Cool Zone O

Cool Zone O Uses, Dosage, Side Effects, Food Interaction and all others data.

Omeprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, that suppress gastric acid secretion by specific inhibition of the H+/K+ ATPase enzyme system at the secretory surface of the gastric parietal cell. Because this enzyme system is regarded as the acid (proton) pump within the gastric mucosa, omeprazole has been characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid production. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.

Clinical advantage of omeprazole mups tablet compared to conventional modified-release omeprazole tablets and pellet-filled omeprazole capsules:

Ensures greater bioavailabilityEnsures uniform emptying of micro pellets from stomach into small intestine facilitates rapid dissolution of enteric coating and drug release resulting in early Tmax and Cmax (peak time and peak plasma concentration)Ensures lesser possibility of dose dumpingIs a combination of fast acting and sustained actionEnsures uniform drug releaseOnce daily dosingEnsures lesser chance of localized irritationEnsures better and more uniform drug absorptionBetter than capsules in reducing the esophageal residence timeMinimizes fluctuation in plasma concentration of drugEffects on gastric acid secretion

This drug decreases gastric acid secretion . After oral administration, the onset of the antisecretory effect of omeprazole is usually achieved within one hour, with the maximum effect occurring by 2 hours after administration. The inhibitory effect of omeprazole on acid secretion increases with repeated once-daily dosing, reaching a plateau after four days .

Ondansetron is a selective 5-HT3 receptor antagonist. While its mechanism of action has not been fully characterized, ondansetron is not a dopamine-receptor antagonist. Serotonin receptors of the 5-HT3 type are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema. It is not certain whether ondansetron's antiemetic action is mediated centrally, peripherally, or in both sites. However, cytotoxic chemotherapy appears to be associated with release of serotonin from the enterochromaffin cells of the small intestine.

Ondansetron is a highly specific and selective serotonin 5-HT3 receptor antagonist, not shown to have activity at other known serotonin receptors and with low affinity for dopamine receptors , . The serotonin 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema , . The temporal relationship between the emetogenic action of emetogenic drugs and the release of serotonin, as well as the efficacy of antiemetic agents, suggest that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract , . The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting , .

Moreover, the effect of ondansetron on the QTc interval was evaluated in a double-blind, randomized, placebo and positive (moxifloxacin) controlled, crossover study in 58 healthy adult men and women . Ondansetron was tested at single doses of 8 mg and 32 mg infused intravenously over 15 minutes . At the highest tested dose of 32 mg, prolongation of the Fridericia-corrected QTc interval (QT/RR0.33=QTcF) was observed from 15 min to 4 h after the start of the 15 min infusion, with a maximum mean (upper limit of 90% CI) difference in QTcF from placebo after baseline-correction of 19.6 (21.5) msec at 20 min . At the lower tested dose of 8 mg, QTc prolongation was observed from 15 min to 1 h after the start of the 15-minute infusion, with a maximum mean (upper limit of 90% CI) difference in QTcF from placebo after baseline-correction of 5.8 (7.8) msec at 15 min . The magnitude of QTc prolongation with ondansetron is expected to be greater if the infusion rate is faster than 15 minutes . The 32 mg intravenous dose of ondansetron must not be administered . No treatment-related effects on the QRS duration or the PR interval were observed at either the 8 or 32 mg dose .

An ECG assessment study has not been performed for orally administered ondansetron . On the basis of pharmacokinetic-pharmacodynamic modelling, an 8 mg oral dose of ondansetron is predicted to cause a mean QTcF increase of 0.7 ms (90% CI -2.1, 3.3) at steady-state, assuming a mean maximal plasma concentration of 24.7 ng/mL (95% CI 21.1, 29.0) . The magnitude of QTc prolongation at the recommended 5 mg/m2 dose in pediatrics has not been studied, but pharmacokinetic-pharmacodynamic modeling predicts a mean increase of 6.6 ms (90% CI 2.8, 10.7) at maximal plasma concentrations .

