Difmetre

Package leaflet: Information for the patient

DIFMETRÉ 25 mg + 75 mg + 2 mg film-coated tablets
DIFMETRÉ 50 mg + 150 mg + 8 mg suppositories
DIFMETRÉ 25 mg + 75 mg + 4 mg suppositories
indometacin, caffeine, prochlorperazine maleate
Please read this leaflet carefully before taking this medicine because it contains
important information for you.
Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their
symptoms are the same as yours, as it could be harmful.
If you experience any side effects, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.
Contents of this leaflet:

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

1. What DIFMETRÉ is and what it is used for

DIFMETRÉ is a medicine containing three active substances that act in different ways against pain:

• indometacin, belonging to the class of non-steroidal anti-inflammatory drugs (NSAIDs);
• prochlorperazine, belonging to the class of phenothiazines, which also acts against vomiting;
• caffeine, which enhances the analgesic effect of the medicine.

This medicine is used to treat headache pain, particularly:

• migraine, a type of pain that usually affects one half of the head. This pain is pulsating, worsens with movement, coughing, sneezing, physical exertion, and exposure to light; lasts from 4 to 72 hours; and may be associated with nausea, vomiting and/or visual disturbances (such as flashes of light, shimmering images, sparkling spots);
• migraine with aura. In these cases, the migraine is preceded by visual disturbances or tingling sensations, most frequently affecting the mouth, fingers, tongue, and arm. These symptoms develop gradually over 5–20 minutes and last less than 60 minutes;
• tension-type headache, a diffuse headache associated with a sensation of muscle tension in the head and/or neck.

2. What you need to know before taking DIFMETRÉ

Do not take DIFMETRÉ:

• if you are allergic to the active substances or to any of the other ingredients of this medicine (listed in section 6);
• if you have had an allergic reaction after taking other non-steroidal anti-inflammatory drugs (NSAIDs), for example acetylsalicylic acid, commonly known as aspirin;
• if you have had two or more separate episodes of stomach or intestinal ulceration or bleeding (including blood in vomit or during bowel movements, or black, tarry stools);
• if you have ever experienced a single episode of stomach or intestinal ulcer, perforation, or bleeding caused by taking medications;
• if you have severe heart problems;
• if you suffer from psychiatric disorders, for example depression or mood disturbances;
• if you have epileptic seizures;
• if you have Parkinson’s disease, characterized by resting tremor, muscle rigidity, and slowness of movement;
• after the sixth month of pregnancy (see “Pregnancy and breastfeeding”). Do not use DIFMETRÉ suppositories if you have inflammation or bleeding of the rectum (proctitis or rectorrhagia).

Warnings and precautions
Talk to your doctor or pharmacist before using DIFMETRÉ if:

• you are taking medicines that act on the brain (neuroleptics) or other NSAIDs;
• you have had stomach or intestinal disorders, such as Crohn’s disease or ulcerative colitis;
• you are elderly, as you are more likely to develop side effects. In particular, consult your doctor cautiously if:
• someone in your family has an abnormality on electrocardiogram (QT prolongation);
• you have heart or blood vessel problems, such as stroke, heart attack, or congestive heart failure, or think you may be at risk for these conditions (for example, if you have high blood pressure, diabetes, high cholesterol, or smoke), since medicines like DIFMETRÉ may be associated with a small increased risk of heart attack (myocardial infarction) or stroke. IN ALL THESE CASES, YOUR DOCTOR WILL EVALUATE WHETHER MONITORING TESTS ARE NEEDED.

BE CAREFUL, because during treatment with all NSAIDs:

• at any time, with or without warning symptoms, even in patients without previous serious gastrointestinal problems, gastrointestinal bleeding, ulceration, or perforation of the stomach or intestine have been reported, which can be fatal;
• pre-existing depression, epilepsy, or movement disorders (parkinsonism) may worsen;
• very rarely, serious skin reactions, some of which have been fatal, have been reported, presenting as redness, blistering, and skin peeling (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis). During the initial stages of therapy, patients appear to be at higher risk: such reactions occur in most cases within the first month of treatment. The risk of side effects increases with higher doses and prolonged treatment. Do not exceed the recommended dose of DIFMETRÉ or take it for long periods; always follow your doctor’s instructions carefully.

STOP treatment and contact your doctor if:

• you develop any symptoms affecting the stomach or intestine (gastrointestinal), especially if bleeding occurs;
• you develop a skin rash, mucosal lesions, or any other sign of an allergic reaction (e.g., redness, itching, swelling of the face and throat, sudden drop in blood pressure);
• you develop tremor, muscle rigidity, or persistent involuntary movements that you cannot control (signs of parkinsonism).

