Download Tecfidera® Use in Multiple Sclerosis: A Patient Case

®
Tecfidera
Use in Multiple
Sclerosis: A Patient Case
Stefanie L. Drahuschak
PharmD Candidate Class of 2014
University of Pittsburgh School of Pharmacy
Walgreens Specialty Pharmacy
March 12, 2014
Objectives
1) Review the basics of Multiple Sclerosis
as a disease state.
 2) Understand the important counseling
points, adverse events, and dosing of
Tecfidera®.
 3) Apply the knowledge of MS and
Tecfidera® to a specific patient case.

Patient: CH

57 yo female

No known drug allergies

Diagnosis: Multiple Sclerosis
◦ ICD9 Code: 340
Patient: CH

MS treatment history
◦ 2006 – 2010
 Avonex® (interferon beta-1a) 30 mcg/0.5 mL
◦ 2010 – 2013
 Copaxone® (glatiramer acetate) 20 mg/mL
◦ 2013 – present
 Tecfidera® (dimethyl fumarate) 120 mg PO BID x 7
days  240 mg PO BID thereafter
Patient: CH

Current Medications:
◦
◦
◦
◦
◦
◦
◦
◦
Tecfidera® 240 mg PO BID
Prempro® 0.3/1.5 mg PO qday
Simvastatin 80 mg PO qHS
Sertraline 50 mg PO qday
Amlodipine 10 mg PO qday
HCTZ 25 mg PO qday
Enalapril 20 mg PO qday
Levothyroxine 100 mcg qAM
Multiple Sclerosis
MS is an inflammatory disease of the CNS
 The term multiple sclerosis refers to two
characteristics of the disease:

◦ 1) Multiple areas of brain and spinal cord
affected producing multiple neurologic
symptoms
◦ 2) Characteristic plaques or sclerosed areas
Bainbridge JL, Corboy JR. “Multiple Sclerosis.” Pharmacotherapy, Ed. Dipiro JT, Talbert
RL,Yee GC, et al. New York: McGraw-Hill Companies, Inc, 2008. 963-978.
Epidemiology
Usually diagnosed between 15-45 yo
 ~10,000 new cases diagnosed/yr in US
 Woman > men in 2:1 ratio
 Prevalence is higher the greater the
distance from equator

◦ Inverse relationship between MS and vitamin
D exposure?

Occurs more frequently in whites of
Scandinavian ancestry
Bainbridge JL, Corboy JR. “Multiple Sclerosis.” Pharmacotherapy, Ed. Dipiro JT, Talbert
RL,Yee GC, et al. New York: McGraw-Hill Companies, Inc, 2008. 963-978.
Clinical Presentation

Primary S/Sx
•Visual
complaints/optic
neuritis
•Gait problems and
falls
•Parasthesias
•Pain
•Spasticity
•Weakness
•Sexual dysfunction
•Ataxia
•Speech difficulty
•Psychological
changes
•Cognitive
changes
•Fatigue
•Bowel/bladder
dysfunction
•Tremor
Bainbridge JL, Corboy JR. “Multiple Sclerosis.” Pharmacotherapy, Ed. Dipiro JT, Talbert RL,
Yee GC, et al. New York: McGraw-Hill Companies, Inc, 2008. 963-978.
Diagnosis

Diagnosis of exclusion
◦ Sx can often be attributed to other
neurological issues
Occurrence of at least 2 episodes of
neurologic disturbance reflecting distinct
sites of damage in the CNS that cannot
be explained by another mechanism
 Since 2010, McDonald criteria has been
considered the gold standard for
diagnosis

Bainbridge JL, Corboy JR. “Multiple Sclerosis.” Pharmacotherapy, Ed. Dipiro JT, Talbert
RL,Yee GC, et al. New York: McGraw-Hill Companies, Inc, 2008. 963-978.
McDonald Criteria
http://www.radiologyassistant.nl/en/p4556dea65db62/multiple-sclerosis.html
Types of MS

1) Relapsing-Remitting MS (RRMS)
◦ Most common, about 85% initially diagnosed

2) Secondary-Progressive MS (SPMS)
◦ Symptoms worsen steadily over time

3) Primary-Progressive MS (PPMS)
◦ Only ~10% of patients

4) Progressive-Relapsing MS (PRMS)
◦ Rare (5%)
Bainbridge JL, Corboy JR. “Multiple Sclerosis.” Pharmacotherapy, Ed. Dipiro JT,
Talbert RL,Yee GC, et al. New York: McGraw-Hill Companies, Inc, 2008. 963-978.
Treatment

Three broad categories
◦ 1) Symptomatic therapy
◦ 2) Treatment of acute attacks
◦ 3) Disease-modifying therapy
Symptomatic Therapy Tx

