بريجابالين

تصف ورقة منشورة في مجلة Frontiers in Veterinary Science البريجابالين (pregabalin) والغابابنتين بأنهما من الأدوية المضادة للاختلاج، وبأن لهما فعالية سريرية مثبتة لدى البشر. تذكر مراجعة في مجلة Journal of Feline Medicine and Surgery أن البريجابالين يُستطب أساساً لتقليل القلق الحاد لدى القطط.

ما هو الدواء وإلى أي صنف ينتمي

يحمل البريجابالين، بحسب نشرة DailyMed الأمريكية لمستحضر بيطري فموي للقطط، الاسم الكيميائي (3S)-3-(أمينوميثيل)-5-ميثيل هكسانويك أسيد. يذكر دليل MSD البيطري أن البريجابالين ينتمي إلى الفئة الدوائية نفسها التي ينتمي إليها الغابابنتين، وأن آلية عمله مشابهة لآلية عمل الغابابنتين.

آلية العمل

تصف مراجعة Journal of Feline Medicine and Surgery البريجابالين والغابابنتين بأنهما يرتبطان بالوحدة الفرعية ألفا-2-دلتا قبل المشبكية للقنوات الكالسيومية المعتمدة على الجهد داخل الجهاز العصبي المركزي. يذكر مركز الطب البيطري في إدارة الغذاء والدواء الأمريكية (FDA CVM) أن البريجابالين يُستعمل لتدبير الألم المرتبط بالأعصاب، وأنه يعمل بتقليل إطلاق النواقل العصبية التي تنقل إشارات الألم في الحبل الشوكي.

الاستعمالات البيطرية

يشرح FDA CVM، في سياق موافقته المشروطة على مستحضر يحتوي البريجابالين للكلاب، أن تشوه كياري (Chiari-like malformation) حالة وراثية تكون فيها جمجمة الكلب أصغر من دماغه. يورد دليل MSD البيطري دراسة مفتوحة صُنّف فيها سبعة من أحد عشر كلباً مصاباً بصرع مقاوم على أنهم استجابوا استجابة إيجابية للعلاج بالبريجابالين.

السلامة

يذكر دليل MSD البيطري أن الآثار الضائرة للبريجابالين تشمل التركين والرنح، كما هو الحال مع الغابابنتين. تذكر نشرة DailyMed الأمريكية لمستحضر البريجابالين الفموي للقطط أن سلامة استعماله لدى القطط المخصصة للتربية والحوامل والمرضعات لم تُقيَّم.

الوضع التنظيمي

منح FDA CVM موافقة مشروطة لأقراص مضغ تحتوي البريجابالين للكلاب. يوضح FDA CVM أن الموافقة المشروطة تعني أن إدارة الغذاء والدواء الأمريكية قررت أن مستحضر البريجابالين للكلاب آمن، وأن توقع فعاليته في الاستعمال المقصود معقول. ربط FDA CVM أهلية مستحضر البريجابالين للكلاب للموافقة المشروطة بكونه موجهاً إلى حالة خطيرة أو مهددة للحياة وبسدّه حاجة غير ملباة في صحة الحيوان. بحسب FDA CVM، يُتاح مستحضر البريجابالين للكلاب بوصفة طبية لأن تشخيص تشوه كياري وتكهّف النخاع (syringomyelia) ومتابعة سلامة الاستعمال يتطلبان خبرة بيطرية.

The text below is quoted verbatim from approved veterinary drug labels published by the US FDA (Animal Drugs @ FDA) and DailyMed.

Indications (3)

Cats (1)
  • For alleviation of acute anxiety and fear associated with transportation and veterinary visits in cats.

    Bonqat®

Dogs (1)
  • LIAVIUM™-CA1 is indicated for the management of pain and clinical signs associated with Chiari-like malformation and syringomyelia in dogs.

    LIAVIUM™-CA1

Species not stated (1)
  • BONQAT is indicated for alleviation of acute anxiety and fear associated with transportation and veterinary visits in cats.

    Bonqat®

Mechanism of action (1)

Species not stated (1)
  • Absorption BONQAT is rapidly absorbed after oral administration in cats. Following oral administration of 5 mg/kg to fasted cats the maximum observed concentration (Cmax) in plasma was 10.1 ± 0.8 (SD) μg/mL and occurred at 0.5-1.0 hours post-dose. The area under plasma concentration time curve from time zero to the last quantifiable time point (AUClast) was 199±27 μg*h/mL. The mean absolute oral bioavailability was 94.3%. Distribution BONQAT has a relatively large volume of distribution. After intravenous (IV) bolus administration of 2.5 mg/kg, the volume of distribution at the steady state (Vss) was 0.4±0.02 L/kg in cats. BONQAT is not known to bind to plasma proteins in other species, but this has not been studied in cats. Metabolism and excretion BONQAT is slowly eliminated from the body of cats. After IV bolus administration of 2.5 mg/kg, total plasma clearance was 0.03±0.008 L/h/kg. The mean half-life of elimination from circulation was 12.3±3.1 hours after IV administration of 2.5 mg/kg and 14.7±2.7 hours after oral administration of 5 mg/kg. Elimination of the parent compound as well as the methylation metabolite from circulation occurs almost exclusively by renal excretion in other species. This has not been studied in cats. Mechanism of Action Pregabalin is a ligand of alpha2-delta subunit of voltage-gated calcium channels. It reduces the presynaptic calcium influx in neurons and thereby the release of various neurotransmitters, including glutamate, norepinephrine, serotonin, dopamine, substance P and calcitonin gene-related peptide.

