Migrane-Neuridal

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Migrane-Neuridal uses

Migrane-Neuridal consists of Acetaminophen, Metoclopramide Hydrochloride.

Acetaminophen:


Pharmacological action

Migrane-Neuridal is an analgesic-antipyretic. It has analgesic, antipyretic and weak anti-inflammatory action. The mechanism of action is associated with inhibition of prostaglandin synthesis, the predominant influence on the thermoregulation center in the hypothalamus, enhances heat transfer.

Why is Migrane-Neuridal (Acetaminophen) prescribed?

Pain weak and moderate intensity of different genesis (including headache, migraine, toothache, neuralgia, myalgia, algomenorrhea; pain in trauma, burns). Fever in infectious and inflammatory diseases.

Migrane-Neuridal dosage and administration

Oral or rectally adults and adolescents with a body weight over 60 kg is used in a single dose of 500 mg, the multiplicity of admission - up to 4 times / Maximum duration of treatment - 5-7 days.

Maximum dose: single - 1 g, daily - 4 g.

Single dose for oral administration for children aged 6-12 years - 250-500 mg, 1-5 years - 120-250 mg, from 3 months to 1 year - 60-120 mg, up to 3 months - 10 mg / kg. Single dose rectal in children aged 6-12 years - 250-500 mg, 1-5 years - 125-250 mg.

Multiplicity - 4 at intervals of not less than 4 h. The maximum duration of treatment - 3 days.

Maximum dose: 4 single dose per day.

Migrane-Neuridal side effects, adverse reactions

Digestive system: rarely - dyspepsia; long-term use at high doses - hepatotoxic effects, methemoglobinemia, renal dysfunction and liver, hypochromic anemia. Hemopoietic system: rarely - thrombocytopenia, leukopenia, pancytopenia, neutropenia, agranulocytosis. Allergic reactions: rarely - skin rash, itching, hives.

Contraindications

Chronic active alcoholism, increased sensitivity to Migrane-Neuridal, marked disturbances of liver function and / or kidney disease, anemia, pregnancy (I term).

Using during pregnancy and breastfeeding

Migrane-Neuridal (Acetaminophen) crosses the placental barrier. So far, no observed adverse effects of Migrane-Neuridal (Acetaminophen) on the fetus in humans.

Migrane-Neuridal (Acetaminophen) is excreted in breast milk: the content in milk was 0.04-0.23% of the dose adopted mother.

If necessary, use of Migrane-Neuridal (Acetaminophen) during pregnancy and lactation (breastfeeding) should carefully weigh the potential benefits of therapy for the mother and the potential risk to the fetus or child.

In experimental studies found no embryotoxic, teratogenic and mutagenic action of Migrane-Neuridal (Acetaminophen).

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Special Instructions

Migrane-Neuridal is used with caution in patients with disorders of the liver and kidneys, with benign hyperbilirubinemia, as well as in elderly patients.

With prolonged use of Migrane-Neuridal (Acetaminophen) is necessary to monitor patterns of peripheral blood and functional state of the liver.

Used for treatment of premenstrual tension syndrome in combination with pamabrom (diuretic, a derivative of xanthine) and mepyramine (Histamine H1-receptors blocker).

Migrane-Neuridal (Acetaminophen) Drug Interactions

With the simultaneous use with inducers of microsomal liver enzymes, means having hepatotoxic effect, increasing the risk of hepatotoxic action of Migrane-Neuridal (Acetaminophen).

With the simultaneous use of anticoagulants may be slight to moderate increase in prothrombin time.

With the simultaneous use of anticholinergics may decrease absorption of Migrane-Neuridal (Acetaminophen).

With the simultaneous use of oral contraceptives accelerated excretion of Migrane-Neuridal (Acetaminophen) from the body and may reduce its analgesic action.

With the simultaneous use with urological means reduced their effectiveness.

With the simultaneous use of activated charcoal reduced bioavailability of Migrane-Neuridal (Acetaminophen).

When Migrane-Neuridal (Acetaminophen) applied simultaneously with diazepam may decrease excretion of diazepam.

