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MODULE 5: SPECIALTY DISEASE MANAGEMENT II: NEUROLOGY, RARE & INFECTIOUS
Section 5.2: Multiple Sclerosis, ALS, and Epilepsy Therapies
A deep dive into the diverse pharmacologic arsenal for MS (DMTs), ALS, and refractory epilepsy, focusing on adherence, monitoring, and toxicity management.
SECTION 5.2
Managing the Neural Network: A High-Touch Pharmacist’s Guide
From Drug Interactions to Risk Mitigation: Mastering High-Stakes Neurology.
5.2.1 The “Why”: From Dispenser to High-Touch Care Manager
In the previous section, we explored chronic neurodegenerative diseases where your role was to balance polypharmacy and quality of life. In this section, we escalate the stakes. The three conditions we will cover—Multiple Sclerosis (MS), ALS, and Refractory Epilepsy—represent some of the most complex, high-cost, and high-risk pharmacotherapy in all of medicine.
Your role here transcends traditional dispensing. You are no longer just a pharmacist; you are a logistical coordinator for billion-dollar infusion drugs, a toxicity manager for therapies with black box warnings, an adherence coach for patients on complex injection or infusion schedules, and a financial navigator helping patients access $100,000/year medications. The therapies for MS (DMTs) are a masterclass in specialty pharmacy. The management of refractory epilepsy is a deep dive into the most complex drug-drug interactions you will ever encounter. And the care for ALS is a profound lesson in supportive, palliative polypharmacy.
Your existing skills in counseling, DUR, and adherence are the foundation. This section will build upon them, translating your community pharmacy expertise into the high-stakes world of specialty neurology. You will learn to manage Risk Evaluation and Mitigation Strategies (REMS), interpret complex genetic and antibody tests to guide therapy, and serve as the central hub of communication between the patient, the prescriber, and the specialty pharmacy.
Pharmacist Analogy: The Aviation Crew Chief
In community pharmacy, you are an expert at managing reliable, “daily-driver” sedans like statins and ACE inhibitors. You ensure they have fuel (refills) and regular oil changes (adherence).
Welcome to specialty neurology. You are now the Crew Chief for a squadron of F-35 fighter jets. These are high-performance, astronomically expensive, and incredibly complex machines (Disease-Modifying Therapies). Your job is no longer just “refilling the tank.”
- Pre-Flight Check (Baseline Monitoring): You would never let a jet take off without a full systems check. You will never dispense a DMT like Natalizumab without first checking the “pre-flight” JCV antibody test. You will never start an S1P modulator without ensuring the “pre-flight” cardiac and ophthalmologic exams are complete.
- In-Flight Monitoring (Adherence Calls): You don’t just “hope” the pilot is okay. You are in constant communication. This is your monthly adherence and side-effect management call. “How are the injections? Any flu-like symptoms? Are you experiencing any new flushing or GI upset?”
- Emergency Procedures (Toxicity Management): When a warning light flashes (a patient reports a new, severe headache on Tysabri), you don’t “wait and see.” You ground the plane (hold the dose) and immediately escalate to the pilot (prescriber) to check for a catastrophic failure (PML). You are the master of the emergency checklist (REMS programs).
This is your new role. You are the systems expert, the safety manager, and the mission-critical coordinator ensuring this powerful, dangerous, and life-changing technology is used safely and effectively.
5.2.2 Deep Dive: Multiple Sclerosis (MS)
Multiple Sclerosis is the quintessential specialty pharmacy disease state. It is a chronic, immune-mediated, inflammatory, and neurodegenerative disease of the central nervous system (CNS). Mastering its treatment is a core competency of an advanced pharmacist.
Pathophysiology Masterclass: The “Frayed Wire”
The simplest and most effective analogy for MS is that of an electrical wire.
- The Axon: The “copper wire” of the neuron, carrying the electrical signal.
