LaroxyL

Patient Information Leaflet: Information for the Patient

LAROXYL 10 mg film-coated tablets, 25 mg film-coated tablets, 40 mg/ml oral drops solution

Amitriptyline
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 their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Laroxyl is and what it is used for

Laroxyl belongs to a group of medicines known as tricyclic antidepressants.
This medicine is used to treat:

• depression in adults (major depressive episodes)
• neuropathic pain in adults
• prophylaxis of chronic tension-type headache in adults
• prophylaxis of migraine in adults
• involuntary loss of urine during the night in children aged 6 years and older, only when organic causes such as spina bifida and related disorders have been excluded and no response has been achieved with all other non-pharmacological and pharmacological treatments, including muscle relaxants and desmopressin. This medicine must be prescribed exclusively by a healthcare professional experienced in the treatment of persistent enuresis.

2. What you should know before taking Laroxyl

Do not use Laroxyl:

• if you are allergic to amitriptiline or to any of the other ingredients of this medicine (listed in section 6);
• if you have recently had a heart attack (myocardial infarction);
• if you have heart problems such as evident cardiac rhythm disorders on electrocardiogram (ECG), heart block, or coronary artery disease;
• if you are taking medicines known as monoamine oxidase inhibitors (MAOIs);
• if you have taken MAOIs within the last 14 days;
• if you have taken moclobemide the previous day;
• if you have severe liver disease.
  If you are currently being treated with Laroxyl, you must stop taking this medicine and wait 14 days before starting treatment with an MAOI.

This medicine must not be used in children under 6 years of age.
Warnings and precautions
Talk to your doctor or pharmacist before taking Laroxyl.
If you receive a high dose of amitriptiline, cardiac rhythm disturbances and hypotension may occur.
These may also occur at usual doses in patients with pre-existing heart disease.
Prolongation of the QT interval
With Laroxyl, a heart problem called "QT interval prolongation" (visible on electrocardiogram, ECG) and cardiac rhythm disturbances (fast or irregular heartbeat) have been reported.
Inform your doctor if:

• you have a slow heartbeat;
• you have or have had heart failure (a condition in which the heart cannot pump blood properly);
• you are taking any other medicine that may cause heart problems;
• you have low levels of potassium or magnesium, or high levels of potassium in your blood;
• you are scheduled for surgery, because it may be necessary to stop treatment with amitriptiline before receiving anaesthetics. In case of emergency surgery, the anaesthetist must be informed about your treatment with amitriptiline;
• you have an overactive thyroid or are taking medicines for the thyroid.

Suicidal thoughts and worsening of depression
If you are depressed, you may sometimes have thoughts of harming yourself or of suicide.
These thoughts may increase at the beginning of treatment with antidepressants, because the effect of these medicines does not occur immediately, but only after two weeks or even longer.
You are more likely to have such thoughts:

• if you have previously thought about 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 being treated with an antidepressant.
  If at any time you think about harming yourself or committing suicide, contact your doctor immediately or go to hospital.
  If you are depressed, it may be helpful to inform a family member or friend and ask them to read this leaflet. You may also ask them to inform you if they think your depression or anxiety is worsening or if they are concerned about changes in your behaviour.

Manic episodes
Some patients with bipolar disorder may enter a manic phase. This is characterised by rapidly changing thoughts, exaggerated cheerfulness, and excessive physical activity. In such cases, it is important to contact your doctor, who will likely adjust your treatment.
Inform your doctor if you have or have previously had any medical condition, especially:

• narrow-angle glaucoma (loss of vision due to abnormally increased pressure inside the eye);
• epilepsy, a history of seizures or convulsions;
• difficulty urinating;
• enlarged prostate;
• thyroid disease;
• bipolar disorder;
• schizophrenia;
• severe liver disease;
• severe heart disease;
• pyloric stenosis (narrowing of the stomach outlet) and paralytic ileus (intestinal blockage);
• diabetes, because treatment with antidiabetic medicines may need to be adjusted.

If you are taking antidepressants such as serotonin reuptake inhibitors (SSRIs), your doctor may consider adjusting the dose of the medicine (see also section 2 Other medicines and Laroxyl and section 3).
Elderly patients are more likely to experience certain adverse effects, such as dizziness upon standing, due to low blood pressure (see also section 4 Possible side effects).
Children and adolescents
Depression, neuropathic pain, chronic tension headache and migraine prophylaxis
Do not give this medicine to children and adolescents under 18 years of age for the treatment of these conditions, as long-term safety and efficacy have not been established in this age group.
Nocturnal enuresis (involuntary loss of urine during the night)

• Before starting amitriptiline therapy, an ECG should be performed to rule out long QT syndrome.
• This medicine must not be taken at the same time as an anticholinergic (see also section 2 Other medicines and Laroxyl).
• Suicidal thoughts and behaviours may occur at the beginning of treatment with antidepressants, even in patients suffering from disorders other than depression; therefore, the same precautions used in treating patients with depression should be adopted when treating patients with enuresis.

