Solufen: applications, side effects, interactions, dosage/pill trip (2023)

Caution should be exercised in patients with certain medical conditions:

- Systemic lupus erythematosus, as well as those with mixed collagenosis due to the increased risk of aseptic meningitis.

- Diseases of the gastrointestinal tract and inflammatory bowel disease, as these diseases can be aggravated (ulcerative colitis, Crohn's disease).

- Caution should be exercised before initiating treatment in patients with a history of hypertension and/or heart failure. Oedema, high blood pressure and/or heart failure may deteriorate kidney function and/or fluid retention may occur.

- Kidney failure, as kidney function may deteriorate.

- Liver failure.

Adverse effects can be minimized by using the lowest effective dose for the shortest time possible to control symptoms (see gastrointestinal and cardiovascular risks below).

Older people are at a higher risk of suffering the serious consequences of side effectsespecially gastrointestinal bleeding and perforation, which can be fatal.

Bronchospasm can be induced in patients who have or have a history of bronchial asthma or an allergic condition.

Use in conjunction with NSAIDs, including specific cyclooxygenase-2 inhibitorsmust be avoided.

Cardiovascular and cerebrovascular effects

Clinical studies suggest that the use of Solufen, particularly at high doses (2400 mg/day), may be associated with a small increased risk of arterial thrombotic events (eg, myocardial infarction or stroke).

In general, epidemiological studies do not suggest that low doses of Solufen (eg, 1200 mg daily) are associated with an increased risk of arterial thrombotic events.

Patients with uncontrolled hypertension, congestive heart failure (NYHA II-III), established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease should only be treated with Solufen after careful consideration and high doses (2400 mg/kg) should be avoided . Day). .

Careful consideration should be given to initiation of long-term treatment in patients with risk factors for cardiovascular events (eg, hypertension, hyperlipidaemia, diabetes mellitus, smoking), particularly when high doses of Solufen (2400 mg/day) are administered.

There is evidence that drugs that inhibit cyclooxygenase/prostaglandin synthesis can impair female fertility by affecting ovulation. This is reversible upon discontinuation of treatment.

Gastrointestinal (GI) bleeding, ulceration, or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a history of serious gastrointestinal effects (including ulcerative colitis, Crohn's disease).

The risk of gastrointestinal bleeding, ulceration or perforation is greater with increasing doses of NSAIDs, in patients with a history of ulcer, particularly if complicated by bleeding or perforation, and in elderly patients. These patients should start treatment on the lowest available dose.

Patients with a history of GI toxicity, particularly the elderly, should report any unusual abdominal symptoms (especially GI bleeding), particularly at the start of treatment.

Caution is advised in patients receiving concomitant medicinal products that may increase the risk of gastrotoxicity or bleeding, e.g. B. corticosteroids or anticoagulants, such as warfarin, selective serotonin reuptake inhibitors, or platelet aggregation inhibitors, such as aspirin.

If gastrointestinal bleeding or ulceration occurs in patients receiving Solufen, treatment should be discontinued immediately.

dermatological

Severe skin reactions, some fatal, such as exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported very rarely in association with the use of NSAIDs. Patients appear to be at greater risk for these reactions when starting treatment: the reaction occurs in most cases within the first month of treatment. Solufen should be discontinued at the first appearance of rash, mucosal lesions or other signs of hypersensitivity.

Patients with rare hereditary problems of fructose intolerance should not take this medicine because this product contains sucrose.

Each tablet contains 67 mg of sucrose. This must be taken into account in patients with diabetes mellitus.

Dehydrated children and adolescents ages 12 to 18 are at risk for kidney failure.

The tag contains:

12-18 years: If symptoms worsen or last longer than 3 days, or new symptoms appear, contact your doctor.

Adults: If symptoms get worse or last longer than 10 days, or if new symptoms appear, contact your doctor or pharmacist.

Please read the attached leaflet before taking this product.

