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The following serious adverse reactions are described elsewhere in the prescribing information:

  • Hepatotoxicity [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]
  • Bone Marrow Effects/Immunosuppression Potential/Infections [see WARNINGS AND PRECAUTIONS]
  • Peripheral Neuropathy [see WARNINGS AND PRECAUTIONS]
  • Skin Reactions [see WARNINGS AND PRECAUTIONS]
  • Increased Blood Pressure [see WARNINGS AND PRECAUTIONS]
  • Respiratory Effects [see WARNINGS AND PRECAUTIONS]

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.

A total of 2047 patients receiving AUBAGIO (7 mg or 14 mg once daily) constituted the safety population in the pooled analysis of placebo controlled studies in patients with relapsing forms of multiple sclerosis; of these, 71% were female. The average age was 37 years.

Table 1 lists adverse reactions in placebo-controlled trials with rates that were at least 2% for AUBAGIO patients and also at least 2% above the rate in placebo patients. The most common were headache, an increase in ALT, diarrhea, alopecia, and nausea. The adverse reaction most commonly associated with discontinuation was an increase in ALT (3.3%, 2.6%, and 2.3% of all patients in the AUBAGIO 7 mg, AUBAGIO 14 mg, and placebo treatment arms, respectively).

Table 1: Adverse Reactions in Pooled Placebo-Controlled Studies in Patients with Relapsing Forms of Multiple Sclerosis

Adverse Reaction AUBAGIO 7 mg
(N=1045)
AUBAGIO 14 mg
(N=1002)
Placebo
(N=997)
Headache 18% 16% 15%
Increase in Alanine aminotransferase 13% 15% 9%
Diarrhea 13% 14% 8%
Alopecia 10% 13% 5%
Nausea 8% 11% 7%
Paresthesia 8% 9% 7%
Arthralgia 8% 6% 5%
Neutropenia 4% 6% 2%
Hypertension 3% 4% 2%

Cardiovascular Deaths

Four cardiovascular deaths, including three sudden deaths, and one myocardial infarction in a patient with a history of hyperlipidemia and hypertension were reported among approximately 2600 patients exposed to AUBAGIO in the premarketing database. These cardiovascular deaths occurred during uncontrolled extension studies, one to nine years after initiation of treatment. A relationship between AUBAGIO and cardiovascular death has not been established.

Acute Renal Failure

In placebo-controlled studies, creatinine values increased more than 100% over baseline in 8/1045 (0.8%) patients in the 7 mg AUBAGIO group and 6/1002 (0.6%) patients in the 14 mg AUBAGIO group versus 4/997 (0.4%) patients in the placebo group. These elevations were transient. Some elevations were accompanied by hyperkalemia. AUBAGIO may cause acute uric acid nephropathy with transient acute renal failure because AUBAGIO increases renal uric acid clearance.

Hypophosphatemia

In clinical trials, 18% of AUBAGIO-treated patients had hypophosphatemia with serum phosphorus levels of at least 0.6 mmol/L, compared to 7% of placebo-treated patients; 4% of AUBAGIO-treated patients had hypophosphatemia with serum phosphorus levels at least 0.3 mmol/L but less than 0.6 mmol/L, compared to 0.8% of placebo-treated patients. No patient in any treatment group had a serum phosphorus below 0.3 mmol/L.