PACKAGE LEAFLET: INFORMATION FOR THE USER

SEVITREX 20 mg/5 mg/12.5 mg film-coated tablets, 40 mg/5 mg/12.5 mg film-coated tablets, 40 mg/10 mg/12.5 mg film-coated tablets, 40 mg/5 mg/25 mg film-coated tablets, 40 mg/10 mg/25 mg film-coated tablets

(olmesartan medoxomil/amlodipine/hydrochlorothiazide)
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their signs and symptoms are the same as yours, as it may be harmful.
If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

What Sevitrex is and what it is used for
What you need to know before taking Sevitrex
How to take Sevitrex
Possible side effects
How to store Sevitrex
Contents of the pack and other information

1. What Sevitrex is and what it is used for

Sevitrex contains three substances called olmesartan medoxomil, amlodipine (as amlodipine besilate), and hydrochlorothiazide. All of these help control hypertension.

Olmesartan medoxomil belongs to a group of medicines known as “angiotensin II receptor antagonists” which lower blood pressure by relaxing blood vessels.
Amlodipine belongs to a group of substances known as “calcium antagonists”. Amlodipine also lowers blood pressure by relaxing blood vessels.
Hydrochlorothiazide belongs to a group of substances known as “thiazide diuretics” (medicines that stimulate diuresis). It reduces blood pressure by helping the body eliminate excess water, increasing urine production by the kidneys.

The combined action of these substances contributes to lowering blood pressure.
Sevitrex is used to treat high blood pressure:

in adult patients whose blood pressure is not adequately controlled by a fixed combination of olmesartan medoxomil and amlodipine, or
in patients who are already taking a fixed combination of olmesartan medoxomil and hydrochlorothiazide plus amlodipine as a single tablet, or a fixed combination of olmesartan medoxomil and amlodipine plus hydrochlorothiazide as a single tablet.

2. What you should know before taking Sevitrex

Do not take Sevitrex if:

you are allergic to olmesartan medoxomil, amlodipine, or a specific group of calcium antagonists (dihydropyridines), hydrochlorothiazide, or substances similar to hydrochlorothiazide (called sulfonamides), or to any of the excipients of this medicine listed in section 6. If you think you may be allergic, speak with your doctor before taking Sevitrex.
you have severe kidney problems.
you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren.
you have low levels of potassium or sodium, or high levels of calcium or uric acid (with symptoms of gout or kidney stones) in your blood that do not improve with treatment.
you are more than three months pregnant (it is better to avoid taking Sevitrex even in the early stages of pregnancy – see section “Pregnancy and breastfeeding”).
you have severe liver problems, if bile secretion is impaired or bile flow is blocked (for example, due to gallstones), or if you have jaundice (yellowing of the skin and eyes).
you have reduced blood flow to tissues with symptoms such as low blood pressure, weak pulse, rapid heartbeat, or shock (including cardiogenic shock, meaning shock due to severe heart problems).
you have very low blood pressure.
blood flow from your heart is slow or obstructed. This occurs if the blood vessels or valves carrying blood out of the heart are narrowed (aortic stenosis).
you have reduced cardiac output due to a heart attack (acute myocardial infarction). Reduced cardiac output may present with difficulty breathing or swelling of feet and ankles.

If you think you are in any of the conditions described above, do not take Sevitrex.
Warnings and precautions
Talk to your doctor or pharmacist before taking Sevitrex.
Consult your doctor if you are taking any of the following medicines used to treat high blood pressure:

an ACE inhibitor (e.g., enalapril, lisinopril, ramipril), particularly if you have kidney problems related to diabetes.
aliskiren

