Granisetron Hydrochloride

Pronunciation: (gra-NI-se-tron HYE-droe-KLOR-ide)
Class: 5-HT ₃ receptor antagonist

Trade Names

Kytril
- Injection 1 mg/mL
- Tablets 1 mg

Sancuso
- Transdermal 3.1 mg per 24 h (34.3 mg per 52 cm ² )

Pharmacology

Serotonin receptors of the 5-HT ₃ type are located peripherally on vagal nerve terminals, enteric neurons in the GI tract, and centrally in the chemoreceptor trigger zone. During chemotherapy, mucosal enterochromaffin cells from the small intestine release serotonin, which stimulates the 5-HT ₃ receptors. This evokes vagal afferent discharge, inducing vomiting.

Pharmacokinetics

Absorption

Mean C _max is 64 ng/mL.

Transdermal

T _max is 48 h. C _max is 5 ng/mL. Mean AUC _0-168h is 527 ng•h/mL.

Distribution

Vd is about 3 L/kg. Protein binding is 65%.

Metabolism

Involves N-demethylation and aromatic ring oxidation followed by conjugation.

Elimination

Mean t _{1/ 2} is 5 h. Mean Cl is 0.79 L/h/kg. Cl is predominately by hepatic metabolism.

IV

Approximately 12% is excreted unchanged in the urine; the rest is excreted as metabolites, 49% in urine and 34% in feces.

Peak

5 to 30 sec (injection).

Special Populations

Renal Function Impairment

Cl not affected in patients with severe renal failure.

Hepatic Function Impairment

Total Cl decreased by about 50%.

Elderly

Mean C _max is 57 ng/mL. Mean t _{1/ 2} is 7.69 h. Mean Cl is 0.44 L/h/kg. Mean Vd is about 4 L/kg.

Cancer patients

C _max is 84 ng/mL. Mean t _{1/ 2} is 9 h. Cl is 0.38 L/h/kg.

Indications and Usage

Adults

Prevention of chemotherapy-induced nausea and vomiting; prevention of radiation-induced nausea and vomiting (oral only); postoperative nausea and vomiting (injection only).

Children (2 to 16 yr of age)

Prevention of chemotherapy-induced nausea and vomiting (injection only). Safety and efficacy not established in patients younger than 2 yr of age.

Contraindications

Standard considerations.

Dosage and Administration

Chemotherapy-Induced Nausea and Vomiting
Adults

IV 10 mcg/kg (commonly rounded to nearest 1 mg), given up to 30 min before starting chemotherapy. Give only on day(s) of chemotherapy.

Adults

PO 1 mg twice daily. Give the first oral dose up to 1 h before chemotherapy and the second dose 12 h later. Give granisetron only on day(s) of chemotherapy. Alternately, a single 2 mg dose may be given up to 1 h before chemotherapy.

Adults

Transdermal 1 patch to the upper outer arm a minimum of 24 h before chemotherapy; may be applied up to a max of 48 h before chemotherapy, as appropriate. Remove the patch a minimum of 24 h after completion of chemotherapy. The patch can be worn for up to 7 days, depending on the duration of the chemotherapy regimen.

Children

IV 10 mcg/kg, given up to 30 min before starting chemotherapy. Give only on day(s) of chemotherapy.

Prevention/Treatment Postoperative Nausea and Vomiting
Adults

IV For prevention, use 1 mg, undiluted, administered over 30 seconds, before induction of anesthesia or immediately before reversal of anesthesia. For treatment, use 1 mg, undiluted, administered over 30 seconds, after surgery.

Radiation-Induced Nausea and Vomiting
Adults

PO 2 mg once daily. Give the dose up to 1 h before radiation therapy. Give granisetron only on day(s) of radiation therapy.

Storage/Stability

Store transdermal patch at 59° to 86°F.

Drug Interactions

CYP-450 enzymes

Granisetron does not induce or inhibit the CYP-450 system; however, it is metabolized partially by CYP-450 3A enzymes. Medications that induce or inhibit CYP-450 3A isoenzymes may alter granisetron metabolism.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Angina pectoris, atrial fibrillation, hypertension, hypotension, syncope.

CNS

Headache (3%); agitation, anxiety, asthenia, dizziness, mood changes, insomnia, somnolence.

Dermatologic

Rash.

GI

Constipation (5%); abnormal pain, decreased appetite, diarrhea, elevated AST and ALT, nausea, vomiting.

Musculoskeletal

Asthenia.

Miscellaneous

Alopecia, fever, hypersensitivity reactions (eg, anaphylaxis, shortness of breath, urticaria), shivers, taste disorder.

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy of the injection in children younger than 2 yr of age not established. Safety and efficacy of the transdermal patch in children younger than 18 yr of age not established.

Photosensitivity

May occur.

Delayed nausea and vomiting

Granisetron is not consistently effective for treating delayed nausea and vomiting.

GI

May mask a progressive ileus and/or gastric distention.

Overdosage

Symptoms

Headache.

Patient Information

Advise patient, family, or caregiver that IV medication will be prepared and administered by health care provider in a medical facility.
Review dosing schedule with patient. Caution patient taking oral medication that tablets or solution must be taken no more than 1 h before chemotherapy administration or radiation therapy to provide greatest protection against nausea and vomiting.
Advise patient that medication will greatly reduce likelihood of nausea or vomiting, but that these events are still possible.
Instruct patient to inform health care provider if medication does not prevent nausea or vomiting.
Advise patient to report any of the following to health care provider: intolerable headache; persistent or intolerable constipation or diarrhea; persistent weakness.
Advise patient that if severe or generalized skin reaction occurs when using the transdermal patch, to remove the patch.
Advise patient to cover the patch application site with clothing if there is a risk of exposure to sunlight during the period of wear and for 10 days following its removal.