HYPONAL Ampoules are 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 hyoscine – N – butylbromide). When used in endoscopy this dose may need to be repeated more frequently.
Maximum daily dose of 100mg.
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.
Pediatric population:
Not recommended for children.
HYPONAL Ampoules should not be taken on a continuous daily basis or for extended periods without investigating the cause of abdominal pain.

HYPONAL Ampoules are contraindicated in patients with: Hypersensitivity to the active substance or to any of the excipients. Narrow angle glaucoma. Hypertrophy of the prostate with urinary retention. Mechanical stenosis in the gastrointestinal tract. Paralytical or obstructive ileus. Megacolon. Tachycardia. Myasthenia gravis HYPONAL Ampoules should not be given by intramuscular injection to patients being treated with anticoagulant drugs since intramuscular haematoma may occur. Do not administer injections preserved with benzyl alcohol to neonates, pregnant women, or nursing mothers. Benzyl alcohol has been associated with serious adverse events and death, particulary in pediatric patients.

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 aetiology of the symptoms.
HYPONAL Ampoules 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, HYPONAL should be administered with caution to patients with pyrexia.
Elevation of intraocular pressure may be produced by the administration of anticholinergic agents such as HYPONAL in patients with undiagnosed and therefore untreated narrow angle glaucoma.
Therefore, patients should seek urgent ophthalmological advice if they develop a painful, red eye with loss of vision after the injection of HYPONAL.
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 HYPONAL by injection should be kept under observation.
HYPONAL contains benzyl alcohol which is potentially toxic when administered locally to neural tissue.

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 HYPONAL.
The tachycardic effects of beta-adrenergic agents may be enhanced by HYPONAL.
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. As a precautionary measure HYPONAL 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 HYPONAL 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 to 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 HYPONAL Ampoules. 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 HYPONAL.
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*: Decreased blood pressure, 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 HYPONAL, due to its chemical structure as a quaternary ammonium derivative, 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 HYPONAL.
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:
Egyptian Pharmaceutical Vigilance Center E mail:pv.center@eda.mohealth.gov.eg

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 Cheyne-Stokes respiration has been reported.
Therapy:
Symptoms of HYPONAL 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.
To report any side effects:
• Saudi Arabia:
The National Pharmacovigilance and Drug Safety Centre NPC
Fax: +966‐11‐205‐7662
Call NPC at +966‐11‐2038222, Exts 2317‐2356‐2353‐2354‐2334‐2340.
Toll free phone: 8002490000
E‐mail: npc.drug@sfda.gov.sa
Website: www.sfda.gov.sa/npc
Or Other GCC States:
Please contact the relevant competent authority.

ATC code: A03BB01
HYPONAL 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 (t½α = 4 min, t½β = 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 (t½γ) 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.
Pediatric population:
No particular pharmacokinetic studies concerning hyoscine butylbromide have been performed in children.

None stated.

Benzyl alcohol, mannitol, sodium citrate anhydrous, 1N Hydrochloric acid, water for injection.

None known.

3 years.

Store below 30°C.

Carton box containing 1 plastic tray containing 5 amber glass type I ampoules, each of 1 ml solution and insert leaflet.

None known.