Package leaflet: Information for the user

Zaredrop 75 mg/ml oral solution

Venlafaxine hydrochloride
Please read this entire leaflet carefully before you start 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 others, even if they have the same symptoms as yours, because it could be harmful.
If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Zaredrop is and what it is used for

Zaredrop is an antidepressant that belongs to a class of medicines known as serotonin and noradrenaline reuptake inhibitors (SNRIs). These medicines are used to treat depression and other conditions, such as anxiety disorders. It is believed that people suffering from depression and/or anxiety have lower levels of serotonin and noradrenaline in the brain. The exact mechanism of action of antidepressants is not yet fully understood, but these medicines may help by increasing the levels of serotonin and noradrenaline in the brain.
Zaredrop is a treatment for depression in adults. Proper treatment of depression is important to help you feel better. If left untreated, your condition may not improve and could become more severe and more difficult to treat.

2. What you should know before taking Zaredrop

Do not take Zaredrop

If you are allergic to venlafaxine or to any of the other ingredients of this medicine (listed in section 6).
If you are currently taking or have taken within the last 14 days medicines known as irreversible monoamine oxidase inhibitors (MAOIs), used in the treatment of depression or Parkinson’s disease. The concomitant use of irreversible MAOIs and other medicines, including Zaredrop, may cause serious, potentially fatal adverse effects. In addition, you must wait at least 7 days after stopping Zaredrop before starting any MAOI (also see the sections titled “Serotonin syndrome” and “Other medicines and Zaredrop”).

Warnings and precautions
Talk to your doctor or pharmacist before taking Zaredrop

If you are taking other medicines that, when taken together with Zaredrop, could increase the risk of serotonin syndrome (see the section titled “Other medicines and Zaredrop”).
If you are taking other medicines that, when taken together with Zaredrop, could alter heart rhythm (see the section titled “Other medicines and Zaredrop”).
If you have eye disorders, such as certain forms of glaucoma (increased pressure inside the eye).
If you have a history of high blood pressure.
If you have a history of heart problems.
If you have been told you have an abnormal heart rhythm.
If you have a history of epileptic seizures (convulsions).
If you have a history of low sodium levels in the blood (hyponatraemia).
If you tend to bruise easily or bleed easily (history of bleeding disorders), or if you are taking other medicines that may increase the risk of bleeding, e.g. warfarin (used to prevent blood clots), or if you are pregnant (see “Pregnancy, breastfeeding and fertility”).
If your cholesterol levels increase.
If you are taking medicines used for weight loss (including phentermine).
If you or a family member has or has had episodes of mania or bipolar disorder (feelings of hyperexcitability or euphoria).
If you have a history of aggressive behaviour.
If your doctor has informed you that you have an intolerance to certain sugars, contact them before using this medicine, as your blood glucose levels may be affected by Zaredrop. Therefore, adjustment of your diabetes medication dosage may be necessary. Zaredrop may cause restlessness or inability to remain still while sitting or standing during the first weeks of treatment. If this happens to you, inform your doctor. If any of these conditions apply to you, please discuss them with your doctor before taking Zaredrop.

Medicines such as Zaredrop (so-called serotonin-noradrenaline reuptake inhibitors (SNRIs)) may cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms may persist after discontinuation of treatment.
Do not consume alcohol during treatment with Zaredrop, as this may cause extreme drowsiness and unconsciousness. The concomitant use of alcohol and/or certain medicines may worsen symptoms of depression and other conditions, such as anxiety disorders.
Suicidal thoughts and worsening of depression or anxiety disorder.
If you feel depressed and/or suffer from anxiety disorders, you may occasionally have thoughts of harming yourself or of suicide.
These thoughts may increase when starting treatment with antidepressants, as these medicines require time to take effect, usually about two weeks, sometimes longer. These thoughts may also occur when the dose is reduced or during discontinuation of treatment with Zaredrop.
You may experience such thoughts:

If you have previously had thoughts of suicide or self-harm.
If you are a young adult. Clinical trial data have shown an increased risk of suicidal behaviour in young adults (under 25 years) with psychiatric disorders treated with antidepressants. If at any time you think about harming yourself or committing suicide, inform your doctor immediately or go to the nearest hospital. It may help to confide in a family member or friend that you are depressed or have anxiety, and ask them to read this leaflet. You may ask them to inform you if they believe your depression or anxiety is worsening, or if they are concerned about changes in your behaviour.

