Metozolv ODT

Black Box Warnings

May cause tardive dyskinesia (often irreversible)

Risk of developing tardive dyskinesia increases with treatment duration and total cumulative dose

Discontinue with signs or symptoms of tardive dyskinesia

No known treatment exists for tardive dyskinesia

Symptoms may lessen or resolve after metoclopramide treatment is stopped

Do not administer for longer than 12 weeks, except in rare cases where therapeutic benefit is thought to outweigh risk of tardive dyskinesia

Contraindications

Hypersensitivity to metoclopramide or procainamide

History of tardive dyskinesia (TD) or a dystonic reaction to metoclopramide

When stimulation of gastrointestinal motility might be dangerous (e.g., in the presence of gastrointestinal hemorrhage, mechanical obstruction, or perforation)

Presence of pheochromocytoma or other catecholamine-releasing paragangliomas

Patients with history of epilepsy

Other drugs causing extrapyramidal symptoms (eg, phenothiazines, butyrophenones)

Cautions

Mental depression reported; use with caution in patients with history of mental illness

Use with caution or avoid in parkinson disease patients; may have increased risk of extrapyramidal symptoms

Use with caution after GI anastomosis or closure; promotility agents reported to increase pressure in suture lines

Use caution in patients with hypertension, CHF, renal impairment, cirrhosis

Use caution in patients who are at risk of fluid overload

Can cause tardive dyskinesia (see Black Box Warnings), especially in elderly; discontinue if signs or symptoms of tardive dyskinesia develop (metoclopramide itself may completely or partially suppress these manifestations); tardive dyskinesia may persist even after drug is discontinued

Diphenhydramine 50 mg IM can be given for extrapyramidal symptoms

Pseudoparkisonism (eg, tremor, rigidity) may occur within 6 months of therapy; reversible within 2-3 months of discontinuing therapy

Metoclopramide IV administration associated with catecholamine release; use caution in patients with hypertension

Hypertensive crisis reported in patients with undiagnosed pheochromocytoma; discontinue therapy immediately with any sudden increase in blood pressure during therapy

May cause QT prolongation and torsades de pointes in some patients with heart failure patients that also have renal impairment; data on healthy males have failed to show similar effects; implicatiosn unclear; use caution in cardiovascular disease

Pregnancy

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 metoclopramide during pregnancy. There are potential risks to neonate following exposure in utero to metoclopramide during delivery; in animal reproduction studies, no adverse developmental effects were observed with oral administration of metoclopramide to pregnant rats and rabbits at exposures about 6 and 12 times the maximum recommended human dose (MRHD)

Metoclopramide crosses the placental barrier and may cause extrapyramidal signs and methemoglobinemia in neonates with maternal administration during delivery; monitor neonates for extrapyramidal signs

Lactation

Limited published data report the presence of metoclopramide in human milk in variable amounts; breastfed infants exposed to metoclopramide have experienced gastrointestinal adverse reactions, including intestinal discomfort and increased intestinal gas formation; metoclopramide elevates prolactin levels; however, published data are not adequate to support drug effects on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from therapy or from underlying maternal condition

Monitor breastfeeding neonates because metoclopramide may cause extrapyramidal signs (dystonias) and methemoglobinemia

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

IV Incompatibilities

Solution: D5W (at high drug concentration)

Additive: Dexamethasone sodium phosphate with lorazepam and diphenhydramine, erythromycin lactobionate, floxacillin, fluorouracil, furosemide

Syringe: Ampicillin, calcium gluconate, chloramphenicol sodium succinate, furosemide, methotrexate, penicillin G potassium, sodium bicarbonate

Y-site: Allopurinol, amphotericin B cholesteryl sulfate, amsacrine, cefepime, doxorubicin liposomal, furosemide, propofol

IV Compatibilities

Additive: Cimetidine, clindamycin, meperidine, meropenem, morphine sulphate, potassium chloride, verapamil

Syringe (partial list): Butorphanol, chlorpromazine, cisplatin, cyclophosphamide, cytarabine, dexamethasone, dimenhydrinate, diphenhydramine, doxorubicin, fentanyl, fentanyl with midazolam, fluorouracil, heparin, hydromorphone, hydroxyzine, insulin, lidocaine, magnesium sulfate, meperidine, midazolam, morphine, ondansetron, pentazocine, prochlorperazine, promethazine, ranitidine, vitamins B and C

Y-site (partial list): Aztreonam, bivalirudin, ciprofloxacin, cisplatin, cytarabine, diltiazem, docetaxel, doxorubicin, famotidine, fentanyl, fluconazole, fluorouracil, heparin, hydromorphone, linezolid, meperidine, morphine sulfate, ondansetron, quinupristin-dalfopristin, zidovudine

