Cuvposa
(glycopyrrolate)Dosage & Administration
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Cuvposa Prescribing Information
CUVPOSA is indicated to reduce chronic severe drooling in patients aged 3 to 16 years with neurologic conditions associated with problem drooling (e.g., cerebral palsy).
CUVPOSA must be measured and administered with an accurate measuring device [see Patient Counseling Information (17)].
Initiate dosing at 0.02 mg/kg orally three times daily and titrate in increments of 0.02 mg/kg every 5-7 days based on therapeutic response and adverse reactions. The maximum recommended dosage is 0.1 mg/kg three times daily not to exceed 1.5-3 mg per dose based upon weight. For greater detail, see Table 1.
During the four-week titration period, dosing can be increased with the recommended dose titration schedule while ensuring that the anticholinergic adverse events are tolerable. Prior to each increase in dose, review the tolerability of the current dose level with the patient's caregiver.
CUVPOSA should be dosed at least one hour before or two hours after meals.
The presence of high fat food reduces the oral bioavailability of CUVPOSA if taken shortly after a meal [see Clinical Pharmacology (12.3)].
| Weight | Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Dose Level 5 | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| kg | lbs | (~0.02 mg/kg) | (~0.04 mg/kg) | (~0.06 mg/kg) | (~0.08 mg/kg) | (~0.1 mg/kg) | |||||
| 13-17 | 27-38 | 0.3 mg | 1.5 mL | 0.6 mg | 3 mL | 0.9 mg | 4.5 mL | 1.2 mg | 6 mL | 1.5 mg | 7.5 mL |
| 18-22 | 39-49 | 0.4 mg | 2 mL | 0.8 mL | 4 mL | 1.2 mg | 6 mL | 1.6 mg | 8 mL | 2.0 mg | 10 mL |
| 23-27 | 50-60 | 0.5 mg | 2.5 mL | 1.0 mg | 5 mL | 1.5 mg | 7.5 mL | 2.0 mg | 10 mL | 2.5 mg | 12.5 mL |
| 28-32 | 61-71 | 0.6 mg | 3 mL | 1.2 mg | 6 mL | 1.8 mg | 9 mL | 2.4 mg | 12 mL | 3.0 mg | 15 mL |
| 33-37 | 72-82 | 0.7 mg | 3.5 mL | 1.4 mg | 7 mL | 2.1 mg | 10.5 mL | 2.8 mg | 14 mL | 3.0 mg | 15 mL |
| 38-42 | 83-93 | 0.8 mg | 4 mL | 1.6 mg | 8 mL | 2.4 mg | 12 mL | 3.0 mg | 15 mL | 3.0 mg | 15 mL |
| 43-47 | 94-104 | 0.9 mg | 4.5 mL | 1.8 mg | 9 mL | 2.7 mg | 13.5 mL | 3.0 mg | 15 mL | 3.0 mg | 15 mL |
| ≥48 | ≥105 | 1.0 mg | 5 mL | 2.0 mg | 10 mL | 3.0 mg | 15 mL | 3.0 mg | 15 mL | 3.0 mg | 15 mL |
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)].
CUVPOSA is contraindicated in:
- Patients with medical conditions that preclude anticholinergic therapy (e.g., glaucoma, paralytic ileus, unstable cardiovascular status in acute hemorrhage, severe ulcerative colitis, toxic megacolon complicating ulcerative colitis, myasthenia gravis).
- Patients taking solid oral dosage forms of potassium chloride. The passage of potassium chloride tablets through the gastrointestinal (GI) tract may be arrested or delayed with coadministration of CUVPOSA.
Constipation or Intestinal Pseudo-obstruction
Constipation is a common dose-limiting adverse reaction which sometimes leads to glycopyrrolate discontinuation [see Adverse Reactions (6.1)]. Assess patients for constipation, particularly within 4-5 days of initial dosing or after a dose increase. Intestinal pseudo-obstruction has been reported and may present as abdominal distention, pain, nausea or vomiting.
Incomplete Mechanical Intestinal Obstruction
Diarrhea may be an early symptom of incomplete mechanical intestinal obstruction, especially in patients with ileostomy or colostomy. If incomplete mechanical intestinal obstruction is suspected, discontinue treatment with CUVPOSA and evaluate for intestinal obstruction.
High Ambient Temperatures
In the presence of high ambient temperature, heat prostration (fever and heat stroke due to decreased sweating) can occur with the use of anticholinergic drugs such as CUVPOSA. Advise patients/caregivers to avoid exposure of the patient to hot or very warm environmental temperatures.
Operating Machinery or an Automobile
CUVPOSA may produce drowsiness or blurred vision. As appropriate for a given age, warn the patient not to engage in activities requiring mental alertness such as operating a motor vehicle or other machinery, or performing hazardous work while taking CUVPOSA.
Anticholinergic Drug Effects
Use CUVPOSA with caution in patients with conditions that are exacerbated by anticholinergic drug effects including:
- Autonomic neuropathy
- Renal disease
- Ulcerative colitis – Large doses may suppress intestinal motility to the point of producing a paralytic ileus and for this reason may precipitate or aggravate "toxic megacolon", a serious complication of the disease
- Hyperthyroidism
- Coronary heart disease, congestive heart failure, cardiac tachyarrhythmias, tachycardia, and hypertension
- Hiatal hernia associated with reflux esophagitis, since anticholinergic drugs may aggravate this condition