ferric maltol 30 MG Oral Capsule [Accrufer]

INDICATIONS AND USAGE ACCRUFER is indicated for the treatment of iron deficiency in adult and pediatric patients 10 years of age and older. ACCRUFER is an iron replacement product indicated for the treatment of iron deficiency in adult and pediatric patients 10 years of age and older. ( 1 )

DOSAGE AND ADMINISTRATION 30 mg orally twice daily on an empty stomach 1 hour before or 2 hours after meals ( 2.1 ) Swallow capsules whole. Do not open, break, or chew capsules. ( 2.1 ) Continue as long as necessary to replenish body iron stores ( 2.1 ) 2.1 Recommended Dosage Adults and Children Aged 10 Years and Above ​ The recommended dosage of ACCRUFER is 30 mg orally twice daily, on an empty stomach 1 hour before or 2 hours after meals. Swallow capsules whole. Do not open, break, or chew capsules. Treatment duration will depend on the severity of iron deficiency but generally at least 12 weeks of treatment is required. The treatment should be continued as long as necessary until ferritin levels are within the normal range.

WARNINGS AND PRECAUTIONS IBD Flare: Avoid use in patients with IBD flare ( 5.1 ) Iron Overload: Do not administer to patients with iron overload or those receiving intravenous iron. ( 5.2 ) Risk of Overdosage in Children Due to Accidental Ingestion: Keep out of reach of children. ( 5.3 ) 5.1 Increased Risk of Inflammatory Bowel Disease (IBD) Flare Avoid use of ACCRUFER in patients with an active inflammatory bowel disease (IBD) flare, as there is potential risk of increased inflammation in the gastrointestinal tract. 5.2 Iron Overload Excessive therapy with iron products can lead to excess storage of iron with the possibility of iatrogenic hemosiderosis. Do not administer ACCRUFER to patients with evidence of iron overload or patients receiving intravenous iron [see Contraindications ( 4 )] . Assess iron parameters prior to initiating ACCRUFER and monitor iron parameters while on therapy [see Overdosage ( 10 ) and Clinical Pharmacology ( 12.2 )] . 5.3 Risk of Overdosage in Children Due to Accidental Ingestion Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. Keep this product out of reach of children. In case of accidental overdose, call a doctor or poison control center immediately.

CONTRAINDICATIONS ACCRUFER is contraindicated in patients with a history of: Hypersensitivity to the active substance or to any of the excipients [see Description ( 11 )] . Reactions could include shock, clinically significant hypotension, loss of consciousness, and/or collapse. Hemochromatosis and other iron overload syndromes [see Warnings and Precautions ( 5.1 )] . Use may result in iron overdose [see Overdosage ( 10 )]. Receiving repeated blood transfusions. Use may result in iron overload [see Warnings and Precautions ( 5.2 ) and Overdosage ( 10 )]. Hypersensitivity to the active substance or any excipient ( 4 ) Hemochromatosis and other iron overload syndromes ( 4 ) Patients receiving repeated blood transfusions ( 4 )

CLINICAL PHARMACOLOGY 12.1 Mechanism of Action ACCRUFER delivers iron for uptake across the intestinal wall and transfer to transferrin and ferritin. 12.2 Pharmacodynamics ACCRUFER has been shown to increase serum iron parameters, including ferritin and transferrin saturation (TSAT) in adults and pediatric patients 10 years and older. 12.3 Pharmacokinetics Adults The pharmacokinetic properties of serum iron after administration of ACCRUFER was assessed in subjects with iron deficiency (with or without anemia) following a single dose and at steady state (after 1 week) of ACCRUFER 30 mg, 60 mg, or 90 mg twice daily (1 to 3 times the approved recommended dosage). Total serum iron concentrations increase in a less than dose proportional manner with increasing ACCRUFER doses. Total serum iron peak values were reached 1.5 to 3 hours after administration of ACCRUFER, and were comparable between Day 1 and Day 8. Pediatric Population In a pharmacokinetic substudy of the FORTIS trial [see Clinical Studies ( 14.3 )] in pediatric patients with iron-deficiency anemia, ferric maltol 15 mg or 30 mg was administered orally twice daily, for 7-10 days in children aged 10 to <18 years. After a single dose of 30 mg on Day 1, baseline-corrected serum iron reached peak concentration (C max = 119 µg/dL) at 2 hours, with a AUC 0-t of 374 h·µg/dL in children aged 12 to <18 years. After a single dose of 15 mg on Day 1, baseline-corrected serum iron reached peak concentration (C max = 40 µg/dL) at 2.1 hours, with a AUC 0-t of 60.1 h·µg/dL in children aged 10 to 11 years. No accumulation of maltol glucuronide was observed. Absorption ACCRUFER dissociates upon uptake from the gastrointestinal tract allowing iron and maltol to be absorbed separately. Effect of Food Food has been shown to decrease the bioavailability of iron after administration of ferric maltol capsules. Drug Interaction Studies In vitro Of the drugs screened for an interaction with ferric maltol in vitro at pH 1.2, 4.5 and 6.8, only mycophenolate and ethinyl estradiol showed any potential for interaction. Mycophenolate recovery was reduced by up to 16% at pH 1.2 but there was no interaction at pH 4.5; due to solubility issues data are not available for pH 6.8. Ethinyl estradiol recovery was reduced by up to 35% at pH 4.5; due to solubility issues data are not available for pH 1.2 and pH 6.8. These potential oral interactions can be avoided by spacing the administration of those drugs and ACCRUFER [see Drug Interactions ( 7.2 )] . Lisinopril, metoprolol and warfarin showed no interaction at any of the 3 pH conditions and can be taken with ACCRUFER. No interaction with ferric maltol was observed for atorvastatin (pH 6.8), and norgestimate (pH 1.2) (data were not obtainable at the other pH conditions due to solubility issues). In vivo No clinical studies evaluating the drug interaction potential of ACCRUFER have been conducted. Iron-containing preparations may decrease ciprofloxacin absorption into the bloodstream, resulting in lower serum and urine levels and reduced effectiveness. Absorption of tetracyclines including doxycycline is reported to be impaired by iron-containing preparations. 12.6 Maltol Phamacokinetics Maltol is metabolized through glucuronidation (UGT1A6) and sulphation in vitro . Of the total maltol ingested, a mean of between 39.8% and 60% was excreted in the urine as maltol glucuronide. There was no clinically meaningful change in exposure of maltol or maltol glucuronide in subjects with non-dialysis dependent chronic kidney disease (eGFR of > 15 mL/min/1.73m 2 and <60 mL/min/1.73m 2 ).