IV Administration

NS is preferred diluent because drug is most stable in this solution

Dose ≤10 mg: IV push over 1-2 minutes

Dose >10 mg: Dilute in 50 mL D5W or NS, and infuse over at least 15 minutes

Protect from light

• If you have an allergy to metoclopramide or any other part of Metozolv ODT.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have ever had trouble controlling body movements or other muscle problems when taking this medicine.
• If you have or have ever had low mood (depression) or thoughts of killing yourself.
• If you have any of these health problems: GI (gastrointestinal) bleeding, hole in the GI tract, bowel block, pheochromocytoma, seizures, Parkinson's disease, or high blood pressure.
• If you are taking any drugs that may raise the chance of body movements you cannot control. There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure.
• If you take any drugs (prescription or OTC, natural products, vitamins) that must not be taken with Metozolv ODT, like certain drugs that are used for depression, pain, or Parkinson's disease. There are many drugs that must not be taken with this medicine.

This is not a list of all drugs or health problems that interact with Metozolv ODT.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

5 mg Tablets:  Each white round 5 mg tablet is debossed with “5” on one side and plain on the other.

10 mg Tablets:  Each white round 10 mg tablet is debossed with “10” on one side and plain on the other.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.

A total of 86 subjects entered three studies with Metozolv ODT; 12 subjects entered a pilot bioavailability study (BA); 44 subjects entered a bioequivalence (BE) study, and 30 subjects entered a food-effect study.  The adverse reactions from the BE and food-effect study are summarized in Table 1.  The pilot BA study data are not included because it was performed with a formulation different from the Metozolv ODT formulation.    

The adverse experience profile seen with Metozolv ODT was similar to metoclopramide tablets.  Thirty-three (33) adverse reactions were reported after receiving Metozolv ODT and 30 adverse reactions were reported after receiving metoclopramide tablets.

Table 1: Adverse Reactions in BE and Food-Effect Study in ≥ 2% of Subjects

The most frequently reported adverse reactions (greater than 2%) associated with Metozolv ODT were:  nausea, vomiting, fatigue, somnolence and headache.  The most frequently reported adverse reactions (greater than 2%) associated with metoclopramide tablets were:  nausea, headache, fatigue, somnolence, and dizziness.  The combined data from the fasted BE study and the food-effect study did not demonstrate any significant differences in the adverse event profile for Metozolv ODT compared to metoclopramide tablets.

Post-Marketing Experience

The following adverse reactions are from the cumulative post-marketing experience with metoclopramide tablets.  Since the 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.

CNS Effects:  Restlessness, drowsiness, fatigue, and lassitude occur in approximately 10% of patients receiving the most commonly prescribed dosage of 10 mg four times a day.  Insomnia, headache, confusion, dizziness, or depression with suicidal ideation occurs less frequently.  The incidence of drowsiness is greater at higher doses.  There are isolated reports of seizures without clear-cut relationship to metoclopramide.  Rarely, hallucinations have been reported.

Extrapyramidal Syndromes (EPS): 
Acute dystonic reactions, the most common type of EPS associated with metoclopramide, occur in approximately 0.2% of patients (1 in 500) treated with 30 to 40 mg of metoclopramide per day. Symptoms include involuntary movements of limbs, facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of tongue, bulbar type of speech, trismus, opisthotonus (tetanus-like reactions), and rarely, stridor and dyspnea possibly due to laryngospasm; ordinarily these symptoms are readily reversed by diphenhydramine [see Warnings and Precautions (5.1)].

Drug-induced Parkinsonian-like symptoms may include bradykinesia, tremor, cogwheel rigidity, mask-like facies [see Warnings and Precautions (5.2)].

Tardive dyskinesia is most frequently characterized by involuntary movements of the tongue, face, mouth, or jaw, and sometimes by involuntary movements of the trunk and/or extremities; movements may be choreoathetotic in appearance.  Motor restlessness (akathisia) may include inability to sit still, pacing, and foot tapping.  These symptoms may disappear spontaneously or respond to a reduction in dosage.

Neuroleptic Malignant Syndrome:  Rare occurrences of Neuroleptic Malignant Syndrome (NMS) have been reported [see Warnings and Precautions (5.3)]. 

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

Cardiovascular:  Hypotension, hypertension, supraventricular tachycardia, bradycardia, fluid retention, acute congestive heart failure, possible AV block.

Gastrointestinal:  Nausea, bowel disturbances, primarily diarrhea.

Hepatic:  Rarely, cases of hepatotoxicity characterized by such findings as jaundice and altered liver function tests, when metoclopramide was administered with other drugs with known hepatotoxic potential.

Renal:  Urinary frequency and incontinence.

