FDA Updates

The US Food and Drug Administration (FDA) has approved dabigatran etexilate (Pradaxa) oral pellets for the treatment of venous thromboembolism (VTE) in children aged 3 months to less than 12 years. The drug is to be administered immediately after patients have completed a 5-day course of an anticoagulant given by injection.

The most common side effects include digestive system symptoms and bleeding. Dabigatran etexilate can cause serious and fatal bleeding and is not recommended for patients with bioprosthetic heart valves or triple-positive antiphospholipid syndrome.

A boxed warning cautions that stopping treatment early may increase the risk for clots and that spinal or epidural hematomas in patients undergoing spinal procedures may cause serious side effects.

Dabigatran etexilate was originally approved in 2010 for adults with nonvalvular atrial fibrillation to reduce risk for stroke and systemic embolism.

Source: FDA

The US FDA has approved Chimerix’s brincidofovir (BCV, Tembexa) to treat smallpox. Fearful of a possible bioweapon attack, the United States has been steadily preparing a defense through the Biomedical Advanced Research and Development Authority. BCV is neither a new nor unknown drug. It is a lipid conjugate of cidofovir, a drug used to treat cytomegalovirus (CMV) in patients with AIDS.

Dose:

• ≥48 kg (tablet or oral suspension): 200 mg PO qWeek x 2 doses (on Days 1 and 8)
• <48 kg (oral suspension): 4 mg/kg PO qWeek x 2 doses (on Days 1 and 8)

Adverse Effect: Diarrhea (8%), Nausea (5%), Vomiting (4%), Serum creatinine elevated (>1.5-3x ULN) (4%), Abdominal pain (3%), ALT elevated (>3 to 20x ULN) (2-3%), Total bilirubin elevated (>1.5 to 10x ULN) (1-3%), AST elevated (>3 to 20x ULN) (1-2%)

Tecovirimat was the first drug for smallpox, approved in 2018.

Source: FDA

The US FDA approved Wegovy (semaglutide) injection a GLP-1 receptor agonists (2.4 mg once weekly SC) for chronic weight management in adults with obesity or overweight with at least one weight-related condition (such as high blood pressure, type 2 diabetes, or high cholesterol), for use in addition to a reduced-calorie diet and increased physical activity.

The drug is indicated for chronic weight management in patients with a body mass index (BMI) of 27 kg/m2 or greater who have at least one weight-related ailment or in patients with a BMI of 30 kg/m2 or greater.

Side effects: nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue, dyspepsia, dizziness, abdominal distension, eructation (belching), hypoglycemia in patients with type 2 diabetes, flatulence (gas buildup), gastroenteritis and GERD.

Warning: risk of thyroid C-cell tumors, not to be used in patients with a personal or family history of medullary thyroid carcinoma or in patients with a rare condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Source: FDA

Sotorasib (Lumakras), specifically targets the KRAS G12C mutation, which accounts for about 13% of NSCLC mutations. KRAS mutations are the most common mutations to occur in NSCLC tumors, accounting for about 25% of them, but for a long time, they appeared to be resistant to drug therapy.

Dose: 960 mg once daily

Side effects: The most common adverse reactions (≥ 20%) were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity, and cough. The most common laboratory abnormalities (≥ 25%) were decreased lymphocytes, decreased hemoglobin, increased aspartate aminotransferase, increased alanine aminotransferase, decreased calcium, increased alkaline phosphatase, increased urine protein, and decreased sodium.

Contraindications: Interstitial lung disease, CLD, along with drugs that are substrates of the P-glycoprotein.

Source: FDA

The US FDA has approved ozanimod (Zeposia) for adults with moderately to severely active ulcerative colitis (UC), the company has announced. Ozanimod (0.92 mg), an oral medication taken once daily, is the first sphingosine-1-phosphate (S1P) receptor modulator approved for UC.

In March 2020, the FDA approved ozanimod for adults with relapsing forms of multiple sclerosis

The approval, awarded to Bristol Myers Squibb, was based on the data from a placebo-controlled phase 3 trial dubbed True North. In the study, researchers evaluated ozanimod as a single, daily oral therapy for both adults and pediatric patients at least 12 years old with moderately to severely active ulcerative colitis.

More Info: FDA

The US Food and Drug Administration (FDA) has approved dapagliflozin (Farxiga, AstraZeneca) to reduce the risk for kidney function decline, kidney failure, cardiovascular death, and hospitalization for heart failure in adult patients with chronic kidney disease (CKD) at risk for disease progression.

Dapagliflozin  (5mg, 10mg OD) is a selective sodium-glucose transporter-2 (SGLT2) inhibitor.

Uses:

1. Type 2 Diabetes Mellitus: Initial 5 mg PO qDay in AM
2. Reduce the risk of hospitalization for heart failure: 10 mg PO qDay in AM. Used in Heart Failure with a reduced ejection fraction
3. Chronic Kidney Disease: Indicated to reduce risk of sustained eGFR decline, end-stage kidney disease (ESKD), cardiovascular death, and hospitalization for HF in adults with CKD who are at risk of progression

Dosage Modifications:
1. Renal impairment
eGFR ≥45mL/min/1.73 m2: No dosage adjustment required

2. eGFR 25 to <45 mL/min/1.73 m2
T2DM: Not recommended
3. HF or CKD: No dosage adjustment required
4. eGFR <25 mL/min/1.73 m2
Initiation not recommended
5. Patients with HF or CKD may continue 10 mg/day to reduce risk of eGFR decline, ESKD, CV death, and HF hospitalization
​6. ESRD/dialysis: Contraindicated

7.  Hepatic impairment
Mild or moderate: No dosage adjustment required
Severe: Not studied
Dosing Considerations

Source: FDA

The novel combined oral contraceptive, marketed as Nextstellis, contains 3 mg drospirenone (DRSP) and 14.2 mg of estetrol (E4) in tablet form. Estetrol is an estrogen that is naturally produced during pregnancy, but will now be produced from a plant source; it has not previously been used in oral contraceptives.

Source: FDA