Active Ingredient(s):
Teriflunomide 7mg, 14mg; tablets.

Company
Genzyme Corporation

Indication(s):

Relapsing forms of multiple sclerosis (MS).

Pharmacology:

Teriflunomide, an immunomodulatory agent with anti-inflammatory properties, inhibits dihydroorotate dehydrogenase, a mitochondrial enzyme involved in de novo pyrimidine synthesis. The mechanism by which teriflunomide exerts its therapeutic effect is unknown but may involve a reduction in the number of activated lymphocytes in CNS.

Clinical Trials:

The efficacy of teriflunomide was demonstrated in Study 1, a double-blind, placebo-controlled study that eva luated patients with relapsing forms of multiple sclerosis (RMS) over 108 weeks. A total of 1088 patients with RMS were randomized to receive 7mg (n=366) or 14mg (n=359) of teriflunomide or placebo (n=363). The primary endpoint was the annualized relapse rate (ARR). The ARR was significantly reduced in patients treated with either 7mg or 14mg of teriflunomide compared to patients who received ­placebo (0.370, 0.369 vs. 0.539, respectively).
 
The time to disability progression sustained for 12 weeks (as measured by at least a 1-point increase from baseline Expanded Disability Status Scale (EDSS) ≤ 5.5 or a 0.5 point increase for those with a baseline EDSS > 5.5) was statistically significantly reduced only in the teriflunomide 14mg group compared to placebo. The change in total lesion volume from baseline was significantly lower in the 7mg and 14mg groups than in the placebo group. Patients in both teriflunomide groups had significantly fewer gadolinium-enhancing lesions per T1-weighted scan than those in the placebo group.
 
The effect of teriflunomide on MRI activity was also demonstrated in Study 2. The mean number of unique active lesions per brain MRI scan during the 36-week treatment period was lower in patients treated with teriflunomide 14mg (0.98) and 7mg (1.06) as compared to placebo (2.69), the difference being statistically significant for both (P=0.0052 and P=0.0234, respectively).

Legal Classification:

Rx

Adults:

7mg or 14mg once daily.

Children:

Not established.

Contraindication(s):

Severe hepatic impairment. Pregnancy (Category X), women of childbearing potential not using reliable contraception. Co-administration with leflunomide.

Warnings/Precautions:

Perform accelerated elimination procedure (see literature) after drug discontinuance. Severe liver injury may be possible; obtain transaminase and bilirubin levels within 6 months before starting, monitor ALT at least monthly for 6 months after starting. Discontinue if drug-induced liver injury suspected; monitor liver tests weekly until normalized. Pre-existing liver disease: increased risk of developing elevated serum transaminases. Obtain CBCs within 6 months prior to starting. Severe immunodeficiency, bone marrow disease, or severe, uncontrolled infections: not recommended. Screen for latent TB; do not start therapy until infection resolved. Monitor BP before starting and periodically. Diabetes, >60 years: increased risk of peripheral neuropathy. Monitor for new onset or worsening pulmonary symptoms, discontinue if interstitial lung disease suspected. Male patients: undergo elimination procedure before fathering child. Nursing mothers: not recommended.

Interaction(s)

See Contraindications. Live vaccines: not recommended. Risk of liver injury with ­hepatotoxic drugs. Risk of peripheral neuropathy with neurotoxic drugs. Potentiates drugs metab­olized by CYP2C8 (eg, repaglinide, paclitaxel, ­pioglitazone, rosiglitazone), oral contraceptives. Antagonizes drugs metabolized by CYP1A2 (eg, duloxetine, alosetron, theophylline, tizanidine). Monitor INR. Concomi­tant immunosuppressives, immunomodulators: not eva luated.

Adverse Reaction(s)

ALT increased, alopecia, diarrhea, influenza, nausea, paresthesia; bone marrow suppression, immunosuppression potential, infection (consider suspending therapy), peripheral neurop­athy; hyperkalemia, acute renal failure (check K+ ­levels); possible severe skin reactions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis; ­discontinue if occurs), respiratory effects.

How Supplied:

Tabs—5, 28

LAST UPDATED:

11/5/2012