Hematologic:  A few cases of neutropenia, leukopenia, or agranulocytosis, generally without clear-cut relationship to metoclopramide.  Methemoglobinemia in adults and especially with overdosage in neonates.  Sulfhemoglobinemia in adults.

Allergic Reactions:  A few cases of rash, urticaria, or bronchospasm, especially in patients with a history of asthma.  Rarely, angioneurotic edema, including glossal or laryngeal edema.

Miscellaneous:  Visual disturbances.  Porphyria.

METOZOLV®(MĔ-tō-zolv) ODT

(metoclopramide hydrochloride)

 Orally Disintegrating Tablets

Read the Medication Guide that comes with Metozolv ODT before you take it and each time you get a refill. There may be new information. If you take another product that contains metoclopramide (such as REGLAN tablets, REGLAN ODT, REGLAN injection or metoclopramide oral solution), you should read the Medication Guide that comes with that product. Some of the information may be different. This Medication Guide does not take the place of talking with your doctor about your medical condition or your treatment.

 What is the most important information I should know about Metozolv ODT?

Metozolv ODT 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 Metozolv ODT. There is no treatment for tardive dyskinesia, but symptoms may lessen or go away over time after you stop taking Metozolv ODT.

Your chances for getting tardive dyskinesia go up:

• the longer you take Metozolv ODT and the more Metozolv ODT you take. You should not take Metozolv ODT 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 doctor to know if you will get tardive dyskinesia if you take Metozolv ODT.

Call your doctor right away if you have movements you can not stop or control, such as:

• lip smacking, chewing, or puckering of your lips
• 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 Metozolv ODT?” for more information about side effects.

 What is Metozolv ODT?

Metozolv ODT is a prescription medicine used in adults:

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

It is not known if Metozolv ODT is safe or works in children.

Who should not take Metozolv ODT?

Do not take Metozolv ODT if you:

• have stomach or intestine problems that could get worse with Metozolv ODT, such as bleeding, blockage or a tear in your stomach or bowel wall 
• have an adrenal tumor called pheochromocytoma 
• are allergic to metoclopramide or any of the ingredients in Metozolv ODT. See the end of this Medication Guide for a list of ingredients in Metozolv ODT. 
• take medicines that can cause uncontrolled movements, such as medicines for mental illness.
• have seizures

What should I tell my doctor before taking Metozolv ODT?

Before you take Metozolv ODT, tell your doctor if you:

• have kidney or liver disease
• have depression or mental illness
• have high blood pressure
• have heart failure or heart rhythm problems
• have diabetes. Your dose of insulin may need to be changed.
• have Parkinson’s disease
• have any other medical conditions
• drink alcohol 
• are pregnant or plan to become pregnant. It is not known if Metozolv ODT will harm your unborn baby. 
• are breast-feeding or plan to breast-feed. Metozolv ODT can pass into your milk and may harm your baby. You and your doctor should decide if you will take Metozolv ODT or breast-feed. You should not do both.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Metozolv ODT and some medicines can affect each other and may not work as well, or cause possible side effects. Do not start any new medicine while taking Metozolv ODT until you talk with your doctor.

 Especially tell your doctor if you take: 

• another medicine that contains metoclopramide, such as REGLAN tablets, REGLAN ODT, or metoclopramide oral syrup
• a blood pressure medicine
• a medicine for depression, especially a monoamine oxidase inhibitor (MAOI)
• an anti-psychotic medicine
• insulin
• medicines that can make you sleepy, such as anti-anxiety medicines, sleep medicines, and narcotics.

Ask your doctor or pharmacist if you are not sure if your medication is listed above.

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

How should I take Metozolv ODT? 

• Metozolv ODT comes as a tablet that melts in your mouth. 
• Take Metozolv ODT exactly as prescribed by your doctor. Do not change your dose unless your doctor tells you to. 
• You should not take Metozolv ODT for more than 12 weeks. 
• Take Metozolv ODT at least 30 minutes before eating and at bedtime.

To take Metozolv ODT: 

1. Leave the tablet in the sealed blister Metozolv ODT pack until you are ready to take it. 
2. Use dry hands to open a blister and take out a tablet. If the tablet breaks or crumbles throw it away and take a new tablet out of the blister pack. 
3. Put the tablet on your tongue right away. Let it melt and then swallow. You do not need water to take Metozolv ODT.

If you take too much Metozolv ODT, call your doctor or Poison Control Center.

What should I avoid while taking Metozolv ODT? 

• Do not drink alcohol while taking Metozolv ODT. Alcohol may make some side effects of Metozolv ODT worse, such as feeling sleepy. 
• Do not drive, work with machines, or do dangerous tasks until you know how Metozolv ODT affects you. Metozolv ODT may cause sleepiness.

What are the possible side effects of Metozolv ODT?

