Loxacon (LOXAPINE)

brands

Class

• Neuroscience-based Nomenclature: dopamine, serotonin receptor antagonist (DS-RAn)
• Conventional antipsychotic (neuroleptic, dopamine 2 antagonist, serotonin– dopamine antagonist)

Loxacon commonly prescribed for

(Bold for FDA approved)

How Loxacon works

• Blocks dopamine 2 receptors, reducing positive symptoms of psychosis

• Although classified as a conventional antipsychotic, loxapine is a potent serotonin 2A antagonist

• Serotonin 2A antagonist properties might be relevant at low doses, but generally are overwhelmed by high dosing

How long until Loxacon works

• Psychotic symptoms can improve within 1 week, but it may take several weeks for full effect on behavior

Notable Side Effects

• Neuroleptic-induced deficit syndrome

• Akathisia

• Drug-induced parkinsonism

• Risk of potentially irreversible involuntary dyskinetic movements may increase with cumulative dose and treatment duration

• Rare tachycardia

• Galactorrhea, amenorrhea

• Sedation

• Dry mouth, constipation, vision disturbance, urinary retention

• Hypotension, tachycardia

Life Threatening Side Effects

• Rare neuroleptic malignant syndrome may cause hyperpyrexia, muscle rigidity, delirium, and autonomic instability with elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure

• Rare agranulocytosis

• Rare hepatocellular injury

• Rare seizures

• As a class, antipsychotics are associated with an increased risk of death and cerebrovascular events in elderly patients with dementia; not approved for treatment of dementia-related psychosis

• Bronchospasm, with the potential to lead to respiratory distress and respiratory arrest (inhalant)

weight gain

unusual

sedation

common

What to do about Loxacon side effects

• Wait

• Wait

• Wait

• For drug-induced parkinsonism, add an anticholinergic agent

• Beta blockers, benzodiazepines, or serotonin 2A antagonists (e.g., mirtazapine, cyproheptadine) may reduce akathisia

• Reduce the dose

• For sedation, give at night

• Switch to an atypical antipsychotic

• Weight loss, exercise programs, and medical management for high BMIs, diabetes, dyslipidemia

• Metformin may help prevent or reverse antipsychotic-induced weight gain

usual dosage range

• 60–100 mg/day in divided doses

Dosage Forms

• Capsule 6.8 mg loxapine succinate equivalent to 5 mg loxapine, 13.6 mg loxapine succinate equivalent to 10 mg loxapine, 34.0 mg loxapine succinate equivalent to 25 mg loxapine, 68.1 mg loxapine succinate equivalent to 50 mg loxapine

• Oral liquid 25 mg/mL (discontinued in USA)

• Injection 50 mg/mL (discontinued in USA)

• Inhalant 10 mg unit in a single-use inhaler

long term use

• Should periodically reevaluate long-term usefulness in individual patients, but treatment may need to continue for many years

habit forming

• No

Renal Impairment

• Use with caution

Hepatic Impairment

• Use with caution

Cardiac Impairment

• Use with caution

Elderly

• Some patients may tolerate lower doses better

• Although conventional antipsychotics are commonly used for behavioral disturbances in dementia, no agent has been approved for treatment of elderly patients with behavioral symptoms of dementia such as agitation

• Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo, and also have an increased risk of cerebrovascular events

Children and Adolescents

• Safety and efficacy not established

• Generally, consider second-line after atypical antipsychotics

Pregnancy

• Effective June 30, 2015, the FDA requires changes to the content and format of pregnancy and lactation information in prescription drug labels, including the elimination of the pregnancy letter categories; the Pregnancy and Lactation Labeling Rule (PLLR or final rule) applies only to prescription drugs and will be phased in gradually for drugs approved on or after June 30, 2001

• Controlled studies have not been conducted in pregnant women

• There is a risk of abnormal muscle movements and withdrawal symptoms in newborns whose mothers took an antipsychotic during the third trimester; symptoms may include agitation, abnormally increased or decreased muscle tone, tremor, sleepiness, severe difficulty breathing, and difficulty feeding

• Renal papillary abnormalities have been seen in rats during pregnancy

• Psychotic symptoms may worsen during pregnancy and some form of treatment may be necessary

• Atypical antipsychotics may be preferable to conventional antipsychotics or anticonvulsant mood stabilizers if treatment is required during pregnancy

Breast Feeding

• Unknown if loxapine is secreted in human breast milk, but all psychotropics are assumed to be secreted in breast milk

• Recommended either to discontinue drug or bottle feed