Do not take if you:

- you have ever had a stomach ulcer, perforation or bleeding

- you are allergic to Solufen (or any other ingredients of this medicine), aspirin or other related pain medicines

- you are taking other NSAID painkillers or aspirin with a daily dose greater than 75 mg

- are in the last 3 months of pregnancy.

Talk to a pharmacist or your doctor before taking it if:

- Asthma, diabetes, high cholesterol, high blood pressure, had a stroke, heart, liver, kidney or bowel problems

- Are you smoker

- you are pregnant

Elderly patients are more likely to experience adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which can be fatal.

Breathing:

Bronchospasm can be induced in patients who have or have a history of bronchial asthma or an allergic condition.

Other NSAIDs:

Concomitant use of ibuprofen with NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.

SLE and Mixed Collagenosis:

Systemic lupus erythematosus and those with mixed collagenosis: increased risk of aseptic meningitis

Rins:

Kidney failure, as kidney function may further deteriorate.

Dehydrated children and teens are at risk for kidney failure

Reader:

liver dysfunction

Cardiovascular and cerebrovascular effects:

Caution is advised (discussion with physician or pharmacist) in patients with a history of hypertension and/or heart failure, as cases of fluid retention, hypertension and edema associated with treatment with NSAIDs have been reported.

NOTICES

Allergy notice:Ibuprofen can cause a severe allergic reaction, especially in people who are allergic to aspirin. Symptoms can include:

Urticaria
Hichazon facial treatment
asthma (wheezing)
Schock
skin redness
skin irritation
Blow

If an allergic reaction occurs, discontinue use and seek medical attention immediately.

Stomach bleeding warning:This product contains an NSAID which can cause severe stomach bleeding. The chance is greater if you:

if you have had stomach ulcers or bleeding problems
Take an anticoagulant or steroid medication
are 60 years old or older
are taking other prescription or over-the-counter NSAIDs [aspirin, ibuprofen, naproxen, or others]
drink 3 or more alcoholic beverages daily while using this product
take longer or longer than indicated

do not use

if you have ever had an allergic reaction to other pain relievers/fever reducers
immediately before or after heart surgery

Consult a physician before use if

Stomach bleeding warning applies to you
have a history of stomach problems, such as heartburn
You have high blood pressure, heart disease, liver cirrhosis or kidney disease
Are you taking a diuretic?
Have serious problems or side effects when taking pain relievers or fever reducers
you have asthma

If necessary, consult a doctor or pharmacist before use.

under a doctor's care for any serious illness
Take aspirin if you are having a heart attack or stroke, as ibuprofen can reduce this aspirin benefit
take any other medicine

When using this product

take with food or milk if you have stomach problems
The risk of heart attack or stroke may increase if you use more or for longer than recommended

Stop use and ask a doctor if

if you notice any of the following signs of stomach bleeding:
- feel-be silly
- have bloody or black stools
- blood vomit
- have stomach pains that don't get better
Pain gets worse or lasts longer than 10 days
Fever gets worse or lasts for more than 3 days
there is redness or swelling in the painful area
any new symptoms appear

If you are pregnant or breastfeeding,

Ask a doctor before use. It is especially important not to use ibuprofen during the last 3 months of pregnancy unless specifically directed by a doctor, as it may cause problems with the fetus or complications during delivery.

Keep away from children.

PRECAUTIONS

verNOTICESprevious section.

). Like other NSAIDs, ibuprofen can mask signs of infection.

Concomitant use of Brufen with NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided due to an increased risk of ulceration or bleeding.

Geezer

Elderly patients are more likely to experience adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, which can be fatal.

pediatric population

Dehydrated children and adolescents are at risk for kidney failure.

Gastrointestinal bleeding, ulceration and perforation

Patients with a history of GI disease, particularly the elderly, should report any unusual abdominal symptoms (especially GI bleeding), particularly in the early stages of treatment.

If gastrointestinal bleeding or ulceration occurs in patients receiving Brufen, treatment should be discontinued.

