Oramorph

Patient Information Leaflet

Oramorph, 20 mg/ml, oral drops, solution
Morphini sulfas
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Oramorph is and what it is used for

The name of the medicine is Oramorph, 20 mg/ml, oral drops, solution. In this leaflet, the shorter name Oramorph is used. Oramorph contains morphine (as sulfate) as the active substance. It belongs to a group of medicines called "opioids".
Oramorph is used for the treatment of severe pain or pain that cannot be controlled by other medicines (particularly cancer pain) in adults, adolescents, and children (over 1 year of age).

2. Important information before using Oramorph

When not to take Oramorph

• if the patient is allergic to morphine sulfate or any of the other ingredients of this medicine (listed in section 6)
• if the patient has consumed a large amount of alcohol ("alcohol intoxication")
• if the patient is highly agitated due to alcohol consumption or taking sleeping medicines ("hypnotics")
• in case of suspected intestinal obstruction
• in case of acute abdomen syndrome
• in case of acute liver diseases
• in case of head injury or increased intracranial pressure
• in case of asthma or sudden or serious breathing problems
• in case of serious breathing difficulties ("respiratory depression")
• if the patient is taking MAO inhibitors (used to treat depression) or has taken them within the last 2 weeks
• during pregnancy or breastfeeding.

Do not take Oramorph if any of the above apply to the patient. If in doubt, consult a doctor or pharmacist before starting treatment with Oramorph.
Warnings and precautions
Before starting treatment with Oramorph, discuss with your doctor or pharmacist if the patient:

• has breathing problems caused by airway obstruction or diseases affecting respiration (such as scoliosis, emphysema, or severe obesity)
• has heart and breathing problems (cor pulmonale)
• has increased intracranial pressure
• has low blood pressure combined with low circulating blood volume
• is not fully conscious
• has undergone surgery within the last 24 hours
• is due to undergo surgery within 24 hours for pain relief ("cordotomy")
• has chronic kidney or liver problems, pancreatitis, hypothyroidism, adrenal gland disorders, or tumors called "pheochromocytoma"
• has benign prostatic hyperplasia with urinary retention
• has inflammatory bowel conditions or intestinal problems causing obstruction
• has biliary or urinary tract obstruction
• has colicky pain caused by gallstones or kidney stones
• has undergone biliary tract surgery
• has problems with normal emptying of the stomach
• has epilepsy or occasionally experiences seizures (fits)
• is taking medicines similar to morphine (such as buprenorphine, nalbuphine, pentazocine) or medicines that reverse the effects of morphine (such as naloxone).

If any of the above apply to the patient (or if the patient is unsure), consult a doctor or pharmacist before using Oramorph.
If any of the following symptoms occur during treatment with Oramorph, consult a doctor or pharmacist:

• Increased sensitivity to pain despite increasing doses (hyperalgesia). The doctor will decide whether a dose adjustment or a change in strong painkiller ("analgesic") is needed (see section 3).
• Weakness, fatigue, loss of appetite, nausea, vomiting, or low blood pressure. This may indicate that the adrenal glands are producing too little cortisol, and hormone supplementation may be necessary.
• Loss of libido, impotence, cessation of menstruation. This may be due to reduced production of sex hormones.
• If the patient is or has been addicted to drugs or alcohol. The patient should also inform the doctor if they feel becoming dependent on Oramorph while using it. If so, the patient may frequently think about when they can take the next dose, even if it is not needed for pain relief.
• Cases of acute generalized exanthematous pustulosis (AGEP) have been reported with Oramorph treatment. Symptoms usually occur within the first 10 days of treatment. Inform the doctor if the patient has ever experienced severe skin rash, skin peeling, blisters, and/or oral mucosal ulcers after taking Oramorph or other opioids. Discontinue Oramorph immediately and seek medical attention promptly if the patient notices any of the following symptoms: appearance of blisters, extensive skin peeling, or pustular lesions accompanied by fever.
• Sleep-related breathing disorders. Oramorph may cause sleep-related breathing disorders such as sleep apnea (pauses in breathing during sleep) and sleep-related hypoxemia (low oxygen levels in the blood). Symptoms may include episodes of stopped breathing during sleep, waking up at night due to breathlessness, difficulty maintaining sleep, or excessive daytime sleepiness. Consult a doctor if the patient or someone else notices these symptoms. The doctor may consider reducing the dose.
• Contact the doctor if the patient develops severe upper abdominal pain radiating to the back, nausea, vomiting, or fever, as these may be symptoms of pancreatitis or biliary tract disorders.
• Withdrawal symptoms or dependence. The most common withdrawal symptoms are listed in section 3. If they occur, the doctor may change the type of medicine or the interval between doses.

