What is the oral dose equivalent of 5 milligrams of subcutaneous (SC) loxapine?

From the Guidelines

To convert 5mg of SC loxapine to oral loxapine, the equivalent oral dose would be approximately 10mg, using a 1:2 conversion ratio, as the oral dose should be twice the SC dose due to first-pass metabolism in the liver. When switching from SC to oral loxapine, it's crucial to consider the differences in bioavailability and onset of action between the two routes of administration. The SC formulation bypasses the first-pass effect, allowing more of the drug to reach systemic circulation, whereas oral loxapine undergoes significant first-pass metabolism, resulting in lower bioavailability 1.

Key Considerations for Conversion

• The conversion ratio of 1:2 is based on the pharmacokinetic properties of loxapine, with the oral dose needing to be twice the SC dose to achieve similar systemic concentrations.
• Monitoring the patient for efficacy and side effects after switching routes is essential, as individual responses may vary.
• Oral loxapine should be administered according to the prescribed schedule, typically starting with divided doses and adjusting based on clinical response.
• Common side effects to watch for include sedation, anticholinergic effects, and potential extrapyramidal symptoms, as noted in the guidelines for managing behavior and mood disorders 1.

Clinical Implications

• If the patient was receiving SC loxapine for acute agitation, consider that oral formulations have a slower onset of action compared to the rapid effect of SC administration.
• The choice of loxapine formulation should be based on the patient's specific needs and the clinical context, taking into account the potential benefits and risks of each route of administration.
• As loxapine is a typical antipsychotic agent, it's associated with significant side effects, including extrapyramidal symptoms and tardive dyskinesia, especially with long-term use 1.

From the FDA Drug Label

Each capsule for oral administration, contains loxapine succinate, USP 6.8 mg, 13.6 mg, 34. 0 mg or 68. 0 mg equivalent to 5 mg, 10 mg, 25 mg or 50 mg of loxapine base respectively.

To convert 5mg of SC loxapine to oral loxapine, we can use the information provided in the drug label. Since the label states that 6.8 mg of loxapine succinate is equivalent to 5 mg of loxapine base, and this is the amount in a 5 mg capsule, the oral equivalent of 5mg of SC loxapine is 5mg of oral loxapine 2.

From the Research

Conversion of SC Loxapine to Oral Loxapine

• The provided studies do not directly address the conversion of 5mg of SC loxapine to oral loxapine.
• However, study 3 mentions that inhaled loxapine 5 or 10 mg significantly reduced agitation in patients with bipolar I disorder or schizophrenia.
• Study 4 reports that patients received loxapine orally as add-on analgesic in a dose-escalating manner, with daily doses of 20,30,40, or 60 mg loxapine, and a clinically relevant analgesic effect was found at a daily dose of 20-30 mg of loxapine in two patients.
• There is no direct evidence to support a specific conversion ratio between SC and oral loxapine, and the optimal oral dose may vary depending on the individual patient and the specific clinical context 5, 6, 7.

Pharmacokinetics and Pharmacodynamics

• Study 3 reports that maximum plasma loxapine concentrations are reached in a median of 2 min with inhaled loxapine.
• The studies do not provide information on the pharmacokinetics of SC loxapine or the conversion to oral loxapine.
• The efficacy and tolerability of loxapine may vary depending on the route of administration and the individual patient 6, 4.

Clinical Considerations

• Loxapine is a dibenzoxazepine tricyclic antipsychotic agent with a well-established profile, available for oral, intramuscular, and inhalatory administration 5, 6.
• The antipsychotic efficacy of loxapine is similar to that of other typical or atypical antipsychotics, with an adverse effects profile comparable to that of typical antipsychotics at high doses for chronic treatment 6.
• Loxapine may be beneficial for negative symptoms and refractory states, but controlled fixed-dose designs employing current outcome methodologies are needed to confirm this 7.