Gastro-Timelets

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Gastro-Timelets uses


1 INDICATIONS AND USAGE

Gastro-Timelets tablets are indicated for the:

  • Treatment for 4 to 12 weeks of symptomatic, documented gastroesophageal reflux in adults who fail to respond to conventional therapy.
  • Relief of symptoms in adults with acute and recurrent diabetic gastroparesis.

Limitations of Use:

Gastro-Timelets tablets are not recommended for use in pediatric patients due to the risk of developing tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates [see Use in Specific Populations ( 8.4 ) ].

Gastro-Timelets tablets are indicated for the:

  • Treatment for 4 to 12 weeks of symptomatic, documented gastroesophageal reflux in adults who fail to respond to conventional therapy. (1)
  • Relief of symptoms in adults with acute and recurrent diabetic gastroparesis. (1)

Limitations of Use:

Gastro-Timelets tablets are not recommended for use in pediatric patients due to the risk of tardive dyskinesia (TD) and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates. (1, 8.4)

2 DOSAGE AND ADMINISTRATION

Gastroesophageal Reflux

  • Administer Gastro-Timelets continuously or intermittently:
    • Continuous: Administer 10 to 15 mg, 30 minutes before each meal and at bedtime (maximum of 60 mg per day) for 4 to 12 weeks.
    • Intermittent: Single doses up to 20 mg prior to provoking situation.

Acute and Recurrent Diabetic Gastroparesis (2.3)

  • Administer 10 mg, 30 minutes before each meal and at bedtime (maximum of 40 mg per day) for 2 to 8 weeks

Dosage Adjustment in Specific Populations (2.2, 2.3)

  • For gastroesophageal reflux and acute and recurrent diabetic gastroparesis, see Full Prescribing Information for recommended dosage reductions for elderly patients, in patients with moderate or severe hepatic or renal impairment, and cytochrome P450 2D6 (CYP2D6) poor metabolizers.

2.1 Important Administration Instructions

Avoid treatment with Gastro-Timelets for longer than 12 weeks because of the increased risk of developing TD with longer-term use [see Dosage and Administration (2.2, 2.3), Warnings and Precautions (5.1)].

2.2 Dosage for Gastroesophageal Reflux

Gastro-Timelets tablets may be administered continuously or intermittently in patients with symptomatic gastroesophageal reflux who fail to respond to conventional therapy:

Continuous Dosing

The recommended adult dosage of Gastro-Timelets is 10 to 15 mg four times daily for 4 to 12 weeks. The treatment duration is determined by endoscopic response. Administer the dosage thirty minutes before each meal and at bedtime. The maximum recommended daily dosage is 60 mg.

Table 1 displays the recommended daily dosage and maximum daily dosage for adults and dosage adjustments for patients with moderate or severe hepatic impairment, in patients with creatinine clearance less than 60 mL/minute, in cytochrome P450 2D6 (CYP2D6) poor metabolizers, and with concomitant use with strong CYP2D6 inhibitors.

Intermittent Dosing

If symptoms only occur intermittently or at specific times of the day, administer Gastro-Timelets in single dose up to 20 mg prior to the provoking situation. Consider dosage reductions for the populations and situations in Table 1.


Recommended Dosage


Maximum Recommended Daily Dosage


Adult patients


10 to 15 mg four times daily (thirty minutes before each meal and at bedtime)


60 mg


Mild hepatic impairment (Child-Pugh A)


Elderly patients [see Use in Specific Populations (8.5)]


5 mgElderly patients may be more sensitive to the therapeutic or adverse effects of Gastro-Timelets; therefore, consider a lower starting dosage of 5 mg four times daily with titration to the recommended adult dosage of 10 to 15 mg four times daily based upon response and tolerability. four times daily (thirty minutes before each meal and at bedtime)


Moderate or severe hepatic impairment (Child-Pugh B or C) [see Use in Specific Populations (8.7)]


5 mg four times daily (thirty minutes before each meal and at bedtime), or

10 mg taken three times daily


30 mg


CYP2D6 poor metabolizers [see Use in Specific Populations (8.9)]


Concomitant use with strong CYP2D6 inhibitors (e.g., quinidine, bupropion, fluoxetine, and paroxetine) [see Drug Interactions (7.1)]


Moderate or severe renal impairment (creatinine clearance less than or equal to 60 mL/minute) [see Use in Specific Populations (8.6)]


Patients with End-Stage Renal Disease (ESRD) including those treated with hemodialysis and continuous ambulatory peritoneal dialysis [see Use in Specific Populations (8.6)]


5 mg four times daily (thirty minutes before each meal and at bedtime) or 10 mg twice daily


20 mg

2.3 Dosage for Acute and Recurrent Diabetic Gastroparesis

The recommended adult dosage for the treatment of acute and recurrent diabetic gastroparesis is 10 mg four times daily for 2 to 8 weeks, depending on symptomatic response. Avoid Gastro-Timelets treatment for greater than 12 weeks [see Warnings and Precautions (5.1)]. Administer the dosage thirty minutes before each meal and at bedtime. The maximum recommended daily dosage is 40 mg.

Table 2 displays the recommended daily dosage and maximum daily dosage for adults and dosage adjustments for patients with moderate or severe hepatic impairment (Child-Pugh B or C), in patients with creatinine clearance less than 60 mL/minute, in cytochrome P450 2D6 (CYP2D6) poor metabolizers, and with concomitant use with strong CYP2D6 inhibitors.

If patients with diabetic gastroparesis have severe nausea or vomiting and are unable to take oral Gastro-Timelets tablets, consider starting therapy with Gastro-Timelets injection given intramuscularly or intravenously for up to 10 days. After patients are able to take oral therapy, switch to Gastro-Timelets tablets.


