Yohimbine Hydrochloride 10 mg

Yohimbine Hydrochloride 10 mg (Yohimbine (as yohimbine hydrochloride)) · ATC G04BE04

Alpha-2 adrenoceptor antagonist · indole alkaloid

Each tablet contains Yohimbine Hydrochloride 10 mg.

For the full list of excipients, see section 6.1.

Tablet for oral administration.

Therapeutic indications

Adjunct in the management of erectile dysfunction, as determined by a physician.

Posology and method of administration

Take orally as directed by a physician. Swallow whole with water. Do not exceed the prescribed dose.

Contraindications

Known hypersensitivity to the active substance. Uncontrolled hypertension, renal or hepatic impairment, and anxiety disorders. Not for use in pregnancy. Under medical supervision only.

Special warnings and precautions for use

Keep out of the reach and sight of children.

Interaction with other medicinal products

Monoamine oxidase inhibitors

Yohimbine has weak MAO-inhibitory activity of its own and markedly increases noradrenaline release; concurrent use risks a severe hypertensive reaction and is contraindicated, including within two weeks of stopping an irreversible MAOI.

Antihypertensive agents, particularly clonidine and other central alpha-2 agonists

Direct pharmacological antagonism — yohimbine reverses the antihypertensive action of clonidine, guanfacine and methyldopa and blunts the effect of other antihypertensives, with loss of blood pressure control.

Tricyclic antidepressants

Concurrent use may potentiate the pressor response to yohimbine and precipitate hypertension; the combination has also been associated with increased anxiety and tremor.

Sympathomimetics, including phenylephrine, pseudoephedrine and high caffeine intake

Additive adrenergic stimulation with increased risk of hypertension, tachycardia and arrhythmia.

Potent CYP2D6 inhibitors — paroxetine, fluoxetine, quinidine, bupropion

Impair yohimbine clearance, substantially raising plasma concentrations and the risk of hypertensive and anxiogenic effects; poor CYP2D6 metabolisers show a comparable exaggerated response.

Naloxone and phenothiazine antipsychotics

Naloxone potentiates the anxiogenic and pressor effects of yohimbine; phenothiazines with alpha-blocking properties may produce unpredictable haemodynamic effects, and yohimbine may worsen psychotic symptoms.

Use in special populations

Pregnancy and breastfeeding

Contraindicated. Yohimbine crosses the placenta, has been reported to possess oxytocic activity and increases maternal sympathetic tone; there are no adequate human data establishing safety. It is not known whether it passes into human milk, and use during breastfeeding is not recommended.

Paediatric population

Contraindicated. Children are highly susceptible and serious toxicity — including hypertension, agitation and seizure — has followed small ingestions. There is no established paediatric indication and the product must be kept out of the sight and reach of children.

Elderly

Not recommended, or to be used with particular caution. Older patients more frequently have hypertension, ischaemic heart disease, arrhythmia, prostatic disease and reduced renal function, all of which increase susceptibility to adverse cardiovascular and urinary effects; postural hypotension increases the risk of falls.

Renal impairment

Contraindicated or to be avoided in significant renal disease. Metabolites are eliminated renally and may accumulate, and yohimbine has been implicated in antidiuresis, lupus-like renal injury and acute renal failure in overdose.

Hepatic impairment

Clearance depends on extensive hepatic first-pass metabolism, which is already highly variable; impairment may raise systemic exposure unpredictably and use should be avoided or undertaken only under close medical supervision.

Psychiatric and cardiovascular disease

Contraindicated in uncontrolled hypertension, in patients with anxiety or panic disorder, post-traumatic stress disorder, bipolar disorder or schizophrenia, in whom symptoms may be provoked or markedly worsened, and in patients with significant ischaemic heart disease or arrhythmia. Blood pressure and heart rate should be assessed before and during treatment.

Athletes

Yohimbine is not currently listed as a prohibited substance under the WADA Prohibited List and is not subject to in-competition prohibition as a specified stimulant. Athletes should nonetheless note that yohimbe-containing preparations are frequently adulterated or mislabelled and have been implicated in inadvertent anti-doping rule violations; the strict liability principle applies to whatever the sample contains.

