Metoclopramide Oral Solution

Use metoclopramide oral solution as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Do not take more than what your doctor told you to take. Taking more than you are told may raise your chance of very bad side effects.
• Take at least 30 minutes before eating and at bedtime unless your doctor has told you otherwise.
• Measure liquid doses carefully. Use the measuring device that comes with this medicine. If there is none, ask the pharmacist for a device to measure metoclopramide oral solution.

What do I do if I miss a dose?

• If you take this medicine on a regular basis, take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.
• Many times metoclopramide oral solution is taken on an as needed basis. Do not take more often than told by the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Loose stools (diarrhea).
• Feeling sleepy.
• Upset stomach.
• Feeling tired or weak.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Metoclopramide should not be used whenever stimulation of gastrointestinal motility might be dangerous, e.g., in the presence of gastrointestinal hemorrhage, mechanical obstruction, or perforation.

Metoclopramide is contraindicated in patients with pheochromocytoma because the drug may cause a hypertensive crisis, probably due to release of catecholamines from the tumor. Such hypertensive crises may be controlled by phentolamine.

Metoclopramide is contraindicated in patients with known sensitivity or intolerance to the drug.

Metoclopramide should not be used in epileptics or patients receiving other drugs which are likely to cause extrapyramidal reactions, since the frequency and severity of seizures or extrapyramidal reactions may be increased.

General

In one study in hypertensive patients, intravenously administered metoclopramide was shown to release catecholamines; hence, caution should be exercised when metoclopramide is used in patients with hypertension.

Because metoclopramide produces a transient increase in plasma aldosterone, certain patients, especially those with cirrhosis or congestive heart failure, may be at risk of developing fluid retention and volume overload. If these side effects occur at any time during metoclopramide therapy, the drug should be discontinued.

Adverse reactions, especially those involving the nervous system, may occur after stopping the use of metoclopramide. A small number of patients may experience a withdrawal period after stopping metoclopramide that could include dizziness, nervousness, and/or headaches.

Information for Patients

The use of Metoclopramide Oral Solution is recommended for adults only. Metoclopramide may impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving a motor vehicle. The ambulatory patient should be cautioned accordingly.

Drug Interactions

The effects of metoclopramide on gastrointestinal motility are antagonized by anticholinergic drugs and narcotic analgesics. Additive sedative effects can occur when metoclopramide is given with alcohol, sedatives, hypnotics, narcotics or tranquilizers.

The finding that metoclopramide releases catecholamines in patients with essential hypertension suggests that it should be used cautiously, if at all, in patients receiving monoamine oxidase inhibitors.

Absorption of drugs from the stomach may be diminished (e.g., digoxin) by metoclopramide, whereas the rate and/or extent of absorption of drugs from the small bowel may be increased (e.g., acetaminophen, tetracycline, levodopa, ethanol, cyclosporine).

Gastroparesis (gastric stasis) may be responsible for poor diabetic control in some patients. Exogenously administered insulin may begin to act before food has left the stomach and lead to hypoglycemia. Because the action of metoclopramide will influence the delivery of food to the intestines and thus the rate of absorption, insulin dosage or timing of dosage may require adjustment.

Carcinogenesis, Mutagenesis, Impairment of Fertility

A 77-week study was conducted in rats with oral doses up to about 40 times the maximum recommended human daily dose. Metoclopramide elevates prolactin levels and the elevation persists during chronic administration. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin-dependent in vitro, a factor of potential importance if the prescription of metoclopramide is contemplated in a patient with previously detected breast cancer. Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported with prolactin-elevating drugs, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of prolactin-stimulating neuroleptic drugs and metoclopramide. Neither clinical studies nor epidemiologic studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis; the available evidence is too limited to be conclusive at this time.

An Ames mutagenicity test performed on metoclopramide was negative.

Pregnancy Category B

Reproduction studies performed in rats, mice, and rabbits by the I.V., I.M., S.C. and oral routes at maximum levels ranging from 12 to 250 times the human dose have demonstrated no impairment of fertility or significant harm to the fetus due to metoclopramide. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Metoclopramide is excreted in human milk. Caution should be exercised when metoclopramide is administered to a nursing mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established (see OVERDOSAGE).

