Alendronate Sodium
**Alendronate sodium** is an orally administered nitrogen-containing bisphosphonate primarily used to inhibit osteoclastic bone resorption. **Key Clinical Highlights:** * **Primary Indications:** Utilized in veterinary medicine for refractory hypercalcemia (e.g., idiopathic hypercalcemia in cats, hypercalcemia of malignancy), feline odontoclastic resorptive lesions (FORLs), and as an adjunctive treatment for osteosarcoma or histiocytic sarcoma. * **Investigational Status:** Clinical experience in small animals remains highly limited. Dosages and safety profiles are still being established. * **Bioavailability Challenges:** Oral absorption is exceptionally poor (<2%) and is drastically reduced by food, requiring strict fasting protocols. * **Esophageal Risk:** Known to cause severe esophageal irritation and erosions in humans; specific administration techniques (e.g., water chasers, buttering lips) are required in pets to ensure rapid gastric transit.
Mecanismo: Alendronate is a nitrogenous bisphosphonate that strongly binds to **hydroxyapatite** crystals in the bone matrix. * **Mechanism:** During bone resorption, the drug is locally released and endocytosed by **osteoclasts**. * **Intracellular Pathway:** Inside the osteoclast, alendronate inhibits the enzyme **farnesyl pyrophosphate synthase (FPPS)** within the mevalonate pathway → prevents the prenylation (lipid modification) of small GTP-binding proteins (such as Ras, Rho, and Rab) → disrupts osteoclast cytoskeletal organization and ruffled border formation → induces osteoclast **apoptosis**. * **Secondary Effects:** By inhibiting osteoclastogenesis and promoting apoptosis, it indirectly reduces angiogenesis and may inhibit cancer cell proliferation in osteogenic neoplasms.
Dosificación por especie
- Feline odontoclastic resorptive lesions (FORLs) · 3 mg/kg · PO · q12h · Note: Use for this indication in cats is at present very controversial. (Plumb 2006)
- Idiopathic hypercalcemia (after dietary change has been attempted) · Initially 2 mg/kg. Most cats respond to 10 mg (total dose). · PO · once weekly · Administer at least 6 mL of water after administration and butter the lips to increase salivation and increase transit. If efficacious, effects usually seen in 3-4 weeks. Monitor via serum ionized calcium.
- Refractory hypercalcemia · 0.5-1 mg/kg · PO · once daily
- Investigational treatment of histiocytic sarcoma complex · Loading dose of 70 mg/m 2 (NOT mg/kg) · PO · daily for 14 days, then every other day for 14 days, then once weekly · Monitor for esophageal problems (excessive salivation, regurgitation).
Las dosis son una referencia clínica para médicos veterinarios. Confirme siempre con la información vigente del producto y el paciente individual.
Vías de administración
Contraindicaciones
- Esophageal abnormalities (e.g., strictures, achalasia) that delay esophageal emptying
- Inability to stand or sit upright for 30 minutes post-administration (human guideline; veterinary relevance is managed via water chasers/activity)
- Severe renal dysfunction (Creatinine Clearance < 35 mL/min)
- Known hypersensitivity to alendronate or other bisphosphonates
Efectos adversos
- Upper GI irritation and erosions
- Esophageal stricture or ulceration
- Vomiting
- Inappetence
- Jaw osteonecrosis (rare but documented in humans)
- Musculoskeletal pain
- Hypocalcemia (with overdose)
- Hypophosphatemia (with overdose)
Interacciones farmacológicas
- Aspirin · Increased risk of upper GI adverse effects and erosions.
- Calcium-containing oral products or food · Likely to significantly decrease the already low oral bioavailability of alendronate.
- Ranitidine (IV) · Increased oral alendronate bioavailability two-fold in a human study.
- NSAIDs · Humans taking NSAIDs with alendronate had no higher rates of GI adverse reactions than when NSAIDs were used with placebo, though caution is still advised. · moderate
- Antacids (Aluminum, Magnesium, Calcium) · Significantly decreases alendronate absorption · major
- Iron supplements · Decreases alendronate absorption · major
Monitoreo
- Serum ionized calcium
- Serum phosphorus
- Serum potassium and sodium
- Signs of GI adverse effects (excessive salivation, regurgitation, dysphagia, inappetence)
Sobredosis
**Toxicity Profile:** No lethality was observed in dogs receiving doses up to 200 mg/kg. Lethality in rodents occurs at >550 mg/kg. **Clinical Signs of Overdose:** Hypocalcemia, hypophosphatemia, and severe upper GI reactions (ulceration, erosions). **Treatment:** * **DO NOT induce vomiting** due to the risk of severe esophageal irritation. * Administer **oral antacids or milk** immediately to bind the drug and prevent systemic absorption. * Monitor serum calcium and phosphorus levels closely. * Provide supportive care as needed.
La referencia de fármacos de VetSheet está destinada a médicos veterinarios como apoyo a la decisión clínica; no sustituye el juicio profesional ni la información vigente del fabricante.