Recommended Dosage


Maximum Recommended Daily Dosage


Adult Patients


10 mg four times daily (30 minutes before each meal and at bedtime)


40 mg


Mild hepatic impairment (Child-Pugh A)


Elderly patients [see Use in Specific Populations (8.5)]


5 mgElderly patients may be more sensitive to the therapeutic or adverse effects of Gastro-Timelets; therefore, consider a lower dosage of 5 mg four times daily with titration to the recommended adult dosage of 10 mg four time daily based upon response and tolerability. four times daily (30 minutes before each meal and at bedtime)


Moderate or severe hepatic impairment (Child-Pugh B or C) [see Use in Specific Populations (8.7)]


5 mg four times daily (30 minutes before each meal and at bedtime)


20 mg


CYP2D6 poor metabolizers [see Use in Specific Populations (8.9)]


Concomitant use with strong CYP2D6 inhibitors (e.g., quinidine, bupropion, fluoxetine, and paroxetine) [see Drug Interactions (7.1)]


Moderate or severe renal impairment (creatinine clearance less than 60 mL/minute) [see Use in Specific Populations (8.6)]


Patients with End-Stage Renal Disease (ESRD) including those treated with hemodialysis and continuous ambulatory peritoneal dialysis [see Use in Specific Populations (8.6)]


5 mg twice daily


10 mg

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3 DOSAGE FORMS AND STRENGTHS

Tablets:

  • 5 mg Gastro-Timelets: white, round, unscored, debossed “TV” on one side and “2204” on the other side.
  • 10 mg Gastro-Timelets: white, round, scored, debossed “TEVA” on one side and “2203” above the score on the other side.

Tablets: 5 mg and 10 mg Gastro-Timelets (3)

4 CONTRAINDICATIONS

Gastro-Timelets is contraindicated:

  • In patients with a history of tardive dyskinesia (TD) or a dystonic reaction to Gastro-Timelets [see Warnings and Precautions ( 5.1, 5.2 ) ].
  • When stimulation of gastrointestinal motility might be dangerous (e.g., in the presence of gastrointestinal hemorrhage, mechanical obstruction, or perforation).
  • In patients with pheochromocytoma or other catecholamine-releasing paragangliomas. Gastro-Timelets may cause a hypertensive/pheochromocytoma crisis, probably due to release of catecholamines from the tumor [see Warnings and Precautions (5.5)].
  • In patients with epilepsy. Gastro-Timelets may increase the frequency and severity of seizures [see Adverse Reactions (6)].
  • In patients with hypersensitivity to Gastro-Timelets. Reactions have included laryngeal and glossal angioedema and bronchospasm [see Adverse Reactions (6)].
  • History of TD or dystonic reaction to Gastro-Timelets (4)
  • When stimulation of gastrointestinal motility might be dangerous (4)
  • Pheochromocytoma, catecholamine-releasing paragangliomas (4)
  • Epilepsy (4)
  • Hypersensitivity to Gastro-Timelets (4)
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5 WARNINGS AND PRECAUTIONS

  • Tardive Dyskinesia, Other Extrapyramidal Symptoms (EPS), and Neuroleptic Malignant Syndrome (NMS): Avoid concomitant use of other drugs known to cause TD/EPS/NMS and avoid use in patients with Parkinson’s Disease. If symptoms occur, discontinue Gastro-Timelets and seek immediate medical attention. (5.1, 5.2, 5.3, 7.1, 7.2)
  • Depression and suicidal ideation/suicide: Avoid use. (5.4)

5.1 Tardive Dyskinesia

Gastro-Timelets can cause tardive dyskinesia (TD), a syndrome of potentially irreversible and disfiguring involuntary movements of the face or tongue, and sometimes of the trunk and/or extremities. Movements may be choreoathetotic in appearance. The risk of developing TD and the likelihood that TD will become irreversible increases with duration of treatment and total cumulative dosage. Additionally, the risk of developing TD is increased among the elderly, especially elderly women [see Use in Specific Populations (8.5)], and in patients with diabetes mellitus. Due to the risk of developing TD, avoid treatment with Gastro-Timelets for longer than 12 weeks and reduce the dosage in elderly patients [see Dosage and Administration (2.2, 2.3)].

Discontinue Gastro-Timelets immediately in patients who develop signs and symptoms of TD. There is no known effective treatment for established cases of TD, although in some patients TD may remit, partially or completely, within several weeks to months after Gastro-Timelets is withdrawn.

Gastro-Timelets itself may suppress, or partially suppress, the signs of TD, thereby masking the underlying disease process. The effect of this symptomatic suppression upon the long-term course of TD is unknown. Gastro-Timelets is contraindicated in patients with a history of TD [see Contraindications (4)]. Avoid Gastro-Timelets in patients receiving other drugs that are likely to cause TD (e.g., antipsychotics).

5.2 Other Extrapyramidal Symptoms

In addition to TD, Gastro-Timelets may cause other extrapyramidal symptoms, parkinsonian symptoms, and motor restlessness. Advise patients to seek immediate medical attention if such symptoms occur and to discontinue Gastro-Timelets.

  • Extrapyramidal symptoms (EPS), such as acute dystonic reactions, occurred in patients treated with Gastro-Timelets dosages of 30 mg to 40 mg daily. Such reactions occurred more frequently in adults less than 30 years of age and at higher than recommended dosages. EPS occurred more frequently in pediatric patients compared to adults (metoclopramide is not approved for use in pediatric patients). Symptoms can occur in the first 24 to 48 hours after starting Gastro-Timelets. Symptoms included involuntary movements of limbs and facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of tongue, bulbar type of speech, trismus, or dystonic reactions resembling tetanus. Rarely, dystonic reactions were present as stridor and dyspnea, possibly due to laryngospasm. Diphenhydramine hydrochloride or benztropine mesylate may be used to treat these adverse reactions. Avoid Gastro-Timelets in patients receiving other drugs that can cause EPS (e.g., antipsychotics).
  • Parkinsonian symptoms (bradykinesia, tremor, cogwheel rigidity, mask-like facies) have occurred after starting Gastro-Timelets, more commonly within the first 6 months, but also after longer periods. Symptoms generally have subsided within 2 to 3 months after discontinuation of Gastro-Timelets. Avoid Gastro-Timelets in patients with Parkinson’s disease and other patients being treated with antiparkinsonian drugs due to potential exacerbation of symptoms. Avoid treatment with Gastro-Timelets for more than 12 weeks [see Dosage and Administration (2.2, 2.3), Warnings and Precautions (5.1)].
  • Motor restlessness (akathisia) has developed and consisted of feelings of anxiety, agitation, jitteriness, and insomnia, as well as inability to sit still, pacing, and foot tapping. If symptoms resolve, consider restarting at a lower dosage.