There have been reports about the possibility of enhancing mielodepression effect of zidovudine while applying with Migrane-Neuridal (Acetaminophen). A case of severe toxic liver injury.

Described cases of toxic effects of Migrane-Neuridal (Acetaminophen), while the use of isoniazid.

When applied simultaneously with carbamazepine, phenytoin, phenobarbital, primidonom decreases the effectiveness of Migrane-Neuridal (Acetaminophen), which is caused by an increase in its metabolism and excretion from the body. Cases of hepatotoxicity, while the use of Migrane-Neuridal (Acetaminophen) and phenobarbital.

In applying cholestyramine a period of less than 1 h after administration of Migrane-Neuridal (Acetaminophen) may decrease of its absorption.

At simultaneous application with lamotrigine moderately increased excretion of lamotrigine from the body.

With the simultaneous use of metoclopramide may increase absorption of Migrane-Neuridal (Acetaminophen) and its increased concentration in blood plasma.

When applied simultaneously with probenecid may decrease clearance of Migrane-Neuridal (Acetaminophen), with rifampicin, sulfinpyrazone - may increase clearance of Migrane-Neuridal (Acetaminophen) due to increasing its metabolism in the liver.

At simultaneous application of Migrane-Neuridal (Acetaminophen) with ethinylestradiol increases absorption of Migrane-Neuridal (Acetaminophen) from the gut.

Enhances the effect of indirect anticoagulants (coumarin derivatives and indandione). Antipyretic and analgesic activity of caffeine increases, reduce - rifampicin, phenobarbital and alcohol (accelerated biotransformation, inducing microsomal liver enzymes).

Migrane-Neuridal in case of emergency / overdose

At a reception in toxic doses (10-15 g in adults) may develop liver necrosis.

Symptoms of overdose may include: nausea, vomiting, loss of appetite, sweating, extreme tiredness, unusual bleeding or bruising, pain in the upper right part of the stomach, yellowing of the skin or eyes, flu-like symptoms

Metoclopramide Hydrochloride:


1 INDICATIONS AND USAGE

Migrane-Neuridal (Metoclopramide Hydrochloride) 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:

Migrane-Neuridal (Metoclopramide Hydrochloride) 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 ) ].

Migrane-Neuridal (Metoclopramide Hydrochloride) 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:

Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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

Migrane-Neuridal 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 (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.

Intermittent Dosing

If symptoms only occur intermittently or at specific times of the day, administer Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride); 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) tablets, consider starting therapy with Migrane-Neuridal (Metoclopramide Hydrochloride) injection given intramuscularly or intravenously for up to 10 days injection). After patients are able to take oral therapy, switch to Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride); 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 Migrane-Neuridal (Metoclopramide Hydrochloride): white, round, unscored, debossed “TV” on one side and “2204” on the other side.
  • 10 mg Migrane-Neuridal (Metoclopramide Hydrochloride): white, round, scored, debossed “TEVA” on one side and “2203” above the score on the other side.

Tablets: 5 mg and 10 mg Migrane-Neuridal (Metoclopramide Hydrochloride) (3)

4 CONTRAINDICATIONS

Migrane-Neuridal (Metoclopramide Hydrochloride) is contraindicated:

  • In patients with a history of tardive dyskinesia (TD) or a dystonic reaction to Migrane-Neuridal (Metoclopramide Hydrochloride) [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. Migrane-Neuridal (Metoclopramide Hydrochloride) 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. Migrane-Neuridal (Metoclopramide Hydrochloride) may increase the frequency and severity of seizures [see Adverse Reactions (6)].
  • In patients with hypersensitivity to Migrane-Neuridal (Metoclopramide Hydrochloride). Reactions have included laryngeal and glossal angioedema and bronchospasm [see Adverse Reactions (6)].
  • History of TD or dystonic reaction to Migrane-Neuridal (Metoclopramide Hydrochloride) (4)
  • When stimulation of gastrointestinal motility might be dangerous (4)
  • Pheochromocytoma, catecholamine-releasing paragangliomas (4)
  • Epilepsy (4)
  • Hypersensitivity to Migrane-Neuridal (Metoclopramide Hydrochloride) (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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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

Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) for longer than 12 weeks and reduce the dosage in elderly patients [see Dosage and Administration (2.2, 2.3)].