- The Myelin Sheath: The “rubber insulation” that surrounds the axon, allowing the signal to travel quickly and efficiently.
In MS, the body’s own immune system (specifically T-cells and B-cells) mistakenly attacks and destroys the myelin sheath. This “demyelination” leaves the axon “frayed” and exposed. The result is a short-circuit. The electrical signal is slowed, distorted, or stopped completely. This is what causes the diverse, unpredictable symptoms of MS.
Clinical Presentation: Knowing the Phenotypes
You cannot manage MS if you don’t know which *type* of MS the patient has, as therapies are approved for specific phenotypes.
- Clinically Isolated Syndrome (CIS): The *first* demyelinating “attack” (e.g., optic neuritis, transverse myelitis). It may or may not become MS, but this is often when we start therapy.
- Relapsing-Remitting MS (RRMS): The most common form (~85%). Patients have clear “relapses” (new or worsening symptoms) followed by periods of “remission” (recovery).
- Secondary Progressive MS (SPMS): A patient who *started* with RRMS now begins to have a steady, progressive worsening of disability, with or without relapses.
- Primary Progressive MS (PPMS): A rare form (~15%). From the onset, the patient has a steady, progressive worsening of disability with *no* history of relapses.
Setting Expectations: The DMT Counseling Goal
This is a critical counseling point. A patient newly diagnosed is terrified. You must be clear about what the therapy does.
The Script: “I want to be very clear about the goal of this medication. This is what we call a ‘Disease-Modifying Therapy,’ or DMT. It is not a cure for MS, and it is not designed to treat your current symptoms like fatigue or numbness. Think of it as a long-term shield for your brain and spinal cord. The entire goal of this therapy is to prevent future attacks, slow down the progression of the disease, and prevent new ‘lesions’ or ‘scars’ from forming. It’s a proactive, preventative medicine, and the most important thing is to take it consistently, even on the days you feel perfectly fine.”
5.2.3 The MS Arsenal: A Masterclass in Disease-Modifying Therapies (DMTs)
The landscape of DMTs has exploded from two injectable drugs in the 1990s to over 20 different options. Your job is to be the expert on all of them. We will group them by their route of administration, which aligns with the patient experience and pharmacy logistics.
A. The Platform Injectables (The “Old Guard”)
These are the original DMTs. They are considered “low-to-moderate” efficacy but have decades of safety data. They are still used first-line in patients who prefer a long-trusted medication over higher efficacy.
1. Interferon-Beta (IFN-β)
- Drugs: Avonex (IFN-β-1a, IM once weekly), Rebif (IFN-β-1a, SC 3x/week), Betaseron (IFN-β-1b, SC every other day), Plegridy (Peginterferon-β-1a, SC every 14 days).
- Mechanism: Not fully known. Believed to shift the immune system from a pro-inflammatory to an anti-inflammatory state.
- Monitoring: LFTs, CBC (can cause leukopenia), Thyroid Function.
Tutorial: The Interferon Counseling Script
“This injection works by calming down the immune system. The most common side effect, especially when you start, is feeling like you have the flu for about 24 hours after the injection. This is actually a sign the medicine is working.
Here is the plan to manage it:
1. Timing: Take your injection at night, right before bed. This way, you sleep through the worst of the flu-like feelings.
2. Pre-medication: About 30-60 minutes before your injection, take an over-the-counter NSAID like Ibuprofen or Naproxen.
3. Hydration: Make sure you drink plenty of water on your injection day.
4. Rotation: We will also go over your auto-injector training. You must rotate your injection sites (thighs, abdomen, back of arms) with every dose to prevent painful skin reactions.”
2. Glatiramer Acetate (Copaxone, Glatopa)
- Mechanism: A “decoy” drug. It’s a synthetic polypeptide that mimics Myelin Basic Protein. It’s thought to “distract” the immune system, causing it to attack the drug instead of the real myelin.
- Dosing: 20mg SC daily OR 40mg SC 3x/week.