Children and adolescents under 18 years of age
Do not administer DIFMETRÉ to children and adolescents under 18 years of age.
Other medicines and DIFMETRÉ
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Some medicines may interact with DIFMETRÉ or increase the risk of side effects, even serious ones.
In particular, contact your doctor if you are taking:

• other pain and inflammation-reducing medicines (NSAIDs, salicylates, acetylsalicylic acid, commonly known as aspirin);
• medicines containing cortisone (corticosteroids);
• medicines that thin the blood (anticoagulants and antiplatelets), for example warfarin;
• medicines for depression, such as selective serotonin reuptake inhibitors or lithium; medicines for high blood pressure (hypertension), such as diuretics, ACE inhibitors, angiotensin II antagonists;
• medicines that cause changes in blood ions;
• digoxin, a medicine used for heart conditions;
• medicines that cause changes in the electrocardiogram (QT prolongation);
• medicines that act on the brain (neuroleptics);
• medicines used for Parkinson’s disease;
• benzodiazepines, medicines used for anxiety and with a calming effect;
• anticholinergic medicines, used for example in urinary incontinence or to treat muscle spasms;
• theophylline, used for example in the treatment of asthma.

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.
Pregnancy
Do not use DIFMETRÉ during the last three months of pregnancy, as this medicine may cause problems with the baby’s heart, lungs, or kidneys and complications during delivery. It may affect the bleeding tendency in both mother and baby and may delay or prolong labor beyond expected duration.
Consult your doctor before taking DIFMETRÉ during the first months of pregnancy (up to the sixth month), as this medicine should only be used when strictly necessary.
If treatment is required during this period or during attempts to conceive, the lowest possible dose for the shortest possible time should be used.
From week 20 of pregnancy, DIFMETRÉ may cause kidney problems in the fetus if taken for more than a few days, thereby reducing the levels of amniotic fluid surrounding the baby (oligohydramnios) or causing narrowing of a blood vessel (ductus arteriosus) in the baby’s heart. If treatment is required for more than a few days, your doctor may recommend additional monitoring.
Breastfeeding
Be cautious if you are breastfeeding: wait at least 24 hours after taking DIFMETRÉ before breastfeeding.
Driving and using machines
DIFMETRÉ may cause visual disturbances, drowsiness, and dizziness. Exercise particular caution before driving or operating machinery.
Information about excipients
DIFMETRÉ film-coated tablets contain: sucrose.
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.

3. How to take DIFMETRÉ

Take this medicine exactly as directed by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist.
Your doctor will determine the appropriate formulation (suppositories or tablets) and dosage based on your condition.

Adults (aged between 18 and 65 years)
DIFMETRÉ tablets
The recommended initial dose is 1 tablet at the onset of headache.
Your doctor may advise you to take another tablet if headache persists 2 hours after taking DIFMETRÉ.
The maximum dose is 8 tablets per day.
If headache recurs 24–48 hours after the first dose of DIFMETRÉ, your doctor may recommend taking another tablet.

DIFMETRÉ suppositories
Your doctor will prescribe DIFMETRÉ suppositories if your headache is accompanied by nausea or vomiting.
The recommended initial dose is 1 suppository at the onset of headache.
Your doctor may advise you to use another suppository if headache persists 2 hours after administration of DIFMETRÉ.
The maximum dose is 4 suppositories per day.
If headache recurs 24–48 hours after the first dose of DIFMETRÉ, your doctor may recommend using another suppository.

Children and adolescents under 18 years of age
DIFMETRÉ must not be used in children and adolescents under 18 years of age.

Elderly patients (over 65 years)
Your doctor will determine the appropriate formulation and dosage according to your general health condition.

Method of administration
DIFMETRÉ tablets: swallow the tablets orally.
DIFMETRÉ suppositories: administer the suppositories rectally.

If you take more DIFMETRÉ than you should, symptoms such as resting tremor, muscle rigidity, slowness of movement, difficult-to-control involuntary movements (extrapyramidal symptoms) may occur, accompanied by mental confusion, drowsiness or agitation, concentration disturbances, seizures, or electrocardiogram abnormalities. You may also experience gastrointestinal symptoms.

DIFMETRÉ contains caffeine. High doses of caffeine may cause: nausea, vomiting, anxiety, muscle tremor, seizures, changes or increased heart rate (arrhythmia or tachycardia), low blood pressure (hypotension), decreased blood potassium levels or blood pH (hypokalaemia, metabolic lactic acidosis).
In case of overdose, contact your doctor immediately or go to the nearest hospital, as appropriate medical measures may be required.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Inform your doctor if you experience any of the following side effects:

Common side effects (may affect up to 1 in 10 people)

• increased heart rate (tachycardia);
• dizziness, vertigo, tremors;
• nausea.

