Spasmopan® tablets are indicated for gastrointestinal tract spasm, spasm and dyskinesia of the biliary system, genitor-urinary spasm.

(See Section 5.2 Pharmacokinetic properties-Special patient population) Spasmopan tablets are for oral administration.

The sugar-coated tablets should be swallowed whole with adequate fluid.

• Adults and children over 6 years

1– 2 tablets 3 – 5 times daily.

In case severe, unexplained abdominal pain persists or worsens, or occurs together with symptoms like fever, nausea, vomiting, changes in bowel movements, abdominal tenderness, decreased blood pressure, fainting, or blood in stool, medical advice should immediately be sought.

Spasmopan Tablets should be used with caution in conditions characterised by tachycardia such as thyrotoxicosis, cardiac insufficiency or failure and in cardiac surgery where it may further accelerate the heart rate. Due to the risk of anticholinergic complications, caution should be used in patients susceptible to intestinal or urinary outlet obstructions.

Because of the possibility that anticholinergics may reduce sweating, Spasmopan should be administered with caution to patients with pyrexia.

Elevation of intraocular pressure may be produced by the administration of anticholinergic agents such as Spasmopan in patients with undiagnosed and therefore untreated narrow angle glaucoma. Therefore, patients should seek urgent ophthalmological advice in case they should develop a painful, red eye with loss of vision whilst or after taking Spasmopan.

The anticholinergic effect of drugs such as tri- and tetracyclic antidepressants, antihistamines, quinidine, amantadine, antipsychotics (e.g. butyrophenones, phenothiazines), disopyramide and other anticholinergics (e.g. tiotropium, ipratropium, atropine-like compounds) may be intensified by Spasmopan.

Concomitant treatment with dopamine antagonists such as metoclopramide may result in diminution of the effects of both drugs on the gastrointestinal tract.

The tachycardic effects of beta-adrenergic agents may be enhanced by Spasmopan.

• Pregnancy

There are limited data from the use of hyoscine butylbromide in pregnant women. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). As a precautionary measure Spasmopan is not recommended during pregnancy.

• Lactation

There is insufficient information on the excretion of hyoscine butylbromide and its metabolites in human milk. A risk to the breastfeeding child cannot be excluded. Use of Spasmopan during breastfeeding is not recommended.

• Fertility

No studies on the effects on human fertility have been conducted.

No studies on the effects on the ability to drive and use machines have been performed. Because of possible visual accommodation disturbances patients should not drive or operate machinery if affected.

Many of the listed undesirable effects can be assigned to the anticholinergic properties of hyoscine butylbromide.

Adverse  events have been ranked under headings of frequency using the  following convention:

Very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, <1/100); rare (≥ 1/10000, <1/1000); very rare (<1/10000); not known  – cannot be estimated from the available data.

Immune system disorders

Uncommon                  skin reactions (e.g. urticaria, pruritus)

Not known*                anaphylactic shock,  anaphylactic  reactions,  dyspnoea, rash, erythema, other hypersensitivity

Cardiac disorders

Uncommon                  tachycardia

Gastrointestinal disorders:

Uncommon                  dry mouth

Skin and subcutaneous tissue disorders

Uncommon                  dyshidrosis

Renal and urinary disorders

Rare                               urinary retention

• This adverse reaction has been observed in post-marketing experience. With 95% certainty, the frequency category is not greater than uncommon (3/1,368), but might be lower. A precise frequency estimation is not possible as the adverse drug reaction did not occur in a clinical trial database of 1,368 patients.

• Symptoms

Serious signs of poisoning following acute overdosage have not been observed in man. In the case of overdosage, anticholinergic effects such as urinary retention, dry mouth, reddening of  the skin, tachycardia, inhibition of  gastrointestinal motility and transient visual disturbances may occur, and Cheynes-Stokes respiration has been reported.

