Neonatal (<2 weeks of age) and pediatric (<6 months of age) patients have physiologic differences compared with adult patients (including a less developed sympathetic nervous system, lower cardiovascular reserve, immature renal function, and decreased hepatic metabolic capability) that may necessitate specialized drug selection and dosages. Neonatal patients also have higher body water content, and volume of distribution may be greater for water-soluble drugs, leading to lower plasma concentrations.
Following are guidelines to help avoid drug-related adverse effects in neonatal and pediatric patients.
Do: Consult Package Inserts & Labels for Safety Information
Package inserts include information summaries of safety assessments and can include unexpected effects identified in young patients (eg, oclacitinib is contraindicated in dogs <1 year of age because of the risk for systemic infections in puppies with immature immune systems1,2). Package labels may indicate a specific age range. For example, many parasiticides have been evaluated in kittens and puppies as young as 3 to 6 weeks of age. Analgesics are also frequently evaluated in relatively young patients (6 weeks to 6 months of age) and labeled accordingly.
Safety information can also be obtained from company representatives for products FDA-approved for use in animals or from the Freedom of Information summary (often available online) for a particular product. Although most drugs are not tested in neonates, the package insert indicates whether testing in neonates has occurred.
Do: Choose Beta-Lactams & Opioids for Neonatal & Pediatric Patients
Beta-lactam antibiotics have a wide margin of safety and a favorable adverse effects profile.
Opioids typically have minimal impact on cardiovascular function, although respiratory depression is possible. Neonatal patients may be more sensitive to opioids, and the dose should be reduced by 50% for premedication and 30% for analgesia.3,4 In patients 2 weeks to 3 months of age, the low end of the adult dose range can be used for opioids and the dose titrated to effect. Opioids can be reversed if adverse effects are noted.
Don’t: Use Fluoroquinolones in Patients Receiving a Milk-Based Diet or Dogs Undergoing Skeletal Development
Fluoroquinolones are chelated by calcium ions in milk and may not be absorbed appropriately in nursing patients. Fluoroquinolones also chelate divalent cations in bone and cartilage. Magnesium chelation in developing cartilage leads to loss of proteoglycan and formation of bullae, which can manifest clinically as lameness and swelling. Dogs 1 to 7 months of age are most susceptible, and the effect is concentration dependent; in most reported clinical cases, the maximum daily dose was exceeded, but histopathologic lesions have been observed with a dosage as low as 5 mg/kg every 24 hours.5 Lesions are exacerbated by activity. Puppies that require fluoroquinolones (eg, for sepsis, other life-threatening infections) should therefore be confined to help reduce the chance of clinical lameness.6 Although the length of optimal confinement is unknown, confinement for at least the duration of treatment is recommended. Treatment risks should be discussed with pet owners so informed consent can be obtained.
Joint lesions have not been documented in kittens, but caution with fluoroquinolones in cats is needed lifelong due to the possibility of retinal toxicosis.5
Don’t: Use Tetracyclines in Patients With Developing Teeth
Tetracyclines complex with calcium orthophosphate and can stain developing enamel. The degree of staining depends on the drug, dosage, duration, and stage of enamel development. Minocycline and doxycycline are more lipid soluble and less likely to cause dental staining than older tetracyclines.7 Although there are some recommendations to avoid tetracyclines until patients are 6 months of age,7 the majority of hard tissue formation of permanent teeth occurs by 8 weeks of age. Dental staining with doxycycline and minocycline occurs in humans but is anecdotal in dogs and appears to be rare.
Don’t: Use NSAIDs in Patients <6 Weeks of Age or in Patients With Organ Dysfunction
In dogs and cats, nephrogenesis continues for 2 to 3 weeks after birth. Renal blood flow, glomerular filtration rate, and hepatic metabolic processes (eg, glucuronidation) do not approach adult values until patients are 6 to 8 weeks of age and may not be fully mature for several months. NSAIDs may interfere with renal maturation in neonatal patients, as cyclooxygenase-2 is necessary for renal development; therefore, NSAIDs are contraindicated in neonatal patients and should be used with caution and according to label directions in pediatric patients.
Neonatal and pediatric patients with organ dysfunction may be more susceptible to NSAID toxicity, as NSAIDs have a relatively narrow margin of safety, undergo extensive hepatic metabolism, and are more likely to cause adverse effects in patients with decreased renal function or perfusion.
Don’t: Use Alpha-2 Agonists or Acepromazine in Neonatal Patients If Other Viable Options Exist
Alpha-2 agonists and acepromazine can cause dose-dependent hypotension. In neonatal patients, increasing cardiac output depends primarily on increasing heart rate, which is inhibited by alpha-2 agonists. Acepromazine undergoes hepatic metabolism and has a long half-life; therefore, this drug should be avoided if possible in patients <12 weeks of age. If acepromazine must be used for sedation in patients close to 12 weeks of age, the dose should be reduced to 0.005-0.025 mg/kg SC, and dilution in sterile water or sodium chloride should be considered for dose accuracy.
Don’t: Presumptively Reduce Antibiotic Doses in Neonatal or Early Pediatric (≤6 Weeks of Age) Patients
Puppies and kittens have a higher total body water content than adults (80% versus 65%); water-soluble drugs are therefore distributed into a larger volume, resulting in lower concentrations in plasma and interstitial fluid. The dose of water-soluble antibiotics with a wide margin of safety (eg, amoxicillin) should not be presumptively reduced, as this may compromise efficacy.