Silvergate Pharmaceuticals Release: Xatmep - The First and Only Ready-To-Use Methotrexate Oral Solution Is Now Available

DENVER, July 31, 2017 /PRNewswire/ -- Silvergate Pharmaceuticals, Inc. (www.silvergatepharma.com), leaders in the development and commercialization of innovative and safe medicines for children, today announced that Xatmep (methotrexate) Oral Solution, the first and only FDA-approved methotrexate oral solution, is now available for ordering. Xatmep is indicated for the treatment of acute lymphoblastic leukemia (ALL) and the management of polyarticular juvenile idiopathic arthritis (pJIA) in pediatric patients.

"Xatmep is an exciting product in that it provides an FDA-approved, ready-to-use oral solution of methotrexate for children without the need for needles, crushing of tablets, or compounding into a liquid formulation," said Frank Segrave, President & CEO, Silvergate Pharmaceuticals, Inc. "As a company, we continue to focus on pediatric medications that are safe, effective, and readily available."

Xatmep (methotrexate) Oral Solution, 2.5 mg/mL, is a ready-to-use product that requires no preparation, facilitating ease of dispensing at the pharmacy. Xatmep is manufactured under CGMPs in accordance with FDA regulations. It eliminates the need for needles, crushing or splitting tablets, or compounding tablets into a liquid formulation. It requires refrigeration, but may be stored at room temperature for 60 days after dispensing to the patient. Xatmep will be available through an extensive network of pharmacies. For additional information on how to obtain Xatmep, please call 1-855-379-0382.

INDICATIONS

Xatmep is a folate analog metabolic inhibitor indicated for the:

• treatment of pediatric patients with acute lymphoblastic leukemia (ALL) as part of a multi-phase, combination chemotherapy maintenance regimen.
• management of pediatric patients with active polyarticular juvenile idiopathic arthritis (pJIA) who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including full-dose non-steroidal anti-inflammatory agents (NSAIDs).

About Xatmep

Xatmep (methotrexate) Oral Solution was developed, primarily, to meet the need for a ready-to-use, 2.5 mg/mL, methotrexate oral solution for the treatment of pediatric patients for the indications stated above. Prior to Xatmep, there was no FDA-approved, ready-to-use oral liquid formulation of methotrexate for use by pediatric patients requiring body surface-area (BSA) dosing (mg/m²), or those who have difficulty swallowing or cannot consume tablets, or those with a fear of needles/injections. Silvergate's Xatmep resolves these unmet medical needs in pediatric patients.

IMPORTANT SAFETY INFORMATION 

BOXED WARNING: SEVERE TOXIC REACTIONS, INCLUDING EMBRYO-FETAL TOXICITY
See full Prescribing Information for complete boxed warning.
Methotrexate can cause the following severe or fatal adverse reactions.
Monitor closely and modify dose or discontinue methotrexate as appropriate.

• Bone marrow suppression [see Warnings and Precautions (5.1)]
• Serious infections [see Warnings and Precautions (5.2)]
• Renal toxicity and increased toxicity with renal impairment [see Warnings and Precautions (5.3)]
• Gastrointestinal toxicity [see Warnings and Precautions (5.4)]
• Hepatic toxicity [see Warnings and Precautions (5.5)]
• Pulmonary toxicity [see Warnings and Precautions (5.6)]
• Hypersensitivity and dermatologic reactions [see Warnings and Precautions (5.7)]
• Methotrexate can cause embryo-fetal toxicity, including fetal death. Use in pJIA is contraindicated in pregnancy. Consider the benefits and risks of XATMEP and risks to the fetus when prescribing XATMEP to a pregnant patient with a neoplastic disease. Advise females and males of reproductive potential to use effective contraception during and after treatment with XATMEP [see Contraindications (4), Warnings and Precautions (5.9), Use in Specific Populations (8.1, 8.3)].

ADDITIONAL SAFETY INFORMATION
Contraindications:
Xatmep is contraindicated in pregnant patients with non-malignant disease and in patients with severe hypersensitivity to methotrexate.

Warnings and Precautions: See full Prescribing Information for additional information.

