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DRUGS & SUPPLEMENTS
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Ondansetron Hydrochloride:
Doran-O Tablets is a 5-HT3 receptor antagonist indicated for:
Doran-O Tablets (Ondansetron Hydrochloride) (ondansetron) oral soluble film is indicated for the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin ≥50 mg/m2 .
Doran-O Tablets is indicated for the prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy .
Doran-O Tablets (Ondansetron Hydrochloride) is indicated for the prevention of nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen .
Doran-O Tablets (Ondansetron Hydrochloride) is indicated for the prevention of postoperative nausea and/or vomiting. As with other antiemetics, routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively. In patients where nausea and/or vomiting must be avoided postoperatively, Doran-O Tablets (Ondansetron Hydrochloride) is recommended even where the incidence of postoperative nausea and/or vomiting is low .
Adults
The recommended adult oral dosage of Doran-O Tablets (Ondansetron Hydrochloride) (ondansetron) oral soluble film is 24 mg given successively as three 8 mg films administered 30 minutes before the start of single-day highly emetogenic chemotherapy, including cisplatin ≥50 mg/m2. Each Doran-O Tablets (Ondansetron Hydrochloride) oral soluble film should be allowed to dissolve completely before administering the next film [see Dosage and Administration (2.6 )]. Multiday, single-dose administration of a 24 mg dosage has not been studied.
Pediatrics
Safety and effectiveness of Doran-O Tablets (Ondansetron Hydrochloride) in pediatric patients have not been established for this indication.
Adults
The recommended adult oral dosage is one 8 mg Doran-O Tablets oral soluble film given twice a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. One 8 mg Doran-O Tablets (Ondansetron Hydrochloride) oral soluble film should be administered twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy .
Pediatrics
For pediatric patients 12 years of age and older, the dosage is the same as for adults. For pediatric patients 4 through 11 years of age, the dosage is one 4 mg Doran-O Tablets (Ondansetron Hydrochloride) oral soluble film given three times a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with subsequent doses 4 and 8 hours after the first dose. One 4 mg Doran-O Tablets (Ondansetron Hydrochloride) oral soluble film should be administered three times a day (every 8 hours) for 1 to 2 days after completion of chemotherapy .
Adults
The recommended adult oral dosage of Doran-O Tablets (Ondansetron Hydrochloride) oral soluble film is one 8 mg film given three times a day .
For total body irradiation, one 8 mg Doran-O Tablets (Ondansetron Hydrochloride) oral soluble film should be administered 1 to 2 hours before each fraction of radiotherapy administered each day.
For single high-dose fraction radiotherapy to the abdomen, one 8 mg Doran-O Tablets (Ondansetron Hydrochloride) oral soluble film should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for 1 to 2 days after completion of radiotherapy.
For daily fractionated radiotherapy to the abdomen, one 8 mg Doran-O Tablets (Ondansetron Hydrochloride) oral soluble film should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for each day radiotherapy is given.
Pediatrics
Safety and effectiveness of Doran-O Tablets (Ondansetron Hydrochloride) in pediatric patients have not been established for this indication.
Adults
The recommended adult oral dosage of Doran-O Tablets oral soluble film is 16 mg given successively as two 8 mg films 1 hour before induction of anesthesia. Each Doran-O Tablets (Ondansetron Hydrochloride) oral soluble film should be allowed to dissolve completely before administering the next film .
Pediatrics
Safety and effectiveness of Doran-O Tablets (Ondansetron Hydrochloride) in pediatric patients have not been established for this indication.
In patients with severe hepatic impairment (Child-Pugh score of 10 or greater)2, clearance is reduced and apparent volume of distribution is increased with a resultant increase in plasma half-life . In such patients, a total daily dose of 8 mg should not be exceeded.
With dry hands, fold the pouch along the dotted line to expose the tear notch. While still folded, tear the pouch carefully along the edge and remove the Doran-O Tablets (Ondansetron Hydrochloride) oral soluble film from the pouch. Immediately place the film on top of the tongue where it dissolves in 4 to 20 seconds. Once the Doran-O Tablets (Ondansetron Hydrochloride) oral soluble film is dissolved, swallow with or without liquid . Wash hands after taking Doran-O Tablets (Ondansetron Hydrochloride).
Doran-O Tablets (Ondansetron Hydrochloride) (ondansetron) oral soluble film is available in 4 mg and 8 mg strengths. The thin white opaque films are rectangularly shaped strips with a printed identifier in black ink of “4 mg” for Doran-O Tablets (Ondansetron Hydrochloride) 4 mg or “8 mg” for Doran-O Tablets (Ondansetron Hydrochloride) 8 mg.
The concomitant use of apomorphine with Doran-O Tablets (Ondansetron Hydrochloride) is contraindicated based on reports of profound hypotension and loss of consciousness when apomorphine was administered with Doran-O Tablets (Ondansetron Hydrochloride).
Doran-O Tablets (Ondansetron Hydrochloride) (ondansetron) oral soluble film is contraindicated for patients known to have hypersensitivity to the drug. Anaphylactic reactions have been reported in patients taking Doran-O Tablets (Ondansetron Hydrochloride).
Hypersensitivity reactions, including anaphylaxis and bronchospasm, have been reported in patients who have exhibited hypersensitivity to other selective 5-HT3 receptor antagonists. Doran-O Tablets (Ondansetron Hydrochloride) (ondansetron) oral soluble film should be discontinued immediately at the first sign of hypersensitivity.
ECG changes including QT interval prolongation have been seen in patients receiving Doran-O Tablets. In addition, post-marketing cases of Torsade de Pointes have been reported in patients using Doran-O Tablets (Ondansetron Hydrochloride). Avoid Doran-O Tablets (Ondansetron Hydrochloride) in patients with congenital long QT syndrome. ECG monitoring is recommended in patients with electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, bradyarrhythmias or patients taking other medicinal products that lead to QT prolongation.
The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists. Most reports have been associated with concomitant use of serotonergic drugs (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and intravenous methylene blue). Some of the reported cases were fatal. Serotonin syndrome occurring with overdose of Doran-O Tablets (Ondansetron Hydrochloride) alone has also been reported. The majority of reports of serotonin syndrome related to 5-HT3 receptor antagonist use occurred in a post anesthesia care unit or an infusion center.
Symptoms associated with serotonin syndrome may include the following combination of signs and symptoms: mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, with or without gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome, especially with concomitant use of Doran-O Tablets (Ondansetron Hydrochloride) and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue Doran-O Tablets (Ondansetron Hydrochloride) and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if Doran-O Tablets (Ondansetron Hydrochloride) is used concomitantly with other serotonergic drugs [see Drug Interactions (7.3), Overdosage (10.), Patient Counseling Information (17.)].
