Zuplenz

2.1 Prevention of Nausea and Vomiting Associated with Highly Emetogenic Cancer Chemotherapy

Adults
The recommended adult oral dosage of ZUPLENZ (ondansetron) oral soluble film is 24 mg given successively as three 8 mg films administered 30 minutes before the start of single-day highly emetogenic chemotherapy, including cisplatin ≥50 mg/m2. Each ZUPLENZ oral soluble film should be allowed to dissolve completely before administering the next film [see Dosage and Administration (2.6)]. Multiday, single-dose administration of a 24 mg dosage has not been studied.

Pediatrics
Safety and effectiveness of ZUPLENZ in pediatric patients have not been established for this indication.

2.2 Prevention of Nausea and Vomiting Associated with Moderately Emetogenic Cancer Chemotherapy

Adults
The recommended adult oral dosage is one 8 mg ZUPLENZ oral soluble film given twice a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. One 8 mg ZUPLENZ oral soluble film should be administered twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy [see Dosage and Administration (2.6)].

Pediatrics
For pediatric patients 12 years of age and older, the dosage is the same as for adults. For pediatric patients 4 through 11 years of age, the dosage is one 4 mg ZUPLENZ oral soluble film given three times a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with subsequent doses 4 and 8 hours after the first dose. One 4 mg ZUPLENZ oral soluble film should be administered three times a day (every 8 hours) for 1 to 2 days after completion of chemotherapy [see Dosage and Administration (2.6)].

2.3 Prevention of Nausea and Vomiting Associated with Radiotherapy

Adults
The recommended adult oral dosage of ZUPLENZ oral soluble film is one 8 mg film given three times a day [see Dosage and Administration (2.6)].

For total body irradiation, one 8 mg ZUPLENZ oral soluble film should be administered 1 to 2 hours before each fraction of radiotherapy administered each day.

For single high-dose fraction radiotherapy to the abdomen, one 8 mg ZUPLENZ oral soluble film should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for 1 to 2 days after completion of radiotherapy.

For daily fractionated radiotherapy to the abdomen, one 8 mg ZUPLENZ oral soluble film should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for each day radiotherapy is given.

Pediatrics
Safety and effectiveness of ZUPLENZ in pediatric patients have not been established for this indication.

2.4 Prevention of Postoperative Nausea and/or Vomiting

Adults
The recommended adult oral dosage of ZUPLENZ oral soluble film is 16 mg given successively as two 8 mg films 1 hour before induction of anesthesia. Each ZUPLENZ oral soluble film should be allowed to dissolve completely before administering the next film [see Dosage and Administration (2.6)].

Pediatrics
Safety and effectiveness of ZUPLENZ in pediatric patients have not been established for this indication.

2.5 Dosage Adjustment for Patients with Impaired Hepatic Function

In patients with severe hepatic impairment (Child-Pugh score of 10 or greater)2, clearance is reduced and apparent volume of distribution is increased with a resultant increase in plasma half-life [see Clinical Pharmacology (12.3)]. In such patients, a total daily dose of 8 mg should not be exceeded.

2.6 Important Administration Instructions

With dry hands, fold the pouch along the dotted line to expose the tear notch. While still folded, tear the pouch carefully along the edge and remove the ZUPLENZ oral soluble film from the pouch. Immediately place the film on top of the tongue where it dissolves in 4 to 20 seconds. Once the ZUPLENZ oral soluble film is dissolved, swallow with or without liquid [see Clinical Pharmacology (12.3)]. Wash hands after taking ZUPLENZ.

Adults

The dose of clonidine hydrochloride tablets must be adjusted according to the patient's individual blood pressure response. The following is a general guide to its administration.

Initial Dose

0.1 mg tablet twice daily (morning and bedtime). Elderly patients may benefit from a lower initial dose.

Maintenance Dose

Further increments of 0.1 mg per day may be made at weekly intervals if necessary until the desired response is achieved. Taking the larger portion of the oral daily dose at bedtime may minimize transient adjustment effects of dry mouth and drowsiness. The therapeutic doses most commonly employed have ranged from 0.2 mg to 0.6 mg per day given in divided doses.

Studies have indicated that 2.4 mg is the maximum effective daily dose, but doses as high as this have rarely been employed.

Renal Impairment

Patients with renal impairment may benefit from a lower initial dose. Patients should be carefully monitored. Since only a minimal amount of clonidine is removed during routine hemodialysis, there is no need to give supplemental clonidine following dialysis.