DOLVIRAN TABLETS

Introduction

Package Leaflet: Information for the User

Dolvirán 400 mg/ 9.6 mg/ 50 mg Tablets

Acetylsalicylic Acid/ Codeine Phosphate Hemihydrate/ Caffeine

Contents of the Package Leaflet:

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

1. What is Dolvirán and what is it used for

Dolvirán is used in adults and adolescents over 16 years of age for the symptomatic relief of occasional mild or moderate pain, such as headaches, dental pain, menstrual pain, muscular pain (cramps) or back pain (lumbago).

This medicine contains codeine. Codeine belongs to a group of medicines called opioid analgesics that act by relieving pain. It can be used alone or in combination with other analgesics such as paracetamol.

2. What you need to know before you start taking Dolvirán

Do not take Dolvirán

• If you are allergic to acetylsalicylic acid, codeine, or any of the other components of this medicine (listed in section 6)
• If you have active, chronic, or recurrent gastroduodenal ulcers.
• If you have asthma
• If you have or have had coagulation disorders, mainly hemophilia or hypoprothrombinemia.
• If you have severe renal or hepatic impairment.
• If you are being treated with oral anticoagulants.
• If you have nasal polyps associated with asthma that are induced or exacerbated by acetylsalicylic acid.
• Do not administer to children under 16 years of age with febrile processes, flu, or chickenpox, as in these cases the use of acetylsalicylic acid has been associated with the onset of Reye's syndrome.
• To relieve pain in children and adolescents (0-18 years of age) after tonsillectomy or adenoidectomy due to obstructive sleep apnea syndrome.
• If you are hypersensitive to codeine and in conditions where respiratory center depression should be avoided.
• If you know you metabolize codeine to morphine very quickly.
• Do not take during prolonged periods with chronic constipation.
• If you have chronic cardiopulmonary insufficiency or heart conditions.
• If you have biliary disorders, as codeine, like all morphine derivatives, can cause spasms of the Oddi sphincter.
• If you are in the third trimester of pregnancy.
• If you are breastfeeding.

If you think you are affected by any of these cases, consult your doctor before taking this medicine.

Warnings and precautions

Consult your doctor if the pain persists for more than 5 days, fever for more than 3 days, or if the pain or fever worsens or other symptoms appear

• Caution is recommended in debilitated and elderly patients, with intracranial injuries, hypothyroidism, adrenal insufficiency, and prostatic hypertrophy.
• Administration of acetylsalicylic acid should be avoided in patients before or after dental extraction or surgical intervention. Administration of this medicine should be suspended one week before surgical interventions.
• Do not administer systematically as a preventive measure for possible discomfort caused by vaccinations.
• Do not take sedatives during treatment with this medicine.
• As with all medicines that contain codeine, dependence may develop after prolonged administration of high doses of this medicine, with a withdrawal syndrome if treatment is interrupted abruptly.
• Do not exceed the recommended dose (see section 3. "How to take Dolvirán"), as serious side effects may occur (see section 4. "Possible side effects").
• If you have any heart disease, such as sinus tachycardia/extrasystoles, liver failure, hyperthyroidism, or any anxiety syndrome, you should take caffeine in reduced doses (no more than 100 mg, equivalent to two Dolvirán tablets) or preferably under medical supervision.

Treatment with non-steroidal anti-inflammatory drugs is associated with the onset of bleeding, ulceration, and perforation of the upper digestive tract. In case of appearance of melena, hematemesis, marked asthenia, or any other sign or symptom suggestive of gastric bleeding, treatment should be interrupted immediately.

This medicine should be administered under close medical supervision in case of hypersensitivity to other anti-inflammatory/anti-rheumatic drugs, glucose-6-phosphate dehydrogenase deficiency, urticaria, rhinitis, or arterial hypertension.

Codeine is transformed into morphine in the liver by an enzyme. Morphine is the substance that produces pain relief. Some people have a variation of this enzyme that can affect people in different ways. In some people, morphine is not produced or is produced in very low quantities, and it will not provide sufficient pain relief. Other people are more likely to suffer serious adverse reactions because they produce a very high amount of morphine. If you experience any of the following side effects, you should stop taking this medicine and seek medical help immediately: slow or shallow breathing, confusion, drowsiness, constricted pupils, nausea or vomiting, constipation, loss of appetite.

Use in elderly patients

Elderly patients should not take this medicine without consulting their doctor, as they are more prone to its side effects.

Other medicines and Dolvirán

Certain medicines may interact with Dolvirán. In these cases, it may be necessary to change the dose or interrupt treatment with one of the medicines, so they should not be used without consulting a doctor.

Concomitant use of this medicine and sedative medicines such as benzodiazepines or related medicines increases the risk of drowsiness, breathing difficulties (respiratory depression), coma, and can be fatal. Therefore, concomitant use should only be considered when other treatment options are not possible.

