Yufol

INSTRUCTIONS for medical use of the medicinal product YUFOL (YUFOL)

Composition:

Active substance: morphine sulfate;

1 ml of solution contains morphine sulfate 10 mg;

Excipients: sodium chloride, sodium metabisulfite (E 223), water for injections.

* The pH value is adjusted by adding 10% sodium hydroxide solution or 10% sulfuric acid.

Pharmaceutical form. Solution for injection.

Main physico-chemical properties: clear, colorless or almost colorless solution free from visible particles.

Pharmacotherapeutic group. Natural opium alkaloids.

ATC code N02A A01.

Pharmacological Properties

Pharmacodynamics

Morphine is a narcotic analgesic derived from opium, acting primarily on the central nervous system (CNS) and smooth muscles.

The potent analgesic effect of morphine is associated with its competitive agonist action on mu-receptors, which is believed to mediate many of its other effects, such as respiratory depression, euphoria, gastrointestinal motility suppression, and physical dependence. Activation of mu-1 receptors by morphine causes analgesia, euphoria, and dependence. Stimulation of mu-2 receptors leads to respiratory and gastrointestinal motility depression.

Morphine acts as a competitive agonist at kappa receptors; their activation results in spinal analgesia, miosis, and sedation. Morphine has low affinity for the two other major opioid receptors: delta and sigma receptors.

Morphine suppresses the cough reflex by direct action on the cough center in the medulla oblongata. It may also stimulate chemoreceptors in the trigger zone of the upper medulla oblongata, inducing nausea and vomiting. Morphine causes histamine release.

Pharmacokinetics

Absorption

After oral administration, the rate of absorption may vary, while morphine is rapidly absorbed into the bloodstream following subcutaneous or intramuscular injection.

Plasma Concentration

After oral administration of 10 mg morphine sulfate, peak free morphine concentration in plasma (approximately 10 ng/mL) is reached within 15–60 minutes; after intramuscular injection of 10 mg morphine sulfate, peak plasma morphine concentration (70–80 ng/mL) is achieved within 10–20 minutes; after intravenous injection of 10 mg morphine sulfate, peak plasma concentration (approximately 60 ng/mL) is reached within 15 minutes, declining to 30 ng/mL within 30 minutes and to 10 ng/mL within 3 hours; after subcutaneous injection, plasma concentrations similar to those after intramuscular injection are achieved within 15 minutes, but remain slightly higher over the subsequent 3 hours. Plasma morphine concentration measured shortly after administration correlates significantly with patient age and increases in elderly individuals.

Half-life

The elimination half-life from plasma during the period from 10 minutes to 6 hours after intravenous administration is 2 to 3 hours; the half-life from plasma during the period from 6 hours and beyond ranges from 10 to 44 hours.

Distribution

Morphine is widely distributed throughout the body, primarily in the kidneys, liver, lungs, and spleen, and to a lesser extent in the brain and muscles. It crosses the placenta, is excreted in sweat in trace amounts, and passes into breast milk. Approximately 35% of morphine binds to plasma proteins—albumin and immunoglobulins—at concentrations within the therapeutic range.

Biotransformation

Morphine is primarily conjugated with glucuronic acid, forming morphine-3-glucuronide and morphine-6-glucuronide. Sulfate conjugation also occurs.
N-demethylation, O-methylation, and formation of N-oxide glucuronide take place in the intestinal mucosa and liver. N-demethylation occurs to a greater extent after oral administration than after parenteral administration. The O-methylation pathway for codeine formation is impaired, and metabolites of codeine and norcodeine in urine may arise from codeine impurities present in the tested morphine sample.

Excretion

After oral administration, approximately 60% of the drug is excreted in urine within 24 hours, of which about 3% is excreted as free morphine within 48 hours. After parenteral administration, approximately 90% is excreted within 24 hours, including about 10% as free morphine, 65–70% as conjugated morphine, 1% as normorphine, and 3% as normorphine glucuronide. After administration of large doses in dependent individuals, approximately 0.1% of the dose is excreted as norcodeine. Morphine excretion in urine is partially pH-dependent: increased urine acidity enhances excretion of free morphine, while increased alkalinity promotes excretion of the glucuronide conjugate. Up to 10% of the dose may be excreted in bile.

Preclinical Safety Data

Reduced fertility and chromosomal damage in male rat gametes have been reported.

