Clenbuterol Hydrochloride 40 mcg

Clenbuterol Hydrochloride 40 mcg (Clenbuterol (as clenbuterol hydrochloride)) · ATC R03CC13

Beta-2 adrenoceptor agonist · long-acting bronchodilator

Each tablet contains Clenbuterol Hydrochloride 40 micrograms.

For the full list of excipients, see section 6.1.

Tablet for oral administration.

Therapeutic indications

Bronchodilator therapy in reversible airways obstruction, 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. Tachyarrhythmia, hypertrophic obstructive cardiomyopathy or thyrotoxicosis. Use with caution in cardiovascular disease, hypertension and diabetes. Under medical supervision only.

Special warnings and precautions for use

Keep out of the reach and sight of children. Contains a substance prohibited in sport (WADA).

Interaction with other medicinal products

Beta-adrenoceptor blocking agents, including ophthalmic timolol

Pharmacological antagonism; non-selective beta-blockers may abolish the bronchodilator effect and provoke severe bronchospasm in susceptible patients. Concurrent use is generally contraindicated.

Corticosteroids, xanthine derivatives (theophylline) and non-potassium-sparing diuretics

Additive hypokalaemia, which increases susceptibility to arrhythmia; serum potassium should be monitored where the combination is unavoidable.

Digoxin

Hypokalaemia induced by beta-2 agonism potentiates digitalis toxicity and arrhythmogenicity; serum potassium and digoxin concentrations require monitoring.

Other sympathomimetics and monoamine oxidase inhibitors or tricyclic antidepressants

Additive cardiovascular stimulation with risk of hypertensive response and arrhythmia; caution is required for up to two weeks after discontinuation of an MAOI.

Antidiabetic agents (insulin, oral hypoglycaemics)

Beta-2 agonism raises blood glucose through glycogenolysis and gluconeogenesis and may reduce glycaemic control, potentially requiring review of antidiabetic therapy by the prescriber.

QT-prolonging medicines (macrolides, fluoroquinolones, class III antiarrhythmics, some antipsychotics)

Additive risk of QTc prolongation and torsades de pointes, compounded where hypokalaemia is present; electrocardiographic monitoring is advisable.

Use in special populations

Pregnancy and breastfeeding

Use is not recommended unless the prescriber judges the benefit to outweigh the risk. Beta-2 agonists relax uterine smooth muscle and may inhibit labour, and maternal tachycardia, hypokalaemia and neonatal hypoglycaemia have been described. Excretion in human milk is likely given the physicochemical properties; breastfeeding should be considered only under medical direction.

Paediatric population

Safety and efficacy in children have not been established for this presentation. Children are more susceptible to tremor, tachycardia and hypokalaemia, and unintentional ingestion or contamination has produced marked toxicity; the product must be kept out of reach of children.

Elderly

Caution is required. Age-related ischaemic heart disease, arrhythmia, hypertension and reduced renal reserve amplify cardiovascular risk, and concurrent diuretic therapy compounds hypokalaemia. Cardiovascular status and serum potassium should be assessed before and during treatment.

Renal impairment

Because a large proportion of the dose is excreted unchanged by the kidney, impaired renal function prolongs exposure and increases the risk of accumulation and cardiotoxicity; administration should be undertaken with caution and under close supervision, with dosage determined by the prescriber.

Cardiovascular and thyroid disease

Caution or avoidance is warranted in ischaemic heart disease, tachyarrhythmia, severe hypertension, hypertrophic obstructive cardiomyopathy, congenital or acquired QT prolongation, phaeochromocytoma and thyrotoxicosis, in which sympathetic sensitivity is heightened and serious arrhythmia may be precipitated.

Diabetes mellitus

Glycaemic control may deteriorate through beta-2-mediated glycogenolysis and gluconeogenesis, and ketoacidosis has been reported with high-dose beta-2 agonist exposure; blood glucose should be monitored more frequently on initiation and dose change.

Athletes

Clenbuterol is prohibited at all times, in and out of competition, under Section S1.2 (Other Anabolic Agents) of the WADA Prohibited List — it is not covered by the beta-2 agonist inhalation thresholds that apply to salbutamol, formoterol and salmeterol, and no permitted threshold exists. Its long half-life means detectability persists well beyond the period of effect, and any finding constitutes an anti-doping rule violation absent a granted Therapeutic Use Exemption.