However, if your doctor prescribes this medicine along with sedative medicines, the dose and duration of concomitant treatment should be limited by your doctor.

Inform your doctor about all sedative medicines you are taking and follow your doctor's recommendations regarding the dose carefully. It may be useful to inform friends or family members so they are aware of the signs and symptoms mentioned above. Contact your doctor when you experience such symptoms.

Acetylsalicylic acid interacts with ethanol, cimetidine, ranitidine, anticoagulants, non-steroidal anti-inflammatory drugs, corticosteroids, phenytoin, oral hypoglycemics or insulin, methotrexate, uricosurics, vancomycin, zidovudine, valproic acid, sulfonamides, digoxin, barbiturates, and lithium.

If administered together, metamizole (a substance to reduce pain and fever) may reduce the effect of acetylsalicylic acid on platelet aggregation (blood cells that clump together and form a blood clot). Therefore, this combination should be used with caution in patients who are taking low doses of acetylsalicylic acid as a cardioprotector.

Caffeine may interfere with disulfiram, sedatives, antihistamines, sympathomimetics, adrenergic bronchodilators, mexiletine, benzodiazepines, oral contraceptives, cimetidine, theophylline, and gyrase inhibitors.

Codeine may interact with central nervous system depressant drugs, alcohol, and morphine agonist-antagonists.

Inform your doctor or pharmacist if you are using or have recently used any other medicine, including those obtained without a prescription.

If you are going to have any diagnostic tests (including blood tests, urine tests, etc.), inform your doctor that you are taking this medicine, as it may alter the results.

Taking Dolvirán with food, drinks, and alcohol

Take this medicine after meals or with some food.

Do not drink alcoholic beverages during treatment.

Concomitant consumption of this medicine with beverages containing caffeine may cause excessive stimulation of the nervous system and produce nervousness, irritability, or insomnia.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

This medicine should not be used during the third trimester of pregnancy.

Additionally, it should not be taken during the rest of pregnancy unless your doctor considers it strictly necessary.

Do not take this medicine if you are breastfeeding, as its components pass into breast milk and may affect the baby. Codeine and morphine pass into breast milk.

Use in children and adolescents

Do not administer to children under 16 years of age.

Use in children and adolescents after surgery

Codeine should not be used to relieve pain in children and adolescents after tonsillectomy or adenoidectomy due to obstructive sleep apnea syndrome.

Use in children with respiratory problems

Codeine is not recommended for use in children with respiratory problems, as the symptoms of morphine toxicity can be worse in these children.

Driving and using machines

Codeine may cause drowsiness, altering the mental and/or physical ability required for the performance of potentially hazardous activities, such as driving vehicles or operating machines. Avoid driving vehicles or using machines during treatment.

3. How to take Dolvirán

Follow exactly the administration instructions of this medicine indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The tablets should be taken after meals, swallowed with a little water or dissolved in half a glass of water.

Do not exceed the recommended dose. Always use the lowest effective dose.

This medicine should not be taken for more than 3 days. If the pain does not improve after 3 days, consult your doctor again.

The recommended dose is:

Adults and adolescents over 16 years of age: 1 or 2 tablets every 8 or 12 hours (2 or 3 times a day). The maximum daily dose is 6 tablets, with a minimum time of 8 hours between each dose.

Patient with renal or hepatic insufficiency: your doctor will indicate the appropriate dose.

Elderly patients: your doctor will indicate the appropriate dose

Use in children and adolescents under 16 years of age:

Do not administer to children and adolescents under 16 years of age:

• Do not administer to children under 16 years of age with febrile processes, flu, or chickenpox, as in these cases the use of acetylsalicylic acid has been associated with the onset of Reye's syndrome.
• Children under 12 years of age should not take codeine due to the risk of serious respiratory problems.

If you take more Dolvirán than you should

This may lead to an overdose, so the effects due to acetylsalicylic acid, codeine, and caffeine should be taken into account.

In case of overdose, the characteristic symptoms of acetylsalicylic acid poisoning may appear, such as nausea, vomiting, tinnitus, deafness, sweating, vasodilation, and hyperventilation, headache, blurred vision, and occasionally diarrhea as signs of overdose. Signs of acute poisoning are neurological disorders, such as confusion, delirium, convulsions, and coma.

