Pediatric Pharmacology Lecture 10 (PDF)

PEDIATRIC Matthew T. Vaughn, O D OCULAR FAAO Pediatric Optometry and Vision Development PHARMACOLOGY July 9, 2024 1 § Introduction § Ocular Diagnostics § Antibiotics § Antivirals § Anti-infl...

PEDIATRIC Matthew T. Vaughn, O D OCULAR FAAO Pediatric Optometry and Vision Development PHARMACOLOGY July 9, 2024 1 § Introduction § Ocular Diagnostics § Antibiotics § Antivirals § Anti-inflammatories § Ocular Allergy § Glaucom a § Hyphema § Systemic M eds 2  § Only ~25% of drugs marketed in US are labeled for use in infants and young children FDA DRUG § About ~50% of commonly used topical LABELING FOR ophthalmic drugs have labeling regarding pediatric use PEDIATRICS § Terminology § Not Established (NE) § Not Recommended (NR) 3  Newborns: Birth to 1 month Infants: 1 month to 2 FDA years SUBCATEGORIES OF PEDIATRICS Children: 2 to 12 years Adolescent: 12 to 16 years 4  § Small Size – but they’re not just little adults! § Physiological Differences § Absorption § Naso-lacrim al system , G I absorption, absorption through skin § Distribution throughout the body § Immature protein bind ing and blood brain barrier, smaller fluid volume § Metabolism § Liver § Excretion § Kidneys – immature enzymes à making the drug more effective § Poisoning more common from ingestion of meds -nasolacrimal system absorbs the medication readily as well as GI absorption and skin membrane -protein binding is not great and 5  § Q: Which of the following does NOT reduce systemic absorption of a topical medication? A. Immobilize child during instillation B. Instill several drops at a time C. Punctal occlusion à absorbs the drug more in children than in adults D. Keep lids closed after instillation E. Blot away excess drugà the drug gets absorbed in the skin -we don’t want to instill several drops at a time 6  Topical Drugs (solution, suspensions) § Advantages: ADMINISTRATION § Easy to instill in cooperative children § Less messy OF OPHTHALMIC § § Less of an effect on vision Disadvantages DRUGS § Systemic absorption à going thru nasolacrimal system § Minimal contact time bc it’s a liquid § Difficult administration in uncooperative children 7  Topical Ointments ADMINISTRATION § Advantages § More comfortable during instillation à doesn’t sting OF OPHTHALMIC § R ed uced potential for systemic toxicity § Longer contact time on the ocular surface DRUGS § Disadvantages § Transient blurred vision à instilling during the day can effect vision § Increased potential for contact dermatitis 8  Oral à children are usually prescribed liquid over solid ADMINISTRATION § § Liquids (suspensions, solutions) Solids (pills, capsules, tablets) OF OPHTHALMIC § Commonly used oral pharmaceuticals § Antihistamines DRUGS § Decongestants § Antibiotics 9 OCULAR DIAGNOSTICS 10  § Decreases corneal sensitivity § Improves transport of other agents across cornea § Indications § Before administration of other drops** § Corneal foreign body or injury § Tonometry à for glaucoma suspect § 0.5%/1% proparacaine, 0.4% benoxinate § With or without Fluorescein dye -use anesthetics in children when we are about to instill other drops such as tropicamide bc we know it stings so putting an anesthetic helps with comfort 11 Tropicamide § Muscarinic antagonist: paralyzes the iris sphincter and ciliary muscle § Concentrations: 0.5%, 1.0% § 0.5% used in younger than 1 yo and lighter irides § Poor cyclop legia effect with 0.5%! (can use that in albinism) § Rarely can cause C S N disturbance § Onset: 15-30 minutes § Duration 4-6 hours 12  Phenylephrine HCl (Neo-synephrine) § No cycloplegic effect § 2.5% maximum dose: 2 gtts spaced 5 mins apart § Use with caution in children with cardiovascular disease, premature infants and children in the first 6 months of life à 2.5% concentration § D O