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What is Proben-50 and what is it used for?

Proben-50 contains Itopride Hydrochloride 50 mg in tablet form. It is a gastroprokinetic agent. Proben-50 is used in the treatment of gastrointestinal symptoms of

 

How does it work?

Proben-50 works by increasing gastric motility (movement), increases the lower esophageal sphincter pressure, accelerates gastric emptying, and improves gastro-duodenal coordination.

 

How to take Proben-50?

Adult: 50 mg three times a day; the dose may be reduced according to the patient’s age and symptoms.

  • Proben-50 cannot be prescribed to any child who is below the age of 16 years.
  • Best efficacy if taken one hour before or two hours after meal.

 

What if you miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

                                                                                             

What to do in case of overdose?

The likelihood of an overdose is very less. However, contact your doctor if an overdose is suspected.

 

What do you need to know before you take Proben-50?

Do not take Proben-50

 

Warnings and precautions

  • This drug should not be consumed continuously for an extended period when no improvement of gastrointestinal symptoms is observed.
  • Children below 16 years of age
  • Elderly population

 

Proben-50 and other medications

Proben-50 increases gastric motility that could influence the absorption of concomitantly orally administered medicinal products. Particular attention should be taken to drugs administered orally.

 

Pregnancy and breast-feeding

Pregnancy

Safety of Proben-50 in pregnancy was not verified. Therefore it can be used in case of utmost necessity.

 

Breast-feeding

Data about excretion in mother milk is known only in animals. Because of lack of experience with use of Proben-50 during breast-feeding, it is not recommended for breast-feeding women.

Driving and using machines

Although no effects on ability to drive and use machines have been reported, impairment of

alertness cannot be ruled out since dizziness may occur very rarely.

 

Proben-50 and special population

Patients with hepatic or renal impairment

Itopride is metabolized in liver. Itopride and its metabolites are excreted mainly via kidneys. Patients with reduced hepatic or renal functions should be carefully monitored and in case of adverse reactions it is necessary to take appropriate measures, as e.g. to reduce the dosage or to discontinue the therapy.

 

Elderly

It was shown in clinical studies that the incidence of adverse effects in patients aged 65 years and older was not higher than in younger patients. Itopride should be administered in elderly patients with adequate caution because of increased incidence of hepatic and renal function disorders, other diseases or treatment with additional drugs.

 

What are the possible side effects?

Mechanism of action:

Itopride has anticholinesterase (AchE) activity as well as dopamine D2 receptor antagonistic activity. It is well established that M3 receptors exist on the smooth muscle layer throughout the gut and acetylcholine (ACh) released from enteric nerve endings stimulates the contraction of smooth muscle through M3 receptors. The enzyme AChE hydrolyses the released ACh, inactivates it and thus inhibits the gastric motility leading to various digestive disorders.

 

Besides ACh, dopamine is present in significant amounts in the gastrointestinal tract and has several inhibitory effects on gastrointestinal motility, including reduction of lower esophageal sphincter and intragastric pressure. Itopride, by virtue of its dopamine D2 receptor antagonism, removes the inhibitory effects on Ach release.

 

The net effect is an increase in ACh concentration, which in turn, promotes gastric motility, increases the lower esophageal sphincter pressure, accelerates gastric emptying and improves gastro-duodenal coordination. This dual mode of action of Itopride is unique and different from the actions of other prokinetic agents available in the market.

 

Pharmacokinetic properties:

Absorption: Proben-50 (Itopride hydrochloride) is rapidly and almost completely absorbed from the gastrointestinal tract. Relative bioavailability is calculated to be 60% due to liver first pass metabolism. There is no effect of food on bioavailability.

Peak plasma levels (Cmax 0.28 |ig/mL) are reached after 0.5 to 0.75 hours after 50 mg of itopride hydrochloride. Following multiple oral doses ranging from 50 mg to 200 mg tid, itopride hydrochloride and its metabolites showed linear pharmacokinetics over a treatment period of seven days, with minimal accumulation.

Volume of distribution: Approximately 96% of Ganaton (Itopride hydrochloride) is bound to plasma proteins. Albumin accounts for most of the binding. Alpha-1 -acid-glycoprotein accounts for less than 15% of binding.

Metabolism: Proben-50 (Itopride hydrochloride) undergoes extensive hepatic metabolism in humans. Three (3) metabolites have been identified, of which only one exerts minor activity without pharmacological relevance (approximately 2-3% of that of itopride). The primary metabolite in humans is the N-oxide, generated by oxidation of the tertiary amine N-dimethyl group.

Proben-50 is metabolized by a flavin-dependent mono-oxygenase (FMO3). The abundance and efficiency of the human FMOisozymes can be subject to genetic polymorphisms, which can lead to a rare autosomal recessive condition known as trimethylaminuria (fish odor syndrome).

The half-life of itopride may therefore be longer in trimethylaminuria patients. In vivo pharmacokinetic studies on CYP-mediated reactions revealed that itopride showed neither inhibitory nor inductory effect on CYP2C19 and CYP2E1. CYP content and uridine diphosphate glucuronosyl transferase activity were not altered with the administration of itopride.

Excretion: Itopride hydrochloride and its metabolites are primarily excreted in the urine. The urinary excretions of itopride and its N-oxide were 3.7% and 75.4%, respectively, in healthy subjects after oral administration of a single therapeutic dose.

Elimination Half-life: The terminal phase half-life is approximately six (6) hours.

Drug Interactions

  • No interactions on level of cytochrome P450 are expected to occur because itopride is metabolised mainly by flavine monooxygenase.
  • No interaction was detected when itopride was administered concomitantly with warfarin, diazepam, diclofenac, ticlopidine, nifedipine and nicardipine.
  • Itopride has gastro-kinetic effect that could influence the absorption of concomitantly orally administered medicinal products. Particular attention should be taken to drugs with a narrow therapeutic index, drugs with prolonged-release of active substance and enteric-coated drug formulations.
  • Anticholinergic agents may reduce the action of itopride.
  • Substances as cimetidine, ranitidine, teprenone and cetrexate do not affect prokinetic activity of itopride.