Cuvposa

In the U.S.

• Cuvposa
• Glycate
• Robinul
• Robinul Forte

Available Dosage Forms:

• Tablet
• Solution

Therapeutic Class: Gastrointestinal Agent

Pharmacologic Class: Antimuscarinic

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of glycopyrrolate in children 3 to 16 years of age. However, safety and efficacy have not been established in children younger than 3 years of age.

Geriatric

No information is available on whether the risk of glycopyrrolate-induced adverse effects are increased in the elderly; however, it should be used with caution because elderly patients are more likely to have age related liver disease, kidney disease, heart disease, or prostate problems. This may require a dosage adjustment or careful monitoring in elderly patients receiving glycopyrrolate.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Potassium

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Bupropion
• Donepezil
• Tiotropium

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Colostomy (bowel surgical procedure) or
• Congestive heart failure or
• Heart disease or
• Heart rhythm problems or
• Hiatal hernia with gastroesophageal reflux disease (GERD) or
• Hypertension (high blood pressure) or
• Hyperthyroidism (overactive thyroid) or
• Ileostomy (bowel surgical procedure) or
• Liver disease or
• Nerve problems (e.g., neuropathy) or
• Prostatic hypertrophy (enlarged prostate) or
• Ulcerative colitis—Use with caution. May make these conditions worse.

• Glaucoma or
• Myasthenia gravis (severe muscle weakness) or
• Obstructive uropathy (urinary blockage due to enlarged prostate or other condition) or
• Paralytic ileus (bowel blockage) or
• Stomach or intestinal problems (e.g., ulcerative colitis, toxic megacolon, bowel obstruction), severe or
• Trouble urinating—Should not be used in patients with these conditions.

• Kidney disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

• It is used to reduce drooling.
• It may be given to you for other reasons. Talk with the doctor.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Cuvposa is available as a 1mg/5 mL clear, cherry-flavored solution for oral administration in 16 ounce bottles.

Pregnancy

Risk Summary

There are no available data in pregnant women for Cuvposa to inform decisions concerning any drug-associated risks. In pregnant rats, daily oral administration of glycopyrrolate during organogenesis at dose exposures 2.5 to 113 times the exposure at the maximum recommended human dose (MRHD) did not result in an increased incidence of gross external or visceral defects [see Data]. When glycopyrrolate was administered intravenously to pregnant rabbits during organogenesis at dose exposures equivalent to up to approximately 7.8 times the exposure at the MRHD, no adverse effects on embryo-fetal development were seen. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Animal Data

Glycopyrrolate was orally administered to pregnant rats at dosages of 50, 200, and 400 mg/kg/day during the period of organogenesis. These dosages resulted in systemic exposures (estimated AUC0-inf values) approximately 2.5, 23, and 113 times, respectively, the estimated systemic exposure in humans at the MRHD (9 mg per day, administered in three divided doses). Glycopyrrolate had no effect on maternal survival, but significantly reduced mean maternal body weight gain over the period of dosing at all dosages evaluated. Mean fetal weight was significantly reduced in the 200 and 400 mg/kg/day dose groups. There were two litters with all resorbed fetuses in the 400 mg/kg/day dose group. There were no effects of treatment on the incidence of gross external or visceral defects. Minor treatment-related skeletal effects included reduced ossification of various bones in the 200 and 400 mg/kg/day dose groups; these skeletal effects were likely secondary to maternal toxicity.

Glycopyrrolate was intravenously administered to pregnant rabbits at dosages of 0.1, 0.5, and 1.0 mg/kg/day during the period of organogenesis. These dosages resulted in systemic exposures (estimated AUC0-inf values) approximately 0.8, 4.6, and 7.8 times, respectively, the estimated systemic exposure in humans at the MRHD. Glycopyrrolate did not affect maternal survival under the conditions of this study. Mean maternal body weight gain and mean food consumption over the period of dosing were lower than the corresponding control value in the 0.5 and 1.0 mg/kg/day treatment groups. There were no effects of treatment on fetal parameters, including fetal survival, mean fetal weight, and the incidence of external, visceral, or skeletal defects.

