Ketamine Molteni

Package leaflet: Information for the patient

KETAMINE MOLTENI 50 mg/ml injection solution

Ketamine hydrochloride
Generic medicine
Read all of this leaflet carefully before you take 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 nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

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

1. What Ketamina Molteni is and what it is used for

Ketamina Molteni contains the active substance ketamine hydrochloride, which belongs to a group
of medicines called general anaesthetics, used to induce sleep before a surgical procedure.
Ketamina Molteni is indicated as an anaesthetic in the following cases:

• used alone for short surgical procedures and for complex medical examinations;
• in combination with other general anaesthetics;
• prior to administering other general anaesthetics.

2. What you need to know before using Ketamina Molteni

Do not use Ketamina Molteni if:

• you are allergic to ketamine hydrochloride or to any of the other ingredients of this medicine (listed in section 6);
• you are in a physical condition where an increase in blood pressure could be dangerous;
• you have had a pregnancy complicated by a disorder called eclampsia or pre-eclampsia, which causes high blood pressure;
• you suffer from severe disorders of blood circulation in the brain (cerebrovascular disorders) or have had head trauma;
• you suffer from serious heart problems (myocardial disorders, severe heart failure);
• you are pregnant (See section “Pregnancy and breastfeeding”).

Warnings and precautions
Talk to your doctor or nurse before being administered Ketamina Molteni.
This medicine must be administered under the close supervision of a specialist doctor experienced in the use of general anaesthetics, in a properly equipped specialized centre.
Before being administered this medicine, inform your doctor if:

• you are taking medicines that induce sleep (barbiturates, narcotics), as this may prolong your recovery time (See section “Other medicines and Ketamina Molteni”);
• you have a history of drug abuse or dependence, because ketamine is a medicine with potential for abuse. If used daily for a few weeks, it may cause confusion, anxiety, depression, insomnia, hallucinations, flashbacks, and dependence and tolerance may develop. For this reason, it must be used with caution and under close medical supervision;
• you suffer from chest pain due to heart problems (unstable angina) or have recently had a heart attack (myocardial infarction);
• you suffer from high blood pressure (hypertension), rapid heartbeat (tachycardia), or heart function problems (heart failure);
• you suffer from increased pressure inside the brain (intracranial hypertension, hydrocephalus) or have had brain trauma;
• you drink or have drunk large amounts of alcohol (chronic or acute alcoholism);
• you suffer from eye problems (glaucoma, perforating eye injuries);
• you suffer from mental disorders (schizophrenia, acute psychosis or neurotic disorders);
• you suffer from liver problems (liver failure, cirrhosis);
• you suffer from acute intermittent porphyria, a genetic disease;
• you have experienced seizures;
• you suffer from thyroid problems (hyperthyroidism) or are taking thyroid hormones;
• you suffer from lung or bronchial problems.

During the recovery phase from anaesthesia, you may experience excitatory reactions and agitation with hallucinations and/or delirium. If necessary, your doctor may administer medicines to reduce these agitated states (diazepam, droperidol, thiobarbiturate) (See section “Possible side effects”).
If you have undergone surgery in an outpatient hospital setting but have not been admitted (hospitalized), you will be kept under observation until you have fully recovered from anaesthesia and must be accompanied home by a responsible adult.
Other medicines and Ketamina Molteni
Inform your doctor if you are taking, have recently taken, or might take any other medicines, including over-the-counter medicines, because Ketamina Molteni may affect how some medicines work, or other medicines may affect how Ketamina Molteni works.
Ketamina Molteni should be administered with caution if you are taking the following medicines:

• medicines that slow down brain activity (barbiturates, narcotics, benzodiazepines), as concomitant use of Ketamina Molteni may delay awakening from anaesthesia. In addition, benzodiazepines such as diazepam may increase ketamine blood levels;
• diazepam (a medicine with calming, sedative, muscle-relaxant and anticonvulsant effects);
• medicines used to induce general anaesthesia, such as halothane and enflurane, because they may reduce heart activity. Moreover, halothane may affect the effects and liver metabolism of ketamine;
• medicines and substances that reduce nervous system activity (central nervous system depressants such as phenothiazines, sedative antihistamines, muscle relaxants, alcohol);
• thyroid hormones, because concomitant use with Ketamina Molteni may cause an increase in blood pressure (hypertension) and heart rate (tachycardia);
• theophylline and aminophylline, used to treat asthma, because concomitant use increases the risk of seizures;
• certain medicines that relax (gallamine and pancuronium, atracurium) or block (tubocurarine) muscles;
• medicines that lower blood pressure (antihypertensives);
• sympathomimetic medicines and vasopressin;
• ergometrine (a vasoconstrictor).