Metozolv ODT can cause serious side effects, including: 

• Tardive dyskinesia (abnormal muscle movements) See “What is the most important information I should know about Metozolv ODT?” 
• 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. These spasms usually start within the first 2 days of treatment. These spasms happen more often in children and adults younger than 30. 
• Depression, thoughts about suicide, and suicide. Some people who take Metozolv ODT may become depressed. You may have thoughts about hurting or killing yourself. Some people who have taken metoclopramide products have ended their own lives (suicide). 
• Neuroleptic Malignant Syndrome (NMS). NMS is a rare but very serious condition that can happen with Metozolv ODT. 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. 
• Parkinsonism. Symptoms include slight shaking, body stiffness, trouble moving or keeping your balance. If you have Parkinson’s Disease, your symptoms may become worse while you are taking Metozolv ODT. 
• High blood pressure. Metozolv ODT can cause your blood pressure to increase. 
• Too much body water. People who have certain liver problems or heart failure and take Metozolv ODT 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.

Call your doctor 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 Metozolv ODT are: 

• headache 
• nausea 
• vomiting 
• tiredness
• sleepiness

You may have more side effects the longer you take Metozolv ODT and the more Metozolv ODT you take.

You may still have side effects after you stop Metozolv ODT. You may have symptoms from stopping (withdrawal) Metozolv ODT such as headaches, and feeling dizzy or nervous.

Tell your doctor about any side effects that bother you or do not go away. These are not all the possible side effects of Metozolv ODT.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1–800–FDA-1088.

How do I store Metozolv ODT? 

• Store Metozolv ODT at room temperature, between 68°F to 77°F (20°C to 25°C). 
• Keep Metozolv ODT away from moisture. 
• Throw away any Metozolv ODT that is not used.

Keep Metozolv ODT and all medicines away from children.

General information about Metozolv ODT

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Metozolv ODT for a condition for which it was not prescribed. Do not give Metozolv ODT to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about Metozolv ODT. If you would like more information about Metozolv ODT, talk with your doctor. You can ask your doctor or pharmacist for information about Metozolv ODT that is written for health professionals. For more information, call 1-866-669-7597.

 What are the ingredients in Metozolv ODT?

Active ingredients: metoclopramide hydrochloride

Inactive ingredients: gelatin, mannitol, mint flavoring, Acesulfame potassium (artificial sweetener), and trace amounts of sodium chloride and sodium hydroxide

Salix Pharmaceuticals, Inc.

Raleigh, NC 27615, USA

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

VENART 144-2/OCT 2011

Metozolv ODT (metoclopramide orally disintegrating tablets) increases muscle contractions in the upper digestive tract. This speeds up the rate at which the stomach empties into the intestines.

Metozolv ODT is used to treat slow gastric emptying in people with diabetes (also called diabetic gastroparesis), which can cause nausea, vomiting, heartburn, loss of appetite, and a feeling of fullness after meals.

Metozolv ODT melts on the tongue without the need for water, and offers patients who have trouble swallowing tablets a more convenient option than traditional metoclopramide tablets.

Metozolv ODT may also be used for purposes not listed in this medication guide.

Take Metozolv ODT exactly as prescribed by your doctor. Metozolv ODT is usually taken for only 4 to 12 weeks. Follow the directions on your prescription label.

NEVER TAKE METOZOLV ODT IN LARGER AMOUNTS THAN RECOMMENDED, OR FOR LONGER THAN 12 WEEKS.

High doses or long-term use of Metozolv ODT can cause a serious movement disorder that may not be reversible. Symptoms of this disorder include uncontrollable muscle movements of your lips, tongue, eyes, face, arms, or legs. The longer you take Metozolv ODT, the more likely you are to develop a serious movement disorder. The risk of this side effect is higher in women, diabetics, and older adults.

Take Metozolv ODT 30 minutes before eating. Metozolv ODT is usually taken before meals and at bedtime. Your doctor may want you to take the medication as needed only with meals that usually cause heartburn. Follow your doctor's instructions.

To take metoclopramide orally disintegrating tablet (Metozolv ODT):

• Keep the tablet in its bottle or blister pack until you are ready to take the medicine. Make sure your hands are dry before handling a tablet. If the tablet breaks or melts in your hand, throw it away and use a new tablet.

• Place the tablet on your tongue. It will begin to melt right away. Do not swallow the tablet whole. Allow it to melt in your mouth without chewing.

• Swallow several times as the tablet melt. You do not need to drink liquid to help the tablet melt.

Do not take two different forms of metoclopramide (such as tablets and oral syrup) at the same time.

Store Metozolv ODT at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use. After you stop taking Metozolv ODT, you may have unpleasant withdrawal symptoms such as headache, dizziness, or nervousness. Talk to your doctor about how to avoid withdrawal symptoms when stopping the medication.