NOT USE 10% ! § 1% used in Cyclomydril generally safe in all infants § Paremyd (0.25% tropicamide and 1.0% p-hydroxyamphetamine) § Combo spray/drops: 0.5%Tropic + 2.5% Phenyl + 0.5% Cyclo à don’t last very long -don’t use it that much unless pt is a high myope -premature infants have immature kidneys but in general infants have immature kidneys 13  Atropine § Muscarinic antagonist: paralyzes the iris sphincter and ciliary muscle § Approved for 3 months and older CYCLOPLEGICS § 0.5% in light irides; 1.0% in darkly pigmented irides § Ointment or gtts instilled qhs for 3 nights before exam § Onset: 3-6 hours § Duration: 1 week (blur), 2 weeks (pupil dilation) -1% is approved for 3 months an older infants 14  Atropine § FDA approved for: dilation, cycloplegia, penalization (amblyopia), uveitis § Off-label use: myopia management (low CYCLOPLEGICS concentrations) § Children with Down syndrome, spastic paralysis, brain damage and very light pigmentation may be hypersensitive to the cholinergic antagonists § Ocular side effects: photophobia, blurred near vision, dilated pupils -only FDA approved myopia management is Misight aka multifocal CL 15  Atropine § Peripheral Signs of Atropine Toxicity § M u c o u s m em branes: D ry eyes, mouth, throat § Skin: Flushed, dry, hot, rash on face/mask CYCLOPLEGICS § Cardiovascular: Tachycardia, HTN § Respiratory: Tachypnea § G I : D ecreased peristalsis, abdom inal distension in infants § Genitourinary: Bladder distention, urgency § Other: Fever, headache -want to educate the parent on side effects before prescribing 16  Atropine § Central Signs of Atropine Toxicity § N eurologic Dysfunction: M uscle tremors, weakness § C erebellar Dysfunction: Ataxia, dysarthria, muscle incoordination CYCLOPLEGICS § Confusional psychosis: Restlessness, irritability, violent and aggressive behavior, confusion, disorientation, visual and tactile hallucinations § Term inal Phenom ena: convulsions, stupor, com a, death § Antidote: Physostigmine Salicylate -want to educate the parent on side effects before prescribing à put an effort to emphasize how dangerous the medication can be -does cross the BBB 17  Cyclopentolate § Muscarinic antagonist § Concentrations: (2 gtts separated by 5 minutes) § Under 1 year: 0.5% § O ve r 1 year: 1.0% CYCLOPLEGICS § Premature or LBW:1 gtt C yclom yd ril (0.2% C/1% PE) § Down syndrome § Onset: 15-30 minutes § Maximum Cycloplegia: 40 minutes à need to wait the full 40 mins to do cycloplegic testing § Duration: 6-8 hours, up to 24 hours à parents usually complain that child still has blurred vision post drops and ensure parent it is normal § Do N O T use 2% due to risk of side effects -dr. Vaughn uses 1% phenyl in down syndrome children bc they have lower accommodation to being with you don’t need a high dosage 18  Cyclopentolate § Used vs. atropine for shorter duration of action § Used vs. tropicamide for stronger cycloplegic effect CYCLOPLEGICS § Ocular side effects: photophobia, blurred near vision, pupil dilation § Systemic adverse effects: similar to atropine, but occur less frequently § Nervous system alterations have been reported: hallucinations, disorientation, memory loss, confusion 19  Tropicamide 1% § Less potent cycloplegic: very safe, less adverse effects compared to atropine § Onset: 15-30 minutes CYCLOPLEGICS § § Duration 4-6 hours Myopes: 2 gtts 1% T 5 mins apart is as effective in cycloplegia as 1% C (cyclopentolate should still be used in hyperopes!) § Scopolamine and Homatropine: rarely used 20 § Healthy 7-month-old infant: 0.5% cyclopentalate (2 gtt 5 mins apart) § 3-year-old Hispanic child: 1% cyclopentalate (2gtt 5 mins apart) § 3-year-old child with esotropia that did not dilate with 2 gtts 1% cyclo: 1% atropine at bedtime, 3 nights once a night before the exam) § 2-year-old