5.3 Neuroleptic Malignant Syndrome

Gastro-Timelets may cause a potentially fatal symptom complex called neuroleptic malignant syndrome (NMS). NMS has been reported in association with Gastro-Timelets overdosage and concomitant treatment with another drug associated with NMS. Avoid Gastro-Timelets in patients receiving other drugs associated with NMS, including typical and atypical antipsychotics.

Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status, and manifestations of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac arrhythmias). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Patients with such symptoms should be evaluated immediately.

In the diagnostic evaluation, consider the presence of other serious medical conditions (e.g., pneumonia, systemic infection) and untreated or inadequately treated extrapyramidal signs and symptoms. Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, malignant hyperthermia, drug fever, serotonin syndrome, and primary central nervous system pathology.

Management of NMS includes:

  • Immediate discontinuation of Gastro-Timelets and other drugs not essential to concurrent therapy [see Drug Interactions (7.1)].
  • Intensive symptomatic treatment and medical monitoring.
  • Treatment of any concomitant serious medical problems for which specific treatments are available.

5.4 Depression

Depression has occurred in metoclopramide-treated patients with and without a history of depression. Symptoms have included suicidal ideation and suicide. Avoid Gastro-Timelets use in patients with a history of depression.

5.5 Hypertension

Gastro-Timelets may elevate blood pressure. In one study in hypertensive patients, intravenously administered Gastro-Timelets was shown to release catecholamines; hence, avoid use in patients with hypertension or in patients taking monoamine oxidase inhibitors [see Drug Interactions ].

There are also clinical reports of hypertensive crises in patients with undiagnosed pheochromocytoma. Gastro-Timelets is contraindicated in patients with pheochromocytoma or other catecholamine-releasing paragangliomas [see Contraindications (4)]. Discontinue Gastro-Timelets in any patient with a rapid rise in blood pressure.

5.6 Fluid Retention

Because Gastro-Timelets produces a transient increase in plasma aldosterone, patients with cirrhosis or congestive heart failure may be at risk of developing fluid retention and volume overload. Discontinue Gastro-Timelets if any of these adverse reactions occur.

5.7 Hyperprolactinemia

As with other dopamine D2 receptor antagonists, Gastro-Timelets elevates prolactin levels.

Hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported with prolactin-elevating drugs, including Gastro-Timelets.

Hyperprolactinemia may potentially stimulate prolactin-dependent breast cancer. However, some clinical studies and epidemiology studies have not shown an association between administration of dopamine D2 receptor antagonists and tumorigenesis in humans [see Nonclinical Toxicology ].

5.8 Effects of the Ability to Drive and Operate Machinery

Gastro-Timelets may impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving a motor vehicle. Concomitant use of central nervous system (CNS) depressants or drugs associated with EPS may increase this effect (e.g., alcohol, sedatives, hypnotics, opiates, and anxiolytics). Avoid Gastro-Timelets or the interacting drug, depending on the importance of the drug to the patient [see Drug Interactions (7.1)].

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6 ADVERSE REACTIONS

The following adverse reactions are described, or described in greater detail, in other sections of the labeling:

  • Tardive dyskinesia [see Boxed Warning and Warnings and Precautions (5.1)]
  • Other extrapyramidal effects [see Warnings and Precautions (5.2)]
  • Neuroleptic malignant syndrome [see Warnings and Precautions (5.3)]
  • Depression [see Warnings and Precautions (5.4)]
  • Hypertension [see Warnings and Precautions (5.5)]
  • Fluid retention [see Warnings and Precautions (5.6)]
  • Hyperprolactinemia [see Warnings and Precautions (5.7)]
  • Effects on the ability to drive and operate machinery [see Warnings and Precautions (5.8)]

The following adverse reactions have been identified from clinical studies or postmarketing reports of Gastro-Timelets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The most common adverse reactions (in approximately 10% of patients receiving 10 mg of Gastro-Timelets four times daily) were restlessness, drowsiness, fatigue, and lassitude. In general, the incidence of adverse reactions correlated with the dosage and duration of Gastro-Timelets administration.

Adverse reactions, especially those involving the nervous system, occurred after stopping Gastro-Timelets including dizziness, nervousness, and headaches.

Central Nervous System Disorders

  • Tardive dyskinesia, acute dystonic reactions, drug-induced parkinsonism, akathisia, and other extrapyramidal symptoms
  • Convulsive seizures
  • Hallucinations
  • Restlessness, drowsiness, fatigue, and lassitude occurred in approximately 10% of patients who received 10 mg four times daily. Insomnia, headache, confusion, dizziness, or depression with suicidal ideation occurred less frequently.
  • Neuroleptic malignant syndrome, serotonin syndrome (in combination with serotonergic agents).

Endocrine Disorders: Fluid retention secondary to transient elevation of aldosterone. Galactorrhea, amenorrhea, gynecomastia, impotence secondary to hyperprolactinemia

Cardiovascular Disorders: Acute congestive heart failure, possible atrioventricular block, hypotension, hypertension, supraventricular tachycardia, bradycardia, fluid retention

Gastrointestinal Disorders: Nausea, bowel disturbances (primarily diarrhea)

Hepatic Disorders: Hepatotoxicity, characterized by, e.g., jaundice and altered liver function tests, when Gastro-Timelets was administered with other drugs with known hepatotoxic potential

Renal and Urinary Disorders: Urinary frequency, urinary incontinence

Hematologic Disorders: Agranulocytosis, neutropenia, leukopenia, methemoglobinemia, sulfhemoglobinemia

Hypersensitivity Reactions: Bronchospasm (especially in patients with a history of asthma), urticaria; rash; angioedema, including glossal or laryngeal edema

Eye Disorders: Visual disturbances

Metabolism Disorders: Porphyria

  • Most common adverse reactions (> 10%) are restlessness, drowsiness, fatigue, and lassitude. (6)

To report SUSPECTED ADVERSE REACTIONS, contact TEVA USA, PHARMACOVIGILANCE at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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7 DRUG INTERACTIONS

  • Antipsychotics: Potential for additive effects, including TD, EPS, and NMS; avoid concomitant use.
  • CNS depressants: Increased risk of CNS depression. Avoid concomitant use and monitor for adverse reactions. (7.1)
  • Strong CYP2D6 inhibitors (e.g., quinidine, bupropion, fluoxetine, and paroxetine): See Full Prescribing Information for recommended dosage reductions. (2.2, 2.3, 7.1)
  • MAO inhibitors: Increased risk of hypertension; avoid concomitant use. (5.5, 7.1)
  • Additional drug interactions: See Full Prescribing Information. (7.1, 7.2)

7.1 Effects of Other Drugs on Gastro-Timelets

Table 3 displays the effects of other drugs on Gastro-Timelets.