Cool Zone O
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Cool Zone O
Generic	Omeprazole + Ondansetron
Type	Tablet
Therapeutic Class
Manufacturer	Minova Life Sciences Pvt Ltd
Available Country	India
Last Updated:	September 19, 2023 at 7:00 am

Uses

Each film coated MUPS tablet contains 20 mg Omeprazole enteric coated micro pellets

Omeprazole (Multiple-Unit Pellet System) is indixated in-

Duodenal and Gastric ulcers
NSAID-induced gastric and duodenal ulcers
Reflux Oesophagitis
GERD (Gastroesophageal Reflux Disease)
Eradication of H. pylori with appropriate antibiotics
Zollinger-Ellison Syndrome

MUPS is abbreviation for Multiple-Unit Pellet System. However, from pharmaceutical industry and research perspective, the term in general refers to MUPS compacted into tablets. Thus, the resulting tablets prepared by compaction of modified release coated multiparticulates or pellets are called as MUPS. It is the more recent and challenging technology that combines the advantages of both tablets and pellet filled capsules in one dosage form.

MUPS ensure rapid and uniform gastric emptying and subsequently uniform drug dissolution of pellets in the gastrointestinal tract due to their small size and larger surface, uniform drug absorption is facilitated which results in consistent and controlled pharmacological action.

A further reduction in inter- and intra-subject variability in drug absorption and clinical response is facilitated since the number of pellets per MUPS dosage form is much more than a conventional pellet-filled capsule and possibility of dose dumping(in stomach) and incomplete drug release is further minimized.

Ondansetron is used for:

Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy
Prevention of nausea and vomiting associated with radiotherapy
Prevention of post operative nausea and vomiting

Cool Zone O is also used to associated treatment for these conditions: Ankylosing Spondylitis (AS), Duodenal Ulcer, Erosive Esophagitis, Gastric Ulcer, Gastro-esophageal Reflux Disease (GERD), Healing, Heartburn, Helicobacter Pylori Infection, NSAID Associated Gastric Ulcers, Osteoarthritis (OA), Rheumatoid Arthritis, Zollinger-Ellison Syndrome, Hypersecretory conditions, Multiple endocrine adenomasChemotherapy-Induced Nausea and Vomiting (CINV), Cholestatic pruritus, Post Operative Nausea and Vomiting (PONV), Uremic Pruritus, Radiation therapy induced nausea and vomiting, Severe Hyperemesis gravidarum

How Cool Zone O works

Hydrochloric acid (HCl) secretion into the gastric lumen is a process regulated mainly by the H(+)/K(+)-ATPase of the proton pump , expressed in high quantities by the parietal cells of the stomach. ATPase is an enzyme on the parietal cell membrane that facilitates hydrogen and potassium exchange through the cell, which normally results in the extrusion of potassium and formation of HCl (gastric acid) .

Omeprazole is a member of a class of antisecretory compounds, the substituted benzimidazoles, that stop gastric acid secretion by selective inhibition of the H+/K+ ATPase enzyme system. Proton-pump inhibitors such as omeprazole bind covalently to cysteine residues via disulfide bridges on the alpha subunit of the H+/K+ ATPase pump, inhibiting gastric acid secretion for up to 36 hours . This antisecretory effect is dose-related and leads to the inhibition of both basal and stimulated acid secretion, regardless of the stimulus .

Mechanism of H. pylori eradication

Peptic ulcer disease (PUD) is frequently associated with Helicobacter pylori bacterial infection (NSAIDs) . The treatment of H. pylori infection may include the addition of omeprazole or other proton pump inhibitors as part of the treatment regimen , . H. pylori replicates most effectively at a neutral pH . Acid inhibition in H. pylori eradication therapy, including proton-pump inhibitors such as omeprazole, raises gastric pH, discouraging the growth of H.pylori . It is generally believed that proton pump inhibitors inhibit the urease enzyme, which increases the pathogenesis of H. pylori in gastric-acid related conditions .

Ondansetron is a selective antagonist of the serotonin receptor subtype, 5-HT3 .

Cytotoxic chemotherapy and radiotherapy are associated with the release of serotonin (5-HT) from enterochromaffin cells of the small intestine, presumably initiating a vomiting reflex through stimulation of 5-HT3 receptors located on vagal afferents . Ondansetron may block the initiation of this reflex. Activation of vagal afferents may also cause a central release of serotonin from the chemoreceptor trigger zone of the area postrema, located on the floor of the fourth ventricle . Thus, the antiemetic effect of ondansetron is probably due to the selective antagonism of 5-HT3 receptors on neurons located in either the peripheral or central nervous systems, or both .