toddler with Down syndrome: 0.5% cyclopentalate (punctal occlude according to the literature) or 1% cyclopentalate can be used 21  § First time patients: tropicamide and cyclopentolate § Amblyogenic dry retinoscopy: cyclopentolate THEN tropicamide § Degenerative myope (s amblyopia): tropicamide and phenylephrine “WHAT DROPS § Low to moderate myopes (s amblyopia): 2 gtts 1% T 5 mins apart DOYOU WANT TO § Low hyperope with 20/20 vision and no systemic issues: tropicamide USE?” § Persistent amblyopia: cyclopentolate THEN tropicamide § Low refractive error with normal DFE last year: no drops! Dilate every 2 years § Pick the most important drop first! 22 ANTIBIOTICS 23 § Uses: § Bacterial conjunctivitis § Corneal ulcer § Corneal abrasion § Conjunctivitis 2^ nasolacrimal duct obstruction (NLDO) § Considerations: § Culturing not routine in children § Broad spectrum A b to cover most common bugs § Long acting § Cost 24  § MOA: Inhibits bacterial DNA gyrase § (1) Ciloxan (Ciprofloxacin 0.3%) – ung or gtt, >2 yrs à cheapest § (2) Ocuflox (Ofloxacin 0.3%) >1 yr § (3) Quixin (Levofloxacin 0.5%) >6 yrs à not typically prescribing § (4) Zymar (Gatifloxacin 0.3%) >1 yr § (4) Vigamox (Moxifloxacin 0.5%) all ages § (4) Moxeza (Moxifloxacin 0.5%) ≥4 mos § (5) Besivance (Besifloxacin 0.6%) >1 yr -don’t memorize the generations all of them! -know which one has the youngest approval, which is the cheapest 25 Aminoglycosides § MOA: Inhibit protein synthesis (30S ribo) § Tobrex (Tobramycin 0.3%) soln and ung; infants ≥ 2 mos à don’t use by itself, usually use in combo § Neomycin (only in combination) – NE § Gentam icin; ≥ 6 years à pediatricians love to use this Macrolides à larger subunit § MOA: Inhibits protein synthesis (50S ribo) § *Erythromycin 0.5%; ung, oral and IV; infants/newborns à ointment so its lubricating § Azasite (Azithromycin 1%); ≥ 1 year; good dosing à BID so tw ice a day but it is expensive so not prescribed as m uch 26 Polytrim (Polymixin B + Bacitracin (ung) Trimethoprim) § MOA: Inhibits bacterial cell wall synthesis § Polymixin B MOA: disrupts § Ung integrity of cell wall membrane § NE § Trimethoprim MOA: inhibits folic acid synthesis Polysporin (Bacitracin + § Approved for ≥ 2 mos Polymixin B) § *MRSA susceptible to § Ung Trimethoprim § NE Mupirocin – skin infections Sulfacetamide 10%, 15% (rarely used) 27 Oral Antibiotics Commonly Used in Children § Penicillins § Inhibit bacterial wall formation § i.e. Amoxicillin, dicloxacillin § C om m on allergy* § Cephalosporin § Similar structure and action in P C N § i.e. cefazolin, cefaclor, ceftriaxone § C om m on allergy* § Macrolides § Erythromycin § Tetracyclines – NOT used in children under age 8: permanent darkening of teeth, delays in osteogenesis 28 -3 YO boy here for urgent vision and eyelid was getting worse by day -preceptal cellulitis formed from hordeolum -pt was sent immediately to the hospital 29 § Septum forms barrier: deep orbital soft tissue v. superficial structures § Inflammation limited by septum: preseptal cellulitis v. posterior to septum: orbital cellulitis 30 § Paranasal sinuses are most common cause of orbital cellulitis § Ethmoidal sinusitis has been reported in 84-100% of orbital cellulitis § Breaches in skin barrier: trauma, insect bites are most common cause of preseptal cellulitis but also adjacent infections: hordeolum, dacryocystitis § Staphylococcus Aureus and Streptococcus bacteria are majority of causes of preseptal or orbital cellulitis 31 § Only ethmoid sinuses are well developed at birth § Maxillary sinus develops within first 2 years but not fully developed until 6 years of age § This explains why almost exclusively, orbital cellulitis is caused by ethmoidal sinusitis in first 5 years of life § Ethmoidal, maxillary, and frontal sinusitis are causes in children