Fusilev (Levoleucovorin Calcium) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

Clinical Studies Experience

Since 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 practice. The following table presents the frequency of adverse reactions which occurred during the administration of 58 courses of high dose methotrexate 12 grams/m² followed by Fusilev rescue for osteosarcoma in 16 patients age 6-21. Most patients received Fusilev 7.5 mg every 6 hours for 60 hours or longer beginning 24 hours after completion of methotrexate.

Table 2 Adverse Reactions

Body System/Adverse Reactions	Number (%) of Patients with Adverse Reactions		Number (%) of Courses with Adverse Reactions
	(N =16)		(N = 58)
	All	Grade 3+	All	Grade 3+
Gastrointestinal
Stomatitis	6 (37.5)	1 (6.3)	10 (17.2)	1 (1.7)
Vomiting	6 (37.5)	0	14 (24.1)	0
Nausea	3 (18.8)	0	3 (5.2)	0
Diarrhea	1 (6.3)	0	1 (1.7)	0
Dyspepsia	1 (6.3)	0	1 (1.7)	0
Typhlitis	1 (6.3)	1 (6.3)	1 (1.7)	1 (1.7)
Respiratory
Dyspnea	1 (6.3)	0	1 (1.7)	0
Skin and Appendages
Dermatitis	1 (6.3)	0	1 (1.7)	0
Other
Confusion	1 (6.3)	0	1 (1.7)	0
Neuropathy	1 (6.3)	0	1 (1.7)	0
Renal function abnormal	1 (6.3)	0	3 (5.2)	0
Taste perversion	1 (6.3)	0	1 (1.7)	0
Total number of patients	9 (56.3)		2 (12.5)
Total number of courses	25 (43.1)		2 (3.4)

The incidence of adverse reactions may be underestimated because not all patients were fully evaluable for toxicity for all cycles in the clinical trials. Leukopenia and thrombocytopenia were observed, but could not be attributed to high dose methotrexate with Fusilev rescue because patients were receiving other myelosuppressive chemotherapy.

Postmarketing Experience

Since adverse reactions from spontaneous reports are provided voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure. Spontaneously reported adverse reactions collected by the WHO Collaborating Center for International Drug Monitoring in Uppsala Sweden have yielded seven cases where levoleucovorin was administered with a regimen of methotrexate. The events were dyspnea, pruritus, rash, temperature change and rigors. For 217 adverse reactions (108 reports) where levoleucovorin was a suspected or interacting medication, there were 40 occurrences of “possible allergic reaction.”

REPORTS OF SUSPECTED FUSILEV SIDE EFFECTS / ADVERSE REACTIONS

Possible Fusilev side effects / adverse reactions in 49 year old male

Reported by a health professional (non-physician/pharmacist) from United States on 2012-07-06

Patient: 49 year old male weighing 58.5 kg (128.7 pounds)

Reactions: Hypoglycaemic Coma

Adverse event resulted in: death, hospitalization

Suspect drug(s):
Fluorouracil
    Dosage: 4000 mg for 48 hrs, on day 1, intravenous, 690 mg on day 1, intravenous
    Indication: Colon Cancer
    Start date: 2012-03-21

Fluorouracil
    Dosage: 4000 mg for 48 hrs, on day 1, intravenous, 690 mg on day 1, intravenous
    Indication: Colon Cancer
    Start date: 2012-03-21

Fusilev
    Dosage: 690 mg, q 14, 590 mg, q14 days, with oxaliplatin, intravenous
    Indication: Colon Cancer
    Start date: 2012-03-21

Oxaliplatin
    Dosage: 147 mg, q 14, 147 mg, q 14 days, with fusilev, intravenous
    Indication: Colon Cancer
    Start date: 2012-03-21

Other drugs received by patient: Dexamethasone Sodium Phosphate; Antiemetics (Antiemetics); Pain Medication (Pain Medication); Aloxi