Yosprala

Unless your doctor tells you otherwise, continue your normal diet.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take: 

• Clopidogrel
• Ticagrelor
• Anticoagulant (blood thinner) medications such as warfarin (Coumadin,), heparin, enoxaparin (Lovenox), fondaparinux (Arixtra), rivaroxaban (Xarelto), and apixaban (Eliquis) 
• Methotrexate: omeprazole may elevate methotrexate levels, which may lead to bone marrow toxicity
• Antiretroviral drugs used for HIV such as rilpivirine, atazanavir, nelfinavir and saquinavir
• Citalopram
• Cilostazol
• Phenytoin
• Diazepam
• Digoxin
• Medications that require acidic pH in stomach for absorption such as: iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, ketoconazole/itraconazole 
• St. John's Wort
• Rifampin
• Tacrolimus
• ACE-inhibitors such as benazepril (Lotensin, Lotensin HCT), captopril (Capoten, Capozide), enalapril (Vasotec, Vaseretic), lisinopril (Prinivil, Prinzide, Zestril, Zestoretic), quinapril (Accupril, Accuretic, Quinaretic)
• Diuretics such as acetazolamide (Diamox), amiloride (Midamor), bumetanide (Bumex), chlorothiazide (Diuril), chlorthalidone (Thalitone), furosemide (Lasix), hydrochlorothiazide (Microzide, HCTZ), metolazone (Zaroxolyn), torsemide (Demadex), triamterene (Dyrenium, Dyazide, Maxzide)
• Beta blockers such as metoprolol (Toprol XL, Lopressor), carvedilol (Coreg), bisoprolol (Zebeta), betaxolol (Kerlone), nebivolol (Bystolic), propranolol (Inderal)
• Valproic acid
• Cyclosporine
• Disulfiram
• Voriconazole

This is not a complete list of Yosprala drug interactions. Ask your doctor or pharmacist for more information. 

Tell your doctor if you are breastfeeding or plan to breastfeed. 

There is no information about the presence of Yosprala in human milk; however, the individual components of Yosprala, aspirin and omeprazole, are present in human milk. Because of the possibility for adverse reactions in nursing infants from Yosprala, a choice should be made whether to stop nursing or to stop use of this medication. The importance of the drug to the mother should be considered. 

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following: 

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication 

The recommended dose range of Yosprala is one delayed-release tablet daily. Yosprala is available in the following dosage forms and strengths:

• 81 mg delayed-release aspirin/40 mg immediate-release omeprazole
• 325 mg delayed-release aspirin/40 mg immediate-release omeprazole 

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include ringing in your ears, increased thirst, muscle pain or weakness, trouble breathing, or feeling cold.

Taking regular aspirin together with omeprazole (Prilosec) will not work the same way as taking combination aspirin and omeprazole (Yosprala). Do not substitute this medicine with over-the-counter products.

Avoid drinking alcohol. Alcohol may increase your risk of stomach bleeding.

Ask a doctor or pharmacist before using any cold, allergy, or pain medicine. Many combination medicines contain aspirin. Also avoid taking over-the-counter Prilosec without your doctor's approval. Taking certain products together can cause you to get too much of the medicines.

It is important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it.

Do not use this medicine if you are also using medicines containing rilpivirine (Edurant®, Complera®, Odefsey®). Using these medicines together may cause unwanted side effects.

Tell your doctor if you are of Asian descent, such as Filipino, Chinese, Japanese, Korean, or Taiwanese. You may need a lower dose of this medicine.

Serious stomach conditions may occur while taking this medicine. Check with your doctor immediately if you are having more than one of these symptoms: abdominal or stomach cramps, bloated feeling, watery and severe diarrhea which may also be bloody sometimes, fever, nausea or vomiting, or unusual tiredness or weakness.

Check with your doctor right away if you have a bloody urine, decrease amount of urine, a fever, joint pain, lower back or side pain, skin rash, trouble breathing, swelling of the body, feet, or ankles, or unusual weight gain after using this medicine. These may be symptoms of a serious kidney problem (including acute interstitial nephritis).

This medicine may increase your risk of having fractures of the hip, wrist, and spine. This is more likely if you are 50 years of age and older, if you receive high doses of this medicine, or use it for one year or more.

Cutaneous or systemic lupus erythematosus may occur or gets worse in lupus patients and are taking PPI. Call your doctor right away if you have a joint pain or skin rash on your cheeks or arms that gets worse when exposed in the sun.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Drinking alcohol while using this medicine may increase your risk of liver damage. If you drink 3 or more alcoholic drinks every day, tell your doctor.

Taking this medicine for a long time may make it harder for your body to absorb vitamin B12. Tell your doctor if you have concerns about vitamin B12 deficiency.

