The ABCs of OTCs Over the Counter Products

The ABCs of OTCs Over the Counter Products ROLAND HALIL, BSC(HON), BSC. PHARM, ACPR, PHARMD BRUYERE ACADEMIC FAMILY HEALTH TEAM DEPARTMENT OF FAMILY MEDICINE, UOTTAWA RHALIL@BRUYERE. ORG AUG 2015

Objectives 1. Simplify the understanding of OTCs 2. Dispel myths of brand competition 3. Discuss basic pharmacological ingredients common to most products 4. Rationalize the choice of therapy when considering OTC products 5. Identify factors that may alter management by the primary provider

Table of Contents Antihistamines Analgesics Cough & Cold Emergency Contraception Anti-fungals & Anti-parasitics Vitamins and Minerals Antacids Laxatives Herbals & Natural Products (Briefly!)

Choosing Therapy Rational prescribing requires a process. Consider (in order): 1. 2. 3. 4. Efficacy Toxicity Cost Convenience When evidence for efficacy is strong: o Balance population-based efficacy with individual potential toxicities. When evidence for efficacy is weak: First, Do No Harm (ie. Toxicity outweighs Efficacy)

OTCs Large variety of OTC products Many brand extensions But, most OTCs have… The same ingredients mixed in many combos Poor evidence for efficacy or good evidence of limited efficacy Important safety precautions An incorrect presumption of safety Are monetized versions of ‘home remedies’ Focus on the Risk/Benefit of these limited ingredients Choice of therapeutics will be informed by understanding their pharmacology Identify at-risk populations

Antihistamines

Antihistamines - Allergies 1 st generation 2 nd generation More sedating Less-sedating Less specific for H 1 rec More specific for H 1 rec Anticholinergic etc. Shorter acting (8 hrs) More potent: Diphenhydramine (Benadryl®) Chlorpheniramine (Chlor. Tripolon®) Doxylamine Longer acting (24 hrs) But less potent (Des)-Loratadine (Claritin®, Aerius®) Cetirizine (Reactine®) Fexofenadine (Allegra®) Marketed as non-sedating!

Antihistamines - Bottom Line First Generation Efficacy Equivalent More potent vs 2 nd gen Toxicity Equivalent Cost Generics cheaper Convenience Equivalent amongst 1 st generation Q 8 h dosing Second Generation Efficacy Equivalent Less potent vs 1 st gen Toxicity Equivalent Cost Generics much cheaper Convenience Equivalent amongst 2 nd generation Q 24 h dosing

Cough & Cold Flu & Sinus

Cough & Cold Flu & Sinus Everything is some combination of: Antihistamine Diphenhydramine, chlorpheniramine, doxylamine Analgesic / Antipyretic Acetaminophen, ibuprofen, ASA Decongestant Phenylephrine, pseudephedrine Anti-tussive Dextromethorphan, codeine Expectorant guaifenesin

Cough & Cold Flu & Sinus There is no evidence for benefit, only symptomatic relief! There is certainly risk of harm! Products pulled for kids < 2 y. o. Will be relabelled for use > 6 y. o. Plenty of risks for adults too… Take Home: Only use if really needed and non-pharms are ineffective for relief

Analgesics / Anti-pyretics Acetaminophen or NSAIDs (ASA, Ibuprofen) Efficacy – no difference (in analgesia, nor anti-pyresis) Toxicity: ____________ Cost – no difference (cheap & generic) Convenience: no difference (all q 4 h) Pierce CA et al. Efficacy and safety of ibuprofen and acetaminophen in children and adults: a meta-analysis and qualitative review. Ann Pharmacother. 2010 Mar; 44(3): 489 -506. PMID: 20150507

Analgesics / Anti-pyretics Acetaminophen or NSAIDs (ASA, Ibuprofen) Toxicity: (generally well tolerated) Acetaminophen: Risk in overdose: hepatotoxicity Especially with combo products! Ibuprofen & ASA (as well as Naproxen and topical Diclofenac) 1) Risk of acute renal failure (ARF) • Avoid in renal disease, or with ACEinh, ARBs, diuretics 2) Risk of GI bleed • Avoid with anti-thrombotics, or history of bleeding 3) Risk of hypertension • Avoid in HTN, vasculopaths etc