Your doctor may monitor your kidney function, blood pressure, and levels of electrolytes (e.g., potassium) in your blood at regular intervals.
See also the section “Do not take Sevitrex if.”
Inform your doctor if you also have any of the following health conditions:

kidney problems or kidney transplant.
liver disease.
heart failure or problems with heart valves or heart muscle.
severe vomiting, diarrhea, treatment with high doses of diuretics, or if you are on a low-salt diet.
elevated potassium levels in the blood.
problems with adrenal glands (hormone-producing glands located above the kidneys).
diabetes.
systemic lupus erythematosus (an autoimmune disease).
allergies or asthma.
skin reactions such as sunburn or rash after exposure to sunlight or sunlamps.
if you have previously had skin cancer or if you develop an unexpected skin lesion during treatment. Treatment with hydrochlorothiazide, particularly long-term use with high doses, may increase the risk of certain types of skin and lip cancer (non-melanoma skin cancer). Protect your skin from exposure to sunlight and UV rays while taking Sevitrex. if you have previously experienced breathing or lung problems (including inflammation or fluid in the lungs) after taking hydrochlorothiazide. If you develop shortness of breath or severe breathing difficulties after taking Sevitrex, consult a doctor immediately.

Inform your doctor if any of the following symptoms occur:

severe and prolonged diarrhea with significant weight loss. Your doctor will assess your symptoms and decide whether to continue this antihypertensive treatment.
changes in vision or eye pain. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased pressure in your eye and may occur within hours or weeks after starting Sevitrex. If untreated, this increase in pressure may lead to permanent vision impairment.

Contact your doctor if, after taking Sevitrex, you experience abdominal pain, nausea, vomiting, or diarrhea. Your doctor will decide whether to continue treatment. Do not stop taking Sevitrex on your own.
As with any medicine that lowers blood pressure, excessive reduction in blood pressure in patients with circulatory disorders of the heart or brain may lead to a heart attack or stroke. Your doctor will therefore carefully monitor your blood pressure.
Sevitrex may increase levels of fats and uric acid (a cause of gout – painful joint swelling) in the blood. Your doctor may want to perform periodic blood tests to monitor these conditions.
Levels of certain substances called electrolytes in the blood may change. Your doctor may want to perform periodic blood tests to monitor these conditions.
Signs of electrolyte imbalance include: thirst, dry mouth, muscle pain or cramps, muscle fatigue, low blood pressure (hypotension), weakness, lethargy, tiredness, drowsiness or lack of rest, nausea, vomiting, reduced need to urinate, rapid heartbeat. Inform your doctor if these symptoms occur.
If you are scheduled for tests assessing parathyroid function, stop taking Sevitrex before the tests are performed.
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Sevitrex is not recommended during early pregnancy and must not be taken if you are more than three months pregnant, as it may cause serious harm to the baby if taken during this period (see section “Pregnancy and breastfeeding”).
Children and adolescents (up to 18 years)
Sevitrex is not recommended for children and adolescents under 18 years of age.
Other medicines and Sevitrex
Inform your doctor or pharmacist if you are currently taking, have recently taken, or might take any of the following medicines:

Other medicines that lower blood pressure, as they may enhance the effect of Sevitrex.
Your doctor may consider it necessary to adjust the dose and/or take other precautions: if you are taking an ACE inhibitor or aliskiren (see also sections “Do not take Sevitrex if” and “Warnings and precautions”).
Lithium (a medicine used to treat mood swings and certain types of depression) used together with Sevitrex may increase lithium toxicity. If you need to take lithium, your doctor will monitor lithium levels in your blood.
Diltiazem, verapamil, medicines used for heart rhythm problems and high blood pressure.
Rifampicin, erythromycin, clarithromycin, tetracyclines or sparfloxacin, antibiotics used for tuberculosis and other infections.
St. John’s wort (Hypericum perforatum), a herbal remedy for depression.
Cisapride, used to speed up food transit through the stomach and intestines.
Diphenhydramine, used to treat slow heart rate or reduce sweating.
Halofantrine, used for malaria.
Vincamine i.v., used to improve circulation in the nervous system.
Amantadine, used for Parkinson’s disease.
Potassium supplements, potassium-containing salt substitutes, diuretics, or heparin (to thin the blood and prevent thrombosis), ACE inhibitors (to lower blood pressure), laxatives, steroids, adrenocorticotropic hormone (ACTH),

carbenoxolone (a medicine used to treat mouth and stomach ulcers),
sodium penicillin G (also known as benzylpenicillin sodium, an antibiotic), certain
painkillers such as acetylsalicylic acid (aspirin) or salicylates. Taking these
medicines together with Sevitrex may alter potassium levels in the blood.

Non-steroidal anti-inflammatory drugs (NSAIDs, medicines used to reduce pain, swelling, and other symptoms of inflammation, including arthritis) used together with Sevitrex may increase the risk of kidney failure. The effectiveness of Sevitrex may be reduced by NSAIDs. In case of high-dose salicylate intake, central nervous system toxic effects may be increased.
Sleeping pills, sedatives, and antidepressants, used together with Sevitrex, may cause a sudden drop in blood pressure when standing up.
Colesevelam hydrochloride, a medicine that reduces cholesterol levels in the blood, which may reduce the effect of Sevitrex. Your doctor may advise you to take Sevitrex at least 4 hours before colesevelam hydrochloride.
Some antacids (used for indigestion or stomach acidity) may slightly reduce the effectiveness of Sevitrex.
Some muscle relaxants, such as baclofen and tubocurarine.
Anticholinergic medicines, such as atropine and biperiden.
Calcium supplements.
Dantrolene (infusion for severe body temperature disturbances).
Simvastatin, a substance used to reduce cholesterol and fat (triglyceride) levels in the blood.
Medicines used to control your body’s immune response (such as tacrolimus, sirolimus, temsirolimus, everolimus, and cyclosporine) that help your body accept transplanted organs.

In addition, inform your doctor or pharmacist if you are currently taking, have recently taken, or might take any of the following medicines for:

Treating certain mental disorders such as thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, amisulpride, pimozide, sultopride, tiapride, droperidol, or haloperidol.
Treating hypoglycemia (e.g., diazoxide) or hypertension (beta-blockers, methyldopa), as Sevitrex may affect the action of these medicines.
Treating heart rhythm disorders such as mizolastine, pentamidine, terfenadine, dofetilide, ibutilide, or injectable erythromycin.
Treating HIV/AIDS (e.g., ritonavir, indinavir, nelfinavir).
Treating fungal infections (e.g., ketoconazole, itraconazole, amphotericin).
Treating heart conditions such as quinidine, hydroquinidine, disopyramide, amiodarone, sotalol, bepridil, or digitalis.
Treating tumors such as amifostine, cyclophosphamide, or methotrexate.
Increasing blood pressure and slowing heart rate such as noradrenaline.
Treating gout such as probenecid, sulfinpyrazone, and allopurinol.
Reducing blood fat levels such as cholestyramine and colestipol.
Reducing blood sugar levels such as metformin or insulin.

Inform your doctor or pharmacist if you are taking, have recently taken, or plan to take any other medicine.
Sevitrex with food and drinks
Sevitrex can be taken with or without food.
People taking Sevitrex must not consume grapefruit or grapefruit juice, as grapefruit and its juice may increase blood levels of the active substance amlodipine, which could lead to an unpredictable increase in the hypotensive effect of Sevitrex.
Be cautious when drinking alcohol while taking Sevitrex, as some individuals may feel weak or confused. If this happens, do not drink alcohol.
Elderly
If you are over 65 years of age, your doctor will regularly monitor your blood pressure with each dose increase to prevent excessive lowering.
Pregnancy and breastfeeding
Pregnancy
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Normally, your doctor will advise you to stop taking Sevitrex before becoming pregnant or as soon as you find out you are pregnant, and will recommend an alternative medicine. Sevitrex is not recommended during pregnancy and must not be taken if you are more than three months pregnant, as it may cause serious harm to the baby if taken after the third month of pregnancy.
If you become pregnant while taking Sevitrex, inform and see your doctor immediately.
Breastfeeding
Inform your doctor if you are breastfeeding or planning to breastfeed. It has been shown that amlodipine passes into breast milk in small amounts. Sevitrex is not recommended for breastfeeding women, and your doctor may choose an alternative treatment if you wish to breastfeed.
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, ask your doctor or pharmacist for advice before taking any medicine.
Driving and using machines
You may experience drowsiness, confusion, dizziness, or headache during treatment for high blood pressure. If this occurs, do not drive or operate machinery until symptoms resolve. Consult your doctor for advice.

3. How to take Sevitrex

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

The recommended dose of Sevitrex is one tablet per day.
The tablet can be taken with or without food. Swallow the tablet with some liquid (such as a glass of water). The tablets must not be chewed. Do not take it with grapefruit juice.
If possible, take your daily dose at the same time each day, for example with breakfast.

If you take more Sevitrex than you should
If you take more tablets than prescribed, you may experience a drop in blood pressure with symptoms such as dizziness, or a faster or slower heartbeat.
If you take more tablets than you should, or if a child accidentally swallows any, go immediately to your doctor or the nearest emergency department, taking the medicine pack or this leaflet with you.
Excess fluid may accumulate in the lungs (pulmonary edema), causing breathlessness, which may develop up to 24–48 hours after ingestion.

If you forget to take Sevitrex
If you forget to take a dose, take your usual dose the next day. Do not take a double dose to make up for the missed dose.

If you stop taking Sevitrex
It is important to continue taking Sevitrex unless your doctor tells you to stop.

If you have any questions about how to use this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them. If they occur, they are mostly mild and do not require discontinuation of treatment.
Although not occurring in all individuals, the following adverse effects can be serious:
During treatment with Sevitrex, allergic reactions may occur, with swelling of the face, mouth and/or larynx (site of the vocal cords), associated with itching and skin rash. If this occurs, stop taking Sevitrex and contact your doctor immediately.
Sevitrex may cause excessive lowering of blood pressure in sensitive individuals. This could lead to severe dizziness or fainting. If this occurs, stop taking Sevitrex, contact your doctor immediately, and remain lying down.
Frequency not known: if you experience yellowing of the whites of the eyes, dark urine, or skin itching, even if you have been taking Sevitrex for a long time, contact your doctor immediately. Your doctor will assess your symptoms and decide how to proceed with your treatment for high blood pressure.

Sevitrex is a combination of three active substances. The information below first lists other adverse effects reported so far with the combination Sevitrex (in addition to those already mentioned above), followed by adverse effects known for each of the three individual components or when two components are administered together.
To give you an idea of how many patients have experienced these adverse effects, they are categorized as common, uncommon, rare, and very rare.

These are the other adverse effects with Sevitrex known so far:
If they occur, they are mostly mild and do not require discontinuation of treatment.

Common (may affect up to 1 in 10 people):
Upper respiratory tract infection; inflammation of the throat and nose; urinary tract infection; dizziness; headache; awareness of heartbeat; low blood pressure; nausea; diarrhoea; constipation; cramps; joint swelling; feeling of urgency to urinate; weakness; swelling of the ankles; fatigue; laboratory test abnormalities.

Uncommon (may affect up to 1 in 100 people):
Dizziness upon standing; vertigo; rapid heartbeat; feeling of weakness; facial flushing and sensation of warmth; cough; dry mouth; muscle weakness; inability to achieve or maintain erection.

These are the adverse effects known for each of the components when taken alone or for two components taken together:
These may also be adverse effects of Sevitrex, even if they have not been observed so far with Sevitrex.

Very common (may affect more than 1 in 10 people):
Edema (fluid retention).

Common (may affect up to 1 in 10 people):
Bronchitis; gastric and intestinal infection; vomiting; increased blood glucose; glucose in urine; confusion; drowsiness; visual disturbances (including double and blurred vision); runny or stuffy nose; throat inflammation; breathing difficulty; cough; abdominal pain; heartburn; gastric discomfort; flatulence; joint or bone pain; back pain; skeletal pain; blood in urine; influenza-like symptoms; chest pain; pain.

Uncommon (may affect up to 1 in 100 people):
Reduction in a type of blood cell called platelets, which may lead to easy bruising or prolonged bleeding time; anaphylactic reactions; abnormally reduced appetite (anorexia); difficulty falling asleep; irritability; mood changes including anxiety; feeling of depression; chills; sleep disturbances; taste alterations; loss of consciousness; reduced tactile sensitivity; tingling; worsening of near vision; ringing in the ears (tinnitus); angina (chest pain or discomfort, known as angina pectoris); irregular heartbeat; rash; hair loss; allergic skin inflammation; skin redness; red spots or dots on the skin due to small hemorrhages (purpura); skin discoloration; itchy red welts (urticaria); excessive sweating; itching; skin rash; skin reactions to light such as sunburn or rash; muscle pain; difficulty urinating; nocturnal urgency to urinate; breast enlargement in men; reduced sexual desire; facial swelling; feeling of malaise; weight gain or loss; exhaustion.

Rare (may affect up to 1 in 1,000 people):
Swelling and pain in the salivary glands; reduced number of white blood cells in the blood, which may increase the risk of infections; low number of red blood cells (anaemia); bone marrow damage; lack of rest; lack of interest (apathy); seizures; seeing yellow objects; dry eyes; blood clots (thrombosis or embolism); fluid accumulation in the lungs; pneumonia; inflammation of blood vessels and small cutaneous blood vessels; pancreatitis; yellowing of the skin and eyes; acute inflammation of the gallbladder; symptoms of systemic lupus erythematosus such as rash, joint pain, and cold fingers and hands; severe skin reactions including intense rash, urticaria, widespread skin redness, severe itching, blisters, skin peeling and swelling, mucosal inflammation (Stevens-Johnson syndrome, toxic epidermal necrolysis); impaired movement; acute kidney failure; non-infectious kidney inflammation; reduced kidney function; fever; intestinal angioedema: swelling in the intestine presenting with symptoms such as abdominal pain, nausea, vomiting and diarrhoea.

Very rare (may affect up to 1 in 10,000 people):
Increased muscle tone; numbness of hands or feet; heart attack; stomach inflammation; gum overgrowth; intestinal obstruction; liver inflammation.
Acute respiratory distress (signs include severe shortness of breath, fever, weakness, and confusion).

Not known (frequency cannot be estimated from available data):
Vision loss or eye pain (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma). Tremor, rigid posture, mask-like facial expression, slow movements, and unbalanced, shuffling gait.
Skin and lip cancer (non-melanoma skin cancer).

Reporting of adverse effects
If you experience any adverse effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report adverse effects directly via the national reporting system at:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. How to store Sevitrex

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after "EXP",
on the vial and on the blister pack after EXP. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist
how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Sevitrex contains
The active substances are olmesartan medoxomil, amlodipine (as amlodipine besilate) and
hydrochlorothiazide.
Each film-coated tablet contains 20 mg of olmesartan medoxomil, 5 mg of
amlodipine (as besilate) and 12.5 mg of hydrochlorothiazide.
Each film-coated tablet contains 40 mg of olmesartan medoxomil, 5 mg of
amlodipine (as besilate) and 12.5 mg of hydrochlorothiazide.
Each film-coated tablet contains 40 mg of olmesartan medoxomil, 10 mg of
amlodipine (as besilate) and 12.5 mg of hydrochlorothiazide.
Each film-coated tablet contains 40 mg of olmesartan medoxomil, 5 mg of
amlodipine (as besilate) and 25 mg of hydrochlorothiazide.
Each film-coated tablet contains 40 mg of olmesartan medoxomil, 10 mg of
amlodipine (as besilate) and 25 mg of hydrochlorothiazide.
The other components are:
Tablet core: pregelatinized maize starch, silicified microcrystalline cellulose (microcrystalline cellulose and anhydrous colloidal silica), sodium croscarmellose, magnesium stearate.
Coating: polyvinyl alcohol, macrogol 3350, talc, titanium dioxide (E171), yellow iron (III) oxide (E172), red iron (III) oxide (E172) (only in Sevitrex 20 mg/5 mg/12.5 mg, 40 mg/10 mg/12.5 mg and 40 mg/10 mg/25 mg film-coated tablets), black iron (II, III) oxide (E172) (only in Sevitrex 20 mg/5 mg/12.5 mg film-coated tablets).
This medicine contains less than 1 mmol of sodium (23 mg) per film-coated tablet, i.e. it is essentially sodium-free.

Description of the appearance of Sevitrex and pack contents
Sevitrex 20 mg/5 mg/12.5 mg film-coated tablets: 8 mm, light orange, round, film-coated tablets with the code C51 engraved on one side.
Sevitrex 40 mg/5 mg/12.5 mg film-coated tablets: 9.5 mm, light yellow, round, film-coated tablets with the code C53 engraved on one side.
Sevitrex 40 mg/10 mg/12.5 mg film-coated tablets: 9.5 mm, greyish-red, round, film-coated tablets with the code C55 engraved on one side.
Sevitrex 40 mg/5 mg/25 mg film-coated tablets: 15 x 7 mm, light yellow, oval, film-coated tablets with the code C54 engraved on one side.
Sevitrex 40 mg/10 mg/25 mg film-coated tablets: 15 x 7 mm, greyish-red, oval, film-coated tablets with the code C57 engraved on one side.

Sevitrex film-coated tablets are available in:

packs of 14, 28, 30, 56, 84, 90, 98, 10x28 and 10x30 film-coated tablets in blister packs
packs of 10, 50 and 500 film-coated tablets in unit dose divisible blister packs
HDPE bottles containing 7, 30 or 90 film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder
Daiichi Sankyo Italia SpA
Via Paolo di Dono, 73
00142 Rome
Italy

Manufacturers
Daiichi Sankyo Europe GmbH
Luitpoldstrasse, 1
85276 Pfaffenhofen (Germany)
Berlin-Chemie AG
Glienicker Weg 125
12489 Berlin (Germany)
Menarini – Von Heyden GmbH
Leipziger Strasse 7-13
01097 Dresden (Germany)

This medicine is authorized in the European Economic Area member states under the following names:

Austria, Germany, Greece, Netherlands, United Kingdom, Romania, Spain:
Sevikar HCT 20 mg/5 mg/12.5 mg
Sevikar HCT 40 mg/5 mg/12.5 mg
Sevikar HCT 40 mg/10 mg/12.5 mg
Sevikar HCT 40 mg/5 mg/25 mg
Sevikar HCT 40 mg/10 mg/25 mg

Belgium and Luxembourg:
Sevikar/HCT 20 mg/5 mg/12.5 mg
Sevikar/HCT 40 mg/5 mg/12.5 mg
Sevikar/HCT 40 mg/10 mg/12.5 mg
Sevikar/HCT 40 mg/5 mg/25 mg
Sevikar/HCT 40 mg/10 mg/25 mg

Denmark, Iceland:
Sevikar Comp 20 mg/5 mg/12.5 mg
Sevikar Comp 40 mg/5 mg/12.5 mg
Sevikar Comp 40 mg/10 mg/12.5 mg
Sevikar Comp 40 mg/5 mg/25 mg
Sevikar Comp 40 mg/10 mg/25 mg

Ireland:
Sevikar Plus 20 mg/5 mg/12.5 mg
Sevikar Plus 40 mg/5 mg/12.5 mg
Sevikar Plus 40 mg/10 mg/12.5 mg
Sevikar Plus 40 mg/5 mg/25 mg
Sevikar Plus 40 mg/10 mg/25 mg

Italy:
Sevitrex 20 mg/5 mg/12.5 mg
Sevitrex 40 mg/5 mg/12.5 mg
Sevitrex 40 mg/10 mg/12.5 mg
Sevitrex 40 mg/5 mg/25 mg
Sevitrex 40 mg/10 mg/25 mg

Doping
For individuals engaged in sports: using this medicine without a therapeutic need constitutes doping and may result in a positive anti-doping test.