Esketamine Orifarm
Esketamine hydrochloride – Solution for injection 5 mg/ml & 25 mg/ml
Quick facts about Esketamine Orifarm
Key takeaways about Esketamine Orifarm
- Hospital-administered only: Esketamine Orifarm must be given by healthcare professionals experienced in anesthesia, in a clinical setting with resuscitation equipment available
- Twice the potency of racemic ketamine: Esketamine is the more active S(+)-enantiomer, requiring approximately half the dose of racemic ketamine for equivalent anesthesia
- Preserves airway reflexes: Unlike most general anesthetics, esketamine maintains protective laryngeal and pharyngeal reflexes to a greater degree, though aspiration risk is not eliminated
- Increases blood pressure and heart rate: Due to sympathomimetic effects, esketamine is contraindicated in patients with uncontrolled hypertension, raised intracranial pressure, or eclampsia
- Emergence reactions possible: Vivid dreams, nightmares, hallucinations, and restlessness may occur during recovery from anesthesia, particularly in adults
What Is Esketamine Orifarm and What Is It Used For?
Esketamine Orifarm is a general anesthetic belonging to the class of dissociative anesthetics. It contains esketamine hydrochloride, the pharmacologically more active S(+)-enantiomer of ketamine, and is used for induction and maintenance of anesthesia, procedural sedation, and emergency pain relief. It is administered intravenously or intramuscularly by qualified healthcare professionals.
Esketamine works by blocking the N-methyl-D-aspartate (NMDA) receptor in the central nervous system, producing a unique state known as dissociative anesthesia. This state is characterized by profound analgesia (pain relief) and sedation while maintaining many protective reflexes, including those of the airway. This mechanism makes esketamine particularly valuable in emergency medicine and situations where maintaining airway patency is critical.
Unlike traditional general anesthetics such as propofol or thiopental, esketamine does not suppress cardiovascular function. Instead, it has sympathomimetic properties that increase heart rate and blood pressure, which can be advantageous in hemodynamically unstable patients such as those in shock or with trauma. The European Society of Anaesthesiology and Intensive Care (ESAIC) recognizes ketamine-based agents as important tools in emergency and trauma anesthesia.
Esketamine Orifarm may be used as the sole anesthetic agent for short surgical procedures, or in combination with other anesthetic drugs for more complex operations. It is also used as an adjunct to regional and local anesthesia, providing supplementary sedation and analgesia. In emergency settings, esketamine is valued for its rapid onset of action and reliable analgesic properties, making it suitable for painful procedures, fracture reduction, and wound management in both pre-hospital and emergency department settings.
The drug is approved in the European Economic Area (EEA) under the trade name Esketamine Orifarm and is manufactured by Orifarm Generics A/S, headquartered in Odense, Denmark. It is available in Denmark, Sweden, and Finland. Esketamine Orifarm is supplied as a clear, colorless solution in glass ampoules, with the 5 mg/ml strength marked with green and white rings and the 25 mg/ml strength marked with red and white rings.
Esketamine Orifarm (injectable solution for anesthesia) should not be confused with esketamine nasal spray (marketed as Spravato), which is approved for treatment-resistant depression. The two products have entirely different indications, dosage forms, and administration routes. This article covers only the injectable anesthetic formulation.
What Should You Know Before Receiving Esketamine Orifarm?
Esketamine Orifarm is contraindicated in patients with uncontrolled hypertension, raised intracranial pressure, eclampsia or pre-eclampsia, and must not be combined with ergometrine or xanthine derivatives. Your physician will assess your medical history carefully before administering this anesthetic.