Uncommon side effects (may affect up to 1 in 100 people)

• visual disturbances;
• vomiting, indigestion (dyspepsia), inflammation of the stomach (gastritis), upper abdominal pain;
• fatigue (asthenia), malaise, chills, widespread pain;
• influenza-like illness;
• altered sensation (paresthesia), loss of consciousness even with lack of response to external stimuli (stupor), drowsiness, attention disturbances, headache associated with a feeling of muscle tension in the head and/or neck (tension-type headache);
• agitation, restlessness;
• breathing difficulty (dyspnea);
• sweating;
• drop in blood pressure.

Other side effects that may occur during treatment with DIFMETRÉ

• changes in heart rhythm (arrhythmias);

• dry mouth, diarrhea;

• blood abnormalities, increased blood pressure;

• confusion;

• sudden or abrupt appearance of skin lesions, for example, patchy or widespread skin discoloration (skin rash). Some side effects observed with other medicines containing prochlorperazine or other NSAIDs may also occur during treatment with DIFMETRÉ. These include:

• severe stomach problems, burning or abdominal pain due to stomach or duodenal (peptic) ulcer;

• sudden, severe pain in the upper abdomen (perforation of the ulcer);

• vomiting blood (haematemesis) or black stools (melena), associated with bleeding from the stomach or intestine (gastrointestinal), or unusual fatigue with reduced urine output (due to non-visible bleeding);

• nausea, intestinal gas (flatulence), difficulty passing stools (constipation and obstipation), abdominal pain, inflammation of the mouth lining with ulcers (ulcerative stomatitis), worsening of colon inflammation (colitis) and Crohn's disease;

• severe skin rashes with redness, blistering and peeling (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis);

• heart attack (myocardial infarction) or stroke, swelling (edema), reduced heart function (heart failure);

• resting tremor, muscle rigidity, involuntary and hard-to-control movements (extrapyramidal symptoms);

• changes in the electrocardiogram (ECG QT prolongation), disturbances in heart rhythm (ventricular arrhythmias such as torsades de pointes, ventricular tachycardia, ventricular fibrillation), cardiac arrest, sudden death. Additionally, the following may occur: agitation, restlessness, difficulty falling asleep (insomnia), muscle tremors, increased blood pressure, increased heart rate (tachycardia), sensation of the heart pounding (palpitations), due to excessive stimulation caused by caffeine (hyperstimulation).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor or pharmacist. You can also report side effects directly via the national reporting system at the website
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store DIFMETRÉ

Keep this medicine out of the sight and reach of children.
DIFMETRÉ 25 mg + 75 mg + 2 mg film-coated tablets.
This medicine does not require any special storage conditions.
DIFMETRÉ 50 mg + 150 mg + 8 mg suppositories
Do not store above 25°C.
DIFMETRÉ 25 mg + 75 mg + 4 mg suppositories
Do not store above 25°C.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the
last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What DIFMETRÉ contains
DIFMETRÉ 25 mg + 75 mg + 2 mg film-coated tablets.
The active substances are: indometacin, caffeine and prochlorperazine dimaleate.
The other components are: mannitol (E421), hydrated colloidal silica (E551), povidone (E1201),
talc (E553b), maize starch, magnesium stearate (E470b), arabic gum, sucrose, white
carnauba wax.
DIFMETRÉ 50 mg + 150 mg + 8 mg suppositories
The active substances are: indometacin, caffeine and prochlorperazine dimaleate.
The other components are: solid semisynthetic glycerides.
DIFMETRÉ 25 mg + 75 mg + 4 mg suppositories
The active substances are: indometacin, caffeine and prochlorperazine dimaleate.
The other components are: solid semisynthetic glycerides.

Description of the appearance of DIFMETRÉ and contents of the pack
DIFMETRÉ 25 mg + 75 mg + 2 mg film-coated tablets
20 film-coated tablets in PVC/Al blister packs
DIFMETRÉ 50 mg + 150 mg + 8 mg suppositories
6 suppositories in PVC/PE blister packs
DIFMETRÉ 25 mg + 75 mg + 4 mg suppositories
6 suppositories in PVC/PE blister packs

Marketing Authorization Holder
Viatris Italia S.r.l.
Via Vittor Pisani 20
20124 Milano, Italy

Manufacturer
DIFMETRÉ 25 mg + 75 mg + 2 mg film-coated tablets
DIFMETRÉ 50 mg + 150 mg + 8 mg suppositories
DIFMETRÉ 25 mg + 75 mg + 4 mg suppositories
Meribel Pharma Parets, S.L.U., Ramón y Cajal 2, 08150 Parets del Vallés, Spain