Other medicines and Laroxyl
Some medicines may alter the effect of other medicines, and this may sometimes cause serious adverse effects.
Inform your doctor or pharmacist if you are taking or have recently taken any other medicine, such as:

• Monoamine oxidase inhibitors (MAOIs) such as phenelzine, iproniazid, isocarboxazid, nialamide or tranylcypromine (used to treat depression), or selegiline (used to treat Parkinson's disease). These medicines must not be taken at the same time as Laroxyl (see section 2 Do not take Laroxyl).
• Adrenaline, ephedrine, isoprenaline, noradrenaline, phenylephrine and phenylpropanolamine (may be present in cough or cold remedies and in some anaesthetics).
• Medicines for high blood pressure, such as calcium antagonists (e.g. diltiazem and verapamil), guanethidine, betanidine, clonidine, reserpine and methyldopa.
• Anticholinergics, such as certain medicines for Parkinson's disease and gastrointestinal disorders (e.g. atropine, hyoscyamine).
• Thioridazine (used to treat schizophrenia).
• Tramadol (a painkiller).
• Medicines for fungal infections (e.g. fluconazole, terbinafine, ketoconazole and itraconazole).
• Sedatives (e.g. barbiturates).
• Antidepressants (e.g. SSRIs (fluoxetine, paroxetine, fluvoxamine), duloxetine and bupropion).
• Medicines for certain heart conditions (e.g. beta-blockers and antiarrhythmics).
• Cimetidine (used to treat stomach ulcers).
• Methylphenidate (used to treat ADHD).
• Ritonavir (used to treat HIV).
• Oral contraceptives.
• Rifampicin (used to treat infections).
• Phenytoin and carbamazepine (used to treat epilepsy).
• St. John's wort (Hypericum perforatum), a herbal remedy used for depression.
• Thyroid medicines.
• Valproic acid.

Also inform your doctor if you are taking or have recently taken medicines that may affect heart rhythm, such as:

• medicines for irregular heartbeat (e.g. quinidine and sotalol);
• astemizole and terfenadine (used to treat allergies and hay fever);
• medicines used to treat certain mental illnesses (e.g. pimozide and sertindole);
• cisapride (used to treat certain digestive disorders);
• halofantrine (used to treat malaria);
• methadone (used to treat pain and detoxification);
• diuretics (medicines that increase urine production, e.g. furosemide).

If you are undergoing surgery and are to receive general or local anaesthetics, inform your doctor that you are taking this medicine.
Similarly, inform your dentist that you are taking this medicine if you are to receive a local anaesthetic.
Laroxyl and alcohol
It is not advisable to consume alcoholic beverages during treatment with this medicine, as it may increase the sedative effect.
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor before taking this medicine.
Amitriptyline is not recommended during pregnancy, unless your doctor considers it clearly necessary, and only after careful assessment of benefit versus risk. If you have taken this medicine during the last months of pregnancy, the newborn may show withdrawal symptoms such as irritability, increased muscle tone, tremor, irregular breathing, feeding difficulties, loud crying, urinary retention and constipation.
Your doctor will advise you whether to start/continue/stop breastfeeding or discontinue use of this medicine, taking into account the benefit of breastfeeding for the child and the benefit of the treatment for you.
Driving and using machines
This medicine may cause drowsiness and dizziness, especially at the beginning of treatment. Do not drive or operate tools or machinery if you experience these symptoms.
Laroxyl coated tablets contain lactose and sucrose.
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

3. How to take Laroxyl

Take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor.
Not all dosage regimens may be achievable with every pharmaceutical form/strength. The appropriate formulation/strength must be selected for starting doses and subsequent dose increases.
One drop contains 2 mg of amitriptyline.

Depression
Adults
The recommended starting dose is 25 mg twice daily.
Depending on your response to the medicine, your doctor may gradually increase the dose up to a maximum of 150 mg per day, divided into two doses.

Elderly (over 65 years of age) and patients with cardiovascular disease
The recommended starting dose is 10 mg – 25 mg per day.
Depending on your response to the medicine, your doctor may gradually increase the dose up to a total daily dose of 100 mg, divided into two doses. If you are receiving doses of 100 mg – 150 mg, your doctor may perform more frequent monitoring.

Use in children and adolescents
This medicine must not be given to children or adolescents for the treatment of depression. For further information, see section 2.

Neuropathic pain, chronic tension-type headache and migraine prophylaxis
Your doctor will adjust treatment according to your symptoms and response to therapy.
Adults
The recommended starting dose is 10 mg – 25 mg at bedtime.
The recommended daily dose is 25 mg – 75 mg.
Depending on your response to the medicine, your doctor may gradually increase the dose.
If you receive doses exceeding 100 mg per day, your doctor may perform more frequent monitoring. Your doctor will advise whether you should take the dose once daily or divided into two doses.