Although the mechanisms of action of ondansetron in treating postoperative nausea and vomiting and cytotoxic induced nausea and vomiting may share similar pathways, the role of ondansetron in opiate-induced emesis has not yet been formally established .

Dosage

Cool Zone O dosage

Adult:

GERD (Gastroesophageal Reflux Disease):20 mg Once daily for 4 weeks
Gastric ulcer:20 mg Once daily for 4-8 weeks; in severe cases Twice daily
Duodenal ulcer:20 mg Once daily for 2-4 weeks; in severe cases Twice daily
NSAID-induced ulceration:20 mg Once daily for 4-8 weeks
Reflux esophagitis:20 mg Once daily for 4-8 weeks; in severe cases Twice daily
H. pylori eradication (Omeprazole MUPS tablet with Amoxicillin and Clarithromycin or Metronidazole):20 mg Twice daily for 1 week
Zollinger-Ellison Syndrome:60 mg Once daily; Usual maintenance, 20-120mg daily

Children:

Acid regurgitation in GERD (Gastroesophageal Reflux Disease):20 mg Once daily for 2-4 week
Reflux esophagitis:20 mg Once daily for 4-8 weeks

Prevention of chemotherapy induced nausea & vomiting (CINV):

Adult-

Tablet and oral solution: The recommended adult oral dosage of Ondansetron is 24 mg given as three 8 mg tablets in highly emetogenic chemotherapy. In case of moderately emetogenic chemotherapy the oral dose is one 8 mg Ondansetron tablet or 10 ml of Ondansetron oral solution given twice daily.
Injection: The recommended i.v. dose of Ondansetron is a single 32 mg dose or three 0.15 mg/kg doses. A single 32 mg dose is infused over 15 minutes beginning 30 minutes before the start of emetogenic chemotherapy. Subsequent doses (0.15 mg/kg) are administered 4 and 8 hours after the first dose of Ondansetron.
Suppository: The recommended adult dose is one 16 mg suppository 1-2 hours before treatment. Ondansetron should be continued for upto 5 days after a course of treatment.The recommended dose is one suppository daily.

Pediatric patients-

Tablet and oral solution:for pediatric patients 4 through 11 years of age the dosage is one 4 mg Ondansetron tablet or 5ml of Ondansetron solution should be administered 3 times a day for 1 to 2 days after completion of chemotherapy.
Injection: the dosage in pediatric patients 4 to 18 years of age should three 0.15-mg/kg doses.
Suppository:Not recommended.

Radiotherapy induced nausea and vomiting:

Adult-

Tablet and oral solution: the recommended oral dosage is one 8mg Ondansetron tablet or 10ml of Ondansetron oral solution given 3 times daily.

Post operative nausea & vomiting (PONV):

Adult-

Tablet and oral solution: The recommended dosage is 16 mg given as two 8 mg Ondansetron tablets or 20 ml of Ondansetron oral solution 1hour before induction of anesthesia.
Injection: The recommended I.V. dosage of Ondansetron for adults is 4 mg undiluted administered intravenously in not less than 30 seconds, preferably over 2 to 5 minutes, immediately before induction of anesthesia, or postoperatively if the patient experiences nausea and/or vomiting occurring shortly after surgery. Alternatively, 4 mg undiluted may be administered intramuscularly as a single injection for adults. In patients who do not achieve adequate control of postoperative nausea and vomiting following a single, prophylactic, preinduction, I.V. dose of Ondansetron 4 mg, administration of a second I.V. dose of 4 mg Ondansetron postoperatively does not provide additional control of nausea and vomiting.
Suppository: The recommended adult dose is one 16 mg suppository 1-2 hours before treatment. Ondansetron should be continued for upto 5 days after a course of treatment.The recommended dose is one suppository daily.

Pediatric patients-

Injection: The recommended I.V. dosage of Ondansetron for pediatric patients (2 to 12 years of age) isa single 0.1-mg/kg dose for pediatric patients weighing 40 kg or less, or a single 4 mg dose for pediatric patients weighing more than 40 kg. The rate of administration should not be less than 30 seconds, preferably over 2 to 5 minutes. Little information is available about dosage in pediatric patients younger than 2 years of age.
Suppository: Not recommended.

