PHARMAFREN 200 mg/30 mg HARD CAPSULES

2. What you need to know before taking Pharmafren

Do not take Pharmafren

• if you are allergic to ibuprofen, pseudoephedrine, or any of the other ingredients of this medicine (listed in section 6),
• if you are under 15 years of age,
• if you are pregnant or breastfeeding,
• if you have previously suffered an allergic reaction or asthma, skin rash, itching, and nasal congestion when you have taken this medicine, ibuprofen, acetylsalicylic acid, or similar medicines,
• if you have a history of recurrent stomach or duodenal ulcers, or have previously suffered gastrointestinal bleeding related to the use of NSAIDs,
• if you have severe liver disease,
• if you have severe kidney disease, acute (sudden) or chronic (long-term), or kidney failure,
• if you have heart problems (such as coronary insufficiency),
• if you have a history of heart attack (myocardial infarction),
• if you have very high blood pressure (severe hypertension) or uncontrolled hypertension,
• if you have had a stroke or have been told you are at risk of having a stroke,
• if you have a history of seizures (epileptic fits),
• if you have disorders of unknown origin in the formation of blood elements,
• if you have high eye pressure (angle-closure glaucoma),
• if you have difficulty urinating due to prostate problems,
• if you have been diagnosed with Systemic Lupus Erythematosus (SLE), a disease that affects the immune system and causes joint pain, skin changes, and other problems,
• if you are taking:
• • other nasal decongestants (vasoconstrictor medicines) administered orally or nasally (e.g., phenylpropanolamine, phenylephrine, ephedrine, xylometazoline, or oxymetazoline) or methylphenidate,
  • medicines for depression such as non-selective Monoamine Oxidase Inhibitors (known as MAOIs, e.g., iproniazid) or have taken them in the last 14 days.
• if you are suffering from significant dehydration due to vomiting, diarrhea, or insufficient fluid intake.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Pharmafren:

• if you have asthma; the use of this medicine may provoke an asthma attack,
• if you have a history of gastrointestinal disorders (such as hiatal hernia, gastrointestinal bleeding, peptic or duodenal ulcers) and a chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease),
• if you have heart problems including heart failure, angina (chest pain), or if you have had a heart attack, bypass surgery, peripheral arteriopathy (circulation problems in the legs or feet due to narrowing or blockage of the arteries), or any type of stroke (including a "mini-stroke" or transient ischemic attack "TIA"),
• if you have high blood pressure, diabetes, high cholesterol, have a family history of heart disease or stroke, or if you are a smoker,
• if you have hyperthyroidism (overactive thyroid gland),
• if you have systemic lupus erythematosus (a disease of the connective tissue) and mixed connective tissue disease, or a congenital disorder of porphyrin metabolism,
• if you are taking medicines that interact with Pharmafren, see the list below,
• with Pharmafren, the blood flow carried to the optic nerve may be reduced. If you suffer a sudden loss of vision, stop taking Pharmafren and contact your doctor or seek immediate medical attention. See section 4.
• if you have an infection; see the "Infections" heading below.
• with ibuprofen, signs of allergic reaction to this medicine have been reported, such as respiratory problems, facial and neck swelling (angioedema), and chest pain. Stop using Pharmafren immediately and contact your doctor or seek immediate medical attention if you observe any of these signs.

Medicines like ibuprofen may be associated with a small increased risk of having a heart attack or stroke, especially when used at high doses. Do not exceed the recommended dose or treatment duration.

There have been reports of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) after the use of medicines containing pseudoephedrine. PRES and RCVS are rare diseases that may involve reduced blood flow to the brain. Stop using Pharmafren immediately and seek immediate medical attention if you present symptoms that may be signs of PRES or RCVS (to know the symptoms, see section 4 "Possible side effects").

Special caution is recommended with Pharmafren

Skin reactions

Severe skin reactions, such as exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), have been reported in association with Pharmafren treatment. Discontinue Pharmafren treatment and seek immediate medical attention if you notice any of the symptoms related to these severe skin reactions described in section 4.