Clinical Characteristics

Indications

Symptomatic relief of severe pain, relief of dyspnea in left ventricular heart failure and pulmonary edema, and in the preoperative period.

Contraindications

• Hypersensitivity to the active substance or to any of the excipients.
• Acute respiratory depression.
• Asthma attack or chronic obstructive pulmonary disease.
• Alcohol intoxication.
• Biliary colic.
• Head injuries, coma, or increased intracranial pressure. The sedative effect and changes in pupil size may interfere with accurate patient monitoring.
• Cardiac failure due to lung disease.
• Treatment with monoamine oxidase inhibitors (including moclobemide) or within a two-week period after discontinuation of such treatment.
• Risk of paralytic intestinal obstruction.
• Pheochromocytoma (due to the risk of pressor response caused by histamine release).
• Acute diarrheal conditions associated with antibiotic-associated pseudomembranous colitis or diarrhea caused by poisoning (until the toxic substance is eliminated).

Interaction with other medicinal products and other forms of interaction

Alcohol

Enhancement of sedative and hypertensive effects.

Antiarrhythmic agents

Possible slowing of mexiletine absorption.

Antibacterial agents

It has been shown that the opioid analgesic papaveretum reduces plasma concentrations of ciprofloxacin. The manufacturer of ciprofloxacin recommends avoiding premedication with opioid analgesics.

Antidepressants, anxiolytics, hypnotics

Severe CNS excitation or depression (hypertension or hypotension) has been reported with concomitant use of pethidine and monoamine oxidase inhibitors (MAOIs), such as selegiline, moclobemide, and linezolid. Since a similar interaction may occur with other opioid analgesics, morphine should be administered with caution, and dose reduction should be considered in patients receiving MAOIs.

The sedative effect of morphine (opioid analgesics) is enhanced when used concomitantly with CNS depressants, including hypnotics, anxiolytics, tricyclic antidepressants, and sedative antihistamines.

Morphine should be used with caution in patients who are concurrently receiving other CNS depressants, including sedatives or hypnotics, general anesthetics, phenothiazines, other tranquilizers, muscle relaxants, antihypertensives, gabapentin or pregabalin, and alcohol. Effects leading to respiratory depression, hypotension, profound sedation, or coma may occur when these agents are used concurrently with usual doses of morphine.

Antipsychotics

Possible enhancement of sedative and hypotensive effects.

Antidiarrheal and antiperistaltic agents (such as loperamide and kaolin)

Concomitant use increases the risk of severe constipation.

Antimuscarinic agents

Agents such as atropine may counteract morphine-induced respiratory depression and may partially relieve biliary tract spasm, but they enhance effects on the gastrointestinal and urinary tracts. As a result, severe constipation and urinary retention may occur during intensive therapy with antimuscarinic analgesics.

Metoclopramide and domperidone

Possible antagonism of gastrointestinal effects of metoclopramide and domperidone.

Oral antiplatelet therapy with P2Y12 inhibitors

In patients with acute coronary syndrome receiving morphine, delayed and reduced effects of oral antiplatelet therapy with P2Y12 inhibitors have been observed. This interaction may be related to decreased gastrointestinal motility and occurs with the use of other opioids. The clinical significance of this interaction is unknown, but available data suggest a potential reduction in the efficacy of P2Y12 inhibitors in patients receiving morphine and a P2Y12 inhibitor concomitantly (see section "Special precautions for use"). In patients with acute coronary syndrome in whom morphine cannot be discontinued and rapid P2Y12 inhibition is considered critical, parenteral administration of a P2Y12 inhibitor may be appropriate.

Central nervous system depressants

Concomitant use of the medicinal product Yufol, 10 mg/mL, and sedatives such as benzodiazepines or similar-acting agents may result in sedation, respiratory depression, coma, and fatal outcomes. The lowest effective dose should be used, and the duration of treatment should be as short as possible (see section "Special precautions for use").

Special precautions for use

Since repeated administration may lead to tolerance and dependence, morphine should be prescribed with caution. Dose reduction may be appropriate in elderly patients and in the presence of the following conditions:

• hypotension;
• hypothyroidism;
• reduced respiratory reserve;
• prostatic hypertrophy;
• impaired liver or kidney function (morphine should be avoided or the dose reduced);
• seizure disorders;
• asthma (avoid administration during an attack);
• adrenal insufficiency;
• urethral stricture;
• inflammatory or obstructive gastrointestinal disorders.