This medicine may cause hypomagnesemia (low magnesium in the blood). This is more likely to occur if you are taking this medicine for more than one year, or if you are taking this medicine together with digoxin (Lanoxin®) or certain diuretics or "water pills". Check with your doctor right away if you have convulsions (seizures), fast, racing, or uneven heartbeat, muscle spasms (tetany), tremors, or unusual tiredness or weakness.

Do not stop using this medicine suddenly without asking your doctor. You may need to slowly decrease your dose before stopping it completely.

Using this medicine during the later part of pregnancy can harm your unborn baby. If you think you have become pregnant while using this medicine, tell your doctor right away.

This medicine may cause a delay in ovulation for women and may affect their ability to have children. If you plan to have children, talk with your doctor before using this medicine.

Make sure any doctor or dentist who treats you knows that you are using this medicine. You may need to stop using this medicine several days before you have medical tests.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

• Abdominal or stomach pain, cramping, or burning
• abdominal or stomach tenderness
• black, tarry stools blisters, hives, or itching
• bloody urine
• chest pain
• constipation
• decreased frequency or amount of urine
• diarrhea
• drowsiness
• fever and chills
• general feeling of discomfort or illness
• hair loss
• headaches
• heartburn
• increased thirst
• indigestion
• loss of appetite
• lower back or side pain
• mood or mental changes
• muscle or joint pain
• muscle spasms (tetany) or twitching
• nausea or vomiting
• pain or swelling in the arms or legs without any injury
• seizures
• severe abdominal or stomach cramps and pain
• skin rash
• sore throat
• swelling of the face, fingers, or lower legs
• swollen glands
• trembling
• troubled breathing
• unusual tiredness or weakness
• vomiting of blood or material that looks like coffee grounds
• watery and severe diarrhea, which may also be bloody
• weight gain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• If you have an allergy to Yosprala (aspirin and omeprazole) or any part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Asthma, bleeding problems, nose polyps, or rhinitis.
• If you have any of these health problems: Kidney disease or liver disease.
• If you are having trouble getting pregnant or you are having your fertility checked.
• If you are pregnant or may be pregnant. Do not take Yosprala if you are in the third trimester of pregnancy. You may also need to avoid this medicine at other times during pregnancy. Talk with your doctor to see when you need to avoid taking Yosprala during pregnancy.
• If you are breast-feeding. Do not breast-feed while you take this medicine.
• If you are taking any of these drugs: Atazanavir, clopidogrel, nelfinavir, rifampin, rilpivirine, St. John's wort, ticagrelor, or voriconazole.
• If you are taking another drug that has the same drug in it.
• If you are taking any other NSAID.

Children:

• If your child or teenager has or is getting better from flu signs, chickenpox, or other viral infections. The risk of a very bad problem called Reye's syndrome may be raised. Do not give Yosprala to a child or teenager who has or is getting better from a viral infection.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Yosprala with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Belly pain or heartburn.
• Upset stomach or throwing up.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• Store in the original container at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep lid tightly closed.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

6.1       Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Yosprala 325 mg/40 mg was studied primarily in two randomized, double-blind controlled clinical trials (n=524) of 6 months duration. Table 1 lists adverse reactions that occurred in >2% of patients in the Yosprala arm and were more common than in the control arm, consisting of 325 mg of enteric coated (EC)-aspirin.

*Adverse reactions occurring in ≥2% of Yosprala-treated patients and more common than in the control arm

In Study 1 and Study 2 combined, 7% of patients taking Yosprala discontinued due to adverse reactions compared to 11% of patients taking EC-aspirin alone. The most common reasons for discontinuations due to adverse reactions in the Yosprala treatment group were upper abdominal pain (<1%, n=2), diarrhea (<1%, n=2) and dyspepsia (<1%, n=2).

Less Common Adverse Reactions

In Yosprala-treated patients in the clinical trials there were 2 patients with upper GI bleeding (gastric or duodenal) and 2 patients with lower GI bleeding (hematochezia and large intestinal hemorrhage) and one additional patient experienced obstruction in the small bowel.

See also the full prescribing information of aspirin and omeprazole products for additional adverse reactions.