- Monitoring: None required. This is its biggest selling point.
Critical Counseling: The Post-Injection Reaction
About 1 in 10 patients will experience this at some point. It is not an allergy, but it is terrifying.
The Script: “I need to tell you about a very important, but ultimately harmless, reaction. Within a few minutes of your injection, you might suddenly feel flushing, chest tightness, shortness of breath, and your heart pounding. It can feel like you’re having a heart attack. This is a known reaction to the medication. It is not dangerous and it will go away on its own in 10-15 minutes. Do not call 911 unless the symptoms continue to get worse or don’t resolve. Just sit down, breathe, and wait for it to pass.”
B. The Oral DMTs (The “New Wave”)
The development of oral DMTs revolutionized MS care, freeing patients from injections. However, they carry different and sometimes more serious systemic risks.
1. S1P Modulators (The “Lymph Node Trappers”)
- Drugs: Fingolimod (Gilenya), Siponimod (Mayzent), Ozanimod (Zeposia), Ponesimod (Ponvory).
- Mechanism: They are S1P receptor modulators. They “trap” lymphocytes (T and B cells) inside the lymph nodes, preventing them from getting into the CNS to attack the myelin.
- The Result: A dramatic drop in circulating lymphocytes (lymphopenia).
Critical Protocol: The S1P “First-Dose Observation”
This is a core specialty pharmacist function. S1P receptors are also on the heart. When you first block them, it can cause a transient bradycardia (slowed heart rate) and AV block.
Fingolimod (Gilenya): Because it’s “non-selective,” the effect is strongest. The patient must be monitored in a clinic or infusion center for 6 hours after their *first dose*. This includes a baseline EKG and hourly vitals. Your pharmacy cannot dispense this drug until this observation is scheduled and confirmed.
Newer Agents (Siponimod, Ozanimod, Ponvory): These are more selective and “auto-titrate” to avoid this. They come in titration starter packs that you must counsel on. For example, Ozanimod starts at 0.23mg for 4 days, then 0.46mg for 3 days, then the 0.92mg maintenance dose. This slow start *avoids* the need for first-dose observation (in most patients). Adherence to this titration is a critical safety issue.
Masterclass Table: Comparing the S1P Modulators
| Drug | Pharmacist’s “Must-Know” Fact | Core Monitoring |
|---|---|---|
| Fingolimod (Gilenya) | First-Dose Observation: 6-hour cardiac monitoring required. |
|
| Siponimod (Mayzent) | CYP2C9 Genotyping: The dose is dependent on the patient’s CYP2C9 genotype. You *must* confirm this genetic test is done before dispensing. | |
| Ozanimod (Zeposia) | MAOI Interactions: It is a weak MAO inhibitor. Counsel patient on avoiding high-tyramine foods and checking for serotonergic drug interactions (SSRIs, etc.). | |
| Ponesimod (Ponvory) |
2. Nrf2 Activators (The “Flushing” Drugs)
- Drugs: Dimethyl Fumarate (Tecfidera), Diroximel Fumarate (Vumerity).
- Mechanism: Activates the Nrf2 pathway, which is anti-inflammatory and cytoprotective.
- Counseling:
- Flushing: A very common side effect. The Script: “30-60 minutes after your dose, you might get very red, hot, and flush. This is harmless. To prevent it, you can take a non-coated Aspirin 325mg 30 minutes before your dose.”
- GI Upset: Also very common. The Script: “You must take this medication with food. Not a snack, a real meal. This will help your stomach tolerate it.”
- Vumerity vs. Tecfidera: Vumerity is a pro-drug designed to cause *less* GI upset. This is its only purpose.
Critical Monitoring: Lymphopenia and PML
These drugs can cause lymphopenia (low white blood cell count). While not as profound as S1Ps, it can be severe and prolonged. This lymphopenia is a major risk factor for a rare but fatal brain infection: Progressive Multifocal Leukoencephalopathy (PML), caused by the JC Virus.