Surgery, examinations, and monitoring

• Patients taking Oramorph are at higher risk of gastrointestinal or breathing problems after surgery. Therefore, doctors will exercise particular caution before and after the procedure.
• The pain-relieving effect of morphine may mask serious postoperative complications, such as intestinal perforation.
• If the patient has adrenal gland disorders, doctors will perform monitoring tests in case steroid medications become necessary.

Tolerance, dependence, and compulsive use
This medicine contains morphine, which is an opioid. If the patient takes Oramorph for a long time, their body may become accustomed to it (called "tolerance"). This means the medicine will become less effective.

• This is less likely to happen if the amount taken is just sufficient to relieve pain. To reduce this risk, always take Oramorph exactly as prescribed by the doctor.
• The dose should be taken as directed by the doctor, daily and at the correct time.

Repeated use of opioids may reduce the effectiveness of the medicine (the patient becomes accustomed to it, known as drug tolerance). Repeated use of Oramorph may also lead to dependence, abuse, and compulsive use, which may result in life-threatening overdose. The risk of these adverse effects may increase with higher doses and longer duration of use.
Dependence or compulsive use may cause the patient to feel a loss of control over how much medicine to take or how often to take it.
The risk of dependence or compulsive use varies among individuals. The risk of becoming dependent on or compulsively using Oramorph may be higher if:

• the patient or any of their relatives has ever abused or been dependent on alcohol, prescription medicines, or drugs ("addiction");
• the patient smokes cigarettes;
• the patient has ever had mood disorders (depression, anxiety disorders, or personality disorders) or has been treated by a psychiatrist for other mental illnesses.

If any of the following symptoms occur while taking Oramorph, this may indicate dependence or compulsive use:

• the patient needs to take this medicine longer than prescribed by the doctor;
• the patient needs to take a higher dose than prescribed;
• the patient uses this medicine for reasons other than those for which the doctor prescribed it, e.g., "to calm down" or "to help sleep";
• the patient has made multiple unsuccessful attempts to stop or control use of this medicine;
• after stopping this medicine, the patient feels unwell and feels better when taking it again ("withdrawal effect").

If any of these symptoms are noticed, discuss with the doctor the best treatment strategy for the patient, including when it is appropriate to discontinue treatment and how it can be safely stopped (see section 3 "Stopping treatment with Oramorph").
Children and adolescents
Due to its concentration, Oramorph is not suitable for children under 1 year of age.
Oramorph and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, including over-the-counter medicines and herbal supplements.
The patient should not take this medicine and should inform their doctor or pharmacist if they are taking or using any of the following medicines:

• MAO inhibitors (used to treat depression), including if the patient has taken them within the last 2 weeks
• medicines similar to morphine (such as buprenorphine, nalbuphine, pentazocine) or medicines that reverse the effects of morphine (such as naloxone). The patient should not take Oramorph if any of the above apply. If in doubt, consult a doctor or pharmacist before starting treatment with Oramorph. The patient should also inform the doctor or pharmacist if they are taking or using any of the following medicines:
• medicines that help with sleep or cause sedation—such as sedatives, anesthetics, and sleeping pills
• sedative medicines, such as benzodiazepines or related drugs. Concurrent use with Oramorph increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, which may be life-threatening. For this reason, concurrent use should only be considered if no other treatment options are possible. If the doctor prescribes Oramorph together with other sedative medicines, the dose and duration of concurrent treatment should be limited by the doctor. Inform the doctor about all sedative medicines the patient is taking and follow dosage instructions exactly. It may be helpful to inform friends or relatives to be aware of the symptoms mentioned above. Contact the doctor if such symptoms occur.
• medicines for mental health problems, such as depression (called "tricyclic antidepressants") or schizophrenia (called "phenothiazines"), such as clomipramine and amitriptyline.
• These medicines may enhance the "depressant" effect of Oramorph, especially on breathing. Alcohol also has this depressant effect.
• other medicines for mental health problems.
• These medicines may worsen side effects such as constipation, dry mouth, and difficulty urinating (so-called "anticholinergic" side effects).
• medicines called "antihistamines"
• medicines to prevent vomiting (antiemetics)
• medicines used to treat Parkinson's disease
• cimetidine—used to treat stomach ulcers and other stomach problems
• muscle relaxants used during surgical procedures
• medicines used to treat high blood pressure
• rifampicin—an antibiotic used to treat, for example, tuberculosis
• some medicines used to treat blood clots (e.g., clopidogrel, prasugrel, ticagrelor) may have delayed and reduced effects when taken with morphine
• gabapentin or pregabalin used to treat epilepsy and nerve-related pain (neuropathic pain).

If any of the above apply to the patient, consult a doctor or pharmacist before using Oramorph.
Oramorph and alcohol
Do not drink alcohol while taking Oramorph.
Pregnancy, breastfeeding, and fertility

• Do not use Oramorph if the patient is pregnant, suspects she may be pregnant, or is planning to become pregnant. This may affect the unborn child. If Oramorph is used for a prolonged period during pregnancy, there is a risk that the newborn will experience withdrawal symptoms, which should be treated by a doctor.
• Do not breastfeed while taking Oramorph, as small amounts may pass into breast milk.
• Do not plan pregnancy while taking this medicine. The patient and her partner should use effective contraception during treatment. If pregnancy occurs during this time, contact the doctor immediately.

Driving and operating machinery

• Do not drive, ride a bicycle, or operate any tools or machinery while taking this medicine. The patient may feel drowsy and less alert—even at normal doses.
• This effect is more pronounced at the beginning of treatment or after a dose increase. The effect is also stronger if the patient drinks alcohol or takes other medicines that cause drowsiness. The time after which it is safe to resume driving or operating machinery is highly individual and must be determined by the doctor.

Oramorph contains sodium benzoate. This medicine contains 1 mg of sodium benzoate per ml (16 drops).

• Sodium This medicine contains less than 1 mmol of sodium per ml (16 drops), meaning the medicine is considered "sodium-free".

3. How to take Oramorph

This medicine should always be taken exactly as directed by the doctor. If in doubt, consult the doctor or pharmacist.
Before starting treatment and regularly during therapy, the doctor will discuss with the patient what to expect from taking Oramorph, when and for how long the medicine should be taken, when to contact the doctor, and when to stop taking the medicine (see also "Stopping Oramorph" in this section).
Dosage
The doctor will determine the dose based on the intensity of pain, the patient's age, concomitant use of other medicines, and liver function.
The doctor may increase the dose depending on:

• intensity of pain
• previous use of pain-relieving medicines.

For lower doses, Oramorph is available as an oral solution 2 mg/ml.
What dose should be taken
Oral administration.
The solution should be taken with a drink (water or juice). This medicine may be taken regardless of meals.
The dosing intervals of 4 or 4 to 6 hours must be strictly observed. The effect of this medicine lasts approximately 4 hours.

How to measure the dose

• To open the bottle, press down and turn the cap at the same time.
• To measure the dose, count the drops from the 20 ml bottle (1 drop = 1.25 mg of morphine sulfate):
  4 drops = 5 mg morphine
  8 drops = 10 mg morphine
  16 drops = 20 mg morphine
  24 drops = 30 mg morphine
• After pouring the medicine, close the bottle tightly with the cap. Oramorph is not suitable for long-term use.