Use of Ketamina Molteni with food and drink
You are advised not to eat or drink for at least 6 hours before anaesthesia.
KETAMINA MOLTENI is usually administered on an empty stomach. However, KETAMINA MOLTENI may still be used in emergency situations when this is not possible.
Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or nurse before being administered this medicine.
Pregnancy
Ketamine readily crosses the placental barrier: cases of newborns with breathing difficulties and low Apgar scores requiring resuscitation have been reported after the mother received ketamine during delivery.
High doses of ketamine have caused increased blood pressure and uterine tone in the mother. The safety of ketamine use during pregnancy has not been established; therefore, its use is not recommended.
Breastfeeding
The safety of ketamine use during breastfeeding has not been established; therefore, its use is not recommended.
Driving and using machines
This medicine may affect your level of consciousness; therefore, avoid driving or operating machinery for 24 hours after the procedure.
Your doctor will advise you when you can resume driving or operating machinery.

3. How to use Ketamina Molteni

This medicine will be administered to you in a hospital setting by specialized healthcare personnel. If you have any doubts, consult your doctor or nurse.

Ketamina Molteni may be administered:

• on an empty stomach, when used in combination with other medicines to induce anaesthesia. Therefore, it is recommended not to eat food or drink liquids at least 6 hours before the procedure.
• with food in the stomach, when used as the sole anaesthetic.

Your doctor will administer Ketamina Molteni to you via a very slow injection into a muscle (intramuscularly) or into a vein (intravenously), as rapid administration may cause breathing problems (respiratory depression, apnoea) or changes in blood pressure. The doctor will determine the appropriate dose of ketamine for you.

The dose depends on the type of procedure, and other factors such as, for example, your health status, age and weight. In any case, the lowest possible effective dose will be administered.

If used in combination with other anaesthetics, your doctor may reduce the dose of Ketamina Molteni.

If you use more Ketamina Molteni than you should

Since this medicine will be administered by specialized personnel, overdose is unlikely. However, if an excessive amount of this medicine is administered, you may experience slowed breathing (respiratory depression).

If you are concerned that you may have received a higher-than-intended dose, inform your doctor or nurse immediately.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The following side effects may occur:

Common (may affect up to 1 in 10 people)

• increased blood pressure (hypertension);
• increased heart rate (tachycardia);
• hallucinations, nightmares and unusual dreams, confusion, agitation and abnormal behaviour;
• involuntary eye movements (nystagmus), increased muscle tone (hypertonia), increased muscle tone and contractions (tonic-clonic movements);
• double vision (diplopia);
• increased respiratory rate;
• nausea, vomiting;
• skin irritations (erythema, morbilliform rash).

Uncommon (may affect up to 1 in 100 people)

• loss of appetite (anorexia);
• anxiety;
• low blood pressure (hypotension), reduced heart rate (bradycardia), irregular heart rhythm (arrhythmia);
• increased oxygen consumption;
• breathing difficulties (laryngospasm), slowed breathing (respiratory depression);
• pain and irritation of the skin at the injection site.

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

• cardiac arrest;
• severe allergic reaction (anaphylactic reaction);
• delirium, recurrent hallucinations (flashbacks), depression (dysphoria);
• insomnia;
• disorientation;
• respiratory tract disorders, lack of air (apnoea);
• increased saliva production (hypersalivation);
• cystitis and haemorrhagic cystitis.

Side effects of unknown frequency

• increased eye pressure;
• abnormal results in blood tests (liver function tests), liver damage with prolonged use (more than 3 days) and drug abuse.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, tell your doctor 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 Ketamina Molteni

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.
This medicine does not require any special storage conditions.
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 Ketamina Molteni contains

• The active substance is ketamine hydrochloride. 1 ml of injectable solution contains 57.67 mg of ketamine hydrochloride (equivalent to 50 mg of ketamine base).
• The other component is water for injections.