Swallow the tablet whole with a glass of water. The tablet must not be chewed or crushed. OR

If the patients have trouble swallowing the tablets, put the tablet into a glass of water (Do not use other liquids). Stir the preparation until the tablets disintegrate. Then drink the liquid within 30 minutes. Stir the mixture just always before drinking.

Prior to IV infusion, dilute in 50 ml dextrose 5% inj or normal saline.

Side Effects

The most common adverse effects include headache, constipation, diarrhea. In chemotherapy induced nausea and vomiting rash has occurred in approximately 1% of patients receiving Ondansetron. Blurred vision, chest pain with or without ST segment depression, cardiac arrhythmias, hypotension and bradycardia have been rarely reported.

Toxicity

Oral acute (LD50): 4000 mg/kg (mouse), 2210 mg/kg (rat) .

Overdose

Symptoms of overdose include confusion, drowsiness, blurred vision, tachycardia, nausea, diaphoresis, flushing, headache, and dry mouth.

Carcinogenesis and mutagenesis

In 24-month studies in rats, a dose-related significant increase in gastric carcinoid tumors and ECL cell hyperplasia was seen in male and female animals. Carcinoid tumors have also been found in rats treated with a fundectomy or long-term treatment with other proton pump inhibitors, or high doses of H2-receptor antagonists .

Omeprazole showed positive clastogenic effects in an in vitro human lymphocyte chromosomal aberration study, in one of two in vivo mouse micronucleus tests, and in an in vivo bone marrow cell chromosomal aberration test. Omeprazole tested negative in the in vitro Ames test, an in vitro mouse lymphoma cell forward mutation assay, and an in vivo rat liver DNA damage assay .

The use in breastfeeding

Limited data indicate that omeprazole may be present in human milk. There is currently no information on the effects of omeprazole on the breastfed infant or production of milk. The benefits of breastfeeding should be considered along with the level of need for omeprazole and any potential adverse effects on the breastfed infant from omeprazole .

Effects on fertility

Effects of omeprazole at oral doses up to 138 mg/kg/day in rats (about 34 times an oral human dose) was found to have no impact on fertility and reproductive performance .

At present, there is little information concerning overdosage with ondansetron . Nevertheless, there have been certain cases of somewhat idiosyncratic adverse effects associated with particular dosages of ondansetron used .

“Sudden blindness” (amaurosis) of 2 to 3 minutes duration plus severe constipation occurred in one patient that was administered 72 mg of ondansetron intravenously as a single dose . Hypotension (and faintness) occurred in another patient that took 48 mg of oral ondansetron . Following infusion of 32 mg over only a 4-minute period, a vasovagal episode with transient second-degree heart block was observed . Neuromuscular abnormalities, autonomic instability, somnolence, and a brief generalized tonic-clonic seizure (which resolved after a dose of benzodiazepine) were observed in a 12-month-old infant who ingested seven or eight 8-mg ondansetron tablets (approximately forty times the recommended 0.1-0.15 mg/kg dose for a pediatric patient) . In all instances, however, the events resolved completely .

The safety of ondansetron for use in human pregnancy has not been established . Ondansetron is not teratogenic in animals . However, as animal studies are not always predictive of human response, the use of ondansetron in pregnancy is not recommended .

Ondansetron is excreted in the milk of lactating rats . It is not known if it is excreted in human milk, however, nursing is not recommended during treatment with ondansetron .

Insufficient information is available to provide dosage recommendations for children 3 years of age or younger .

Precaution

Omeprazole tablet should be used carefully if the patient has severe liver dysfunction and severe renal impairment.

Hypersensitivity reactions have been reported in patients who have exhibited hypersensitivity to other 5-HT3 receptor antagonists. Ondansetron is not a drug that stimulates gastric or intestinal peristalsis. It should not be used instead of nasogastric suction. The use of Ondansetron in patients following abdominal surgery or in patients with chemotherapy-induced nausea and vomiting may mask a progressive ileus and/or gastric distension.

Interaction

Omeprazole is metabolized through CYP2C19 . When starting or stopping treatment with Omeprazole should be taken into account potential interactions with medicines which are CYP2C19 metabolized.

In patients treated with potent inducers of CYP3A4 (i.e Phenytoin, Carbamazepine or Rifampicin), the oral clearance of Ondansetron was increased and Ondansetron blood concentrations were decreased. Data from small studies indicate that Ondansetron may reduce the analgesic effect of tramadol.

