Content on this page requires a newer version of Adobe Flash Player.

Get Adobe Flash player

 
 
 
 
 
 
 
 
 
 

NAVOLUM

Quick Overview

Our aim is to reach out to the globe within shortest possible time frame


To promote this objective, not only we distribute and market our Gastroenterology range of products globally through our distribution channels but we also undertake ‘contract manufacturing’& ‘formulation development ’of our wide range of generic products such as Navolum tab which contains Domperidone Maleate BP Equivalent to Domperidone10 mg.

Navolum 10

Double click on above image to view full picture

Zoom Out
Zoom In

Details

Each film coated tablet contains:

Domperidone Maleate BP

Equivalentto Domperidone …10 mg

Excipients    q.s.

Colour : Tartrazine Lake &Titanium Dioxide

CHEMICAL NAME: 5-chloro-1-[1-[3-(2-oxo-2,3-dihydro-1H-benzimidazol­1- yl)propyl] piperidin-4-y1]-1,3-dihydro-2H-benzimidazol-2-one hydrogen (Z)- butenedioate.

 CATEGORY: Antiemetic.

 CLINICAL PHARMACOLOGY Pharmacokinetic Actions

Absorption

In fasting subjects, domperidone is rapidly absorbed after oral administration, with peak plasma concentrations at 30 to 60 minutes. The low absolute bioavailability of oral domperidone (approximately 15%) is due to an extensive first-pass metabolism in the gut wall and liver. Although domperidone bioavailability is enhanced in normal subjects when taken after a meal, patients with gastro-intestinal complaints should take domperidone 15-30 minutes before a meal. Reduced gastric acidity impairs the absorption of domperidone. Oral bioavailability is decreased by prior concomitant administration of cimetidine and sodium bicarbonate. The lime of peak absorption is slightly delayed and the AUC somewhat increased when the oral drug is taken with l meal.

Distribution

Oral domperidone does not appear to accumulate or induce its own metabolism; a peak plasma level after 90 minutes of 2 ng/ml after two weeks oral administration of 30 mg per day was almost the same as that of 18 ng/ml after the first dose. Domperidone is 91-93% bound to plasma proteins. Reported distribution studies with radiolabelled drug in animals have shown wide tissue distribution, but low brain concentration and small amount of drug crosses the placenta in rats.

Metabolism

Domperidone undergoes rapid and extensive hepatic metabolism by hydroxylation and N-dealkIdalion. In reported In vitro metabolism experiments with diagnostic inhibitors revealed that CYP3A4 is a major form of cytochrome P-450 involved in the N-dealkIdalion of domperidone, whereas CYP3A4, CYP1A2 and CYP2E1 are involved in domperidone aromatic hydroxylation.

Excretion

Urinary and fecal excretion accounts to 31 and 66% of the oral dose respectively. The proportion of the drug excreted unchanged is small (10% of fecal excretion and approximately 1% of urinary excretion). The plasma half- life after a single oral dose is 7- 9 hours in healthy subjects but is prolonged in patients with severe renal insufficiency.

MECHANISM OF ACTION:

Domperidone is a dopamine antagonist with anti-emetic properties, it does not readily cross the blood-brain barrier. In domperidone users, especially in adults, extrapyramidal side effects are very rare, but it promotes the release of prolactin from the pituitary gland. Its anti-emetic effect may be due to a combination of peripheral (gastroldnelic) effects and antagonism of dopamine receptors in the chemoreceptor trigger zone, which lies outside the blood-brain barrier in the area postrema. In reported animal studies, together with the low concentrations found in the brain, indicate a predominantly peripheral effect of domperidone on dopamine receptors. Studies in man have shown oral domperidone to increase lower esophageal pressure, improve antroduodenal motility and accelerate gastric emptying. There is no effect on gastric secretion.

Drug interactions

The main metabolic pathway of domperidone is through CYP3A4. In vitro data suggest that the concomitant use of drugs that significantly inhibit this enzyme may result in increased plasma levels of domperidone. In vivo interaction studies with ketoconazole revealed a marked inhibition of domperidone CYP3A4 mediated first pass metabolism by ketoconazole. A pharmacokinetic study has demonstrated that the AUC and the peak plasma concentration of domperidone are increased by a factor of 3 when oral ketoconazole is administered concomitantly (at steady state). A slight QT- prolonging effect (mean less than 10msec) of this combination was reported, which was greater than the one seen with ketoconazole alone. A QT prolonging effect could not be detected when domperidone was given alone in patients with no co-morbidity, even at high oral doses (up to 160 mg/day). The results of this interaction study should be taken into account when prescribing domperidone concomitantly with strong CYP3A4 inhibitors: for example: ketoconazole, ritonavir and erythromycin. While adverse interactions have not been reported in general clinical use, domperidone has the potential to interact with dopamine agonist (e.g. bromocriptine), antimuscarinics and opioid analgesics. it may also enhance the absorption of concomitantly administered drugs especially in cases of delayed gastric emptying.

