granisetron (Sustol, Sancuso, Granisol Oral Solution)
Dosing and uses of Sustol, Sancusco (granisetron)
Adult dosage forms and strengths
injectable solution
- Avalailable as generics
- 0.1mg/mL
- 1mg/mL
extended relase SC injection
- 10mg/0.4mL single-dose prefilled syringe (Sustol)
patch
- 3.1mg/24hr (Sancuso)
tablets
- 1mg (generic)
oral solution
- 1mg/5mL (Granisol)
Chemotherapy Induced Nausea & Vomiting
OraL
- 1 mg PO 1 hr before chemotherapy, then 1 mg 12 hr after 1st dose; OR 2 mg 1 hr before chemotherapy
IV
- 0.01 mg/kg/dose infused over 5 min or direct injected over 30 sec, 30 min before chemotherapy
Patch (Sancuso)
- 1 patch 24-48 hr before chemotherapy; keep at least 24 hr post-chemo treatment
- May wear same patch for up to 7 days
SC (Sustol)
- Indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens
- 10 mg SC in combination with dexamethasone at least 30 minutes before the initiation of MEC or AC combination chemotherapy
- Administer on Day 1 of chemotherapy and not more frequently than once q7days because of the extended-release properties of the formulation
- Also see Administration
- Dexamethasone with Sustol
- MEC regimen: Dexamethasone 8 mg IV on Day 1
- AC combination chemotherapy regimens: Dexamethasone 20 mg IV on Day 1, followed by 8 mg PO BID on Days 2, 3, and 4
- If administered with an NK1 receptor antagonist, see the prescribing information of the NK1 receptor antagonist for the recommended dexamethasone dosage
Radiation-Induced Nausea & Vomiting
2 mg PO, 1 hr before radiation treatment
Postoperative Nausea & Vomiting
Prevention: 1 mg (undiluted) IV push over 30 seconds; administer before anesthetic induction or immediately before reversal of anesthesia
Treatment: 1 mg (undiluted) IV push over 30 seconds
Dosage modifications
Renal impairment
- SC (Sustol)
- Moderate (CrCl 30-59 mL/min): Administer on Day 1 of chemotherapy and not more frequently than once q14days
- Severe (CrCl <30 mL/min): Avoid use
- IV
- Severe (CrCl <30 mL/min): Total clearance was not affected in patients with severe renal failure who received a single 40 mcg/kg IV dose
- PO
- No dosage adjustment required
Hepatic impairment
- No dosage adjustment required
Pediatric dosage forms and strengths
injectable solution
- 0.1mg/mL
- 1mg/mL
Chemotherapy Induced Nausea & Vomiting
<2 years: Safey and efficacy not established
2-16 years: As adults; 0.01 mg/kg infused over 5 min or direct inj over 30 sec, 30 min before chemotherapy
Oral administration: Currently FDA-approved for IV administration in children; safety and efficacy of oral administration is not established
Postoperative Nausea & Vomiting
Safety and efficacy not established
Not approved for postoperative N/V in pediatric patients because of lack of efficacy and QT prolongation observed in clinical trials
Geriatric dosage forms and strengths
Chemotherapy Induced Nausea & Vomiting
Oral: 2 mg 1 hr before chemotherapy, then 1 mg 12 hr after 1st dose; OR 2 mg 1 hr before chemo
IV: 0.01 mg/kg/dose infused over 5 min or direct injected over 30 sec, 30 min before chemotherapy
Patch: 1 patch 24-48 hr before chemotherapy; keep at least 24 hr post-chemo treatment; may wear same patch for up to 7 days
Extended-release SC: 10 mg SC in combination with dexamethasone at least 30 minutes before the initiation of MEC or AC combination chemotherapy
Radiation-Induced Nausea & Vomiting
2 mg PO, 1 hr before radiation treatment
Postoperative Nausea & Vomiting
Prevention: 1 mg (undiluted) IV push over 30 seconds; administer before anesthetic induction or immediately before reversal of anesthesia
Treatment: 1 mg (undiluted) IV push over 30 seconds
Renal impairment
SC (Sustol): Moderate (CrCl 30-59 mL/min): Administer on Day 1 of chemotherapy and not more frequently than once q14days
SC (Sustol): Severe (CrCl <30 mL/min): Avoid use
IV: Severe (CrCl <30 mL/min): Total clearance was not affected in patients with severe renal failure who received a single 40 mcg/kg IV dose
PO: No dosage adjustment required
Hepatic impairment
No dosage adjustment required
Sustol, Sancusco (granisetron) adverse (side) effects
>10%
Headache (10-21%)
1-10%
Diarrhea (1-9%)
Constipation (3-18%)
Asthenia (5%)
Somnolence (10%)
Sedation (10%)
Drowsiness (10%)
Frequency not defined
Anxiety
Fatigue
Malaise
Increased LFTs
Postmarketing reports
Administration site reactions: Pain, pruritus, erythema, rash, irritation, vesicles, burn, discoloration, urticaria