Discontinue Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) is withdrawn.

Migrane-Neuridal (Metoclopramide Hydrochloride) 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. Migrane-Neuridal (Metoclopramide Hydrochloride) is contraindicated in patients with a history of TD [see Contraindications (4)]. Avoid Migrane-Neuridal (Metoclopramide Hydrochloride) in patients receiving other drugs that are likely to cause TD (e.g., antipsychotics).

5.2 Other Extrapyramidal Symptoms

In addition to TD, Migrane-Neuridal may cause other extrapyramidal symptoms (EPS), parkinsonian symptoms, and motor restlessness. Advise patients to seek immediate medical attention if such symptoms occur and to discontinue Migrane-Neuridal (Metoclopramide Hydrochloride).

  • Extrapyramidal symptoms (EPS), such as acute dystonic reactions, occurred in patients treated with Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride). 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride), more commonly within the first 6 months, but also after longer periods. Symptoms generally have subsided within 2 to 3 months after discontinuation of Migrane-Neuridal (Metoclopramide Hydrochloride). Avoid Migrane-Neuridal (Metoclopramide Hydrochloride) in patients with Parkinson’s disease and other patients being treated with antiparkinsonian drugs due to potential exacerbation of symptoms. Avoid treatment with Migrane-Neuridal (Metoclopramide Hydrochloride) 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

Migrane-Neuridal (Metoclopramide Hydrochloride) may cause a potentially fatal symptom complex called neuroleptic malignant syndrome (NMS). NMS has been reported in association with Migrane-Neuridal (Metoclopramide Hydrochloride) overdosage and concomitant treatment with another drug associated with NMS. Avoid Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal use in patients with a history of depression.

5.5 Hypertension

Migrane-Neuridal (Metoclopramide Hydrochloride) may elevate blood pressure. In one study in hypertensive patients, intravenously administered Migrane-Neuridal (Metoclopramide Hydrochloride) was shown to release catecholamines; hence, avoid use in patients with hypertension or in patients taking monoamine oxidase inhibitors [see Drug Interactions (7.1)].

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

5.6 Fluid Retention

Because Migrane-Neuridal 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 Migrane-Neuridal (Metoclopramide Hydrochloride) if any of these adverse reactions occur.

5.7 Hyperprolactinemia

As with other dopamine D2 receptor antagonists, Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride).

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 ( 13.1 ) ].

5.8 Effects of the Ability to Drive and Operate Machinery

Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride). 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 Migrane-Neuridal (Metoclopramide Hydrochloride) four times daily) were restlessness, drowsiness, fatigue, and lassitude. In general, the incidence of adverse reactions correlated with the dosage and duration of Migrane-Neuridal (Metoclopramide Hydrochloride) administration.

Adverse reactions, especially those involving the nervous system, occurred after stopping Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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.

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 Migrane-Neuridal (Metoclopramide Hydrochloride)

Table 3 displays the effects of other drugs on Migrane-Neuridal (Metoclopramide Hydrochloride).


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 Migrane-Neuridal (Metoclopramide Hydrochloride); risk of exacerbation of extrapyramidal symptoms [see Clinical Pharmacology (12.3)].


Intervention


Reduce the Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride).


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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal on Other Drugs

Table 4 displays the effects of Migrane-Neuridal (Metoclopramide Hydrochloride) on other drugs.


Dopaminergic Agonists and Drugs Increasing Dopamine Concentrations


Clinical Impact


Opposing effects of Migrane-Neuridal (Metoclopramide Hydrochloride) 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


Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) on other drugs is variable. Increased gastrointestinal (GI) motility by Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal during pregnancy.

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

Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) were observed.

8.2 Lactation

Risk Summary

Limited published data report the presence of Migrane-Neuridal (Metoclopramide Hydrochloride) in human milk in variable amounts. Breastfed infants exposed to Migrane-Neuridal (Metoclopramide Hydrochloride) have experienced gastrointestinal adverse reactions, including intestinal discomfort and increased intestinal gas formation [see Data]. Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) and any potential adverse effects on the breastfed child from Migrane-Neuridal (Metoclopramide Hydrochloride) or from the underlying maternal condition.