Elderly (over 65 years of age) and patients with cardiovascular disease
The recommended starting dose is 10 mg – 25 mg at bedtime.
Depending on your response to the medicine, your doctor may gradually increase the dose.
If you receive doses exceeding 75 mg per day, your doctor may perform more frequent monitoring.

Use in children and adolescents
This medicine must not be given to children or adolescents for the treatment of neuropathic pain, chronic tension-type headache prophylaxis or migraine prophylaxis. For further information, see section 2.

Nocturnal enuresis (involuntary loss of urine during the night)
Use in children and adolescents
Recommended doses for children:

• Under 6 years of age: see section 2. Do not take Laroxyl.
• 6 to 10 years of age: 10 mg – 20 mg per day. A more suitable dosage form should be used for this patient group.
• 11 years of age and older: 25 mg – 50 mg per day.

Increase the dose gradually.
Take this medicine 1 to 1.5 hours before bedtime.
Before starting treatment, your doctor will perform an electrocardiogram (ECG) to check for any signs of abnormal heart rhythm.
Your doctor will re-evaluate the treatment after 3 months and, if necessary, perform an ECG.
Do not stop treatment without consulting your doctor.

Patients at particular risk
Patients with liver disease or individuals who are "slow metabolizers" generally receive lower doses.
Your doctor may take blood samples to determine the level of amitriptyline in your blood (see also section 2).

How and when to take Laroxyl
This medicine may be taken with or without food.
Swallow the tablets with a glass of water. Do not chew them.

Duration of treatment
Do not change the dose or stop treatment without consulting your doctor.

Depression
As with other medicines used to treat depression, it may take several weeks before improvement is noticed.
The duration of treatment for depression varies individually and is generally at least 6 months. Your doctor will determine the appropriate duration of treatment.
Continue taking this medicine for the entire time recommended by your doctor.
The underlying condition may persist for a long time. If treatment is stopped too early, symptoms may return.

Neuropathic pain, chronic tension-type headache and migraine prophylaxis
It may take several weeks before improvement in pain is noticed.
Consult your doctor regarding the duration of treatment and continue taking this medicine for the entire time recommended by your doctor.

Nocturnal enuresis
After 3 months, your doctor will decide whether treatment should continue.

If you take more Laroxyl than you should
Contact your doctor or the nearest hospital emergency department immediately, even if no symptoms or signs of poisoning are present. If you go to a doctor or hospital, bring the medicine container with you.
Symptoms of overdose include:

• dilated pupils,
• rapid or irregular heartbeat,
• difficulty urinating,
• dry mouth and tongue,
• intestinal obstruction,
• seizures,
• fever,
• agitation,
• confusion,
• hallucinations,
• uncontrolled movements,
• low blood pressure, weak pulse, pallor,
• breathing difficulties,
• bluish discoloration of the skin,
• reduced heart rate,
• stupor,
• loss of consciousness,
• coma,
• various heart-related symptoms such as cardiac block, heart failure, hypotension, cardiogenic shock, metabolic acidosis, hypokalemia.

Overdose with amitriptyline in children may have serious consequences. Children are particularly susceptible to coma, cardiac symptoms, breathing difficulties, epileptic seizures, low blood sodium levels, lethargy, drowsiness, nausea, vomiting and high blood sugar levels.

If you forget to take Laroxyl
Take the next dose at your usual time. Do not take a double dose to make up for the missed dose.

If you stop taking Laroxyl
Your doctor will decide when and how to discontinue treatment to avoid unpleasant symptoms that may occur if treatment is stopped abruptly (e.g. headache, malaise, insomnia and irritability).

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor immediately if you notice any of the following symptoms:

• Episodes of intermittent blurred vision, seeing rainbows, and eye pain.
• You must be examined immediately by an ophthalmologist before continuing treatment with this medicine. These symptoms may be signs of acute glaucoma. Very rare side effect: may affect up to 1 in 10,000 people.
• A heart problem called "QT interval prolongation" (visible on electrocardiogram, ECG). Common side effect: may affect up to 1 in 10 people.
• Severe constipation, stomach swelling, fever, and vomiting.
• These symptoms may be due to paralysis of parts of the intestine. Rare side effect: may affect up to 1 in 1,000 people.
• Yellowing of the skin and whites of the eyes (jaundice).
• This may indicate liver problems. Rare side effect: may affect up to 1 in 1,000 people.
• Bruising, bleeding, paleness, or persistent sore throat and fever.
• These symptoms may be early signs of blood or bone marrow problems.
• Blood-related effects include a reduction in the number of red blood cells (which carry oxygen throughout the body), white blood cells (which help fight infections), and platelets (which aid blood clotting). Rare side effect: may affect up to 1 in 1,000 people.
• Suicidal behaviour or thoughts. Rare side effect: may affect up to 1 in 1,000 people.

