Setil

Setil Uses, Dosage, Side Effects, Food Interaction and all others data.

Setil is a potent phenothiazine antipsychotic, derivative of the piperazine group, now largely used as an antiemetic and to treat vertigo. The effects of this drug is apparent at all levels of the nervous system. It antagonizes postsynaptic dopamine D1 receptor that activates adenylate cyclase and synthesis of cAMP. It also antagonizes D2 receptors which do not activate adenylate cyclase. It also inhinits pre- and post synaptic adrenoreceptors and also acetylcholine, serotonin and histamine receptors. These various pharacodynamic actions combine to produce not only antipsychotic, but also central antiemetic and sedative effects.

Setil is an antipsychotic agent that works to promote postsynaptic inhibition of dopaminergic neurons. It also exerts its anti-emetic actions via anti-dopaminergic effects, where it displays similar efficacy as ondansteron, a 5HT-3 receptor antagonist and anti-emetic, in preventing delayed nausea and vomiting. Setil was shown to inhibit histaminergic, cholinergic and alpha-1 adrenergic receptors. The blockade of alpha-1 adrenergic receptors may result in sedation, muscle relaxation, and hypotension. It displays anti-anxiety effects as well. Compared to other phenothiazine derivatives, prochlorperazine is less sedating and has a weak propensity for causing hypotension or potentiating the effects of CNS depressants and anesthetics. Other than its primary action on D2 receptors, one study showed that prochlorperazine may inhibit the P2X7 receptor in human macrophages, leading to inhibition of calcium ion influx.

Trade Name Setil
Availability Rx and/or OTC
Generic Prochlorperazine
Prochlorperazine Other Names Capazine, Chlormeprazine, Chloropernazine, Prochlorperazin, Prochlorpérazine, Prochlorperazine, Prochlorperazinum, Prochlorpermazine, Prochlorpromazine, Procloperazine, Proclorperazina
Related Drugs escitalopram, alprazolam, duloxetine, hydroxyzine, Lexapro, lorazepam, ondansetron, Xanax, Cymbalta, Zofran
Type Tablet
Formula C20H24ClN3S
Weight Average: 373.943
Monoisotopic: 373.13794618
Protein binding

There is limited data on protein binding of prochlorperazine.

Groups Approved, Vet approved
Therapeutic Class Anti vertigo drugs, Anti-emetic drugs
Manufacturer Ind Swift Laboratories Ltd
Available Country India
Last Updated: September 19, 2023 at 7:00 am
Setil
Setil

Uses

Setil Maleate Tablet: Each tablet contains Setil maleate 5 mg.

Setil Mesilate Syrup: Each 5 ml syrup contains Setil maleate 5 mg

Setil Mesilate Injection: Each 1 ml ampoule contains Setil mesilate 12.5 mg.

  • For control of severe nausea and vomiting caused by radiation therapy, cancer chemotherapy, surgery, and other conditions.
  • Relieving nausea, vomiting and attacks of dizziness or spinning sensations (vertigo) associated with Meniere's disease and other inner ear disorders.
  • For the treatment of psychotic illness such as schizophrenia (hallucinations and hostility).
  • Acute mania.
  • For the short-term treatment of generalized non-psychotic anxiety.

Setil is also used to associated treatment for these conditions: Acute Migraine, Schizophrenia, Tension Headache, Non-psychotic generalized anxiety, Severe Nausea and vomiting

How Setil works

The mechanism of action of prochlorperazine has not been fully determined, but may be primarily related to its anti-dopaminergic effects. Setil blocks the D2 dopamine receptors in the brain, which are somatodendritic autoreceptors. Inhibition of D2 receptor signaling results in the blockade of postsynaptic dopamine receptors in the mesolimbic system and an increased dopamine turnover. Nausea and vomiting are proposed to arise from peripheral or central stimulation of serotonin type 3 (5-HT3) and dopamine type 2 receptors, the predominant receptors expressed at the chemoreceptor trigger zone (CTZ). Setil exerts antiemetic effects and was shown to inhibit apomorphine-induced vomiting by blocking D2 dopamine receptors in the CTZ..