NSAIDs should be given with caution in patients with a history of ulcerative colitis or Crohn's disease, as these conditions may worsen.

respiratory diseases and hypersensitivity reactions

Caution should be exercised when Brufen is administered to patients suffering from or having a history of bronchial asthma, chronic rhinitis or allergic diseases, as NSAIDs have been reported to induce bronchospasm, urticaria or angioedema in these patients.

Heart, kidney and liver failure

Administration of an NSAID may cause a dose-dependent reduction in prostaglandin production and lead to renal failure).

Brufen should be used with caution in patients with heart failure or a history of hypertension, as edema has been reported with the use of ibuprofen.

Cardiovascular and cerebrovascular effects

Patients with a history of hypertension and/or mild to moderate congestive heart failure require adequate monitoring and counseling, as fluid retention and edema have been reported with NSAID treatment.

Clinical studies suggest that the use of ibuprofen, particularly at high doses (2400 mg/day), may be associated with a small increased risk of arterial thrombotic events such as myocardial infarction or stroke. In general, epidemiological studies do not suggest that low doses of ibuprofen (eg, 1200 mg/day) are associated with an increased risk of arterial thrombotic events.

Patients with uncontrolled hypertension, congestive heart failure (NYHA II-III), established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should be treated with ibuprofen only after careful consideration, and high doses (2400 mg/kg) should be avoided. Day). Careful consideration should be given to initiation of long-term treatment in patients with risk factors for cardiovascular events (eg, hypertension, hyperlipidaemia, diabetes mellitus, smoking), particularly when high doses of ibuprofen (2400 mg/day) are administered.

kidney effects

Caution should be exercised when initiating treatment with ibuprofen in severely dehydrated patients.

As with other NSAIDs, prolonged use of ibuprofen has resulted in renal papillary necrosis and other renal pathologies. Renal toxicity has also been observed in patients in whom renal prostaglandins play a compensatory role in maintaining renal blood flow. In these patients, NSAID administration may cause a dose-dependent reduction in prostaglandin production and, secondarily, in renal blood flow, which may lead to renal failure. Those most at risk of this reaction are patients with kidney failure, heart failure, liver failure, patients taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID treatment is usually followed by recovery to the pre-treatment state.

SLE and mixed collagenosis

dermatological effects

Severe skin reactions, some fatal, such as exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported very rarely in association with the use of NSAIDs. Patients appear to be at greatest risk for these reactions early in therapy, with most cases starting within the first month of treatment. Brufen should be discontinued at the first appearance of rash, mucosal lesions or any other sign of hypersensitivity.

hematological effects

Like other NSAIDs, ibuprofen can disrupt platelet aggregation and prolong bleeding time in healthy individuals.

Aseptic Meningitis

Aseptic meningitis has been reported rarely in patients taking ibuprofen. Although it is probably more common in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients without underlying chronic disease.

impaired female fertility

The use of Brufen can impair female fertility and is not recommended in women trying to conceive. Discontinuation of Brufen should be considered in women who have difficulty conceiving or who are being evaluated for infertility.

NOTICES

Included as part ofPRECAUTIONSSection.

PRECAUTIONS

Cardiovascular thrombotic events

Clinical trials of up to three years' duration with various COX-2 selective and non-selective NSAIDs have demonstrated an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear whether the risk of cardiovascular thrombotic events is similar for all NSAIDs. The relative increase from baseline in NSAID-induced major cardiovascular thrombotic events appears to be similar in patients with and without known cardiovascular disease or risk factors for cardiovascular disease. However, patients with known cardiovascular disease or risk factors had a higher absolute incidence of excessive major cardiovascular thrombotic events due to their higher baseline rate. Some observational studies have shown that this increased risk of serious cardiovascular thrombotic events began within the first few weeks of treatment. An increased risk of cardiovascular thrombosis was seen more consistently at higher doses.

To minimize the potential risk of an adverse cardiovascular event in patients treated with NSAIDs, use the lowest effective dose for the shortest possible time. Physicians and patients should be alert to the development of such events during treatment, even in the absence of previous cardiovascular symptoms. Patients should be informed about the symptoms of serious cardiovascular events and the actions to be taken if they occur.

