Unigan

Each film coated tablet contains: Paracetamol 500 mg, Hyoscine-N-butylbromide 10 mg.

Pharmacology: Mechanism of Actions: PARACETAMOL: Analgesic action: May act predominantly by inhibiting prostaglandin synthesis in the central nervous system (CNS) and, to a lesser extent, through a peripheral action by blocking pain-impulse generation. The peripheral action may also be due to inhibition of prostaglandin synthesis or to inhibition of the synthesis or actions of other substances that sensitize pain receptors to mechanical or chemical stimulation.
HYOSCINE-N-BUTYLBROMIDE: Depending on the dose, anticholinergics may reduce the motility and secretory activity of the gastrointestinal system, and the tone of the ureter and urinary bladder and may have a slight relaxant action on the bile ducts and gallbladder.
Antiemetic: Scopolamine act primarily by reducing the excitability of the labyrinthine receptors and by depressing conduction in the vestibular cerebellar pathway.
Antivertigo: The exact mechanism by which Scopolamine exert their antimotion sickness and antivertigo effects is unknown; however, the probably act either on the cortex or more peripherally on the maculae of the utricle and saccule.
Pharmacokinetics: PARACETAMOL: Absorption: Oral: Rapid and almost complete: may be decreased if Acetaminophen is taken following a high-carbohydrate meal. Rectal- The rate and extent of absorption from the suppository dosage form may vary, depending on the composition of the base.
Distribution: In breast milk- Peak concentrations of 10 to 15 mcg per mL (66.2 to 99.3 micromoles/L) have been measured 1 to 2 hours following maternal ingestion of a single 650 mg dose. The half-life in breast milk is 1.35 to 3.5 hours.
Protein binding: Not significant with doses producing plasma concentrations below 60 mcg per mL (397.2 micromoles may reach moderate levels with high or toxic doses.
Biotransformation: Approximately 90 to 95% of a dose is metabolized in the liver, primarily by conjugation with glucuronic acid, sulfuric acid, and cystein. An intermediate metabolite, which may accumulate in overdosage after the primary metabolic pathways become saturated, is hepatotoxic and possibly nephrotoxic.
Half-life: 1 to 4 hours; does not change with renal failure but may be prolonged in acute overdosage, in some forms of hepatic disease, in the elderly, and in the neonate; may be somewhat shortened in children.
Time to peak concentration: 0.5 to 2 hours.
Peak plasma concentration: 5 to 20 mcg per mL (33. 1 to 132.4 micromoles/L), with doses up to 650 mg.
Time to peak effect: 1 to 3 hours.
Duration of action: 3 to 4 hours.
Elimination: Renal, as metabolites, primarily conjugates; 3% of a dose may be excreted unchanged. In dialysis- Hemodialysis: 120 mL per minute (for unmetabolized drug); metabolites are also cleared rapidly. Hemoperfusion: 200 mL per minute. Peritoneal dialysis: <10 mL per minute.
HYOSCINE-N-BUTYLBROMIDE: Absorption: Tertiary amines: Rapidly absorbed from gastrointestinal tract; also enter the circulation through the mucosal surfaces of the body.
Quaternary ammonium compounds: Gastrointestinal absorption is poor and irregular. Total absorption after an oral dose is about 10 to 25%.
Distribution: Exact distribution of anticholinergics has not been fully determined. However, tertiary amines appear to the distributed throughout the entire body and readily cross the blood-brain barrier and into the eye.
Biotransformation: Most anticholinergics- hepatic, by enzymatic hydrolysis.
Half-life: Elimination: 8 hours.
Time to peak effect: Elimination (% excreted unchanged): Renal.

For the relief from the pain or stronger abdominal cramps including menstrual cramps and urinary tract spasm.

Oral: The tablets should not be chewed, but swallowed in whole with a sufficient amount of water.
Adult: 1-2 tablets, 3 times daily.
The total daily dose should not exceed 6 tablets.
Children ≥10 years: May be used if required. UNIGAN should not be taken over prolonged period of time or in higher doses without a prescription from the physician or dentist.

Symptoms: Signs of overdose of Hyoscine-N-butylbromide may include pallor, nausea, vomiting, anorexia and abdominal pain. Patients may then experience a temporary subjective improvement but mild abdominal pain possibly indicative of liver damage may persist. A single dose of Paracetamol of approximately ≥6 g in adults or 140 mg/Kg in children may cause hepatocellular necrosis. This may lead to complete irreversible necrosis and subsequently to hepatocellular insufficiency, metabolic acidosis and encephalopathy, which may in turn progress to coma and death. Concurrent rises in liver transaminases [aspartate transaminase (AST), alanine transaminase (ALT)], lactate dehydrogenase and bilirubin and an increase in prothrombin time, occurring 12-48 hrs after ingestion, have been observed.
Clinical symptoms of liver damage are normally apparent after 2 days and reach a maximum after 4-6 days.
Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage.
Other non-hepatic symptoms e.g. myocardial abnormalities and pancreatitis have also been reported to occur after Paracetamol overdosage.
Treatment: If required, parasympathomimetic drugs should be administered. Ophthalmological advice should be sought urgently in cases of glaucoma. Cardiovascular complications should be treated according to usual therapeutic principles. In case of respiratory paralysis, intubation, artificial respiration should be considered.
Catherization may be required for urinary retention.
In addition, appropriate supportive measures should be used as required. Where Paracetamol intoxication is suspected, IV administration of SH group donators e.g. N-acetylcysteine within the first 10 hrs after ingestion is indicated. Although N-acetylcysteine is most effective if initiated within this period, it can still offer some degree of protection if given as late as 48 hrs after ingestion; in this case. it is taken for longer. The plasma concentration of Paracetamol can be decreased by dialysis. Determinations of the plasma concentration of Paracetamol are recommended. Further measures will depend on the severity, nature and course of clinical symptoms of Paracetamol intoxication and should follow standard intensive care protocols.