• Xatmep suppresses hematopoiesis and can cause severe and life-threatening pancytopenia, anemia, leukopenia, neutropenia, and thrombocytopenia. Obtain blood counts at baseline and periodically; monitor patients for complications of bone marrow suppression.
• Patients treated with Xatmep are at increased risk for developing life-threatening or fatal bacterial, fungal, or viral infections, including Pneumocystis jiroveci pneumonia, invasive fungal infections, hepatitis B reactivation, tuberculosis (primary or reactivation), disseminated Herpes zoster and cytomegalovirus infections.
• Renal toxicity and increased toxicity with renal impairment, including acute renal failure. Consider administration of glucarpidase in patients with toxic plasma methotrexate concentrations (> 1 micromole/liter) and delayed clearance due to impaired renal function.
• Xatmep can cause diarrhea, stomatitis, vomiting, hemorrhagic enteritis, and fatal intestinal perforation. Patients with peptic ulcer disease and ulcerative colitis are at increased risk for severe gastrointestinal adverse reactions. Unexpected severe and fatal gastrointestinal toxicity can occur with concomitant use of NSAIDs.
• Hepatic toxicity: severe and potentially irreversible hepatotoxicity, including fibrosis, cirrhosis, and fatal liver failure can occur. Avoid use of Xatmep in patients with chronic liver disease.
• Pulmonary toxicity: acute or chronic interstitial pneumonitis and irreversible or fatal cases can occur at all dose levels.
• Hypersensitivity: anaphylaxis or other serious hypersensitivity reactions. Discontinue methotrexate.
• Severe, including fatal, dermatologic reactions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, skin necrosis, erythema multiforme can occur. Radiation dermatitis and sunburn may be "recalled."
• Secondary malignancies can occur at all dose levels. Lymphoproliferative disease has been reported with low-dose oral methotrexate which regressed when methotrexate is withdrawn.
• Methotrexate can cause embryo-fetal toxicity and fetal death when administered during pregnancy. Consider the risks and benefits of Xatmep and risks to the fetus when prescribing to a pregnant patient with a neoplastic disease. Effective contraception should be practiced by patients of reproductive potential while receiving Xatmep therapy, and for 3 and 6 months afterwards for males and females, respectively. Xatmep is contraindicated in non-neoplastic disease.
• Effects on reproduction: Methotrexate can cause impairment of fertility, oligospermia, and menstrual dysfunction. It is unknown if the infertility is reversible in affected patients.
• Increased toxicity in third-space accumulation. Evacuate significant third-space accumulation prior to methotrexate administration.
• Immunizations may be ineffective when given during Xatmep therapy.
• Immunization with live virus vaccines is not recommended during Xatmep therapy.
• Concomitant radiation therapy increases the risk of soft tissue necrosis and osteonecrosis associated with methotrexate.
• Closely monitor laboratory parameters for hematology, renal function, and liver function. Increase monitoring during initial dosing, dose changes, and during periods of increased risk of elevated methotrexate blood levels (e.g., dehydration).
• Pulmonary function tests may be useful if methotrexate-induced lung disease is suspected, especially if baseline measurements are available.
• Risk of improper dosing: Once-weekly dosing is appropriate. Fatal toxicity has been reported with daily dosing. An accurate milliliter measuring device should be used. Inform patients that a household teaspoon is not an accurate measuring device and could lead to overdosage.
• Advise women not to breastfeed during Xatmep therapy.

Adverse Reactions: See full Prescribing Information for additional adverse reactions.

• Most common adverse reactions are ulcerative stomatitis, leukopenia, nausea, abdominal distress, and elevated liver function tests.
• Other frequently reported reactions are malaise, fatigue, chills and fever, dizziness, and decreased resistance to infection.
• The approximate incidences of adverse reactions reported in pediatric patients with JIA treated with oral, weekly doses of methotrexate (5 to 20 mg/m²/week or 0.1 to 0.65 mg/kg/week) were as follows (virtually all patients were receiving concomitant nonsteroidal anti-inflammatory drugs, and some also were taking low doses of corticosteroids): elevated liver function tests, 14%; gastrointestinal reactions (e.g., nausea, vomiting, diarrhea), 11%; stomatitis, 2%; leukopenia, 2%; headache, 1.2%; alopecia, 0.5%; dizziness, 0.2%; and rash, 0.2%. Although there is experience with dosing up to 30 mg/m²/week in JIA, the published data for doses above 20 mg/m²/week are too limited to provide reliable estimates of adverse reaction rates.

Drug Interactions:

• Penicillins may reduce the clearance of methotrexate; increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with methotrexate. Monitor patients accordingly.
• Trimethoprim/sulfamethoxazole has been reported to increase bone marrow suppression in patients receiving methotrexate. Monitor patients accordingly.
• Hepatotoxins: May increase hepatotoxicity. Monitor patients receiving concomitant hepatotoxins for signs of hepatotoxicity.
• Probenecid may reduce renal elimination of methotrexate; consider alternative drugs.
• Theophylline: May decrease theophylline clearance. Monitor theophylline levels.

Keep this and all medications out of reach of children.

To report SUSPECTED ADVERSE REACTIONS, contact Silvergate Pharmaceuticals at 1-855-379-0383, or FDA at 1-800-FDA-1088 or www.fda.gov/MedWatch.

Please see full Prescribing Information, including the complete BOXED WARNING.

About Silvergate Pharmaceuticals, Inc.

Headquartered near Denver, Colorado, Silvergate Pharmaceuticals, Inc., is a privately held pharmaceutical company dedicated to leading the way in the development and commercialization of innovative pediatric medications that are safe, effective, and readily available.

Silvergate Pharmaceuticals is committed to filling the unmet needs of children, developing innovative medications that will help improve the quality of care and outcomes for pediatric patients. For more information, please visit www.Xatmep.com.

Reference: Xatmep [prescribing information]. Greenwood Village, CO: Silvergate Pharmaceuticals, Inc.; 2017.

Contact:
Silvergate Pharmaceuticals, Inc.
(855) 379-0382
silvergatepharma@silvergatepharma.com

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SOURCE Silvergate Pharmaceuticals, Inc.