Clinical Considerations

Monitor breastfeeding neonates because Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) received by the breastfed infant was less than 10% of the maternal weight-adjusted dose. In one study, the estimated daily amount of Migrane-Neuridal (Metoclopramide Hydrochloride) 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

Migrane-Neuridal is 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. The safety and effectiveness of Migrane-Neuridal (Metoclopramide Hydrochloride) in pediatric patients have not been established.

Dystonias and other extrapyramidal symptoms associated with Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) use in neonates [see Use in Specific Populations (8.8)].

8.5 Geriatric Use

Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride); therefore, consider a reduced dosage of Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal 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 Migrane-Neuridal (Metoclopramide Hydrochloride) dosage in patients with moderate and severe renal impairment (creatinine clearance less than or equal to 60 mL/minute), 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 Migrane-Neuridal (Metoclopramide Hydrochloride) clearance (by approximately 50%) compared to patients with normal hepatic function. The resulting increase in Migrane-Neuridal (Metoclopramide Hydrochloride) blood concentrations increases the risk of adverse reactions. There is no pharmacokinetic data in patients with moderate hepatic impairment (Child-Pugh B). Reduce Migrane-Neuridal (Metoclopramide Hydrochloride) 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, Migrane-Neuridal (Metoclopramide Hydrochloride), 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

Migrane-Neuridal (Metoclopramide Hydrochloride) is a substrate of CYP2D6. The elimination of Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) [see Clinical Pharmacology (12.3)]. Reduce the Migrane-Neuridal (Metoclopramide Hydrochloride) dosage in patients who are poor CYP2D6 metabolizers [see Dosage and Administration (2.2, 2.3)].

10 OVERDOSAGE

Manifestations of Migrane-Neuridal (Metoclopramide Hydrochloride) overdosage included drowsiness, disorientation, extrapyramidal reactions, other adverse reactions associated with Migrane-Neuridal (Metoclopramide Hydrochloride) use (including, e.g., methemoglobinemia), and sometimes death. Neuroleptic malignant syndrome (NMS) has been reported in association with Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride).

11 DESCRIPTION

Migrane-Neuridal (Metoclopramide Hydrochloride) hydrochloride, USP, the active ingredient of Migrane-Neuridal (Metoclopramide Hydrochloride) tablets, is a dopamine-2 receptor antagonist. Migrane-Neuridal (Metoclopramide Hydrochloride) 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

Migrane-Neuridal (Metoclopramide Hydrochloride) tablets are for oral administration. Migrane-Neuridal (Metoclopramide Hydrochloride) tablets are available in 5 mg and 10 mg tablets.

  • Each Migrane-Neuridal (Metoclopramide Hydrochloride) tablet, 5 mg contains 5 mg Migrane-Neuridal (Metoclopramide Hydrochloride) (equivalent to 5.91 mg of Migrane-Neuridal (Metoclopramide Hydrochloride) hydrochloride, USP).
  • Each Migrane-Neuridal (Metoclopramide Hydrochloride) tablet, 10 mg contains 10 mg Migrane-Neuridal (Metoclopramide Hydrochloride) (equivalent to 11.82 mg of Migrane-Neuridal (Metoclopramide Hydrochloride) 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

Migrane-Neuridal stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary, or pancreatic secretions. The exact mechanism of action of Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) on motility is not dependent on intact vagal innervation, but it can be abolished by anticholinergic drugs.

Migrane-Neuridal (Metoclopramide Hydrochloride) increases the tone and amplitude of gastric (especially antral) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride).

Distribution

Migrane-Neuridal (Metoclopramide Hydrochloride) 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: Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) in patients with moderate to severe renal impairment was about 2-fold the AUC in subjects with normal renal function. The AUC of Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) on CYP2D6 Substrates

Although in vitro studies suggest that Migrane-Neuridal (Metoclopramide Hydrochloride) can inhibit CYP2D6, Migrane-Neuridal (Metoclopramide Hydrochloride) is unlikely to interact with CYP2D6 substrates in vivo at therapeutically relevant concentrations.

