DDR60 mg

Erosive Esophagitis (EE)

DDR is an established, FDA-approved indication for healing of all grades of erosive esophagitis for up to 8 weeks in adults and adolescents 12 years of age and older. DDR is also indicated for maintenance of healed erosive esophagitis and relief of heartburn for up to 6 months in adults (up to 16 weeks in patients 12 to 17 years of age).

Symptomatic Non-Erosive Gastroesophageal Reflux Disease (GERD)

DDR is an established indication for treatment of heartburn associated with symptomatic non-erosive GERD for 4 weeks in adults and adolescents 12 years of age and older.

Each Dexlansoprazole delayed-release capsule contains Dexlansoprazole 30 mg or Dexlansoprazole 60 mg as the active ingredient.

DDR is a proton pump inhibitor (PPI) medicine used to reduce the amount of acid produced in the stomach. DDR is commonly prescribed to heal acid-related damage to the food pipe (erosive esophagitis) and to relieve persistent heartburn caused by acid reflux (GERD). DDR uses a special dual delayed-release capsule technology that releases DDR in two stages, allowing once-daily dosing to control stomach acid over a longer period. DDR is taken by mouth, usually once a day, with or without food, and the dose and length of treatment with DDR depend on the condition being treated. As with all proton pump inhibitors, DDR should be used at the lowest effective dose for the shortest duration appropriate for the condition.

Proton Pump Inhibitor (PPI)

Dexlansoprazole is the R-enantiomer of lansoprazole and works by irreversibly inhibiting the hydrogen-potassium ATPase (proton pump) enzyme system at the secretory surface of gastric parietal cells, blocking the final step of acid production. Dexlansoprazole is formulated as a Dual Delayed-Release (DDR) capsule containing two types of enteric-coated granules with different pH-dependent release profiles, producing two separate plasma concentration peaks (approximately 1-2 hours and 4-5 hours after dosing) and extending the duration of acid suppression compared with conventional single-release PPIs. Dexlansoprazole is extensively metabolized in the liver, mainly via the CYP2C19 and CYP3A4 enzyme pathways, and has an elimination half-life of approximately 1-2 hours.

• DDR capsules may be taken with or without food.
• Swallow the DDR capsule whole; do not crush or chew it.
• If swallowing the capsule whole is difficult, the DDR capsule may be opened and the granules sprinkled onto a tablespoon of applesauce, then swallowed immediately without chewing; the mixture should not be stored for later use.
• As directed by a healthcare professional, the granules from an opened DDR capsule may also be mixed with water and given through an oral syringe or a nasogastric tube.
• If a dose of DDR is missed, take it as soon as remembered; if it is almost time for the next dose, skip the missed dose and continue with the regular schedule. Do not take two doses of DDR at one time.
• Take DDR at the same time each day for the best effect.

• Clopidogrel: DDR may modestly reduce formation of the active metabolite of clopidogrel through CYP2C19 inhibition; in clinical studies with DDR this reduction was small (about 9%) and was not considered clinically important, but clinical judgment is advised when DDR is combined with clopidogrel.
• Methotrexate (high-dose): Concomitant use of DDR with high-dose methotrexate may elevate and/or prolong serum methotrexate levels, increasing the risk of methotrexate toxicity; a temporary interruption of DDR may be considered by the prescriber.
• Warfarin: Concomitant use with DDR may increase INR and prothrombin time, raising bleeding risk; INR/PT monitoring is recommended.
• Drugs dependent on gastric pH for absorption (e.g., certain antifungal and antiretroviral drugs such as ketoconazole, itraconazole, atazanavir): Because DDR reduces stomach acidity, DDR can lower the absorption and effectiveness of these drugs.
• Rilpivirine-containing products: Concurrent use with DDR is contraindicated because DDR significantly decreases rilpivirine plasma concentrations and can cause loss of antiviral effect.
• Tacrolimus: DDR may increase tacrolimus blood concentrations, particularly in patients who are CYP2C19 intermediate or poor metabolizers; monitoring of tacrolimus levels is advised.
• Digoxin: DDR may increase digoxin exposure; monitoring for digoxin toxicity is recommended.
• Strong CYP2C19/CYP3A4 inducers (e.g., rifampin, St. John's Wort): These may substantially decrease DDR concentrations and reduce its effectiveness; concomitant use should generally be avoided.

Common Side Effects

Diarrhea, abdominal pain, nausea, upper respiratory tract infection, vomiting, and flatulence are the most commonly reported side effects of DDR. In adolescents (12-17 years), headache, abdominal pain, diarrhea, nasopharyngitis, and oropharyngeal pain have also been reported with DDR.

Serious Side Effects - Seek Medical Attention

• Signs of a severe allergic reaction (anaphylaxis) such as swelling of the face or throat, severe rash, or difficulty breathing.
• Severe skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis (blistering or peeling skin).
• Signs of kidney problems (acute tubulointerstitial nephritis), such as decreased urination, blood in urine, or swelling.
• Persistent, watery, or bloody diarrhea, which may indicate Clostridioides difficile-associated diarrhea (see Precautions and Warnings).
• Signs of liver problems, such as yellowing of the skin or eyes, dark urine, or severe abdominal pain.
• New or worsening joint pain with a rash on the cheeks or arms that worsens in sunlight (possible cutaneous or systemic lupus erythematosus).
• Signs of low magnesium, such as seizures, irregular heartbeat, tremors, or muscle spasms, particularly with long-term DDR use (see Precautions and Warnings).
• A bone fracture, particularly of the hip, wrist, or spine, associated with long-term DDR use (see Precautions and Warnings).

