TAFLOTAN

INSTRUCTIONS FOR MEDICAL USE OF OXYCODONE KALCEKS (OXYCODONE KALCEKS)

Composition

active substance: oxycodone; 1 ml of solution (1 ampoule) contains 10 mg of oxycodone hydrochloride; 2 ml of solution (1 ampoule) contains 20 mg of oxycodone hydrochloride; 1 ml of solution (1 ampoule) contains 50 mg of oxycodone hydrochloride; excipients: monohydrate citric acid, sodium citrate, sodium chloride, hydrochloric acid, sodium hydroxide, water for injection.

Pharmaceutical Form

Solution for injection.

Main Physical and Chemical Properties

Transparent colorless solution.

Pharmacotherapeutic Group

Analgesics. Opioids. Natural opium alkaloids. Oxycodone. ATC Code N02A A05.

Pharmacological Properties

Pharmacodynamics

Oxycodone is an opioid agonist without antagonist properties. It has an affinity for kappa-, mu-, and delta-opioid receptors in the brain and spinal cord. Oxycodone is similar to morphine in its action. The therapeutic effect is mainly analgesic, anxiolytic, antitussive, and sedative. In the gastrointestinal tract, opioids can cause sphincter of Oddi spasm.

Pharmacokinetics

Absorption Pharmacokinetic studies in healthy subjects have demonstrated equivalent bioavailability of oxycodone when administered at a dose of 5 mg intravenously and subcutaneously, as a single bolus dose or as a continuous infusion over 8 hours.

In female subjects, the concentration of oxycodone in plasma is on average 25% higher than in men, taking into account body weight.

Distribution

After absorption, oxycodone is distributed throughout the body. Approximately 45% is bound to plasma proteins. The drug crosses the placenta and is found in breast milk.

Metabolism and Elimination

Oxycodone is metabolized in the liver to form noroxycodone, oxymorphone, and various glucuronide conjugates. The analgesic effect of metabolites is clinically insignificant. The active substance and its metabolites are excreted in urine and feces.

Special Patient Groups

Elderly Patients

The concentration of oxycodone in plasma is minimally dependent on age; it is 15% higher in elderly patients compared to young patients.

Patients with Hepatic and Renal Impairment

Compared to patients with normal liver function, patients with mild or severe liver function impairment may have higher concentrations of oxycodone and noroxycodone in plasma and lower concentrations of oxymorphone in plasma. Possible increase in the half-life of oxycodone, which may be accompanied by an increase in the effect of the drug.

Compared to patients with normal kidney function, patients with renal dysfunction from mild to severe may have higher concentrations of oxycodone and its metabolites in plasma. Possible increase in the half-life of oxycodone, which may be accompanied by an increase in the effect of the drug.

Clinical Characteristics

Indications

For the treatment of moderate or severe pain in cancer patients or in the postoperative period.

For the treatment of severe pain that requires the use of a strong opioid.

Oxycodone Kalceks should only be used in adults.

Contraindications

Increased sensitivity to the active substance or to any of the excipients of the drug.

Oxycodone should not be used in any situations where opioids are contraindicated:

• known sensitivity to morphine or other opioids;
• severe respiratory depression with hypoxia;
• severe chronic obstructive pulmonary disease;
• pulmonary heart (cor pulmonale);
• severe bronchial asthma;
• increased carbon dioxide level in the blood;
• paralytic intestinal obstruction;
• acute abdomen;
• liver failure of moderate or severe degree;
• chronic constipation.

Interaction with Other Medicinal Products and Other Types of Interactions

Concomitant use of sedative drugs, such as benzodiazepines or related compounds, with opioids increases the risk of sedation, respiratory depression, coma, and lethal outcome due to the additive depressive effect on the CNS. Dosing and duration of concomitant use should be limited (see "Special Instructions").

Drugs that affect the CNS include, but are not limited to, tranquilizers, anesthetics, sleeping pills, antidepressants, non-benzodiazepine sedatives, phenothiazines, antipsychotic drugs, alcohol, other opioids, muscle relaxants, and antihypertensive drugs.

Anticholinergic Drugs

Concomitant use of oxycodone with anticholinergic drugs or drugs with anticholinergic activity (e.g., tricyclic antidepressants, antihistamines, antipsychotic drugs, muscle relaxants, antiparkinsonian drugs) may lead to an increase in anticholinergic side effects. In patients taking these drugs, oxycodone should be used with caution and may require a dose reduction.