Effect of CYP2D6 Inhibitors on Migrane-Neuridal (Metoclopramide Hydrochloride)

In healthy subjects, 20 mg of Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) and fluoxetine had a 40% and 90% increase in Migrane-Neuridal (Metoclopramide Hydrochloride) Cmax and AUC0-∞, respectively, compared to patients who received Migrane-Neuridal (Metoclopramide Hydrochloride) alone [see Drug Interactions (7.1)].


Parameter


Migrane-Neuridal (Metoclopramide Hydrochloride) alone

(mean SD)


Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) doses up to 40 mg/kg/day (about six times the maximum recommended human dose on body surface area basis). Migrane-Neuridal (Metoclopramide Hydrochloride) elevated prolactin levels and the elevation persisted during chronic administration. An increase in mammary neoplasms was found in rodents after chronic administration of Migrane-Neuridal (Metoclopramide Hydrochloride) [see Warnings and Precautions (5.7)]. In a rat model for assessing the tumor promotion potential, a 2-week oral treatment with Migrane-Neuridal (Metoclopramide Hydrochloride) 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

Migrane-Neuridal (Metoclopramide Hydrochloride) 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

Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) tablet, USP contains Migrane-Neuridal (Metoclopramide Hydrochloride) hydrochloride, USP equivalent to 5 mg Migrane-Neuridal (Metoclopramide Hydrochloride). 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 Migrane-Neuridal (Metoclopramide Hydrochloride) tablet, USP contains Migrane-Neuridal (Metoclopramide Hydrochloride) hydrochloride, USP equivalent to 10 mg Migrane-Neuridal (Metoclopramide Hydrochloride). 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 Migrane-Neuridal (Metoclopramide Hydrochloride) can cause serious adverse reactions. Instruct patients to discontinue Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride).

Inform patients or their caregivers that Migrane-Neuridal (Metoclopramide Hydrochloride) 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

Migrane-Neuridal (Metoclopramide Hydrochloride) TABLETS, USP

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


Read this Medication Guide before you start taking Migrane-Neuridal (Metoclopramide Hydrochloride) tablets and each time you get a refill. There may be new information. If you take another product that contains Migrane-Neuridal (Metoclopramide Hydrochloride) (such as Migrane-Neuridal (Metoclopramide Hydrochloride) injection, Migrane-Neuridal (Metoclopramide Hydrochloride) orally disintegrating tablets, or Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) tablets?

Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) tablets. There is no treatment for tardive dyskinesia, but symptoms may decrease or go away over time after you stop taking Migrane-Neuridal (Metoclopramide Hydrochloride) tablets.

Your chances for getting tardive dyskinesia increase:

  • the longer you take Migrane-Neuridal (Metoclopramide Hydrochloride) tablets and the more Migrane-Neuridal (Metoclopramide Hydrochloride) tablets you take. You should not take Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) tablets?” for more information about side effects.


What are Migrane-Neuridal (Metoclopramide Hydrochloride) tablets?

Migrane-Neuridal (Metoclopramide Hydrochloride) 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.

Migrane-Neuridal (Metoclopramide Hydrochloride) tablets are not recommended for use in children.


Do not take Migrane-Neuridal (Metoclopramide Hydrochloride) tablets if you:

  • have a history of tardive dyskinesia or have a problem controlling your muscles and movements after taking Migrane-Neuridal (Metoclopramide Hydrochloride) tablets or a medicine that works like Migrane-Neuridal (Metoclopramide Hydrochloride) tablets.
  • have stomach or intestine problems that could get worse with Migrane-Neuridal (Metoclopramide Hydrochloride) 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). Migrane-Neuridal (Metoclopramide Hydrochloride) tablets can increase your chance for seizures and make them worse.
  • are allergic to Migrane-Neuridal (Metoclopramide Hydrochloride). Migrane-Neuridal (Metoclopramide Hydrochloride) tablets can cause serious allergic reactions. Stop taking Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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. Migrane-Neuridal (Metoclopramide Hydrochloride) tablets may harm your unborn baby if taken during the end of pregnancy. Talk to your healthcare provider if you become pregnant while taking Migrane-Neuridal (Metoclopramide Hydrochloride) tablets.
  • are breastfeeding or plan to breastfeed. Migrane-Neuridal (Metoclopramide Hydrochloride) can pass into your breast milk and may harm your baby. You and your healthcare provider should decide if you will take Migrane-Neuridal (Metoclopramide Hydrochloride) tablets or breastfeed.

