FENTANIL 50 MICROGRAMS/ML Injectable solution

Зміст інструкції

1. Fentanil Kalceks 50 micrograms/ml injectable solution
2. Fentanil
   1. What is Fentanil Kalceks and what is it used for
   2. What you need to know before you are given Fentanil Kalceks
   3. How Fentanil Kalceks is administered
   4. Possible side effects
   5. How to store Fentanil Kalceks
   6. Package contents and other information

Fentanil Kalceks 50 micrograms/ml injectable solution

Equivalent Medicinal Product

Fentanil

Read this leaflet carefully before using this medicine as 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 nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

• 1. What Fentanil Kalceks is and what it is used for
• 2. What you need to know before you are given Fentanil Kalceks
• 3. How Fentanil Kalceks is administered
• 4. Possible side effects
• 5. How to store Fentanil Kalceks
• 6. Contents of the pack and other information

1. What is Fentanil Kalceks and what is it used for

Fentanil Kalceks 50 micrograms/ml injectable solution is a liquid that is injected. Fentanil is
a substance that reduces pain and determines the action of this medicine. Fentanil belongs to a
group of strong narcotic analgesics, also called opioid analgesics.
This medicine will be administered to you during surgery to ensure that you do not feel
any pain.

2. What you need to know before you are given Fentanil Kalceks

You must not be given Fentanil Kalceks

• If you are allergic to fentanil or any of the other ingredients of this medicine (listed in section 6). Also, if you are hypersensitive to other strong analgesics (narcotics), this medicine must not be given to you.
• If your lungs are not functioning well (without mechanical ventilation).

Warnings and precautions
After the administration of this medicine, your breathing may slow down or weaken
abnormally. In this case, it is important that you immediately inform the doctor. Since
this can also occur some time after surgery, you will be kept
under observation for a certain period of time after the operation.
Consult your doctor or nurse before you are given Fentanil Kalceks:

• if your kidneys, liver or thyroid are not functioning normally;
• if you have lung or airway diseases;
• if you use alcohol or drugs;
• if you suffer from a certain muscle disorder (myasthenia gravis);
• if you are using certain medicines for depression (see “Other medicines and Fentanil Kalceks”);
• in elderly or debilitated patients and in children (see section 3).

Tell your doctor if any of these warnings apply to you. After the administration of this
medicine, careful medical monitoring may be necessary. It may also be
necessary to adjust the dose.
Tell your doctor if you have ever had problems with abuse of or dependence on opioids, alcohol, prescription drugs or illicit substances.
Repeated use of the product may cause a reduction in the effectiveness of the medicine (because you
become accustomed to the medicine) or a dependence on the medicine.
If treatment is stopped, withdrawal symptoms may occur. Tell your doctor or
nurse if you think this is happening to you (see also section 4, “Possible side effects”).

Children
There is no experience in the use of this medicine in children under 2 years of age. It is therefore
not recommended to give this medicine to children under 2 years of age.

Other medicines and Fentanil Kalceks
Tell your doctor or nurse if you are taking, have recently taken or might take any other
medicines. Do this even if they are medicines purchased without a prescription.
This is particularly important in the case of the medicines listed below, as it may be
necessary to adjust the dose of this medicine or other medicines, or it may be
necessary to subject you to closer monitoring.
Tell your doctor if you are taking or have recently taken:

• selective serotonin reuptake inhibitors (SSRIs);
• norepinephrine reuptake inhibitors (SNRIs);
• monoamine oxidase inhibitors (MAO inhibitors). If used together, mood changes (e.g. agitation, hallucinations [perceiving things that do not actually exist], coma), body temperature above 38 °C, faster heartbeat, unstable blood pressure and more reactive reflexes, muscle stiffness, lack of coordination and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhea) may occur. The doctor will determine if this medicine is suitable for you. If you are using MAO inhibitors, the doctor, when possible, will have you stop treatment with these medicines at least 2 weeks before you are given this medicine.
• strong painkillers for a prolonged period of time;
• medicines to treat psychosis or Parkinson's disease;
• sleeping pills;
• tranquilizers;
• antiepileptic medicines (e.g. carbamazepine, phenytoin);
• medicines to reduce anxiety;
• medicines to treat certain mental illnesses;
• medicines to treat fungal infections (e.g. fluconazole or voriconazole);
• ritonavir (a medicine to treat HIV infection). If you are given a single dose of fentanyl, the doctor will pay particular attention to you. In case of prolonged use, you may be prescribed a lower dose of this medicine.