Antipsychotics


Clinical Impact


Potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS).


Intervention


Avoid concomitant use [see Warnings and Precautions (5.1, 5.2, 5.3)].


Strong CYP2D6 Inhibitors, not Included in Antipsychotic Category Above


Clinical Impact


Increased plasma concentrations of Gastro-Timelets; risk of exacerbation of extrapyramidal symptoms [see Clinical Pharmacology (12.3)].


Intervention


Reduce the Gastro-Timelets dosage [see Dosage and Administration (2.2, 2.3)].


Examples


quinidine, bupropion, fluoxetine, and paroxetine


Monoamine Oxidase Inhibitors


Clinical Impact


Increased risk of hypertension [see Warnings and Precautions (5.5)].


Intervention


Avoid concomitant use.


Central Nervous System (CNS) Depressants


Clinical Impact


Increased risk of CNS depression [see Warnings and Precautions (5.8)].


Intervention


Avoid Gastro-Timelets or the interacting drug, depending on the importance of the drug to the patient.


Examples


alcohol, sedatives, hypnotics, opiates and anxiolytics


Drugs that Impair Gastrointestinal Motility


Clinical Impact


Decreased systemic absorption of Gastro-Timelets.


Intervention


Monitor for reduced therapeutic effect.


Examples


antiperistaltic antidiarrheal drugs, anticholinergic drugs, and opiates


Dopaminergic Agonists and Other Drugs that Increase Dopamine Concentrations


Clinical Impact


Decreased therapeutic effect of Gastro-Timelets due to opposing effects on dopamine.


Intervention


Monitor for reduced therapeutic effect.


Examples


apomorphine, bromocriptine, cabergoline, levodopa, pramipexole, ropinirole, and rotigotine

7.2 Effects of Gastro-Timelets on Other Drugs

Table 4 displays the effects of Gastro-Timelets on other drugs.


Dopaminergic Agonists and Drugs Increasing Dopamine Concentrations


Clinical Impact


Opposing effects of Gastro-Timelets and the interacting drug on dopamine. Potential exacerbation of symptoms (e.g., parkinsonian symptoms).


Intervention


Avoid concomitant use [see Warnings and Precautions (5.2)].


Examples


Apomorphine, bromocriptine, cabergoline, levodopa, pramipexole, ropinirole, rotigotine


Succinylcholine, Mivacurium


Clinical Impact


Gastro-Timelets inhibits plasma cholinesterase leading to enhanced neuromuscular blockade.


Intervention


Monitor for signs and symptoms of prolonged neuromuscular blockade


Drugs with Absorption Altered due to Increased Gastrointestinal Motility


Clinical Impact


The effect of Gastro-Timelets on other drugs is variable. Increased gastrointestinal (GI) motility by Gastro-Timelets may impact absorption of other drugs leading to decreased or increased drug exposure.


Intervention


Drugs with Decreased Absorption (e.g., digoxin, atovaquone, posaconazole oral suspension Interaction does not apply to posaconazole delayed-release tablets, fosfomycin): Monitor for reduced therapeutic effect of the interacting drug. For digoxin monitor therapeutic drug concentrations and increase the digoxin dose as needed.

Drugs with Increased Absorption (e.g., sirolimus, tacrolimus, cyclosporine): Monitor therapeutic drug concentrations and adjust the dose as needed. See prescribing information for the interacting drug.


Insulin


Clinical Impact


Increased GI motility by Gastro-Timelets may increase delivery of food to the intestines and increase blood glucose.


Intervention


Monitor blood glucose and adjust insulin dosage regimen as needed.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Published studies, including retrospective cohort studies, national registry studies, and meta-analyses, do not report an increased risk of adverse pregnancy-related outcomes with use of Gastro-Timelets during pregnancy.

There are potential risks to the neonate following exposure in utero to Gastro-Timelets during delivery [see Clinical Considerations]. In animal reproduction studies, no adverse developmental effects were observed with oral administration of Gastro-Timelets to pregnant rats and rabbits at exposures about 6 and 12 times the maximum recommended human dose [see Data].

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in the clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Gastro-Timelets crosses the placental barrier and may cause extrapyramidal signs and methemoglobinemia in neonates with maternal administration during delivery. Monitor neonates for extrapyramidal signs [see Warnings and Precautions (5.1, 5.2), Use in Specific Populations (8.4)].

Data

Animal Data

Reproduction studies have been performed following administration of oral Gastro-Timelets during organogenesis in pregnant rats at about 6 times the MRHD calculated on body surface area and in pregnant rabbits at about 12 times the MRHD calculated on body surface area. No evidence of adverse developmental effects due to Gastro-Timelets were observed.

8.2 Lactation

Risk Summary

Limited published data report the presence of Gastro-Timelets in human milk in variable amounts. Breastfed infants exposed to Gastro-Timelets have experienced gastrointestinal adverse reactions, including intestinal discomfort and increased intestinal gas formation [see Data]. Gastro-Timelets elevates prolactin levels [see Warnings and Precautions (5.7)]; however, the published data are not adequate to support drug effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Gastro-Timelets and any potential adverse effects on the breastfed child from Gastro-Timelets or from the underlying maternal condition.

Clinical Considerations

Monitor breastfeeding neonates because Gastro-Timelets may cause extrapyramidal signs (dystonias) and methemoglobinemia [see Warnings and Precautions (5.1, 5.2), Use in Specific Populations (8.4)].

