Nikethamide

Approved Indications:

• Respiratory depression due to:
• Drug overdose (e.g., barbiturates, opioids, or sedatives)
• Post-anesthesia respiratory suppression
• Central respiratory failure

Clinically accepted off-label uses:

• Temporary respiratory stimulation in conditions with reduced respiratory drive (e.g., acute asphyxia or drowning)
• Supportive therapy in cardiopulmonary resuscitation (rare/emergency use)
• Occasionally used in neonatal apnea (not commonly recommended today due to safety concerns)

Note: Nikethamide is no longer widely used in many developed countries due to safety concerns and the availability of better alternatives.

Route of Administration: Oral, Intramuscular (IM), Intravenous (IV), or Subcutaneous (SC)

Adults:

• Oral: 100–200 mg, 2 to 3 times daily
• IM/SC: 1–2 mL of 250 mg/mL solution (i.e., 250–500 mg), 1–2 times daily
• IV: 1 mL of 250 mg/mL solution administered slowly over several minutes; may repeat after a few hours under monitoring

Pediatrics:

• Not recommended due to risk of seizures and unpredictable CNS stimulation

Elderly:

• Use with caution; lower initial dose recommended due to increased CNS sensitivity

Renal/Hepatic Impairment:

• No specific adjustment established; monitor closely for toxicity

Administration Precautions:

• IV injections should be administered slowly to avoid CNS or cardiovascular complications
• Avoid exceeding total daily dose of 1 g
• Not intended for long-term use

Nikethamide acts as a central nervous system (CNS) stimulant, primarily targeting the medullary respiratory centers in the brainstem. It increases the excitability of chemoreceptors and neural centers involved in regulating breathing. This leads to enhanced depth and rate of respiration, especially in cases where respiratory drive is suppressed (e.g., during drug-induced respiratory depression). Its stimulatory effects are mild and short-acting, making it suitable for temporary use only.

• Absorption: Rapidly absorbed from the gastrointestinal tract and injection sites
• Distribution: Distributes well into tissues, including the central nervous system
• Metabolism: Undergoes hepatic metabolism via hydrolysis
• Elimination: Mainly excreted via kidneys as metabolites
• Onset of action: Within 2–5 minutes (IV); 15–30 minutes (oral)
• Half-life: Short; approximately 1–2 hours

• Pregnancy:
• Not classified under the former FDA category system
• Limited data available; animal studies are insufficient
• Use only when benefits outweigh risks
• Lactation:
• Unknown if excreted into breast milk
• Not recommended unless necessary
• Monitor infant for CNS stimulation or feeding problems if used during breastfeeding

• CNS stimulant
• Respiratory analeptic (non-specific respiratory stimulant)

• Hypersensitivity to nikethamide or any formulation component
• Epilepsy or seizure disorders
• Severe hypertension or cardiovascular instability
• Hyperthyroidism
• Agitation or psychiatric disorders with risk of CNS overstimulation

• Seizures: May provoke or worsen seizures; contraindicated in epilepsy
• Cardiovascular Risk: Can cause tachycardia, arrhythmias, and hypertension
• CNS Effects: May cause anxiety, restlessness, tremors, and confusion
• Misuse potential: Risk of inappropriate use in athletes for performance stimulation
• Monitoring required: Continuous monitoring during IV administration for respiratory rate, blood pressure, and neurological status
• Not a substitute for mechanical ventilation in severe respiratory failure

Common:

• Restlessness
• Headache
• Flushing
• Nausea or vomiting
• Dizziness

Less Common but Serious:

• Convulsions/seizures
• Cardiac arrhythmias
• Hypertension
• Respiratory muscle tremors
• Anxiety, agitation, or hallucinations
• Allergic skin reactions (rash, pruritus)

• Other CNS stimulants (e.g., caffeine, amphetamines): Additive effects increase risk of seizures and hypertension
• CNS depressants (e.g., opioids, barbiturates): May antagonize respiratory depression but should be used cautiously
• MAO inhibitors or SSRIs: Potential for serotonin-related CNS adverse effects
• No significant CYP450 involvement identified

• Nikethamide use has declined substantially and is not recommended in modern clinical guidelines in countries like the USA, UK, or EU
• Removed from some formularies due to safety concerns and lack of proven efficacy compared to modern interventions (e.g., naloxone, mechanical ventilation)
• Remains available in some countries under strict regulation for emergency or supportive use

• Temperature: Store between 15°C and 25°C (59°F and 77°F)
• Protection: Protect from light and excessive moisture
• Handling: Keep ampoules sealed and discard if solution becomes cloudy or discolored
• Shelf life: Follow manufacturer's expiration guidelines
• Keep out of reach of children