Patients with biliary tract disorders should avoid the use of opioids such as morphine, or should receive them together with spasmolytics.

Hepatobiliary system disorders

Morphine may cause dysfunction and spasm of the sphincter of Oddi, thereby increasing intra-abdominal pressure and increasing the risk of symptoms related to the biliary tract and pancreatitis. Therefore, in patients with biliary tract diseases, morphine may exacerbate pain (use in biliary colic is contraindicated; see section "Contraindications").

In patients who received morphine after cholecystectomy, exacerbation of biliary pain has been observed.

Palliative care: In patients with incurable disease, these conditions do not necessarily have to be limiting factors when using morphine for pain relief.

Risk associated with concomitant use of sedatives such as benzodiazepines or similar-acting medicinal products

Concomitant use of the medicinal product Yufol, 10 mg/mL, solution for injection, and sedative drugs such as benzodiazepines or similar-acting agents may result in sedation, respiratory depression, coma, and fatal outcome. Due to these risks, opioids should be prescribed together with these sedative medicinal products only to patients for whom alternative treatment options are not feasible. If the decision is made to prescribe Yufol, 10 mg/mL, solution for injection, concomitantly with sedative medicinal products, the lowest effective dose should be used and the duration of treatment should be as short as possible.

Patients must be closely monitored for signs and symptoms of respiratory depression and sedation. Therefore, it is strongly recommended to inform patients and caregivers about the potential occurrence of these symptoms (see section "Interaction with other medicinal products and other forms of interaction").

Acute chest syndrome (ACS) in patients with sickle cell anemia (SCA)

Due to a possible association between ACS and morphine use in patients with SCA receiving morphine during vaso-occlusive crisis, careful monitoring for symptoms of ACS is required.

Adrenal insufficiency

Opioid analgesics may cause reversible adrenal insufficiency, which requires monitoring and replacement therapy with glucocorticoids. Adrenal insufficiency may present with symptoms such as nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, or low blood pressure.

Reduction in sex hormone levels and increased prolactin levels

Long-term use of opioid analgesics may lead to decreased levels of sex hormones and increased prolactin levels. Symptoms include reduced libido, impotence, or amenorrhea.

Cases of hyperalgesia, where increasing doses of morphine do not result in analgesic effect, may occur, particularly with high-dose administration. In such cases, the dose should be reduced or the drug replaced with another opioid medicinal product.

Morphine, like other potent opioid receptor agonists, has abuse potential and should be used with particular caution in patients with a history of alcohol or drug dependence.

Disorders related to opioid use (abuse and dependence)

Repeated use of opioid analgesics such as Yufol, 10 mg/mL, solution for injection, may lead to the development of tolerance and physical and/or psychological dependence.

Repeated use of the medicinal product Yufol, 10 mg/mL, solution for injection, may lead to opioid use disorders (OUD). Higher doses and longer duration of opioid treatment may increase the risk of developing OUD. Abuse or intentional misuse of Yufol, 10 mg/mL, solution for injection, may result in overdose and/or fatal outcome. The risk of developing OUD is increased in patients with a personal or family history (parents or siblings) of substance use disorders (including alcohol use disorders), in current tobacco users, or in patients with other psychiatric disorders (e.g., major depression, anxiety, and personality disorders).

Before initiating and during treatment with Yufol, 10 mg/mL, solution for injection, the treatment goals and a plan for discontinuation should be discussed with the patient (see section "Posology and method of administration"). Patients should also be informed before and during treatment about the risks and signs of OUD. Patients should be advised to contact their physician if such signs occur.

Patients should be monitored for signs of addictive behavior (e.g., early requests for additional doses). This includes monitoring concomitant use of opioids and psychoactive medicinal products (e.g., benzodiazepines). Patients showing signs and symptoms of OUD should be referred for consultation with an addiction specialist.

Rifampicin may reduce plasma concentrations of morphine. The analgesic effect of morphine should be monitored, and the dose adjusted during and after rifampicin treatment.

Yufol, 10 mg/mL, solution for injection, contains sodium

Yufol, 10 mg/mL, solution for injection, contains 3.26 mg/mL of sodium and sodium metabisulfite (E 223). This medicinal product contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially "sodium-free".