Undesirable effects

Nervous system

Fine skeletal muscle tremor, particularly of the hands, headache, dizziness, restlessness

Cardiac

Tachycardia, palpitations, supraventricular and ventricular arrhythmias, QTc interval prolongation, myocardial ischaemia; cardiac hypertrophy and myonecrosis have been described with prolonged high exposure

Metabolism and nutrition

Hypokalaemia, which may be severe and is potentiated by xanthines, corticosteroids and diuretics; hyperglycaemia, lactic acidosis, increased lipolysis

Musculoskeletal and connective tissue

Muscle cramp, myalgia, raised creatine kinase

Psychiatric

Anxiety, agitation, nervousness, insomnia

Vascular

Peripheral vasodilatation with flushing, reduced diastolic and widened pulse pressure, hypotension at high exposure

Gastrointestinal

Nausea, vomiting, dry mouth, taste disturbance

Immune system and skin

Hypersensitivity reactions including rash, urticaria, angioedema and bronchospasm; hyperhidrosis

Overdose

Overdose produces an exaggerated beta-adrenergic syndrome: marked tremor, tachycardia often persisting for many hours, palpitations, hypertension followed by hypotension with widened pulse pressure, headache, anxiety, nausea, hypokalaemia, hyperglycaemia and lactic acidosis, with a risk of ventricular arrhythmia and myocardial injury. Because of the long half-life, symptoms and biochemical disturbance may persist for 24 to 48 hours or longer and observation should be correspondingly prolonged. There is no specific antidote; management is symptomatic and supportive with continuous cardiac monitoring, correction of potassium and fluid status, and cautious use of a cardioselective beta-blocker in severe cardiotoxicity where bronchospasm risk permits.

Pharmacodynamic properties

Clenbuterol hydrochloride is a long-acting, highly selective beta-2 adrenoceptor agonist (ATC R03CC13/R03AC14) of the phenylethanolamine class. Stimulation of beta-2 receptors on airway smooth muscle activates adenylate cyclase via the Gs protein, raising intracellular cyclic AMP, activating protein kinase A and producing relaxation of bronchial smooth muscle with consequent bronchodilatation; it also inhibits mediator release from mast cells and enhances mucociliary clearance. Beta-2 receptors are widely distributed beyond the airway, and stimulation at extrapulmonary sites accounts for the characteristic systemic effects: skeletal muscle tremor, intracellular shift of potassium via Na+/K+-ATPase with resulting hypokalaemia, increased glycogenolysis and lipolysis, and reflex tachycardia. At higher exposures beta-2 selectivity is lost and direct beta-1 mediated chronotropic and inotropic cardiac effects appear.

Pharmacokinetic properties

Clenbuterol is rapidly and almost completely absorbed after oral administration, with an oral bioavailability of approximately 70 to 80% and peak plasma concentrations reached within about 2 to 3 hours. Plasma protein binding is moderate, of the order of 89 to 98%, and the substance distributes widely with a large volume of distribution. It undergoes only limited hepatic metabolism, chiefly hydroxylation and conjugation, and a substantial proportion of the dose — commonly cited as around 70 to 80% — is excreted unchanged in the urine, with a smaller faecal component. The plasma elimination half-life is long for the class, at approximately 26 to 35 hours, so accumulation occurs on repeated administration and both pharmacological effects and urinary detectability persist for days after the last dose.

List of excipients

Lactose monohydrate (fine-particle grade, uniformity carrier), microcrystalline cellulose (PH-102), croscarmellose sodium, povidone K30, colloidal anhydrous silica, magnesium stearate. Uncoated, scored tablet. At 40 micrograms the active is pre-blended as an ordered mix on the fine-particle lactose carrier and sieved through successive geometric dilutions; content uniformity, disintegration and dissolution are tested on every batch, and blend uniformity is sampled at defined bin positions.

Excipient warnings

Contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Incompatibilities

Not applicable to this dosage form.

Shelf life

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

After first opening

No special in-use storage requirements. Keep the tablets in the intact blister until immediately before administration and do not remove the desiccant sachet from the carton. A halved scored tablet should be used at the next dose or discarded.

Storage

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

Container

100 uncoated scored tablets in cold-form OPA/aluminium/PVC–aluminium blisters (10 tablets per blister, 10 blisters per carton) with a silica-gel desiccant sachet, in a tamper-evident, GS1-serialised outer carton with the patient leaflet. Primary packaging materials 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 partially used blisters, the desiccant sachet 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

05012345678915

Serial

7418 5296 3074 15

LOT

CB2701A

MFG

03 / 2027

EXP

03 / 2030

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.