There is no consistent evidence that the concomitant use of aspirin reduces the increased risk of cardiovascular thrombotic events associated with the use of NSAIDs. Concomitant use of aspirin and an NSAID such as ibuprofen increases the risk of serious gastrointestinal (GI) events.

Status after coronary artery bypass grafting (CABG) surgery.

Two large controlled clinical trials using a COX-2 selective NSAID to treat pain in the first 10 to 14 days after coronary artery bypass surgery showed an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in CABG.

post MI patients

Observational studies conducted in the Danish National Registry showed that patients treated with NSAIDs in the post-myocardial infarction period had an increased risk of reinfarction, cardiovascular death and all-cause mortality from the first week of treatment. In the same cohort, the incidence of deaths in the first year after myocardial infarction was 20 per 100 person-years in patients treated with NSAIDs compared with 12 per 100 person-years in patients not exposed to NSAIDs. Although the absolute mortality rate declined somewhat after the first year after myocardial infarction, the increased relative risk of death in NSAID users persisted for at least the next four years of follow-up.

Avoid using Solufen in patients with a recent myocardial infarction unless the benefit is expected to outweigh the risk of recurrent cardiovascular thrombotic events. When Solufen is administered to patients with a recent myocardial infarction, patients should be monitored for signs of cardiac ischemia.

Gastrointestinal bleeding, ulceration and perforation

NSAIDs, including ibuprofen, cause serious gastrointestinal (GI) adverse events, including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or colon, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients who develop a serious upper GI adverse event while on NSAID treatment is symptomatic. Upper gastrointestinal ulcers, excessive bleeding, or perforation caused by NSAIDs occurred in approximately 1% of patients treated for 3 to 6 months and in approximately 2% to 4% of patients treated for 1 year. However, even short-term therapy is not risk-free.

Risk factors for gastrointestinal bleeding, ulceration and perforation

Patients with a history of peptic ulcer disease and/or GI bleeding who were taking NSAIDs had a 10-fold increased risk of GI bleeding compared to patients without these risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); of smoking; alcohol consumption; Older; and poor general condition. Most post-marketing reports of fatal gastrointestinal events have occurred in elderly or debilitated patients. Furthermore, there is an increased risk of gastrointestinal bleeding in patients with advanced liver disease and/or coagulopathy.

Strategies to minimize gastrointestinal risks in patients treated with NSAIDs:

Use the lowest effective dose for the shortest time possible.
Avoid administering more than one NSAID at the same time.
Avoid use in high-risk patients unless the benefit is expected to outweigh the increased risk of bleeding. For these patients, as well as for patients with active GI bleeding, therapies other than NSAIDs should be considered.
Watch for signs and symptoms of gastrointestinal ulceration and bleeding during NSAID treatment.
If a serious gastrointestinal adverse event is suspected, initiate investigation and treatment immediately and discontinue use of Solufen until a serious gastrointestinal adverse event has been ruled out.
Patients should be monitored more closely for evidence of gastrointestinal bleeding when co-administered with low-dose aspirin for cardiac prophylaxis.

hepatotoxicity

Elevations of ALT or AST (at least 3 times the upper limit of normal [ULN]) have been reported in approximately 1% of patients treated with NSAIDs in clinical studies. In addition, rare, sometimes fatal, cases of severe liver injury including fulminant hepatitis, liver necrosis and liver failure have been reported.

ALT or AST elevations (less than three times the ULN) may occur in up to 15% of patients treated with NSAIDs, including ibuprofen.

Educate patients about the warning signs and symptoms of hepatotoxicity (eg, nausea, fatigue, lethargy, diarrhea, itching, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). If clinical signs and symptoms consistent with liver disease occur or if systemic manifestations occur (eg, eosinophilia, rash, etc.), discontinue use of Solufen immediately and conduct a clinical evaluation of the patient.

hypertension

NSAIDs, including Solufen, can cause high blood pressure to return or make the condition worse-Existing hypertension, any of which may contribute to an increased incidence of cardiovascular events. Patients taking angiotensin-converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics may have poor responses to these therapies when taking NSAIDs.

