Sancuso (granisetron transdermal patch system)

Sancuso (granisetron transdermal patch system) is an anti-nauseant and antiemetic used to prevent nausea and vomiting resulting from chemotherapy for cancer. Other formulations of granisetron (for example, Kytril) are administered by mouth or injection. 

Certain chemotherapeutic agents used for treating cancer stimulate the release of a neurotransmitter called serotonin from nerves in the brain. Neurotransmitters are chemicals that nerves use to communicate with one another. 

Released serotonin binds to other nerves in an area of the brain called the chemoreceptor trigger zone, causing nausea and vomiting. Granisetron, the active ingredient in Sancuso, prevents serotonin from binding to nerves in the chemoreceptor trigger zone thereby preventing nausea and vomiting. 

Common side effects of Sancuso include

• constipation,
• headache,
• anxiety,
• dizziness,
• diarrhea,
• abdominal pain,
• chest pain, and
• application site reactions (redness, bumps, rashes, blisters).

Allergic reactions may occur rarely.

Serious side effects of Sancuso include severe

• redness, itching, swelling, or other irritation where the patch is worn; and
• high levels of serotonin in the body (symptoms include agitation, hallucinations, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting).

Drug interaction studies have not been conducted with Sancuso. Sancuso is broken down in the body by cytochrome P-450 liver enzymes. 

Drugs that increase (for example, phenobarbital) or decrease (for example, ketoconazole) the activity of cytochrome P-450 liver enzymes may affect the levels of Sancuso in the body. 

There are no adequate and well-controlled studies of Sancuso in pregnant women. Sancuso should be used during pregnancy only if clearly needed. 

It is unknown if Sancuso is excreted in breast milk. Nursing mothers should consider not breastfeeding.

The most common adverse effects of granisetron are

• constipation and
• headache.

Other adverse effects include

• anxiety,
• dizziness,
• diarrhea,
• abdominal pain, and
• chest pain.

Allergic reactions may occur rarely.

Application site reactions (redness, bumps, rashes, blisters) may occur. The patch must be removed if serious skin reactions or generalized skin reactions occur. Light exposure (sunlight, sun lamps, tanning beds) may reduce the effect of granisetron, and granisetron may cause light sensitivity.

To avoid light exposure, the application site should be covered with clothing during therapy and for 10 days after the patch is removed. Granisetron may mask the symptoms of certain gastrointestinal conditions, for example, gastroparesis or ileus (paralysis of the muscles of the stomach and small intestine, respectively) by reducing the nausea and vomiting that are their primary symptoms.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety of Sancuso was evaluated in a total of 404 patients undergoing chemotherapy who participated in two double-blind, comparator studies with patch treatment durations of up to 7 days. The control groups included a total of 406 patients who received a daily dose of 2 mg oral granisetron, for 1 to 5 days.

Adverse reactions occurred in 8.7% (35/404) of patients receiving Sancuso and 7.1% (29/406) of patients receiving oral granisetron. The most common adverse reaction was constipation that occurred in 5.4% of patients in the Sancuso group and 3.0% of patients in the oral granisetron group.

Table 1 lists the adverse reactions that occurred in at least 3% of patients treated with Sancuso or oral granisetron.

Table 1: Incidence of Adverse Reactions in Double-Blind, Active Comparator Controlled Studies in Cancer Patients Receiving Chemotherapy (Events ≥ 3% in either group)

5-HT3 receptor antagonists, such as granisetron, may be associated with arrhythmias or ECG abnormalities. Three ECGs were performed on 588 patients in a randomized, parallel group, double-blind, double-dummy study: at baseline before treatment, the first day of chemotherapy, and 5 to 7 days after starting chemotherapy.

QTcF prolongation greater than 450 milliseconds was seen in a total of 11 (1.9%) patients after receiving granisetron, 8 (2.7%) on oral granisetron, and 3 (1.1%) on the patch. No new QTcF prolongation greater than 480 milliseconds was observed in any patient in this study. No arrhythmias were detected in this study.

Adverse reactions reported in clinical trials with other formulations of granisetron include the following:

• Gastrointestinal: abdominal pain, diarrhea, constipation, elevation of ALT and AST levels, nausea and vomiting
• Cardiovascular: Hypertension, hypotension, angina pectoris, atrial fibrillation and syncope have been observed rarely
• Central Nervous System: dizziness, insomnia, headache, anxiety, somnolence and asthenia
• Hypersensitivity: rare cases of hypersensitivity reactions, sometimes severe (e.g. anaphylaxis, shortness of breath, hypotension, urticaria) have been reported
• Other: fever; events often associated with chemotherapy have also been reported: leucopenia, decreased appetite, anemia, alopecia, thrombocytopenia.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of Sancuso. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

• General Disorders and Administration Site Conditions: Application site reactions (pain, pruritus, erythema, rash, irritation, vesicles, burn, discoloration, urticaria); patch non-adhesion)
• Cardiac Disorders: bradycardia, chest pain, palpitations, sick sinus syndrome