The following side effects have been reported with the following frequencies:
Very common: may affect more than 1 in 10 people

• drowsiness/stupor
• tremor in hands or other body parts
• dizziness
• headache
• irregular, strong, or rapid heartbeat
• dizziness upon standing, due to low blood pressure (orthostatic hypotension)
• dry mouth
• constipation
• nausea
• excessive sweating
• weight gain
• slurred or slowed speech
• aggression
• nasal congestion

Common: may affect up to 1 in 10 people

• confusion
• sexual dysfunction (reduced sexual desire, erectile dysfunction)
• attention disturbance
• taste alterations
• numbness or tingling in arms or legs
• coordination problems
• dilated pupils
• heart block
• fatigue
• low sodium concentration in the blood
• agitation
• urinary disorders
• sensation of thirst

Uncommon: may affect up to 1 in 100 people

• excitement, anxiety, difficulty sleeping, nightmares
• seizures
• tinnitus
• increased blood pressure
• diarrhoea, vomiting
• skin rash, hives, facial and tongue swelling
• difficulty urinating
• increased milk production or milk discharge from the breast in people who are not breastfeeding
• increased pressure inside the eye
• collapse conditions
• worsening of heart failure
• worsening of liver function (e.g. cholestatic hepatopathy)

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

• decreased appetite
• delirium (particularly in elderly patients), hallucinations
• abnormalities in heart rhythm or heartbeat sequence
• swelling of the salivary glands
• hair loss
• increased sensitivity to sunlight
• breast enlargement in men
• fever
• weight loss
• changes in liver function test results

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

• cardiomyopathy
• feeling of inner restlessness and an urgent need to keep moving (akathisia)
• peripheral nerve disorders
• acute increase in pressure inside the eye
• specific types of abnormal heart rhythm (called torsades de pointes)
• allergic inflammation of the lung alveoli and lung tissue

Not known: frequency cannot be estimated from the available data

• loss of appetite sensation
• increased or decreased blood sugar levels
• paranoia
• movement disorders (involuntary movements or reduced movements)
• hypersensitivity myocarditis (inflammation of the heart muscle)
• hepatitis
• hot flushes
• dry eyes

In patients taking medicines of this type, an increased risk of bone fractures has been observed.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor. 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 Laroxyl

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp.". The expiry date refers to the last day of that month and to the product in its original, undamaged packaging stored under proper conditions.
This medicine does not require any special storage conditions.
Do not use this medicine if you notice any visible signs of deterioration.
Do not dispose of medicines 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 Laroxyl contains:
Laroxyl 10 mg film-coated tablets
The active substance is: amitriptyline hydrochloride. Each tablet contains 11.32 mg of amitriptyline hydrochloride
(equivalent to 10 mg of amitriptyline base).
The other components are: maize starch; lactose monohydrate; povidone; magnesium stearate; talc; acacia gum,
spray-dried; ethylcellulose; copolymer lacquer; rice starch; iron oxide red (E172); titanium dioxide; light liquid paraffin;
solid paraffin; sucrose.
Laroxyl 25 mg film-coated tablets
The active substance is amitriptyline hydrochloride. Each tablet contains 28.3 mg of amitriptyline hydrochloride (equivalent
to 25 mg of amitriptyline base).
The other components are: maize starch; lactose monohydrate; povidone; magnesium stearate; talc; acacia gum,
spray-dried; ethylcellulose; copolymer lacquer; rice starch; iron oxide red (E172); titanium dioxide; light liquid paraffin;
solid paraffin; sucrose.
Laroxyl 40 mg/ml oral drops solution
The active substance is amitriptyline hydrochloride. One ml of Laroxyl oral drops solution contains 45.28 mg of
amitriptyline hydrochloride (equivalent to 40 mg of amitriptyline base).
The other components are: purified water, hydrochloric acid.

Description of the appearance of Laroxyl and contents of the pack:
Laroxyl 10 mg film-coated tablets: pack of 30 tablets in blister packs.
Laroxyl 25 mg film-coated tablets: pack of 25 tablets in blister packs.
Laroxyl 40 mg/ml oral drops solution: 20 ml bottle.

Marketing Authorization Holder and Manufacturer
Teofarma S.r.l.
Via F.lli Cervi, 8 - 27010 Valle Salimbene (PV)
Fax 0382/525845
e-mail: [email protected]

Manufacturer
Tablets
Teofarma S.r.l.
Viale Certosa, 8/A - 27100 Pavia
Oral drops
Teofarma S.r.l.
Viale Certosa, 8/A - 27100 Pavia