What are the general guidelines for drug dosing?

General Guidelines for Drug Dosing

Drug dosing should be adjusted based on renal function, weight, age, and specific patient characteristics to optimize therapeutic outcomes while minimizing adverse effects. 1, 2

Key Principles of Drug Dosing

Patient-Specific Factors Affecting Dosing

• Renal function: Creatinine clearance is the primary determinant for many medications
  • Formula for estimating creatinine clearance 3:
    • Men: Weight (kg) × (140 - age) ÷ (72 × serum creatinine [mg/dL])
    • Women: 0.85 × the value calculated for men
• Weight: Particularly important for pediatric patients and medications with narrow therapeutic windows
• Age: Pediatric and geriatric populations often require adjusted dosing
• Hepatic function: Alternative pathway for drug elimination when renal function is impaired 3

Dosing Adjustments for Renal Impairment

For most medications, dosing adjustments follow this pattern 1, 3:

• Normal renal function (CrCl >50 mL/min): Standard dosing
• Moderate impairment (CrCl 30-50 mL/min): Reduce dose or extend interval
• Severe impairment (CrCl 5-29 mL/min): Significantly reduce dose or extend interval
• Dialysis: Additional dose after dialysis for many medications

Example from ciprofloxacin FDA label 3:

• CrCl >50 mL/min: Standard dosing
• CrCl 30-50 mL/min: 250-500 mg q12h
• CrCl 5-29 mL/min: 250-500 mg q18h
• Hemodialysis/peritoneal dialysis: 250-500 mg q24h (after dialysis)

Special Population Considerations

Pediatric Dosing

• Calculate doses based on weight (mg/kg) or body surface area (mg/m²) 2, 4
• For children <3 years: 0.25 mL/kg for liquid medications
• For children >3 years: 0.5 mL/kg or as specified 2
• Use proper measuring devices (oral syringes, dosing cups) rather than household utensils 2

Cardiovascular Disease Patients

• Avoid sympathomimetic agents like phentermine in patients with cardiovascular disease 1
• For heart failure patients, follow specific dosing guidelines for ACE inhibitors, ARBs, beta-blockers, and aldosterone antagonists 1

Patients with Infectious Diseases

• For HIV patients with kidney disease, follow specific dosing guidelines for antimicrobials 1
• For tuberculosis treatment, adjust doses based on renal function 1
  • Example: Pyrazinamide - standard dose 25-30 mg/kg/day; for CrCl <10 mL/min, use 50-100% of full dose 1

Therapeutic Drug Monitoring (TDM)

TDM is essential for medications with:

• Narrow therapeutic ranges
• Marked pharmacokinetic variability
• Difficulty monitoring target concentrations
• Known therapeutic and adverse effects 5

Common Pitfalls and How to Avoid Them

1. Failure to adjust for renal function: Always calculate creatinine clearance before prescribing medications eliminated by the kidneys 3

2. Incorrect pediatric dosing: Use weight-based calculations rather than simply reducing adult doses 2, 4

3. Ignoring drug interactions: Consider potential interactions when prescribing multiple medications 1

4. Inadequate monitoring: Implement appropriate monitoring for drugs with narrow therapeutic indices 5

5. Improper administration timing: Some medications require specific timing relative to meals or other medications (e.g., ciprofloxacin should be administered at least 2 hours before or 6 hours after products containing magnesium, aluminum, calcium, iron, or zinc) 3

6. Overlooking special populations: Pregnant patients, elderly patients, and those with hepatic impairment often require special consideration 6

Emergency Medication Dosing

For hypertensive emergencies, intravenous medications follow specific dosing protocols 1:

• Nicardipine: Initial 5 mg/h, increasing every 5 min by 2.5 mg/h to maximum 15 mg/h
• Labetalol: Initial 0.3-1.0 mg/kg dose (maximum 20 mg) slow IV injection every 10 min
• Hydralazine: Initial 10 mg via slow IV infusion (maximum initial dose 20 mg); repeat every 4-6 h as needed

By following these guidelines and considering patient-specific factors, clinicians can optimize drug efficacy while minimizing adverse effects, ultimately improving patient outcomes in terms of morbidity, mortality, and quality of life.