Contraindications
You must not receive Esketamine Orifarm if you have any of the following conditions:
- Allergy to esketamine or any of the other ingredients in the formulation (sodium chloride, hydrochloric acid, sodium hydroxide, water for injections)
- Uncontrolled high blood pressure (hypertension) or raised intracranial pressure
- Eclampsia or pre-eclampsia – serious pregnancy complications causing dangerously elevated blood pressure
- Concurrent use of xanthine derivatives (such as theophylline or aminophylline) and ergometrine (used to induce labor or control postpartum bleeding)
Additionally, Esketamine Orifarm must not be used as the sole anesthetic in patients with coronary artery disease (atherosclerosis of the heart's blood vessels), as the drug's cardiovascular stimulatory effects could increase myocardial oxygen demand and potentially precipitate cardiac ischemia. In these patients, esketamine should only be used in combination with other anesthetic agents that can mitigate its cardiovascular effects.
Warnings and Precautions
Before receiving Esketamine Orifarm, inform your physician if you have or have had any of the following conditions:
- Heart failure (weak heart) with untreated high blood pressure – the sympathomimetic effects of esketamine can further increase cardiac workload
- Angina pectoris (episodes of sudden, severe chest pain) – increased heart rate and blood pressure may worsen symptoms
- Raised intracranial pressure due to stroke or neurological disease – esketamine may further elevate intracranial pressure
- Diseases of the brain or spinal cord – central nervous system conditions require careful assessment
- Need for eye examination or eye surgery – esketamine can increase intraocular pressure
- Alcohol intoxication – concurrent use with central nervous system depressants is dangerous
- History of serious psychiatric disorders – esketamine may exacerbate psychotic symptoms and increase the risk of emergence reactions
- Overactive thyroid (inadequately treated hyperthyroidism) – the cardiovascular effects may be amplified
- Obstetric conditions requiring uterine relaxation (e.g., threatened uterine rupture or umbilical cord prolapse)
- History of substance abuse or dependence – ketamine-related compounds have abuse potential
- Impaired liver function – metabolism of esketamine may be affected, requiring dose adjustment
Prolonged use of esketamine (one month to several years) or misuse has been associated with urinary bladder inflammation (interstitial cystitis) and liver damage (hepatotoxicity observed after continuous use exceeding 3 days). These complications are well-documented in the medical literature and clinicians should monitor patients accordingly during extended therapy.
Pregnancy and Breastfeeding
If you are pregnant, breastfeeding, think you may be pregnant, or are planning to have a baby, consult your physician before receiving this medicine.
Pregnancy: Esketamine Orifarm should not be used during pregnancy unless the physician determines there is no safer alternative. Animal studies and clinical experience suggest that ketamine-based agents can cross the placental barrier. If administered during labor or delivery, esketamine may affect the newborn's respiratory rate. The World Health Organization (WHO) and the European Medicines Agency (EMA) recommend that the benefits and risks be carefully weighed before using any anesthetic during pregnancy.
Breastfeeding: Esketamine can pass into breast milk. However, at recommended therapeutic doses, the amount transferred is considered unlikely to affect the nursing infant. If you are breastfeeding, your healthcare provider will advise you on the appropriate course of action, which may include temporary suspension of breastfeeding after anesthesia.
Driving and Operating Machinery
Do not drive or operate machinery for at least 24 hours after receiving anesthesia with Esketamine Orifarm. The drug impairs reaction time, judgment, and coordination for a significant period after administration. You should be accompanied by a responsible adult when leaving the healthcare facility. You should also abstain from consuming alcohol for at least 24 hours following treatment, as alcohol can potentiate residual sedative effects.
How Does Esketamine Orifarm Interact with Other Drugs?
Esketamine Orifarm can interact with several drug classes, including barbiturates, benzodiazepines, opioids, sympathomimetics, and antipsychotics. Some interactions are clinically exploited (e.g., benzodiazepines to reduce emergence reactions), while others require dose adjustments or are contraindicated.