Monitor blood pressure (BP) at the start of NSAID treatment and during treatment.

heart failure and edema

Meta-analyses of randomized controlled trials of coxib and the Traditional NSAID Trials Collaboration showed an approximately two-fold increase in hospitalizations for heart failure in patients treated selectively with COX-2 and in patients treated with non-selective NSAIDs compared with patients treated with placebo. In a study conducted by the Danish National Registry of Heart Failure Patients, the use of NSAIDs increased the risk of myocardial infarction, hospitalization for heart failure and death.

In addition, fluid retention and edema have been observed in some patients treated with NSAIDs. The use of ibuprofen can blunt the cardiovascular effects of several medications used to treat these conditions (eg, diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]).

Avoid using Solufen in patients with severe heart failure unless the benefit is expected to outweigh the risk of worsening heart failure. When Solufen is used in patients with severe heart failure, monitor patients for signs of worsening heart failure.

Kidney toxicity and hyperkalemia

kidney toxicity

Prolonged administration of NSAIDs has resulted in renal papillary necrosis and other renal lesions.

Renal toxicity has also been observed in patients in whom renal prostaglandins play a compensatory role in maintaining renal blood flow. In these patients, administration of an NSAID may cause a dose-dependent reduction in prostaglandin production and, secondarily, in renal blood flow, which may trigger overt renal decompensation. Those most at risk for this reaction are patients with renal insufficiency, dehydration, hypovolemia, congestive heart failure, hepatic insufficiency, patients taking diuretics and ACE inhibitors or ARBs, and elderly patients. Discontinuation of NSAID treatment is usually followed by recovery to the pre-treatment state.

There is no information from controlled clinical trials on the use of Solufen in patients with advanced kidney disease. The renal effects of Solufen may accelerate the progression of renal dysfunction in patients with pre-existing renal disease.

Correct volume status in dehydrated or hypovolemic patients before starting Solufen. During the use of Solufen, monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration or hypovolemia. Avoid using Solufen in patients with advanced kidney disease unless the benefit is expected to outweigh the risk of worsening kidney function. If Solufen is used in patients with advanced kidney disease, monitor the patient for signs of worsening kidney function.

hyperkalemia

Elevations in serum potassium, including hyperkalemia, have been reported with the use of NSAIDs even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to hyporeninemic hypoaldosteronism.

anaphylactic reactions

Ibuprofen has been associated with anaphylactic reactions in patients with and without known hypersensitivity to ibuprofen and in patients with aspirin-sensitive asthma.

Get emergency help if an anaphylactic reaction occurs.

Asthma exacerbation associated with aspirin sensitivity

A subpopulation of patients with asthma may have aspirin-sensitive asthma, which may include chronic rhinosinusitis complicated by nasal polyps; severe and potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs. As cross-reactivity between aspirin and other NSAIDs has been reported in aspirin-sensitive patients, Solufen is contraindicated in patients with this form of aspirin sensitivity. When Solufen is used in patients with pre-existing asthma (no known aspirin sensitivity), patients should be monitored for changes in asthma signs and symptoms.

severe skin reactions

NSAIDs, including ibuprofen, can cause serious adverse skin reactions, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which can be fatal. These serious events can happen without warning. Educate patients about the signs and symptoms of serious skin reactions and discontinue use of Solufen at the first appearance of a rash or other sign of hypersensitivity. Solufen is contraindicated in patients with a history of severe skin reactions to NSAIDs.

Premature closure of the fetal ductus arteriosus

Ibuprofen can cause premature closure of the fetal ductus arteriosus. Avoid the use of NSAIDs, including Solufen, in pregnant women more than 30 weeks pregnant (third trimester).

hematologic toxicity

Anemia has occurred in patients treated with NSAIDs. This may be due to gross or occult GI blood loss, fluid retention, or an incompletely described effect on erythropoiesis. If signs or symptoms of anemia develop in a patient treated with Solufen, hemoglobin or hematocrit should be monitored.