Decongestants Phenylephrine & Pseudoephedrine 1) Efficacy – equivalent Relief of nasal congestion via vasoconstriction . 2) Toxicity: Sympathomimetic Amphetamine derivatives! Insomnia, tachycardia, hypertension, palpitations , anxiety, agitation, etc. Avoid in vasculopaths , insomniacs, anxious patients, hyperthyroidism, etc! 3) Cost – equivalent 4) Convenience – equivalent Counteracts sedation of antihistamines Also added to “Daytime” formulations No sinus pressure? No decongestant. Won’t dry a runny nose Topical Decongestants: naphazoline, oxymetazoline Rebound congestion with “prolonged” use (> 3 -5 days)

Anti-Tussives & Expectorants Dextromethorphan (DM syrup) & codeine: Codeine is a better anti-tussive vs DM But, it’s kept behind the counter. (Schedule 2) Risk of sedation, CNS effects Constipation with codeine, abuse potential DM cheaper than Codeine preps Equivalent dosing frequency Guaifenasin: expectorant, not anti-tussive No better than adequate hydration Likely more benefit from sticky syrup on throat

Cough & Cold; Sinus & Flu Combination products: Eg. DM + guaifenasin + decongestant Lack of flexibility Not always logical (anti-tussive + expectorant? ) Herbals/Natural Products: (Lozenges) Little evidence to support use Stimulate saliva secretion – throat soothing Echinacea: requires large doses, avoid in autoimmune diseases Vitamin C (>1 g/day) decreases cold sx duration by ½ day Zinc lozenges must be used q 2 h at onset of cold but poor taste/tolerability

Cough & Cold – Take Home Symptomatic relief only Risk of toxicity Especially combinations of combination products! (acetaminophen overdose) Buy individual ingredients based on need Avoid combination products with unnecessary ingredients Antihistamines for runny nose or eyes Analgesics for pain or fever Anti-tussive for cough Avoid decongestants! Try home remedies first

Emergency Contraception

Emergency Contraception Birth control used after intercourse & before implantation It is not an abortifacient Multiple options IUD insertion Within 5 -7 days of unprotected intercourse Hormone tablets Now available Over the Counter

OTC Emergency Contraception Pills (ECPs) 1. aka “morning after” pill Actually, within 72 hrs Combined Regimen (YUZPE): – – 2. Levonorgestrel 500 ug + Ethinyl Estradiol (EE) 100 ug Q 12 H x 2 Eg: Ovral - 2 tab Q 12 H x 2 doses Progestin Only: Plan B® - Levonorgestrel 750 ug 2 tabs stat N. B. Less effective if > 75 kg & ineffective if > 80 kg

Proportion of Pregnancies Prevented by Levonorgestrel vs. Yuzpe, by Timing of Treatment Levonorgestrel Yuzpe 95% 85% 77% 58% 36% 31% Timing of Treatment (hours) N. B. Treatment is more effective the sooner it begins! Task Force on Postovulatory Methods of Fertility Regulation. Lancet. 1998; 352: 428 -433.

Yuzpe Regimen: OC Formulations Brand Name Pills/Dose g EE/ Dose mg levonorgestrel/ Dose Ovral Alesse Levlite Nordette Levlen Levora Lo/Ovral Triphasil Tri-Levlen Trivora 2 white 5 pink 4 light orange 4 white 4 yellow 4 pink 100 100 120 120 0. 50 0. 60 0. 50 Adapted from ACOG Practice Bulletin. Int J Gynecol Obstet. 2002; 78: 191 -198.

OTC Emergency Contraception ECP Safety: No absolute contraindications except known pregnancy (ineffective) If strong contraindications to estrogen (VTE, breast cancer): Use Plan B ECP Side effects: Nausea / Vomiting: Yuzpe (50%), Plan B (20%) Bloating, cramping, breast tenderness Spotting (normal!) Early / late menses

Emergency Contraception – cont’d Missed pills: If >1 hour w/ emesis do not repeat dose If <1 hour w/ emesis repeat dose with antiemetic Second dose late: < 3 hours late – take as usual > 3 hours late – take ASAP then take a 3 rd dose 12 hours later Moot point now with Plan B – 2 tabs stat only

Plan B - Take Home Efficacy More effective vs Yuzpe method Toxicity Fewer side effects vs Yuzpe method Cost ~ $35 -$40 is generally affordable to most Convenience New Dosing – 2 doses stat – improved compliance New OTC status – but sometimes still kept behind the counter to minimize theft

Anti-Fungals

Fungal Infections - Tinea Pedis Superficial infections of the skin or nails Trichophyton rubrum, T. mentagrophytes & Epidermophyton floccosum etc. Acute symptoms Wet Smelly Small blisters that ooze (due to secondary bacterial infection) Chronic symptoms Dry Itchy Scaly skin

