Vomenda

INSTRUCTION for medical use of the medicinal product VOMENDA (VOMENDA)

Composition:

Active substance: ondansetron (ondansetron);

1 ml of solution contains ondansetron hydrochloride dihydrate equivalent to 2 mg of ondansetron;

Excipients: sodium chloride, citric acid monohydrate, trisodium citrate dihydrate, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, colorless solution.

Pharmacotherapeutic group. Antiemetics and antinausea agents. Serotonin 5HT3-receptor antagonists.

ATC code: A04AA01.

Pharmacological properties.

Pharmacodynamics.

Ondansetron is a potent, highly selective antagonist of serotonin (5-HT3) receptors. The mechanism of action of ondansetron in nausea and vomiting is not fully understood. During radiation therapy and administration of cytotoxic drugs, serotonin (5-HT) is released in the small intestine, stimulating the endings of afferent fibers of the vagus nerve via activation of 5-HT3 receptors, thereby initiating the peripheral mechanism of the vomiting reflex. Ondansetron blocks initiation of this reflex. Activation of vagus nerve afferent endings, in turn, may trigger the release of 5-HT in the posterior region of the floor of the fourth ventricle (area postrema), potentially initiating the central mechanism of the vomiting reflex. Thus, the inhibitory effect of ondansetron on chemotherapy- and radiation-induced nausea and vomiting is likely mediated by antagonism at 5-HT3 receptors located both peripherally and in the central nervous system.

The mechanism of action of the drug in postoperative nausea and vomiting is not fully elucidated, but is probably similar to that in cytotoxic nausea and vomiting. Ondansetron does not affect plasma prolactin concentrations.

The role of ondansetron in opioid-induced vomiting is not fully understood.

Pharmacokinetics.

Distribution of ondansetron is similar following oral, intramuscular, and intravenous administration in adults, with a comparable terminal half-life of approximately 3 hours and a steady-state volume of distribution of 140 L. Equivalent systemic exposure is achieved after intramuscular and intravenous administration of ondansetron.

Maximum plasma concentration of the drug is reached within 5 minutes after intravenous infusion of 4 mg ondansetron and within 10 minutes after intramuscular injection.

Ondansetron exhibits moderate plasma protein binding (70–76%). It is eliminated from systemic circulation primarily via hepatic metabolism involving multiple enzyme systems. Less than 5% of the drug is excreted unchanged in urine. The absence of the CYP2D6 isoenzyme (sparteine/debrisoquine polymorphism type) does not affect the pharmacokinetics of ondansetron. Pharmacokinetic parameters of ondansetron remain unchanged with repeated administration.

Special patient groups

Gender

The pharmacokinetics of ondansetron are influenced by patient gender. Women exhibit higher rate and extent of absorption after oral administration and lower systemic clearance and volume of distribution (body weight-adjusted) compared to men.

Children aged 1 month to 17 years

Based on study results, the area under the plasma concentration-time curve (AUC) after oral and intravenous administration in children and adolescents was similar to that in adults, except for infants aged 1 to 4 months. The volume of distribution was age-dependent and lower in adults compared to children. Creatinine clearance was dependent on body weight but not on age (except in children aged 1 to 4 months). It is difficult to draw a definitive conclusion as to whether an additional reduction in ondansetron clearance occurred in children aged 1 to 4 months or whether the observed reduction reflected natural variability due to the small number of patients studied in this age group. Since children under 6 months of age received only a single dose of the drug for postoperative nausea and vomiting, the reduced clearance is unlikely to be of clinical significance.

Elderly patients

Based on available data on ondansetron plasma concentrations and results from modeling the relationship between clinical response and exposure, a more pronounced effect on the QTcF interval is expected in patients aged 75 years and older compared to younger patients. Specific dosage recommendations for intravenous administration are provided for patients aged 65 years and older (see section "Dosage and administration").

Patients with renal impairment

In patients with renal impairment (creatinine clearance 15–60 mL/min), systemic clearance and volume of distribution are reduced after intravenous ondansetron administration, resulting in a slight, clinically insignificant prolongation of the elimination half-life (5.4 hours). Studies in patients with severe renal impairment requiring regular hemodialysis showed no changes in ondansetron pharmacokinetics following intravenous administration.

Patients with hepatic impairment

In patients with severe hepatic impairment, systemic clearance of ondansetron is markedly reduced, with an increase in elimination half-life to 15–32 hours.