The use of Doran-O Tablets in patients following abdominal surgery or in patients with chemotherapy-induced nausea and vomiting may mask a progressive ileus and/or gastric distension.
Doran-O Tablets (Ondansetron Hydrochloride) is not a drug that stimulates gastric or intestinal peristalsis. It should not be used instead of nasogastric suction.
To report SUSPECTED ADVERSE REACTIONS, contact Galena Biopharma, Inc., Portland, OR, 97239, at 1 855 636 5710 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The following adverse events have been reported in clinical trials of patients treated with Doran-O Tablets (Ondansetron Hydrochloride), the active ingredient of Doran-O Tablets (Ondansetron Hydrochloride). A causal relationship to therapy with Doran-O Tablets (Ondansetron Hydrochloride) was unclear in many cases.
Chemotherapy-Induced Nausea and Vomiting
Doran-O Tablets (Ondansetron Hydrochloride) | Doran-O Tablets (Ondansetron Hydrochloride) | Doran-O Tablets (Ondansetron Hydrochloride) | |
24 mg once daily | 8 mg twice daily | 32 mg once daily | |
Adverse Event | N=300 | N=124 | N=117 |
Headache | 33 (11%) | 16 (13%) | 17 (15%) |
Diarrhea | 13 (4%) | 9 (7%) | 3 (3%) |
Doran-O Tablets (Ondansetron Hydrochloride) | Doran-O Tablets (Ondansetron Hydrochloride) | Placebo | |
8 mg twice daily | 8 mg three times daily | ||
Adverse Event | N=242 | N=415 | N=262 |
Headache | 58 (24%) | 113 (27%) | 34 (13%) |
Malaise/fatigue | 32 (13%) | 37 (9%) | 6 (2%) |
Constipation | 22 (9%) | 26 (6%) | 1 (<1%) |
Diarrhea | 15 (6%) | 16 (4%) | 10 (4%) |
Central Nervous System: There have been rare reports consistent with, but not diagnostic of, extrapyramidal reactions in patients receiving Doran-O Tablets (Ondansetron Hydrochloride).
Hepatic: In 723 patients receiving cyclophosphamide-based chemotherapy in US clinical trials, AST and/or ALT values have been reported to exceed twice the upper limit of normal in approximately 1% to 2% of patients receiving Doran-O Tablets (Ondansetron Hydrochloride) HCl tablets. The increases were transient and did not appear to be related to dose or duration of therapy. On repeat exposure, similar transient elevations in transaminase values occurred in some courses, but symptomatic hepatic disease did not occur. The role of cancer chemotherapy in these biochemical changes cannot be clearly determined. There have been reports of liver failure and death in patients with cancer receiving concurrent medications including potentially hepatotoxic cytotoxic chemotherapy and antibiotics. The etiology of the liver failure is unclear.
Integumentary: Rash has occurred in approximately 1% of patients receiving Doran-O Tablets (Ondansetron Hydrochloride).
Other: Rare cases of anaphylaxis, bronchospasm, tachycardia, angina (chest pain), hypokalemia, electrocardiographic alterations, vascular occlusive events, and grand mal seizures have been reported. Except for bronchospasm and anaphylaxis, the relationship to Doran-O Tablets (Ondansetron Hydrochloride) was unclear.
Radiation-Induced Nausea and Vomiting
The adverse events reported in patients receiving Doran-O Tablets (Ondansetron Hydrochloride) HCl tablets and concurrent radiotherapy were similar to those reported in patients receiving Doran-O Tablets (Ondansetron Hydrochloride) HCl tablets and concurrent chemotherapy. The most frequently reported adverse events were headache, constipation, and diarrhea.
Postoperative Nausea and Vomiting
a Adverse Events: With the exception of headache, rates of these events were not significantly different in the Doran-O Tablets (Ondansetron Hydrochloride) and placebo groups. | ||
b Patients were receiving multiple concomitant perioperative and postoperative medications. | ||
Doran-O Tablets (Ondansetron Hydrochloride) 16 mg | Placebo | |
Adverse Event a,b | N=550 | N=531 |
Headache | 49 (9%) | 27 (5%) |
Hypoxia | 49 (9%) | 35 (7%) |
Pyrexia | 45 (8%) | 34 (6%) |
Dizziness | 36 (7%) | 34 (6%) |
Gynecological disorder | 36 (7%) | 33 (6%) |
Anxiety/agitation | 33 (6%) | 29 (5%) |
Urinary retention | 28 (5%) | 18 (3%) |
Pruritus | 27 (5%) | 20 (4%) |
In addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of oral formulations of Doran-O Tablets (Ondansetron Hydrochloride). Because these events are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Doran-O Tablets (Ondansetron Hydrochloride).
Cardiovascular: Rarely and predominantly with intravenous Doran-O Tablets (Ondansetron Hydrochloride), transient ECG changes including QT interval prolongation have been reported.
General: Flushing. Rare cases of hypersensitivity reactions, sometimes severe (e.g., anaphylaxis reactions, angioedema, bronchospasm, shortness of breath, hypotension, laryngeal edema, stridor) have also been reported. Laryngospasm, shock, and cardiopulmonary arrest have occurred during allergic reactions in patients receiving injectable Doran-O Tablets (Ondansetron Hydrochloride).
Hepatobiliary: Liver enzyme abnormalities
Lower Respiratory: Hiccups
Neurology: Oculogyric crisis, appearing alone, as well as with other dystonic reactions
Skin: Urticaria
Eye Disorders: Cases of transient blindness, predominantly during intravenous administration, have been reported. These cases of transient blindness were reported to resolve within a few minutes up to 48 hours.
Doran-O Tablets does not itself appear to induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system of the liver.
Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with Doran-O Tablets (Ondansetron Hydrochloride), the concomitant use of apomorphine with Doran-O Tablets (Ondansetron Hydrochloride) is contraindicated [see Contraindications (4)].
In patients treated with potent inducers of CYP3A4, the clearance of Doran-O Tablets (Ondansetron Hydrochloride) was significantly increased and Doran-O Tablets (Ondansetron Hydrochloride) blood concentrations were decreased. However, on the basis of available data, no dosage adjustment for Doran-O Tablets (Ondansetron Hydrochloride) is recommended for patients on these drugs.1,3
Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms) has been described following the concomitant use of 5-HT 3 receptor antagoinists and other serotonergic drugs, including selective serotonin reuptake inhibitor (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) .