Female rats that were pregnant or nursing were orally dosed with glycopyrrolate daily at dosages of 0, 50, 200, or 400 mg/kg/day, beginning on day 7 of gestation, and continuing until day 20 of lactation. These dosages resulted in systemic exposures (estimated AUC0-inf values) approximately 2.5, 23, and 113 times, respectively, the estimated systemic exposure in humans at the MRHD (9 mg per day, administered in three divided doses). Mean body weight of pups in all treatment groups was reduced compared to the control group during the period of nursing, but eventually recovered to be comparable to the control group, post-weaning. No other notable delivery or litter parameters were affected by treatment in any group, including no effects on mean duration of gestation or mean numbers of live pups per litter. No treatment-related effects on survival or adverse clinical signs were observed in pups. There were no effects of maternal treatment on behavior, learning, memory, or reproductive function of pups.

Lactation

Risk Summary

There are no data on the presence of glycopyrrolate or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Cuvposa and any potential adverse effects on the breastfed infant from Cuvposa or from the underlying maternal condition.

Pediatric Use

Cuvposa was evaluated for chronic severe drooling in patients aged 3-16 years with neurologic conditions associated with problem drooling. Cuvposa has not been studied in subjects under the age of 3 years.

Geriatric Use

Clinical studies of Cuvposa did not include subjects aged 65 and over.

Renal Impairment

Because glycopyrrolate is largely renally eliminated, Cuvposa should be used with caution in patients with renal impairment [see Clinical Pharmacology (12.3)].

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential of glycopyrrolate.

Glycopyrrolate did not elicit any genotoxic effects in the Ames mutagenicity assay, the human lymphocyte chromosome aberration assay, or the micronucleus assay.

Glycopyrrolate was assessed for effects on fertility or general reproductive function in rats. Rats of both genders received glycopyrrolate at dosages up to 100 mg/kg/day via oral gavage, resulting in systemic exposures (estimated AUC0-inf values) in males and females up to approximately 11 and 15 times, respectively, the estimated systemic exposure in humans at the MRHD (9 mg per day, administered in three divided doses). No treatment-related effects on fertility or reproductive parameters were observed in either gender in this study.

NDC 0259-0501-16; 1 mg/5mL clear, cherry-flavored solution; 16 oz. bottle.

Store at room temperature 20° - 25°C (68° - 77°F); excursions permitted to 15° - 30°C (59° - 86°F) [See USP Controlled Room Temperature].

See FDA-approved patient labeling (Patient Information)

• Advise parent/caregivers to measure Cuvposa with an accurate measuring device. A household teaspoon is not an accurate measuring device. Patients/caregivers should use a dosing cup available in pharmacies to accurately measure the correct milliliter dose for the patient. An oral syringe, also available in pharmacies, should be used to dispense Cuvposa into the child's mouth from the cup. A pharmacist can recommend an appropriate measuring device and can provide instructions for measuring the correct dose.
• Administering Cuvposa with a high fat meal substantially reduces the amount of glycopyrrolate absorbed. Administer Cuvposa at least one hour before or two hours after meals.
• Cuvposa is started at a low dose and gradually titrated over a period of weeks based on therapeutic response and adverse reactions. Parents/caregivers should not increase the dose without the physician's permission.
• Common adverse reactions from Cuvposa include overly dry mouth, constipation, vomiting, flushing of the skin or face, and urinary retention. Side effects can sometimes be difficult to detect in some patients with neurologic problems who cannot adequately communicate how they feel. If side effects become troublesome after increasing a dose, decrease the dose to the prior one and contact your physician.
• Constipation is the most common side effect of glycopyrrolate, and if constipation occurs, stop administering glycopyrrolate to the patient and call their healthcare practitioner.
• Inability of the patient to urinate, dry diapers or undergarments, irritability or crying may be signs of urinary retention, and if urinary retention occurs, parents/caregivers should stop administering glycopyrrolate and call their healthcare practitioner.
• If the patient develops a skin rash, hives or an allergic reaction, parents/caregivers should stop administering glycopyrrolate and call their healthcare practitioner as this could be a sign of hypersensitivity to this product.
• Drugs like glycopyrrolate can reduce sweating, and if the patient is in a hot environment and flushing of the skin occurs this may be due to overheating. Patients/caregivers should be advised to avoid exposure of the patient to hot or very warm environmental temperatures to avoid overheating and the possibility of heat exhaustion or heat stroke.