Drug interactions with esketamine are clinically significant and must be carefully managed by the anesthesia team. The pharmacological properties of esketamine – particularly its NMDA receptor antagonism and sympathomimetic effects – create the potential for both beneficial and adverse interactions with numerous drug classes. The following table summarizes the most important known interactions.
| Drug / Drug Class | Type | Clinical Effect | Action Required |
|---|---|---|---|
| Ergometrine | Contraindicated | Risk of severe hypertension and vasospasm | Must not be administered together |
| Xanthine derivatives (theophylline, aminophylline) | Contraindicated | Increased risk of seizures | Must not be administered together |
| Barbiturates (thiopental, phenobarbital) | Major | Prolonged recovery time; physical incompatibility in same syringe | Do not mix in same syringe; use separate IV lines |
| Diazepam | Major | Physical incompatibility – precipitate formation; may prolong recovery | Do not mix in same syringe or needle |
| Doxapram | Major | Physical incompatibility – precipitate formation | Do not mix in same syringe or needle |
| Sympathomimetics (adrenaline, noradrenaline) | Moderate | Additive cardiovascular stimulation; excessive increase in heart rate and blood pressure | Monitor hemodynamics closely; adjust doses |
| Opioids (morphine, fentanyl) | Moderate | Enhanced analgesia but increased respiratory depression risk | Reduce opioid dose; monitor respiratory function |
| Benzodiazepines (midazolam, lorazepam) | Moderate | Reduced emergence reactions but prolonged sedation | Often used deliberately; monitor recovery time |
| Antipsychotics | Moderate | Altered CNS effects; potential for increased confusion | Use with caution; monitor neurological status |
| Thyroid hormones | Minor | Potential for enhanced cardiovascular stimulation in hyperthyroid patients | Ensure thyroid function is adequately controlled |
Pharmaceutical Incompatibilities
Esketamine Orifarm must not be physically mixed with barbiturates, diazepam, or doxapram before injection, as this will cause precipitate formation rendering the solution unusable. These medications should not be administered through the same syringe and needle. For dilution, Esketamine Orifarm may only be mixed with glucose 50 mg/ml (5%) or sodium chloride 9 mg/ml (0.9%). All parenteral products should be visually inspected for particles and discoloration before administration.
Food and Alcohol Interactions
As with all general anesthetics, patients should fast for 4–6 hours before receiving Esketamine Orifarm to reduce the risk of aspiration. Although esketamine preserves airway reflexes to a greater degree than most anesthetics, the risk of aspiration of gastric contents is not entirely eliminated, particularly if vomiting occurs. Alcohol must be avoided for at least 24 hours after anesthesia, as it can enhance residual central nervous system depression.
What Is the Correct Dosage of Esketamine Orifarm?
Esketamine Orifarm is administered exclusively by healthcare professionals experienced in anesthesia. Dosing is individualized based on the patient's weight, clinical condition, and desired depth of anesthesia. The drug is given as a slow intravenous or intramuscular injection and may be repeated or administered as a continuous infusion.
Dosing of esketamine must be individualized by the attending physician. As the S(+)-enantiomer, esketamine is approximately twice as potent as racemic ketamine, meaning that roughly half the dose of racemic ketamine is needed to achieve equivalent anesthetic depth. The following dosage guidelines are based on the approved Summary of Product Characteristics (SmPC) and international anesthesia guidelines.
Adults
Intravenous (IV) Administration
Induction: 0.5–1 mg/kg body weight, administered slowly over at least 60 seconds. Onset of anesthesia occurs within approximately 30 seconds.
Maintenance: Repeat doses of 0.25–0.5 mg/kg IV as needed, or continuous infusion at 0.5–3 mg/kg/hour, adjusted according to clinical response.
Intramuscular (IM) Administration
Induction: 2–4 mg/kg body weight. Onset of anesthesia occurs within approximately 3–4 minutes.
Maintenance: Repeat doses as clinically indicated. The intramuscular route is particularly useful in pre-hospital and emergency settings where IV access may not be immediately available.