over 7 years of age 32 33 § Prescribed empirically, as pathogen is not identified § Typically 2^ local trauma or infection, oral antibiotics are tx of choice § Amoxicillin + Clavulanate (Augmentin) à commonly used § 250-500 mg po TID or 875 mg po BID § Cephalexin (Keflex) § 250-500 mg po TID § Must note PCN and sulfa allergy precautions § If PCN allergy – Azithromycin “Z-Pak” or Levofloxacin § 500mg po § No tetracyclines < 8 years § In severe cases or < 5 years, hospitalization and IV antibiotics are indicated 34 § Nasal decongestants if sinusitis is present § Polysporin or Erythromycin if conjunctivitis present § Abscess § Surgical drainage 35  Internal hordeolum Orbital fracture Amoxicillin/clavulanate (Augmentin) Cephalexin (Keflex) Cephalexin (Keflex) Amoxicillin/clavulanate (Augmentin) Sulfamethoxazole/trimethoprim (Bactrim) Preseptal cellulitis Amoxicillin/clavulanate (Augmentin) Inclusion conjunctivitis Sulfamethoxazole/trimethoprim (Bactrim) Azithromycin Dacryocystitis Posterior blepharitis Amoxicillin/clavulanate (Augmentin) Doxycycline*** Sulfamethoxazole/trimethoprim (Bactrim) Azithromycin Dacryoadenitis Toxoplasmosis Amoxicillin/clavulanate (Augmentin) Sulfamethoxazole/trimethoprim (Bactrim) Cephalexin (Keflex) Hyperacute bacterial conjunctivitis Canaliculitus (nongonococcal) Cephalexin (Keflex) Cephalexin (Keflex) -cheat sheet for peds oral antibiotics -good slide to know! 36  § Follow FDA guidelines § Need to know: § Child’s weight in kilograms § Formulations of medications § Call Pharmacist and/or patient’s Pediatrician § 1tsp = 5mL § E.g. Augmentin: 20-40 mg/kg/day, 3 doses § Determine max and min mg/kg -ex. 5YO and want to prescribe augmentin (weighs 40lbs or 18kg) -20mg/kg * 18kg = 360 mg/day à min -40mg/kg*18kg = 720 mg/day à max -need to prescribe between 360 and 720 and you need prescribe 3 doses and our options are 250 and 500. 250 would be too much so you would cut the 250mg in half and provide 125 3 doses -know how to do this calculation for the final! 37 ANTIVIRALS 38  § Adenovirus à causes pink eye § Rule of 7 § Upper respiratory tract infections are common § Palliative treatment § Cool compresses § Artificial tears § Patient education!! § May consider antibiotic if concerned about secondary infection -there’s really no best medication to help it go away faster so use palliative treatment 39  § Signs/Symptoms § (+) PAN § Watery discharge § FBS § Follicular response -clear is viral -watery mucopurulent is allergic -yellow/green is bacterial 40  § Adenovirus serotypes 8, 19, 37 § Begins unilateral, becomes bilateral in up to 70% § Different from run-of-the-mill viral § Stain the cornea!! § Petechial or subconjunctival hemorrhage § Photophobia § Flu-like symptoms (fever, HA, fatigue) § Betadine: povidone iodine -this has corneal involvement so stain the cornea -presents initially unilateral but progresses bilateral so medication has to be applied in both eyes -wear gloves when a pt comes in with urgent red eye 41  § HSV1 § Not typically dendritic like in adults § Primary manifestation: uniliteral vesicular BKC -unilateral and will stay unilateral! -clear discharge bc its viral 42  Blepharoconjunctivitis Consider immune status of patient Topical or oral antivirals May do both oral and topical antiviral in Cornea immunocompromised Epithelial Oral or topical antiviral Oral acyclovir (about one year) long-term Debridement helps decrease the chance of recurrence of Stromal corneal disease (32% vs. 19% with prophylaxis) Topical steroid and antiviral cover (topical or oral) Endotheliitis (disciform keratitis) Topical steroid and oral antiviral Topical antivirals have poor penetration Uveitis Topical steroid and oral antiviral cover -topicals don’t get to the endothelium -if you’re treating a child long term with oral antiviral