Oral antiplatelet therapy with P2Y12 inhibitors

Reduced effectiveness of P2Y12 inhibitors has been observed during the first 24 hours of concomitant treatment with morphine (see section "Interaction with other medicinal products and other forms of interaction").

Sleep-related breathing disorders

Opioids may 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. For patients with CSA, consideration should be given to reducing the total opioid dose.

Severe cutaneous adverse reactions (SCARs)

Cases of life-threatening or fatal acute generalized exanthematous pustulosis (AGEP) have been reported in association with morphine use. Most of these reactions occurred within the first 10 days of treatment. Patients should be informed about the signs and symptoms of AGEP and advised to seek medical attention if such symptoms occur.

If signs and symptoms suggestive of these skin reactions appear, morphine should be discontinued and alternative treatment considered.

Use during pregnancy or breastfeeding

Pregnancy

Morphine sulfate should be prescribed only if the benefit outweighs the risk. As with other medicinal products, morphine is not recommended during pregnancy.

Morphine crosses the placental barrier. Use during labor may cause respiratory depression in the newborn and gastroparesis during delivery, increasing the risk of aspiration pneumonia. Therefore, the use of morphine during labor is not recommended.

Infants born to mothers with opioid dependence may exhibit withdrawal symptoms such as increased CNS excitability, gastrointestinal dysfunction, respiratory distress, and vague autonomic symptoms including yawning, sneezing, mottled skin, and fever.

Newborns whose mothers received opioid analgesics during pregnancy should be monitored for signs of neonatal withdrawal syndrome (neonatal abstinence syndrome). Treatment may include administration of opioid medicinal products and supportive measures.

Breastfeeding

Although morphine may suppress lactation, the amount of drug that may pass into the infant through breast milk is likely insufficient to cause serious dependence or adverse effects.

Fertility

Animal studies have shown that morphine may reduce fertility (see section "Preclinical safety data").

Ability to influence the speed of reactions while driving or operating machinery

Morphine causes drowsiness; therefore, patients are advised to refrain from driving or operating machinery during treatment with the medicinal product.

The drug may impair cognitive function and affect the patient's ability to safely drive a vehicle. When prescribing the drug, patients should be warned that:

• the drug is likely to affect their ability to drive;

• they should not drive until the effects of the drug have completely subsided;

• driving under the influence of the drug is a legal offense;

• however, they will not be committing a legal offense (so-called "legal protection") if:

• the drug was prescribed for the treatment of medical or dental conditions, and

• they took it as directed by the physician and in accordance with the instructions for medical use, and it did not impair their ability to drive safely.

Administration and Dosage

Dosage

Adults

The dose should be individually adjusted for each patient depending on the severity of pain, the patient's response to analgesia, and the development of tolerance.

The single dose for subcutaneous or intramuscular administration is 10 mg of morphine every 4 hours (as needed), although it may range from 5 mg to 20 mg.

The single dose for intravenous administration is 2.5–15 mg, administered no more frequently than every 4 hours (as needed). However, both dose and dosing interval should be titrated according to the patient's response, adjusting them until adequate pain relief is achieved.

Elderly Patients

Extreme caution must be exercised when prescribing morphine to elderly patients due to its respiratory depressant effects. A reduced dose is recommended.

Children

Children aged 1–5 years

• For acute / postoperative pain

By intramuscular or subcutaneous injection: 2.5–5 mg. Administration may be repeated every 4 hours as needed.

By intravenous injection over at least 5 minutes: 100–200 mcg/kg, repeated every 4 hours as needed (see Table 1).

By intravenous injection and infusion: initially by intravenous injection over at least 5 minutes at a dose of 100–200 mcg/kg (see Table 1), followed by continuous intravenous infusion at 20 mcg/kg/hour, adjusting the dose according to the patient's response.

• For chronic pain

By intramuscular or subcutaneous injection: initially at a dose of 150–200 mcg/kg every 4 hours, adjusting the dose according to the patient's response (see Table 2).

Children aged 6–12 years

• For acute / postoperative pain

By intramuscular or subcutaneous injection: 5–10 mg, repeated every 4 hours as needed.

By intravenous injection over at least 5 minutes: 100–200 mcg/kg, repeated every 4 hours as needed (see Table 1).

By intravenous injection and infusion: initially by intravenous injection (over at least 5 minutes) at a dose of 100–200 mcg/kg (see Table 1), followed by continuous intravenous infusion at 20 mcg/kg/hour, adjusting the dose according to the patient's response.

