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Aubagio

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Aubagio

Side Effects
Interactions

SIDE EFFECTS

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

The most frequent adverse reactions for AUBAGIO (incidence ≥ 10% and ≥ 2% greater than placebo) in the placebo-controlled studies were ALT increased, alopecia, diarrhea, influenza, nausea, and paresthesia. Alopecia was the most common cause of discontinuation because of adverse events in controlled clinical studies as compared to placebo (0.5% and 1.4% of patients on AUBAGIO 7 mg and 14 mg, respectively, and 0% on placebo).

If desired, teriflunomide can be rapidly cleared from the body by the use of an accelerated elimination procedure [see WARNINGS AND PRECAUTIONS].

Clinical Trial Experience

A total of 844 patients on teriflunomide (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 MS (RMS). Approximately 72% of patients were female and the mean age was 38 years.

Study 1 was a 108-week placebo-controlled clinical study in 1086 RMS patients treated with teriflunomide 7 mg (n=368), teriflunomide 14 mg (n=358), or placebo (n=360).

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.

Table 1 : Adverse Reactions in Study 1 (occurring in ≥ 2% of patients, and reported for teriflunomide 7 mg or 14 mg at ≥ 2% higher rate than for placebo)

PRIMARY SYSTEM ORGAN CLASS Preferred Term (%) Teriflunomide
14 mg
(N=358)
7 mg
(N=368)
Placebo
(N=360)
INFECTIONS AND INFESTATIONS
  Influenza 12% 9% 10%
  Upper respiratory tract infection 9% 9% 7%
  Bronchitis 8% 5% 6%
  Sinusitis 6% 4% 4%
  Cystitis 4% 2% 1%
  Gastroenteritis viral 4% 2% 1%
  Oral herpes 4% 2% 2%
BLOOD AND LYMPHATIC SYSTEM DISORDERS
  Neutropenia 4% 2% 0.3%
  Leukopenia 1% 2% 0.3%
IMMUNE SYSTEM DISORDERS
  Seasonal allergy 3% 2% 1%
PSYCHIATRIC DISORDERS
  Anxiety 4% 3% 2%
NERVOUS SYSTEM DISORDERS
  Headache 19% 22% 18%
  Paraesthesia 10% 9% 8%
  Sciatica 3% 1% 1%
  Burning sensation 3% 2% 1%
  Carpal tunnel syndrome 3% 1% 0.3%
EYE DISORDERS
  Vision blurred 3% 3% 1%
  Conjunctivitis 1% 3% 1%
CARDIAC DISORDERS
  Palpitations 2% 3% 1%
VASCULAR DISORDERS
  Hypertension 4% 4% 2%
GASTROINTESTINAL DISORDERS
  Diarrhoea 18% 15% 9%
  Nausea 14% 9% 7%
  Abdominal pain upper 6% 5% 4%
  Toothache 4% 4% 2%
  Abdominal distension 1% 2% 0.3%
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
  Alopecia 13% 10% 3%
  Acne 3% 1% 1%
  Pruritus 3% 4% 2%
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS 
  Musculoskeletal pain 4% 5% 3%
  Myalgia 3% 4% 2%
INVESTIGATIONS
  Alanine aminotransferase increased 14% 12% 7%
  Gamma-glutamyltransferase increased 3% 5% 1%
  Aspartate aminotransferase increased 3% 2% 1%
  Weight decreased 2% 3% 1%
  Neutrophil count decreased 2% 3% 0.3%
  White blood cell count decreased 1% 3% 0%

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 teriflunomide and cardiovascular death has not been established.

Hypophosphatemia

In clinical trials, 18% of teriflunomide-treated subjects had mild hypophosphatemia ( ≥ 0.6 mmol/L and < lower limit of normal), compared to 9% of placebo-treated subjects; 5% of teriflunomide-treated subjects had moderate hypophosphatemia ( ≥ 0.3 mmol/L and < 0.6 mmol/L), compared to 1% of placebo-treated subjects. No subject in either treatment group had a serum phosphorus < 0.3 mmol/L.

Read the Aubagio (teriflunomide tablets) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Effect of teriflunomide on CYP2C8 substrates

There was an increase in mean repaglinide Cmax and AUC (1.7- and 2.4-fold, respectively), following repeated doses of teriflunomide and a single dose of 0.25 mg repaglinide, suggesting that teriflunomide is an inhibitor of CYP2C8 in vivo. The magnitude of interaction could be higher at the recommended repaglinide dose. Therefore, monitoring patients with concomitant use of drugs metabolized by CYP2C8, such as repaglinide, paclitaxel, pioglitazone, or rosiglitazone is recommended as they may have higher exposure.

Effect of teriflunomide on warfarin

A 25% decrease in peak international normalized ratio (INR) was observed when teriflunomide was coadministered with warfarin as compared with warfarin alone. Therefore, when warfarin is coadministered with teriflunomide, close INR follow-up and monitoring is recommended.

Effect of teriflunomide on oral contraceptives

There was an increase in mean ethinylestradiol Cmax and AUC0-24 (1.58- and 1.54-fold, respectively) and levonorgestrel Cmax and AUC0-24 (1.33- and 1.41-fold, respectively) following repeated doses of teriflunomide. Consideration should be given to the type or dose of oral contraceptives used in combination with teriflunomide.

Effect of teriflunomide on CYP1A2 substrates

Repeated doses of teriflunomide decreased mean Cmax and AUC of caffeine (CYP1A2 substrate) by 18% and 55% respectively, suggesting that teriflunomide may be in vivo a weak inducer of CYP1A2. Therefore, patients should be monitored when teriflunomide is coadministered with drugs metabolized by CYP1A2 (such as duloxetine, alosetron, theophylline, and tizanidine), as the efficacy of such drugs could be reduced.

Read the Aubagio Drug Interactions Center for a complete guide to possible interactions

Last reviewed on RxList: 9/21/2012
This monograph has been modified to include the generic and brand name in many instances.

Side Effects
Interactions
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