NSAIDs, including Solufen, may increase the risk of bleeding events. Comorbidities such as coagulopathy, concomitant use of warfarin, other anticoagulants, antiplatelet agents (eg. Monitor these patients for signs of bleeding.

Solufen must be diluted before use. Infusion of undiluted medication may cause hemolysis.

Mask inflammation and fever

Solufen's pharmacological activity in reducing inflammation and possibly fever may reduce the usefulness of diagnostic signs in detecting infection.

laboratory monitoring

Because severe GI bleeding, hepatotoxicity, and kidney damage can occur without warning symptoms or signs, patients on long-term NSAID therapy should be monitored regularly with a blood count and chemical profile.

Ophthalmological effects

Blurred or decreased vision, scotomata and changes in color vision have been reported with oral ibuprofen. Discontinue ibuprofen if a patient develops such symptoms and refer for an ophthalmologic evaluation, including central visual field and color vision tests.

Aseptic Meningitis

Aseptic meningitis with fever and coma has been observed in patients treated with oral ibuprofen. Although it is more likely to occur in patients with systemic lupus erythematosus and related connective tissue diseases, it has been reported in patients without an underlying chronic disease. If signs or symptoms of meningitis develop in a patient taking ibuprofen, assess whether or not the signs or symptoms are related to ibuprofen therapy.

Patient counseling information

Instruct the patient to read the FDA-approved patient label (medication guide) that accompanies each prescription issued. Patients, family members, or caregivers should be provided with the following information prior to initiating Solufen therapy and periodically during ongoing therapy.

Cardiovascular thrombotic events

Advise patients to be alert for symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurred speech, and to report any such symptoms to their physician immediately.

Gastrointestinal bleeding, ulceration and perforation

Advise patients to report their symptoms of ulceration and bleeding, including upper abdominal pain, dyspepsia, melena, and hematemesis, to their physician. Educate patients about the increased risk and signs and symptoms of GI bleeding when using low-dose aspirin concomitantly for cardiac prophylaxis.

hepatotoxicity

Educate patients about the warning signs and symptoms of hepatotoxicity (eg, nausea, fatigue, lethargy, itching, diarrhea, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). In this case, instruct the patient to discontinue Solufen and seek medical attention immediately.

heart failure and edema

Advise patients to look out for symptoms of congestive heart failure, such as shortness of breath, unexplained weight gain, or swelling, and to contact their physician if such symptoms occur.

anaphylactic reactions

Educate patients about the signs of an anaphylactic reaction (eg, difficulty breathing, swelling of the face or throat). Instruct patients to seek emergency help immediately if this occurs.

severe skin reactions

Advise patients to stop taking Solufen immediately if they develop any type of rash and to contact their physician as soon as possible.

female fertility

Educate women of childbearing potential trying to conceive that NSAIDs, including Solufen, may be associated with reversible delay of ovulation.

Fetal Toxicity

Inform pregnant women that they should avoid the use of Solufen and other NSAIDs after 30 weeks of pregnancy due to the risk of premature closure of the fetal ductus arteriosus.

Avoid concomitant use of NSAIDs

Inform patients that concomitant use of Solufen with other NSAIDs or salicylates (eg, diflunisal, salsalate) is not recommended due to increased risk of gastrointestinal toxicity and little or no enhancement of efficacy. Warn patients that NSAIDs can be found in over-the-counter medications used to treat the common cold, fever, or insomnia.

Use of NSAIDs and low-dose aspirin

Advise patients not to use low-dose aspirin at the same time as Solufen until discussed with their physician.

non-clinical toxicology

Carcinogenesis, mutagenesis, impaired fertility

carcinogenesis

Long-term animal studies have not been conducted to evaluate the carcinogenic potential of ibuprofen.

mutagenic

In published studies, ibuprofen was not mutagenicin vitrobacterial reverse mutation assay (Ames assay).

impaired fertility

In a published study, dietary administration of ibuprofen to male and female rats 8 weeks before and during mating at doses of 20 mg/kg (0.06 times the MRHD based on body surface area comparison) had no effect on fertility or in male or female litter size.

