Aloxi (Palonosetron Hydrochloride) - Side Effects and Adverse Reactions

6 ADVERSE REACTIONS

6.1 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 reported in practice.

In clinical trials for the prevention of nausea and vomiting induced by moderately or highly emetogenic chemotherapy, 1374 adult patients received palonosetron. Adverse reactions were similar in frequency and severity with ALOXI and ondansetron or dolasetron. Following is a listing of all adverse reactions reported by ≥ 2% of patients in these trials (Table 1).

Table 1: Adverse Reactions from Chemotherapy-Induced Nausea and Vomiting Studies ≥ 2% in any Treatment Group

Event	Aloxi 0.25 mg (N=633)	Ondansetron 32 mg IV (N=410)	Dolasetron 100 mg IV (N=194)
Headache	60 (9%)	34 (8%)	32 (16%)
Constipation	29 (5%)	8 (2%)	12 (6%)
Diarrhea	8 (1%)	7 (2%)	4 (2%)
Dizziness	8 (1%)	9 (2%)	4 (2%)
Fatigue	3 (< 1%)	4 (1%)	4 (2%)
Abdominal Pain	1 (< 1%)	2 (< 1%)	3 (2%)
Insomnia	1 (< 1%)	3 (1%)	3 (2%)

In other studies, 2 subjects experienced severe constipation following a single palonosetron dose of approximately 0.75 mg, three times the recommended dose. One patient received a 10 mcg/kg oral dose in a post-operative nausea and vomiting study and one healthy subject received a 0.75 mg IV dose in a pharmacokinetic study.

In clinical trials, the following infrequently reported adverse reactions, assessed by investigators as treatment-related or causality unknown, occurred following administration of ALOXI to adult patients receiving concomitant cancer chemotherapy:

Cardiovascular: 1%: non-sustained tachycardia, bradycardia, hypotension, < 1%: hypertension, myocardial ischemia, extrasystoles, sinus tachycardia, sinus arrhythmia, supraventricular extrasystoles and QT prolongation. In many cases, the relationship to ALOXI was unclear.

Dermatological: < 1%: allergic dermatitis, rash.

Hearing and Vision: < 1%: motion sickness, tinnitus, eye irritation and amblyopia.

Gastrointestinal System: 1%: diarrhea, < 1%: dyspepsia, abdominal pain, dry mouth, hiccups and flatulence.

General: 1%: weakness, < 1%: fatigue, fever, hot flash, flu-like syndrome.

Liver: < 1%: transient, asymptomatic increases in AST and/or ALT and bilirubin. These changes occurred predominantly in patients receiving highly emetogenic chemotherapy.

Metabolic: 1%: hyperkalemia, < 1%: electrolyte fluctuations, hyperglycemia, metabolic acidosis, glycosuria, appetite decrease, anorexia.

Musculoskeletal: < 1%: arthralgia.

Nervous System: 1%: dizziness, < 1%: somnolence, insomnia, hypersomnia, paresthesia.

Psychiatric: 1%: anxiety, < 1%: euphoric mood.

Urinary System: < 1%: urinary retention.

Vascular: < 1%: vein discoloration, vein distention.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postapproval use of ALOXI. 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.

Very rare cases (<1/10,000) of hypersensitivity reactions and injection site reactions (burning, induration, discomfort and pain) were reported from postmarketing experience.

REPORTS OF SUSPECTED ALOXI SIDE EFFECTS / ADVERSE REACTIONS

Possible Aloxi side effects / adverse reactions in 34 year old female

Reported by a health professional (non-physician/pharmacist) from Switzerland on 2011-10-26

Patient: 34 year old female

Reactions: Maternal Exposure During Pregnancy

Suspect drug(s):
Cyclophosphamide
    Indication: Breast Cancer
    Start date: 2011-08-09
    End date: 2011-08-09

Cyclophosphamide
    Start date: 2011-07-18
    End date: 2011-07-18

Epirubicin Hydrochloride
    Start date: 2011-07-18
    End date: 2011-07-18

Emend
    Administration route: Oral
    Indication: Breast Cancer
    Start date: 2011-07-18
    End date: 2011-07-20

Aloxi
    Start date: 2011-07-18
    End date: 2011-07-18

Fluorouracil
    Indication: Breast Cancer
    Start date: 2011-08-09
    End date: 2011-08-09

Fluorouracil
    Start date: 2011-07-18
    End date: 2011-07-18

Epirubicin Hydrochloride
    Indication: Breast Cancer
    Start date: 2011-08-09
    End date: 2011-08-09

Aloxi
    Indication: Breast Cancer
    Start date: 2011-08-09
    End date: 2011-08-09

Possible Aloxi side effects / adverse reactions in 76 year old female

Reported by a physician from Germany on 2011-12-09

Patient: 76 year old female weighing 60.0 kg (132.0 pounds)

Reactions: Weight Decreased, Palmar-Plantar Erythrodysaesthesia Syndrome, Skin Striae, Polyneuropathy, Dysgeusia, DRY Mouth, Pollakiuria, Onychoclasis, Muscle Spasms

Suspect drug(s):
Taxol
    Dosage: 1 df= 80mg/qm
    Indication: Breast Cancer

Cyclophosphamide
    Dosage: 1 df= 600mg/qm cycle durn: 21 days

Uromitexan
    Administration route: Oral

Fenistil
    Dosage: 1 df= ampoule

Emend
    Dosage: also 80mg 10mar11, 17feb11.
    Administration route: Oral

Zofran
    Dosage: on 100ml sodium chloride sloutin

Ranitidine
    Dosage: 1 df= 1 ampoule

Aloxi
    Dosage: 1df= 1amp in 100 ml sodium chloride 0.9%

Epirubicin
    Dosage: 90 mg/qm bsa cycle durn: 21 days

Fortecortin

Possible Aloxi side effects / adverse reactions in 76 year old female

Reported by a pharmacist from Germany on 2012-01-11

Patient: 76 year old female weighing 60.0 kg (132.0 pounds)

Reactions: Weight Decreased, Palmar-Plantar Erythrodysaesthesia Syndrome, Skin Striae, Polyneuropathy, Dysgeusia, DRY Mouth, Pollakiuria, Onychoclasis, Muscle Spasms

Suspect drug(s):
Fortecortin
    Dosage: 12 times between 12may11 + 28jul11 3rd admin: 31mar11.

Emend
    Dosage: also 80mg 10mar11, 17feb11. 3rd admin: 31mar11.
    Administration route: Oral

Aloxi
    Dosage: 1df= 1amp in 100 ml sodium chloride 0.9% 3rd admin: 31mar11.

Mesna
    Dosage: also on 10mar11, 31mar11 + 21apr11. 3rd admin: 31mar11.
    Administration route: Oral
    Start date: 2011-02-17

Fenistil
    Dosage: 1 df= ampoule. 12 times between 12may11 + 28jul11

Cyclophosphamide
    Dosage: 1 df= 600mg/qm cycle durn: 21 days after 3 admin event occured 3rd admin: 31mar11.

Zofran
    Dosage: on 100ml sodium chloride sloutin 12 times between 12may11 + 28jul11

Taxol
    Dosage: 1 df= 80mg/qm 12 times between 12may11 + 28jul11.
    Indication: Breast Cancer

Epirubicin
    Dosage: 90 mg/qm bsa cycle durn: 21 days after 3 admin event occured also 972mg 3rd admin: 31mar11.

Ranitidine
    Dosage: 1 df= 1 ampoule 12 times between 12may11 + 28jul11