VEMONIS ULTRA

Package leaflet: Information for the patient

Vemonis Ultra, 400 mg + 60 mg + 80 mg, coated tablets
Metamizolum natricum + Coffeinum + Drotaverini hydrochloridum
Vemonis Ultra may cause abnormally low white blood cell count (agranulocytosis), which can lead to severe and life-threatening infections (see section 4).
Treatment with this medicine should be discontinued and medical advice should be sought immediately if any of the following symptoms occur: fever, chills, sore throat, painful ulcers of the nose, mouth and throat, or in the genital or anal area.
If agranulocytosis has ever occurred in the patient while taking metamizole or similar medicines, this medicine must never be taken again in the future (see section 2).
Please read the entire leaflet carefully before taking this medicine, as it contains important information for the patient.
This medicine should always be taken exactly as described in this patient leaflet or as directed by the physician or pharmacist.

• Keep this leaflet, as you may need to read it again.
• If you need advice or further information, please consult your pharmacist.
• If you experience any adverse reactions, including any possible adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.
• If your condition does not improve or worsens, contact your doctor.

Table of contents

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

1. What Vemonis Ultra is and what it is used for

Vemonis Ultra is intended for use in adults for symptomatic treatment of:

• pain associated with smooth muscle spasms, ranging from mild to severe:
• genitourinary system (renal colic, painful menstruation),
• gastrointestinal tract (intestinal colic, irritable bowel syndrome),
• biliary tract (cholecystitis, cholangitis).
• moderate pain of various origins, when the use of other medicines is contraindicated or ineffective.

Vemonis Ultra is a combination medicine with analgesic properties. Metamizole sodium has analgesic effects, caffeine has a stimulating effect on the central nervous system and causes vasodilation, while drotaverine hydrochloride has spasmolytic effects on smooth muscles.
If there is no improvement or the patient feels worse, medical advice should be sought.

2. Important information before taking Vemonis Ultra

When not to take Vemonis Ultra:

• if the patient has previously experienced a significant decrease in the number of white blood cells called granulocytes, caused by metamizole or other similar drugs known as pyrazolones or pyrazolidines;
• if the patient has bone marrow dysfunction or a condition affecting the production or function of blood cells;
• if the patient is allergic to metamizole, caffeine, drotaverine, pyrazolone derivatives (e.g. phenazone, propyphenazone) or pyrazolidine derivatives (e.g. phenylbutazone, oxyphenbutazone), or any of the other ingredients of this medicine (listed in section 6);
• if the patient suffers from asthma or intolerance associated with taking certain pain-relieving drugs such as salicylates, paracetamol, diclofenac, ibuprofen, indomethacin or naproxen, manifesting as bronchospasm, urticaria, rhinitis, or angioedema;
• if the patient has severe renal or hepatic insufficiency;
• if the patient has severe heart failure;
• if the patient has second- or third-degree atrioventricular block;
• if the patient suffers from certain metabolic disorders (porphyria, glucose-6-phosphate dehydrogenase deficiency);
• if the patient has anaemia;
• if the patient is under 18 years of age;
• if the patient is pregnant or breastfeeding;
• if the patient has hypersensitivity to soy or peanuts (the medicine contains soy lecithin).

Warnings and precautions
Before starting treatment with Vemonis Ultra, consult a doctor or pharmacist if:

• the patient has asthma or intolerance to certain pain-relieving drugs (see section When not to take Vemonis Ultra) manifesting as urticaria, angioedema, particularly if associated with nasal polyposis and sinusitis;
• the patient has bronchial asthma, especially when associated with chronic sinusitis and nasal polyps;
• the patient has allergies or atopy, which may lead to anaphylactic shock. Therefore, particular caution is advised when using metamizole in patients with asthma or atopy (see also section When not to take Vemonis Ultra);
• the patient has chronic urticaria;
• the patient has intolerance to certain dyes (e.g. tartrazine) or preservatives (e.g. benzoates);
• the patient has alcohol intolerance, manifesting as sneezing, lacrimation, and intense facial flushing even after small amounts of alcohol; this may indicate undiagnosed asthma related to certain pain-relieving drugs (see section When not to take Vemonis Ultra);
• the patient has low blood pressure, circulatory problems, or has experienced fluid loss or dehydration;
• the patient has hypertension;
• the patient has high fever;
• the patient has kidney or liver problems;
• the patient is over 65 years of age, in poor general health, or has renal impairment;
• the patient has hypersensitivity to other substances;
• the patient suffers from hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption syndrome.