Your Role: You must ensure the patient gets a CBC at baseline, every 6 months, and annually thereafter. If the absolute lymphocyte count (ALC) drops below 500/µL for more than 6 months, the drug must be stopped. Dispensing this drug without a recent CBC on file is a major safety violation.
3. Pyrimidine Synthesis Inhibitors (The “High-Risk” Pill)
- Drug: Teriflunomide (Aubagio).
- Mechanism: Blocks *dihydroorotate dehydrogenase*, an enzyme needed for new pyrimidine (DNA) synthesis. This stops fast-dividing B and T cells from proliferating.
BLACK BOX WARNING: Hepatotoxicity & Teratogenicity
This is one of the highest-risk oral drugs in MS and requires a REMS-like level of counseling.
1. Hepatotoxicity: Can cause severe liver failure. Monitoring: LFTs at baseline, then monthly for 6 months, then periodically. You must verify these labs.
2. Teratogenicity: This drug is a potent teratogen (Category X). It has an incredibly long half-life and can stay in the body for up to 2 years after stopping.
Your Role:
- Females: Must have a negative pregnancy test before starting. Must be on reliable contraception.
- Males: The drug is present in semen. Men on this drug who wish to father a child must also stop it and undergo the “washout” protocol.
Tutorial: The Aubagio Accelerated Elimination Protocol
If a patient (male or female) wants to get pregnant, or if they have severe liver toxicity, you can’t just “stop the drug.” You must actively “wash it out” of their body. Your pharmacy must know and be able to explain this.
The Protocol:
1. Cholestyramine: 8 grams TID for 11 days. (This is the preferred, fastest method).
OR
2. Activated Charcoal: 50 grams BID for 11 days.
Verification: After the 11-day course, plasma levels must be checked. If they are > 0.02 mg/L, the protocol must be repeated.
C. The High-Efficacy Infusions (The “Big Guns”)
These are the most effective therapies available, reserved for patients with highly active disease or who have failed other DMTs. They are almost all handled by specialty pharmacy infusion services.
1. Anti-CD20 Antibodies (The “B-Cell Depleters”)
- Drugs: Ocrelizumab (Ocrevus, IV), Ofatumumab (Kesimpta, SC), Rituximab (Rituxan, IV off-label).
- Mechanism: These are monoclonal antibodies that bind to the CD20 protein on B-cells, causing them to be destroyed. This removes a key cell type involved in the MS attack.
Masterclass Table: Comparing the Anti-CD20s
| Drug | Dosing | Pharmacist’s “Must-Know” Fact |
|---|---|---|
| Ocrelizumab (Ocrevus) | IV infusion every 6 months. | This is the ONLY DMT approved for Primary Progressive MS (PPMS). This is a game-changer. |
| Ofatumumab (Kesimpta) | Subcutaneous (SC) injection once monthly (at home). | This is a “bio-better” version of Ocrevus, taking the 6-month infusion and turning it into a monthly at-home injection. A huge win for patient access and convenience. |
Pharmacist’s Role (Infusion/Monitoring):
- Pre-Medication: These cause infusion-related reactions. The pharmacist is responsible for ensuring the pre-med protocol is followed: IV Methylprednisolone (100mg), an Antihistamine (Diphenhydramine), and an Antipyretic (Acetaminophen) 30-60 minutes before the infusion.
- Baseline Screening: You are killing B-cells, so you risk reactivating infections. You *must* verify a negative Hepatitis B Panel (HBsAg and anti-HBc) and a TB test before the first dose.
- Infection Risk: Patients will have a suppressed immune system. Counsel them on infection risk and the need to be up-to-date on *inactivated* vaccines.
2. Alpha-4 Integrin Antagonist (The “Bouncer”)
- Drug: Natalizumab (Tysabri).