Data

In published clinical studies, the estimated amount of Gastro-Timelets received by the breastfed infant was less than 10% of the maternal weight-adjusted dose. In one study, the estimated daily amount of Gastro-Timelets received by infants from breast milk ranged from 6 to 24 mcg/kg/day in early puerperium (3 to 9 days postpartum) and from 1 to 13 mcg/kg/day at 8 to 12 weeks postpartum.

8.4 Pediatric Use

Gastro-Timelets is not recommended for use in pediatric patients due to the risk of tardive dyskinesia and other extrapyramidal symptoms as well as the risk of methemoglobinemia in neonates. The safety and effectiveness of Gastro-Timelets in pediatric patients have not been established.

Dystonias and other extrapyramidal symptoms associated with Gastro-Timelets are more common in pediatric patients than in adults [see Warnings and Precautions (5.1, 5.2)]. In addition, neonates have reduced levels of NADH-cytochrome b5 reductase, making them more susceptible to methemoglobinemia, a possible adverse reaction of Gastro-Timelets use in neonates [see Use in Specific Populations (8.8)].

8.5 Geriatric Use

Gastro-Timelets is known to be substantially excreted by the kidney, and the risk of adverse reactions, including tardive dyskinesia (TD), may be greater in patients with impaired renal function [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)]. Elderly patients are more likely to have decreased renal function and may be more sensitive to the therapeutic or adverse effects of Gastro-Timelets; therefore, consider a reduced dosage of Gastro-Timelets in elderly patients [see Boxed Warning, Dosage and Administration (2.2, 2.3), Warnings and Precautions (5.1)].

8.6 Renal Impairment

The clearance of Gastro-Timelets is decreased and the systemic exposure is increased in patients with moderate to severe renal impairment compared to patients with normal renal function, which may increase the risk of adverse reactions. Reduce the Gastro-Timelets dosage in patients with moderate and severe renal impairment, including those receiving hemodialysis and continuous ambulatory peritoneal dialysis [see Dosage and Administration (2.2, 2.3), Clinical Pharmacology (12.3)].

8.7 Hepatic Impairment

Patients with severe hepatic impairment (Child-Pugh C) have reduced systemic Gastro-Timelets clearance (by approximately 50%) compared to patients with normal hepatic function. The resulting increase in Gastro-Timelets blood concentrations increases the risk of adverse reactions. There is no pharmacokinetic data in patients with moderate hepatic impairment (Child-Pugh B). Reduce Gastro-Timelets dosage in patients with moderate or severe (Child-Pugh B or C) hepatic impairment [see Dosage and Administration (2.2, 2.3)]. There is no dosage adjustment required for patients with mild hepatic impairment (Child-Pugh A).

In addition, Gastro-Timelets, by producing a transient increase in plasma aldosterone, may increase the risk of fluid retention in patients with hepatic impairment [see Warnings and Precautions (5.6)].

Monitor patients with hepatic impairment for the occurrence of fluid retention and volume overload.

8.8 NADH-Cytochrome b5 Reductase Deficiency

Metoclopramide-treated patients with NADH-cytochrome b5 reductase deficiency are at an increased risk of developing methemoglobinemia and/or sulfhemoglobinemia. For patients with glucose-6-phosphate dehydrogenase deficiency with metoclopramide-induced methemoglobinemia, methylene blue treatment is not recommended. Methylene blue may cause hemolytic anemia in patients with G6PD deficiency, which may be fatal [see Overdosage (10)].

8.9 CYP2D6 Poor Metabolizers

Gastro-Timelets is a substrate of CYP2D6. The elimination of Gastro-Timelets may be slowed in patients who are CYP2D6 poor metabolizers (compared to patients who are CYP2D6 intermediate, extensive, or ultra-rapid metabolizers); possibly increasing the risk of dystonic and other adverse reactions to Gastro-Timelets [see Clinical Pharmacology (12.3)]. Reduce the Gastro-Timelets dosage in patients who are poor CYP2D6 metabolizers [see Dosage and Administration (2.2, 2.3)].

10 OVERDOSAGE

Manifestations of Gastro-Timelets overdosage included drowsiness, disorientation, extrapyramidal reactions, other adverse reactions associated with Gastro-Timelets use (including, e.g., methemoglobinemia), and sometimes death. Neuroleptic malignant syndrome (NMS) has been reported in association with Gastro-Timelets overdose and concomitant treatment with another drug associated with NMS [see Warnings and Precautions (5.1, 5.2, 5.3)].

There are no specific antidotes for Gastro-Timelets overdosage. If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.

Methemoglobinemia can be reversed by the intravenous administration of methylene blue. However, methylene blue may cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, which may be fatal.

Hemodialysis and continuous ambulatory peritoneal dialysis do not remove significant amounts of Gastro-Timelets.

11 DESCRIPTION

Gastro-Timelets hydrochloride, USP, the active ingredient of Gastro-Timelets tablets, is a dopamine-2 receptor antagonist. Gastro-Timelets hydrochloride (metoclopramide monohydrochloride monohydrate) is a white or practically white, crystalline, odorless or practically odorless powder. It is very soluble in water, freely soluble in alcohol, sparingly soluble in chloroform and practically insoluble in ether. Chemically, it is 4-amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxy benzamide monohydrochloride monohydrate. Its structural formula is as follows:

C14H22ClN3O2-HCl-H2O M.W. 354.3

Gastro-Timelets tablets are for oral administration. Gastro-Timelets tablets are available in 5 mg and 10 mg tablets.

  • Each Gastro-Timelets tablet, 5 mg contains 5 mg Gastro-Timelets (equivalent to 5.91 mg of Gastro-Timelets hydrochloride, USP).
  • Each Gastro-Timelets tablet, 10 mg contains 10 mg Gastro-Timelets (equivalent to 11.82 mg of Gastro-Timelets hydrochloride, USP).

Inactive Ingredients

Corn starch, dibasic calcium phosphate, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate.

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12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Gastro-Timelets stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary, or pancreatic secretions. The exact mechanism of action of Gastro-Timelets in the treatment of gastroesophageal reflux and acute and recurrent diabetic gastroparesis has not been fully established. It seems to sensitize tissues to the action of acetylcholine. The effect of Gastro-Timelets on motility is not dependent on intact vagal innervation, but it can be abolished by anticholinergic drugs.