If in doubt whether any of the above conditions apply, consult the treating physician before starting Vemonis Ultra.
Abnormally low white blood cell count (agranulocytosis)
Vemonis Ultra may cause agranulocytosis, i.e. a very low number of a type of white blood cells called granulocytes, which play an important role in fighting infections (see section 4). Discontinue metamizole and contact a doctor immediately if the following symptoms occur, as they may indicate possible agranulocytosis: chills, fever, sore throat, and painful mucosal ulcers, especially in the oral cavity, nose, throat, genital area, or anus.
The doctor will order laboratory tests to check the patient's blood cell count. If metamizole is taken for fever, some symptoms of developing agranulocytosis may remain unnoticed. Similarly, symptoms may also be masked if the patient is receiving antibiotics.
Agranulocytosis may develop at any time during treatment with Vemonis Ultra, and even shortly after discontinuation of metamizole.
Agranulocytosis may occur even if metamizole was previously administered without complications.
Abnormal platelet and other blood cell counts
Metamizole may cause thrombocytopenia, manifesting as increased bleeding tendency, petechiae, or hemorrhagic spots on the skin and mucous membranes. If symptoms of thrombocytopenia occur, the patient should immediately discontinue the medicine and contact a doctor.
During treatment, severe reduction in red and white blood cells as well as platelets, known as pancytopenia, may also occur. Patients should promptly consult a doctor if symptoms such as malaise, infection, persistent fever, bruising, bleeding, or pallor appear during treatment with Vemonis Ultra. If blood tests reveal abnormalities in blood cell or platelet counts, treatment must be immediately discontinued and blood cell and platelet counts monitored until they return to normal.
Liver-related disorders
Cases of hepatitis have been reported in patients taking metamizole, with symptoms appearing from several days to several months after starting treatment.
Discontinue use of Vemonis Ultra and contact a doctor if the patient experiences liver-related symptoms such as malaise (nausea or vomiting), fever, fatigue, loss of appetite, dark urine, pale stools, jaundice (yellowing of the skin or whites of the eyes), itching, rash, or upper abdominal pain. The doctor will assess liver function.
Patients should not take Vemonis Ultra if they previously used any medicinal products containing metamizole and experienced liver-related adverse effects.
Severe skin reactions
There is a risk of severe skin reactions characterized by blistering of the skin and mucous membranes—such as erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug reaction with eosinophilia and systemic symptoms (DRESS syndrome). If any of these symptoms related to severe skin reactions (listed in section 4) occur, discontinue and do not restart treatment with Vemonis Ultra. Patients should also seek immediate medical attention. Vemonis Ultra should not be used by patients with hypersensitivity to its ingredients (a detailed description of contraindications is provided above in section When not to take Vemonis Ultra).
Severe allergic reaction
A severe allergic reaction, known as anaphylactic reaction, may manifest as facial and throat swelling, generalized urticaria, or bronchospasm, and may be life-threatening. Therefore, Vemonis Ultra should not be used by patients with hypersensitivity to its ingredients or by those with a history of allergic reactions to other pain-relieving drugs (a detailed description of contraindications is provided above in When not to take Vemonis Ultra). Patients who have experienced an anaphylactic or other immunological reaction to metamizole are also at risk of a similar reaction to other pyrazolones and pyrazolidines.
Reduction in blood pressure
Vemonis Ultra may cause a reduction in arterial blood pressure (hypotension), which is likely dose-dependent. The risk of severe hypotension increases in patients with pre-existing low blood pressure, circulatory problems, or those who have experienced fluid loss or dehydration (see above). In such patients, Vemonis Ultra should be used with caution and only after consultation with a doctor.
Elderly patients
See section 3.
Patients with kidney or liver problems
See section 3.
Patients with other allergies
Patients with hypersensitivity (e.g. skin reactions or itching) to other substances (e.g. supplements, preservatives) should use Vemonis Ultra with caution.
Due to the caffeine content, excessive intake of caffeine (e.g. coffee, tea, and certain other beverages) should be avoided during treatment with this medicine.
The medicine should not be taken immediately before going to sleep.
Children and adolescents
Vemonis Ultra should not be used in individuals under 18 years of age (see When not to take Vemonis Ultra in section 2).
Vemonis Ultra and other medicines
Inform your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines planned for future use.
When using Vemonis Ultra with other medicines, consider the following interactions:

• Cyclosporine (used in transplant patients) – serum cyclosporine levels should be monitored, as they may decrease due to interaction with metamizole;
• Methotrexate (used in treating certain cancers) – metamizole may increase methotrexate toxicity to the bone marrow (where new blood cells are produced), especially in elderly patients. Therefore, concomitant use of methotrexate and Vemonis Ultra should be avoided;
• Acetylsalicylic acid – metamizole may reduce the antiplatelet effect of low-dose acetylsalicylic acid. Patients taking low-dose acetylsalicylic acid for cardiovascular prevention should use Vemonis Ultra with caution;
• Bupropion (an antidepressant and smoking cessation aid) – metamizole may reduce bupropion blood concentration. Therefore, caution is advised when using Vemonis Ultra and bupropion concomitantly;
• Efavirenz (used in treating HIV infection (AIDS)) – metamizole may reduce plasma levels of this drug and limit its clinical efficacy;
• Methadone (used in treating addiction to illegal opioids) – metamizole may reduce plasma levels of this drug and limit its clinical efficacy;
• Valproate (used in treating epilepsy or bipolar affective disorder) – metamizole may reduce plasma levels of this drug and limit its clinical efficacy;
• Tacrolimus (used to prevent organ rejection in transplant patients) – metamizole may reduce plasma levels of this drug and limit its clinical efficacy;
• Sertraline (used in treating depression) – metamizole may reduce plasma levels of this drug and limit its clinical efficacy;
• Drugs metabolized by the liver (e.g. clarithromycin, ethinylestradiol, sertraline) – caffeine may increase their blood concentration;
• Salicylates – caffeine may enhance their absorption;
• Cimetidine (a drug reducing gastric acid), oral contraceptives, ciprofloxacin and enoxacin (used in treating infections), mexiletine (used in treating cardiac arrhythmias) – these drugs may increase caffeine blood concentration;
• Muscle relaxants – some muscle relaxants inhibit caffeine metabolism; therefore, concomitant use of Vemonis Ultra with these drugs is not recommended;
• Nicotine – increases caffeine elimination;
• Disulfiram (used in treating alcoholism), ethinylestradiol (used in treating menstrual disorders and as contraception) – may enhance the effects of caffeine;
• Levodopa (used in symptomatic treatment of Parkinson’s disease) – the effect of levodopa may be reduced; therefore, tremors and rigidity may worsen in patients with Parkinson’s disease when Vemonis Ultra and levodopa are used concomitantly. Vemonis Ultra and alcohol Concurrent alcohol consumption may affect concentration and reaction time (see Driving and operating machinery).

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult a doctor or pharmacist before using this medicine.
Do not take Vemonis Ultra during pregnancy or breastfeeding.
Driving and operating machinery
At the recommended dosage, no effect of Vemonis Ultra on concentration and reaction time has been observed. However, at higher doses of metamizole or after alcohol consumption, concentration and reaction time may deteriorate, or drotaverine may cause dizziness, while caffeine may cause psychomotor hyperactivity, nervousness, or exhaustion, posing a risk in situations where these functions are critical (e.g. driving vehicles or operating machinery).
Vemonis Ultra contains monohydrate lactose, soy lecithin, and sodium
Vemonis Ultra contains monohydrate lactose
If the patient has been diagnosed with intolerance to certain sugars, the patient should consult a doctor or pharmacist before taking this medicine.
Vemonis Ultra contains soy lecithin
Do not use this medicine if allergic to peanuts or soy.
Vemonis Ultra contains sodium
Each coated tablet contains 27.6 mg of sodium (the main component of table salt) per tablet, equivalent to 1.4% of the WHO-recommended maximum daily intake of 2 g of sodium for adults.