Stop taking Pharmafren and go to the doctor immediately if you develop any skin rash, lesions on the mucous membranes, blisters, or other signs of allergy, as these may be the first signs of a severe skin reaction. See section 4.

Sudden abdominal pain or rectal bleeding may occur with the use of Pharmafren, due to inflammation of the colon (ischemic colitis). If these gastrointestinal symptoms appear, stop taking Pharmafren and contact your doctor or seek immediate medical attention. See section 4.

If you develop symptoms of a severe allergic reaction such as: severe skin rash, peeling, scaling, or blistering of the skin, facial swelling, unexplained wheezing, difficulty breathing, bruising easily, stop taking Pharmafren and contact your doctor or seek immediate medical attention. See section 4.

Very rarely, severe skin reactions have been reported with the use of an NSAID. It seems that patients are at higher risk of suffering these reactions at the beginning of treatment: in most cases, the onset of the reaction occurs within the first month of treatment. Stop taking Pharmafren and contact your doctor or seek immediate medical attention if you develop a skin rash or lesions on the mucous membranes.

It is advised to avoid the use of Pharmafren during chickenpox.

In patients with systemic lupus erythematosus and mixed connective tissue disease, there may be an increased risk of aseptic meningitis or hepatitis.

Long-term use of any type of pain reliever for headache may worsen it.

If you frequently or daily experience headache despite (or due to) the regular use of medication for it, consult your doctor before taking another pain reliever. Treatment should be discontinued if medication-overuse headache (MOH) is diagnosed.

In case of prolonged administration with ibuprofen, you should contact your doctor to regularly monitor your liver function and perform a hematological review.

The habitual intake of pain relievers, especially in combination with different active principles to relieve pain, can cause permanent kidney damage with a risk of kidney failure (analgesic nephropathy). This risk may increase under physical exertion associated with salt loss and dehydration. Therefore, it should be avoided.

Infections

Pharmafren may hide the signs of an infection, such as fever and pain. Consequently, Pharmafren may delay the appropriate treatment of the infection, which may increase the risk of complications. This has been observed in bacterial pneumonia and bacterial skin infections related to chickenpox. If you take this medicine while having an infection and the symptoms of the infection persist or worsen, consult a doctor without delay.

Interference with laboratory tests

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

Pseudoephedrine may interfere with some blood tests used for diagnosis. You should inform your doctor that you are taking this medicine if a blood test is to be performed.

Children and adolescents

Pharmafren is contraindicated in children and adolescents under 15 years of age. There is a risk of kidney failure in dehydrated adolescents.

Taking Pharmafren with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.

Pharmafren may affect or be affected by other medicines. For example:

• anticoagulant medicines (e.g., to treat coagulation problems/prevent coagulation, e.g., acetylsalicylic acid, warfarin, ticlopidine),
• medicines that lower high blood pressure (ACE inhibitors such as captopril, beta-blockers such as atenolol, and angiotensin-II receptor antagonists such as losartan).

Other medicines may also affect or be affected by treatment with Pharmafren. Therefore, you should always consult your doctor or pharmacist before using Pharmafren with other medicines.

Especially, inform your doctor or pharmacist if you are taking:

• antiplatelet and oral anticoagulant medicines (medicines that thin the blood/prevent coagulation, such as acetylsalicylic acid, warfarin, ticlopidine),
• other NSAIDs, including high doses of acetylsalicylic acid,
• cardiac glycosides (e.g., digoxin),
• corticosteroids,
• injectable heparin,
• certain medicines for depression (e.g., lithium, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase A inhibitors (MAOIs)),
• methotrexate at high doses (more than 20 mg per week),
• quinolone antibiotics (used to treat a wide range of infections),
• cyclosporine, tacrolimus, and trimethoprim,
• medicines for the treatment of high blood pressure (high blood pressure),
• any antimigraine medicine (including medicines derived from ergot alkaloids),
• zidovudine (a medicine for the treatment of HIV/AIDS),
• preparations containing Ginkgo biloba,
• CYP2C9 inhibitors (e.g., voriconazole and fluconazole),
• mifepristone (for abortion).