then you may have to change dosage of the medication bc overtime the child increases in weight hence the change in dosage 43 § Trifluoridine 1% (Viroptic soln) § Oral Acyclovir (Zovirax) § MOA: Inhibits DNA synthesis § MOA: inhibits DNA polymerase § Ages ≥6 years § Ages ≥2 years § Dose: q2h; up to 9x/day § 15 mg/kg/day, 5x/day x7-10 days § More toxic to the cornea, cheaper § Prophylactic dose BID ~1 year § Gancyclovir 0.15% (Zirgan gel) § Kidney and liver function must be monitored § MOA: inhibits DNA replication § Ages ≥2 years § Dosed 5x/day until heals then TID x7 days § Less toxic to the cornea, expensive 44 ANTI-INFLAMMATORIES 45  § Fluoromethalone § 0.1% (FML); 0.25% (FML Forte) § ≥2 years § Ung or soln § Loteprednol etabonate § 0.2% (Alrex); 0.5% (Lotemax) § NE STEROIDS § Prednisolone Acetate 1% (Pred Forte) § NE § Difluprednate 0.05% (Durezol) § NE § Side effects of PSC and elevated IOP are possible! Children are more susceptible and should be monitored closely -for steroids this is the only one that is FDA approved à know this! -however this is not the only one that can be used in kids -the rest of the steroids are off label use 46  § TobraDex (Dexamethasone 0.1% + Tobramycin 0.3%) § ≥2 years § Dose: 1gtt q4-6 hours STEROID + § Maxitrol (Dexamethasone 0.1% + Neomycin0.35% + Polymixin B) ANTIBIOTIC § ≥2 years COMBOS § Dose: 1gtt q4-6 hours § Blephamide (Sulfacetamide 10% + Prednisolone 0.2%) § ≥6 years § Dose: 2 gtts q4 hours -combo drops 47  § Not often prescribed in children § Acular (Ketorolac tromethamine 0.5%) § O n ly one approved; ≥ 2 years NSAIDS § D ose: Q ID § Nepafenac § >10 years 48 § Common Etiologies § Juvenile rheumatoid arthritis, juvenile idiopathic arthritis, traum a (sports), HSV/HZV, adult etiologies m ore rare § Treatment § Same as in adults § Pred Forte QID § Cyclopentolate Q D § Must monitor IOP (steroid responders) § Taper § Steroid Responders: § If IOP increases above 30mmHg: Add timoptic 0.25% § Be aware of contraindications § Co-manage with pediatric rheumatologist 49 -6D of cyl -peached pupils and had cells in AC and PS -bilateral chronic non granulomatous anterior uveitis 50 -can see the PS 51 OCULAR ALLERGY 52  § History § Medical conditions § New pets/environment § Drug/food allergies § Symptomology ALLERGIC § Symptoms – usually bilateral § Itching – but not always! CONJUNCTIVITIS § Redness § Tearing § Eye rubbing § Runny nose § Sneezing 53 § Signs § Papillae § Edema/chemosis § Injection § Caruncle à first place to see papillae in allergies § Allergic shiner 54  § Ketotifen 0.025% – Antihistamine/mast cell stabilizer; ≥3 years § Zaditor BID/ Alaway BID § Epinastine HCl 0.05% – Antihistamine/mast cell stabilizer; ≥2 years § Elestat BID § Azelastine HCl 0.05% – Antihistamine/mast cell stabilizer; ≥3 years § Optivar BID § Bepotastine Besolate 1.5% – Antihistamine/mast cell stabilizer; ≥2 years § Bepreve BID § Emastadine Difumarate 0.05% – Antihistamine; ≥3 years § Emadine QID § Alcaftadine 0.25% – Antihistamine/mast cell stabilizer; ≥2 years § Lastacaft Q D à a l s o a g o o d o p t i o n b c i t s o n c e a d a y a n d cheaper § Olopatadine 0.1%, 0.2%, 0.7% – Antihistamine/mast cell stabilizer; ≥3 years § Pataday Twice Daily Relief, Once Daily Relief, Extra Strength -impt to remember from this slide is we usually go straight to pataday 55 § Pemirolast Potassium 0.1% – Mast cell stabilizer; ≥3 years § Alamast QID § Nedocromil Sodium 2% – Mast cell stabilizer; ≥3 years § Alocril BID § Lodoxamide Trimethamine 0.1% – Mast cell stabilizer; ≥2 years § Alomide § Cromolyn Sodium 4% – mast cell stabilizer; ≥4 years § Opticrom QID / Crolom QID § OFF LABEL § Pred Forte § Durezol § Lotemax/Alrex 56  MTV’S ALLERGIC CONJUNCTIVITIS ALGORITHM O T C antihistamine – Rx antihistamine – Education and cool Alaway/Zaditor