Fentanil Kalceks with alcohol
Tell your doctor or nurse if you are using or have recently used alcohol or drugs.
Alcohol may increase the effects of this medicine. This medicine in turn affects
the effect of alcohol. For these reasons, do not drink alcohol before receiving this medicine or the day
after you have received it.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding with
breast milk, ask your doctor or pharmacist for advice before using this medicine.

Pregnancy
We do not have sufficient data to establish whether the use of this medicine is harmful in case of
pregnancy. The administration of this medicine during childbirth, e.g. caesarean section, is not
recommended because this medicine may cause breathing problems in the newborn.

Breastfeeding
The substance that determines the effect of this medicine passes into breast milk. It is therefore
not recommended to breastfeed with breast milk in the first 24 hours after the administration of
this medicine. Do not use breast milk collected in the 24 hours after the administration of
this medicine. Talk to your doctor.

Driving and operating machinery
Do not drive cars or other vehicles and do not use machinery or tools for at least 24 hours after receiving
this medicine, as it may negatively affect your state of alertness and your
ability to drive. For this reason, the doctor will decide when you can drive
vehicles or use dangerous machinery again after taking this medicine.

Fentanil Kalceks contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per 2 ml vial, i.e. it is essentially
“sodium-free”.
This medicine contains 35.41 mg of sodium (the main component of table salt) per vial
of 10 ml. This corresponds to 1.78% of the recommended daily intake with the diet of an
adult.

3. How Fentanil Kalceks is administered

This medicine is administered by injection into a vein.

Dosage
It is important that you receive the right amount of this medicine. This amount varies from person to
person depending on age, body weight, physical condition, underlying diseases, medications used and the
type of surgery and anesthesia. The doctor will determine how much medicine you need.

Adults
Generally, 4-12 ml of Fentanil Kalceks are administered just before surgery. If the doctor deems it
necessary, another supplemental dose may be administered at a later time.

Elderly and debilitated patients
The dose administered to elderly patients (aged 65 years or older) and debilitated patients just before
surgery is lower than that prescribed for other adults. If the doctor deems it necessary, another
supplemental dose may be administered at a later time.

Children aged 2 years and over
The dose administered to children before surgery depends on their body weight. If the doctor deems it
necessary, another supplemental dose may be administered at a later time.
Adolescents aged between 12 and 17 years receive adult doses.

Children under 2 years of age
There is no experience in the use of this medicine in children under 2 years of age. It is therefore not
recommended to administer this medicine to children in this age group.

Patients with kidney problems
The doctor may decide to reduce the dose to be administered to patients with kidney problems.

Obese patients
The dose administered to obese patients just before surgery may be lower than that prescribed for
other adults. If the doctor deems it necessary, another supplemental dose may be administered at a later
time.

If you have been given too much Fentanil Kalceks
Since this medicine will be administered by hospital staff, it is unlikely that you will receive an
overdose. In any case, immediately inform the doctor or nurse if you experience shallow or slow
breathing or if your breathing stops temporarily.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Some of these side effects may be serious.If you experience any of the side effects
listed below, your doctor may need to decide whether to stop the
treatment immediately:

Not known(the frequency cannot be estimated from the available data):
severe blood vessel problems causing a sudden drop in blood pressure, paleness,
restlessness, weak and rapid pulse, clammy skin and reduced level of consciousness);

• serotonin syndrome (a syndrome characterized by restlessness, hallucinations, coma, palpitations, fluctuating blood pressure, increased body temperature, increased response to stimuli, poor coordination, rigidity, nausea, vomiting and diarrhea).

Other side effects.If they become worse, tell your doctor or nurse.

Very common(may affect more than 1 in 10 people):

• nausea, vomiting;
• muscle stiffness.