Description of the appearance of Ketamina Molteni and contents of the pack
Pack of 5 vials with 2 ml each.
Marketing Authorization Holder and Manufacturer
L. Molteni & C. dei F.lli Alitti Società di Esercizio S.p.A. – Strada Statale 67 Fraz. Granatieri –
Scandicci (FI) – Italy

Package leaflet: information for the doctor

KETAMINA MOLTENI 50 mg/ml injectable solution

Ketamine hydrochloride
Equivalent medicinal product
The following information is intended exclusively for physicians or healthcare professionals
CLINICAL INFORMATION
Specific fields of application or types of procedures

1. Debridement, painful dressings, skin grafting in burn patients, and other superficial surgical procedures.
2. Neurodiagnostic procedures such as pneumoencephalography, ventriculography, myelography, and lumbar punctures.
3. Diagnostic and surgical procedures on the eye, ear, nose, and mouth, including dental extractions. Warning: eye movements may persist during ophthalmological procedures.
4. Diagnostic and surgical procedures on the pharynx, larynx, and bronchial tree. Warning: the use of muscle relaxants is recommended for these procedures (see Special Warnings and Precautions for Use).
5. Sigmoidoscopies and minor surgery of the anus and rectum, circumcision.
6. Extraperitoneal gynecological procedures such as dilation and curettage.
7. Obstetric procedures including dystocic deliveries and cesarean sections.
8. Orthopedic procedures such as closed reductions, femoral nailing, amputations, and biopsies.
9. Anesthesia in patients at high surgical risk with depression of vital functions.
10. Cardiac catheterization.
11. When the intramuscular route is preferred.

Dosage and method of administration
Preoperative preparation
Ketamine has been used alone without complications even with a full stomach, and its use is recommended in non-fasting patients when the anesthetist judges that the benefits of the drug outweigh the possible disadvantages (although vomiting has been reported after ketamine administration, airway protection is generally ensured by the presence of pharyngo-laryngeal reflexes).
However, since it cannot be predicted whether other anesthetics and muscle relaxants will need to be administered, it is advisable during preoperative preparation to withhold oral intake for at least 6 hours before the procedure.
Atropine, scopolamine, or other antisecretory agents should be administered at an appropriate dose before induction.
Administration of Droperidol (0.1 mg/kg intramuscularly) or the use of short-acting benzodiazepines has proven to be an effective premedication to reduce the frequency of emergence reactions.

Onset and duration of anesthesia
As with other general anesthetics, individual response to Ketamina Molteni varies depending on the dose, route of administration, patient age, and concomitant use of other drugs; therefore, fixed dosing regimens cannot be established.
The drug must be dosed according to the needs of each individual case.
Due to the rapid onset after intravenous injection, the patient must be in an appropriate position during administration. An intravenous dose of 2 mg/kg usually induces surgical anesthesia within 30 seconds after injection, and the anesthetic effect generally lasts for 5–10 minutes. A dose of 10 mg/kg administered intramuscularly usually induces surgical anesthesia within 3–4 minutes after injection, and the anesthetic effect lasts for 12–25 minutes. Recovery of consciousness is gradual.

• As a sole anesthetic for surgical and diagnostic procedures

Induction of anesthesia
Intravenous route: the initial dose of Ketamina Molteni may range from 1 mg/kg to 4.5 mg/kg of ketamine base. The average dose required to achieve 5–10 minutes of surgical anesthesia is 2 mg/kg.
Slow intravenous injection (over more than 60 seconds) is recommended. More rapid administration may lead to respiratory depression and a more pronounced pressor response.
Intramuscular route: the initial dose of Ketamina Molteni may range from 6.5 to 13 mg/kg in terms of ketamine base. A dose of 10 mg/kg generally produces 12–25 minutes of surgical anesthesia.

Maintenance of anesthesia
Lightening of anesthesia may manifest as nystagmus, movement in response to stimulation, or vocalization. Anesthesia is maintained by administering additional doses of Ketamina Molteni intravenously or intramuscularly, regardless of the route used for induction. If the intravenous route is chosen for maintenance, each additional dose may range from half to the full intravenous dose previously indicated. If the intramuscular route is chosen for maintenance, each additional dose may range from half to the full intramuscular dose previously indicated. The greater the total dose administered, the longer the time required for complete recovery. During anesthesia, irrational and tonic-clonic movements may occur. These movements do not indicate a light plane of anesthesia and do not require an additional dose of anesthetic.

• To induce anesthesia prior to administration of other general anesthetics
  Induction is achieved with a full intravenous or intramuscular dose of Ketamina Molteni as described above, followed by administration of the primary anesthetic. The timing of administration of the primary anesthetic depends on the route of administration of Ketamina Molteni and the time required for the primary anesthetic to exert its full effect. If Ketamina Molteni is administered intravenously and the primary anesthetic has a slow onset, a second dose of Ketamina Molteni may be required 5–8 minutes after the initial dose. If Ketamina Molteni is administered intramuscularly and the primary anesthetic has a rapid onset, administration of the primary anesthetic may be delayed up to 15 minutes after injection of Ketamina Molteni.