Care should be exercised in administering metoclopramide to neonates since prolonged clearance may produce excessive serum concentrations (see CLINICAL PHARMACOLOGY Pharmacokinetics). In addition, neonates have reduced levels of NADH-cytochrome b5 reductase, which, in combination with the aforementioned pharmacokinetic factors, make neonates more susceptible to methemoglobinemia (see OVERDOSAGE).

The safety profile of metoclopramide in adults cannot be extrapolated to pediatric patients. Dystonias and other extrapyramidal reactions associated with metoclopramide are more common in the pediatric population than in adults. (See WARNINGS and ADVERSE REACTIONS Extrapyramidal Reactions.)

Geriatric Use

Clinical studies of metoclopramide did not include sufficient numbers of subjects aged 65 and over to determine whether elderly subjects respond differently from younger subjects.

The risk of developing parkinsonian-like side effects increases with ascending dose. Geriatric patients should receive the lowest dose of metoclopramide that is effective. If parkinsonian-like symptoms develop in a geriatric patient receiving metoclopramide, metoclopramide should generally be discontinued before initiating any specific antiparkinsonian agents (see WARNINGS and DOSAGE AND ADMINISTRATION - For the Relief of Symptomatic Gastroesophageal Reflux).

The elderly may be at greater risk for tardive dyskinesia (see WARNINGS - Tardive Dyskinesia).

Sedation has been reported in metoclopramide users. Sedation may cause confusion and manifest as over-sedation in the elderly (see CLINICAL PHARMACOLOGY, PRECAUTIONS - Information for Patients and ADVERSE REACTIONS - CNS Effects).

Metoclopramide is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function (see DOSAGE AND ADMINISTRATION - USE IN PATIENTS WITH RENAL OR HEPATIC IMPAIRMENT).

For these reasons, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased renal functions, concomitant disease, or other drug therapy in the elderly (see DOSAGE AND ADMINISTRATION - For the Relief of Symptomatic Gastroesophageal Reflux and USE IN PATIENTS WITH RENAL OR HEPATIC IMPAIRMENT).

Other Special Populations

Patients with NADH-cytochrome b5 reductase deficiency are at an increased risk of developing methemoglobinemia and/or sulfhemoglobinemia when metoclopramide is administered. In patients with G6PD deficiency who experience metoclopramide-induced methemoglobinemia, methylene blue treatment is not recommended (see OVERDOSAGE).

Metoclopramide (met-o-KLO-pra-mide)
Oral Solution USP

Read the Medication Guide that comes with Metoclopramide before you start taking 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, or REGLAN injection), 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 Metoclopramide?

Metoclopramide can cause serious side effects, including:

Abnormal muscle movements called tardive dyskinesia. These movements happen mostly in the face muscles. You cannot control these movements. They may not go away even after stopping Metoclopramide. There is no treatment for tardive dyskinesia, but symptoms may lessen or go away over time after you stop taking Metoclopramide

Your chances for getting tardive dyskinesia go up:

• the longer you take Metoclopramide and the more Metoclopramide you take. You should not take Metoclopramide for more than 12 weeks.
• if you are older, especially if you are a woman
• if you have diabetes

It is not possible for your doctor to know if you will get tardive dyskinesia if you take Metoclopramide.

Call your doctor 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

Your doctor may decide to stop Metoclopramide.

See the section "What are the possible side effects of Metoclopramide?"

What is Metoclopramide?

Metoclopramide is a prescription medicine used:

• in adults for 4 to 12 weeks to relieve heartburn symptoms with gastroesophageal reflux disease (GERD) when certain other treatments do not work. Metoclopramide relieves daytime heartburn and heartburn after meals. It also helps ulcers in the esophagus to heal.
• to relieve symptoms of slow stomach emptying in people with diabetes. Metoclopramide helps treat symptoms such as nausea, vomiting, heartburn, feeling full long after a meal, and loss of appetite. All these symptoms do not get better at the same time.

It is not known if Metoclopramide is safe and works in children.

Who should not take Metoclopramide?

Do not take Metoclopramide if you:

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

What should I tell my doctor before taking Metoclopramide?