Dry mouth
This effect has been reported in 10% of patients treated with venlafaxine. This symptom may increase the risk of dental caries. Therefore, meticulous dental hygiene is essential.
Diabetes
Your blood glucose levels may be affected by the use of Zaredrop. Therefore, the dosage of your diabetes medications may require adjustment.
Children and adolescents
Zaredrop is generally not recommended for use in children and adolescents under 18 years of age. In addition, it should be noted that patients under 18 years of age have a higher risk of adverse effects, such as suicide attempts, suicidal thoughts and hostility (mainly aggression, hostile behaviour and anger), when taking this class of medicines. However, your doctor may prescribe Zaredrop to patients under 18 years of age if they consider it to be in their best interest. If your doctor has prescribed Zaredrop to a patient under 18 years of age and you wish to discuss this, please speak to them. If any of the above-mentioned symptoms appear or worsen in patients under 18 years of age treated with Zaredrop, you must inform your doctor. Furthermore, the long-term effects of Zaredrop on physical growth, maturation, and cognitive and behavioural development in this age group have not yet been evaluated.

Other medicines and Zaredrop
Please inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Your doctor will decide whether you can take Zaredrop together with other medicines.
Do not start or stop taking any medicine, including those available without a prescription, natural or herbal products, before consulting your doctor or pharmacist.

Monoamine oxidase inhibitors (MAOIs), used in the treatment of depression or Parkinson’s disease, must not be taken with Zaredrop. Inform your doctor if you have taken these medicines within the last 14 days (MAOIs: see section “What you should know before taking Zaredrop”).
Serotonin syndrome, a potentially life-threatening condition, or reactions similar to neuroleptic malignant syndrome (NMS) (see section “Possible side effects”), may occur during treatment with venlafaxine, particularly when taken concomitantly with other medicines. Examples of such medicines include:
Triptans (used for migraine)
Medicines for the treatment of depression, e.g. serotonin-noradrenaline reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), tricyclics, or medicines containing lithium
Medicines containing amphetamines (used to treat attention deficit hyperactivity disorder (ADHD), narcolepsy and obesity)
Medicines containing linezolid, an antibiotic (used to treat infections)
Medicines containing moclobemide, an MAOI (used to treat depression)
Medicines containing sibutramine (used for weight loss)
Medicines containing tramadol, fentanyl, tapentadol, pethidine, medicines containing buprenorphine or pentazocine (used to treat severe pain)
Medicines containing dextromethorphan (used to treat cough)
Medicines containing methadone (used to treat opioid dependence or severe pain)
Medicines containing methylene blue (used to treat high levels of methaemoglobin in the blood)
Products containing St. John’s wort (also known as Hypericum perforatum, a natural or herbal remedy used to treat mild depression)
Products containing tryptophan (used for problems such as sleep disorders and depression)
Antipsychotics (used to treat symptoms such as hearing, seeing or sensing things that are not there, having false beliefs, unusual suspiciousness or confused thinking, or withdrawal).

Signs and symptoms of serotonin syndrome may include a combination of the following: restlessness, hallucinations, loss of coordination, rapid heartbeat, increased body temperature, rapid changes in blood pressure, hyperactive reflexes, diarrhoea, coma, nausea, vomiting.
In its most severe form, serotonin syndrome may present as neuroleptic malignant syndrome (NMS). Signs and symptoms of NMS may include a combination of fever, rapid heartbeat, sweating, severe muscle rigidity, confusion and increased muscle enzymes (assessed via blood test).
Seek immediate medical help or go to the nearest hospital emergency department if you suspect you have serotonin syndrome.

The following medicines may interact with venlafaxine and alter heart rhythm, and therefore their concomitant administration must be avoided:

Antiarrhythmics (medicines such as quinidine, amiodarone, sotalol or dofetilide)
Certain medicines used to treat psychiatric conditions (thioridazine). (See also above: “Serotonin syndrome”)
Certain antibiotics such as erythromycin or moxifloxacin
Certain antihistamines

Cases of unintended pregnancies have been reported in individuals taking oral contraceptives during treatment with venlafaxine.
There is no clear evidence that these pregnancies were due to a pharmacological interaction with venlafaxine. Inform your doctor if you are taking oral contraceptives.
The following medicines may interact with Zaredrop and should be used with caution. It is particularly important to inform your doctor or pharmacist if you are taking medicines containing:

ketoconazole, itraconazole, voriconazole, posaconazole (antifungal medicines)
clarithromycin, telithromycin (antibiotics used to treat infections)
atazanavir, indinavir, nelfinavir, ritonavir, saquinavir (used in the treatment of HIV infection)
haloperidol, risperidone, diazepam or imipramine (for the treatment of psychiatric disorders)
metoprolol (a beta-blocker used to treat high blood pressure and heart problems).