Clinical characteristics.

Indications.

Adults

• Nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy.
• Prevention and treatment of postoperative nausea and vomiting.

Children

• Nausea and vomiting induced by cytotoxic chemotherapy in children aged 6 months and older, and prevention and treatment of postoperative nausea and vomiting in children aged 1 month and older.

Contraindications.

Concomitant use of ondansetron with apomorphine hydrochloride is contraindicated, as cases of severe arterial hypotension and loss of consciousness have been observed during their simultaneous administration.

Hypersensitivity to any component of the drug.

Interaction with other medicinal products and other forms of interaction.

Ondansetron does not accelerate or inhibit the metabolism of other drugs when used concomitantly. Specific studies have shown that ondansetron does not interact with alcohol, temazepam, furosemide, alfentanil, tramadol, morphine, lidocaine, thiopental, or propofol.

Ondansetron is metabolized by various hepatic cytochrome P450 enzymes: CYP3A4, CYP2D6, and CYP1A2. Due to the diversity of ondansetron-metabolizing enzymes, inhibition or reduced activity of one of them (e.g., genetic deficiency of CYP2D6) is normally compensated by other enzymes and will not affect overall creatinine clearance or will have only a negligible effect.

Ondansetron should be used with caution together with medicinal products that prolong the QT interval and/or cause electrolyte imbalances (see section "Special warnings and precautions for use").

Concomitant use of ondansetron with other medicinal products that prolong the QT interval may result in additional QT prolongation. Concurrent use of ondansetron with cardiotoxic medicinal products (e.g., anthracyclines (doxorubicin, daunorubicin) or trastuzumab), antibiotics (erythromycin), antifungal agents (ketoconazole), antiarrhythmics (amiodarone), and beta-blockers (atenolol or timolol) increases the risk of arrhythmias (see section "Special warnings and precautions for use").

Serotonergic agents (e.g., SSRIs and SNRIs)

Serotonin syndrome (including changes in mental status, autonomic instability, and neuromuscular disturbances) has been reported following concomitant use of ondansetron and other serotonergic agents, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) (see section "Special warnings and precautions for use").

Apomorphine

Concomitant use of ondansetron with apomorphine hydrochloride is contraindicated, as cases of severe arterial hypotension and loss of consciousness have been observed during combined administration.

Phenytoin, carbamazepine, and rifampicin

In patients receiving potential inducers of CYP3A4 (e.g., phenytoin, carbamazepine, and rifampicin), the clearance of ondansetron is increased and its blood concentration is decreased.

Tramadol

According to data from a limited number of clinical studies, ondansetron may reduce the analgesic effect of tramadol.

Special precautions for use

In patients with a history of hypersensitivity to other selective 5-HT3 receptor antagonists, hypersensitivity reactions have been observed.

Respiratory-related reactions should be treated symptomatically. Healthcare providers should pay special attention to such reactions, as they may be signs of hypersensitivity to the medicinal product.

Ondansetron prolongs the QT interval in a dose-dependent manner (see section "Pharmacological properties"). Additionally, post-marketing surveillance data have reported cases of ventricular flutter/fibrillation (torsade de pointes) following ondansetron administration. Ondansetron should be avoided in patients with congenital long QT syndrome. Ondansetron should be used with caution in patients who have or may develop QT interval prolongation, including patients with electrolyte imbalances, congestive heart failure, bradyarrhythmias, or those receiving other medicinal products that may induce QT prolongation or electrolyte disturbances.

Cases of myocardial ischemia have been reported in patients receiving ondansetron. In some patients, particularly following intravenous administration, symptoms appeared immediately after ondansetron administration. Patients should be informed about the signs and symptoms of myocardial ischemia.

Hypokalemia and hypomagnesemia should be corrected prior to initiating treatment.

Serotonin syndrome, including mental status changes, autonomic instability, and neuromuscular abnormalities, has been reported following concomitant use of ondansetron and other serotonergic medicinal products (see section "Interaction with other medicinal products and other forms of interaction"). If concomitant treatment with ondansetron and other serotonergic agents is clinically justified, appropriate patient monitoring is recommended.

Since ondansetron reduces gastrointestinal motility, careful monitoring is required in patients with signs of subacute intestinal obstruction during treatment.

In patients undergoing adenotonsillar surgery, the use of ondansetron for the prevention of nausea and vomiting may mask the occurrence of postoperative bleeding. Therefore, such patients require careful monitoring after ondansetron administration.