MAO Inhibitors

It is known that MAO inhibitors interact with narcotic analgesics. MAO inhibitors can cause CNS excitement or depression, associated with hypertensive or hypotensive crisis (see "Special Instructions"). Oxycodone should be used with caution in patients taking MAO inhibitors or who have received MAO inhibitors within the last 2 weeks (see "Special Instructions").

Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

Concomitant use of oxycodone with serotonergic agents, such as selective serotonin reuptake inhibitors (SSRIs) (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) or serotonin-norepinephrine reuptake inhibitors (SNRIs) (e.g., duloxetine, venlafaxine), may cause serotonin toxicity. Serotonin toxicity may manifest as changes in mental status (e.g., agitation, hallucinations, coma), instability of the autonomic nervous system (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular abnormalities (e.g., hyperreflexia, coordination disorders, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Oxycodone should be used with caution, and patients taking these medications may require a dose reduction.

Alcohol

Alcohol may enhance the pharmacodynamic effect of oxycodone; concomitant use should be avoided.

CYP3A4 Inhibitors

Oxycodone is metabolized mainly by CYP3A4 with the participation of CYP2D6. The activity of these metabolic pathways can be inhibited or induced by various medications or food ingredients administered together.

CYP3A4 inhibitors, such as macrolide antibiotics (e.g., clarithromycin, erythromycin, and telithromycin), antifungal agents of the azole group (e.g., ketoconazole, voriconazole, itraconazole, and posaconazole), protease inhibitors (e.g., boceprevir, ritonavir, and indinavir, nelfinavir, and saquinavir), cimetidine, and grapefruit juice may lead to a decrease in the clearance of oxycodone, which may result in an increase in the concentration of oxycodone in the blood plasma. Therefore, the dose of oxycodone may need to be adjusted accordingly.

CYP2D6 Inhibitors

Drugs that inhibit CYP2D6 activity, such as paroxetine and quinidine, may cause a decrease in the clearance of oxycodone, which may result in an increase in the concentration of oxycodone in the blood plasma.

Special Instructions

The main risk of opioid overdose is respiratory depression. Caution should be exercised when administering oxycodone to frail elderly patients, patients with severe respiratory dysfunction, patients with liver or kidney dysfunction, patients with mixedema, hypothyroidism, Addison's disease, toxic psychosis, prostatic hyperplasia, adrenocortical insufficiency, alcoholism, delirium tremens, biliary tract disease, pancreatitis, inflammatory bowel disease, hypotension, hypovolemia, increased intracranial pressure, head trauma (due to the risk of increased intracranial pressure), or patients taking benzodiazepines, other CNS depressants (including alcohol), or MAO inhibitors.

Risk of Concomitant Use of Sedative Drugs, such as Benzodiazepines or Related Compounds

Concomitant use of benzodiazepines and opioids may lead to sedation, respiratory depression, coma, and lethal outcome. Due to these risks, concomitant prescription of sedative drugs, such as benzodiazepines or related compounds, with opioids should be reserved for patients for whom alternative treatment options are not possible. If the decision is made to prescribe benzodiazepines concomitantly with opioids, the lowest effective dose should be used, and the duration of treatment should be as short as possible (see also "Method of Administration and Dosage"). Patients should be closely monitored for signs and symptoms of respiratory depression and sedation. In this regard, it is strongly recommended to inform patients and their surroundings about these symptoms (see "Interaction with Other Medicinal Products and Other Types of Interactions").

Surgical Procedures

Oxycodone should be used with caution before or during surgical procedures and during the first 12-24 hours after surgery.

As with all opioid preparations, caution should be exercised when using oxycodone after abdominal surgery, as opioids are known to impair intestinal motility and should not be used until the doctor is sure that intestinal function has normalized.

Non-Malignant Pain

For patients suffering from chronic non-malignant pain, opioids can be used as part of a comprehensive treatment program that includes other medications and methods of treatment, as appropriate. An important part of assessing the patient's condition with chronic non-malignant pain is the presence of a history of substance abuse in the patient's history.

If opioid treatment is considered suitable for the patient, the primary goal of treatment is not to minimize opioid doses but to achieve a dose that provides adequate pain relief with minimal side effects.

Endocrine System

Opioids can affect the hypothalamic-pituitary-adrenal axis and the gonads. Some visible changes include increased prolactin levels in serum and decreased cortisol and testosterone levels in plasma. These hormonal changes can manifest as clinical symptoms.

Sleep-Related Breathing Disorders

Opioids can cause sleep-related breathing disorders, including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent manner. In patients with CSA, it is necessary to consider reducing the total opioid dose.

