Rcxsaine! 



SOLUTION *-^minoxidil2% 



The only product ever 

 proven to regrow hair. 



What la ROGAINE7 



ROGAINE Topical Solution is a prescnplion medicine lor use on the scalp tliat is used to treat a type ot hair loss in men and women known as androgeoetic 

 alopecia: hair loss ol the scalp vertex (top or crown ol Itie head) in men and dittuse hair loss or thinning ol the Iront and lop ol the scalp in women, 

 ROGAINE IS a topical loim ol minoxidil, loi use on the scalp 



How effective la ROGAINE? 



In men: Clinical studies wilh ROGAINE ol over 2.300 men with male pattern baldness involving the top (ver1ex),ol the head were conducted by physicians in 

 27 US medical cenleis Based on patient evaluations ol tegrowth at the end ol 4 months, 26% ol the patients using ROGAINE had moderate to dense hair 

 regrowth compared with 11% who used a placebo treatmeni (no active ingredient} No regrowlh was reported by 41% ot those using ROGAINE and 58% ol 

 those using a placebo By the end ot I year. 48% ol those who continued to use ROGAINE raled their hatr growth as moderate or better 



In women: Clinical studies with ROGAINE were conducted by physicians in 11 US and 10 European medical centers involving over 600 women with hatr 

 loss Based on palieni evaluations ol regrowth after 32 weeks (8 months). 23% ol the women using ROGAINE had at least moderate regrowth compared with 

 9% ol those using a placebo No regrowth was reported by 43% ot the group using ROGAINE and 60% of the group using placebo 



How aoon can I expect reauKa from uaing ROGAINE? 



Studies show that the response lime to ROGAINE may differ greatly from one person to another Some people using ROGAINE may see results faster than 

 others: others may respond with a slower rate ol hair regrowth. You should not expect visible regrowth in less than 4 months. 



How long do I need to uae ROGAINE? 



ROGAINE is a hait-loss treatment, not a cure tl you have new hair growth, you will need to continue using ROGAINE to keep ot increase hair regrowth. If you 

 do not begin to show new hair growth with ROGAINE after a reasonable period of time (at least 4 months), your doctor may advise you to discontinue using 

 ROGAINE 



What happena If I atop uaIng ROGAINE? Will I keep the new hair? 



Probably not People have reported that new hair growth was shed after they stopped using ROGAINE 



How much ROGAINE ahould I use? 



You should apply a 1-mL dose ol ROGAINE twice a day to your clean dry scalp, once in the morning and once at night before bedtime Wash your hands after 

 use if your fingers are used to apply ROGAINE ROGAINE must remain on the scalp tor at least 4 hours to ensure penetration into the scalp. Do not wash your 

 hair tor at least 4 hours alter applying it II you wash your hair before applying ROGAINE. be sure your scalp and hair are dry when you apply il Please reler 

 to /he InsUdclms /or (yse m the package 



What H I miss a dose or forget to use ROGAINE? 



Do not try to make up for missed apptications ot ROGAINE You should restart your twice-daily doses and return to your usual schedule. 



What are the most common aide effects reported In clinical studies with ROGAINE? 



ttching and other skin irntations of the treated scalp area were the most common side effects directly linked to ROGAINE in clinical studies. About 7 of every 

 too people who used ROGAINE (7%) had these complaints 



Other side effects, including light-headedness. dizziness, and headaches, were reported both by people using ROGAINE and by those using the placebo 

 solution with no minoxidil You should ask your doctor to discuss side effects ol ROGAINE with you 



People who are extra sensitive or allergic to minoxidil, propylene glycol, or ethanol should not use ROGAINE 



ROfiAINE Topical Solution contains alcohol, which could cause burning or irritation ol the eyes or sensitive skin areas II ROGAINE accidentally gels into 

 these areas, rinse the area wth large amounts ol cool lap water Contact your doctor if the irritation does not go away 



What are acme of the aide effects people have reported? 