One injection of the medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e., is essentially "sodium-free".

Children

In children receiving ondansetron concomitantly with hepatotoxic chemotherapeutic agents, careful monitoring for possible hepatic function impairment is required.

Dosing regimens

When dosing is based on body weight and three doses are administered at 4-hour intervals, the total daily dose will be higher than when using a single 5 mg/m² dose followed by one oral dose. The comparative efficacy of these two dosing regimens has not been evaluated in clinical trials. However, comparison of results from different studies suggests similar efficacy for both regimens.

Use during pregnancy or breastfeeding

Women of childbearing potential

Women of childbearing potential should use contraceptive measures.

Pregnancy

Epidemiological data from human experience raise concerns about the potential risk of craniofacial malformations following ondansetron use during the first trimester of pregnancy.

In one cohort study involving 1.8 million pregnancies, ondansetron use during the first trimester was associated with an increased risk of oral clefts (3 additional cases per 10,000 women treated; adjusted relative risk 1.24 (95% CI 1.03–1.48)).

Epidemiological studies on congenital heart defects have yielded conflicting results. Animal studies have not indicated direct or indirect harmful effects with regard to reproductive toxicity.

Ondansetron should not be used during the first trimester of pregnancy.

The safety of ondansetron use during human pregnancy has not been established. Experimental animal studies showed that ondansetron does not interfere with embryonic or fetal development, nor does it affect the course of pregnancy or peri- and postnatal development. However, since animal studies are not always predictive of human response, the use of ondansetron during pregnancy is not recommended.

Breastfeeding

Experimental studies have shown that ondansetron passes into the milk of animals. If treatment with ondansetron is necessary, breastfeeding should be discontinued.

Fertility

There is no information available on the effects of ondansetron on human fertility.

Ability to affect reaction speed when driving or operating machinery

Psychomotor tests have shown that ondansetron does not impair the ability to drive or operate machinery and has no sedative effect. However, the adverse effect profile of the medicinal product should be taken into account when assessing the ability to drive or operate machinery.

Method of Administration and Dosage

Nausea and vomiting induced by chemotherapy and radiotherapy

Adults

The emetogenic potential of cancer therapy varies depending on the dose and combination of chemotherapy and radiotherapy regimens. The choice of dosage regimen depends on the severity of emetogenic impact. The dose of the drug (range from 8 to 32 mg per day) and route of administration should be selected according to the information below.

Chemotherapy and radiotherapy with emetogenic potential

Ondansetron can be administered orally, intravenously, or intramuscularly, depending on the pharmaceutical form.

For most patients, the recommended intravenous or intramuscular dose is 8 mg given as a slow intravenous injection over at least 30 seconds or as an intramuscular injection immediately before treatment, followed by oral administration of 8 mg every 12 hours.

To prevent delayed or prolonged vomiting after the first 24 hours, oral ondansetron is recommended for up to 5 days after completion of the treatment course.

Highly emetogenic chemotherapy (e.g., high-dose cisplatin)

For such patients, ondansetron may be administered orally, intravenously, or intramuscularly. Ondansetron has shown equivalent efficacy in the following dosage regimens during the first 24 hours of chemotherapy:

• A single dose of 8 mg may be administered immediately before chemotherapy as a slow intravenous injection (over at least 30 seconds) or as an intramuscular injection;
• For highly emetogenic chemotherapy, 8 mg of the drug or a lower dose does not need to be diluted and can be administered as a slow intravenous injection (over at least 30 seconds) or intramuscular injection immediately before chemotherapy, followed by two additional intravenous (over at least 30 seconds) or intramuscular doses of 8 mg given at 2 and 4 hours, or by continuous infusion of 1 mg/hour for 24 hours;
• An initial dose exceeding 8 mg (up to 16 mg) may be administered only as an intravenous infusion in 50–100 mL of 0.9% sodium chloride solution or another suitable diluent (see below "Instructions for Use"); the infusion should last at least 15 minutes immediately before chemotherapy. The initial 8 mg dose of the drug may also be administered with two additional intravenous (over at least 30 seconds) or intramuscular injections given at 4-hour intervals between injections.

Single doses exceeding 16 mg should not be used, as higher doses increase the risk of QT interval prolongation (see section "Special Warnings and Precautions for Use").