6.2       Post-Marketing Experience

The following adverse reactions have been identified during post-approval use of aspirin and omeprazole separately. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Aspirin
Body as a Whole:Fever, hypothermia, thirst
Cardiovascular: Dysrhythmias, hypotension, tachycardia
Central Nervous System: Agitation, cerebral edema, coma, confusion, dizziness, headache, subdural or intracranial hemorrhage, lethargy, seizures
Fluid and Electrolyte: Dehydration, hyperkalemia, metabolic acidosis, respiratory alkalosis
Gastrointestinal: Dyspepsia, GI bleeding, ulceration and perforation, nausea, vomiting, transient elevations of hepatic enzymes, hepatitis, Reye's Syndrome [seeContraindications (4)], pancreatitis
Hematologic: Prolongation of the prothrombin time, disseminated intravascular coagulation, coagulopathy, thrombocytopenia
Hypersensitivity: Acute anaphylaxis, angioedema, asthma, bronchospasm, laryngeal edema, urticaria
Musculoskeletal: Rhabdomyolysis
Metabolism: Hypoglycemia (in pediatrics), hyperglycemia
Reproductive: Prolonged pregnancy and labor, stillbirths, lower birth weight infants, antepartum and postpartum bleeding
Respiratory: Hyperpnea, pulmonary edema, tachypnea
Special Senses: Hearing loss, tinnitus. Patients with high frequency hearing loss may have difficulty perceiving tinnitus.  In these patients, tinnitus cannot be used as a clinical indicator of salicylism.
Urogenital: Interstitial nephritis, papillary necrosis, proteinuria, renal impairment and failure

Omeprazole
Body As a Whole: Hypersensitivity reactions including anaphylaxis, anaphylactic shock, angioedema, bronchospasm [see Contraindications (4)], interstitial nephritis, urticaria (see also Skin below), systemic lupus erythematosus, fever, pain, fatigue, malaise
Cardiovascular: Chest pain or angina, tachycardia, bradycardia, palpitations, elevated blood pressure, peripheral edema
Endocrine: Gynecomastia
Gastrointestinal: Pancreatitis (some fatal), anorexia, irritable colon, fecal discoloration, esophageal candidiasis, mucosal atrophy of the tongue, stomatitis, abdominal swelling, dry mouth, microscopic colitis
Benign gastric fundic gland polyps have been noted rarely and appear to be reversible when treatment is discontinued.
Gastroduodenal carcinoids have been reported in patients with Zollinger-Ellison syndrome on long-term treatment with omeprazole. This finding is believed to be a manifestation of the underlying condition, which is known to be associated with such tumors.
Hematologic: Agranulocytosis (some fatal), hemolytic anemia, pancytopenia, neutropenia, anemia, thrombocytopenia, leukopenia, leukocytosis
Hepatic: Liver disease including hepatic failure (some fatal), liver necrosis (some fatal), hepatic encephalopathy hepatocellular disease, cholestatic disease, mixed hepatitis, jaundice, and elevations of liver function tests [ALT, AST, GGT, alkaline phosphatase, and bilirubin]
Infections and Infestations: Clostridium difficile-associated diarrhea [see Warnings and Precautions (5.9)]
Metabolism and Nutritional disorders: Hypoglycemia, hypomagnesemia, with or without hypocalcemia and/or hypokalemia, hyponatremia, weight gain
Musculoskeletal: Muscle weakness, myalgia, muscle cramps, joint pain, leg pain, bone fracture
Nervous System/Psychiatric: Psychiatric and sleep disturbances including depression, agitation, aggression, hallucinations, confusion, insomnia, nervousness, apathy, somnolence, anxiety, and dream abnormalities; tremors, paresthesia; vertigo
Respiratory: Epistaxis, pharyngeal pain
Skin: Severe generalized skin reactions including toxic epidermal necrolysis (some fatal), Stevens-Johnson syndrome, cutaneous lupus erythematosus and erythema multiforme; photosensitivity; urticaria; rash; skin inflammation; pruritus; petechiae; purpura; alopecia; dry skin; hyperhidrosis
Special Senses: Tinnitus, taste perversion
Ocular: Optic atrophy, anterior ischemic optic neuropathy, optic neuritis, dry eye syndrome, ocular irritation, blurred vision, double vision
Urogenital: Interstitial nephritis, hematuria, proteinuria, elevated serum creatinine, microscopic pyuria, urinary tract infection, glycosuria, urinary frequency, testicular pain

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Applies to aspirin / omeprazole: oral delayed release tablet

General

The most frequently reported side effects were gastritis, nausea, diarrhea, gastric polyps, and non-cardiac chest pain.[Ref]

Gastrointestinal

Very common (10% or more): Gastritis (18%)
Common (1% to 10%): Nausea, diarrhea, gastric polyp
Frequency not reported: Gastric bleeding, duodenal bleeding, hematochezia, large intestinal hemorrhage, small bowel obstruction

Aspirin:
-Very common (10% or more): Gastritis (16%)
-Common (1% to 10%): Nausea, diarrhea, gastric polyp
-Postmarketing reports: Dyspepsia, gastrointestinal (GI) bleeding, GI ulceration, GI perforation, vomiting, pancreatitis

Omeprazole:
-Postmarketing reports: Pancreatitis, colon irritable, fecal discoloration, stomatitis, abdominal swelling, dry mouth, microscopic colitis[Ref]