ROGAINE was used by 3.857 patients (347 females) in placebo-controlled clinical trials Except for dermatologic events (involving the skin), no individual 

 reaction or reactions grouped by body systems appeared to be more common in the minoxidil-trealed patients than in pfacebo-treated patients 



OermitolOBic: irritant or allergic contact dermatitis— 7 36%, Respiratory: bronchitis, upper respiratory infection, sinusitis— 7 16%: Gaslrofnlesll- 

 nal: diarrhea, nausea, vomiting— 4 33%, Neurologic: headache, dizziness, laintness, light-headedness— 3 42%. Musculosketetal: tractures. back 

 pain, tendinitis, aches and nains— 2 59%. Cardiovascular: edema, chest pain, blood pressure increases/decreases. palpitations, pulse rate increases/ 

 decreases— 1 53%: Allergic: nonspecihc allergic reactions, hives, allergic rhinitis, tacial swelling, and sensitivity— 1 27%. Melabotic-Hulrillonat: 

 edema, weight gam— 1 24%: Special Scncei: coniunctivitis. ear inlections, vertigo— 1 17%. Genital Tract: prostatitis, epididymitis, vaginitis, vulvitis, 

 vaginal discharge/ilchmg— 9i%. Urinary Trad: urinary tract infections, renal calculi, urethritis- 93%. Endocrine: menstrual cnanges. breast 

 symptoms— 47%: Piychlatrtc: anxiety, depression, fatigue- 36%. Hertatotogic: lymphadenopalhy. thrombocytopenia, anemia— 31% 



ROGAINE use has been monitored for up to 5 years, and there has been no change in incidence or severity ot reported adverse reactions. Additional 

 adverse events have been reported since marketing ROGAINE and include eczema, hypertrichosis (excessive hair growth): local erythema (redness): 

 pruritus (itching): dry skin/scalp ftaking: sexual dysfunction: visual disturbances, including decreased visual acuity (clarity), increase in hair toss: and 

 alopecia (hair loss) 



What are the possible side effects that could affect the hearl and circulation when using ROGAINE? 



Serious side effects have not been linked to ROGAINE in clinical studies However, it is possible that they could occur it more than the recommended dose ot 

 ROGAINE were applied, because the active ingredient in ROGAINE is the same as that in minoxidil tablets These effects appear to be dose related: that is. 

 more effects are seen with higher doses 



Because very small amounts ol minoxidil reach the blood when the recommended dose ol ROGAINE is applied to the scalp, you should know about certain 

 effects that may occur when the tablet form of minoxidil is used to treat high blood pressure Minoxidil tablets lower blood pressure by relaxing the arteries, 

 an effect called vasodilation Vasodilation leads to fluid retention and faster heart rate Tfre following effects have occurred in some patients taking minoxidii 

 tablets for high blood pressure: 



Increased heatl rale: some patients have reported that their resting heart rate increased by more than 20 beats per minute. 



Salt and water reterttm: weight gam of more than 5 pounds in a short period of time or swelling of the face, hands, ankles, or stomach area. 



Problems breaming especially when lying down: a result ol a buildup of body fluids or fluid around the heart 



Worsening or new attaa ol angina pectoris: brief, sudden chest pain 



When you apply ROGAINE to normal skin, very tittle minoxidil is absorbed You probably wilt not have the possible effects caused by minoxidil tablets 

 when you use ROGAttiE If however, you experience any ot the possible side effects listed above, stop using ROGAINE and consult your doctor Any such 

 etfects would be most likely il ROGAINE was used on damaged or inflamed skin or in greater than recommended amounts. 



In animal studies, minoxidil, in much larger amounts than would be absorbed from topical use (on skin) in people, has caused important heart-structure 

 damage. This kind of damage has not been seen in humans given minoxidil tablets lor high blood pressure at effective doses. 



What factors may Increase the rlsl( ot serious side effects with ROGAINE? 



People with a known or suspected hearl condition or a tendency lor hearl lailure would be at particular risk il increased heart rate or fluid retention were to 

 occur People with these kinds of heart problems should discuss the possible risks of treatment with their doctor il they choose to use ROGAINE. 



ROGAINE should be used only on the balding scalp Using ROGAINE on other parts of the body may increase minoxidil absorption, which may increase the 

 chances of having side etfects. You stiould not use ROfiAINE it your scalp is irritated or sunburned, and you should not use it il you are using other skin 

 Ireatmenis on your scalp 



Can people with high blood pressure use ROGAINE? 