Pregnancy

There are no adequate, well-controlled studies of DDR use in pregnant women. Animal reproduction studies with DDR showed effects on fetal/offspring bone development (reduced femur weight, femur length, and growth plate thickness) at maternal exposures around 1.8 times the recommended human dose. DDR should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, and pregnant women should discuss the use of DDR with their healthcare provider.

Breastfeeding

It is not known whether DDR passes into human breast milk; related lansoprazole metabolites have been detected in the milk of lactating rats. The decision to use DDR while breastfeeding should weigh the benefits of breastfeeding and the mother's clinical need for DDR against any potential risk to the infant, and should be made in consultation with a healthcare professional.

• Gastric malignancy: A symptomatic response to DDR does not exclude the presence of gastric cancer; consider further evaluation, especially in older patients or those with alarm symptoms such as unexplained weight loss or persistent vomiting.
• Acute tubulointerstitial nephritis: This kidney condition may occur at any point during treatment with DDR; discontinue promptly if it is suspected.
• Clostridioides difficile-associated diarrhea: Proton pump inhibitors such as DDR may be associated with an increased risk of C. difficile infection, particularly in hospitalized patients; use DDR at the lowest effective dose for the shortest duration needed.
• Bone fracture risk: Long-term use of DDR, especially at high doses and for a year or longer, has been associated with an increased risk of osteoporosis-related fractures of the hip, wrist, or spine; at-risk patients should follow guidance on adequate calcium and vitamin D intake and use the lowest effective DDR dose.
• Hypomagnesemia: Low blood magnesium has been reported with prolonged DDR use, generally after 3 months or more and most often after a year; healthcare providers may consider checking magnesium levels before and periodically during long-term DDR therapy.
• Vitamin B12 (cyanocobalamin) deficiency: Long-term use of DDR, generally longer than 3 years, may reduce absorption of vitamin B12; monitor for signs of deficiency if long-term DDR use is required.
• Cutaneous and systemic lupus erythematosus: New-onset or worsening lupus has been reported with PPI use, including DDR; discontinue DDR and refer to a specialist if manifestations occur.
• Fundic gland polyps: Long-term use of DDR, especially beyond 1 year, is associated with an increased risk of benign fundic gland polyps; use the shortest duration of DDR appropriate for the condition.
• Interference with diagnostic testing: DDR can cause false-positive results in tests for neuroendocrine tumors (chromogranin A) and in secretin stimulation tests; DDR should be temporarily stopped before these tests as advised by the prescriber.
• Methotrexate co-administration: See Drug Interactions; high-dose methotrexate combined with DDR may require temporary interruption of DDR.

There is limited experience with DDR overdose, and no cases involving serious harm or death have been reported. If an overdose of DDR is suspected, do not induce vomiting unless specifically directed to do so by a doctor or a poison control center. Seek immediate medical attention or contact an emergency or poison control service. Treatment of DDR overdose is symptomatic and supportive; DDR is not effectively removed by hemodialysis.

Store DDR according to the instructions on the product label, and keep DDR out of the reach of children.

Children

The safety and effectiveness of DDR have been established only in patients 12 years of age and older. DDR is not recommended in children younger than 2 years of age because of a potential risk of heart valve (mitral valve) thickening observed in animal studies, and DDR has not been shown to be effective for symptomatic GERD in infants 1 month to less than 1 year of age. Use of DDR in children below 12 years of age should only occur under specialist guidance.

Elderly

No overall differences in the safety or effectiveness of DDR were observed between elderly and younger patients in clinical trials, although elimination of DDR may be slower and drug exposure somewhat higher in older adults. No dose adjustment of DDR is required based on age alone, but elderly patients using DDR long-term should be monitored for bone, magnesium, and vitamin B12-related risks (see Precautions and Warnings).

Renal Impairment

No dosage adjustment of DDR is required in patients with renal impairment, as DDR is primarily eliminated through the liver rather than the kidneys.

Hepatic Impairment

No dose adjustment of DDR is needed in mild hepatic impairment (Child-Pugh Class A). In moderate hepatic impairment (Child-Pugh Class B), the recommended dose of DDR for healing erosive esophagitis is reduced to 30 mg once daily. DDR is not recommended in patients with severe hepatic impairment (Child-Pugh Class C), as DDR has not been studied in this population.

The duration of DDR treatment depends on the indication: healing of erosive esophagitis is typically treated with DDR for up to 8 weeks; maintenance therapy after healing, to keep the esophagitis healed and control heartburn, may continue with DDR for up to 6 months in adults (up to 16 weeks in patients 12-17 years); and symptomatic non-erosive GERD is generally treated with DDR for 4 weeks. Long-term or repeated courses of DDR should be reviewed periodically by a healthcare professional, given the risks associated with prolonged PPI use (see Precautions and Warnings).

Proton Pump Inhibitor (PPI); Antisecretory / Antiulcer agent

Dexlansoprazole irreversibly binds to and inhibits the hydrogen-potassium ATPase (H+/K+-ATPase) enzyme, or proton pump, located on the surface of gastric parietal cells, thereby blocking the final step of gastric acid secretion regardless of the stimulus.

DDR is approved for use only in patients 12 years of age and older for the labeled indications. The safety and effectiveness of DDR have not been established in children below 12 years of age. DDR is not recommended in children under 2 years of age because of a possible risk of heart valve thickening seen in animal studies, and studies have not shown DDR (or its parent compound lansoprazole) to be effective for symptomatic GERD in infants aged 1 month to less than 1 year.