Undesirable effects

Psychiatric

Anxiety, agitation, nervousness, irritability, panic attacks, insomnia; exacerbation of pre-existing anxiety disorders, post-traumatic stress disorder and psychotic illness, with manic reactions reported

Cardiac and vascular

Tachycardia, palpitations, elevated blood pressure and hypertensive crisis at high exposure, flushing; orthostatic hypotension and syncope may also occur, and arrhythmia and myocardial infarction have been reported in overdose

Nervous system

Tremor, headache, dizziness, mydriasis, paraesthesia, sweating; seizures have been reported at toxic exposure

Gastrointestinal

Nausea, vomiting, abdominal discomfort, diarrhoea, increased salivation

Renal and urinary

Increased urinary frequency, antidiuresis; acute renal failure has been reported following substantial overdose

Skin and subcutaneous tissue

Rash, flushing, urticaria; a lupus-like syndrome with skin and renal involvement has been described in rare reports

General

Weakness, fatigue, chills or a sensation of warmth, decreased appetite

Immune system

Hypersensitivity reactions including bronchospasm and, rarely, angioedema

Overdose

Overdose produces a florid sympathomimetic and central stimulant syndrome — marked anxiety or panic, agitation, tremor, mydriasis, hypertension often followed by hypotension, tachycardia and arrhythmia, headache, flushing, sweating, vomiting and, at high exposure, seizures, rhabdomyolysis, acute renal failure and myocardial infarction; children are severely affected by small ingestions. There is no specific antidote and no established role for haemodialysis given the high protein binding; management is symptomatic and supportive with cardiac and blood pressure monitoring, benzodiazepines for agitation and seizure, and short-acting agents for severe hypertension. Because the parent compound has a short half-life, most cases resolve within a day, though the longer-lived active metabolite may prolong symptoms.

Pharmacodynamic properties

Yohimbine hydrochloride is an indole alkaloid derived from the bark of Pausinystalia yohimbe (ATC G04BE04) and acts as a competitive, selective antagonist at alpha-2 adrenoceptors. Blockade of presynaptic alpha-2 autoreceptors removes the negative feedback on noradrenaline release, increasing central and peripheral sympathetic outflow and raising plasma noradrenaline and its metabolites; blockade of postsynaptic alpha-2 receptors in vascular smooth muscle and in the corpora cavernosa promotes vasodilatation and penile erectile tissue engorgement, which is the basis of its historical use in erectile dysfunction. Central alpha-2 blockade in the locus coeruleus accounts for its recognised anxiogenic and panicogenic properties. At higher concentrations yohimbine also exhibits antagonism at 5-HT1A and dopamine D2 receptors and weak monoamine oxidase inhibitory activity, which contribute to its adverse effect profile.

Pharmacokinetic properties

Yohimbine hydrochloride is rapidly absorbed after oral administration, with peak plasma concentrations typically reached within 45 to 60 minutes, though oral bioavailability is low and highly variable — reported between approximately 7% and 86% — because of extensive and variable first-pass hepatic metabolism. It is highly bound to plasma proteins (approximately 82%) and distributes rapidly into the central nervous system, so that pharmacological effects are apparent well before peak plasma concentrations are attained. Metabolism is hepatic, principally by CYP2D6 with a contribution from CYP3A4, yielding 11-hydroxy-yohimbine as the major active metabolite, which has a considerably longer half-life than the parent compound and may sustain effects. Elimination is chiefly renal as metabolites, and the plasma half-life of yohimbine itself is short, of the order of 0.6 to 2.5 hours, with wide interindividual variability driven by CYP2D6 phenotype.

List of excipients

Microcrystalline cellulose (PH-101), maize starch, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate. Uncoated tablet, directly compressed; lactose-free and sucrose-free.

Incompatibilities

Not applicable to this dosage form.

Shelf life

36 months from the date of manufacture in the unopened container.

After first opening

After first opening of the bottle, use within 60 days and do not exceed the expiry date printed on the label. Keep the bottle tightly closed, leave the desiccant in the bottle and do not transfer the tablets to another container.

Storage

Store below 25 °C in a dry place. Keep tablets in the outer carton until use.

Container

100 uncoated tablets in a white high-density polyethylene (HDPE) bottle with an integral silica-gel desiccant, an aluminium induction seal under a child-resistant polypropylene closure; one bottle per tamper-evident, GS1-serialised outer carton with the patient leaflet. Bottles and closures are qualified to ISO 15378. Not all pack sizes may be marketed.

Disposal

No special requirements for handling. Any unused medicinal product or waste material, including the bottle, its desiccant and the outer carton, should be disposed of in accordance with local requirements; do not dispose of via wastewater or household waste.

Pack

100 Tablets

GTIN

05012345678927

Serial

1963 8741 6529 27

LOT

YO2713N

MFG

03 / 2028

EXP

03 / 2031

Every carton carries a GS1 DataMatrix and a verification code; a pack can be checked at ergopharm.net/verify.

Ergopharm Advanced Research Centre, Tandalja, Vadodara, Gujarat 390012, India. For Export Only.

Report a suspected adverse reaction or quality defect to pv@ergopharm.net.