Kytril (Granisetron Hydrochloride) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

Chemotherapy-Induced Nausea and Vomiting

Over 3700 patients have received KYTRIL Tablets in clinical trials with emetogenic cancer therapies consisting primarily of cyclophosphamide or cisplatin regimens.

In patients receiving KYTRIL Tablets 1 mg bid for 1, 7 or 14 days, or 2 mg qd for 1 day, adverse experiences reported in more than 5% of the patients with comparator and placebo incidences are listed in Table 4.

Table 4 Principal Adverse Events in Clinical Trials

	Percent of Patients With Event
	KYTRIL 1 Tablets 1 mg bid (n=978)	KYTRIL Tablets 2 mg qd (n=1450)	ComparatorMetoclopramide/dexamethasone; phenothiazines/dexamethasone; dexamethasone alone; prochlorperazine. (n=599)	Placebo (n=185)
HeadacheUsually mild to moderate in severity.	21%	20%	13%	12%
Constipation	18%	14%	16%	8%
Asthenia	14%	18%	10%	4%
Diarrhea	8%	9%	10%	4%
Abdominal pain	6%	4%	6%	3%
Dyspepsia	4%	6%	5%	4%

Other adverse events reported in clinical trials were:

Gastrointestinal: In single-day dosing studies in which adverse events were collected for 7 days, nausea (20%) and vomiting (12%) were recorded as adverse events after the 24-hour efficacy assessment period.

Hepatic: In comparative trials, elevation of AST and ALT (>2 times the upper limit of normal) following the administration of KYTRIL Tablets occurred in 5% and 6% of patients, respectively. These frequencies were not significantly different from those seen with comparators (AST: 2%; ALT: 9%).

Cardiovascular: Hypertension (1%); hypotension, angina pectoris, atrial fibrillation, and syncope have been observed rarely.

Central Nervous System: Dizziness (5%), insomnia (5%), anxiety (2%), somnolence (1%). One case compatible with, but not diagnostic of, extrapyramidal symptoms has been reported in a patient treated with KYTRIL Tablets.

Hypersensitivity: Rare cases of hypersensitivity reactions, sometimes severe (eg, anaphylaxis, shortness of breath, hypotension, urticaria) have been reported.

Other: Fever (5%). Events often associated with chemotherapy also have been reported: leukopenia (9%), decreased appetite (6%), anemia (4%), alopecia (3%), thrombocytopenia (2%).

Over 5000 patients have received injectable KYTRIL in clinical trials.

Table 5 gives the comparative frequencies of the five commonly reported adverse events (≥3%) in patients receiving KYTRIL Injection, 40 mcg/kg, in single-day chemotherapy trials. These patients received chemotherapy, primarily cisplatin, and intravenous fluids during the 24-hour period following KYTRIL Injection administration.

Table 5 Principal Adverse Events in Clinical Trials — Single-Day Chemotherapy

	Percent of Patients with Event
	KYTRIL InjectionAdverse events were generally recorded over 7 days post-KYTRIL Injection administration. 40 mcg/kg (n=1268)	ComparatorMetoclopramide/dexamethasone and phenothiazines/dexamethasone. (n=422)
Headache	14%	6%
Asthenia	5%	6%
Somnolence	4%	15%
Diarrhea	4%	6%
Constipation	3%	3%

In the absence of a placebo group, there is uncertainty as to how many of these events should be attributed to KYTRIL, except for headache, which was clearly more frequent than in comparison groups.

Radiation-Induced Nausea and Vomiting

In controlled clinical trials, the adverse events reported by patients receiving KYTRIL Tablets and concurrent radiation were similar to those reported by patients receiving KYTRIL Tablets prior to chemotherapy. The most frequently reported adverse events were diarrhea, asthenia, and constipation. Headache, however, was less prevalent in this patient population.

REPORTS OF SUSPECTED KYTRIL SIDE EFFECTS / ADVERSE REACTIONS

Possible Kytril side effects / adverse reactions in 23 year old male

Reported by a physician from United States on 2011-11-10

Patient: 23 year old male weighing 78.7 kg (173.2 pounds)

Reactions: Pneumonia Fungal, Systemic Mycosis, Dyskinesia, Chest Pain, Sinusitis Fungal, Febrile Neutropenia, Muscle Spasms

Adverse event resulted in: hospitalization

Suspect drug(s):
Study Drug
    Dosage: unk, see text
    Indication: Lymphocytic Leukaemia

Demerol
    Dosage: unk
    Indication: Pain
    Start date: 2011-10-16

Demerol
    Indication: Chills

Kytril
    Indication: Vomiting

Ativan
    Dosage: 1 mg, q6h
    Administration route: Oral
    Indication: Nausea
    Start date: 2011-03-11

Scopolamine
    Indication: Pain

Ativan
    Indication: Anxiety

Fentanyl
    Dosage: 100 mcg, q72h
    Indication: Pain
    Start date: 2011-09-19
    End date: 2011-10-17

Marinol /00897601/
    Dosage: 5 mg, tid
    Administration route: Oral
    Indication: Nausea
    Start date: 2011-04-04
    End date: 2011-10-16