Zaredrop with food, drinks and alcohol
Zaredrop should be taken with food, and the solution must be diluted with water before administration (see section 3 “How to take Zaredrop”).
Do not drink alcohol during treatment with Zaredrop. Concomitant use with alcohol may cause extreme tiredness and unconsciousness, and may worsen symptoms of depression and other conditions such as anxiety disorders.

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor before taking this medicine.
You should use Zaredrop only after discussing with your doctor the potential benefits and potential risks to the fetus.
Ensure that your midwife and/or doctor know that you are taking Zaredrop. When used during pregnancy, similar medicines (SSRIs) may increase the risk of a serious condition in the newborn called persistent pulmonary hypertension of the newborn (PPHN), which causes the baby to breathe faster and appear bluish. These symptoms usually begin within the first 24 hours after birth. If this occurs in your baby, contact your midwife and/or doctor immediately.
If you are taking Zaredrop during pregnancy, inform your midwife and/or doctor, as the baby may experience other symptoms after birth. These include feeding difficulties and breathing problems.
In addition, the following symptoms have been observed: irritability, tremor, muscle weakness, persistent crying and sleep disturbances.
In most cases, these symptoms occur immediately or within 24 hours after birth.
If your baby shows these symptoms at birth and you are concerned, contact your doctor and/or midwife, who will be able to advise you.
Zaredrop is excreted in breast milk. There is a risk of side effects in the breastfed infant, which may cause crying, irritability and sleep disturbances. Withdrawal symptoms have been observed in newborns after discontinuation of breastfeeding. Therefore, you should discuss this with your doctor, who will decide whether to discontinue breastfeeding or stop treatment with Zaredrop.
If you take Zaredrop near the end of pregnancy, there may be an increased risk of heavy vaginal bleeding shortly after delivery, especially if you have bleeding disorders (tendency to bleed easily). Inform your doctor or midwife that you are taking Zaredrop so they can advise you on what to do.

Driving and using machines
Do not drive or operate tools or machinery until you know how Zaredrop affects you.

Zaredrop contains sorbitol
This medicine contains 300 mg of sorbitol per ml.
Sorbitol is a source of fructose. If your doctor has told you that you (or your child) have an intolerance to certain sugars, or if you have a diagnosis of hereditary fructose intolerance, a rare genetic disorder in which patients cannot metabolise fructose, speak to your doctor before you (or your child) take this medicine.
This medicine contains 1 mg of benzoic acid per ml.

Zaredrop contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per ml, i.e. essentially ‘sodium-free’.

Zaredrop contains ethanol
This medicine contains 15.8 mg/ml of ethanol (anise flavouring agent), equivalent to 1.58% p/v. Therefore, a 1 ml dose of Zaredrop is equivalent to less than 1 ml of beer or 1 ml of wine. The small amount of alcohol in this medicine will not produce significant effects.

3. How to take Zaredrop

Always take this medicine exactly as instructed by your doctor. If you have any doubts,
consult your doctor or pharmacist.
The bottle is equipped with a graduated adapter syringe and sealed with a child-resistant screw cap.
0.5 ml of solution corresponds to 37.5 mg of venlafaxine base.
To withdraw the prescribed dose of solution, insert the syringe into the adapter.
While keeping the syringe attached to the bottle, turn the bottle upside down.
Gently pull the plunger downward and withdraw the prescribed dose.
Remove any air bubbles by gently tapping the body of the syringe and slowly pushing the plunger.
The recommended initial dose for the treatment of depression is 75 mg/day, divided into two daily
doses. Your doctor may gradually increase the dose, if necessary, up to a maximum dose of 375 mg per
day for the treatment of depression.
Take Zaredrop approximately at the same time each day, in the morning and in the evening. Zaredrop must be taken with food.
The solution must be diluted with water before use.
For oral use.
If you have liver or kidney problems, inform your doctor, as you may need to take a different dose of Zaredrop.
Do not stop taking Zaredrop without discussing it with your doctor (see the section “If you stop taking Zaredrop”).

If you take more Zaredrop than you should
If you take more Zaredrop than prescribed by your doctor, contact your doctor or pharmacist immediately.
Overdose can be life-threatening, especially when taken together with alcohol and/or certain medicines (see “Other medicines and Zaredrop”).
Symptoms of a possible overdose may include rapid heartbeat, changes in level of consciousness (including drowsiness and coma), blurred vision, seizures or epileptic fits, and vomiting.