• As an adjunct to other anesthetics
  Ketamina Molteni is clinically compatible with commonly used anesthetics and local anesthetics, provided adequate respiratory function is maintained. The dose of Ketamina Molteni used in combination with other anesthetics falls within the same range as the induction dose specified above; however, the use of another anesthetic may allow for a reduction in the dose of Ketamina Molteni.
  For management of patients during emergence, see Special Warnings and Precautions for Use.

Special Warnings
General
KETAMINA MOLTENI must be administered under the supervision of physicians experienced in the administration of general anesthetics, maintenance of airway patency, and control of respiration. Resuscitation equipment must be available and functional, as with any other general anesthetic.
Intravenous injection must be performed slowly, over a period exceeding 60 seconds. More rapid administration may cause respiratory depression or apnea and a more pronounced pressor response.
In the literature, aspiration of contrast medium during ketamine anesthesia has been described; although this is extremely rare in clinical practice, this possibility should be considered.
Overdose of ketamine may cause respiratory depression, in which case assisted ventilation is required. Mechanical respiratory support is preferable to the use of analeptics in such cases.
KETAMINA MOLTENI must not be used alone for surgical or diagnostic procedures on the pharynx, larynx, or bronchial tree, as pharyngo-laryngeal reflexes generally remain intact.
When using only KETAMINA MOLTENI, mechanical stimulation of the pharynx should be avoided if possible.
In such cases, muscle relaxants may be necessary, with adequate respiratory control.
For surgical procedures involving visceral pain pathways, a drug effective against visceral pain should be co-administered.
KETAMINA MOLTENI must not be used as the sole anesthetic in obstetric procedures requiring uterine muscle relaxation.
If KETAMINA MOLTENI is used in hospital outpatient settings but in non-hospitalized patients, they must be retained until they have fully recovered from anesthesia and must be accompanied by a responsible adult.

Management of patients during emergence
Psychological reactions occur during emergence in approximately 12% of treated patients.
These reactions may vary in intensity, and patients may report a phase of excitation (postoperative agitation) characterized by hallucinations, delirium, vivid dreams (pleasant or unpleasant), with or without psychomotor activity, manifesting as confusion and irrational behavior, and may be remembered by some patients as an unpleasant experience. These reactions are similar to those observed with other general anesthetics and usually resolve within a few hours, except in rare cases where they have occurred within 24 hours. There is no evidence that ketamine use causes long-term psychological sequelae.
The frequency of these reactions is minimal in young patients (15 years or younger) and elderly patients (over 65 years). Furthermore, they are less frequent when the drug is administered intramuscularly. The frequency of emergence psychological reactions, particularly those related to dreams and delirium, can be reduced by using low doses of ketamine in combination with intravenous diazepam during induction and maintenance of anesthesia. In addition, the frequency of such reactions may be decreased by minimizing tactile, verbal, and visual stimulation of the patient.
After the procedure, the patient should be monitored but left undisturbed. This does not preclude monitoring of vital signs.
If the patient exhibits symptoms of agitation during emergence, consider administering one of the following drugs: Diazepam (5–10 mg intravenously in adults), or Droperidol (2.5–7.5 mg intravenously or intramuscularly). To terminate a severe emergence reaction, a hypnotic dose of a thiobarbiturate (50–100 mg intravenously) may be used.
When these drugs are used, the emergence period may be prolonged.

Cardiovascular
KETAMINA MOLTENI must be used with caution in patients with hypovolemia, dehydration, cardiac disorders, particularly in patients with coronary disease (congestive heart failure, myocardial ischemia, and myocardial infarction), because ketamine causes a significant increase in myocardial oxygen consumption. Additionally, ketamine must be used with caution in patients with tachyarrhythmias and mild to moderate hypertension.
In patients with cardiac decompensation or hypertension, cardiac function must be monitored throughout the procedure.
Shortly after administration of KETAMINA MOLTENI, there will be an increase in arterial pressure, peaking within a few minutes and usually returning to pre-anesthetic values within 15 minutes. In clinical studies, the mean change in systolic arterial pressure ranged between 20% and 25% above pre-anesthetic values.
Depending on the patient's condition, this increase in arterial pressure may be considered beneficial in some cases or an adverse reaction in others.

Incompatibilities
Ketamine is incompatible with soluble barbiturates.
Barbiturates and KETAMINA MOLTENI must not be injected in the same syringe because they are chemically incompatible and form a precipitate.
Ketamine and diazepam must not be mixed in the same syringe or infusion container. If diazepam is to be used to supplement the dose of ketamine, the two drugs must be administered separately.

Special precautions for disposal and handling
Vials are for single use only: any remaining solution must not be reused.
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.