Cardiac Disorders: bradycardia, chest pain, palpitations, sick sinus syndrome
Warnings
Contraindications
Hypersensitivity
Coadministration with apomorphine; combination reported to cause profound hypotension and loss of consciousness
Cautions
Liver disease
May mask paralytic ileus/gastric distension
Cross-sensitivity among selective 5-HT antagonists may occur
Serotonin syndrome reported with 5-HT3 receptor antagonists alone but particularly with concomitant use of serotonergic drugs including SSRIs, SNRIs, MAO inhibitors, lithium, tramadol, methylene blue IV, and mirtazapine
Protect patch from sunlight
May prolong QT interval; coadministration with drugs known to prolong QT interval may result in serious arrhythmias
Mild application site reactions have occurred; remove patch if severe reactions or generalized skin reaction occur
Avoid exposing granisetron patch and surrounding area to direct external heat sources, such as heating pads; plasma concentration continues to increase during period of heat exposure
Pregnancy and lactation
Pregnancy category: B
Lactation: excretion in milk unknown; use with caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Sustol, Sancusco (granisetron)
Mechanism of action
Selective 5-HT3 receptor antagonist; granisetron binds to 5-HT3 receptors both in the peripheral and central nervous system with primary effects in GI tract
Pharmacokinetics
Half-life: 3-14 hr
Onset: 4-10 min (IV)
Duration: 24 hr (IV)
Bioavailability: 60% (PO)
Release rate (patch): 3.1 mg/24 hr
Protein bound: 65%
Vd: 2-4 L/kg
Metabolism: Extensively metabolized in liver via N-demethylation, oxidation, conjugation, and CYP3A subfamily
Metabolites: Inactive
Total body clearance: 0.2-0.79 L/hr/kg
Excretion
- Feces: 38%
- Urine: 60%
Administration
IV Incompatibilities
Y-site: amphotericin B
IV Compatibilities
Solution: BWI, D5/½NS, D5/NS, D5W, Ns
Additive: dexamethasone sodium phosphate, methylprednisolone sodium succinate
Syringe: dexamethasone sodium phosphate, methylprednisolone sodium succinate
Y-site (partial list): allopurinol, amphotericin B cholSO4, ampicillin, butorphanol, carboplatin, cisplatin, ctarabine, dactinomycin, docetaxel, diphenhydramine, etoposide, famotidine, fluorouracil, furosemide, fluconazole, heparin, hydromorphone, linezolid, lorazepam, MgSO4, meoperidine, morphine, metoclopramide, metronidazole, paclitaxel, KCl, prochlorperazine, promethazine, Na-bicarb, thiotepa, vincristine, vancomycin
IV Preparation
IV infusion: dilute to 20-50 mL with D5W or Ns
IV Administration
IVP undiluted over 30 sec, or
IV infusion over 5 min after dilution to 20-50 mL with D5W or Ns
SC Preparation (Sustol)
At least 60 minutes before administration, remove kit from refrigerator
Unpack the kit to allow the Sustol syringe and all other contents to warm to room temperature
Activate 1 of the syringe warming pouches, and wrap the syringe in the warming pouch for 5-6 minutes to warm Sustol to body temperature
Prior to administration, inspect the Sustol syringe visually for particulate matter and discoloration
Note that the syringe is amber colored glass
Do not administered if particulate matter or discoloration observed, the tip cap is missing or has been tampered with, or if the Luer fitting is missing or dislodged
SC Administration (Sustol)
For SC injection only
Intended for administration by a health care provider
Use standard aseptic technique when performing the SC injection
Administer as a single SC injection in the back of the upper arm or in the skin of the abdomen at least 1-inch away from the umbilicus
Avoid injecting anywhere the skin is burned, hardened, inflamed, swollen, or otherwise compromised
Topical anesthetic may be used at the injection site prior to administration
Due to the viscosity of the liquid, the time required for injection is greater than most medications administered SC; requires a slow, sustained injection which may take up to 20-30 seconds
Pressing the plunger harder will NOT expel the viscous liquid faster
Storage
IV
- Store at controlled room temperature 20-25°C (68-77°F)
- Protect from light and freezing
- Stable for 24 hr after dilution
Extended-release SC (Sustol)
- Refrigerate at 2-8°C (36-46°F)
- Can be placed back in the refrigerator after being kept at room temperature
- Can remain at room temperature for up to a maximum of 7 days
- Protect from light
- Do not freeze