Optivar (azelastine), Rx combo –Pataday compresses family (olopatadine) Pediatrician/Allergist (ketotifen) Lastacaft (alcaftadine) UKS -kids should be showering at night to decrease the amount of allergens -cool compress can be used for light allergies 57 $20 $24 $26 58  § Unusually severe sight-threatening allergic eye disease § Male > female (3-4:1), onset usually before 10 years of age § Mediterranean decent (Italy>>>) § Symptoms § Severe itching and irritation, eye rubbing § Photophobia § FBS § Blurred vision § Blepharospasm -really bad allergic conjunctivitis -vernal implies that it only occurs in the spring but it can occur all year around 59  § Signs § Injection § Conjunctival hyperemia with edema § Edematous ptosis § Thick mucous (white) ropy discharge § Large superior tarsal papillae (“cobblestone”, Tarsal VKC) § Horner-Trantas dots (Limbal VKC), thickening and opacification of limbus § Shield ulcer -limbal is seen more frequently -GPC is only a CL condition 60 -cobblestone papillae 61  § Mild cases are self-limiting, resolve by puberty § Conventional allergic ocular treatment is often insufficient § Mild § Cool compresses § Topical antihistamine VKC TREATMENT § Moderate + MANAGEMENT § Mast cell stabilizer + antihistamine § Severe § Topical steroid: high pulse dose with quick tapering (FML/Lotemax/Alrex) § Oral steroid: sight-threatening cases § Verkazia: cyclosporine 0.1% emulsion § First FDA approved med for VKC! § QID § Penetrates the cornea very well -pt is on long term medication until puberty -regular pataday may not be effective but may want to use a strong combo drug or a steroid -oral steroids are implied when there is shield ulcers 62 63 64  GLAUCOMA MEDICATIONS 65  § 1/10,000 live births § Buphthalmos, blue/hazy cornea, megalocornea § Generally requires surgical intervention § Poor long-term prognosis § REFER to pediatric glaucoma specialist § Medical Treatment Options: § Beta blockers (FDA approved) § Prostaglandin analogs not effective § Alpha-adrenergics (Alphagan) NOT used, central nervous system depression -these kids usually have an IOP of 50-60mmHg 66  HYPHEMA MANAGEMENT 67 § Atropine BID § Taper to Q D once clot heals § Pred Forte for inflammation § q1h or q2h initially, depending on severity § Precautions: § No aspirin or ibuprofen!! § Monitor Q D until hyphema resolved § Monitor IOP § Bed rest, head elevated to 30° 68 COMMON SYSTEMIC MEDICATIONS IN CHILDREN 69 SYSTEMIC MEDS Systemic Steroids § Indications § Asthma, allergies, inflammation § Formulations § Inhaled § Intranasal § Oral § Topical § Side Effects § Weight gain, stomach ulcers, sleep difficulties, ↑blood pressure, ↑blood sugar, ↓wound healing § Cataracts, ↑IOP (glaucoma) 70 § Allergic Rhinitis – nasal spray § Flonase (Fluticasone) § ≥4 years § Veramyst (Fluticasone) § ≥2 years § Nasonex (Nometasone) § ≥2 years § Rhinocort (Budesonide) § ≥6 years § Omnaris (Ciclesonide) § ≥6 years 71 § Allergic Rhinitis – Oral § 1st Generation Antihistamines § Diphenhydramine (Benadryl) § 2nd Generation Antihistamines § Loratadine (Claritin): ≥2 years OTC § Cetirizine (Zyrtec): ≥6 mos § Fexofenadine (Allegra): ≥2 years, syrup or tablet § Desloratadine (Clarinex): ≥6 mos, available in Rx syrup § Montelukast (Singulair): ≥6 mos, granule packet; ≥4 years chewable tablet § Decongestants § Pseudoephedrine (Sudafed) § Phenylephrine HCl § Both ≥4 years 72 § ADHD § Depression + Anxiety + OCD: SSRIs § Ritalin/Concerta (methylphenidate) § Prozac (fluoxetine) § Adderall § Lexapro (escitalopram) (amphetamine/dextroamphetamine) § Zoloft (sertraline) § Strattera (atomoxetine) § Multivitamins/vitamins § Vyvanse (lisdexamfetamine) § Eczema § Seizure Disorders § Hydrocortisone § Keppra (levetiracetam) § Aquaphor, Cetaphil creams § Depakote (valproic acid) § Lamictal (lamotrigine) 73