Dosage

Setil dosage

Antiemetic:

Children (not recommended in children <10 kg or <2 years):

  • 10-14 kg: 2.5 mg every 12-24 hours as needed; maximum: 7.5 mg/day
  • 15-18 kg: 2.5 mg every 8-12 hours as needed; maximum: 10 mg/day
  • 19-39 kg: 2.5 mg every 8 hours or 5 mg every 12 hours as needed; maximum: 15 mg/day

Adults: 5-10 mg 3-4 times/day; usual maximum:40 mg/day

Antipsychotic:

  • Children 2-12 years (not recommended in children <10 kg or <2 years): 2.5 mg 2-3 times/day; increase dosage as needed to maximum daily dose of 20 mg for 2-5 years and 25 mg for 6-12 years
  • Adults: 5-10 mg 3-4 times/day; doses up to 150 mg/day may be required in some patients for treatment of severe disturbances

Nonpsychotic anxiety:

  • Adults: Usual dose: 15-20 mg/day in divided doses; do not give doses >20 mg/day or for longer than 12 weeks
  • Elderly: Initial: 2.5-5 mg 1 -2 times/day; increase dose at 4 to 7 day intervals by 2.5-5 mg/day; increase dosing intervals (twice daily, thrice daily, etc) as necessary to control response or side effects; maximum daily dose should probably not exceed 75 mg in elderly; gradual increases (titration) may prevent some side effects or decrease their severity. Setil may be administered without regards of meal.

Side Effects

Drowsiness, jaw, neck, and back muscle spasms, fine worm-like tongue movements, rhythmic face, mouth, or jaw movements, slow or difficult speech, difficulty swallowing, restlessness and pacing, tremors, shuffling walk, skin rash, yellowing of the skin or eyes.

Toxicity

LD50 and Overdose

Oral LD50 in rats is 750 mg/kg. Intraperitoneal and subcutaneous LD50 in mice are 191 mg/kg and 320 mg/kg, respectively. In placebo-controlled trials, there were increased incidences of mortality in elderly patients with dementia-related psychosis receiving antipsychotic medications. The risk of death in drug-treated patients was about 1.6 to 1.7 times that of placebo-treated patients. Deaths were largely resulting from cardiovascular, such as heart failure and sudden death, or infectious, such as pneumonia, conditions. Due to its antagonist action on dopamine receptors, prochlorperazine is associated with a risk for developing extrapyramidal symptoms such as tardive dyskinesia, which is a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements. This risk is also conferred on other antipsychotic agents that block dopamine receptors. It is proposed that increased duration of the drug treatment is likely thus increased total cumulative dose of antipsychotic drugs administered to the patient leads to increased risk for developing the syndrome and the likelihood that it will become irreversible. As with other antipsychotic agents, prochlorperazine is associated with a risk for causing neuroleptic malignant syndrome (NMS), which is a potentially fatal symptom complex, which is manifested as hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability.

There is no known antidote for prochlorperazine thus overdose treatment should be supportive and symptomatic. Overdose of prochlorperazine may produce dystonic reactions that involve extrapyramidal mechanism. To reduce these symptoms, antiparkinsonism drugs, barbiturates, or diphenhydramine may be used. Symptoms of central nervous system depression, such as somnolence or coma, may also be observed. Amphetamine, destroamphetamine, or caffeine and sodium benzoate may be used to induce stimulatory effects. In contrast, agitation and restlessness may also be seen in case of overdose. Other possible manifestations include convulsions, EKG changes and cardiac arrhythmias, fever, and autonomic reactions such as hypotension, dry mouth and ileus. Hypotension can be responded with the standard measures for managing circulatory shock.

Nonclinical Toxicology

In a rat developmental or reproductive toxicity study, abnormalities in both the reproductive measures and neurobehavioral testing were observed following administration of 25 mg/kg of prochlorperazine.

Use in specific populations

As the use of antipsychotic agents during the third trimester of pregnancy is associated with a risk for extrapyramidal and/or withdrawal symptoms following delivery, the use of prochlorperazine in pregnant patients is generally not recommended and it should be limited after careful consideration of the potential benefit of drug therapy justifying the potential risk to the fetus. Caution should be exercised when prochlorperazine is administered to a nursing mother. While lower doses of prochlorperazine is reported to be safe for elderly patients, caution is still advised, especially those with higher susceptibility to hypotension and neuromuscular reactions.