Common(may affect up to 1 in 10 people):

• involuntary movements, drowsiness, dizziness;
• visual disturbances;
• slow heartbeat, fast heartbeat, heart rhythm disturbances;
• decreased blood pressure, increased blood pressure, pain in the vein;
• spasms of the vocal cords, shortness of breath due to spasms of the airway muscles, weak or interrupted breathing;
• allergic skin inflammation;
• confusion after surgery, nervous system problems due to anesthesia.

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

• agitation or euphoric mood;
• headache;
• superficial vein inflammation, blood pressure fluctuations;
• hyperventilation, hiccups;
• shivering, low body temperature;
• airway problems due to anesthesia, agitation after surgery, complications resulting from surgery.

Not known(the frequency cannot be estimated from the available data):

• hypersensitivity (including skin rash with severe itching and hives; a severe hypersensitivity to the substances contained in this medicine could cause a serious reaction in which blood vessels suddenly become very large, causing a drop in blood pressure and a fast but weak heartbeat, paleness, restlessness and clammy skin);
• delirium (symptoms may include a combination of agitation, restlessness, disorientation, confusion, fear, seeing or hearing things that are not actually there, sleep disturbances, nightmares);
• seizure (convulsion), loss of consciousness, sudden muscle contraction (myoclonus);
• cardiac arrest;
• reduction in strength, depth and frequency of breathing;
• itching;
• symptoms of withdrawal syndrome (which may manifest with the following side effects: nausea, vomiting, diarrhea, anxiety, shivering, tremor and sweating).

Cases of serotonin syndrome have been reported when fentanyl was used with certain
medicines for depression (see section “Other medicines and Fentanil Kalceks”).

Reporting of side effects
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through
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 Fentanil Kalceks

Keep this medicine out of the sight and reach of children.
Store in the original packaging to protect the medicine from light. Do not freeze.
Do not use this medicine after the expiry date which is stated on the outer packaging or on the vial
after “Exp”. The expiry date refers to the last day of that month.
Do not dispose of any medicine in 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 Fentanil Kalceks contains

• The active ingredient is fentanyl (as fentanyl citrate). Each ml of solution contains 50 micrograms of fentanyl (as fentanyl citrate). Each 2 ml vial contains 100 micrograms of fentanyl (as fentanyl citrate). Each 10 ml vial contains 500 micrograms of fentanyl (as fentanyl citrate).
• The other ingredients are: sodium chloride, sodium hydroxide (for pH adjustment), water for injections. This medicine does not contain preservatives.

Description of the appearance of Fentanil Kalceks and contents of the pack
Clear and colourless solution for injection, free from visible particles.
10 glass vials of 2 ml
10 glass vials of 10 ml
Not all pack sizes may be marketed.

Marketing Authorisation Holder
AS KALCEKS
Krustpils iela 53, Rīga, LV-1057, Latvia
Tel.: +371 67083320
E-mail: [email protected]

Manufacturer
AS KALCEKS
Krustpils iela 71E, Rīga, LV-1057, Latvia

This medicinal product is authorised in the Member States of the European Economic Area with the
following denominations:
Netherlands Fentanyl Kalceks 50 microgram/ml solution for injection
Austria Fentanyl Kalceks 50 Mikrogramm/ml Injektionslösung
Bulgaria Fentanyl Kalceks 50 микрограма/ml инжекционен разтвор
Croatia Fentanil Kalceks
Denmark Fentanyl Kalceks
Estonia Fentanyl Kalceks
Finland Fentanyl Kalceks
Germany Fentanyl Kalceks 50 Mikrogramm/ml Injektionslösung
Greece FENTANYL/KALCEKS
Hungary Fentanyl Kalceks 50 mikrogramm/ml oldatos injekció
Ireland Fentanyl 50 micrograms/ml solution for injection
Italy Fentanil Kalceks
Norway Fentanyl Kalceks
Romania Fentanil Kalceks 50 micrograme/ml soluţie injectabilă
Slovakia Fentanyl Kalceks 50 mikrogramov/ml injekčný roztok
Slovenia Fentanil Kalceks 50 mikrogramov/ml raztopina za injiciranje
Spain Fentanyl Kalceks 50 microgramos/ml solución inyectable
Sweden Fentanyl Kalceks
United Kingdom Fentanyl 50 micrograms/ml solution for injection
 ------------------------------------------------------------------------------------------------------------------------
The following information is intended for healthcare professionals:
For a complete description and additional information, see the Summary of Product Characteristics (SmPC).