Opioid-Related Disorders (Abuse and Dependence)

Repeated administration of opioids, such as oxycodone, can lead to tolerance and physical and/or psychological dependence.

Repeated use of Oxycodone Kalceks may lead to opioid-related disorders (ORD). Higher doses and longer treatment with opioids may increase the risk of developing ORD. Abuse or intentional misuse of Oxycodone Kalceks can lead to overdose and/or death. The risk of developing ORD is increased in patients with a history of substance abuse (including alcohol abuse) in their personal or family history, as well as in tobacco users or patients with a history of other mental health disorders (e.g., depression, anxiety, and personality disorders).

Before starting and during treatment with Oxycodone Kalceks, the treatment goals and plan for discontinuation of treatment should be agreed upon with the patient, according to pain treatment recommendations. During treatment, frequent contact between the doctor and the patient should be maintained to assess the need for continued treatment, consider discontinuation of treatment, and adjust the dosage as needed. If symptoms of ORD occur, patients should be advised to consult a doctor. Monitoring of patient behavior is necessary to detect signs of drug-seeking behavior (e.g., premature requests for retreatment). Such monitoring should include a review of concomitant opioids and psychoactive medications (e.g., benzodiazepines). For patients with symptoms and signs of ORD, it is recommended to consider consulting a narcology specialist.

Tolerance

In a patient, tolerance to the drug may develop with chronic use, and they may require progressively higher doses to maintain pain control. Long-term use of the drug can lead to physical dependence, and a withdrawal syndrome may occur when therapy is abruptly discontinued.

Withdrawal Syndrome

When a patient no longer needs treatment with oxycodone, it is advisable to gradually reduce the dose to prevent the occurrence of withdrawal symptoms. Opioid withdrawal or withdrawal syndrome is characterized by some or all of the following symptoms: anxiety, lacrimation, rhinorrhea, yawning, sweating, chills, muscle pain, mydriasis, and tachycardia. Other symptoms may also develop, including irritability, restlessness, back pain, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, as well as increased blood pressure, rapid breathing, or increased heart rate.

As with other opioids, newborns of dependent mothers may experience withdrawal symptoms and respiratory depression at birth.

Alcohol

Concomitant use of alcohol and oxycodone may increase the side effects of oxycodone; concomitant use should be avoided.

Hyperalgesia

Hyperalgesia may occur, in which there is no adequate response to further increases in oxycodone doses, especially when using high doses. It may be necessary to reduce the dose of oxycodone or switch to an alternative opioid.

Disorders of the Hepatobiliary System

Oxycodone may cause dysfunction and spasm of the sphincter of Oddi, thereby increasing intra-biliary pressure and increasing the risk of biliary tract symptoms and pancreatitis. Therefore, oxycodone should be prescribed to patients with pancreatitis and biliary tract disease with caution.

Other

Oxycodone should not be used if there is a risk of paralytic ileus. If paralytic ileus is suspected or occurs, the use of oxycodone should be discontinued immediately.

This medicinal product contains less than 1 mmol (23 mg) of sodium per 1 ml, i.e., it is essentially sodium-free.

Use During Pregnancy or Breastfeeding

Pregnancy

There are limited data on the use of oxycodone in pregnant women. Children born to mothers who received opioids during the last 3-4 weeks before delivery should be under close surveillance for respiratory depression. Withdrawal symptoms may be observed in newborns of mothers undergoing treatment with oxycodone.

No fertility or postnatal studies have been conducted. However, studies in rats and rabbits with oral doses of oxycodone equivalent to 3 and 47 times the adult dose of 160 mg/day, respectively, did not reveal evidence of harm to the fetus due to oxycodone. Injections of oxycodone are not recommended for use during pregnancy or childbirth.

Breastfeeding

Oxycodone may pass into breast milk and may cause respiratory depression in the newborn. Therefore, oxycodone should not be used in breastfeeding mothers.

Ability to Affect Reaction Speed When Driving or Operating Other Mechanisms

Oxycodone may impair the ability to drive a vehicle and operate machinery. Oxycodone may alter the reactions of patients to varying degrees depending on the dosage and individual sensitivity. Therefore, patients should not drive a vehicle or operate machinery if such an effect is observed.

Method of Administration and Dosage

Administered as an intravenous (IV) injection or infusion or subcutaneous (SC) injection or infusion.

The dose should be adjusted according to the severity of pain, the patient's overall condition, and previous or concomitant use of other medications.