Children
Esketamine dosing in pediatric patients follows similar weight-based principles as in adults, though children often require relatively higher doses per kilogram due to faster metabolism. Dosing is determined by the attending anesthesiologist based on the child's age, weight, and clinical needs. Esketamine is widely used in pediatric emergency medicine for procedural sedation due to its favorable safety profile in maintaining airway reflexes.
Elderly and Debilitated Patients
Patients who are elderly, debilitated, or in poor general condition typically require dose reduction. As a general guideline, approximately half the normal dose should be administered, with careful titration based on clinical response. The increased sensitivity in these populations is due to reduced hepatic clearance, altered volume of distribution, and heightened susceptibility to cardiovascular effects.
Special Populations
Patients with multiple injuries or poor general condition require dose reduction, generally to half the standard dose. Patients with hepatic impairment may have reduced esketamine metabolism and should be monitored closely, with dose adjustments as needed. The drug should be administered slowly to minimize the risk of respiratory depression.
Overdose
In cases of acute overdose with Esketamine Orifarm, symptoms may include seizures, cardiac arrhythmias (irregular heartbeat), and respiratory depression (breathing difficulty). There is no specific antidote for esketamine overdose. Treatment is supportive and symptomatic, including airway management, ventilatory support, and cardiovascular monitoring. In a clinical setting, overdose is managed by the anesthesia team with standard resuscitation protocols. If an overdose is suspected outside a healthcare facility, contact emergency services immediately.
Too-rapid intravenous injection or excessive doses of esketamine can lead to respiratory depression. To reduce the risk of increased salivation during anesthesia, atropine or another anticholinergic agent may be administered concurrently as a premedication.
What Are the Side Effects of Esketamine Orifarm?
Like all medicines, Esketamine Orifarm can cause side effects, although not everyone experiences them. The most common side effects include increased heart rate and blood pressure, nausea, vomiting, and emergence reactions (vivid dreams, nightmares, restlessness) upon waking from anesthesia. Serious but rare side effects include anaphylaxis.
Side effects of esketamine are generally related to its pharmacological actions on the central nervous system and cardiovascular system. Many side effects are transient and resolve spontaneously during the recovery period. The anesthesia team will monitor you closely throughout the procedure and during recovery. The following classification uses standard frequency categories based on clinical trial data and post-marketing surveillance.
Common
May affect up to 1 in 10 patients
- Increased heart rate (tachycardia)
- Elevated blood pressure (hypertension)
- Throat spasm (laryngospasm)
- Respiratory depression (weakened breathing)
- Increased pulmonary secretions (mucus in the lungs)
- Blurred vision
- Nausea
- Vomiting
- Increased salivation (hypersalivation)
- Emergence reactions: vivid dreams, nightmares, dizziness, restlessness
Uncommon
May affect up to 1 in 100 patients
- Double vision (diplopia)
- Increased intraocular pressure
- Involuntary body movements resembling seizures
- Measles-like (morbilliform) rash or other skin eruptions
- Pain and redness at the injection site
Rare
May affect up to 1 in 1,000 patients
- Irregular or slow heartbeat (arrhythmia, bradycardia)
- Low blood pressure (hypotension)
- Anaphylactic reaction/shock – sudden skin rash, breathing difficulty, and collapse. This can be life-threatening and requires immediate emergency treatment.
Frequency Not Known
Reported in post-marketing surveillance
- Hallucinations
- Anxiety and confusion
- Mood changes with tension and irritability (dysphoria)
- Abnormal liver function (asymptomatic enzyme elevation)
- Liver damage following prolonged use (more than 3 days)
Emergence Reactions
Emergence reactions are among the most notable side effects of esketamine and other ketamine-based anesthetics. These reactions occur during the recovery period as the patient awakens from anesthesia and may include vivid or disturbing dreams, nightmares, hallucinations, feelings of floating or detachment, dizziness, and restlessness. Emergence reactions are more common in adults than in children and tend to occur more frequently with rapid IV administration.