Therapeutic indications
Fentanil Kalceks 50 micrograms/ml is an anaesthetic analgesic:

• for use as an opioid analgesic adjunct in general or local anaesthesia;
• to be administered with a neuroleptic.

Posology and method of administration
Fentanil Kalceks 50 micrograms/ml may only be administered in an environment that allows monitoring of the airways and with personnel capable of doing so (see section 4.4 of the SmPC).
The dosage of Fentanil Kalceks 50 micrograms/ml must be individualised based on age, body weight, physical condition, underlying disease, medications used and the type of surgical and anaesthetic procedure.

Adults
At induction, generally 200 to 600 micrograms (2.8 to 8.5 micrograms/kg), corresponding to 4-12 ml, are injected intravenously. Doses greater than 200 micrograms must be administered only with ventilation. For maintenance of analgesia, additional intravenous doses of 50 to 200 micrograms (0.7-2.8 micrograms/kg), corresponding to 1-4 ml, may be administered after 30-45 minutes.

Paediatric population

Adolescents aged between 12 and 17 years
Follow the dosage for adults.

Children aged between 2 and 11 years
For induction in children, a dose of 1.25-2.5 micrograms/kg or 0.25-0.5 ml per 10 kg of body weight is generally recommended. For maintenance of analgesia, additional intravenous doses of 0.25 ml per 10 kg may be administered every 30-45 minutes.

Children under 2 years of age
There is no experience with the use of fentanyl in children under 2 years of age.

Use in children
In children with spontaneous breathing, analgesia techniques may only be used within the context of an anaesthesia or sedation/analgesia performed by experienced personnel, in an environment that allows treatment of sudden episodes of muscle rigidity (requiring intubation) or apnoea (requiring ventilation) (see section 4.4 of the SmPC).

Use in the elderly
As with other opioids, the loading dose for elderly (>65 years) and debilitated patients should be reduced. When determining additional doses, the effect of the initial dosage should be taken into consideration.

Use in patients with renal impairment
In patients with renal impairment, a reduction in the dose of Fentanil Kalceks 50 micrograms/ml should be considered and patients should be closely monitored for signs of fentanyl toxicity (see section 5.2 of the SmPC).

Use in obese patients
In obese patients, there is a risk of overdose if the dose is calculated on the basis of body weight. The dose for obese patients (BMI > 30 kg/m²) should be established on the basis of estimated lean body mass rather than solely on body weight. Further titrations should be carried out with caution, based on effect (see section 5.2 of the SmPC).
Method of administration
Administer slowly – over 1-2 minutes – intravenously.

Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in section 6 or to other opioids.
• Poor pulmonary function without mechanical ventilation. This is due to the specific respiratory depression effect of morphinomimetic agents.