Gastro-Timelets increases the tone and amplitude of gastric contractions, relaxes the pyloric sphincter and the duodenal bulb, and increases peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit. It increases the resting tone of the lower esophageal sphincter. It has little, if any, effect on the motility of the colon or gallbladder.

12.2 Pharmacodynamics

Gastroesophageal Reflux

In patients with gastroesophageal reflux and low lower esophageal sphincter pressure (LESP), single oral doses of Gastro-Timelets produced dose-related increases in LESP. Effects began at about 5 mg and increased through 20 mg. The increase in LESP from a 5 mg dose lasted about 45 minutes and that of 20 mg lasted between 2 and 3 hours. Increased rate of stomach emptying was observed with single oral doses of 10 mg.

12.3 Pharmacokinetics

Absorption

Relative to an intravenous dose of 20 mg, the absolute bioavailability of oral Gastro-Timelets is 80% ± 15.5% as demonstrated in a crossover study of 18 subjects. Peak plasma concentrations occurred at about 1 to 2 hours after a single oral dose. Similar time to peak was observed after individual doses at steady state.

In a single dose study of 12 subjects, the area under the drug concentration-time curve increased linearly with doses from 20 to 100 mg (5 times the maximum recommended single dose). Peak concentrations increased linearly with dose; time to peak concentrations remained the same; whole body clearance was unchanged; and the elimination rate remained the same. The mean elimination half-life in subjects with normal renal function was 5 to 6 hours. Linear kinetic processes adequately describe the absorption and elimination of Gastro-Timelets.

Distribution

Gastro-Timelets is not extensively bound to plasma proteins (about 30%). The whole body volume of distribution is high (about 3.5 L/kg), which suggests extensive distribution of drug to the tissues.

Elimination

Metabolism: Gastro-Timelets undergoes enzymatic metabolism via oxidation as well as glucuronide and sulfate conjugation reactions in the liver. Monodeethylmetoclopramide, a major oxidative metabolite, is formed primarily by CYP2D6, an enzyme subject to genetic variability [see Dosage and Administration (2.2, 2.3), Use in Specific Populations (8.9)].

Excretion: Approximately 85% of the radioactivity of an orally administered dose appeared in the urine within 72 hours. After oral administration of 10 or 20 mg, a mean of 18% and 22% of the dose, respectively, was recovered as free Gastro-Timelets in urine within 36 hours.

Specific Populations

Patients with Renal Impairment: In a study of 24 patients with varying degrees of renal impairment (moderate, severe, and end-stage renal disease (ESRD) requiring dialysis), the systemic exposure (AUC) of Gastro-Timelets in patients with moderate to severe renal impairment was about 2-fold the AUC in subjects with normal renal function. The AUC of Gastro-Timelets in patients with ESRD on dialysis was about 3.5-fold the AUC in subjects with normal renal function [see Dosage and Administration (2.2, 2.3) and Use in Specific Populations (8.6)].

Patients with Hepatic Impairment: In a group of 8 patients with severe hepatic impairment (Child-Pugh C), the average Gastro-Timelets clearance was reduced by approximately 50% compared to patients with normal hepatic function [see Dosage and Administration (2.2, 2.3) and Use in Specific Populations (8.7)].

Drug Interaction Studies

Effect of Gastro-Timelets on CYP2D6 Substrates

Although in vitro studies suggest that Gastro-Timelets can inhibit CYP2D6, Gastro-Timelets is unlikely to interact with CYP2D6 substrates in vivo at therapeutically relevant concentrations.

Effect of CYP2D6 Inhibitors on Gastro-Timelets

In healthy subjects, 20 mg of Gastro-Timelets and 60 mg of fluoxetine (a strong CYP2D6 inhibitor) were administered, following prior exposure to 60 mg fluoxetine orally for 8 days. The patients who received concomitant Gastro-Timelets and fluoxetine had a 40% and 90% increase in Gastro-Timelets Cmax and AUC0-∞, respectively, compared to patients who received Gastro-Timelets alone [see Drug Interactions (7.1)].


Parameter


Gastro-Timelets alone

(mean SD)


Gastro-Timelets with fluoxetine

(mean SD)


Cmax (ng/mL)


44 ± 15


62.7 ± 9.2


AUC0-∞ (ng∙h/mL)


313 ± 113


591 ± 140


t1/2 (h)


5.5 ± 1.1


8.5 ± 2.2

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

A 77-week study was conducted in rats with oral Gastro-Timelets doses up to 40 mg/kg/day (about six times the maximum recommended human dose on body surface area basis). Gastro-Timelets elevated prolactin levels and the elevation persisted during chronic administration. An increase in mammary neoplasms was found in rodents after chronic administration of Gastro-Timelets [see Warnings and Precautions (5.7)]. In a rat model for assessing the tumor promotion potential, a 2-week oral treatment with Gastro-Timelets at a dose of 260 mg/kg/day (about 35 times the maximum recommended human dose based on body surface area) enhanced the tumorigenic effect of N-nitrosodiethylamine.

Mutagenesis

Gastro-Timelets was positive in the in vitro Chinese hamster lung cell/HGPRT forward mutation assay for mutagenic effects and in the in vitro human lymphocyte chromosome aberration assay for clastogenic effects. It was negative in the in vitro Ames mutation assay, the in vitro unscheduled DNA synthesis assay with rat and human hepatocytes, and the in vivo rat micronucleus assay.

Impairment of Fertility

Gastro-Timelets at intramuscular doses up to 20 mg/kg/day (about three times the maximum recommended human dose based on body surface area) was found to have no effect on fertility and reproductive performance of male and female rats.

16 HOW SUPPLIED/STORAGE AND HANDLING

Each white, round, unscored, debossed “TV” on one side and “2204” on the other side, compressed Gastro-Timelets tablet, USP contains Gastro-Timelets hydrochloride, USP equivalent to 5 mg Gastro-Timelets. Available in bottles of 100 (NDC 0093-2204-01) and 500 (NDC 0093-2204-05).