To minimize the incidence and severity of emergence reactions, clinicians commonly administer a benzodiazepine (such as midazolam) as premedication or at the end of the procedure. Maintaining a calm, quiet recovery environment with minimal stimulation also helps reduce these reactions. Patients should be monitored until fully alert and oriented.
If you experience any side effects, including those not listed above, inform your healthcare provider. Reporting suspected adverse reactions after the medicine has been authorized is important for ongoing safety monitoring.
How Should Esketamine Orifarm Be Stored?
Esketamine Orifarm should be stored in its original packaging, protected from light, and must not be frozen. Once diluted, the solution should ideally be used immediately but may be stored for up to 48 hours at 25°C or 12 hours at 2–8°C under aseptic conditions.
Proper storage of Esketamine Orifarm is essential to maintain the drug's stability and effectiveness. The following storage guidelines apply:
- Keep out of sight and reach of children
- Store in the original packaging to protect from light – esketamine is light-sensitive
- Do not freeze – freezing can damage the formulation
- Do not use after the expiry date printed on the packaging (EXP). The expiry date refers to the last day of the stated month
- Diluted solution stability: Chemical and physical stability has been demonstrated for up to 48 hours at 25°C when diluted with glucose 5% or sodium chloride 0.9%. From a microbiological standpoint, the diluted solution should be used immediately. If not used immediately, storage should not exceed 12 hours at 2–8°C, unless dilution was performed under controlled and validated aseptic conditions
Do not dispose of medicines via wastewater or household waste. Return unused medicines to a pharmacy for safe disposal. These measures help protect the environment and prevent accidental exposure.
What Does Esketamine Orifarm Contain?
The active substance is esketamine hydrochloride. The medicine is available in two strengths: 5 mg/ml and 25 mg/ml. Inactive ingredients include sodium chloride, hydrochloric acid, sodium hydroxide, and water for injections. The sodium content is less than 1 mmol (23 mg) per ml, making it essentially sodium-free.
Active Ingredient
The active substance is esketamine hydrochloride, equivalent to 5 mg/ml esketamine or 25 mg/ml esketamine, depending on the strength. Esketamine is the S(+)-enantiomer of the racemic drug ketamine. It binds with higher affinity to the NMDA receptor phencyclidine binding site compared to the R(-)-enantiomer, which accounts for its approximately twofold greater anesthetic potency.
Inactive Ingredients (Excipients)
- Sodium chloride – used as an isotonicity agent
- Hydrochloric acid – for pH adjustment
- Sodium hydroxide – for pH adjustment
- Water for injections – solvent
Appearance and Pack Sizes
Esketamine Orifarm is a clear, colorless solution supplied in glass ampoules:
- 5 mg/ml: Ampoules marked with a green and white ring. Available in packs of 5 × 5 ml or 10 × 5 ml
- 25 mg/ml: Ampoules marked with a red and white ring. Available in packs of 5 × 2 ml or 10 × 2 ml
Not all pack sizes may be marketed in all countries.
This medicine contains less than 1 mmol (23 mg) sodium per ml, meaning it is essentially “sodium-free.” This is relevant for patients on sodium-restricted diets.
Frequently Asked Questions About Esketamine Orifarm
Esketamine is the S(+)-enantiomer of racemic ketamine, which is a 50:50 mixture of the S(+) and R(-) enantiomers. Esketamine has approximately twice the anesthetic potency of racemic ketamine at the NMDA receptor, meaning lower doses are needed for equivalent clinical effects. Studies suggest esketamine may also produce faster recovery and potentially fewer psychotomimetic side effects compared to racemic ketamine, although emergence reactions can still occur with either form. The R(-)-enantiomer is thought to contribute more to certain undesirable effects.
No. You must not drive or operate machinery for at least 24 hours after receiving Esketamine Orifarm. The drug significantly impairs reaction time, judgment, and motor coordination. You should be accompanied by a responsible adult when leaving the healthcare facility and should avoid alcohol for 24 hours after the procedure.