Most people with high blood pressure, including those taking high blood pressure medicine, can use ROGAINE but should be monitored cfosely by their 

 doctor Patients taking a blood pressure medicine called guanethidine should not use ROGAINE. 



Should any precautions be followed? 



People who use ROGAINE should see their doctor 1 month after starting ROGAINE and at least every 6 months thereafter Slop using ROGAINE it any of the 

 following occur salt and water retention, problems breathing, faster heart rate, or chest pains. 



Do not use ROGAINE il you are using other drugs applied to the scalp such as corticosteroids, retinoids, petrolatum, or agents that might increase 

 absorption through the skin ROGAINE is for use on the scalp only Each 1 mL ot solution contains 20 mg minoxidil, and accidental ingestion could cause 

 unwanted etfects. 



Are tttere special precautions for women? 



Pregnant women and nursing mothers should not use ROGAINE. Also, its effects on women during labor and delivery are not known. Efficacy in 

 postmenopausal women has not been studied. Studies show the use of ROGAINE will not affect menstrual cycle length, amount of flow, or duration of the 

 menstrual period. Discontinue using ROGAINE and consult your doctor as soon as possible it your menstrual period does not occur at the expected time. 



Can ROGAINE lie used by children? 



No. the safety and effectiveness of ROGAINE has not been tested in people under age 18. 



Caution: Federal law prohibits dispensing without a prescription. You must see a doctor to receive a prescription. 



DERMATOLOGY 

 DIVISION 



©1994 Ttie Upjotin Company, Kalamazoo, Ml 49001, USA 

 USJ 1786.00 February 1994 CB-4-S 



oxygen-enriched atmosphere are evident if 

 one examines evolutionary trees that de- 

 pict the genealogical relationships among 

 living organisms. Lower branches of the 

 tree of life are populated by organisms that 

 cannot utilize oxygen in their metabolism; 

 in fact, for many, oxygen is toxic. Species 

 higher up on the tree of life are able to use 

 oxygen in respiration, the energy-yielding 

 process in which organic molecules are 

 broken down into carbon dioxide and 

 water. In the new environments created by 

 the oxygen revolution, bacteria diversified 

 to form many of the aerobic lineages that 

 are ubiquitous on the modem earth. More 

 ancient, anaerobic microbes retreated 

 along with their environments, from 

 which they continued to play a central role 

 in the cycling of carbon and other ele- 

 ments through ecosystems. 



The earliest organisms were prokary- 

 otic — simple cells whose genes do not re- 

 side in a membrane-bound nucleus. But at 

 some point, other kinds of organisms 

 evolved. These newcomers were eukary- 

 otes, organisms with a clearly defined nu- 

 cleus. These nucleated organisms — which 

 now include protozoans, algae, fungi, 

 plants, and animals — evolved before the 

 oxygen revolution took hold, but were 

 probably only a minor part of early com- 

 munities. Oxygen got eukaryotes started 

 on the road to ecological prominence, not 

 because they evolved respiration them- 

 selves, but because they swallowed bacte- 

 ria that had. Some aerobic bacteria became 

 symbiotically incorporated into nucleated 

 cells, in time evolving into mitochondria 

 (energy-producing organelles in the cells 

 of most modem eukaryotic creatures). In 

 China, North America, and Australia, fos- 

 sils and distinctive biomolecules in an- 

 cient rocks, from 1.9 to 1.7 billion years 

 ago, document that eukaryotic organisms 

 had become significant participants in ma- 

 rine ecosystems. 



The oxygen revolution expanded the 

 range of terrestrial environments enough 

 to accommodate eukaryotic protozoans 

 and algae, but not enough to support the 

 biology of our own kingdom, Animalia. 

 Animals, and their tracks and trails, are 

 conspicuously absent from the geological 

 record until about 600 million years ago. 

 In 1959, J. R. Nursall, of the University of 

 Alberta, suggested that animals appeared 

 so late in the evolutionary day because 

 until then there was not enough oxygen to 

 support their metabolism. Only in the last 

 few years have we accumulated geological 

 evidence to evaluate his idea. 



At oxygen concentrations significanfly 



1 8 Natural History 6/94 



