Spasmopan is indicated in acute spasm, as in renal or biliary colic, in radiology for differential diagnosis of obstruction and to reduce spasm and pain in pyelography, and in other diagnostic procedures where spasm may be a problem, e.g. gastro-duodenal endoscopy.

Adults:
One ampoule (20 mg) intramuscularly or intravenously, repeated after half an hour if necessary. Intravenous injection should be performed 'slowly' (in rare cases a marked drop in blood pressure and even shock may be produced by Spasmopan). When used in endoscopy this dose may need to be repeated more frequently.

Maximum daily dose of 100 mg.

Special populations
Elderly: No specific information on the use of this product in the elderly is available. Clinical trials have included patients over 65 years and no adverse reactions specific to this age group have been reported.

Paediatric population
Not recommended for children.

Spasmopan should not be taken on a continuous daily basis or for extended periods without investigating the cause of abdominal pain.

Diluent:
Spasmopan injection solution may be diluted with dextrose or with sodium chloride 0.9% injection solutions.

Spasmopan is contraindicated in patients with: • Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 • Narrow angle glaucoma • Hypertrophy of the prostate with urinary retention • Mechanical stenosis in the gastrointestinal tract • Paralytical or obstructive ileus • Megacolon • Tachycardia • Myasthenia gravis Spasmopan should not be given by intramuscular injection to patients being treated with anticoagulant drugs since intramuscular haematoma may occur.

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, appropriate diagnostic measures are needed to investigate the etiology of the symptoms.

Spasmopan can cause tachycardia, hypotension and anaphylaxis, therefore use with caution in patients with cardiac conditions such as cardiac failure, coronary heart disease, cardiac arrhythmia or hypertension, and in cardiac surgery. Monitoring of these patients is advised. Emergency equipment and personnel trained in its use must be readily available.

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 after the injection of Spasmopan.

After parenteral administration of hyoscine N-butylbromide, cases of anaphylaxis including episodes of shock have been observed. As with all drugs causing such reactions, patients receiving Spasmopan by injection should be kept under observation.

Spasmopan contains sodium metabisulphite, potassium, sodium and benzyl alcohol
Spasmopan contains sodium metabisulphite. Each ml of Spasmopan 20 mg/ml Solution for Injection contains 1 mg sodium metabisulphite, which may rarely cause severe hypersensitivity reactions and bronchospasm. 

Spasmopan contains potassium. Each ml of Spasmopan 20 mg/ml Solution for Injection contains 0.0245 mmol (0.956 mg) potassium. This medicine contains potassium, less than 1 mmol (39 mg) per ml, i.e. essentially ‘potassium-free’.

Spasmopan contains sodium. Each ml of Spasmopan 20 mg/ml Solution for Injection contains 0.012 mmol (0.276 mg) sodium. This medicine contains less than 1 mmol sodium (23 mg) per ml, that is to say essentially ‘sodium-free’.

Spasmopan contains benzyl alcohol. This medicine contains 10 mg benzyl alcohol in each 1 ml:

• Benzyl alcohol may cause allergic reactions.
• Ask your doctor or pharmacist for advice if you are pregnant or breast‑feeding. This is because large amounts of benzyl alcohol can build-up in your body and may cause side effects (called “metabolic acidosis”).
• Ask your doctor or pharmacist for advice if you have a liver or kidney disease. This is because large amounts of benzyl alcohol can build-up in your body and may cause side effects (called “metabolic acidosis”).

 

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

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

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

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. However, patients should be advised that they may experience undesirable effects such as accommodation disorder or dizziness during treatment with hyoscine butylbromide. Therefore, caution should be recommended when driving a car or operating machinery. If patients experience accommodation disorder or dizziness, they should avoid potentially hazardous tasks such as driving or operating machinery.

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

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

Very common	(≥ 1/10)
Common	(≥ 1/100 to < 1/10)
Uncommon	(≥ 1/1,000 to <1/100)
Rare	(≥ 1/10,000 to <1/1,000)
Very rare	(<1/10,000)
Not known	(cannot be estimated from the available data)

Immune system disorders
Not known^*: anaphylactic shock including cases with fatal outcome, anaphylactic reactions, dyspnoea, and other hypersensitivity.