In other studies, ibuprofen was administered intraperitoneally to adult mice at a dose of 5.6 mg/kg/day (0.0085 times the MRHD based on body surface area comparison) for 35 or 60 days in males and females. 35 days in females. There was no effect on sperm motility or viability in men, but reduced ovulation has been reported in women.

Use in certain population groups

the pregnancy

Risk summary

The use of NSAIDs, including Solufen, during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Avoid the use of NSAIDs, including Solufen, in pregnant women more than 30 weeks pregnant (third trimester).

There are no adequate and well-controlled studies of Solufen in pregnant women. Data from observational studies on the possible embryofetal risks of NSAID use in women in the first or second trimester of pregnancy are inconclusive. In the general US population, all clinically recognized pregnancies, regardless of drug exposure, have a historical rate of 2-4% for severe malformations and 15-20% for missed miscarriages. In published animal reproduction studies, there were no clear developmental effects at doses up to 0.4 times the maximum recommended human dose (MRHD) in rabbits and 0.5 times the MRHD in rats when administered during pregnancy. In contrast, an increase in membranous ventricular septal defects was reported in rats treated with MRHD 0.8 times on days 9 and 10 of gestation. Based on animal data, prostaglandins have been shown to play an important role in endometrial vascular permeability, blastocyst implantation and decidualization. In animal experiments, administration of prostaglandin synthesis inhibitors such as ibuprofen led to increased losses before and after implantation. Inform a pregnant woman of the potential risk to the fetus.

clinical considerations

labor or delivery

There are no studies on the effects of Solufen during labor or delivery. In animal studies, NSAIDs, including ibuprofen, inhibit prostaglandin synthesis, delay labor and increase the incidence of stillbirths.

animal data

In one published study, female rabbits received 7.5, 20, or 60 mg/kg of ibuprofen (0.04, 0.12, or 0.36 times the maximum recommended human daily dose of 3,200 mg of ibuprofen, based on surface area body) no clear treatment-related developmental abnormalities were observed from day 1 to day 29 of pregnancy. This dose was associated with significant maternal toxicity (gastric ulcers, gastric lesions). In the same publication, female rats received 7.5, 20, 60, 180 mg/kg of ibuprofen (0.02, 0.06, 0.18, 0.54 times the maximum daily dose), there was no clear negative impact on development . Maternal toxicity (gastrointestinal lesions) has been observed with doses of 20 mg/kg and above.

In a published study, rats were orally administered 300 mg/kg of ibuprofen (0.912 times the maximum human daily dose of 3200 mg based on body surface area) on days 9 and 10 of gestation (critical time points for cardiac development in rats). . Treatment with ibuprofen resulted in an increased incidence of membranous ventricular septal defects. This dose was associated with significant maternal toxicity, including gastrointestinal toxicity. In fetuses of rabbits treated with 500 mg/kg (3 times the maximum daily human dose), the occurrence of membranous ventricular septal defect and gastroschisis was observed from the 9th to the 11th day of gestation.

lactation

Risk summary

No lactation studies have been conducted with Solufen; however, limited published literature reports that ibuprofen is present in breast milk after oral administration in relative infant doses of 0.06% to 0.6% of the maternal weight-adjusted daily dose. There were no reports of adverse effects in nursing infants or effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Solufen and the possible side effects of Solufen on the infant or the mother's underlying conditions.