Although there are no data on pharmacokinetic drug interactions between Doran-O Tablets and tramadol, data from two small studies indicate that concomitant use of Doran-O Tablets (Ondansetron Hydrochloride) may result in reduced analgesic activity of tramadol. Patients in the studies self-administered tramadol more frequently, leading to an increased cumulative dose in patient controlled administration (PCA) of tramadol.4,5
In humans, carmustine, etoposide, and cisplatin do not affect the pharmacokinetics of Doran-O Tablets (Ondansetron Hydrochloride).
In a crossover study in 76 pediatric patients, intravenous Doran-O Tablets (Ondansetron Hydrochloride) did not increase blood levels of high-dose methotrexate.
The co-administration of Doran-O Tablets had no effect on the pharmacokinetics and pharmacodynamics of temazepam.
Bioavailability of Doran-O Tablets (Ondansetron Hydrochloride) is unaffected by antacids
Doran-O Tablets (Ondansetron Hydrochloride) does not alter the respiratory depressant effects produced by alfentanil or the degree of neuromuscular blockade produced by atracurium. Interactions with general or local anesthetics have not been studied.
Pregnancy Category B. Reproduction studies have been performed in pregnant rats and rabbits at daily oral doses up to 15 and 30 mg/kg/day, respectively (approximately 8 and 30 times the human dose of 16 mg/day, based on body surface area), and have revealed no evidence of impaired fertility or harm to the fetus due to Doran-O Tablets (Ondansetron Hydrochloride). There are, however, no adequate and well- controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Doran-O Tablets (Ondansetron Hydrochloride) (ondansetron) oral soluble film should be used during pregnancy only if clearly needed.
Doran-O Tablets is excreted in the milk of rats. It is not known whether Doran-O Tablets (Ondansetron Hydrochloride) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Doran-O Tablets (Ondansetron Hydrochloride) oral soluble film is administered to a nursing woman.
Little information is available about dosage in pediatric patients less than 4 years of age. For dosage recommendations in the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy for patients 4 years of age and older . The safety and effectiveness in pediatric patients have not been established for the following
Indications: prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, prevention of nausea and vomiting associated with radiotherapy, and prevention of postoperative nausea and/or vomiting.
Of the total number of subjects enrolled in cancer chemotherapy-induced and postoperative nausea and vomiting in US- and foreign- controlled clinical trials, for which there were subgroup analyses, 938 were 65 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Dosage adjustment is not needed in patients over the age of 65 [see Clinical Pharmacology ].
The dosage recommendation is the same as for the general population. There is no experience beyond first-day administration of Doran-O Tablets (Ondansetron Hydrochloride).
In patients with severe hepatic impairment (Child-Pugh score of 10 or greater)2, clearance is reduced and apparent volume of distribution is increased with a resultant increase in plasma half-life [see Clinical Pharmacology (12.3)]. In such patients, a total daily dose of 8 mg should not be exceeded.
Animal studies have shown that Doran-O Tablets (Ondansetron Hydrochloride) is not discriminated as a benzodiazepine nor does it substitute for benzodiazepines in direct addiction studies.
There is no specific antidote for Doran-O Tablets (Ondansetron Hydrochloride) overdose. Patients should be managed with appropriate supportive therapy. Individual intravenous doses as large as 150 mg and total daily intravenous doses as large as 252 mg have been inadvertently administered without significant adverse events. These doses are more than 10 times the recommended daily dose.
In addition to the adverse events listed above, the following events have been described in the setting of Doran-O Tablets (Ondansetron Hydrochloride) overdose: “Sudden blindness” (amaurosis) of 2 to 3 minutes' duration plus severe constipation occurred in 1 patient that was administered 72 mg of Doran-O Tablets (Ondansetron Hydrochloride) intravenously as a single dose. Hypotension (and faintness) occurred in a patient that took 48 mg of Doran-O Tablets (Ondansetron Hydrochloride) HCl tablets. Following infusion of 32 mg over only a 4-minute period, a vasovagal episode with transient second-degree heart block was observed. In all instances, the events resolved completely.
Pediatric cases consistent with serotonin syndrome have been reported after inadvertent oral overdoses of Doran-O Tablets (Ondansetron Hydrochloride) (exceeding estimated ingestion of 5 mg/kg) in young children. Reported symptoms included somnolence, agitation, tachycardia, tachypnea, hypertension, flushing, mydriasis, diaphoresis, myoclonic movements, horizontal nystagmus, hyperreflexia, and seizure. Patients required supportive care, including intubation in some cases, with complete recovery without sequelae within 1 to 2 days.
Doran-O Tablets (Ondansetron Hydrochloride) (ondansetron) oral soluble film is a white opaque orally dissolving film designed to be applied on top of the tongue where it will dissolve in 4 to 20 seconds and then is swallowed with saliva.
Doran-O Tablets (Ondansetron Hydrochloride) does not require water to aid dissolution or swallowing.
The active ingredient in Doran-O Tablets (Ondansetron Hydrochloride) is Doran-O Tablets (Ondansetron Hydrochloride) base, the racemic form of Doran-O Tablets (Ondansetron Hydrochloride), and a selective blocking agent of the serotonin 5-HT3 receptor type. Chemically it is (±) 1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H- carbazol-4-one.
The empirical formula is C18H19N3O representing a molecular weight of 293.3. Each 4-mg Doran-O Tablets (Ondansetron Hydrochloride) oral soluble film for oral administration contains 4 mg Doran-O Tablets (Ondansetron Hydrochloride) base. Each 8-mg Doran-O Tablets (Ondansetron Hydrochloride) oral soluble film for oral administration contains 8 mg Doran-O Tablets (Ondansetron Hydrochloride) base. Each Doran-O Tablets (Ondansetron Hydrochloride) oral soluble film also contains the inactive ingredients butylated hydroxytoluene, calcium carbonate, colloidal silicon dioxide, erythritol, hypromellose, monoammonium glycyrrhizinate, peppermint flavor, polyethylene oxide, sodium bicarbonate, sucralose, titanium dioxide and xanthan gum.
Doran-O Tablets is a selective 5-HT3 receptor antagonist. While its mechanism of action has not been fully characterized, Doran-O Tablets (Ondansetron Hydrochloride) 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. In humans, urinary 5-HIAA (5-hydroxyindoleacetic acid) excretion increases after cisplatin administration in parallel with the onset of emesis. The released serotonin may stimulate the vagal afferents through the 5- HT3 receptors and initiate the vomiting reflex. In animals, the emetic response to cisplatin can be prevented by pretreatment with an inhibitor of serotonin synthesis, bilateral abdominal vagotomy and greater splanchnic nerve section, or pretreatment with a serotonin 5-HT3 receptor antagonist.