Manufactured by:
Mikart, Inc.
Atlanta, GA 30318

Manufactured for:
Merz North America, Inc.
Raleigh, NC 27615

© 2016 Merz Pharmaceuticals, LLC
Cuvposa® is a registered trademark of Merz Pharmaceuticals, LLC

GLY-PI-07

PATIENT and CAREGIVER INFORMATION

Cuvposa (glycopyrrolate) Oral Solution

Please read the Patient and Caregiver Information that comes with Cuvposa before you start giving it to your child, and each time you get a refill. This leaflet does not take the place of talking with your doctor about your child's medical condition or treatment.

What is Cuvposa?

Cuvposa is a prescription medicine used in children with medical conditions that cause too much (abnormal) drooling.

Who should not take Cuvposa?

Do not give Cuvposa to anyone who:

• has problems urinating
• has a bowel problem called paralytic ileus
• lacks normal bowel tone or tension
• has severe ulcerative colitis or certain other serious bowel problems with severe ulcerative colitis
• has myasthenia gravis

What should I tell my doctor before giving Cuvposa to my child?

Tell your doctor if your child:

• has any allergies
• has any stomach or bowel problems, including ulcerative colitis
• has any problems with constipation
• has thyroid problems
• has high blood pressure
• has heart problems or abnormal heart beats
• has a hiatal hernia with gastroesophageal reflux disease (GERD)
• has any eye problems
• has any problems urinating
• has any other medical conditions
• is pregnant or plans to become pregnant. It is not known if Cuvposa can harm an unborn baby.
• is breastfeeding or plans to breastfeed. It is not known if Cuvposa passes into breast milk and if it can harm the baby.

Tell your doctor about all of the medicines that your child takes, including prescription and non-prescription medicines, vitamins, and herbal supplements. Some medicine may affect the way Cuvposa works, and Cuvposa may affect how some other medicines work.

How should I give Cuvposa?

• Give Cuvposa exactly as prescribed by your child's doctor.
• Give Cuvposa 1 hour before or 2 hours after meals.
• Your doctor will tell you how much (milliliters or mLs) of Cuvposa to give your child.
• Do not change the dose of Cuvposa unless your doctor tells you to.
• You must measure the dose of Cuvposa before giving it to your child. Use a special marked dose measuring cup (available at most pharmacies) to measure the right dose of Cuvposa.
• To help make sure that your child swallows the dose, you should use an oral syringe to give the child each dose of Cuvposa, after you measure the dose needed with a dose measuring cup. Oral syringes are also available at most pharmacies.
• If you have questions about how to measure the dose or how to use an oral syringe, ask your pharmacist or doctor.
• The dose of Cuvposa that is needed to control drooling may be different for each child. Cuvposa is usually started at a low dose, and slowly increased as directed by your doctor. This slow increase in dose continues until the best dose for your child is reached, to control drooling.
• During this time it is important to stay in close contact with your child's doctor, and tell the doctor about any side effects that your child has. See "What are the possible side effects of Cuvposa?"

What should I avoid while taking Cuvposa?

• Cuvposa may cause sleepiness or blurred vision. Do not drive a car, operate heavy machinery, or do other dangerous activities while taking Cuvposa.
• Avoid overheating. See "What are the possible side effects of Cuvposa?"

What are possible side effects of Cuvposa?

Cuvposa can cause serious side effects including:

• Constipation. Constipation is common with Cuvposa. Tell your doctor if your child strains with bowel movements, goes longer between bowel movements, cannot have a bowel movement, or their stomach is firm and large. The dose of Cuvposa may need to be decreased or stopped.
• Diarrhea and intestinal blockage. Diarrhea can be an early symptom of a blockage in the intestine. This is especially true if you child has a colostomy or ileostomy. Tell your doctor if your child has any diarrhea while taking Cuvposa.
• Problems with control of body temperature (overheating or heat stroke). Cuvposa can cause your child to sweat less. Your child can become overheated, and develop heat stroke if they are in an area that is very hot. Avoid overheating. Call your doctor right away if your child becomes sick and has any of these symptoms of heatstroke:
  • hot, red skin
  • decreased alertness or passing out (unconsciousness)
  • fast, weak pulse
  • fast, shallow breathing
  • increased body temperature (fever)

The most common side effects of Cuvposa include:

• dry mouth
• vomiting
• flushing of the face or skin
• nasal congestion
• headache
• swollen sinuses (sinusitis)
• upper respiratory tract infection
• problem urinating, difficulty starting urination

Tell your doctor if your child has any side effect that concerns you or that does not go away. These are not all the possible side effects of Cuvposa.