Each white, round, scored, debossed “TEVA” on one side and “2203” above the score on the other side, compressed Gastro-Timelets tablet, USP contains Gastro-Timelets hydrochloride, USP equivalent to 10 mg Gastro-Timelets. Available in bottles of 100 (NDC 0093-2203-01), 500 (NDC 0093-2203-05), and 1000 (NDC 0093-2203-10).

Dispense in a tight, light-resistant container. Store tablets at 20° to 25°C (68° to 77°F).

This product is light sensitive. It should be inspected before use and discarded if either color or particulate is observed.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Inform patients or their caregivers that Gastro-Timelets can cause serious adverse reactions. Instruct patients to discontinue Gastro-Timelets and contact a healthcare provider immediately if the following serious reactions occur:

  • Tardive dyskinesia and other extrapyramidal reactions [see Warnings and Precautions (5.1, 5.2)]
  • Neuroleptic malignant syndrome [see Warnings and Precautions (5.3)]
  • Depression and/or possible suicidal ideation [see Warnings and Precautions (5.4)]

Inform patients or their caregivers that concomitant treatment with numerous other medications can precipitate or worsen serious adverse reactions such as tardive dyskinesia or other extrapyramidal reactions, neuroleptic malignant syndrome, and CNS depression [see Drug Interactions (7.1, 7.2)]. Explain that the prescriber of any other medication must be made aware that the patient is taking Gastro-Timelets.

Inform patients or their caregivers that Gastro-Timelets can cause drowsiness or dizziness, or otherwise impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving a motor vehicle [see Warnings and Precautions (5.8)].

Manufactured In Croatia By:

Pliva Hrvatska d.o.o.

Zagreb, Croatia

Manufactured For:

Teva Pharmaceuticals USA, Inc.

North Wales, PA 19454

Rev. Q 8/2017


MEDICATION GUIDE

Gastro-Timelets TABLETS, USP

(MET-oh-KLOE-pra-mide), oral use


Read this Medication Guide before you start taking Gastro-Timelets tablets and each time you get a refill. There may be new information. If you take another product that contains Gastro-Timelets (such as Gastro-Timelets injection, Gastro-Timelets orally disintegrating tablets, or Gastro-Timelets oral solution), you should read the Medication Guide that comes with that product. Some of the information may be different. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.


What is the most important information I should know about Gastro-Timelets tablets?

Gastro-Timelets tablets can cause serious side effects, including:

Tardive dyskinesia (abnormal muscle movements). These movements happen mostly in the face muscles. You cannot control these movements. They may not go away even after stopping Gastro-Timelets tablets. There is no treatment for tardive dyskinesia, but symptoms may decrease or go away over time after you stop taking Gastro-Timelets tablets.

Your chances for getting tardive dyskinesia increase:

  • the longer you take Gastro-Timelets tablets and the more Gastro-Timelets tablets you take. You should not take Gastro-Timelets tablets for more than 12 weeks.
  • if you are older, especially if you are an older woman.
  • if you have diabetes.

It is not possible for your healthcare provider to know if you will get tardive dyskinesia if you take Gastro-Timelets tablets.

Call your healthcare provider right away if you get movements you cannot stop or control, such as:

  • lip smacking, chewing, or puckering up your mouth
  • frowning or scowling
  • sticking out your tongue
  • blinking and moving your eyes
  • shaking of your arms and legs

See the section “What are the possible side effects of Gastro-Timelets tablets?” for more information about side effects.


What are Gastro-Timelets tablets?

Gastro-Timelets tablets are a prescription medicine used in adults:

  • for 4 to 12 weeks to relieve heartburn symptoms with gastroesophageal reflux when certain other treatments do not work.
  • to relieve the symptoms of slow stomach emptying in people with diabetes.

Gastro-Timelets tablets are not recommended for use in children.


Do not take Gastro-Timelets tablets if you:

  • have a history of tardive dyskinesia or have a problem controlling your muscles and movements after taking Gastro-Timelets tablets or a medicine that works like Gastro-Timelets tablets.
  • have stomach or intestine problems that could get worse with Gastro-Timelets tablets, such as bleeding, blockage or a tear in the stomach or bowel wall.
  • have a type of tumor that can cause high blood pressure such as pheochromocytoma.
  • have epilepsy (seizures). Gastro-Timelets tablets can increase your chance for seizures and make them worse.
  • are allergic to Gastro-Timelets. Gastro-Timelets tablets can cause serious allergic reactions. Stop taking Gastro-Timelets tablets right away and get emergency help if you have any of these symptoms:
    • swelling of your tongue, throat, lips, eyes or face.
    • trouble swallowing or breathing.
    • skin rash, hives, sores in your mouth, or skin blisters.

Before taking Gastro-Timelets tablets, tell your healthcare provider about all of your medical conditions, including if you:

  • have diabetes. Your dose of insulin may need to be changed.
  • had problems controlling your muscle movements after taking any medicine.
  • have Parkinson’s disease.
  • have a type of tumor that can cause high blood pressure (pheochromoctyoma).
  • have kidney or liver disease.
  • have or had depression or mental illness.
  • have high blood pressure.
  • have heart failure or heart rhythm problems.
  • have breast cancer.
  • drink alcohol.
  • have seizures
  • are pregnant or plan to become pregnant. Gastro-Timelets tablets may harm your unborn baby if taken during the end of pregnancy. Talk to your healthcare provider if you become pregnant while taking Gastro-Timelets tablets.
  • are breastfeeding or plan to breastfeed. Gastro-Timelets can pass into your breast milk and may harm your baby. You and your healthcare provider should decide if you will take Gastro-Timelets tablets or breastfeed.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Gastro-Timelets tablets may affect the way other medicines work, and other medicines may affect how Gastro-Timelets tablets work.

Tell your healthcare provider before you start or stop other medicines.

Especially tell your healthcare provider if you take:

  • another medicine that contains Gastro-Timelets, such as Gastro-Timelets injection or Gastro-Timelets oral solution
  • a medicine for Parkinson’s disease
  • a blood pressure medicine
  • a medicine for depression, especially a Monoamine Oxidase Inhibitor (MAOI)
  • an anti-psychotic medicine, used to treat mental illness such as schizophrenia
  • insulin
  • medicines that can make you sleepy, such as anti-anxiety medicines, sleep medicines, and narcotics

If you are not sure if your medicine is one listed above, ask your healthcare provider or pharmacist.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.