Esketamine, like racemic ketamine, has recognized abuse potential. Ketamine is classified as a controlled substance in many jurisdictions due to its psychoactive properties. However, when used appropriately in a clinical setting under medical supervision for anesthesia or procedural sedation, the risk of developing dependence is very low. Long-term misuse or recreational use of ketamine-based drugs can lead to psychological dependence, urinary tract damage, and liver injury. Esketamine Orifarm is only available by prescription and must be administered by qualified healthcare professionals.
Emergence reactions are psychological phenomena that occur during recovery from ketamine or esketamine anesthesia. They may include vivid or disturbing dreams, nightmares, hallucinations, feelings of floating or detachment from the body, confusion, and agitation. These reactions are typically transient and resolve as the drug wears off. They are more common in adults than children and are more frequent with rapid IV administration or higher doses. Clinicians often administer a benzodiazepine (such as midazolam) to prevent or reduce emergence reactions. A calm, quiet recovery environment with minimal sensory stimulation is also recommended.
Yes. Esketamine is widely used in pediatric anesthesia and procedural sedation. Children generally tolerate esketamine well, and the drug's ability to maintain airway reflexes makes it particularly suitable for pediatric procedures. Children tend to experience fewer emergence reactions than adults. Dosing is weight-based and determined by the attending anesthesiologist. Esketamine is commonly used in pediatric emergency departments for painful procedures such as fracture reduction, laceration repair, and burn wound management.
When given intravenously, esketamine produces anesthesia within approximately 30 seconds, with the effect lasting 5–10 minutes from a single dose. When given intramuscularly, onset occurs within 3–4 minutes, and the anesthetic effect lasts approximately 12–25 minutes. Additional doses or a continuous infusion can extend the duration as needed. Full psychomotor recovery typically occurs within 1–2 hours after the last dose, though patients should refrain from driving or operating machinery for at least 24 hours.
References
- European Medicines Agency (EMA). Esketamine – Summary of Product Characteristics (SmPC). EMA/CHMP assessment reports. Available from: www.ema.europa.eu.
- World Health Organization (WHO). WHO Model List of Essential Medicines, 23rd List (2023). Ketamine listed as an essential general anesthetic. Geneva: WHO; 2023.
- Peltoniemi MA, Hagelberg NM, Olkkola KT, Saari TI. Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy. Clinical Pharmacokinetics. 2016;55(9):1059-1077. doi:10.1007/s40262-016-0383-6.
- Trimmel H, Helbok R, Staudinger T, et al. S(+)-ketamine: Current trends in emergency and intensive care medicine. Wiener klinische Wochenschrift. 2018;130(9-10):356-366. doi:10.1007/s00508-017-1299-3.
- Green SM, Roback MG, Kennedy RM, Krauss B. Clinical Practice Guideline for Emergency Department Ketamine Dissociative Sedation: 2011 Update. Annals of Emergency Medicine. 2011;57(5):449-461. doi:10.1016/j.annemergmed.2010.11.030.
- Kurdi MS, Theerth KA, Deva RS. Ketamine: Current applications in anesthesia, pain, and critical care. Anesthesia: Essays and Researches. 2014;8(3):283-290. doi:10.4103/0259-1162.143110.
- British National Formulary (BNF). Ketamine. National Institute for Health and Care Excellence (NICE). Available from: bnf.nice.org.uk.
- European Society of Anaesthesiology and Intensive Care (ESAIC). Guidelines on peri-operative management. Available from: www.esaic.org.
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This article was written and medically reviewed by the iMedic Medical Editorial Team, consisting of licensed physicians specializing in anesthesiology, clinical pharmacology, and emergency medicine. Our team follows the GRADE evidence framework and adheres to international medical guidelines from the WHO, EMA, and professional anesthesiology societies.
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