In normal volunteers, single intravenous doses of 0.15 mg/kg of Doran-O Tablets (Ondansetron Hydrochloride) had no effect on esophageal motility, gastric motility, lower esophageal sphincter pressure, or small intestinal transit time. Multiday administration of Doran-O Tablets (Ondansetron Hydrochloride) has been shown to slow colonic transit in normal volunteers. Doran-O Tablets (Ondansetron Hydrochloride) has no effect on plasma prolactin concentrations.
Absorption
Doran-O Tablets (Ondansetron Hydrochloride) is well absorbed from the gastrointestinal tract and undergoes some first-pass metabolism. After a single dose of Doran-O Tablets (Ondansetron Hydrochloride) (ondansetron) oral soluble film 8 mg under fasting conditions (n=46), the peak plasma concentrations were achieved in 1.3 hours and the mean elimination half-life was 4.6 hours in healthy subjects. The mean (±S.D.) Cmax and AUC were 37.28 (±14.9) ng/mL and 225 (±88.1) ng·h/mL, respectively. In the same study, mean Doran-O Tablets (Ondansetron Hydrochloride) Cmax and AUC following administration of 8 mg Doran-O Tablets (Ondansetron Hydrochloride) oral soluble film were comparable to those after 8 mg Doran-O Tablets (Ondansetron Hydrochloride) ODT (orally disintegrating tablet). The systemic exposure after administration of Doran-O Tablets (Ondansetron Hydrochloride) oral soluble film 8 mg with or without water was found to be comparable.
In a study using Doran-O Tablets (Ondansetron Hydrochloride) tablets, Doran-O Tablets (Ondansetron Hydrochloride) systemic exposure did not increase proportionately to dose. 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.
Food Effect
When administered with a high fat meal, 8 mg Doran-O Tablets (Ondansetron Hydrochloride) (ondansetron) oral soluble film's mean time to peak plasma concentration (tmax) was delayed by approximately 1 hour and its AUC remained similar compared to that of under fasted stated.
Distribution
Plasma protein binding of Doran-O Tablets (Ondansetron Hydrochloride) as measured in vitro was 70% to 76% over the concentration range of 10 to 500 ng/mL. Circulating drug also distributes into erythrocytes.
Metabolism and Excretion
Doran-O Tablets (Ondansetron Hydrochloride) is extensively metabolized in humans, with approximately 5% of a radiolabeled dose recovered as the parent compound from the urine. The metabolites are observed in the urine. The primary metabolic pathway is hydroxylation on the indole ring followed by subsequent glucuronide or sulfate conjugation.
In vitro metabolism studies have shown that Doran-O Tablets (Ondansetron Hydrochloride) is a substrate for human hepatic cytochrome P-450 enzymes, including CYP1A2, CYP2D6, and CYP3A4. In terms of overall Doran-O Tablets (Ondansetron Hydrochloride) turnover, CYP3A4 played the predominant role.
Although some nonconjugated metabolites have pharmacologic activity, these are not found in plasma at concentrations likely to significantly contribute to the biological activity of Doran-O Tablets (Ondansetron Hydrochloride).
Drug Interactions
Doran-O Tablets (Ondansetron Hydrochloride) does not itself appear to induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system of the liver.
Because Doran-O Tablets (Ondansetron Hydrochloride) is metabolized by hepatic cytochrome P-450 drug-metabolizing enzymes (CYP3A4, CYP2D6, CYP1A2), inhibitors of these enzymes may change the clearance and, hence, the half-life of Doran-O Tablets (Ondansetron Hydrochloride). On the basis of available data, no dosage adjustment is recommended for patients on these drugs. Based on the multiplicity of metabolic enzymes capable of metabolizing Doran-O Tablets (Ondansetron Hydrochloride), it is likely that inhibition or loss of one enzyme (e.g., CYP2D6 genetic deficiency) will be compensated by others and may result in little change in overall rates of Doran-O Tablets (Ondansetron Hydrochloride) elimination.
On the basis of available limited data, no dosage adjustment for Doran-O Tablets (Ondansetron Hydrochloride) is recommended for patients on inhibitors of a single CYP enzyme.
Doran-O Tablets (Ondansetron Hydrochloride) elimination may be affected by cytochrome P-450 inducers. In a pharmacokinetic study of 16 epileptic patients maintained chronically on CYP3A4 inducers, carbamazepine, or phenytoin, reduction in AUC, Cmax, and T½ of Doran-O Tablets (Ondansetron Hydrochloride) was observed1; this resulted in a significant increase in clearance. However, on the basis of available data, no dosage adjustment for Doran-O Tablets (Ondansetron Hydrochloride) is recommended.
Specific Populations
Gender
Gender differences were shown in the disposition of Doran-O Tablets (Ondansetron Hydrochloride) given as a single dose. The extent and rate of ondansetron' s absorption is greater in women than men. It is not known whether these gender-related differences are clinically important.
Gender | Mean Weight (kg) | n | C max (ng/mL) | T max (h) | T 1/2 (h) | AUC (h·ng/mL) |
M | 62 | 39 | 35.2 | 1.67 | 4.54 | 207 |
F | 56.7 | 7 | 49.1 | 1.7 | 5.39 | 323 |
Elderly
A reduction in clearance and increase in elimination half-life are seen in patients over 75 years of age. In clinical trials with cancer patients, safety and efficacy was similar in patients over 65 years of age and those under 65 years of age; there was an insufficient number of patients over 75 years of age to permit conclusions in that age-group. No dosage adjustment is recommended in the elderly.
Hepatic Impairment
In patients with mild-to-moderate hepatic impairment, clearance is reduced 2-fold and mean half-life is increased to 11.6 hours compared to 5.7 hours in healthy subjects. In patients with severe hepatic impairment (Child-Pugh score of 10 or greater)2, clearance is reduced 2-fold to 3-fold and apparent volume of distribution is increased with a resultant increase in half-life to 20 hours. In patients with severe hepatic impairment, a total daily dose of 8 mg should not be exceeded.
Renal Impairment
Due to the very small contribution (5%) of renal clearance to the overall clearance, renal impairment was not expected to significantly influence the total clearance of Doran-O Tablets (Ondansetron Hydrochloride). However, Doran-O Tablets (Ondansetron Hydrochloride) oral mean plasma clearance was reduced by about 50% in patients with severe renal impairment (creatinine clearance <30 mL/min). This reduction in clearance is variable and was not consistent with an increase in half-life. No reduction in dose or dosing frequency in these patients is warranted.