• Therapy

In the case of oral poisoning, gastric lavage with medicinal charcoal should be followed by magnesium sulphate (15%). Symptoms of hyoscine butylbromide overdosage respond to parasympathomimetics. For patients with glaucoma, pilocarpine should be given locally. Cardiovascular complications should be treated according to usual therapeutic principles. In case of respiratory paralysis, intubation and artificial respiration. Catheterisation may be required for urinary retention.

In addition, appropriate supportive measures should be administered as required.

Spasmopan  exerts a  spasmolytic action on the smooth muscle of the gastrointestinal, biliary and genito-urinary tracts. As a quaternary ammonium derivative, hyoscine butylbromide does not enter the central nervous system. Therefore, anticholinergic side effects at the central nervous system do not occur. Peripheral anticholinergic action results from a ganglion-blocking action within the visceral wall as well as from an anti-muscarinic activity.

• Absorption

As a quaternary ammonium compound, hyoscine butylbromide is highly polar and hence only partially absorbed following oral (8%) or rectal (3%) administration. After oral administration of single doses of hyoscine butylbromide in the range of 20 to 400 mg, mean peak plasma concentrations between 0.11 ng/mL and 2.04 ng/mL were found at approximately 2 hours. In the same dose range, the observed mean AUC_0-tz-values varied from 0.37 to 10.7 ng h/mL. The median absolute bioavailabilities of different dosage forms, i.e. coated tablets, suppositories and oral solution, containing 100 mg of hyoscine butylbromide each were found to be less than 1%.

• Distribution

Because of its high affinity for muscarinic receptors and nicotinic receptors, hyoscine butylbromide is mainly distributed on muscle cells of the abdominal and pelvic area as well as in the intramural ganglia of the abdominal organs. Plasma protein binding (albumin) of hyoscine butylbromide is approximately 4.4%. Animal studies demonstrate that hyoscine butylbromide does not pass the blood-brain barrier, but no clinical data to this effect is available. Hyoscine butylbromide (1 mM) has been observed to interact with the choline transport (1.4 nM) in epithelial cells of human placenta in vitro.

• Metabolism and elimination

Following oral administration of single doses in the range of 100 to 400 mg, the terminal elimination half-lives ranged from 6.2 to 10.6 hours. The main metabolic pathway is the hydrolytic cleavage of the ester bond. Orally administered hyoscine butylbromide is excreted in the faeces and in the urine. Studies in man show that 2 to 5% of radioactive doses is eliminated renally after oral, and 0.7 to 1.6% after rectal administration. Approximately 90% of recovered radioactivity can be found in the faeces after oral administration. The urinary excretion of hyoscine butylbromide is less than 0.1% of the dose. The mean apparent oral clearances after oral doses of 100 to 400 mg range from 881 to 1420 L/min, whereas the corresponding volumes of distribution for the same range vary from 6.13 to 11.3 x 10⁵ L, probably due to very low systemic availability. The metabolites excreted via the renal route bind poorly to the muscarinic receptors and are therefore not considered to contribute to the effect of the hyoscine butylbromide.

In  limited  reproductive toxicity studies  hyoscine butylbromide showed  no  evidence of teratogenicity in rats at 200 mg/kg in the diet or in rabbits at 200 mg/kg by oral gavage or 50 mg/kg by subcutaneous injection. Fertility in the rat was not impaired at doses of up to 200 mg/kg in the diet.

Core:

- Lactose

- Maize starch

- Colloidal silicone dioxide

- Magnesium stearate

Sub, proper and smoothing coating solution:

- Sugar local

- Povidone K-25

- Titanium dioxide

- Talc powder extra pure

- Colloidal silicon dioxide

- Calcium carbonate

Sealing solution:

- Shellac (Dewaxed Orange)

- Castor Oil

Polishing solution:

- White bees wax

- Carnauba wax

None stated.

Store in a dry place below 30°C, away from light.

Alu/PVC blisters; pack size: 20 tablets.

None stated.