Fungal Infections - Tinea Pedis Pharmacological Options: Acute: antifungal + antibiotic (for Gram[-] infection) Chronic: antifungal agents Butenafine HCl 1% (Dr. Scholl’s®) fungicidal, 90% effective, QD Clotrimazole 1% (Canesten®), Miconazole (Micatin®), Tolnaftate (Tinactin®) fungistatic and weak antibiotic/anti-inflammatory properties, 70 -80% effective, cream, BID Monitoring for resolution: Acute - within 1 week, Chronic - within 6 weeks

Anti-fungals - Take Home Fungus – “slow to grow; slow to go”. Efficacy – about the same Toxicity – about the same Cost – about the same Therefore, compliance and patience are important! Any cream will do (Compliance is more important than published rates of eradication)

Fungal Infections - Vaginitis

Fungal Infections - Vaginitis Imidazole antifungal agents 70 -90% effective 1, 3, 7 -day treatments available Multi-day vs one day treatments Equivalent efficacy, but multi-day is better tolerated (lower toxicity) Miconazole (Monistat®) Clotrimazole (Canesten®) Tioconazole (Gynecure®) Terconazole (Terazol®) Ø Old school: Boric acid 600 mg capsules intravaginally qd - bid x 14 days

Lice - Pediculosis

Pediculosis For body lice: Hot water wash or dry clean clothes; Unwashables sealed in plastic for 10 days; Vaseline for eyelashes For head & pubic lice: Treat all contacts, and re-treat in 1 week Permethrin 1% (Nix Cream Rinse®, Kwellada-P Cream Rinse®) apply to towel dried hair, leave on for 10 min, best ovicidal activity (96 -100% with retreatment) Pyrethrins with piperonyl butoxide (Pronto Lice Control System®, R&C Shampoo/Conditioner®) apply to dry hair White vinegar (Step 2®) apply before lice treatment, soak hair then wrap in towel for 30 -60 min Lindane (PMS Lindane®, Hexit Shampoo®) not first line due to toxicities, (pesticide!) apply to dry hair for 4 min

Pinworms Infection of the colon by Enterobius vermicularis Common in school-age kids (2 -5 y. o. ) Pharm Options: treat all members of the household, retreat in 14 days Pyrantel pamoate (Combantrin®) – single dose - 11 mg/kg suspension, up to max 1 g/day, avoid in pregnancy Pyrivinium pamoate (Vanquin®) – single dose - 5 mg/kg susp up to max 350 mg/day, stains teeth/feces red, preferred in symptomatic pregnant women Non-Pharms: Wash hands/nails before meals and after use of washroom, regular cleaning of linens/clothes Change night clothes & linens at start of each treatment Discourage nail biting/finger sucking

Vitamins & Minerals

Vitamins & Minerals – Take Home All multi-vitamins are created equal Choose individual vitamins & minerals based on specific needs / deficiencies Beware common interactions Eg. Calcium & Iron Ca 2+ (or Fe, Mg 2+, Al 3+) plus: Antibiotics (Fluoroquinolones, Tetracyclines) Levothyroxine

Vitamins – Water soluble Vit B 1 (thiamine) – 50 -100 mg qd - alcoholics Vit B 2 (riboflavin) – 400 mg qd for migraine prophylaxis Vit B 3 (niacin) – 1000 mg for raising HDL (no benefit) Vit B 6 (pyridoxine) – 25 -100 mg - prevention of INH toxicity Vit B 9 (folate) – 0. 4 – 5 mg - prevention of neural tube defects, data for women and men now Vit B 12 (cyanocobalamin) – 1 -2000 mcg for pernicious anemia (PO daily or IM monthly) Vit C – Iron absorption

Vitamins – Fat soluble vitamins (A, E, D, K) Low fat diets, malnutrition, alcoholism 20 g of dietary fat required daily to ensure adequate levels of fat soluble vitamins Vit D – Osteoporosis & Cancer prevention Women on high-dose vitamin D supplementation (1100 IU/day) had a lower risk of all cancers vs. placebo (Lappe et al. Am J Clin Nutr (2007): 85; 1586 -1891) Vit K – 500 mcg qd - reduction in INR variability (Kamali, F. et al. Blood. 2007 Mar 15; 109(6): 2419 -23. )