Gait problems
◦ Ampyra® (dalfampridine)

Fatigue
◦ Modafinil (Provigil®)

Depression
◦ SSRIs

Sexual dysfunction
◦ Cialis®, Viagra®
Bainbridge JL, Corboy JR. “Multiple Sclerosis.” Pharmacotherapy, Ed. Dipiro JT,
Talbert RL,Yee GC, et al. New York: McGraw-Hill Companies, Inc, 2008. 963-978.
Tx of Acute Attacks

When functional ability is affected, IV
high-dose corticosteroids are used
◦ IV methylprednisolone

MOA of corticosteroids is unknown, but
suspected that steroids improve recovery
by decreasing edema is the area of
demyelination
Bainbridge JL, Corboy JR. “Multiple Sclerosis.” Pharmacotherapy, Ed. Dipiro JT, Talbert
RL,Yee GC, et al. New York: McGraw-Hill Companies, Inc, 2008. 963-978.
Disease-Modifying Therapy

Interferons
◦ Betaseron® (IFN-beta1b)
◦ Avonex® (IFN-beta 1a)
◦ Rebif® (IFN-beta 1a)
Copaxone® (glatiramer acetate)
 Tysabri® (natalizumab)
 Gilenya® (Fingolimod)
 Novantrone® (mitoxantrone)
 Tecfidera® (dimethyl fumarate)

Bainbridge JL, Corboy JR. “Multiple Sclerosis.” Pharmacotherapy, Ed. Dipiro JT, Talbert
RL,Yee GC, et al. New York: McGraw-Hill Companies, Inc, 2008. 963-978.
Tecfidera®

Dimethyl fumarate

Indication
◦ Tecfidera® is indicated for the treatment of
patients with relapsing forms of multiple
sclerosis
Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013.
Mechanism of Action
Mostly unknown
 DMF and MMF activate the Nuclear
factor (erythroid-derived 2)-like 2 (NRF2)
pathway
 NRF2 pathway is involved in cellular
response to oxidative stress

Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013.
Tecfidera® Dosing

Initiation dose
◦ 120 mg PO BID x 7 days

Maintenance dose
◦ 240 mg PO BID
Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013.
Tecfidera® Availability

Hard, gelatin delayed release capsules of
120 or 240mg
◦ 120mg: “BG-12 120mg” on capsule
◦ 240mg: “BG-12 240mg” on capsule
30-day Starter Pack
 7-day bottle of 120 mg capsules
 30-day bottle of 240 mg capsules

Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013.
®
Tecfidera
http://www.empr.com/tecfidera-approved-a-first-line-oral-multiple-sclerosistreatment/article/286349/
Tecfidera® Administration
Should be swallowed whole and intact
 Should NOT be crushed or chewed
 Capsule contents should NOT be
sprinkled on food
 Can be without without regard to food
 Administration with food may reduce the
incidence of flushing

Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013.
®
Tecfidera Adverse
Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013.
Reactions
Serious AE - Flushing
Warmth, redness, itching, and/or burning
sensation
 In clinical trials, 40% experienced
 Flushing generally began soon after
initiation and improved over time
 Initiation dose is used to desensitize body
to flushing
 Taking medication with food or premedicating with aspirin may help reduce
incidence

Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013.
Serious AE: Lymphopenia
Mean lymphocyte counts decreased by
~30% during the first year of treatment
and then remained stable
 4 weeks after d/c, lymphocyte counts
increased but did not return to baseline
 Before tx, a baseline CBC should be
conducted, then annually thereafter

Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013.
Pharmacokinetics

Metabolism
◦ Extensively metabolized by esterases
◦ No involvement from CYP450 system

Elimination
◦ Exhalation of CO2 is primary route – 60%
◦ Renal and fecal elimination are minor routes,
accounting for 16% and 1%, respectively
Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013.
Use in Pregnancy

Pregnancy Category C

In animal studies, adverse effects on
offspring survival, growth, sexual
maturation, and neurobehavioral function
were observed at clinically relevant doses

Should only be used if benefit > risk
Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013.
Important Counseling Points

Will be provided two strengths when
starting therapy
◦ Do not crush, swallow whole

Flushing and GI upset are most common
reactions, especially initially
◦ Take with food, aspirin if needed
Inform MD if you become pregnant
 Regular blood tests are important to
monitor lymphocytes

Tecfidera® [package insert]. Cambridge, MA: Biogen, Inc; 2013.
Patient CH: Assessment/Plan

A:
◦ Since patient began Tecfidera® in 2013, no AE
or change in disease state have been reported

P:
◦ Continue Tecfidera® 240 mg PO BID
◦ Continue regular monitoring with MS
specialist
◦ Add additional symptomatic treatment if
necessary
QUESTIONS?