Special warnings and precautions for use

• Fentanil can only be administered in an environment that allows monitoring of the airways and with personnel capable of monitoring the airways.
• Like all potent opioids, fentanyl can produce respiratory depression to a degree related to the dose. Administering doses greater than 200 micrograms of fentanyl (4 ml) will result in significant respiratory depression. This effect can be reversed with naloxone, a specific opioid antagonist. Repeated administration of the opioid antagonist may be necessary as the duration of respiratory depression may be longer than the duration of action of the opioid antagonist. Deep analgesia is accompanied by manifest respiratory depression, which may persist or recur in the postoperative period. It is therefore important that patients are kept under adequate observation. Resuscitation equipment and opioid antagonists must be immediately available. Hyperventilation during anaesthesia may alter the patient's response to CO₂ and may therefore affect breathing even after surgery.
• Muscle rigidity can develop, which can also cause respiratory depression. Its incidence can be reduced by performing slow intravenous injections (this measure is normally sufficient for low doses). The reaction can be treated with artificial ventilation, premedication with benzodiazepines and, if necessary, administration of a muscle relaxant.
• When administering fentanyl, the possibility of anaphylactic reactions should be considered.
• Non-epileptic myoclonic reactions may occur.
• If an insufficient amount of anticholinergic agent is administered or if Fentanil Kalceks 50 micrograms/ml is combined with non-depolarising muscle relaxants, bradycardia and cardiac arrest may occur. Bradycardia can be treated with atropine.
• Opioids can cause hypotension, especially in hypovolaemic patients. Appropriate measures should be taken to maintain stable blood pressure.
• The use of rapid opioid bolus injections should be avoided. In patients with impaired intracranial compliance, a temporary reduction in mean arterial pressure is sometimes accompanied by a short-term reduction in perfusion pressure.
• Patients undergoing chronic opioid treatment, or who are opioid-dependent, may require higher doses.
• In elderly and debilitated patients, a dose reduction is recommended. Opioids should be titrated carefully in patients who present with one or more of the following underlying conditions: uncontrolled hypothyroidism, pneumopathy, impaired pulmonary function or alcoholism. Caution should be exercised in patients with hepatic dysfunction due to possible impairment of metabolism. Patients with renal impairment should be monitored carefully for signs of fentanyl toxicity. As a result of dialysis, the volume of distribution of fentanyl may vary, which may affect serum concentrations. These patients should be observed for a longer period in the postoperative period.
• When Fentanil Kalceks 50 micrograms/ml is administered together with neuroleptics, the operator must be familiar with the specific properties of both agents, in particular the differences in duration of action. The risk of hypotension is greater when this combination is administered. Neuroleptics can cause extrapyramidal symptoms that can be counteracted with antiparkinsonian agents. The combination with antiparkinsonian agents may increase the risk of tardive dyskinesia.
• As with other opioids, due to anticholinergic effects, the administration of fentanyl may lead to an increase in pressure in the biliary tract and occasionally spasms of the sphincter of Oddi may be observed.
• In patients with myasthenia gravis, the use of certain anticholinergic and neuromuscular blocking agents should be carefully evaluated before and during the administration of an anaesthetic regimen involving the intravenous use of fentanyl.
• Caution is advised if Fentanil Kalceks 50 micrograms/ml is administered concomitantly with medicines that affect the serotoninergic neurotransmitter systems. Concomitant use of serotonergic medicines, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), and medicines that inhibit the degradation of serotonin (including monoamine oxidase inhibitors [MAO inhibitors]) may cause a potentially life-threatening serotonin syndrome. This may occur with the recommended dose.

The serotonin syndrome may include alterations in mental status (e.g. agitation, hallucinations, coma), autonomic instability (e.g. tachycardia, labile blood pressure, hyperthermia), neuromuscular abnormalities (e.g. hyperreflexia, poor coordination, rigidity) and/or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea).
If serotonin syndrome is suspected, rapid discontinuation of Fentanil Kalceks 50 micrograms/ml should be considered.
Drug dependence and potential for abuse
Repeated administration of opioids can lead to tolerance, physical dependence and psychological dependence. The risks are greater in patients with a personal history of substance abuse (including drug or alcohol abuse or dependence).
Withdrawal syndrome
Repeated administration at short intervals for prolonged periods may lead to the development of a withdrawal syndrome upon cessation of therapy, which may manifest with the appearance of the following adverse effects: nausea, vomiting, diarrhoea, anxiety, chills, tremor and sweating.
Paediatric population
In children with spontaneous breathing, analgesia techniques may only be used within the context of an anaesthesia or sedation/analgesia performed by experienced personnel, in an environment that allows treatment of sudden episodes of muscle rigidity (requiring intubation) or apnoea (requiring ventilation).

Excipients
This medicine contains:
7.08 mg of sodium per 2 ml vial, i.e. is essentially “sodium-free”.
35.41 mg of sodium per 10 ml vial equivalent to 1.78% of the recommended daily intake by the WHO which corresponds to 2 g of sodium for an adult.