Adults Aged 18 Years and Older

The recommended initial doses are listed below. Gradual dose escalation may be necessary if pain relief is inadequate or if pain worsens.

Oxycodone Kalceks 10 mg/ml:

• IV (bolus): dilute to 1 mg/ml in sodium chloride 9 mg/ml (0.9%) solution for injection, dextrose 50 mg/ml (5%) solution, or water for injection. Administer a bolus dose of 1-10 mg slowly over 1-2 minutes. Doses should be administered no more frequently than every 4 hours;
• IV (infusion): dilute to 1 mg/ml in sodium chloride 9 mg/ml (0.9%) solution for injection, dextrose 50 mg/ml (5%) solution, or water for injection.
• Recommended initial dose is 2 mg/hour;
• IV (patient-controlled analgesia - PCA): dilute to 1 mg/ml in sodium chloride 9 mg/ml (0.9%) solution for injection, dextrose 50 mg/ml (5%) solution, or water for injection.
• Bolus doses of 0.03 mg/kg should be administered, with intervals of at least 5 minutes between doses;
• SC (bolus): use at a concentration of 10 mg/ml. Recommended initial dose is 5 mg, repeated every 4 hours as needed;
• SC (infusion): if necessary, dilute in sodium chloride 9 mg/ml (0.9%) solution for injection, dextrose 50 mg/ml (5%) solution, or water for injection.
• Initial dose of 7.5 mg/day is recommended for patients who have not previously received opioids, gradually titrating the dose according to symptom control;
• Oncology patients who switch from oral oxycodone may require much higher doses (see below Conversion of Patients from Oral to Parenteral Oxycodone).

Oxycodone Kalceks 50 mg/ml:

• IV (bolus): dilute in sodium chloride 9 mg/ml (0.9%) solution for injection, dextrose 50 mg/ml (5%) solution, or water for injection. Administer a bolus dose of 1-10 mg slowly over 1-2 minutes to patients who have not previously received opioids. Doses should be administered no more frequently than every 4 hours;
• IV (infusion): dilute in sodium chloride 9 mg/ml (0.9%) solution for injection, dextrose 50 mg/ml (5%) solution, or water for injection.
• Recommended initial dose is 2 mg/hour for patients who have not previously received opioids;
• IV (patient-controlled analgesia - PCA): dilute in sodium chloride 9 mg/ml (0.9%) solution for injection, dextrose 50 mg/ml (5%) solution, or water for injection.
• Bolus doses of 0.03 mg/kg should be administered, with intervals of at least 5 minutes between doses, to patients who have not previously received opioids;
• SC (bolus): Oxycodone Kalceks 50 mg/ml should be diluted in sodium chloride 9 mg/ml (0.9%) solution for injection, dextrose 50 mg/ml (5%) solution, or water for injection. Recommended initial dose is 5 mg, repeated every 4 hours as needed, to patients who have not previously received opioids;
• SC (infusion): if necessary, dilute in sodium chloride 9 mg/ml (0.9%) solution for injection, dextrose 50 mg/ml (5%) solution, or water for injection.
• Initial dose of 7.5 mg/day is recommended for patients who have not previously received opioids, gradually titrating the dose according to symptom control;
• Oncology patients who switch from oral oxycodone may require much higher doses (see below Conversion of Patients from Oral to Parenteral Oxycodone).

Conversion of Patients from Oral to Parenteral Oxycodone

The dose should be based on the following ratio: 2 mg of oral oxycodone corresponds to 1 mg of parenteral oxycodone. It should be emphasized that this is only a guideline for the necessary dose. The variability between patients requires that the dose be carefully titrated for each patient. When switching opioid preparations, the patient should be under close surveillance until the condition stabilizes.

Elderly Patients

Elderly patients should be treated with caution. The lowest dose should be prescribed with careful titration to control pain.

Patients with Renal and Hepatic Impairment

When prescribing the initial dose, a conservative approach should be taken in these patients. The recommended initial dose for adults should be reduced by 50% (e.g., total daily dose of 10 mg orally in patients who have not received opioids), and each patient should have their dose adjusted to achieve adequate pain control according to their clinical situation (see "Pharmacokinetics").

Use in Non-Malignant Pain

Opioids are not first-line therapy for chronic non-malignant pain and are not recommended as the sole treatment. Types of chronic pain that have been shown to be alleviated by strong opioids include chronic osteoarthritic pain and intervertebral disc disease.