3. How to take Vemonis Ultra

This medicine should always be taken exactly as described in this patient leaflet, or as directed by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist.
Adults
The recommended dose for adults is 1 tablet two or three times daily. The maximum daily dose is 3 tablets.
Children and adolescents
Vemonis Ultra must not be used in individuals under 18 years of age (see When not to take Vemonis Ultra in section 2).
Elderly patients and patients in poor general health or with renal impairment (see also “When not to take Vemonis Ultra” and “Warnings and precautions” in section 2)
In elderly patients, weakened patients, and patients with impaired renal function, the dose of metamizole should be reduced due to the possible prolonged elimination of metamizole metabolites.
In elderly patients with poor general health and reduced creatinine clearance, a lower dose of drotaverine is recommended due to the slower metabolism of this active substance.
Patients with impaired renal or hepatic function (see also “When not to take Vemonis Ultra” and “Warnings and precautions” in section 2)
Due to reduced elimination of metamizole in patients with impaired renal or hepatic function, repeated administration of high doses of metamizole should be avoided. Dose reduction of metamizole is not required for short-term use. There is no experience with long-term use of metamizole.
Method of administration
For oral use.
Taking more Vemonis Ultra than recommended
After ingestion of very high doses, excretion of an innocuous metabolite may cause red discoloration of urine.
Acute overdose may cause nausea, vomiting, abdominal pain, deterioration of kidney function or acute renal failure, and less frequently, symptoms affecting the central nervous system (dizziness, drowsiness, coma, convulsions), as well as hypotension. Patients may also experience chest discomfort, nervousness, irritability, tremor, muscle cramps, headache, insomnia, anxiety, euphoria, confusion, disorientation, or agitation. Palpitations, cardiac arrhythmias, and cardiac dysfunction may also occur, potentially leading to syncope and cardiac arrest. Caffeine overdose may result in the following symptoms: epigastric pain, vomiting, diuresis, tachycardia or cardiac arrhythmias, and central nervous system stimulation (insomnia, restlessness, stimulation, psychomotor agitation, nervousness, tremors, and convulsions).
There are no known cases of drotaverine overdose.
In case of accidental overdose with Vemonis Ultra, inform your doctor or pharmacist immediately, or contact the nearest hospital emergency department for further advice.
Missing a dose of Vemonis Ultra
If you miss a dose, take it as soon as you remember, unless it is almost time for your next dose. Do not take a double dose to make up for a missed dose.
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 will experience them.
Due to the risk to life, the medicine must be discontinued immediately and medical help should be sought if severe allergic (anaphylactic) reactions occur.

Rare adverse effects (occurring in fewer than 1 in 1,000 patients):

• swelling of the face, lips, tongue, and (or) throat, which may cause difficulty swallowing or breathing;
• skin and mucous membrane changes such as itching, burning, redness, rash, urticaria.

Very rare adverse effects (occurring in fewer than 1 in 10,000 patients):

• severe bronchospasm.

Adverse effect occurring with unknown frequency (frequency cannot be estimated from available data):

• anaphylactic shock (life-threatening drop in blood pressure, weakness, fainting) (see Warnings and precautions in section 2).

The medicine must be discontinued immediately and a doctor should be consulted if any of the following serious adverse effects occur:
Very rare adverse effects (occurring in fewer than 1 in 10,000 patients):

• agranulocytosis (complete or near-complete absence of granulocytes in the blood), which may be fatal and manifests as: high fever, chills, sore throat, difficulty swallowing, inflammatory lesions of the oral, nasal, pharyngeal, genital, and rectal mucosa, elevated ESR, hemoglobin, red blood cells, and platelets usually within normal limits, slightly enlarged lymph nodes and spleen, although usually unchanged;
• pancytopenia (marked decrease in all blood cells: red and white blood cells and platelets), manifesting as general malaise, fever, signs of infection, petechiae, bleeding, skin pallor) (see Warnings and precautions in section 2);
• hemolytic anemia, aplastic anemia, bone marrow damage, sometimes leading to death. In patients with glucose-6-phosphate dehydrogenase deficiency, the medicine may cause hemolysis of red blood cells;
• decreased platelet count (thrombocytopenia, usually manifesting as increased tendency to bleeding, appearance of hemorrhagic petechiae on the skin and mucous membranes).