How should I take Gastro-Timelets tablets?

  • Take Gastro-Timelets tablets exactly as your healthcare provider tells you. Do not change your dose unless your healthcare provider tells you to.
  • Gastro-Timelets comes as a tablet you take by mouth.
  • You should not take Gastro-Timelets tablets for more than 12 weeks.
  • Take Gastro-Timelets tablets at least 30 minutes before each meal and at bedtime.
  • If you take too many Gastro-Timelets tablets, call your poison control center at 1-800-222-1222 or go to the nearest emergency room right away.

What should I avoid while taking Gastro-Timelets tablets?

  • Do not drink alcohol while taking Gastro-Timelets tablets. Alcohol may make some side effects of Gastro-Timelets tablets worse, such as feeling sleepy.
  • Do not drive, operate machinery, or do other dangerous activities until you know how Gastro-Timelets tablets affect you. Gastro-Timelets tablets may cause sleepiness or dizziness.

What are the possible side effects of Gastro-Timelets tablets?

  • Tardive dyskinesia (abnormal muscle movements). See “What is the most important information I need to know about Gastro-Timelets tablets?
  • Other changes in muscle control and movement, such as:
    • Uncontrolled spasms of your face and neck muscles, or muscles of your body, arms, and legs (dystonia). These muscle spasms can cause abnormal movements and body positions, and speech problems. These spasms usually start within the first 2 days of treatment. Rarely, these muscle spasms may cause trouble breathing. These spasms happen more often in adults less than 30 years of age.
    • Parkinsonism. Symptoms include slight shaking, body stiffness, trouble moving or keeping your balance. If you already have Parkinson's Disease, your symptoms may become worse while you are taking Gastro-Timelets tablets.
    • Being unable to sit still or feeling you need to move your hands, feet, or body (akathisia). Symptoms can include feeling jittery, anxious, irritated or unable to sleep (insomnia), feeling the need to walk around (pacing) and tapping your feet.
  • Neuroleptic Malignant Syndrome (NMS). NMS is a very rare but very serious condition that can happen with Gastro-Timelets tablets. NMS can cause death and must be treated in a hospital. Symptoms of NMS include: high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating.
  • Depression, thoughts about suicide, and suicide. Some people who take Gastro-Timelets tablets become depressed, even if they have no history of depression. You may have thoughts about hurting or killing yourself. Some people who have taken Gastro-Timelets tablets have ended their own lives (suicide).
  • High blood pressure. Gastro-Timelets tablets can cause your blood pressure to increase.
  • Too much body water. People who have certain liver problems or heart failure and take Gastro-Timelets tablets may hold too much water in their body (fluid retention). Tell your doctor right away if you have sudden weight gain, or swelling of your hands, legs, or feet.
  • Increased prolactin. Tell your doctor if your menstrual periods stop, your breasts get larger and make milk, or you cannot have sex (impotence). These symptoms go away when you stop taking Gastro-Timelets tablets.

Call your healthcare provider and get medical help right away if you:

  • feel depressed or have thoughts about hurting or killing yourself
  • have high fever, stiff muscles, problems thinking, very fast or uneven heartbeat, and increased sweating
  • have muscle movements you cannot stop or control
  • have muscle movements that are new or unusual

The most common side effects of Gastro-Timelets tablets include:

  • restlessness
  • drowsiness
  • tiredness
  • lack of energy

You may have more side effects the longer you take Gastro-Timelets tablets and the more Gastro-Timelets tablets you take.

You may still have side effects after stopping Gastro-Timelets tablets. You may have symptoms from stopping Gastro-Timelets tablets such as headaches, and feeling dizzy or nervous.

Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all the possible side effects of Gastro-Timelets tablets. 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 Gastro-Timelets tablets?

  • Store Gastro-Timelets tablets at room temperature between 68°F to 77°F (20°C to 25°C).
  • Keep Gastro-Timelets tablets in the bottle it comes in and away from light. Keep the bottle closed tightly.

Keep Gastro-Timelets tablets and all medicines out of the reach of children.


General information about the safe and effective use of Gastro-Timelets tablets.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Gastro-Timelets tablets for a condition for which they were not prescribed. Do not give Gastro-Timelets tablets to other people, even if they have the same symptoms that you have. They may harm them.

You can ask your pharmacist or healthcare provider for information about Gastro-Timelets tablets that is written for health professionals. For more information, call 1-888-838-2872.


What are the ingredients in Gastro-Timelets tablets, USP?

Active ingredient: Gastro-Timelets hydrochloride, USP

Inactive ingredients: corn starch, dibasic calcium phosphate, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate


This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured In Croatia By:

Pliva Hrvatska d.o.o.

Zagreb, Croatia

Manufactured For:

Teva Pharmaceuticals USA, Inc.

North Wales, PA 19454

Rev. D 8/2017

NDC 0093-2204-01

Gastro-Timelets

Tablets, USP

5mg

PHARMACIST: Dispense the accompanying

Medication Guide to each patient.

Rx only

100 TABLETS

TEVA

NDC 0093-2203-01

Gastro-Timelets

Tablets, USP

10 mg

PHARMACIST: Dispense the accompanying

Medication Guide to each patient.

Rx only

100 TABLETS

TEVA

Gastro-Timelets pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Gastro-Timelets available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Gastro-Timelets destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Gastro-Timelets Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Gastro-Timelets pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."ANTIEMETIC GASTROKINETIC PILERAN (METOCLOPRAMIDE HYDROCHLORIDE) SOLUTION [HOLLIDAY-SCOTT S.A.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. "metoclopramide". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).
  3. "metoclopramide". http://www.drugbank.ca/drugs/DB0123... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Gastro-Timelets?

Depending on the reaction of the Gastro-Timelets after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Gastro-Timelets 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 Gastro-Timelets 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.

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Review

sdrugs.com conducted a study on Gastro-Timelets, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Gastro-Timelets consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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