Treatment Goals and Discontinuation

Before starting treatment with Oxycodone Kalceks, the treatment strategy, including the duration of treatment and treatment goals, as well as the plan for discontinuation of treatment, should be agreed upon with the patient, according to pain treatment recommendations. During treatment, frequent contact between the doctor and the patient should be maintained to assess the need for continued treatment, consider discontinuation of treatment, and adjust the dosage as needed. When the patient no longer needs oxycodone therapy, it may be advisable to gradually reduce the dose to prevent the occurrence of withdrawal symptoms. If there is inadequate pain control, the possibility of hyperalgesia, tolerance, and progression of the underlying disease should be considered (see "Special Instructions").

Duration of Treatment

Oxycodone should not be used for longer than necessary.

How to Open the Ampoule

1) Turn the ampoule with the colored dot towards you. Gently tap the top of the ampoule with your finger to make the solution flow down to the bottom of the ampoule

2) Use both hands to open the ampoule: holding the bottom of the ampoule in one hand, use the other hand to press the top of the ampoule away from the colored dot

Cannot Use Solution Containing Visible Particles

Use immediately after opening the ampoule. Unused solution should be discarded.

Improper use of the undiluted solution after opening the original ampoule or the diluted solution may compromise the sterility of the product.

Children

There are no data on the use of oxycodone injections in patients under 18 years of age.

Overdose

Symptoms

Acute overdose of oxycodone may manifest as miosis, respiratory depression, hypotension, and hallucinations. Nausea and vomiting often occur in less severe cases. Non-cardiogenic pulmonary edema and rhabdomyolysis are particularly common after intravenous administration of opioid analgesics. In more severe cases, circulatory failure and somnolence may occur, progressing to stupor or coma, hypotension, bradycardia, pulmonary edema, and lethal outcome. Oxycodone overdose has been associated with toxic leukoencephalopathy.

The effect of overdose will be enhanced by concomitant use of alcohol or other psychotropic substances.

Treatment of Overdose

Primary attention should be given to ensuring the patency of the airways and establishing assisted or controlled ventilation of the lungs. Pure opioid antagonists, such as naloxone, are specific antidotes for opioid overdose symptoms. Other supportive measures should be applied as needed.

In the case of massive overdose, naloxone should be administered intravenously (from 0.4 to 2 mg for an adult and 0.01 mg/kg body weight for children) if the patient is in a coma or exhibits respiratory depression. The dose should be repeated at 2-minute intervals if there is no adequate response. If repeated doses are needed, it is advisable to prescribe an infusion of 60% of the initial dose per hour. A solution of 10 mg, prepared in 50 ml of dextrose solution, will give 200 mcg/ml for infusion using an intravenous pump (the dose should be adjusted according to the clinical response). Infusions do not replace frequent assessment of the patient's clinical condition.

Intramuscular naloxone is an alternative if intravenous access is not possible. Since the duration of action of naloxone is relatively short, the patient needs to be closely monitored until spontaneous breathing is reliably restored. Naloxone is a competitive antagonist, and for patients with severe poisoning, large doses (4 mg) may be required.

In less severe overdose, 0.2 mg of naloxone should be administered intravenously, with further increases of 0.1 mg every 2 minutes if necessary.

The patient should be under surveillance for at least 6 hours after the last dose of naloxone.

Naloxone should not be administered in the absence of clinically significant respiratory depression or circulatory depression caused by oxycodone overdose. Naloxone should be administered with caution to individuals with known physical dependence on oxycodone or if there is a suspicion of such dependence. In these cases, sudden or complete reversal of opioid effects may lead to pain and acute withdrawal syndrome.

Undesirable Effects

Undesirable effects are typical of opioid agonists. Tolerance and dependence may occur (see "Special Instructions"). Constipation can be prevented with appropriate laxatives. If nausea or vomiting is a concern, oxycodone can be combined with an antiemetic.

Very common (≥ 1/10), common (from ≥ 1/100 to < 1/10), uncommon (from ≥ 1/1000 to < 1/100), rare (from ≥ 1/10000 to < 1/1000), very rare (< 1/10000), not known (cannot be estimated from available data).

Immune System Disorders

Uncommon – hypersensitivity; not known – anaphylactic reaction, anaphylactoid reaction.

Metabolic and Nutritional Disorders

Common – decreased appetite; uncommon – dehydration.

Psychiatric Disorders

Common – anxiety, confusion, depression, insomnia, nervousness, thinking disorders, strange dreams; uncommon – agitation, emotional instability, euphoric mood, hallucinations, decreased libido, drug dependence (see "Special Instructions"), disorientation, mood changes, restlessness, dysphoria; not known – aggression.