Volume of Distribution

Approximately 0.3 L/kg, corresponding to the volume of extracellular water .

The volume of distribution of ondansetron has been recorded as being approximately 160L .

Elimination Route

Omeprazole delayed-release capsules contain an enteric-coated granule formulation of omeprazole (because omeprazole is acid-labile), so that absorption of omeprazole begins only after the granules exit the stomach .

Absorption of omeprazole occurs rapidly, with peak plasma concentrations of omeprazole achieved within 0.5-3.5 hours .

Absolute bioavailability (compared with intravenous administration) is approximately 30-40% at doses of 20-40 mg, largely due to pre-systemic metabolism. The bioavailability of omeprazole increases slightly upon repeated administration of omeprazole delayed-release capsules .

Ondansetron is absorbed from the gastrointestinal tract and undergoes some limited first-pass metabolism . Mean bioavailability in healthy subjects, following administration of a single 8-mg tablet, was recorded as being approximately 56% to 60% . Bioavailability is also slightly enhanced by the presence of food .

Ondansetron systemic exposure does not increase proportionately to dose . The AUC from a 16-mg tablet was 24% greater than predicted from an 8-mg tablet dose . This may reflect some reduction of first-pass metabolism at higher oral doses .

Half Life

0.5-1 hour (healthy subjects, delayed-release capsule)
Approximately 3 hours (hepatic impairment)

The half-life of ondansetron after either an 8 mg oral dose or intravenous dose was approximately 3-4 hours and could be extended to 6-8 hours in the elderly .

Clearance

Healthy subject (delayed release capsule), total body clearance 500 - 600 mL/min

Geriatric plasma clearance: 250 mL/min

Hepatic impairment plasma clearance: 70 mL/min

The clearance values determined for ondansetron in various patient age groups were recorded as approximately 0.38 L/h/kg in normal adult volunteers aged 19-40 yrs, 0.32 L/h/kg in normal adult volunteers aged 61-74 yrs, 0.26 L/h/kg in normal adult volunteers aged >=75 yrs .

Elimination Route

After a single dose oral dose of a buffered solution of omeprazole, negligible (if any) amounts of unchanged drug were excreted in urine. Most of the dose (about 77%) was eliminated in urine as at least six different metabolites. Two metabolites were identified as hydroxyomeprazole and the corresponding carboxylic acid. The remainder of the dose was found in the feces. This suggests significant biliary excretion of omeprazole metabolites. Three metabolites have been identified in the plasma, the sulfide and sulfone derivatives of omeprazole, and hydroxyomeprazole. These metabolites possess minimal or no antisecretory activity .

Following oral or IV administration, ondansetron is extensively metabolised and excreted in the urine and faeces .

Pregnancy & Breastfeeding use

Not known to be harmful. Omeprazole can be used during pregnancy. Omeprazole is excreted in breast milk but is not likely to influence the child when therapeutic doses are used.

In pregnancy: Pregnancy category B. Reproduction studies at daily oral dose up to 10 and 30 mg/kg/day have been performed in animals and have revealed no evidence of impaired fertility harm to the fetus due to Ondansetron. There are, however, no adequate and well-controlled studies in pregnant women. So the drug should be used in pregnancy only if clearly needed.

In lactation: Ondansetron excretes in milk of lactating animals. Caution should be exercised when Ondansetron is administered to nursing mother.

Contraindication

Omeprazole is contraindicated in those patients who have known hypersensitivity to any other components of the formulation.

Ondansetron is contraindicated in patients with known hypersensitivity to the drug.

Special Warning

Pediatric use: Can be given in children 1 month of age and above.

Geriatric use: No dosage adjustment is necessary in the elderly.Dosage adjustment for patients with impaired hepatic function:

Tablet and Oral Solution: The total daily dose of 8 mg should not be exceeded.
Injection: A single maximal dose of 8 mg to be infused over 15 minutes beginning 30 minutes before the start of the emetogenic chemotherapy is recommended.
Suppository: Not recommended

Acute Overdose

There is no specific antidote for Ondansetron overdose. In addition to the adverse events, hypotension (and faintness) occurred in a patient that took 48 mg of AVONA tablets. In all instances, the events resolved completely.