- Mechanism: It’s a “humanized” monoclonal antibody. Think of it as a “bouncer.” It blocks the “door” (the $\alpha_4\beta_1$-integrin) that T-cells use to get from the blood into the brain. It doesn’t kill any cells; it just keeps them out of the CNS.
- Dosing: IV infusion every 4 weeks.
BLACK BOX WARNING & REMS: Progressive Multifocal Leukoencephalopathy (PML)
This is the most famous REMS program in all of specialty pharmacy. Tysabri is highly effective, but it has one catastrophic risk: PML. By keeping immune cells out of the brain, you are also stopping routine immune surveillance. If a patient is a carrier of the JC Virus (JCV), the virus can reactivate in the brain, causing this fatal, untreatable infection.
Tutorial: The TOUCH REMS Program
As a pharmacist, you are the final checkpoint for this REMS program.
The Workflow:
1. Enrollment: The prescriber, the patient, the infusion center, and the specialty pharmacy must all be enrolled in the TOUCH program.
2. The JCV Test: Before the *first dose*, the patient must have a JCV antibody test.
3. Risk Stratification: You must check this lab.
- JCV Negative: Risk is negligible. Patient can start therapy. Must be re-tested every 6 months (as they can seroconvert).
- JCV Positive: Risk is significant. The prescriber *must* have a discussion with the patient.
- JCV Positive + High Titer + >2 Years on Tysabri: This is the highest-risk group. Many providers will switch therapy.
4. The Pre-Dispense Check: Before *every single infusion*, the pharmacist must log into the TOUCH system and verify: 1) The patient is current on their labs. 2) The patient has answered the safety questionnaire. 3. The authorization is given to infuse. This is your job.
3. Anti-CD52 Antibody (The “Immune Reset”)
- Drug: Alemtuzumab (Lemtrada).
- Mechanism: A “nuke.” It’s a monoclonal antibody that binds to CD52, a protein on *all* T-cells and B-cells, causing their rapid and profound depletion. The immune system then slowly “reboots” over months to years.
- Dosing: This is not chronic therapy. It’s “Selective Immune Reconstitution.”
- Course 1: 12mg IV infusion daily for 5 consecutive days.
- Course 2: Wait 12 months. Then 12mg IV infusion daily for 3 consecutive days.
- …and that’s it. Two courses, one year apart.
BLACK BOX WARNINGS: Autoimmunity, Infusion Reactions, Malignancies, Stroke
This drug is incredibly effective, but also incredibly high-risk, and requires its own REMS program.
1. Infusion Reactions: Nearly 100% of patients have them. Requires a 1-gram Solu-Medrol pre-medication.
2. Malignancies: Increased risk of thyroid cancer and melanoma.
3. Stroke: Rare but has occurred, usually close to the infusion.
4. Autoimmunity: This is the *biggest* risk. By “rebooting” the immune system, it can “reboot wrong.” Up to 40% of patients will develop a *new* autoimmune disease within a few years.
- Thyroid Disease: Most common (Grave’s disease, Hashimoto’s).
- Immune Thrombocytopenic Purpura (ITP): A fatal bleeding disorder.
Your Role (REMS): The REMS program requires monitoring for 48 MONTHS (4 years) after the last dose. This includes monthly CBC, TSH, and SCr. Your specialty pharmacy is responsible for coordinating and tracking this long-term monitoring.
5.2.4 Deep Dive: Amyotrophic Lateral Sclerosis (ALS)
ALS (Lou Gehrig’s Disease) is a relentlessly progressive, fatal neurodegenerative disease characterized by the death of both upper and lower motor neurons. This leads to progressive muscle weakness, paralysis, and eventually, death from respiratory failure, typically 2-5 years after diagnosis.
Unlike MS, our pharmacologic arsenal to *slow* the disease is heartbreakingly small. The *primary* role of the pharmacist in ALS is aggressive, proactive, palliative polypharmacy to manage the devastating symptoms and maintain quality of life.