Females and males with reproductive potential

sterility

Women

Depending on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including Solufen, may delay or prevent ovarian follicle rupture, which has been associated with reversible infertility in some women. Published animal studies have shown that the administration of prostaglandin synthesis inhibitors has the potential to interrupt the prostaglandin-mediated follicular rupture required for ovulation. Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation. Consider discontinuing NSAIDs, including Solufen, in women who are having trouble becoming pregnant or who are being evaluated for infertility.

pediatric use

The safety and efficacy of Solufen for the treatment of pain and fever in pediatric patients aged 6 months and older is supported by evidence of fever reduction from a multicenter open-label study in hospitalized pediatric patients with fever, along with safety data. of Solufen Exposure in 143 pediatric patients aged 6 months and older in two pediatric fever studies and one pediatric pain study, supporting data from other ibuprofen products approved in pediatric patients, and evidence of adequate and well-studied controls in adults. The effectiveness of Solufen in the treatment of pain and fever in pediatric patients less than 6 months of age has not been studied.

geriatric use

Elderly patients are at increased risk of serious cardiovascular, gastrointestinal and/or renal adverse reactions associated with NSAIDs compared to younger patients. If the expected benefits for the elderly patient outweigh these potential risks, initiate dosing at the lower end of the dosing range and monitor patients for side effects.

Clinical trials of Solufen did not include sufficient numbers of subjects age 65 and older to determine whether they responded differently from younger subjects. Dose selection for an elderly patient should be cautious and generally start at the lower end of the dosage range to reflect the greater frequency of decreased liver, kidney, or heart function and concomitant disease or other drug therapy. Elderly patients are at an increased risk of serious gastrointestinal side effects.

Appropriate echocardiography should be performed prior to administration of Solufen to determine hemodynamically significant patency.Canal arterialand to rule out pulmonary hypertension and ductus-dependent congenital heart disease.

Since prophylactic use in the first 3 days of life (beginning within 6 hours of birth) in premature infants less than 28 weeks' gestation has been associated with increased pulmonary and renal side effects, Solufen should not be used prophylactically in no gestational age. In particular, severe hypoxemia with pulmonary hypertension was reported in 3 infants within the first hour after the first infusion, which resolved within 30 minutes of starting therapy with inhaled nitric oxide.

If hypoxemia occurs during or after Solufen infusion, special attention should be paid to pulmonary pressure.

Ibuprofen was shown therein vitroDisplacement of bilirubin from its albumin-binding site may increase the risk of bilirubin encephalopathy in preterm infants. Therefore, ibuprofen should not be used in infants with significantly elevated bilirubin levels.

As a nonsteroidal anti-inflammatory drug (NSAID), ibuprofen can mask the usual signs and symptoms of infection.)

Solufen should be administered with care to avoid extravasation and possible resultant tissue irritation.

As ibuprofen can inhibit platelet aggregation, premature infants should be monitored for signs of bleeding.

Since ibuprofen may decrease the clearance of aminoglycosides, close monitoring of their serum levels is recommended during concomitant use with ibuprofen.

Careful monitoring of renal and gastrointestinal function is recommended.

In preterm infants with a gestational age of less than 27 weeks, the occlusion rate isCanal arterial(33 to 50%) was considered low at the recommended dosage regimen.

This medicinal product contains less than 1 mmol sodium (15 mg) per 2 ml and is therefore essentially “sodium-free”.

NOTICES

Included as part of"PRECAUTIONS"Section

PRECAUTIONS

Generally

There are no long-term studies of infants treated with ibuprofen beyond the 36-week follow-up period after conception. The effects of ibuprofen on neurodevelopment and growth and on pathologic processes associated with prematurity (such as retinopathy of prematurity and chronic lung disease) have not been studied.

Infection

Solufen can change the usual signs of infection. The physician must be constantly vigilant and use the drug with particular caution in controlled infections and in infants at risk of infection.

thrombocyte aggregation

Like other NSAIDs, Solufen can inhibit platelet aggregation. Premature babies should be monitored for signs of bleeding. Ibuprofen has been shown to increase bleeding time (but within the normal range) in normal adult subjects. This effect may be exaggerated in patients with underlying hemostatic defects (seeCONTRAINDICATIONS).

bilirubin shift

Ibuprofen has been shown to displace bilirubin from albumin binding sites; Therefore, it should be used with caution in patients with elevated total bilirubin.

Administration

Solufen should be administered with caution to avoid extravascular injection or leakage, as the solution may be irritating to tissues.

Use in certain population groups

pediatric use

Safety and efficacy have only been established in premature infants.