    Bonqat®

Contraindications (1)

Species not stated (1)
  • Do not use in case of hypersensitivity to pregabalin or to any of the excipients (sodium benzoate, ethyl maltol, hydrochloric acid, sodium hydroxide).

    Bonqat®

Warnings (1)

Species not stated (1)
  • Human Safety Warnings: Not for human use. Appropriate precautions should be taken while handling BONQAT. Avoid skin contact, eye contact, or contact with mucous membranes. Symptoms of exposure to pregabalin include dizziness, sleepiness, blurred vision, weakness, dry mouth, and difficulty with concentration or attention. In case of accidental eye or mucosal exposure, flush with water for 15 minutes. If wearing contact lenses, eyes should be rinsed first, then remove contact lenses and continue rinsing. Seek medical advice if symptoms occur. In case of skin contact, wash with soap and water immediately. Remove contaminated clothing. Seek medical advice if symptoms occur. In case of accidental ingestion, seek medical advice if symptoms occur. Do not drive as sleepiness may occur. In case of ingestion by a child, seek medical attention immediately. Show the package insert or the label to the physician. Drug Abuse, Addiction, and Diversion Controlled Substance: BONQAT contains pregabalin, a Schedule V controlled substance. Abuse: Abuse is defined as the intentional, non-therapeutic use of a drug, even once, to achieve a desired psychological or physiological effect. Pregabalin is not known to be active at receptor sites associated with drugs of abuse. However, pregabalin is associated with drug liking and is known to be misused and abused in the community, particularly in combination with opioids. Consider the potential risks of misuse or abuse before prescribing this product. Signs of pregabalin misuse or abuse include drug seeking behavior. Pregabalin should be handled appropriately to minimize the risk of diversion, including restriction of access, the use of accounting procedures, and proper disposal methods, as appropriate to the clinical setting and as required by law. Note to physician: BONQAT contains pregabalin. The safety data sheet (SDS) contains more detailed occupational safety information. To report adverse reactions in users or to obtain a copy of the SDS for BONQAT contact Zoetis Inc. at 1-888-963-8471. Animal Safety Warnings: Some cats may experience hypothermia, depression, drowsiness, muscle tremors, and/or ataxia. These cats should be kept warm and not offered food or water until BONQAT’s effects have worn off (usually within 6 hours). (See TARGET ANIMAL SAFETY) Keep BONQAT in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose.

    Bonqat®

Adverse reactions (1)

Species not stated (1)
  • In a well-controlled European field study, which included a total of 238 cats (108 treated with BONQAT at the label dose of 5 mg/kg, 29 treated with BONQAT at a dose of 2.5 mg/kg, and 101 administered placebo control), 5 months to 15 years of age and weighing 1.8 to 10.3 kg, the following adverse reactions were reported: Table 1. Adverse reactions Adverse reaction Pregabalin 5 mg/kg N=108 Pregabalin 2.5 mg/kg N=29 Placebo N=101 Ataxia 5 (4.6%) 1 (3.4%) 0 Lethargy 3 (2.8%) 2 (6.9%) 0 Emesis 2 (1.9%) 0 0 Proprioception abnormality 1 (0.9%) 1 (3.4%) 0 Muscle tremor 1 (0.9%) 0 0 Anorexia 1 (0.9%) 0 0 Weight loss 1 (0.9%) 0 0 Mydriasis 0 1 (3.4%) 0

    Bonqat®

Dosage (3)

Cats (1)
  • Administer orally as a single dose of 5 mg/kg (0.1 mL/kg) approximately 1.5 hours before the start of the transportation or veterinary visit.

    Oral

    Bonqat®

Dogs (1)
  • Administer chewable tablets at 5-10 mg/kg orally twice daily with food. The 90 mg tablet is scored and may be split in half along the break-line. The 30 mg and 180 mg tablets should not be split.

    Oral

    LIAVIUM™-CA1

Species not stated (1)
  • Client Information Sheet is on the reverse of this package insert. Always provide client information sheet with prescription. BONQAT is administered orally as a single dose of 5 mg/kg (0.1 mL/kg) approximately 1.5 hours before the start of the transportation or veterinary visit and can be given on two consecutive days. If the cat weighs more than 22 pounds, the total dose will need to be calculated and given in two separate doses as the syringe holds a maximum of 1 mL of solution. A small amount of food can be given with BONQAT.

    ORAL

    Bonqat®

Available strengths (3)

ProductDosage formAvailable strengths
Bonqat®Oral SolutionEach mL contains 50 mg pregabalin
LIAVIUM™-CA1Chewable TabletsEach chewable tablet contains 30 milligrams (mg), 90 mg, or 180 mg of pregabalin.
——50 mg / 1 mL