Interactions with other medicines and other forms of interaction

Effect of other agents on fentanyl

MAO inhibitors and other serotonergic medicines
The concomitant administration of fentanyl and MAO inhibitors may cause paroxysmal stimulation
of the central nervous system (CNS) and hypertension. Concomitant administration should be avoided and, when
possible, treatment with MAO inhibitors should be discontinued for at least 2 weeks before
initiating treatment with Fentanil Kalceks 50 micrograms/ml.
The concomitant administration of fentanyl with a serotonergic agent, such as an SSRI or an
SNRI, or an MAO inhibitor, may increase the risk of serotonin syndrome, a potentially life-threatening condition.
If the concomitant use of Fentanil Kalceks 50 micrograms/ml with SSRIs, SNRIs or MAO inhibitors is
unavoidable, the patient should be monitored for symptoms of serotonin syndrome during
concomitant use.
Agents such as barbiturates, benzodiazepines, neuroleptics, halogenated gases or other agents that exert
a non-selective depressive effect on the central nervous system (including alcohol) may
exacerbate the respiratory depression caused by opioids. In patients who have received these
agents, the dose of fentanyl required may be lower than usual.
Fentanyl, an agent with high clearance, is rapidly and extensively metabolized by
CYP3A4. Oral administration of 200 mg of itraconazole (a potent CYP3A4 inhibitor) per
day for 4 days did not determine any significant effect on the pharmacokinetics of fentanyl
administered intravenously. Oral administration of ritonavir (one of the most potent CYP3A4 inhibitors)
reduced the clearance of fentanyl administered intravenously by two-thirds; however, a single dose of fentanyl intravenously did not have effects on plasma concentrations.
The concomitant administration of fluconazole or voriconazole and fentanyl may increase
exposure to fentanyl by approximately 25-40%. During concomitant use of fluconazole or voriconazole and
fentanyl, patients should be carefully monitored, adjusting the dose of fentanyl as
needed.
When fentanyl is administered in a single dose, special attention and
observation of patients are required when using potent CYP3A4 inhibitors such as
ritonavir.

Inducers of cytochrome P450 3A4 (CYP3A4)
Injection of fentanyl together with strong CYP3A4 inducers (e.g. carbamazepine, phenytoin) may
reduce plasma concentrations of fentanyl, consequently decreasing its efficacy. If
fentanyl is used in conjunction with a strong CYP3A4 inducer, patients should be
carefully monitored for evidence of a reduction in analgesic effects. If necessary,
an increase in the dose of fentanyl should also be considered.

Effects of fentanyl on other agents
The concomitant use of other medicines with a depressive effect on the central nervous system,
including opioids, sedatives, hypnotics, general anesthetic agents, phenothiazines, tranquilizers,
muscle relaxants, sedative antihistamines and alcoholic beverages, may have an additive depressive effect; in
these cases, hypoventilation, hypotension and deep sedation or coma may occur. The concomitant use of fentanyl with any of the agents mentioned above therefore requires special attention and
observation of patients.
During concomitant use with fentanyl, plasma concentrations of etomidate increase
considerably (by a factor of 2-3). During concomitant use, the total plasma clearance and
volume of distribution of etomidate decreased by a factor of 2-3 without alterations
of the half-life.
The concomitant administration of fentanyl and midazolam intravenously results in an increase
in the terminal plasma half-life and a reduction in the plasma clearance of midazolam.
Exposure to midazolam is increased by approximately 50%. The mechanism of interaction is
competitive inhibition of CYP3A4 (see paragraph 5.2 of the SmPC). When midazolam is
administered concomitantly with fentanyl, it may be necessary to reduce the dose of midazolam.

Incompatibilities
This medicine must not be mixed with other medicines.

Special precautions for disposal and handling
Single use only. If only partially used, discard the remaining solution.
Use hand protection when handling the vial.
Instructions for opening the vial:

• 1) Position the vial with the colored point facing upwards. If there is solution in the upper part of the vial, gently tap with your finger to make all the solution descend to the lower part.
• 2) Use both hands to open; holding the lower part of the vial with one hand, detach the upper part with the other in the direction opposite the colored point (see the following images).

Unused medicine and waste derived from such medicine must be disposed of in accordance with
current local regulations.