Carcinogenic effects were not seen in 2-year studies in rats and mice with oral Doran-O Tablets (Ondansetron Hydrochloride) doses up to 10 mg/kg/day and 30 mg/kg/day, respectively (approximately 5 and 8 times the human dose of 16 mg/day, based on body surface area). Doran-O Tablets (Ondansetron Hydrochloride) was not mutagenic in standard tests for mutagenicity. Oral administration of Doran-O Tablets (Ondansetron Hydrochloride) up to 15 mg/kg/day (approximately 8 times the human dose of 16 mg/day, based on body surface area) did not affect fertility or general reproductive performance of male and female rats.
The clinical efficacy of Doran-O Tablets, the active ingredient of Doran-O Tablets (Ondansetron Hydrochloride), was assessed in clinical trials as described below.
Highly Emetogenic Chemotherapy
In 2 randomized, double-blind, monotherapy trials, a single 24 mg Doran-O Tablets (Ondansetron Hydrochloride) HCl tablet was superior to a relevant historical placebo control in the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin ≥50 mg/m2. Steroid administration was excluded from these clinical trials. More than 90% of patients receiving a cisplatin dose ≥50 mg/m2 in the historical placebo comparator experienced vomiting in the absence of antiemetic therapy.
The first trial compared oral doses of Doran-O Tablets (Ondansetron Hydrochloride) 24 mg once a day, 8 mg twice a day, and 32 mg once a day in 357 adult cancer patients receiving chemotherapy regimens containing cisplatin ≥50 mg/m2. A total of 66% of patients in the Doran-O Tablets (Ondansetron Hydrochloride) 24 mg once- a-day group, 55% in the Doran-O Tablets (Ondansetron Hydrochloride) 8 mg twice-a-day group, and 55% in the Doran-O Tablets (Ondansetron Hydrochloride) 32 mg once-a-day group completed the 24- hour study period with 0 emetic episodes and no rescue antiemetic medications, the primary endpoint of efficacy. Each of the 3 treatment groups was shown to be statistically significantly superior to a historical placebo control.
In the same trial, 56% of patients receiving oral Doran-O Tablets (Ondansetron Hydrochloride) 24 mg once a day experienced no nausea during the 24-hour study period, compared with 36% of patients in the oral Doran-O Tablets (Ondansetron Hydrochloride) 8 mg twice-a-day group (p = 0.001) and 50% in the oral Doran-O Tablets (Ondansetron Hydrochloride) 32 mg once-a-day group.
In a second trial, efficacy of the oral Doran-O Tablets (Ondansetron Hydrochloride) 24 mg once-a-day regimen in the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin ≥50 mg/m2, was confirmed.
Moderately Emetogenic Chemotherapy
In 1 double-blind US study in 67 patients, Doran-O Tablets (Ondansetron Hydrochloride) HCl tablets 8 mg administered twice a day were significantly more effective than placebo in preventing vomiting induced by cyclophosphamide-based chemotherapy containing doxorubicin. Treatment response is based on the total number of emetic episodes over the 3-day study period. The results of this study are summarized in Table 5.
a The first dose was administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. An 8-mg Doran-O Tablets (Ondansetron Hydrochloride) HCl tablet was administered twice a day for 2 days after completion of chemotherapy. | |||
b Median undefined since at least 50% of the patients were withdrawn or had more than 2 emetic episodes. | |||
c Median undefined since at least 50% of patients did not have any emetic episodes. | |||
Doran-O Tablets (Ondansetron Hydrochloride) | |||
Tablet | |||
8 mg twice daily a | Placebo | p Value | |
Number of patients | 33 | 34 | |
Treatment response | |||
0 emetic episodes | 20 (61%) | 2 (6%) | <0.001 |
1-2 emetic episodes | 6 (18%) | 8 (24%) | |
>2 emetic episodes/ withdrawn | 7 (21%) | 24 (71%) | <0.001 |
Median number of emetic episodes | 0.0 | Undefinedb | |
Median time to first emetic episode (h) | Undefinedc | 6.5 |
In 1 double-blind US study in 336 patients, Doran-O Tablets (Ondansetron Hydrochloride) HCl tablets 8 mg administered twice a day were as effective as Doran-O Tablets (Ondansetron Hydrochloride) HCl tablets 8 mg administered 3 times a day in preventing nausea and vomiting induced by cyclophosphamide-based chemotherapy containing either methotrexate or doxorubicin.
Treatment response is based on the total number of emetic episodes over the 3-day study period. The results of this study are summarized in Table 6.
a The first dose was administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. An 8-mg Doran-O Tablets (Ondansetron Hydrochloride) HCl tablet was administered twice a day for 2 days after completion of chemotherapy. | ||
b The first dose was administered 30 minutes before the start of emetogenic chemotherapy, with subsequent doses 4 and 8 hours after the first dose. An 8-mg | ||
Doran-O Tablets (Ondansetron Hydrochloride) HCl tablet was administered three times daily for 2 days after completion of chemotherapy. | ||
c Median undefined since at least 50% of patients did not have any emetic episodes. | ||
d Visual analog scale assessment: 0=no nausea, 100=nausea as bad as it can be. | ||
Doran-O Tablets (Ondansetron Hydrochloride) 8 mg twice daily a | Doran-O Tablets (Ondansetron Hydrochloride) 8 mg three times daily b | |
Number of patients | 165 | 171 |
Treatment response | ||
0 emetic episodes | 101 (61%) | 99 (58%) |
1-2 emetic episodes | 16 (10%) | 17 (10%) |
>2 emetic episodes/withdrawn | 48 (29%) | 55 (32%) |
Median number of emetic episodes | 0.0 | 0.0 |
Median time to first emetic episode (h) | Undefinedc | Undefinedc |
Median nausea scores (0-100)d | 6 | 6 |
Retreatment
In uncontrolled trials, 148 patients receiving cyclophosphamide-based chemotherapy were re-treated with Doran-O Tablets (Ondansetron Hydrochloride) HCl tablets 8 mg three times daily during subsequent chemotherapy for a total of 396 re-treatment courses. No emetic episodes occurred in 314 (79%) of the re-treatment courses, and only 1 to 2 emetic episodes occurred in 43 (11%) of the re-treatment courses.