Elderly patients (over 75 years of age)
Elderly individuals (aged 75 years and older) and those generally in poor health may be more sensitive to morphine. Therefore, a lower dose may be given.

Patients with liver, kidney or heart problems
The doctor will exercise particular caution when determining the dose for patients with liver, kidney or heart problems. The same applies to patients with delayed gastric and intestinal motility.

Taking a higher than recommended dose of Oramorph
If a higher than recommended dose of Oramorph is taken, seek immediate medical advice from a doctor or go to the nearest hospital.

In such a case, the following symptoms may occur:

• Breathing difficulties, which may lead to loss of consciousness and even death
• Very small pupils (pupillary constriction)
• Low blood pressure
• Drowsiness – ranging from mild fatigue to profound sleepiness
• Cold and clammy skin

In patients who have taken an excessive dose, aspiration pneumonia caused by inhalation of vomit or foreign bodies may occur; symptoms include shortness of breath, cough and fever.
The effect on the patient depends on the amount of morphine taken.
Information for the physician: see section Information intended exclusively for healthcare professionals.

Missing a dose of Oramorph
This medicine must always be taken strictly as prescribed by the doctor. If a patient forgets to take a dose, they should consult their doctor. Do not take a double dose to make up for a missed dose.

Stopping treatment with Oramorph
Do not stop taking Oramorph without talking to your doctor. If a patient wishes to discontinue treatment with Oramorph, they should consult their doctor on how to gradually reduce the dose to avoid withdrawal symptoms. Withdrawal symptoms may include body aches, tremors, diarrhea, abdominal pain, nausea, flu-like symptoms, rapid heartbeat and dilated pupils. Psychological symptoms may include intense feelings of unease, anxiety and irritability.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.
Important adverse effects or symptoms to watch for and what to do if they occur:

• Severe allergic reaction causing difficulty in breathing or dizziness.
• Severe skin reaction with blistering, widespread peeling of the skin, or pustular rash accompanied by fever. This may be a condition called acute generalised exanthematous pustulosis (AGEP). In case of occurrence of these serious adverse effects, contact your doctor immediately. If you notice any of the following adverse effects, inform your doctor or pharmacist:

Very common: affects more than 1 in 10 patients

• Mood changes, mainly euphoria, but low mood may also occur.

Common: affects 1 in 10 patients

• Dizziness or headache
• Changes in well-being (mainly drowsiness, but sometimes increased activity or restlessness)
• Insomnia
• Thinking and perception disturbances (feeling of anxiety, hallucinations, confusion)
• Constricted pupils
• Nausea or vomiting (more frequent at the beginning of treatment)
• Constipation
• Loss of appetite, abdominal pain or taste disturbances
• Excessive sweating
• Allergic reactions such as urticaria and skin itching.

Uncommon: affects 1 in 100 patients

• Breathing difficulties, bronchial narrowing (bronchospasm)
• Facial flushing
• Disorientation, restlessness, dizziness, drowsiness or excessive drowsiness, or mood changes
• Irregular heartbeat (palpitations)
• Dry mouth
• Colic or biliary colic
• Urinary retention (inability to empty the bladder), passing less urine than usual, urinary tract spasms.

Rare: affects 1 in 1,000 patients

• Severe allergic reactions (anaphylactic and anaphylactoid reactions), asthma attacks in sensitive patients
• Chills or low body temperature
• Increased intracranial pressure
• Blurred vision, double vision, and unusual eye movements
• Low blood pressure, slow or rapid heartbeat, generalised muscle weakness, which may lead to fainting and heart failure
• Increased levels of pancreatic enzymes (shown in blood tests) or symptoms related to inflammation of the pancreas (pancreatitis) and biliary tract, e.g. severe upper abdominal pain radiating to the back, nausea, vomiting, or fever.