Concomitant administration of anli-cholinergic drugs may inhibit the anti- dyspeptic effects of NAVOLUM. Anli-muscarinic agents and opioid analgesics may antagonise the effect of NAVOLUM. It suppresses the peripheral effects (digestive disorders, nausea and vomiting) of dopaminergic agonists. Since domperidone has gastro-kinetic effects, it could influence the absorption of concomitant orally administered medicines, particularly those with sustained release or enteric coated formulations. As domperidone interferes with serum prolactin levels, it may interfere with other hypo prolactin emic agents and with some diagnostic tests.

Antacids and anti-secretory agents lower the oral bioavailability of domperidone. They should be taken after meals and not before meals, i.e. they should not be taken simultaneously with domperidone.

Reduced gastric acidity impairs the absorption of domperidone. Oral bioavailability is decreased by prior administration of cimetidine or sodium bicarbonate. The main metabolic pathway of domperidone is through CYP3A4. In vitro data suggests that concomitant use of drugs that significantly inhibit this enzyme may result in increased plasma levels of domperidone. Examples of CYP3A4 inhibitors include the following:

-           Azole antifungals

-           macrolide antibiotics

-           HIV protease inhibitors

-           nefazodone

General

Symptomatic response to therapy with rabeprazole does not preclude the presence of gastric malignancy.

Pregnancy

There are no adequate and well-controlled studies reported in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Lactation

Since many drugs are excreted in milk, caution should be exercised when this drug is administered to a nursing mother.

DOSAGE AND ADMINISTRATION:

Acute conditions (mainly nausea, vomiting, hiccup)

Adults: Two tablets (20 mg) 3 to 4 limes per day, 15 to 30 minutes before meals and, if necessary, before retiring.

Children 5 to 12 years old: One tablet (10 mg) 3 to 4 limes per day, 15 to 30 minutes before meals and, if necessary, before retiring.

Chronic conditions (mainly dyspepsia)

Adults: One tablet (10 mg) taken 3 limes per day, 15 to 30 minutes before meals and, if necessary, before retiring. The dosage may be doubled.

Children 5 to 12 years old: 1/2 tablet (5 mg) 3 to 4 limes per day, 15 to 30 minutes before meals and if necessary, before retiring.

This formulation is not suited for children under the age of 5 years, but for this group of patients the suspension is available.

Domperidone should be used with caution in patients with renal impairment or in those at risk of fluid retention. In patients with severe renal insufficiency (serum crealinine more than 6 mg/100 mL, ie. more than 0.6 mmoVL) the elimination half-life of domperidone was increased from 7.4 to 20.8 hours. The dosing frequency should be reduced to once or twice daily, depending on the severity of impairment, and the dose may need to be reduced. Patients on prolonged therapy should be reviewed regularly.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS

Side-effects

Allergic reactions, such as rash or urticarial, have been reported. Abdominal cramps have been reported. Dystonic reactions (extrapyramidal phenomena) may occur. Reversible raised serum prolactin levels have been observed which may lead to galactorrhoea and gynaecomastia. Hypertensive crises in patients with phaeochromocytoma may occur with administration of domperidone. Where the blood brain barrier is not fully developed (mainly in young babies) or is impaired, the possible occurrence of neurological side-effects cannot be totally excluded.

Special precautions

Since domperidone is highly metabolised in the liver, NAVOLUM should be used with caution in patients with hepatic impairment (and in the elderly).

ADVERSE EFFECTS:

Domperidone has been found to be associated with increased serum prolactin, which may be associated with galactorrhea, less frequently gynaecomaslia, breast enlargement and soreness. Reduced libido has been reported. Occasional rashes and other allergenic phenomena are also reported. Domperidone does not readily cross the normally functioning blood brain barrier and is therefore less likely to interfere with the central dopaminergic function. However, acute extrapyramidal dystonic reactions have been reported with domperidone.

OVERDOSAGE:

Symptoms of over dosage may include drowsiness, disorientation and extrapyramidal reactions, especially in children.

Treatment

There is no specific antidote to domperidone, but in the event of overdose, gastric lavage as well as the administration of activated charcoal, may be useful. Close medical supervision and supportive therapy is recommended. Anticholinergic, anli-parldnson drugs may be helpful in controlling extrapyramidal reactions.

Packing: Container of 100 tablets.

Storage: Store in cool & dry place, below 25°C. Protect from light. Shelf Life: 36 months.

 

 
OUR PRESENCE:
FIND US ON: