Himavat

Package leaflet: Information for the user

HIMAVAT 10 mg/10 mg tablets, 10 mg/20 mg tablets, 10 mg/40 mg tablets, 10 mg/80 mg tablets

ezetimibe and atorvastatin
Please read all of 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 they have the same symptoms as you, because it may be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What HIMAVAT is and what it is used for
2. What you need to know before taking HIMAVAT
3. How to take HIMAVAT
4. Possible side effects
5. How to store HIMAVAT
6. Contents of the pack and other information

1. What HIMAVAT is and what it is used for

HIMAVAT is a medicine used to lower elevated cholesterol levels. HIMAVAT contains ezetimibe and atorvastatina.
HIMAVAT is used in adults to lower total cholesterol levels, “bad” cholesterol (LDL cholesterol), and blood fats called triglycerides. In addition, HIMAVAT increases levels of “good” cholesterol (HDL cholesterol).
HIMAVAT works in two ways to lower cholesterol. It reduces cholesterol absorbed in the gastrointestinal tract as well as cholesterol naturally produced by the body.
Cholesterol is one of several fatty substances present in the bloodstream. Total cholesterol is mainly composed of LDL and HDL cholesterol.
LDL cholesterol is often called “bad” cholesterol because it can accumulate on the walls of arteries, forming plaques. Over time, this plaque buildup can lead to narrowing of the arteries. This narrowing can slow down or block blood flow to vital organs such as the heart and brain. Such blockage of blood flow may cause a heart attack or stroke.
HDL cholesterol is often called “good” cholesterol because it helps prevent bad cholesterol from building up in the arteries and provides protection against heart disease.
Triglycerides are another form of fat in the blood that may increase the risk of heart disease.
HIMAVAT is used to treat patients in whom diet alone is not sufficient to control cholesterol levels. While taking this medicine, you should still follow a cholesterol-lowering diet.
Your doctor may prescribe HIMAVAT to you if you are already taking atorvastatina and ezetimibe at the same dosage.
HIMAVAT does not help with weight loss.

2. What you need to know before taking HIMAVAT

Do not take HIMAVAT if

• you are allergic to ezetimibe, atorvastatin, or any of the other ingredients of this medicine (listed in section 6)
• you have or have ever had liver disease
• you have had unexplained abnormal blood tests assessing liver function
• you are a woman of childbearing age and you do not use a reliable contraceptive method
• you are pregnant, trying to become pregnant, or breastfeeding
• you are taking the combination glecaprevir/pibrentasvir for the treatment of hepatitis C.

Warnings and precautions
Talk to your doctor or pharmacist before taking HIMAVAT if

• you have previously had a stroke with cerebral haemorrhage or if there are small accumulations of fluid in the brain due to previous strokes
• you have kidney problems
• you have an underactive thyroid gland (hypothyroidism)
• you have had repeated or unexplained episodes of muscle discomfort or pain, or have a personal or family history of muscle disorders
• you have previously experienced muscle problems while being treated with other lipid-lowering medicines (e.g. other "statin" or "fibrate" medicines)
• you are taking or have taken within the last 7 days an oral or injectable medicine called fusidic acid (a medicine for bacterial infections). The combination of fusidic acid and atorvastatin/ezetimibe may lead to serious muscle problems (rhabdomyolysis)
• you regularly consume large amounts of alcohol
• you have a history of liver disease
• you are over 70 years of age

Contact your doctor immediately if you experience unexplained muscle pain, tenderness, or weakness
while taking HIMAVAT. This is because, although rarely, muscle problems can be severe, including muscle breakdown leading to kidney damage.
Before taking HIMAVAT, check with your doctor or pharmacist:

• if you have severe respiratory insufficiency.

If any of these conditions apply to you (or if you are unsure), consult your doctor or pharmacist before taking HIMAVAT, as your doctor may need to request a blood test before and possibly during treatment to assess the risk of muscle-related side effects. It is known that the risk of developing muscle-related adverse effects, such as rhabdomyolysis (breakdown of damaged skeletal muscles), increases when certain medicines are taken concomitantly (see section 2 “Other medicines and HIMAVAT”).
During treatment with this medicine, your doctor will monitor you carefully if you have diabetes or are at risk of developing diabetes. You are at risk of developing diabetes if you have high levels of sugar and fats in the blood, are overweight, or have high blood pressure.
Inform your doctor about all your medical conditions, including allergies.

Children
HIMAVAT is not recommended in children and adolescents.

Other medicines and HIMAVAT
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Fibrates (medicines that lower cholesterol levels) should be avoided while taking HIMAVAT.
Some medicines may alter the effect of HIMAVAT or their effect may be altered by HIMAVAT (see section 3). This type of interaction could reduce the effectiveness of one or both medicines. Alternatively, it could increase the risk of developing adverse effects or their severity, including the serious condition of muscle breakdown known as “rhabdomyolysis” described in section 4:

• cyclosporine (a medicine often used in organ transplant patients)
• erythromycin, clarithromycin, telithromycin, fusidic acid, rifampicin (medicines used to treat bacterial infections)
• ketoconazole, itraconazole, voriconazole, fluconazole, posaconazole (medicines used to treat fungal infections)
• gemfibrozil, other fibrates, nicotinic acid and its derivatives, colestipol, cholestyramine (medicines used to regulate lipid levels)
• certain calcium channel blockers used for angina or hypertension, e.g. amlodipine and diltiazem
• digoxin, verapamil, amiodarone (medicines used to regulate heart rhythm)
• letermovir, a medicine used to prevent cytomegalovirus disease
• medicines used for the treatment of HIV, e.g. ritonavir, lopinavir, atazanavir, indinavir, darunavir, the combination tipranavir/ritonavir, etc. (medicines for AIDS)
• certain medicines used for the treatment of hepatitis C, e.g. telaprevir, boceprevir, and the combination elbasvir/grazoprevir
• if you need to take oral fusidic acid to treat a bacterial infection, you must temporarily stop taking this medicine. Your doctor will advise you when it is safe to restart treatment with HIMAVAT. Taking HIMAVAT with fusidic acid may rarely cause muscle weakness, tenderness, or pain (rhabdomyolysis). See further information on rhabdomyolysis in section 4.
• Other medicines known to interact when used in combination
• oral contraceptives (medicines to prevent pregnancy)
• stiripentol (an anticonvulsant medicine used to treat epilepsy)
• cimetidine (a medicine used to treat heartburn and peptic ulcers)
• phenazone (a painkiller)
• antacids (medicines for digestive problems containing aluminium or magnesium)
• warfarin, phenprocoumon, acenocoumarol, or fluindione (medicines to prevent blood clots)
• colchicine (used to treat gout)
• St John’s wort (a medicine used to treat depression)

HIMAVAT with food and alcohol
For instructions on how to take HIMAVAT, see section 3. Pay attention to the following:
Grapefruit juice
Do not drink more than one or two small glasses of grapefruit juice per day, as large quantities of grapefruit juice may alter the effects of the medicine.
Alcohol
Avoid drinking excessive amounts of alcohol during treatment with this medicine. For further information, consult section 2 “Warnings and precautions”.

Pregnancy, breastfeeding, and fertility
Do not take HIMAVAT if you are pregnant, planning to become pregnant, or suspect you may be pregnant.
Do not take HIMAVAT if you are a woman of childbearing age unless you are using an effective method of contraception. If you become pregnant while taking HIMAVAT, stop treatment immediately and consult your doctor.
Do not take HIMAVAT if you are breastfeeding.
If you are pregnant or breastfeeding, suspect you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines
HIMAVAT is not expected to affect your ability to drive or use machines. However, be aware that some people may experience dizziness after taking HIMAVAT. If you experience dizziness after taking this medicine, avoid driving or using machines.

HIMAVAT contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

HIMAVAT contains sodium
HIMAVAT contains less than 1 mmol of sodium (23 mg) per tablet, i.e. essentially “sodium-free”.

3. How to take HIMAVAT

Always take this medicine exactly as instructed by your doctor. Your doctor will determine the appropriate tablet dosage for you based on your ongoing treatment and individual risk profile. If you have any doubts, consult your doctor or pharmacist.

• Before starting treatment with HIMAVAT, you must already have begun a diet aimed at reducing cholesterol levels.
• During treatment with HIMAVAT, you must continue to follow a cholesterol-lowering diet.

What dose to take
The recommended dose is one HIMAVAT tablet once daily, preferably always at the same time. The tablet must be swallowed whole with sufficient liquid (e.g., a glass of water).

When to take the medicine
You may take HIMAVAT at any time of day. You may take it with or without food.
If your doctor has prescribed HIMAVAT together with colestyramine or another bile acid sequestrant (medicines used to lower cholesterol levels), you must take HIMAVAT at least 2 hours before or 4 hours after taking the bile acid sequestrant.

If you take more HIMAVAT than you should
Contact your doctor or pharmacist.

If you forget to take HIMAVAT
Do not take a double dose to make up for the missed dose; simply take your next dose at the usual time on the following day.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, HIMAVAT may cause side effects, although not everybody experiences them.
If you notice any of the serious side effects or symptoms listed below,
stop taking the tablets immediately and contact your doctor or go to the nearest hospital emergency department, taking the medicine with you.

• severe allergic reaction causing swelling of the face, tongue and throat, which may cause severe breathing difficulties
• severe illness with extensive skin peeling and swelling, blistering of the skin, mouth, eyes, genitals and fever; skin rash with pink-red pustules, particularly on the palms of the hands or soles of the feet, which may develop blisters
• muscle weakness, tenderness, pain or muscle rupture, or red-brown discoloration of urine, especially if associated with feeling unwell and high fever — this may be due to
  unusual muscle breakdown which can be life-threatening and may lead to kidney problems
• lupus-like syndrome (including skin rash, joint problems and effects on blood cells)

If you experience symptoms such as unusual or unexpected bleeding or bruising, consult your doctor as soon as possible, as these may be signs of liver disorder.

Other possible side effects with HIMAVAT:
Common (may affect up to 1 in 10 people):

• inflammation of nasal passages, sore throat, nosebleeds
• allergic reactions
• increased blood glucose levels; diabetic patients should monitor their blood glucose levels regularly
• headache
• nausea, constipation, flatulence, diarrhoea, indigestion, abdominal pain
• pain in the pharynx and/or larynx
• joint and/or hand or foot pain, back pain, muscle pain (myalgia), muscle spasms, joint swelling
• increased blood creatine kinase
• increased liver enzymes ALT and/or AST
• fatigue
• abnormal liver function tests

Uncommon (may affect up to 1 in 100 people):

• swelling due to allergic reaction
• decreased blood glucose levels; diabetic patients should monitor their blood glucose levels regularly
• loss of appetite, weight gain
• cough
• muscle weakness, neck pain, chest pain
• hot flushes, hypertension
• vomiting, belching, inflammation of the pancreas and liver, heartburn, inflammation of the stomach lining, dry mouth
• skin redness, urticaria, rash, itching, hair loss
• nightmares, difficulty falling asleep
• drowsiness, numbness, altered taste, amnesia, abnormal local sensations
• blurred vision
• tinnitus
• feeling unwell, general discomfort or pain
• weakness
• increased levels of the liver enzyme gamma-glutamyltransferase
• positive urine test for white blood cells

Rare (may affect up to 1 in 1,000 people):

• reduced platelet count
• swelling of the deep layer of skin tissue in the face, tongue, throat, abdomen, arms or legs (angioedema)
• widespread rash forming clearly defined red patches or rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals, due to an allergic reaction
• inflammation of skeletal muscle, tendon inflammation sometimes complicated by muscle deterioration and weakness due to loss of skeletal muscle fibres
• vision disorders
• yellowing of the skin and whites of the eyes (jaundice)

Very rare (may affect up to 1 in 10,000 people):

• anaphylactic shock due to allergic reaction
• hearing loss
• liver failure
• breast enlargement in men

Frequency not known (cannot be estimated from available data):

• allergic reaction including rash and swelling of the deep layer of the skin
• shortness of breath, inflammation of the gallbladder, gallstones
• physical weakness and loss of strength, loss of muscle tissue due to autoimmune antibodies
• depression
• dizziness

Additionally, the following side effects have been reported during post-marketing use of some statins (medicines used to reduce cholesterol levels):

• respiratory problems including persistent cough and/or shortness of breath or fever
• diabetes: frequency depends on the presence or absence of risk factors (fasting blood glucose ≥ 5.6 mmol/L, BMI > 30 kg/m², elevated triglycerides, history of hypertension)
• depression
• sexual dysfunction

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via
the national reporting system. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store HIMAVAT

Keep this medicine out of the sight and reach of children.
Do not use HIMAVAT after the expiry date stated on the packaging after "Exp". The expiry date refers to the last day of that month.
Store in the original packaging to protect the medicine from light.
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 HIMAVAT contains

• The active substances are ezetimibe and atorvastatin. Each tablet contains 10 mg of ezetimibe and 10 mg, 20 mg, 40 mg or 80 mg of atorvastatin (as atorvastatin calcium trihydrate).
• The other components are: monohydrate lactose, calcium carbonate, microcrystalline cellulose, sodium lauryl sulfate [E487], sodium croscarmellose, povidone K30, hydroxypropylcellulose, magnesium stearate and polysorbate 80.

Description of the appearance of HIMAVAT and contents of the pack
HIMAVAT 10 mg/10 mg: capsule-shaped tablets (12.7 mm x 5.1 mm), white to off-white in colour, with "1" engraved on one side.
HIMAVAT 10 mg/20 mg: capsule-shaped tablets (14.5 mm x 6.8 mm), white to off-white in colour, with "2" engraved on one side.
HIMAVAT 10 mg/40 mg: capsule-shaped tablets (16.4 mm x 6.3 mm), white to off-white in colour, with "3" engraved on one side.
HIMAVAT 10 mg/80 mg: capsule-shaped tablets (17.0 mm x 8.0 mm), white to off-white in colour, with "4" engraved on one side.
Available in packs of 30 tablets in OPA/Aluminum/PVC blisters, contained in a cardboard carton.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Neopharmed Gentili S.p.A.
Via San Giuseppe Cottolengo n. 15
20143 Milano, Italy

Manufacturer
Hennig Arzneimittel GmbH & Co.KG
Liebistr. 1-2
D-65439 Flörsheim, Germany