• For chronic pain

By intramuscular or subcutaneous injection: initially at a dose of 200 mcg/kg every 4 hours, adjusting the dose according to the patient's response (see Table 2).

Children aged 13–17 years

• For acute / postoperative pain

By intramuscular or subcutaneous injection: 10 mg, repeated every 4 hours (as needed).

By intravenous injection over at least 5 minutes: 2.5–10 mg.

By intravenous injection and infusion: initially by intravenous injection (over at least 5 minutes) at a dose of 2.5–10 mg, followed by continuous intravenous infusion at 20 mcg/kg/hour, adjusting the dose according to the patient's response.

• For chronic pain

By intramuscular or subcutaneous injection: initially at a dose of 5–20 mg every 4 hours, adjusting the dose according to the patient's response.

Hepatic Impairment

In patients with impaired liver function, morphine may precipitate coma; therefore, the use of the drug should be avoided or the dose reduced.

Renal Impairment

In patients with moderate or severe renal impairment, a reduction in the maintenance dose may be required.

In children, administer 75% of the dose if creatinine clearance is 10–50 mL/min/1.73 m², and 50% of the dose if creatinine clearance is <10 mL/min/1.73 m².

Since pediatric doses for children under 12 years of age are often based on body weight, the calculated dose may be verified using the tables provided below. These tables were developed using data based on average body weight values by age.

Table 1

Dose (mcg/kg)	Age (approximately)	Patient body weight (kg)	Dose (mg)	Volume of dose (ml)
100–200	1 year	10	1–2	0,1–0,2
	3 years	15	1,5–3	0,15–0,3
	5 years	18	1,8–3,6	0,18–0,36
	7 years	23	2,3–4,6	0,23–0,46
	10 years	30	3–6	0,3–0,6
	12 years	39	3,9–7,8	0,39–0,78

Table 2

Dose (mcg/kg)	Age (approximately)	Patient body weight (kg)	Dose (mg)	Volume of dose (ml)
150–200	1 year	10	1.5–2	0.15–0.2
	3 years	15	2.25–3	0.23–0.3
	5 years	18	2.7–3.6	0.27–0.36

To avoid errors, doses and volumes for children must be carefully calculated, measured, and verified by qualified healthcare professionals. Particular caution should be exercised when measuring very small volumes.

After calculation, the information in these tables should be used to verify whether the dose and volume correspond to the specific age and body weight of the child.

Method of administration

Morphine should be administered by intramuscular, subcutaneous, or intravenous injection.

The subcutaneous route should not be used in patients with edema.

Since the product contains a preservative, epidural or intrathecal administration must not be used.

Goals of treatment and its discontinuation

Before initiating treatment with Yufol 10 mg/mL solution for injection, a treatment strategy, including duration and objectives of therapy, as well as a plan for treatment discontinuation according to the pain management protocol, should be agreed upon with the patient. During therapy, the physician should maintain regular contact with the patient to assess the need for continued treatment, consider the possibility of discontinuing therapy, and, if necessary, adjust doses. When the patient no longer requires treatment with Yufol 10 mg/mL solution for injection, gradual dose reduction may be appropriate to prevent withdrawal symptoms. In the absence of adequate pain control, the possibility of hyperalgesia, tolerance, and progression of the underlying disease should be considered (see section "Special precautions").

Duration of treatment

Yufol 10 mg/mL solution for injection should not be used longer than necessary.

Children

The use of this medicinal product is not recommended in children under 1 year of age.

Overdose

Symptoms

Toxic doses vary significantly between patients. Patients regularly receiving morphine may tolerate high doses well.

The triad of symptoms—respiratory depression, coma, and pinpoint pupils—is considered indicative of opioid overdose; however, pupillary dilation may occur due to the development of hypoxia. Respiratory depression may lead to fatal outcome.

Other symptoms of opioid overdose include hypothermia, confusion, severe dizziness, profound drowsiness, hypotension, bradycardia, circulatory failure, pulmonary edema, pronounced restlessness or agitation, hallucinations, aspiration pneumonia, and seizures (particularly in infants and children). Cases of rhabdomyolysis progressing to renal failure have been reported in cases of overdose.

Respiratory depression may lead to fatal outcome.