The characteristic symptoms of codeine overdose (drowsiness, skin redness, miosis, vomiting, pruritus, ataxia, headache, skin inflammation, urinary and fecal retention, and respiratory depression that can lead to respiratory arrest) or caffeine (excessive stimulation of the central nervous system, insomnia, restlessness, vomiting, convulsions, and symptoms of excitement) and gastrointestinal irritation (nausea, vomiting, diarrhea, abdominal pain) may also appear.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or go to a medical center immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to take Dolvirán

Do not take a double dose to make up for forgotten doses.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The adverse reactions due to acetylsalicylic acidmay be:

Common(may affect up to 1 in 10 people):

• Gastrointestinal disorders such as stomach upset, nausea, vomiting, abdominal pain, and diarrhea.
• Increased tendency to bleed
• Minor blood loss in the gastrointestinal tract (micro-bleeding).
• Bleeding such as nosebleeds, bleeding gums, skin bleeding, or bleeding in the urinary tract and genital organs with possible extension of bleeding time. This effect can last from 4 to 8 days after ingestion.

Uncommon(may affect up to 1 in 100 people):

• Bleeding in the stomach or intestines. After long-term use of acetylsalicylic acid, anemia (iron deficiency anemia) may occur due to hidden blood loss in the stomach or intestines.
• Intracranial bleeding, blood in the urine.
• Stomach or intestinal ulcers, which can very rarely cause perforation.
• Gastrointestinal inflammation.
• Skin reactions such as urticaria
• Nasal discharge

Rare(may affect up to 1 in 1,000 people):

• Hypersensitivity reactions of the skin, respiratory tract, gastrointestinal system, and cardiovascular system, especially in asthmatics. The following characteristics of the disease may appear: decreased blood pressure, dyspnea attacks, nasal mucosa inflammation, nasal congestion, anaphylactic shock, facial swelling, tongue and larynx edema (Quincke's edema).
• Severe skin reactions such as a rash known as erythema multiforme, and it can present in forms that can be life-threatening, Stevens-Johnson syndrome, and Lyell syndrome.
• Severe bleeding, such as cerebral hemorrhage, especially in patients with uncontrolled high blood pressure and/or concomitant treatment with anticoagulants (anticoagulant medications) that can be life-threatening in individual cases.
• Confusion
• Headache, dizziness
• Hearing impairment or tinnitus (ringing in the ears), especially in children and elderly people, can be signs of an overdose (see also "If you take more Dolvirán tablets than you should").
• Abnormally heavy or prolonged menstrual periods.

Very rare(may affect up to 1 in 10,000 people):

• Disorders in liver function tests.
• Renal dysfunction and acute renal failure.
• Decreased blood sugar (hypoglycemia).
• Acetylsalicylic acid reduces the excretion of uric acid at low doses. This can trigger a gout attack in patients at risk.
• Febrile eruptions with mucous membrane involvement (exudative multiform erythema).

Frequency not known(frequency cannot be estimated from the available data):

• Accelerated or increased breakdown of red blood cells and a certain form of anemia in patients with severe glucose-6-phosphate dehydrogenase deficiency.
• Dizziness

Treatment should be suspended immediately in case the patient experiences any type of deafness, tinnitus, or dizziness. In patients with a history of hypersensitivity to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs, anaphylactic or anaphylactoid reactions may occur. This can also occur in patients who have not previously shown hypersensitivity to these drugs.

The adverse reactions due to codeinemay be:

Rare(may affect up to 1 in 1,000 people):

• Gastrointestinal disorders (constipation, nausea)
• General disorders (discomfort, drowsiness)

Very rare(may affect up to 1 in 10,000 people):

• Blood and lymphatic system disorders (thrombocytopenia, agranulocytosis, leucopenia, neutropenia, hemolytic anemia)
• Metabolism and nutrition disorders (hypoglycemia)
• Gastrointestinal disorders (jaundice)
• General disorders (hypersensitivity reactions ranging from a simple skin rash or urticaria to anaphylactic shock, fever)

The following adverse effects have been observed with caffeine, whose frequency cannot be established with precision:

• Nervousness
• Restlessness
• Stomach or intestine irritation
• Tachycardias

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Dolvirán

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date that appears on the packaging and on the blister after CAD. The expiration date is the last day of the month indicated.

Keep in the original packaging perfectly closed.

Medicines should not be thrown away through wastewater or in the trash. Deposit the packaging and medicines you no longer need at the SIGRE Point of the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Composition of Dolvirán

The active ingredients are acetylsalicylic acid, codeine phosphate hemihydrate, and caffeine.

Each tablet contains 400 mg of acetylsalicylic acid, 9.6 mg of codeine phosphate hemihydrate (equivalent to 7.34 mg of codeine) and 50 mg of caffeine.

The other components are: cornstarch, microcrystalline cellulose, and magnesium stearate.

Appearance of Dolviránand Package Contents

White and round tablets.

It is presented in packages of 20 tablets in PVC/PVCD/AL blister packs.

Marketing Authorization Holder and Manufacturer

Kern Pharma, S.L.

Venus, 72 - Pol. Ind. Colón II

08228 Terrassa - Barcelona

Spain

Date of the Last Revision of this Prospectus: July 2021

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/