Scopolamine
    Dosage: 1.5 mg, q72h
    Indication: Nausea
    Start date: 2011-10-06
    End date: 2011-10-14

Kytril
    Dosage: unk
    Indication: Nausea
    Start date: 2011-10-06

Dilaudid
    Dosage: 2 mg, q3h
    Indication: Pain
    Start date: 2011-06-28
    End date: 2011-10-16

Celexa
    Dosage: unk
    Indication: Depression
    Start date: 2011-03-31

Other drugs received by patient: Hydrocortisone/lidocaine; Omeprazole; Heparin; Nystatin; Colace Capsules; Morphine Sulfate; Senna-Mint WAF; Chlorhexidine Gluconate; Loratadine; Neupogen; Lidocaine; Cipro; Famvir /01226201/; Fluconazole; Mepron /01181501/; Concerta; Polyethylene Glycol

Possible Kytril side effects / adverse reactions in 23 year old male

Reported by a physician from United States on 2011-11-18

Patient: 23 year old male weighing 78.6 kg (172.9 pounds)

Reactions: Abdominal Pain, Confusional State, Pneumonia Fungal, Dyskinesia, Clostridium Difficile Colitis, Toxicity TO Various Agents, Leukaemia Recurrent, Fungal Rhinitis, Neutropenic Infection, Hallucination

Adverse event resulted in: hospitalization

Suspect drug(s):
Ativan
    Indication: Anxiety

Scopolamine
    Indication: Pain

Fentanyl-100
    Indication: Pain
    Start date: 2011-09-19
    End date: 2011-10-17

Scopolamine
    Indication: Vomiting

Kytril
    Administration route: Oral
    Indication: Nausea
    Start date: 2011-10-06

Kytril
    Indication: Vomiting

Demerol
    Dosage: q96h prn
    Indication: Pain
    Start date: 2011-10-16

Marinol
    Dosage: 5 mg tid prn
    Administration route: Oral
    Indication: Nausea
    Start date: 2011-04-04
    End date: 2011-10-16

Ativan
    Dosage: 1 mg q6h prn, tapering
    Administration route: Oral
    Indication: Nausea
    Start date: 2011-03-11

Scopolamine
    Indication: Nausea
    Start date: 2011-10-06
    End date: 2011-10-14

Dilaudid
    Administration route: Oral
    Indication: Pain
    Start date: 2011-06-28
    End date: 2011-10-16

Celexa
    Indication: Depression
    Start date: 2011-03-31

Demerol
    Indication: Chills

Other drugs received by patient: Colace; Cipro; Polyethylene Glycol; Cipro; Mepron; Heparin; Neupogen; Mepron; Fluconazole; Famvir; Hydrocortisone/lidocaine; Fluconazole; Morphine Sulfate; Nystatin; Lidocaine; Omeprazole; Chlorhexidine Gluconate; Concerta; Famvir; Loratadine; Sennosides A+B

Possible Kytril side effects / adverse reactions in 23 year old male

Reported by a consumer/non-health professional from United States on 2011-11-23

Patient: 23 year old male weighing 78.6 kg (172.9 pounds)

Reactions: Abdominal Pain, Pneumonia Fungal, Systemic Mycosis, Dyskinesia, Clostridium Difficile Colitis, Febrile Neutropenia, Toxicity TO Various Agents, Leukaemia Recurrent, Fungal Rhinitis, Chest Pain, Sinusitis Fungal, Muscle Spasms

Adverse event resulted in: hospitalization

Suspect drug(s):
Kytril
    Indication: Vomiting

Celexa
    Dosage: unk
    Indication: Depression
    Start date: 2011-03-31

Scopolamine
    Indication: Pain

Demerol
    Dosage: unk
    Indication: Pain
    Start date: 2011-10-16

Demerol
    Indication: Chills

Dilaudid
    Dosage: 2 mg, q3h
    Indication: Pain
    Start date: 2011-06-28
    End date: 2011-10-16

Kytril
    Dosage: unk
    Indication: Nausea
    Start date: 2011-10-06

Marinol /00897601/
    Dosage: 5 mg, tid
    Administration route: Oral
    Indication: Nausea
    Start date: 2011-04-04
    End date: 2011-10-16

Fentanyl
    Dosage: 100 mcg, q72h
    Indication: Pain
    Start date: 2011-09-19
    End date: 2011-10-17

Ativan
    Dosage: 1 mg, q6h
    Administration route: Oral
    Indication: Nausea
    Start date: 2011-03-11

Ativan
    Indication: Anxiety

Study Drug
    Dosage: unk, see text
    Indication: Lymphocytic Leukaemia

Scopolamine
    Dosage: 1.5 mg, q72h
    Indication: Nausea
    Start date: 2011-10-06
    End date: 2011-10-14

Other drugs received by patient: Morphine Sulfate; Famvir /01226201/; Hydrocortisone W/lidocaine; Heparin; Ciprofloxacin; Fluconazole; Neupogen; Lidocaine; Polyethylene Glycol; Nystatin; Concerta; Omeprazole; Mepron /01181501/; Chlorhexidine Gluconate; Colace Capsules; Senna-Mint WAF; Loratadine