Disease-Slowing Therapies
There are only a few FDA-approved drugs to slow progression. Your job is to manage their logistics and side effects.
1. Riluzole (Rilutek, Tiglutik, Exservan)
- Mechanism: A glutamate inhibitor. It’s thought to protect motor neurons from glutamate-induced excitotoxicity.
- Efficacy: Modest at best. It extends survival by an average of 2-3 months. This is a vital, but difficult, counseling point.
- Monitoring: LFTs. It can be hepatotoxic. You must monitor LFTs monthly for the first 3 months, then quarterly.
- Formulations:
- Rilutek: 50mg tablet.
- Tiglutik: A thickened oral suspension for patients who develop dysphagia (difficulty swallowing).
- Exservan: An oral film that dissolves on the tongue.
2. Edaravone (Radicava, Radicava ORS)
- Mechanism: A potent antioxidant and free radical scavenger.
- Efficacy: In a subset of patients, it was shown to slow the *rate* of functional decline.
Tutorial: The Radicava Dosing Calendar
This is a core specialty pharmacy coordination task. The original IV formulation has a complex, non-intuitive dosing cycle that you *must* manage for the patient.
The Protocol:
– Cycle 1 (Loading): The patient receives a 60mg IV infusion daily for 14 consecutive days. This is followed by a 14-day drug-free period.
– Cycles 2 and beyond: The patient receives a 60mg IV infusion daily for 10 days (within a 14-day window). This is followed by a 14-day drug-free period.
Your pharmacy is responsible for scheduling these infusions, managing the calendar, and conducting adherence calls to ensure the patient doesn’t miss their “on” and “off” windows.
Radicava ORS: The new oral suspension has greatly simplified this. It is dosed once daily in the morning, on an empty stomach (fasting for 8 hours). However, it still follows the “on-off” cycle (14 days on, 14 off; then 10 of 14 on, 14 off). This is still a complex adherence counseling challenge.
The Pharmacist’s True Role: Symptomatic Polypharmacy
This is where you will have the greatest impact on your patient’s daily life. You will be managing a “palliative care” regimen from the beginning.
Masterclass Table: The ALS Symptom Management Playbook
| Symptom | Problem | Pharmacist’s “Go-To” Toolkit | Clinical Pearls |
|---|---|---|---|
| Sialorrhea (Drooling) | The patient isn’t making more saliva; their weak pharyngeal muscles mean they can’t swallow it. | Anticholinergics:
– Glycopyrrolate (tablets) – Atropine 1% ophthalmic drops (used sublingually) – Scopolamine patch – Botulinum toxin (Botox) injections into the salivary glands. |
|
| Pseudobulbar Affect (PBA) | Involuntary, uncontrollable, or exaggerated episodes of laughing or crying. | Nuedexta (Dextromethorphan/Quinidine) |
|
| Spasticity & Cramps | Painful muscle stiffness and cramps from motor neuron damage. | – Baclofen (a GABA-B agonist)
– Tizanidine (an alpha-2 agonist) |
|
| Thick Mucus | Patient can’t cough effectively, leading to thick, tenacious secretions. | – Guaifenesin (to thin mucus)
– Nebulized Acetylcysteine (Mucomyst) – A “cough-assist” machine (non-pharm) |
|
5.2.5 Deep Dive: Refractory Epilepsy
Epilepsy is a spectrum, but this section focuses on refractory epilepsy, defined as the failure to achieve seizure freedom after an adequate trial of two or more appropriate Anti-Epileptic Drugs (AEDs). These patients are on complex, multi-drug regimens and are at high risk for both seizures and side effects.
Your Role: In refractory epilepsy, the pharmacist is the drug-drug interaction (DDI) manager and the therapeutic drug monitoring (TDM) expert. Epilepsy is the single most DDI-heavy field in neurology.