 Eye disorders
Common: accommodation disorders
Not known^*: mydriasis, increased intraocular pressure

 Cardiac disorders
Common: tachycardia

 Vascular disorders
Common: dizziness
Not known^*: blood pressure decreased, flushing

 Gastrointestinal disorders
Common: dry mouth
Constipation

 Skin and subcutaneous tissue disorders
Not known*: skin reactions (e.g. urticaria, rash, erythema, pruritus), abnormal sweating

Renal and urinary disorders
Not known^*: urinary retention

Injection site pain, particularly after intramuscular use, occurs.

Hyoscine butylbromide, the active ingredient of Spasmopan, due to its chemical structure as a quaternary ammonium derivate, is not expected to enter the central nervous system. Hyoscine butylbromide does not readily pass the blood-brain barrier. However, it cannot totally be ruled out that under certain circumstances psychiatric disorders (e.g. confusion) may also occur after administration of hyoscine butylbromide.

*This adverse reaction has been observed in post-marketing experience. With 95% certainty, the frequency category is not greater than common, 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 185 patients.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:

• Saudi Arabia

The National Pharmacovigilance Centre (NPC)
SFDA Call Center: 19999
E-mail: npc.drug@sfda.gov.sa
Website: https://ade.sfda.gov.sa

• Other GCC States

Please contact the relevant competent authority.

Symptoms
Serious signs of poisoning following acute overdosage have not been observed in man. In the case of overdosage, anticholinergic symptoms 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
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, artificial respiration should be considered. Catheterisation may be required for urinary retention.

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

Spasmopan is an antispasmodic agent which relaxes smooth muscle of the organs of the abdominal and pelvic cavities. It is believed to act predominantly on the intramural parasympathetic ganglia of these organs.

Absorption and distribution
After intravenous administration hyoscine butylbromide is rapidly distributed (t_½α = 4 min, t_½β = 29 min) into the tissues. The volume of distribution (Vss) is 128 L (corresponding to approx. 1.7 L/kg). 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
The main metabolic pathway is the hydrolytic cleavage of the ester bond. The half-life of the terminal elimination phase (t_½γ) is approximately 5 hours. The total clearance is 1.2 L/min. Clinical studies with radiolabeled hyoscine butylbromide show that after intravenous injection 42 to 61% of the radioactive dose is excreted renally and 28.3 to 37% faecally.

The portion of unchanged active ingredient excreted in the urine is approximately 50%. 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.

Paediatric population
No particular pharmacokinetic studies concerning hyoscine butylbromide have been performed in children.

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.

-   Citric acid

-   Potassium citrate

-   Sodium metabisulphite

-   Disodium edetate

-   Benzyl alcohol

-   Water for injection

 

None known

Unopened: 60 months. Once opened: Use immediately and discard any unused contents. Chemical and physical in-use stability has been tested for 24 hours at room temperature (20-25°C) and at (2-8°C). From a microbiological point of view, the diluted solution should be used immediately. After dilution: It is recommended that the solutions should be prepared right before use and administered right after its preparation. If any particular circumstances force the storage of the diluted solutions before use, it can be stored for 24 hours either at room temperature (20-25°C) or at (2-8 °C) as the product is stable in both conditions.

Store below 30°C.

Protect from light.

Store in the original package.

Type I colourless glass ampoules.

Pack size: 5 Ampoules (1 ml).

For single use only. Any unused solution should be discarded.

Spasmopan 20 mg/ml Solution for Injection, adminstrated intravenously or intramuscularly, may be diluted with dextrose or with sodium chloride 0.9% injection solutions as per the following table:

Spasmopan Strength	Diluent	Volume of diluent added (ml)	Approximate Concentration after Dilution (mg/ml)
One Ampoule of Spasmopan 20 mg/ml Injection	5% Dextrose Solution	100	0.2
	10% Dextrose Solution
	0.9% Sodium Chloride Injection Solution