Pediatrics
Three open-label, uncontrolled, foreign trials have been performed with 182 pediatric patients 4 to 18 years old with cancer who were given a variety of cisplatin or non-cisplatin regimens. In these foreign trials, the initial dose of Doran-O Tablets (Ondansetron Hydrochloride) HCl injection ranged from 0.04 mg/kg to 0.87 mg/kg for a total dose of 2.16 mg to 12 mg. This was followed by the administration of Doran-O Tablets (Ondansetron Hydrochloride) HCl tablets ranging from 4 mg to 24 mg daily for 3 days. In these studies, 58% of the 170 evaluable patients had a complete response (no emetic episodes) on day 1. Two studies showed the response rates for patients less than 12 years of age who received Doran-O Tablets (Ondansetron Hydrochloride) HCl tablets 4 mg three times daily to be similar to those in patients 12 to 18 years of age who received Doran-O Tablets (Ondansetron Hydrochloride) HCl tablets 8 mg three times daily. Thus, prevention of emesis in these pediatric patients was essentially the same as for patients older than 18 years of age. Overall, Doran-O Tablets (Ondansetron Hydrochloride) HCl tablets were tolerated in these pediatric patients.
Total Body Irradiation
In a randomized, double-blind study in 20 patients, Doran-O Tablets HCl tablets (8 mg given 1.5 hours before each fraction of radiotherapy for 4 days) were significantly more effective than placebo in preventing vomiting induced by total body irradiation. Total body irradiation consisted of 11 fractions (120 cGy per fraction) over 4 days for a total of 1,320 cGy. Patients received 3 fractions for 3 days, then 2 fractions on day 4.
Single High-Dose Fraction Radiotherapy
Doran-O Tablets (Ondansetron Hydrochloride) was significantly more effective than metoclopramide with respect to complete control of emesis (0 emetic episodes) in a double-blind trial in 105 patients receiving single high-dose radiotherapy (800 to 1,000 cGy) over an anterior or posterior field size of ≥80 cm2 to the abdomen. Patients received the first dose of Doran-O Tablets (Ondansetron Hydrochloride) HCl tablets (8 mg) or metoclopramide (10 mg) 1 to 2 hours before radiotherapy. If radiotherapy was given in the morning, 2 additional doses of study treatment were given (1 tablet late afternoon and 1 tablet before bedtime). If radiotherapy was given in the afternoon, patients took only 1 further tablet that day before bedtime. Patients continued the oral medication on a three times daily basis for 3 days.
Daily Fractionated Radiotherapy
Doran-O Tablets (Ondansetron Hydrochloride) was significantly more effective than prochlorperazine with respect to complete control of emesis (0 emetic episodes) in a double-blind trial in 135 patients receiving a 1- to 4-week course of fractionated radiotherapy (180 cGy doses) over a field size of >100 cm2 to the abdomen. Patients received the first dose of Doran-O Tablets (Ondansetron Hydrochloride) HCl tablets (8 mg) or prochlorperazine (10 mg) 1 to 2 hours before the patient received the first daily radiotherapy fraction, with 2 subsequent doses on a three times a day basis. Patients continued the oral medication on a three times daily basis on each day of radiotherapy.
Surgical patients who received Doran-O Tablets (Ondansetron Hydrochloride) 1 hour before the induction of general balanced anesthesia (barbiturate: thiopental, methohexital, or thiamylal; opioid: alfentanil, sufentanil, morphine, or fentanyl; nitrous oxide; neuromuscular blockade: succinylcholine/curare or gallamine and/or vecuronium, pancuronium, or atracurium; and supplemental isoflurane or enflurane) were evaluated in 2 double-blind studies (1 US study, 1 foreign) involving 865 patients. Doran-O Tablets (Ondansetron Hydrochloride) HCl tablets (16 mg) were significantly more effective than placebo in preventing postoperative nausea and vomiting.
The study populations in all trials thus far consisted of women undergoing inpatient surgical procedures. No studies have been performed in males. No controlled clinical study comparing Doran-O Tablets (Ondansetron Hydrochloride) HCl tablets to Doran-O Tablets (Ondansetron Hydrochloride) injection has been performed.
Doran-O Tablets (Ondansetron Hydrochloride) (ondansetron) oral soluble film 4 mg and Doran-O Tablets (Ondansetron Hydrochloride) (ondansetron) oral soluble film 8 mg, are supplied as thin rectangular white opaque films in individual foil-foil sealed child resistant pouches. Individual films are identified by “4 mg” or “8 mg”, according to the respective strengths, which is printed using pharmaceutical grade edible ink.
Individual pouches of Doran-O Tablets (Ondansetron Hydrochloride) 4 mg oral soluble film are packaged in boxes of 10 (NDC 57881-444-10) and packaged in boxes of 1 (NDC 57881-444-01). Individual pouches of Doran-O Tablets (Ondansetron Hydrochloride) 8 mg oral soluble film are packaged in boxes of 10 (NDC 57881-448-10) and packaged in boxes of 1 (NDC 57881-448-01).
Store at controlled room temperature 20° to 25°C (68° to 77°F). Store pouches in cartons. Keep product in pouch until ready to use.
See FDA-Approved Patient Labeling
Advise patients to carefully read the “Patient Information” and “Instructions for Use” accompanying each package of Doran-O Tablets (Ondansetron Hydrochloride) (ondansetron) oral soluble film.
Inform patients that Doran-O Tablets (Ondansetron Hydrochloride) may cause serious cardiac arrhythmias such as QT prolongation. Instruct patients to tell their healthcare provider right away if they perceive a change in their heart rate, if they feel lightheaded, or if they have a syncopal episode.
Inform patients that the chances of developing severe cardiac arrhythmias such as QT prolongation and Torsade de Pointes are higher in the following people:
Inform patients that Doran-O Tablets (Ondansetron Hydrochloride) film may cause headache, malaise/fatigue, constipation, and diarrhea. The patient should report the use of all medications, especially apomorphine or any drug of the 5HT3 antagonist class, to their health care provider. Concomitant use of apomorphine and Doran-O Tablets (Ondansetron Hydrochloride) may cause a significant drop in blood pressure and loss of consciousness.
Inform patients that Doran-O Tablets (Ondansetron Hydrochloride) may cause hypersensitivity reactions, some as severe as anaphylaxis and bronchospasm. The patient should report any hypersensitivity reactions to this and other 5-HT3 receptor antagonists to their health care provider.
