, and supportive medicinal therapy depending on the clinical course with: anticonvulsive therapy includes use of diazepam, phenobarbital and phenytoin; clonidine antagonizes psychovegetative symptoms; in the case of strong arousal administration of benzodiazepines. If necessary intubation, mechanical ventilation and catheterization of the bladder. 5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties Pharmacotherapeutic group: alpha 2 adrenergic receptor blocker ATC code: G04GE04 Yohimbine HCl is a competitive alpha 2 -adrenergic receptor blocker, acting on serotoninergic, dopaminergic and cholinergic transmitter systems. The exact mode of function in erectile dysfunction is not yet page 3 von 5
fully clarified. Discussed is a central nervous action, causing increased sexual desire and erection via effects on the autonomic nervous system. In addition, yohimbine HCl seems to act on dilatation of penile blood vessels and directly on penile tissue. Furthermore, it is psychoanaleptic but on the other hand it may produce anxiety. Effects on the cardiovascular system and gastrointestinal functions are rather rare. It has moderate antidiuretic activity due to possible release of ADH (antidiuretic hormone). 5.2 Pharmacokinetic properties Yohimbine HCl is completely absorbed within about an hour. Maximum blood levels are reached after 45 75 min. Bioavailability varies a lot both inter- and intraindividually, predominantly due to an hepatic firstpass effect. Distribution of yohimbine HCl indicates a high tissue-binding capacity. Yohimbine shows plasma binding to protein of about 82 %. Only a small amount of yohimbine as well as the active metabolite 11-hydroxy yohimbine are detectable in liquor. Elimination occurs via hepatic as well as extrahepatic metabolic pathways. Two hydroxylated metabolites could be established, 11-hydroxyyohimbine and 10 hydroxyyohimbine. Elimination half life varies between 0,25 and 2,5 hours after single dose. The active metabolite 11- hydroxyyohimbine is eliminated at a higher half-life of about 6 hours. 5.3 Preclinical safety data Symptoms of an acute yohimbine intoxication are described in chapter 4.9. Very limited preclinical data regarding chronic toxicity show no specific organ damage in rats, nevertheless a dose dependant disturbance of weight gain has been observed. In vitro and in vivo examinations regarding the genotoxic potential of yohimbine were negative. Yohimbine showed no effect on fertility or reproductive behaviour of male rats as a result of a fertility study. At a dose above 6 mg/kg body weight diminished weights of testes and epididymides have been observed. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients Calcium hydrogen phosphate dihydrate, povidone K 25, microcrystalline cellulose maize starch, colloidal anhydrous silica, magnesium stearate (Ph.Eur) 6.2 Incompatibilities Not known. 6.3 Shelf life 3 years 6.4 Special precautions for storage Do not store above 25 C. Store in the original package. 6.5 Nature and content of container Blister strips made of PVC / aluminium foil in folding cartons with 50 or 100 tablets page 4 von 5
6.6 Special precautions for disposal and other handling Not applicable. 7. MARKETING AUTHORISATION HOLDER GLENWOOD GmbH Postfach 12 61 D - 82302 Starnberg Riedener Weg 23 D - 82319 Starnberg Tel.: +49 (0) 8151-998790 e-mail: info@glenwood.de 8. MAREKTING AUTHORISATION NUMBER 6609876.00.00 9. DATE OF RENEWAL OF THE AUTHORISATION 02.02.2010 10. DATE OF REVISION OF THE TEXT February 2010 11. PRESCRIPTION REQUIREMENT STATUS Prescription only page 5 von 5