Tell your doctor about all your medical conditions, including if you have:

• depression
• Parkinson's disease
• high blood pressure
• kidney problems. Your doctor may start with a lower dose.
• liver problems or heart failure. Metoclopramide may cause your body to hold fluids.
• diabetes. Your dose of insulin may need to be changed.
• breast cancer
• you are pregnant or plan to become pregnant. It is not known if Metoclopramide will harm your unborn baby.
• you are breast-feeding. Metoclopramide can pass into breast milk and may harm your baby. Talk with your doctor about the best way to feed your baby if you take Metoclopramide.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Metoclopramide and some other medicines may interact with each other and may not work as well, or cause possible side effects. Do not start any new medicines while taking Metoclopramide until you talk with your doctor. Especially tell your doctor if you take:

• another medicine that contains Metoclopramide, such as REGLAN tablets, REGLAN ODT.
• a blood pressure medicine
• a medicine for depression, especially a Monoamine Oxidase Inhibitor (MAOI)
• insulin
• a medicine that can make you sleepy, such as anti-anxiety medicine, sleep medicines, and narcotics.

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

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

How should I take Metoclopramide?

• Take Metoclopramide exactly as your doctor tells you. Do not change the dose unless your doctor tells you.
• You should not take Metoclopramide for more than 12 weeks.
• If you take too much Metoclopramide, call your doctor or Poison Control Center right away.

What should I avoid while taking Metoclopramide?

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

What are the possible side effects of Metoclopramide?

Metoclopramide can cause serious side effects, including:

• Tardive dyskinesia (abnormal muscle movements). See "What is the most important information I need to know about Metoclopramide?"
• 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 under age 30.
• Depression, thoughts about suicide, and suicide. Some people who take Metoclopramide become depressed. You may have thoughts about hurting or killing yourself. Some people who take Metoclopramide have ended their own lives (committed suicide).
• Neuroleptic Malignant Syndrome (NMS). NMS is a very rare but very serious condition that can happen with certain medicines, such as Metoclopramide. 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 already have Parkinson's disease, your symptoms may become worse while you are receiving Metoclopramide.

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

Common side effects of Metoclopramide include:

• feeling restless, sleepy, tired, dizzy, or exhausted
• headache
• confusion
• trouble sleeping

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

You may still have side effects after stopping Metoclopramide. You may have symptoms from stopping (withdrawal) Metoclopramide 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 Metoclopramide.

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 Metoclopramide?

• Keep Metoclopramide at room temperature between 68ºF to 77ºF (20ºC to 25ºC).
• Keep Metoclopramide in the bottle it comes in. Keep the bottle closed tightly.

Keep Metoclopramide and all medicines out of the reach of children.

General information about Metoclopramide

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Metoclopramide for a condition for which it was not prescribed. Do not give Metoclopramide 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 Metoclopramide. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Metoclopramide that is written for health professionals. For more information, go to www.paipharma.com or call 1-800-845-8210.

What are the ingredients in Metoclopramide?

Active ingredient: Metoclopramide

Inactive ingredients: citric acid, FD&C Yellow No. 6 (Sunset Yellow), flavoring, glycerin, methylparaben, propylparaben, purified water, and sorbitol solution.

Pharmaceutical Associates, Inc.
Greenville, SC 29605
www.paipharma.com

R10/12

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

NDC 0121-0576-16
NSN 6505-01-212-8750

Metoclopramide
Oral Solution USP

5 mg/5 mL*

*Each 5 mL (1 teaspoonful) contains:
Metoclopramide 5 mg
(present as the hydrochloride)

PHARMACIST: Dispense the accompanying
Medication Guide to each patient.

Rx ONLY

16 fl oz (473 mL)

Pharmaceutical
Associates, Inc.
Greenville, SC 29605

Side effects that you should report to your doctor or health care professional as soon as possible:

• allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
• abnormal production of milk in females
• breast enlargement in both males and females
• change in the way you walk
• difficulty moving, speaking or swallowing
• drooling, lip smacking, or rapid movements of the tongue
• excessive sweating
• fever
• involuntary or uncontrollable movements of the eyes, head, arms and legs
• irregular heartbeat or palpitations
• muscle twitches and spasms
• unusually weak or tired

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):

• change in sex drive or performance
• depressed mood
• diarrhea
• difficulty sleeping
• headache
• menstrual changes
• restless or nervous

• acetaminophen
• cyclosporine
• digoxin
• medicines for blood pressure
• medicines for diabetes, including insulin
• medicines for hay fever and other allergies
• medicines for depression, especially an Monoamine Oxidase Inhibitor (MAOI)
• medicines for Parkinson's disease, like levodopa
• medicines for sleep or for pain
• tetracycline