Adverse effect occurring with unknown frequency (frequency cannot be estimated from available data):

• bullous erythema multiforme – Stevens-Johnson syndrome (blisters progressing to erosions on the mucous membranes of the mouth, conjunctiva, and genital organs);
• severe skin reactions, including toxic epidermal necrolysis – Lyell's syndrome (erythematous-bullous lesions of the skin and mucous membranes leading to detachment of large areas of the epidermis and exposure of extensive skin surfaces) (see Warnings and precautions in section 2);
• acute generalized exanthematous pustulosis;
• skin blisters (bullous dermatosis);
• acute kidney failure, which may present with low urine output (oliguria), absence of urine output (anuria), or excess protein in urine (proteinuria), acute interstitial nephritis, red discoloration of urine;
• Kounis syndrome (acute coronary syndrome);
• liver damage;
• excessive drop in blood pressure (occurs with unknown frequency for metamizole, rarely for drotaverine; see Warnings and precautions in section 2);
• analgesic-induced asthma (see "When not to use Vemonis Ultra" in section 2), asthma attacks.

You must stop taking Vemonis Ultra and seek immediate medical help
if any of the following symptoms occur:
feeling unwell (nausea or vomiting), fever, fatigue, loss of appetite, dark urine, pale stools, yellowing of the skin or whites of the eyes, itching, rash, or pain in the upper abdomen. These may be symptoms of liver damage. See also section 2 "Warnings and precautions".

Other adverse effects:
Uncommon (occurring in fewer than 1 in 100 patients):

• drug rash (transient rash of various types: papular, macular, vesicular, erythematous).

Rare (occurring in fewer than 1 in 1,000 patients):

• papular-macular skin changes;
• leukopenia (reduced number of white blood cells in the blood);
• insomnia (related to drotaverine);
• tremor;
• palpitations.

Frequency unknown (frequency cannot be estimated from available data):

• gastrointestinal disorders, peptic ulcers and bleeding, vomiting, heartburn, bloating, nausea, abdominal pain, constipation, gastric irritation, diarrhea, dry mouth;
• hepatitis, jaundice (yellowing of the skin and whites of the eyes), increased liver enzyme activity in blood;
• headache and dizziness;
• red discoloration of urine (after very high doses of metamizole);
• changes in blood glucose levels (high and low glucose levels);
• irritability, insomnia (related to caffeine), nervousness, restlessness;
• psychomotor hyperactivity;
• increased myocardial contractility, irregular heart rhythm (arrhythmia), rapid heartbeat (tachycardia);
• flushing of the face, neck, and upper chest;
• rashes/skin eruptions of various types, exudative lesions, excessive sweating;
• muscle cramps;
• exhaustion;
• low blood pressure;
• drug withdrawal syndrome (the most common symptom of caffeine withdrawal is headache), nervousness;
• rapid heartbeat, increased urine flow, elevated creatinine clearance, increased excretion of sodium and calcium.

Severe skin reactions
The use of Vemonis Ultra must be discontinued and immediate medical attention sought if the patient develops any of the following serious adverse effects:

• red, flat spots on the trunk in the shape of a target or circular lesions, often with blisters in the center, skin peeling, ulceration in the mouth, throat, nose, genital organs, and around the eyes. Such serious skin eruptions may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis);
• widespread rash, high body temperature, and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309,
website: https://smz.ezdrowie.gov.pl
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Vemonis Ultra

Do not store above 30°C. Store in the original packaging to protect from moisture.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister pack following EXP.
The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Vemonis Ultra contains

• The active substances are: metamizole sodium in the form of monohydrate metamizole sodium, caffeine, drotaverine hydrochloride.
• Other components (excipients) are: microcrystalline cellulose (type 112), monohydrate lactose, crospovidone (type A), talc, magnesium stearate, polyvinyl alcohol, titanium dioxide (E 171), yellow iron oxide (E 172), soy lecithin, xanthan gum.

What Vemonis Ultra looks like and contents of the pack
Film-coated tablets, yellowish, oval-shaped, with the engraved mark "80" on one side.
Aluminum/PA/PVC/Aluminum foil blisters containing 4, 6, 8, 12 or 24 film-coated tablets in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów
tel.: +48 22 732 77 00

Manufacturer
Adamed Pharma S.A.
ul. Marszałka J. Piłsudskiego 5
95-200 Pabianice