If you forget to take Zaredrop
If you miss a dose, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and take only your next single dose as usual. Do not take more than the daily amount of Zaredrop prescribed to you in one day.

If you stop taking Zaredrop
Do not stop treatment or reduce the dose without consulting your doctor, even if you feel better. If your doctor decides that you no longer need to take Zaredrop, they may instruct you to gradually reduce the dose before completely stopping treatment. It is known that stopping treatment with Zaredrop may cause side effects, especially if Zaredrop is stopped abruptly or if the dose is reduced too quickly. Some patients may experience symptoms such as suicidal thoughts, aggression, fatigue, dizziness, feeling of lightheadedness, headache, insomnia, nightmares, dry mouth, loss of appetite, nausea and/or vomiting, tremor, diarrhoea, nervousness, agitation, confusion, ringing in the ears (tinnitus), tingling sensations, or rarely, electric shock-like sensations, weakness, sweating, seizures, or flu-like symptoms, vision problems, and increased blood pressure (which may cause headache, dizziness, ringing in the ears, sweating, etc.).
Your doctor will advise you on how to gradually discontinue treatment with Zaredrop.
This process may take several weeks or months. In some patients, discontinuation may need to be very gradual over months or longer periods.
If you experience any of these symptoms or other bothersome symptoms, consult your doctor for further advice.
If you have further questions about using this product, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
If any of the following symptoms occur, stop taking Zaredrop immediately and contact your doctor or go to the nearest hospital emergency department:
Uncommon (may affect up to 1 in 100 people)
Swelling of the face, mouth, tongue, throat, hands or feet and/or a raised itchy rash (urticaria), difficulty swallowing or breathing.

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

Tightness in the chest, wheezing, difficulty swallowing or breathing
Nervousness or anxiety, dizziness, palpitations, sudden skin redness and/or hot flushes
Severe skin rash, itching or hives (raised, red or pale patches on the skin that often itch)
Signs and symptoms of serotonin syndrome, which may include restlessness, hallucinations, loss of coordination, rapid heartbeat, increased body temperature, rapid changes in blood pressure, overactive reflexes, diarrhoea, coma, nausea, vomiting. In its most severe form, serotonin syndrome may present as Neuroleptic Malignant Syndrome (NMS). Signs and symptoms of NMS may include a combination of fever, rapid heartbeat, sweating, severe muscle rigidity, confusion and increased muscle enzymes (detected via blood test).
Signs of infection such as high fever, chills, tremors, headache, sweating, flu-like symptoms. This may be due to a blood disorder causing an increased risk of infection.
- Severe skin rash, which may lead to serious blisters and skin peeling;
- Unexplained muscle pain, tenderness or weakness. This could be a sign of rhabdomyolysis.

Frequency not known (cannot be estimated from available data)

Signs and symptoms of a condition called "stress cardiomyopathy" which may include chest pain, shortness of breath, dizziness, fainting, irregular heartbeat.

Other side effects that you should report to your doctor include: (The frequency of these side effects is included in the list "Other side effects that may occur" below)

Cough, wheezing, difficulty breathing and fever
Black (tarry) stools or blood in the stool
Yellowing of the skin or eyes, itching, dark urine, which may be symptoms of liver inflammation (hepatitis)
Heart problems, such as rapid or irregular heartbeat, increased blood pressure
Eye problems, such as blurred vision, dilated pupils
Nervous system problems, such as dizziness, tingling, movement disorders (muscle spasms or stiffness), seizures or epileptic fits
Psychiatric disorders, such as hyperactivity and euphoria (feeling unusually overexcited)
Withdrawal symptoms (see section “How to take Zaredrop – If you stop taking Zaredrop”)
Prolonged bleeding – if you cut or injure yourself, it may take longer than usual for the bleeding to stop.

Other side effects may occur:
Very common (may affect more than 1 in 10 people)

dizziness; headache; drowsiness
insomnia
nausea; dry mouth; constipation
sweating (including night sweats)

Common (may affect up to 1 in 10 people)

reduced appetite
confusion; feeling detached or separated from oneself
absence of orgasm; reduced sexual desire
restlessness; nervousness; abnormal dreams
tremor; feeling restless or unable to sit still; tingling; altered taste; increased muscle tension
vision disturbances, including blurred vision; dilated pupils; inability of the eye to focus from far to near
ringing in the ears (tinnitus)
rapid heartbeat; palpitations
increased blood pressure; hot flushes
shortness of breath; yawning
vomiting; diarrhoea
mild skin rash; itching
increased frequency of urination; inability to urinate; difficulty urinating
menstrual irregularities such as increased bleeding or irregular and increased bleeding; abnormal ejaculation/orgasm (males); erectile dysfunction (impotence)
weakness (asthenia); fatigue; chills
increased cholesterol levels
weight gain, weight loss
drowsiness