Very rare: affects fewer than 1 in 10,000 patients

• Sudden shortness of breath
• Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) with low blood sodium levels
• Tremor, involuntary muscle twitching, seizures
• Morphine dependence
• Low libido or sexual impotence
• Intestinal obstruction, abdominal pain
• Increased liver enzyme levels (shown in blood tests)
• Other skin reactions such as rash and skin swelling (resolves upon discontinuation of the medicine). Morphine releases histamine and may consequently cause urticaria, other skin reactions, and itching
• Muscle spasms, muscle stiffness.

Frequency not known: frequency cannot be estimated from available data

• Sleep apnoea (episodes of breathing cessation during sleep)
• Increased sensitivity to pain
• Withdrawal symptoms (symptoms – see section 3: Discontinuation of Oramorph treatment).

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, phone: +48 22 4921301, fax: +48 22 4921309. Website: https://smz.ezdrowie.gov.pl.
Reporting adverse effects helps to provide more information on the safety of the medicine.
Adverse effects can also be reported to the marketing authorisation holder.

5. How to store Oramorph

The bottle should be stored in the outer carton to protect it from light.
Do not store above 25°C.
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and bottle after:
"EXP". The expiry date refers to the last day of the stated month.
Expiry date after opening the Oramorph bottle: 3 months.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Oramorph contains

• The active substance is morphine sulfate. 1 ml of the aqueous solution contains 20 mg of morphine sulfate.
• The other ingredients are: edetate disodium, sodium benzoate (E 211), citric acid (for pH adjustment), and purified water.

What Oramorph looks like and contents of the pack
Oramorph is a nearly colourless aqueous solution for oral use, available in a 20 ml bottle with a dropper.
Marketing Authorisation Holder and Manufacturer
L. Molteni & C. dei F.lli Alitti Società di Esercizio S.p.A.,
Strada Statale 67, Tosco Romagnola,
50018 Scandicci (FI),
Italy
This medicinal product is authorised in the EEA Member States under the following names:
Austria: Oramorph, 20 mg/ml
Croatia: Oramorph, 20 mg/ml
Czech Republic: Morfin sulfát Ardez, 20 mg/ml
Slovenia: Oramorph, 20 mg/ml, peroralna kapljice, raztopina

Information intended exclusively for medical personnel:

Overdose
Symptoms:
Signs of morphine intoxication and overdose include: respiratory depression, aspiration pneumonia, miosis (pinpoint pupils), and hypotension. In cases of significant hypoxia, pupils may become dilated, accompanied by respiratory depression (respiratory rate 2–4 breaths per minute), and the patient may become cyanotic.
In more severe cases, circulatory failure and deep coma may occur. Initially, blood pressure remains within normal limits but drops noticeably as intoxication progresses. Persistent hypotension may lead to shock. Tachycardia, bradycardia, and rhabdomyolysis may occur. Body temperature decreases. Skeletal muscles become relaxed, and generalized seizures may occasionally occur, particularly in children. Respiratory failure or complications such as pulmonary edema may result in death.

Treatment of overdose:
Primary measures include airway clearance and maintenance of airway patency, as well as assisted or controlled ventilation.
In cases of significant overdose, intravenous administration of 0.4–0.8 mg naloxone is recommended. If necessary, doses may be repeated at 2–3 minute intervals or replaced by an infusion of 2 mg in 500 ml of normal saline or 5% dextrose solution (0.004 mg/ml). The infusion rate should be adjusted according to previously administered doses and the patient's response. Since the effect of naloxone wears off after a relatively short time (2–3 hours), close monitoring of the patient is essential until spontaneous respiration is fully restored.
The single dose of naloxone in children is 0.01 mg per kg body weight.

Naloxone should not be administered if morphine overdose does not cause clinically significant respiratory or circulatory depression. Naloxone must be administered with extreme caution to individuals with known or suspected physical dependence on morphine. In such cases, sudden or complete antagonism of opioid effects may precipitate an acute withdrawal syndrome.
Additional supportive measures (oxygen administration, vasopressor agents, intravenous fluid volume supplementation) should be applied according to the patient's condition. Gastric lavage should be performed within the first 2 hours after morphine ingestion and only in patients responding to treatment.