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

Migrane-Neuridal (Metoclopramide Hydrochloride) tablets may affect the way other medicines work, and other medicines may affect how Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride), such as Migrane-Neuridal (Metoclopramide Hydrochloride) injection or Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) tablets?

  • Take Migrane-Neuridal (Metoclopramide Hydrochloride) tablets exactly as your healthcare provider tells you. Do not change your dose unless your healthcare provider tells you to.
  • Migrane-Neuridal (Metoclopramide Hydrochloride) comes as a tablet you take by mouth.
  • You should not take Migrane-Neuridal (Metoclopramide Hydrochloride) tablets for more than 12 weeks.
  • Take Migrane-Neuridal (Metoclopramide Hydrochloride) tablets at least 30 minutes before each meal and at bedtime.
  • If you take too many Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) tablets?

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

What are the possible side effects of Migrane-Neuridal (Metoclopramide Hydrochloride) tablets?

  • Tardive dyskinesia (abnormal muscle movements). See “What is the most important information I need to know about Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) tablets have ended their own lives (suicide).
  • High blood pressure. Migrane-Neuridal (Metoclopramide Hydrochloride) tablets can cause your blood pressure to increase.
  • Too much body water. People who have certain liver problems or heart failure and take Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) tablets include:

  • restlessness
  • drowsiness
  • tiredness
  • lack of energy

You may have more side effects the longer you take Migrane-Neuridal (Metoclopramide Hydrochloride) tablets and the more Migrane-Neuridal (Metoclopramide Hydrochloride) tablets you take.

You may still have side effects after stopping Migrane-Neuridal (Metoclopramide Hydrochloride) tablets. You may have symptoms from stopping Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) tablets?

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

Keep Migrane-Neuridal (Metoclopramide Hydrochloride) tablets and all medicines out of the reach of children.


General information about the safe and effective use of Migrane-Neuridal (Metoclopramide Hydrochloride) tablets.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Migrane-Neuridal (Metoclopramide Hydrochloride) tablets for a condition for which they were not prescribed. Do not give Migrane-Neuridal (Metoclopramide Hydrochloride) 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 Migrane-Neuridal (Metoclopramide Hydrochloride) tablets that is written for health professionals. For more information, call 1-888-838-2872.


What are the ingredients in Migrane-Neuridal (Metoclopramide Hydrochloride) tablets, USP?

Active ingredient: Migrane-Neuridal (Metoclopramide Hydrochloride) 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

Migrane-Neuridal (Metoclopramide Hydrochloride)

Tablets, USP

5mg

PHARMACIST: Dispense the accompanying

Medication Guide to each patient.

Rx only

100 TABLETS

TEVA

NDC 0093-2203-01

Migrane-Neuridal (Metoclopramide Hydrochloride)

Tablets, USP

10 mg

PHARMACIST: Dispense the accompanying

Medication Guide to each patient.

Rx only

100 TABLETS

TEVA

Migrane-Neuridal 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.


Migrane-Neuridal 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.


Migrane-Neuridal 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.


Migrane-Neuridal 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.


Migrane-Neuridal 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. Dailymed."FEVERALL INFANTS (ACETAMINOPHEN) SUPPOSITORY [ACTAVIS MID ATLANTIC LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. Dailymed."ACETAMINOPHEN; ASPIRIN; CAFFEINE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Migrane-Neuridal?

Depending on the reaction of the Migrane-Neuridal after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Migrane-Neuridal 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 Migrane-Neuridal 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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The information was verified by Dr. Rachana Salvi, MD Pharmacology

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