Pharmafren should not be used in combination with:

• other vasoconstrictor medicines used as nasal decongestants, whether administered orally or nasally (e.g., phenylpropanolamine, phenylephrine, and ephedrine) or methylphenidate,
• non-selective monoamine oxidase inhibitors (MAOIs) (such as iproniazid), which are used to treat certain depressions.

Due to the administration of pseudoephedrine, acute hypertension may occur in the perioperative period. Therefore, discontinue Pharmafren treatment several days before surgery and inform your anesthesiologist.

Taking Pharmafren with food, drinks, and alcohol

The capsules should not be taken with beverages containing alcohol.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor or pharmacist before using this medicine.

It may cause kidney and heart problems in your fetus. It may affect your tendency and that of your baby to bleed and delay or prolong labor more than expected.

From the 20th week of pregnancy, Pharmafren may cause kidney problems in your fetus if taken for more than a few days, which may lead to low levels of the fluid surrounding the baby (oligohydramnios).

Pharmafren is contraindicated during pregnancy and breastfeeding.

Athletes

Pseudoephedrine hydrochloride may give positive results in doping tests.

Driving and using machines

Pharmafren may cause dizziness and/or blurred vision and may temporarily affect your ability to drive and use machines.

Pharmafren contains sodium

This medicine contains less than 23 mg of sodium (1mmol) per capsule; this is, essentially "sodium-free".

3. How to take Pharmafren

Follow exactly the administration instructions of the medicine contained in this leaflet or as indicated by your doctor or pharmacist. In case of doubt, ask your doctor or pharmacist.

This medicine is only for short-term use. The lowest effective dose should be used for the shortest necessary duration to relieve symptoms. If you have an infection, consult a doctor without delay if the symptoms (such as fever and pain) persist or worsen (see section 2).

Do not take for more than 5 days unless your doctor tells you to.

The recommended dose is:

Adults and adolescents from 15 years of age: 1 capsule every 6 hours if necessary. For more intense symptoms, take 2 capsules every 6 hours, if necessary.

Never exceed the maximum daily dose of 6 capsules per day (equivalent to 1200 mg of ibuprofen and 180 mg of pseudoephedrine hydrochloride).

The capsules should be swallowed with liquid, a glass of water, and preferably during meals.

Use in children and adolescents

Pharmafren is contraindicated in children and adolescents under 15 years of age.

If adolescents need to take this medicine for more than 3 days, or if symptoms worsen, they should consult a doctor.

If you take more Pharmafren than you should

If you have taken more Pharmafren than you should, or if a child has accidentally ingested the medicine, consult a doctor immediately or go to the nearest hospital to find out about the risk and ask for advice on the measures to be taken.

Symptoms of overdose may include nausea, stomach pain, vomiting (which may contain blood), gastrointestinal bleeding (see section 4), diarrhea, headache, ringing in the ears, confusion, and involuntary eye movement. Agitation, disorientation, or coma may also occur. At high doses, symptoms such as drowsiness, chest pain, palpitations, loss of consciousness, seizures (mainly in children), weakness, and dizziness, blood in the urine, low potassium levels in the blood, chills, and breathing problems have been reported.

In addition, the prothrombin time/INR may be prolonged, probably due to interference with the actions of circulating coagulation factors.

Acute kidney failure and liver damage may occur.

Exacerbation of asthma is possible in asthmatics. Additionally, there may be low blood pressure and reduced breathing.

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

If you forget to take Pharmafren

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

If you have any other doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Severe adverse effects (frequency not known): severe diseases that affect the blood vessels of the brain, known as posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS).