Instruct patients on how to use Doran-O Tablets (Ondansetron Hydrochloride) films:
The patient should keep the film in the pouch until ready to use and not to chew or swallow the film. With dry hands, the patient should fold the pouch along the dotted line to expose the tear notch. While still folded, the patient should tear the pouch carefully along the edge and remove the Doran-O Tablets (Ondansetron Hydrochloride) oral soluble film from the pouch. The patient should immediately place the film on top of the tongue where it dissolves in 4 to 20 seconds, then swallow with saliva. Once the film dissolves, the patient may swallow liquid but it is not required. The patient should wash his hands after taking Doran-O Tablets (Ondansetron Hydrochloride).
Patient Information
Doran-O Tablets (Ondansetron Hydrochloride) ® (ZOO-plenz)
(ondansetron)
Oral Soluble Film
What is Doran-O Tablets (Ondansetron Hydrochloride) ® ?
Doran-O Tablets (Ondansetron Hydrochloride) is a prescription medicine that is used in adults to prevent nausea and vomiting:
In children 4 years of age and older, Doran-O Tablets (Ondansetron Hydrochloride) is only used to prevent nausea and vomiting that happens with certain cancer chemotherapy medicines.
It is not known if Doran-O Tablets (Ondansetron Hydrochloride) is safe and works in children to prevent nausea and vomiting with radiation therapy, or nausea and vomiting that may happen after surgery in children.
Who should not take Doran-O Tablets (Ondansetron Hydrochloride)? Do not take Doran-O Tablets (Ondansetron Hydrochloride) if you:
What should I tell my doctor before taking Doran-O Tablets (Ondansetron Hydrochloride)? Before you take Doran-O Tablets (Ondansetron Hydrochloride), tell you doctor if you:
Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines may affect how Doran-O Tablets (Ondansetron Hydrochloride) works, and Doran-O Tablets (Ondansetron Hydrochloride) may affect how other medicines work. Taking Doran-O Tablets (Ondansetron Hydrochloride) with certain other medicines may cause serious side effects. Especially tell your doctor if you take:
Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.
How should I take Doran-O Tablets (Ondansetron Hydrochloride)?
Read the Instructions for Use at the end of this Patient Information for information about the right way to take Doran-O Tablets (Ondansetron Hydrochloride).
What should I avoid while taking Doran-O Tablets (Ondansetron Hydrochloride)?
Doran-O Tablets (Ondansetron Hydrochloride) may cause dizziness. Do not drive, operate machinery, or do other dangerous activities until you know how Doran-O Tablets (Ondansetron Hydrochloride) affects you.
What are the possible side effects of Doran-O Tablets (Ondansetron Hydrochloride)?
Doran-O Tablets (Ondansetron Hydrochloride) may cause serious side effects, including:
The most common side effects of Doran-O Tablets (Ondansetron Hydrochloride) include:
These are not all the possible side effects of Doran-O Tablets (Ondansetron Hydrochloride). For more information, ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store Doran-O Tablets (Ondansetron Hydrochloride)?
Keep Doran-O Tablets (Ondansetron Hydrochloride) and all medicines out of the reach of children.
General information about the safe and effective use of Doran-O Tablets (Ondansetron Hydrochloride)
Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use Doran-O Tablets (Ondansetron Hydrochloride) for a condition for which it was not prescribed. Do not give Doran-O Tablets (Ondansetron Hydrochloride) to other people, even if they have the same symptoms that you have. It may harm them.
You can ask your doctor or pharmacist for information about Doran-O Tablets (Ondansetron Hydrochloride) that is written for health professionals.
For more information, go to www. ZUPLENZ.com or call 1 855 636 5710.
What are the ingredients in Doran-O Tablets (Ondansetron Hydrochloride)?
Active ingredient: Doran-O Tablets (Ondansetron Hydrochloride)
Inactive ingredients: butylated hydroxytoluene, calcium carbonate, colloidal silicon dioxide, erythritol, hypromellose, monoammonium glycyrrhizinate, peppermint flavor, polyethylene oxide, sodium bicarbonate, sucralose, titanium dioxide and xanthan gum.
This Patient Information has been approved by the U.S. Food and Drug Administration.
Manufactured by:
Monosol Rx, LLC
Warren, NJ 07059
Manufactured for:
Galena Biopharma, Inc.
Portland, OR 97239
Distributed by:
Galena Biopharma, Inc. Portland, OR 97239
Revised: September 2014
Instructions for Use
Doran-O Tablets (Ondansetron Hydrochloride) ® (ZOO-plenz)
(ondansetron)
Oral Soluble Film
Step 1. Keep the Doran-O Tablets (Ondansetron Hydrochloride) film in the foil pouch until ready to use. Use Doran-O Tablets (Ondansetron Hydrochloride) film right away after you take it out of the pouch.
Step 2. Make sure your hands are dry.
Step 3. Fold the pouch along the dotted line to expose the tear notch. See Figure A.
Principal Display Panel - 4 mg
Principal Display Panel - Box Label
TO OPEN: Fold along dotted line and
tear down at slit along the arrow.
PHYSICIAN SAMPLE
NOT FOR SALE
NDC 57881-444-01
Doran-O Tablets (Ondansetron Hydrochloride) ®
(ondansetron) oral soluble film
4 mg
Rx only
1 Film
Principal Display Panel - 8 mg
Principal Display Panel - Box Label
TO OPEN: Fold along dotted line and
tear down at slit along the arrow.
PHYSICIAN SAMPLE
NOT FOR SALE
NDC 57881-448-01
Doran-O Tablets (Ondansetron Hydrochloride) ®
(ondansetron) oral soluble film
8 mg
Rx only
1 Film
Ranitidine Hydrochloride:
Doran-O Tablets is a blocker of histamine H2-receptors. Inhibits basal and stimulated by histamine, gastrin and acetylcholine (to a lesser extent) the secretion of hydrochloric acid. Increases the pH of gastric contents and reduces the activity of pepsin. The duration of action of Doran-O Tablets (Ranitidine Hydrochloride) with a single admission - 12 hours.
After oral administration, Doran-O Tablets (Ranitidine Hydrochloride) is rapidly absorbed from the gastrointestinal tract. Eating and antacids significantly affect the extent of absorption. Subjected to the effect of "first passage" through the liver. Cmax in plasma is reached within 2 h after a single oral administration. After IM injection Doran-O Tablets (Ranitidine Hydrochloride) rapidly and almost completely absorbed from the injection site. Cmax achieved within 15 min.
Protein binding - 15%. Vd - 1.4 L / kg. Doran-O Tablets (Ranitidine Hydrochloride) is excreted in breast milk.
T1/2 is 2-3 h. About 30% of the dose excreted in the urine in unchanged form. Elimination rate decreases with abnormal liver function or renal function.