Hypersensitivity to Hyoscine-N-butylbromide, Paracetamol or any of the excipients of UNIGAN.
Patients with myasthenia gravis, megacolon or severe hepatocellular insufficiency.
In case of rare hereditary conditions that may be incompatible with its excipient, the use of UNIGAN is contraindicated.

In case severe, unexplained abdominal pain persists or worsens or occurs together with symptoms e.g. fever, nausea. vomiting, changes in bowel movements, abdominal tenderness, decreased blood pressure, fainting or blood in stool, medical advice should immediately be sought.
To prevent overdosing, ensure that any other drugs taken concurrently do not contain Paracetamol.
UNIGAN should be used with caution in glucose-6-phosphate-dehydrogenase (G6PD) deficiency, hepatic dysfunction (e.g. due to chronic alcohol abuse, hepatitis), impaired renal function. Gilbert's syndrome and hepatocellular insufficiency. In such cases, UNIGAN should only be used under medical supervision and, if necessary, the dose reduced or the intervals between the individual administrations prolonged.
The blood count and renal and liver function should be monitored after prolonged use.
Extensive use of analgesics, especially at high doses, may induce headaches that must not be treated with increased doses of UNIGAN. Severe acute hypersensitivity reactions (e.g. anaphylactic shock) are very infrequently observed. Treatment must be discontinued at the 1st signs of a hypersensitivity reaction following the administration of UNIGAN.
Liver damage may result if the recommended dosage is exceeded. Abrupt discontinuation of analgesic after prolonged use at high doses may induce withdrawal symptoms (e.g. headache, tiredness, nervousness), that typically resolve within few days. Reintake of analgesics should depend upon physician's advice and withdrawal symptoms abated.
UNIGAN should not be taken for >3 days unless directed by a physician. If pain persists or gets worse. if new symptoms occur or if redness or swelling is present, a physician should be consulted because these could be signs of a serious condition.
Because of the potential risk of anticholinergic complications, caution should be used in patients prone to narrow angle glaucoma as well as in patients susceptible to intestinal or urinary outlet obstructions and in those inclined to tachyarrhythmia.
Use in children: UNIGAN is not suitable for children <10 years.

Pregnancy: There are no adequate data on use of UNIGAN during pregnancy. Long experience with the mono substances has shown no evidence of adverse effects during human pregnancy.
During pregnancy, Paracetamol should not be taken for prolonged periods, in high doses, or in combination with other medicinal products as the safety has not been confirmed in such cases. Therefore, UNIGAN is not recommended during pregnancy.
Lactation: PARACETAMOL: Paracetamol enters breast milk. but is not likely to affect the infant when therapeutic doses are used.
HYOSCINE-N-BUTYLBROMIDE: Safety during lactation has not yet been established. However, adverse effects on the newborn have not been reported.
Fertility: No studies on the effects on human fertility have been conducted.

UNIGAN Tablet may cause: Blood and Lymphatic System Disorders: Pancytopenia, agranulocytosis, thrombocytopenia, leukopenia.
Immune System Disorder, Skin and Subcutaneous Tissue Disorders: Skin reactions, dyshidrosis, pruritus, urticaria, nausea, erythema, decreased blood pressure including shock, anaphylactic shock, anaphylactic reactions, drug eruption, dyspnea, hypersensitivity, angioedema, rash, exanthema.
Cardiac Disorders: Tachycardia.
Respiratory, Thoracic and Mediastinal Disorders: Bronchospasm (especially in patients with a history of bronchial asthma or allergy).
Hepatobiliary Disorders: Increased transaminases.
Renal and Urinal Disorders: Urinary retention.

Certain hypnotics and anti-epileptics (e.g. Glutethimide. Phenobarbital, Phenytoin, Carbamazepine) as well as Rifampicin. The same applies to potentially hepatotoxic substances and alcohol abuse.
Long-term use of Paracetamol in patients being treated with oral anti-coagulants is only advisable under medical supervision.
Concomitant use of Paracetamol and Zidovudine [azidothymidine (AZT) or Retrovir] enhances the tendency towards reducing leukocytes (neutropenia). Therefore, UNIGAN should only be taken together with Zidovudine following medical advice.
The Paracetamol dose should be reduced during concurrent administration with Probenecid.
Cholestyramine reduces the absorption or Paracetamol.
The anticholinergic effect of drugs e.g. tri- and tetracyclic antidepressants, antihistamines. antipsychotics, Quinidine, Amantadine, Disopyramide and other anticholinergics (e.g. Tiotropium, Ipratropium, atropine-like compounds) may be intensified by UNIGAN.
Concomitant treatment with dopamine antagonists e.g. metoclopramide may result in diminution of the effects of both drugs on the gastrointestinal tract.
The tachycardic effects of β-adrenergic agents may be enhanced by UNIGAN.

Store at temperatures not exceeding 30°C.

Antispasmodics

N02BE51 - paracetamol, combinations excl. psycholeptics ; Belongs to the class of anilide preparations. Used to relieve pain and fever.
A03DB04 - butylscopolamine and analgesics ; Belongs to the class of belladonna and derivatives antispasmodics in combination with analgesics. Used in the treatment of functional gastrointestinal disorders.

Non-Rx