Stop using Pharmafren immediately and seek urgent medical attention if you experience symptoms that may be signs of posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS). These include:

• sudden severe headache
• discomfort
• vomiting
• confusion
• seizures
• changes in vision

Stop taking Pharmafren and contact your doctor immediately if you notice:

• Signs of intestinal bleedingsuch as: bright red stools (defecation), black tarry stools, vomiting blood or dark particles that resemble coffee grounds.
• Signs of a severe allergic reactionsuch as: severe skin rashes, peeling, blistering of the skin, swelling of the face, unknown lung noises, difficulty breathing, easy bruising.
• A severe skin reactionknown as DRESS syndrome (by its English acronym) may occur. The symptoms of DRESS syndrome include: widespread skin rash, elevated body temperature, inflammation of the lymph nodes, and elevated eosinophils (a type of white blood cell).
• Widespread, red, and scaly rash, with bumps under the skin and blisters, accompanied by fever. Symptoms usually appear at the start of treatment (acute generalized exanthematous pustulosis).
• Reddish, non-elevated patches, target-like or circular on the trunk, often with blisters in the center, skin peeling, mouth, throat, nose, genital, and eye ulcers. These severe skin rashes can be preceded by fever and flu-like symptoms [exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis].

Frequency "not known"

• Widespread, red, scaly rash, with bumps under the skin and blisters, mainly located in skin folds, trunk, and upper limbs, accompanied by fever at the start of treatment (acute generalized exanthematous pustulosis).
• Inflammation of the colon due to insufficient blood irrigation (ischemic colitis).

• Decreased blood flow to the optic nerve (ischemic optic neuropathy).
• The skin becomes sensitive to light.

Stop taking Pharmafren if these symptoms appear and contact your doctor or seek medical attention immediately. See also section 2.

Consult your doctor if you have any of the following adverse effects, if they worsen, or if you notice any unmentioned effect.

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

• indigestion, acidity, abdominal pain, nausea, vomiting, flatulence, diarrhea, constipation.

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

• headache, dizziness, fatigue, difficulty sleeping, agitation, irritability, or fatigue,
• visual impairment,
• stomach or intestinal ulcers, sometimes with bleeding and perforation, worsening of colitis and Crohn's disease,
• skin rashes.

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

• tinnitus (ringing in the ears),
• kidney damage.

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

• problems with the formation of blood cells that can cause easy bruising or facilitate the appearance of infections,
• severe allergic reactions,
• psychotic reactions and depression,
• high blood pressure, palpitations, heart attack,
• inflammation of blood vessels (vasculitis),
• liver damage,
• severe skin reactions,
• difficulty urinating.

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

• increased skin sensitivity to the sun.
• chest pain, which can be a sign of a potentially severe allergic reaction called Kounis syndrome.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Pharmafren

Keep this medicine out of sight and reach of children.

This medicine does not require special storage conditions.

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

Medicines should not be thrown down the drain or into the trash. Deposit the packaging and medicines you no longer need at the SIGRE Point in 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 Pharmafren

• The active ingredients are ibuprofen and pseudoephedrine hydrochloride. Each hard capsule contains 200 mg of ibuprofen and 30 mg of pseudoephedrine hydrochloride.

• The other components (excipients) are:

Core: cornstarch, anhydrous colloidal silica, pregelatinized cornstarch, sodium croscarmellose, stearic acid, sodium lauryl sulfate.

Capsule: gelatin, titanium dioxide (E-171), patent blue V (E-131), erythrosine (E-127).

Appearance of the Product and Package Contents

Pharmafren is presented in the form of hard blue capsules in PVC-PVDC/Alu blisters.

Each package contains 10 or 20 hard capsules.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Laboratorios Cinfa, S.A.

Carretera Olaz-Chipi, 10. Polígono Industrial Areta

31620 Huarte (Navarra) - Spain

Date of the Last Revision of this Prospectus: September 2024

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