Treatment

In the presence of coma or bradypnea, pharmacological treatment of overdose involves immediate administration of the specific opioid antagonist naloxone according to one of the recommended dosing regimens. Support of respiratory and cardiovascular function should be provided as needed.

Side effects

The most serious risk associated with morphine treatment is respiratory depression (see section "Overdose"). The most commonly observed side effects of morphine are nausea, vomiting, constipation, drowsiness, and dizziness.

Tolerance usually develops with prolonged use, but does not develop for constipation. Other possible adverse reactions:

Immune system disorders: Rare cases of anaphylactic reactions after intravenous injection and anaphylactoid reactions have been reported.

Psychiatric disorders: Drug dependence.

Nervous system disorders: Myoclonus, clouding of consciousness, confusion (with high-dose use), hallucinations, headache, vertigo, mood changes (including dysphoria), euphoria, allodynia, hyperalgesia (see section "Special precautions"), hyperhidrosis.

Eye disorders: Blurred or double vision, other visual disturbances, miosis.

Cardiac disorders: Bradycardia, palpitations, tachycardia, orthostatic hypotension.

Respiratory, thoracic and mediastinal disorders: Central sleep apnoea syndrome.

Gastrointestinal disorders: Dry mouth, biliary tract spasms, pancreatitis.

Hepatobiliary disorders: Spasm of the sphincter of Oddi.

Skin and subcutaneous tissue disorders: Itching, urticaria, rash, sweating. Contact dermatitis has been reported. Pain and irritation at the injection site, facial flushing, acute generalized exanthematous pustulosis (AGEP) may occur.

Musculoskeletal and connective tissue disorders: Muscle rigidity.

Renal and urinary disorders: Urination difficulties, urethral spasm, urinary retention, antidiuretic effect.

Reproductive system and breast disorders: Prolonged use may lead to reversible decrease in libido or potency.

General disorders and administration site conditions: Drug withdrawal syndrome (abstinence syndrome).

Tolerance develops to the effects of opioids on the urinary bladder.

The euphoric effect of morphine may lead to drug abuse, potentially causing physical and psychological dependence (see section "Special precautions").

Description of selected adverse reactions

Drug dependence and withdrawal syndrome (abstinence syndrome)

The use of opioid analgesics such as Yufol, 10 mg/mL, solution for injection, may be associated with the development of tolerance and physical and/or psychological dependence. Abrupt discontinuation of treatment or administration of opioid antagonists may precipitate withdrawal syndrome. In some cases, withdrawal symptoms may occur between doses (see section "Special precautions").

Repeated use of Yufol, 10 mg/mL, solution for injection, may lead to drug dependence, even at therapeutic doses. The risk of developing drug dependence may vary depending on individual patient risk factors, dosage, and duration of opioid treatment (see section "Special precautions").

Physiological withdrawal symptoms include body aches, tremor, restless legs syndrome, diarrhea, abdominal cramps, nausea, flu-like symptoms, tachycardia, and mydriasis. Psychological symptoms include dysphoria, anxiety, and irritability. Drug dependence often manifests as "drug craving."

Reporting suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare and pharmacy professionals, as well as patients or their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions

Store at temperatures not exceeding 25°C, protected from light. Keep in original packaging. Store out of reach of children.

Incompatibilities

Morphine salts are sensitive to pH changes; morphine may precipitate in alkaline environments.

Morphine salts are incompatible with aminophylline, sodium barbiturates, and phenytoin. Other reported incompatibilities (sometimes specific to individual products) include sodium acyclovir, doxorubicin, fluorouracil, furosemide, sodium heparin, meperidine hydrochloride, promethazine hydrochloride, and tetracyclines. For specific compatibility information, consult specialized sources.

Physical-chemical incompatibility (precipitate formation) has been reported between morphine sulfate solutions and 5-fluorouracil.

Packaging

1 mL in a glass ampoule, 5 ampoules in a blister pack, 2 blisters per cardboard box.

Prescription status. Prescription only.

Manufacturer

MACARTHYS LABORATORIES LIMITED T/A MARTINDALE PHARMA.

Manufacturer's address

BAMPTON ROAD, HAROLD HILL, ROMFORD, RM3 8UG, UNITED KINGDOM.

Marketing Authorization Holder

Yuria-Pharm LLC.

Address of the Marketing Authorization Holder

10 M. Amosova St., Kyiv, 03680, Ukraine.