Minerals Calcium: Osteoporosis: >1000 mg/day Iron (Fe): Pregnancy: increase Fe needs in 2 nd/3 rd trimesters (RDA = 27 mg/day) Fe-deficiency anemia - Treatment: 150 -200 mg ele Fe/day; Prophylaxis: 60 -100 mg ele Fe/day Fe Gluconate 300 mg = 35 mg ele Fe; Fe Sulfate 300 mg = 65 mg ele Fe; Fe Fumarate 300 mg = 100 mg ele Fe

Anti-acids

Anti-acids Buffers Mechanism of Action: Raise gastric p. H Duration: 0. 5 - 3 hours N. B. Drug interactions – antibiotics, levothyroxine Advantages: fast action, easy availability

Anti-acids - Buffers Calcium carbonate (TUMS®, Rolaids®) Most potent; chew 1 -3 tabs prn Side effects: Constipation Sodium bicarb (Alka-Seltzer®) Side effects: flatulence, belching. Contraindicated in CHF, edema, renal dysfunction Mg/Al hydroxide (Gelusil®, Maalox liquid®) Chew 2 -4 tabs QID between meals and at hs Contraindicated in CKD, ARF Alginic Acid (Gaviscon®): MOA: Forms a foam layer on top of gastric contents to protect esophageal mucosa (in combo with traditional buffers) 2 -4 tsps QID pc or at hs to max 16 tsps/day

Anti-acids • H 2 Receptor Antagonists (Zantac® / Pepcid®): Effective in treatment/prevention of mild-moderate GERD MOA: Competitively inhibit H 2 receptors on parietal cells decreasing gastric acid secretion Onset: 30 -90 min, Duration: 9 hours Ranitidine (Zantac®) – 75 mg to 150 mg BID N. B. 150 mg tab was Rx strength! Famotidine (Pepcid AC®) – 10 -20 mg BID N. B. 20 mg tab – Rx strength!

Anti-acids – Take Home Step-up therapy vs Step-down therapy Step-up: start with simple buffers, step-up to H 2 RAs; consider Rx PPI’s if not effective or chronic use. Step-down: start with H 2 RA – get immediate relief, then trial lowest effective dose, or step down to buffer antacids Always obtain PMHx – assess for contraindications! Calcium carbonate – safest bet Ensure no drug interactions with cations (Al 3+, Mg 2+, Ca 2+, Fe) Refer chronic users – risk of malignancy

Laxatives

Laxatives Emollients/Lubricants: “All mush, no push” Allow water and fat to penetrate fecal mass Docusate sodium (Colace®, Soflax®) Mineral oil (Lansoyl®) Not recommended in children <1 year, bedridden pts, GERD aspiration risk (lipoid pneumonitis) Not recommended for long-term use (risk of fat soluble vitamin malabsorption) ? trial vegetable oil Bulk-Forming Agents: Psyllium (Metamucil®) Most effect prevention method Water absorption causes distention Take with plenty of water, else more constipation!

Laxatives Osmotics: Draws water into colon; acidification, irritation, stretch stimulation Eg. Lactulose, sodium phosphate (Fleet®), Magnesium hydroxide/citrate (Milk of Magnesia®), glycerin, PEG Stimulants: Stimulate peristalsis in GI mucosa Preferred in narcotic-induced constipation Eg. Senna (Senekot®), Bisacodyl (Dulcolax®), Castor Oil

Constipation Comparison of Agents Pharmacological Rankings Stimulant > osmotics > bulk > stool softeners Onset/Duration Lubricants > osmotics > stimulants > bulk = stool softeners Side Effects Stimulants > lubricants > osmotics = bulk > stool softeners Cost (least to most) Bulk < stool softeners < osmotics = stimulants = lubricants Convenience Bulk > stool softeners = osmotics = stimulants = lubricants See: http: //www. clinicalgeriatrics. com/article/7346

Laxatives – Take Home Ensure no obstruction Choose simplest laxative for job at hand Psyllium – for prevention / maintenance Stimulants or Osmotics – for narcotic-induced constipation Emollients for hard, painful stool

Herbals & Natural Products Lots of them! – ask your pharmacist! Efficacy Less well researched Lower requirements for license to sell, but claims of efficacy are more restricted Toxicity Lower quality control requirements Risk of drug interactions Cost – Billions spent per year Convenience – no Rx needed. More “natural”.

Summary This is not an exhaustive list Recommend discussion with the pharmacist, even if the product is OTC Even a 5 minute discussion can reveal a lot! Most product benefits are marketing Any agent within a class will do. Avoid combination products. Target therapy with individual ingredients

References Patient Self-Care, First Edition. Canadian Pharmacists’ Association, 2002. Ottawa, Canada