Nervous System Disorders

Very common – somnolence, dizziness, headache; common – tremor, lethargy, sedation; uncommon – amnesia, seizures, hypertension, hypesthesia, muscle spasms, speech disorders, syncope, paresthesia, dysgeusia, hypotension; not known – hyperalgesia.

Eye Disorders

Uncommon - vision disorders, miosis.

Ear and Labyrinth Disorders

Uncommon - vertigo.

Cardiac Disorders

Uncommon - tachycardia (in the context of withdrawal syndrome), supraventricular tachycardia.

Vascular Disorders

Uncommon – vasodilation, facial flushing; rare – hypotension, orthostatic hypotension.

Respiratory, Thoracic, and Mediastinal Disorders

Common – dyspnea, bronchospasm, weakened cough; uncommon – respiratory depression, hiccups; not known - central sleep apnea syndrome.

Gastrointestinal Disorders

Very common – constipation, nausea, vomiting; common – abdominal pain, diarrhea, dry mouth, dyspepsia; uncommon – dysphagia, flatulence, eructation, intestinal obstruction, gastritis; not known – tooth decay.

Hepatobiliary Disorders

Uncommon – increased liver enzyme activity, biliary colic; not known – cholestasis, dysfunction of the sphincter of Oddi.

Skin and Subcutaneous Tissue Disorders

Very common – itching; common – rash, hyperhidrosis; uncommon – dry skin, exfoliative dermatitis; rare – urticaria.

Renal and Urinary Disorders

Uncommon – urinary retention, ureteral spasm.

Reproductive System and Breast Disorders

Uncommon – erectile dysfunction, hypogonadism; not known – amenorrhea.

General Disorders and Administration Site Conditions

Common – asthenia, fatigue; uncommon – drug withdrawal syndrome, malaise, edema, peripheral edema, drug tolerance, thirst, hyperthermia, chills; not known – drug withdrawal syndrome in newborns.

Drug Dependence

Repeated use of Oxycodone Kalceks may lead to drug dependence, even at therapeutic doses. The risk of drug dependence may vary depending on individual patient risk factors, dosing, and duration of opioid treatment (see "Special Instructions").

Shelf Life

2 years.

Do not use after the expiration date stated on the packaging.

After First Opening

After opening the ampoule, the medicinal product must be used immediately.

Shelf Life After Dilution

Chemical and physical stability has been demonstrated for 24 hours at 25 °C and at a temperature of 2 °C to 8 °C.

From a microbiological point of view, diluted solutions should be used immediately. If they are not used immediately, the duration and conditions of storage prior to administration are the responsibility of the user, and they should not normally exceed 24 hours at 2 °C – 8 °C, unless the dilution has been carried out under controlled and validated aseptic conditions.

Storage Conditions

No special storage conditions are required.

Do not freeze.

Keep out of the reach of children.

Incompatibility

Cyclizine at concentrations of 3 mg/ml (or lower) when mixed with Oxycodone Kalceks, either undiluted or diluted with water for injection, does not show signs of precipitation for 24 hours at room temperature. Precipitation has been shown to occur in mixtures with Oxycodone Kalceks at cyclizine concentrations exceeding 3 mg/ml or when diluted with sodium chloride 9 mg/ml (0.9%) solution for injection. However, when the dose of Oxycodone Kalceks is reduced to 50 mg/ml and sufficiently diluted with water for injection, concentrations above 3 mg/ml are possible. It is recommended to use water for injection as a diluent when cyclizine and oxycodone hydrochloride are administered concomitantly, either intravenously or subcutaneously, as an infusion.

Prochlorperazine is chemically incompatible with Oxycodone Kalceks.

Packaging

1 ml (for 10 mg/ml and 50 mg/ml concentrations) or 2 ml (for 10 mg/ml concentration) in an ampoule made of colorless glass of hydrolytic class I with marking rings and a break point.

5 ampoules in a contour cell pack made of polyvinyl chloride film.

1 or 2 contour cell packs, together with instructions for medical use, in a carton box.

Release Category

Prescription only.

Manufacturer

The manufacturer responsible for the batch release: JSC Kalceks.

Manufacturer's Location and Address

Krustpils street 71E, Riga, LV-1057, Latvia.

Applicant

JSC Kalceks.

Applicant's Location

Krustpils street 71E, Riga, LV-1057, Latvia.