Pathophysiology Masterclass: The GABA/Glutamate Scale
For our purposes, seizures are a “short circuit” in the brain. They represent a state of hyperexcitability, where the “accelerator” (Glutamate) is pushed too hard, and the “brake” (GABA) is not strong enough.
Nearly every AED we have works on one of four main principles:
- Pressing the “Brake” (Enhancing GABA): Benzodiazepines, Phenobarbital, Valproic Acid.
- Easing off the “Accelerator” (Blocking Glutamate): Lamotrigine, Topiramate.
- Blocking Sodium Channels (Stopping the signal): Phenytoin, Carbamazepine, Lamotrigine, Lacosamide.
- Blocking Calcium Channels (Stopping release): Gabapentin, Pregabalin, Ethosuximide.
The Pharmacist’s Role: The “DDI” and “TDM” Manager
Your retail DUR skills are now your primary clinical weapon. The “older” AEDs are the most powerful enzyme inducers and inhibitors in the P450 system. They are notorious for destroying the efficacy of other drugs or boosting them to toxic levels.
Masterclass Table 1: The AED Interaction “Hit List”
| Class | The “Perpetrators” | The Mechanism | Your “Must-Stop-and-Check” Victims |
|---|---|---|---|
| Broad-Spectrum INDUCERS | – Phenytoin (Dilantin)
– Carbamazepine (Tegretol) – Phenobarbital – Oxcarbazepine (>1200mg) – Topiramate (>200mg) |
These drugs “chew up” other medications by up-regulating (inducing) CYP enzymes (3A4, 2C9, 2C19). They DECREASE the levels of other drugs. |
|
| Broad-Spectrum INHIBITOR | – Valproic Acid (Depakote) | This drug “boosts” other medications by INHIBITING UGT and CYP enzymes. It INCREASES the levels of other drugs. | |
| The “Cleaner” Agents | – Levetiracetam (Keppra)
– Lacosamide (Vimpat) – Gabapentin (Neurontin) – Brivaracetam (Briviact) |
These are the “good guys” in polypharmacy. They have minimal to no CYP interactions, making them the preferred add-on agents in refractory patients. |
|
Critical Protocol: The Lamotrigine (Lamictal) Titration
This is arguably the most dangerous common titration in all of pharmacy. The risk is the fatal Stevens-Johnson Syndrome (SJS) / Toxic Epidermal Necrolysis (TEN) rash. The risk is 100% related to titrating too fast or an interaction.
Your Role: You are the guardian of the titration kit.
– Standard (Orange Kit): Weeks 1-2 = 25mg daily. Weeks 3-4 = 50mg daily.
– Added Inducer (Green Kit) (e.g., on Carbamazepine): Titration is *FASTER* (starts at 50mg/day).
– Added Inhibitor (Blue Kit) (e.g., on Valproic Acid): Titration is *DANGEROUSLY SLOW* (starts at 25mg every other day).
The Script: “We are starting this medicine, Lamotrigine, extremely slowly. This is to protect your skin from a rare but very serious rash. You must follow this titration pack *exactly*. Never take more, never ‘double up’ on missed doses, and never restart at a high dose if you’ve stopped for more than a few days. If you develop *any* rash, especially with a fever or blisters in your mouth, you must stop the drug and go to the emergency room immediately.”
Masterclass Table 2: The AED Toxicity & Monitoring Playbook
| AED | TDM (Therapeutic Range) | Critical Monitoring & “Must-Know” Toxicity |
|---|---|---|
| Phenytoin (Dilantin) | 10-20 mcg/mL (Total)
1-2 mcg/mL (Free) |
|
| Carbamazepine (Tegretol) | 4-12 mcg/mL |
|
| Valproic Acid (Depakote) | 50-100 mcg/mL |
|
| Levetiracetam (Keppra) | Not routine. |
|
| Lacosamide (Vimpat) | Not routine. |
|
| Cannabidiol (Epidiolex) | Not routine. |
|