The choice of dosage regimen depends on the severity of emetogenic effect. The efficacy of the drug in highly emetogenic chemotherapy may be enhanced by additional single intravenous administration of 20 mg of sodium dexamethasone phosphate before chemotherapy.

To prevent delayed or prolonged vomiting after the first 24 hours, oral administration of the drug is recommended for up to 5 days after completion of the treatment course.

Children aged 6 months and adolescents

The drug dose can be calculated based on body surface area or body weight.

In pediatric practice, the drug should be administered by intravenous infusion in 25–50 mL of 0.9% sodium chloride solution or another suitable diluent (see below "Instructions for Use") over 15 minutes.

The total daily dose calculated by body weight is higher than the total daily dose calculated by body surface area.

The drug should be diluted with 5% dextrose solution, 0.9% sodium chloride solution, or another suitable infusion solution and administered by intravenous infusion over at least 15 minutes.

There are no data from controlled clinical studies regarding the use of the drug for the prevention of delayed or prolonged vomiting and nausea caused by chemotherapy. There are no data from controlled clinical studies regarding the use of the drug for the treatment of nausea and vomiting caused by radiotherapy in children.

Dosage calculation according to body surface area

The drug should be administered as a single intravenous injection of 5 mg/m² immediately before chemotherapy. The intravenous dose should not exceed 8 mg.

Oral administration may be initiated 12 hours later and may continue for up to 5 days. The total daily dose of ondansetron (divided into multiple doses) should not exceed the adult dose of 32 mg.

a The intravenous dose should not exceed 8 mg.

b The total daily dose, divided into multiple administrations, should not exceed the adult dose (32 mg).

Dose calculation based on body weight of the child

The total daily dose calculated by body weight is higher compared to the total daily dose calculated by body surface area.

The drug should be administered immediately before chemotherapy as a single intravenous injection at a dose of 0.15 mg/kg. The intravenous dose should not exceed 8 mg. Subsequently, administration of two intravenous injections with an interval of 4 hours may be considered. Oral administration of the drug may be initiated 12 hours later and may continue for up to 5 days. The total daily dose of ondansetron (divided into multiple administrations) should not exceed the adult dose of 32 mg.

a The intravenous dose should not exceed 8 mg.

b The total daily dose, divided into several administrations, should not exceed the adult dose (32 mg).

Elderly patients

For patients aged 65 to 74 years, the initial dose of ondansetron is 8 mg or 16 mg. All intravenous injection doses should be dissolved in 50–100 ml of 0.9% sodium chloride solution or another suitable diluent (see below "Instructions for use") and administered over 15 minutes.

For patients aged 75 years and older, the initial intravenous injection of ondansetron should not exceed 8 mg. All intravenous injection doses should be dissolved in 50–100 ml of 0.9% sodium chloride solution or another suitable diluent (see below "Instructions for use") and administered over 15 minutes. After the initial 8 mg dose, treatment may continue with two additional 8 mg doses administered by infusion over 15 minutes, with at least 4 hours between administrations.

Patients with renal impairment

There is no need to adjust the dosing regimen or route of administration in patients with impaired renal function.

Patients with hepatic impairment

In patients with moderate to severe hepatic impairment, ondansetron clearance is significantly reduced and serum half-life is prolonged. For such patients, the maximum daily dose of the drug should not exceed 8 mg.

Patients with impaired metabolism of sparteine/debrisoquine

The elimination half-life of ondansetron in patients with impaired sparteine and debrisoquine metabolism is unchanged. In these patients, plasma concentrations after repeated administration are similar to those in patients with normal metabolism. Therefore, dose adjustment or change in frequency of administration is not required.

Postoperative nausea and vomiting

Adults

For prevention of postoperative nausea and vomiting, the recommended dose of ondansetron is 4 mg as a single intramuscular or slow intravenous injection administered during induction of anesthesia.

For treatment of postoperative nausea and vomiting, the recommended single dose of ondansetron is 4 mg as an intramuscular or slow intravenous injection.

Children aged 1 month and adolescents

For prevention and treatment of postoperative nausea and vomiting in children undergoing general anesthesia, the drug may be administered at a dose of 0.1 mg/kg body weight (maximum 4 mg) by slow intravenous injection (over no less than 30 seconds) before, during, after induction of anesthesia, or after surgery.

There are no clinical data on the use of injectable ondansetron in children under 2 years of age for prevention and treatment of postoperative nausea and vomiting.