Cardiovascular

Aspirin:
-Postmarketing reports: Dysrhythmia, hypotension, tachycardia

Omeprazole:
-Postmarketing reports: Chest pain/angina, tachycardia, bradycardia, palpitation, blood pressure elevated[Ref]

Dermatologic

Aspirin:
-Postmarketing reports: Urticaria, angioedema

Omeprazole:
-Postmarketing reports: Urticaria, angioedema, toxic epidermal necrolysis, Stevens-Johnson syndrome, cutaneous lupus erythematosus, erythema multiforme, photosensitivity, rash, skin inflammation, pruritus, petechiae, purpura, alopecia, dry skin, hyperhidrosis[Ref]

Hematologic

Aspirin:
-Postmarketing reports: Prothrombin time prolonged, disseminated intravascular coagulation, coagulopathy, thrombocytopenia

Omeprazole:
-Postmarketing reports: Agranulocytosis, hemolytic anemia, pancytopenia, neutropenia, anemia, thrombocytopenia, leukopenia, leukocytosis[Ref]

Other

Common (1% to 10%): Non-cardiac chest pain

Aspirin:
-Common (1% to 10%): Noncardiac chest pain
-Postmarketing reports: Fever, hypothermia, thirst, pregnancy prolonged, labor prolonged, stillbirth, low birth weight infant, antepartum bleeding, postpartum bleeding, hearing loss, tinnitus

Omeprazole:
-Postmarketing reports: Fever, pain, fatigue, malaise, esophageal candidiasis, mucosal atrophy of tongue, clostridium difficile-associated diarrhea, weight gain, vertigo, tinnitus, peripheral edema[Ref]

Genitourinary

Aspirin:
-Postmarketing reports: Proteinuria

Omeprazole:
-Postmarketing reports: Hematuria, proteinuria, microscopic pyuria, urinary tract infection, glycosuria, urinary frequency, testicular pain[Ref]

Hepatic

Aspirin:
-Postmarketing reports: Reye's Syndrome, hepatitis, hepatic enzymes elevated

Omeprazole:
-Postmarketing reports: Liver disease, hepatic failure, liver necrosis, hepatic encephalopathy, hepatocellular disease, cholestatic disease, mixed hepatitis, jaundice, ALT increased, AST increased, bilirubin increased, alkaline phosphatase increased, gamma-glutamyl transferase increased[Ref]

Metabolic

Aspirin:
-Postmarketing reports: Dehydration, hyperkalemia, metabolic acidosis, hypoglycemia, hyperglycemia

Omeprazole:
-Postmarketing reports: Anorexia, hypoglycemia, hypomagnesemia, hypocalcemia, hypokalemia, hyponatremia[Ref]

Musculoskeletal

Aspirin:
-Postmarketing reports: Rhabdomyolysis

Omeprazole:
-Postmarketing reports: Systemic lupus erythematosus, muscle weakness, myalgia, muscle cramps, joint pain, leg pain, bone fracture[Ref]

Nervous system

Aspirin:
-Postmarketing reports: Cerebral edema, coma, dizziness, headache, subdural hemorrhage, intracranial hemorrhage, lethargy, seizure

Omeprazole:
-Postmarketing reports: Paresthesia, tremor, taste perversion, optic neuritis[Ref]

Endocrine

Omeprazole:
-Postmarketing reports: Gynecomastia[Ref]

Oncologic

Omeprazole:
-Postmarketing reports: Benign gastric fundic gland polyp, gastroduodenal carcinoid[Ref]

Psychiatric

Aspirin:
-Postmarketing reports: Agitation, confusion

Omeprazole:
-Postmarketing reports: Depression, agitation, aggression, hallucination, confusion, insomnia, nervousness, apathy, somnolence, anxiety, abnormal dream[Ref]

Renal

Aspirin:
-Postmarketing reports: Interstitial nephritis, papillary necrosis, renal impairment, renal failure

Omeprazole:
-Postmarketing reports: Interstitial nephritis, serum creatinine increased[Ref]

Respiratory

Aspirin:
-Postmarketing reports: Respiratory alkalosis, laryngeal edema, bronchospasm, asthma, hyperpnea, pulmonary edema, tachypnea

Omeprazole:
-Postmarketing reports: Bronchospasm, epistaxis, pharyngeal pain[Ref]

Ocular

Omeprazole:
-Postmarketing reports: Optic atrophy, anterior ischemic optic neuropathy, dry eye syndrome, ocular irritation, blurred vision, double vision[Ref]

Immunologic

Aspirin:
-Postmarketing reports: Acute anaphylaxis

Omeprazole:
-Postmarketing reports: Hypersensitivity reaction, anaphylaxis, anaphylactic shock[Ref]

Some side effects of Yosprala may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.