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 Cuvposa?

Store Cuvposa between 68°F to 77°F (20°C to 25°C).

Keep Cuvposa out of the reach of children.

General information and Cuvposa:

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Cuvposa for a condition for which it was not prescribed. Do not give Cuvposa to other people even if they have the same condition. It may harm them.

This leaflet summarizes the most important information about Cuvposa. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Cuvposa that is written for health professionals.

For more information, go to: www.Cuvposa.com or call 866-862-1211.

What are the ingredients in Cuvposa?

Active Ingredient: glycopyrrolate

Inactive Ingredients: citric acid, glycerin, natural and artificial cherry flavor, methylparaben, propylene glycol, propylparaben, saccharin sodium, sodium citrate, sorbitol solution, and purified water

Issued May 2011

Manufactured by:
Mikart, Inc.
Atlanta, GA 30318

Manufactured for:
Merz North America, Inc.
Raleigh, NC 27615

© 2016 Merz Pharmaceuticals, LLC
Cuvposa® is a registered trademark of Merz Pharmaceuticals, LLC

GLY-PPI-07
Rev 04/2016

PRINCIPAL DISPLAY PANEL - 473 mL Bottle Carton

NDC: 0259-0501-16

16 fl. oz.
(473 mL)

Cuvposa®
(glycopyrrolate) oral solution
1 mg/5 mL
(0.2 mg/mL)

Rx Only
For Oral Use Only

Manufactured for:
Merz Pharmaceuticals, LLC
Greensboro, NC 27410

Manufactured by:
Mikart, Inc.
Atlanta, GA 30318

Cuvposa (glycopyrrolate) reduces the secretions of certain organs in the body.

Cuvposa is used to reduce drooling in children ages 3 to 16 who have certain medical conditions, such as cerebral palsy.

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

You should not use Cuvposa if you are allergic to glycopyrrolate, or if you have:

• a bladder obstruction or other urination problems;

• a blockage in your digestive tract (stomach or intestines), severe constipation;

• severe ulcerative colitis or toxic megacolon;

• eye problems;

• glaucoma; or

• myasthenia gravis.

To make sure Cuvposa is safe for you, tell your doctor if you have ever had:

• liver or kidney disease;

• heart disease, a heart rhythm disorder;

• high blood pressure;

• a stomach disorder such as hiatal hernia, reflux disease, or slow digestion;

• a colostomy or ileostomy;

• a thyroid disorder; or

• a nerve disorder.

It is not known whether Cuvposa will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether glycopyrrolate passes into breast milk or if it could affect the nursing baby. This medicine can slow breast milk production. Tell your doctor if you are breast-feeding.

Do not give Cuvposa to a child without medical advice.

Get emergency medical help if you have signs of an allergic reaction to Cuvposa: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using Cuvposa and call your doctor at once if you have:

• severe constipation, severe stomach pain and bloating;

• diarrhea (especially if you have a colostomy or ileostomy);

• painful or difficult urination;

• fast or pounding heartbeats, fluttering in your chest;

• confusion, severe drowsiness;

• fever, shallow breathing, weak pulse, hot and red skin; or

• (in a child taking glycopyrrolate) dry diapers, fussiness, or excessive crying.

Common Cuvposa side effects may include:

• constipation, nausea, vomiting, bloating;

• drowsiness, dizziness, weakness;

• sleep problems (insomnia);

• blurred vision;

• dry mouth, stuffy nose;

• decreased sweating;

• flushing (warmth, redness, or tingly feeling);

• headache; or

• rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective.

Other drugs may interact with glycopyrrolate, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.