Elderly patients

Experience with ondansetron for prevention and treatment of postoperative nausea and vomiting in elderly patients is limited; however, ondansetron was well tolerated in patients aged 65 years and older who received chemotherapy.

Patients with renal impairment

There is no need to modify the dosing regimen or route of administration in patients with impaired renal function.

Patients with hepatic impairment

In patients with moderate to severe hepatic impairment, ondansetron clearance is significantly reduced and serum half-life is prolonged. For such patients, the maximum daily dose of the drug should not exceed 8 mg.

Patients with impaired metabolism of sparteine/debrisoquine

The elimination half-life of ondansetron in subjects with impaired sparteine and debrisoquine metabolism is unchanged. In these patients, plasma concentrations after repeated administration are similar to those in patients with intact metabolism. Therefore, dose adjustment or change in frequency of administration is not required.

Instructions for use

The vial contains no preservatives, and the solution should be used immediately after opening. Do not use the drug if the solution is not clear or if a precipitate forms. Any unused solution must be discarded. The vial must not be autoclaved.

After dilution

After dilution in compatible infusion solutions, the drug is stable under normal room lighting or daylight conditions for at least 24 hours; protection from light during infusion is not required.

Compatibility with other intravenous fluids

For preparation of Vomendy infusion solution, only the following recommended diluents should be used: 0.9% sodium chloride solution; 5% glucose solution; 10% mannitol solution; Ringer's solution; 0.3% potassium chloride in 0.9% sodium chloride solution; 0.3% potassium chloride in 5% glucose solution.

If prolonged storage of the drug is required, dilution should be performed under appropriate aseptic conditions. Infusion solutions should be prepared immediately before use or stored in a refrigerator at 2–8°C for no more than 24 hours prior to administration.

It has been established that ondansetron remains stable when using polyethylene and glass vials. Ondansetron diluted with 0.9% sodium chloride or 5% glucose solution has been shown to remain stable in polypropylene syringes. Stability in polypropylene syringes has also been demonstrated when ondansetron is diluted with other recommended diluents.

Compatibility with other drugs

Vomendy can be administered as an intravenous infusion at a rate of 1 mg/hour. The infusion solution containing ondansetron at concentrations of 16–160 μg/ml (e.g., 8 mg/500 ml or 8 mg/50 ml, respectively) may be administered via a Y-site catheter with the following drugs:

• cisplatin at concentrations up to 0.48 mg/ml (e.g., 240 mg/500 ml) over 1–8 hours;
• 5-fluorouracil at concentrations up to 0.8 mg/ml (e.g., 2.4 g in 3 L or 400 mg in 500 ml) at a rate not exceeding 20 ml/hour (500 ml over 24 hours). Higher concentrations of 5-fluorouracil may cause precipitation of ondansetron. The 5-fluorouracil infusion solution may contain up to 0.045% magnesium chloride in addition to other compatible excipients;
• carboplatin at concentrations ranging from 0.18 mg/ml to 9.9 mg/ml (e.g., from 90 mg in 500 ml to 990 mg in 100 ml) over 10–60 minutes;
• etoposide at concentrations ranging from 0.14 mg/ml to 0.25 mg/ml (e.g., from 72 mg in 500 ml to 250 mg in 1 L) over 30–60 minutes;
• ceftazidime at doses from 250 mg to 2 g, diluted in water for injection (e.g., 2.5 ml per 250 mg or 10 ml per 2 g ceftazidime), administered as an intravenous bolus over 5 minutes;
• cyclophosphamide at doses from 100 mg to 1 g, diluted in water for injection (5 ml per 100 mg cyclophosphamide), administered as an intravenous bolus over 5 minutes;
• doxorubicin at doses from 10 mg to 100 mg, diluted in water for injection (5 ml per 10 mg doxorubicin), administered as an intravenous bolus over 5 minutes;
• dexamethasone at a dose of 20 mg, administered as a slow intravenous injection over 2–5 minutes (concurrently with 8 mg or 16 mg ondansetron diluted in 50–100 ml of infusion solution) over approximately 15 minutes. Since these drugs are compatible, they may be administered through the same infusion line, with dexamethasone phosphate (as sodium salt) concentrations ranging from 32 μg to 2.5 mg per 1 ml and ondansetron concentrations from 8 μg to 1 mg per 1 ml.

Children

For use in children aged 6 months (during chemotherapy) and aged 1 month (for prevention and treatment of postoperative nausea and vomiting).