Gastric ulcer and duodenal ulcer in acute phase; prevention of relapse of peptic ulcer; symptomatic ulcer; erosive and reflux esophagitis; Zollinger-Ellison syndrome; prevention of "stress" ulcers of the gastrointestinal tract, postoperative ulcers, recurrent bleeding from upper gastrointestinal tract; prevention of aspiration of gastric juice during operations under general anesthesia.
Individual. For oral administration for treatment of adults and children over 14 years daily Doran-O Tablets dose is 300-450 mg; if necessary, the daily dose was increased to 600-900 mg; multiplicity of administration is 2-3 times / day. For the prevention of exacerbations of disease are used by 150 mg / day at bedtime. The duration of treatment is determined by the indications for use.
The dose of Doran-O Tablets (Ranitidine Hydrochloride) for patients with renal insufficiency at the level of creatinine more than 3.3 mg / 100 ml is 75 mg 2 times / day.
IV or IM by 50-100 mg every 6-8 hours.
Cardio-vascular system: in a few cases (for IV administration) - AV-blockade.
Digestive system: rarely - diarrhea, constipation, and in isolated cases - hepatitis.
CNS: Rarely - headache, dizziness, fatigue, blurred vision, and in isolated cases (at seriously ill patients) - confusion, hallucinations.
Hematopoietic system: rarely - thrombocytopenia, prolonged use at high doses - leukopenia.
Metabolism: rarely - a slight increase of creatinine in serum at the beginning of treatment.
Endocrine system: long-term use in high doses may increase the content of prolactin, gynecomastia, amenorrhea, impotence, decreased libido.
From the musculoskeletal system: very rarely - arthralgia, myalgia.
Allergic reactions: rarely - a skin rash, urticaria, angioedema, anaphylactic shock, bronchospasm, hypotension.
Other: rarely - recurrent parotitis, and in isolated cases - hair loss.
Pregnancy, lactation (breastfeeding), increased sensitivity to Doran-O Tablets (Ranitidine Hydrochloride).
Adequate and well controlled studies of the safety of Doran-O Tablets during pregnancy has not been conducted, therefore the use during pregnancy is contraindicated.
If necessary the use of Doran-O Tablets (Ranitidine Hydrochloride) during lactation should stop breastfeeding.
With careful use in patients with impaired renal excretory function.
Before treatment with Doran-O Tablets (Ranitidine Hydrochloride) is necessary to exclude the possibility of a malignant disease of the esophagus, stomach or duodenum.
With long-term treatment of debilitated patients under stress conditions may be bacterial lesions of the stomach with subsequent spread of infection.
Undesirable abrupt discontinuation of Doran-O Tablets (Ranitidine Hydrochloride) because of the risk of recurrence of peptic ulcer. Effectiveness of prophylactic treatment of peptic ulcer above while taking Doran-O Tablets (Ranitidine Hydrochloride) courses for 45 days in spring and autumn than during the reception. Quick intravenous injection of Doran-O Tablets (Ranitidine Hydrochloride) in rare cases cause bradycardia, usually in patients predisposed to cardiac arrhythmias.
There are a few reports that Doran-O Tablets (Ranitidine Hydrochloride) might contribute to the development of acute attacks of porphyria, in connection with what is necessary to avoid its use in patients with acute porphyria in history.
Therapy with Doran-O Tablets (Ranitidine Hydrochloride) possible distortions of laboratory data: increased creatinine, the activity of gamma-glutamyl transpeptidase and liver transaminases in the blood plasma.
In cases where Doran-O Tablets (Ranitidine Hydrochloride) is used in combination with antacids, the break between taking antacids and Doran-O Tablets (Ranitidine Hydrochloride) should be at least 1-2 hours (antacids may cause undesired absorption of Doran-O Tablets (Ranitidine Hydrochloride)).
Clinical data on the safety of Doran-O Tablets (Ranitidine Hydrochloride) in pediatric patients is limited.
In an application with antacids may decrease absorption of Doran-O Tablets (Ranitidine Hydrochloride).
In an application of Doran-O Tablets (Ranitidine Hydrochloride) with anticholinergics may be in breach of memory and attention in elderly patients.
Probably that histamine H2-blockers reduce receptor ulcerogenic action of NSAIDs on the gastric mucosa.
In an application with warfarin may decrease clearance of warfarin. There is one case of gipoprotrombinemiey and bleeding in patients receiving warfarin.
In an application with bismuth tripotassium dicitrate may increase unwanted absorption of bismuth, with glyburide - described the cases of hypoglycemia, with ketoconazole, itraconazole - decreased absorption of ketoconazole, itraconazole.
In an application with metoprolol may increase the plasma concentrations and increased AUC and T1 / 2 of metoprolol.
In an application with sucralfate in high doses (2 g) possible violation of the absorption of Doran-O Tablets (Ranitidine Hydrochloride).
In an application Doran-O Tablets (Ranitidine Hydrochloride) with procainamide may be decrease excretion of procainamide by the kidneys which leads to an increase in its concentration in blood plasma.
There is a data of increased absorption of triazolam in its simultaneous application, apparently due to changes in pH of gastric contents under the influence of Doran-O Tablets (Ranitidine Hydrochloride).
Probably that while the application with phenytoin may increase the concentration of phenytoin in plasma and increased risk of toxicity.
In an application with furosemide moderately expressed increasing the bioavailability of furosemide.
There is a described case of ventricular arrhythmias (bigeminy) with simultaneous application of quinidine, with cisapride - described a case of cardiotoxicity.
It can not be excluded some increase in cyclosporine concentration in blood plasma in its simultaneous application with Doran-O Tablets (Ranitidine Hydrochloride).
Symptoms: seizures, bradycardia, ventricular arrhythmias.
Treatment: induction of vomiting or gastric lavage, symptomatic therapy. In convulsions - diazepam IV, bradycardia - atropine, ventricular arrhythmias - lidocaine.
Depending on the reaction of the Doran-O Tablets after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Doran-O Tablets not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.
Is Doran-O Tablets addictive or habit forming?Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
Visitors | % | ||
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It has side effects | 1 | 100.0% |
Visitors | % | ||
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1-5mg | 1 | 100.0% |
Visitors | % | ||
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2 days | 1 | 100.0% |
Visitors | % | ||
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After food | 1 | 100.0% |
Visitors | % | ||
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30-45 | 1 | 33.3% | |
1-5 | 1 | 33.3% | |
6-15 | 1 | 33.3% |
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The information was verified by Dr. Rachana Salvi, MD Pharmacology