Uncommon (may affect up to 1 in 100 people)

hallucinations; feeling detached from reality; abnormal orgasm; lack of feelings or emotions; feeling overexcited or euphoric; teeth grinding;
Hyperactivity, racing thoughts and reduced need for sleep (mania);
fainting; involuntary muscle movements; coordination and balance problems; dizziness (especially when standing up too quickly); decreased blood pressure;
vomiting blood; black stools or blood in the stool, which could indicate internal bleeding
sensitivity to daylight; bruising; skin rash; abnormal hair loss
involuntary loss of urine
muscle stiffness, spasms and involuntary movements
slight changes in blood levels of liver enzymes.

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

seizures or epileptic fits
cough, wheezing and shortness of breath which may be accompanied by high temperature
disorientation and confusion, often accompanied by hallucinations (delirium)
excessive water intake (known as SIADH)
low sodium levels in the blood
severe eye pain and reduced or blurred vision
abnormal, rapid or irregular heartbeat, which may lead to fainting
severe abdominal or back pain (which may indicate a serious problem with the intestine, liver or pancreas)
itching, yellowing of the skin or eyes, dark urine or flu-like symptoms, which are signs of liver inflammation (hepatitis)

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

Prolonged bleeding, which may indicate a reduced number of platelets in the blood, leading to an increased risk of bruising or bleeding;
Abnormal production of breast milk
Unexpected bleeding, e.g. bleeding gums, blood in urine or vomit, or unexplained bruising or blood vessel rupture (vein rupture)

Not known (frequency cannot be estimated from available data)

Suicidal or self-harming thoughts; cases of suicidal ideation and suicidal behaviour have been reported during treatment with venlafaxine or immediately after discontinuation of treatment (see section 2, “What you should know before taking Zaredrop”);
aggression;
vertigo;
Heavy vaginal bleeding shortly after childbirth (postpartum haemorrhage); see section 2 “Pregnancy, breastfeeding and fertility” for further information.

Zaredrop may sometimes cause side effects that you may not notice, such as increased blood pressure or abnormal heartbeat; slight changes in liver enzyme levels, sodium and cholesterol levels in the blood. Less frequently, Zaredrop may reduce platelet function in the blood, increasing the risk of bruising and bleeding. Therefore, your doctor may occasionally wish to perform blood tests, especially if you have been taking Zaredrop for a long time.
If any of the side effects worsen, or if you notice any side effects not listed in this leaflet, please consult your doctor or pharmacist.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please contact your doctor, pharmacist or nurse.
You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Zaredrop

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the pack after "Exp". The expiry date refers to the last day of that month.
Store in the original packaging and keep the bottle in its outer cardboard carton.
After first opening, the solution is stable for 4 months.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Zaredrop contains
The active substance is venlafaxine hydrochloride. Each ml of oral solution contains 84.86 mg of
venlafaxine hydrochloride, equivalent to 75 mg of venlafaxine.
The other components are:
Liquid sorbitol E420, sodium saccharin E954, sodium benzoate E211, anise flavour (anethole,
water, ethanol), sodium hydroxide, concentrated hydrochloric acid, purified water.

Description of the appearance of Zaredrop and contents of the pack
Zaredrop is a clear, colourless or slightly yellowish oral solution. It is supplied in a bottle containing 60 ml of solution, equipped with a syringe adapter and a graduated syringe for administration of the medicine.

Marketing Authorisation Holder
Italfarmaco S.p.A.
Viale Fulvio Testi, 330
20126 Milan
Italy
Tel: +39.02.64431
Fax: +39.02.644346
e-mail: [email protected]

Manufacturer
Italfarmaco S.A.
28108 Alcobendas (Madrid) (E), San Rafael, 3 Polig. Industrial Alcobendas
Tel: +34.916572323
Fax: +34.916572361
E-mail: [email protected]

This medicinal product is authorised in the Member States of the European Economic Area under the
following names:
Italy: ZAREDROP 75 mg/ml Oral solution
Greece: ZAREDROP 75 mg/ml Πόσιμο διάλυμα
Spain: ZAREDROP 75 mg/ml Solución oral
Portugal: ZAREDROP 75 mg/ml Solução oral