Overdose

Symptoms and signs. Data on ondansetron overdose are limited. In most cases, symptoms are similar to those observed in patients receiving recommended doses (see section "Adverse reactions"). Reported manifestations of overdose include visual disturbances, severe constipation, hypotension, vasovagal reactions with transient second-degree atrioventricular block. In all cases, these effects were fully reversible.

Ondansetron prolongs the QT interval in a dose-dependent manner. In case of overdose, ECG monitoring is recommended.

Children. Serotonin syndrome has been reported in infants and children aged 12 months to 2 years following accidental overdose of the oral formulation (doses exceeding the recommended level of 4 mg/kg).

Treatment. There is no specific antidote; therefore, symptomatic and supportive therapy should be administered in cases of overdose.

Further management of patients should be based on clinical judgment or, whenever possible, in accordance with recommendations from the national poison control center.

The use of ipecacuanha for treatment of ondansetron overdose is not recommended, as its emetic effect may be ineffective due to the antiemetic action of the drug.

Adverse Reactions

The adverse effects listed below are classified by system organ class and frequency of occurrence. The frequency categories are defined as follows: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), and not known (cannot be estimated from the available data).

Immune system disorders:

rare: immediate-type hypersensitivity reactions, sometimes severe, up to anaphylaxis.

Nervous system disorders:

very common: headache;

uncommon: seizures, movement disorders (including extrapyramidal reactions such as dystonic reactions, oculogyric crisis, and dyskinesia without persistent clinical consequences) (1);

rare: dizziness, mainly during rapid intravenous administration.

Eye disorders:

rare: transient visual disturbances (blurred vision), mainly during intravenous administration;

very rare: transient blindness, mainly during intravenous administration (2).

Cardiac disorders:

uncommon: arrhythmias, chest pain (with or without ST segment depression), bradycardia;

rare: QT interval prolongation (including ventricular fibrillation/tachycardia (torsade de pointes));

not known: myocardial ischemia ⃰ (see section "Special precautions for use").

Vascular disorders:

common: sensation of warmth or flushing;

uncommon: hypotension.

Respiratory, thoracic and mediastinal disorders:

uncommon: hiccups.

Gastrointestinal disorders:

common: constipation.

Hepatobiliary disorders:

uncommon: asymptomatic elevation of liver function tests (3).

Skin and subcutaneous tissue disorders:

very rare: toxic skin eruptions, including toxic epidermal necrolysis.

General disorders and administration site conditions:

common: local reactions at the site of intravenous administration.

• Persistent clinical consequences have not been definitively established in these observations.
  • Transient blindness resolved within 20 minutes in most cases. Most patients were receiving chemotherapy regimens containing cisplatin. Some cases of transient cortical blindness have been reported.
    • These cases were primarily observed in patients receiving cisplatin-containing chemotherapy regimens.

* These adverse reactions were identified from post-marketing experience with ondansetron based on spontaneous case reports and published case literature. As these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency and thus they are classified as "not known."

The following adverse reactions have been observed during post-marketing surveillance:

Cardiovascular system: chest pain and discomfort, extrasystoles, tachycardia including ventricular and supraventricular tachycardia, atrial fibrillation, palpitations, syncope, ECG changes.

Hypersensitivity reactions: anaphylactic reactions, angioedema, bronchospasm, anaphylactic shock, pruritus, skin rashes, urticaria.

Nervous system disorders: gait disturbances, chorea, myoclonus, restlessness, burning sensation, tongue protrusion, diplopia, paresthesia.

General disorders and administration site reactions: increased body temperature, pain, redness, burning at the injection site.

Other: hypokalemia.

Shelf life.

2 years.

Storage conditions.

Store in the original packaging to protect from light at a temperature not exceeding 25 °C.

Keep out of reach of children.

Incompatibilities.

The medicinal product must not be mixed in the same syringe or infusion solution with other medicinal products. The injectable form of the product may only be combined with the recommended infusion solutions (see section "Dosage and method of administration").

Packaging.

2 ml (4 mg) or 4 ml (8 mg) in a vial; 5 or 10 vials per cardboard box.

Prescription status. Prescription only.

Manufacturer. Aspiro Pharma Limited.

Manufacturer's address.

Sy.No.321, Biotech park, Phase-III, Karkapatla Village, Markook Mandal, Siddipet Dist-502281, Telangana State, India.