Precaution

Caution should be taken while performing tasks that require alertness, such as driving or using machinery. Use of alcohol can cause extreme drowsiness. This medication may increase sensitivity to sunlight. Prolonged sun exposure should be avoided and a sunscreen and protective clothing should be taken when anybody is exposed to the sun. This medication can reduce sweating making more susceptible to heat stroke.

Interaction

Alcohol, barbiturate & other sedatives may increase the CNS depressant action. Some drugs like Antacids, antiparkinson's drug, lithium may interfere the absorption of Setil. This drug may interfere the plasma concentration of Propanolol, Phenobarbital.

Food Interaction

  • Avoid alcohol. The drug may intensify or prolong the action of central nervous system depressants.

Setil Alcohol interaction

[Moderate] GENERALLY AVOID:

Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment.

Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines.

The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.



Patients should be advised to avoid alcohol during phenothiazine therapy.

Volume of Distribution

In a preliminary pharmacokinetic study involving healthy volunteers, the mean apparent volume of distribution following intravenous administration of 6.25 mg and 12.5 mg prochlorperazine were approximately 1401 L and 1548 L, respectively. Setil is reported to be distributed to most body tissues with high concentrations being distributed into liver and spleen. There is evidence that phenothiazines are excreted in the breast milk of nursing mothers.

Elimination Route

Following oral administration, prochlorperazine is reported to be well absorbed from the gastrointestinal tract. The onset of pharmacological action is about 30 to 40 minutes following oral administration and 10 to 20 minutes following intramuscular administration. The duration of action for all routes is about 3 to 4 hours. Following oral administration in healthy volunteers, the mean oral bioavailability was about 12.5%. In these patients, the time to reach the peak plasma concentrations was about 5 hours. Repeated oral dosing resulted in an accumulation of prochlorperazine and its metabolite. Following multiple twice daily dosing, the steady state of prochlorperazine was reached by 7 days.

Half Life

Following intravenous and single oral dose administration, the terminal elimination half live were 9 and 8 hours, respectively.

Clearance

The mean plasma clearance (CL) of prochlorperazine following intravenous administration in healthy volunteers was approximately 0.98L/h x kg. The mean renal clearance was about 23.6 mL/h.

Elimination Route

Setil is reported to be mainly excreted via the feces and bile. Low quantities of unchanged prochlorperazine and its metabolite were detectable in the urine.

Pregnancy & Breastfeeding use

No evidence of adverse effects of this drug has been reported during pregnancy & lactation.

Contraindication

Hypersensitivity to prochlorperazine or any component of the formulation, severe CNS depression; coma; should not be used in children <2 years of age or <10 kg.

Acute Overdose

Symptoms of overdose include deep sleep, coma, extrapyramidal symptoms, abnormal involuntary muscle movements, and hypotension.

Storage Condition

Store in a cool and dry place, protected from light and moisture.

Innovators Monograph

You find simplified version here Setil

Setil contains Prochlorperazine see full prescribing information from innovator Setil Monograph, Setil MSDS, Setil FDA label

FAQ

What is Setil used for?

Setil used to treat nausea, schizophrenia, migraines, and anxiety. It is a less preferred medication for anxiety.

How safe is Setil?

Setil is not suitable for some people. Tell your doctor or pharmacist if you: have had an allergic reaction to prochlorperazine or any other medicines in the past.

How does Setil work?

Setil work by blocking the action of a chemical called dopamine in the brain.

What are the common side effects of Setil?

Common side effects of Setil are include:

  • feeling sleepy or drowsy.
  • blurred vision.
  • dry mouth.
  • headaches.
  • stuffy nose.

Is Setil safe during pregnancy?

There's no evidence that Setil will harm your baby, but for safety it's best to take it for the shortest possible time

Is Setil safe during breastfeeding?

Setil passes into breast milk in small amounts. Talk to your doctor, as other medicines might be better while you're breastfeeding. If your baby was premature, had a low birthweight or is not feeding as usual, speak to your doctor before taking any anti-sickness medicine.

Can I drink alcohol with Setil?

It is best not to drink alcohol when taking Setil. Drinking alcohol can make side effects worse, such as feeling sleepy or an irregular heartbeat.

Can I drink alcohol with Setil?

Do not drive a car or ride a bike if Setil makes you sleepy, or if you have an irregular heartbeat caused by taking Setil.

When should be taken of Setil?

It is best to take Setil buccal tablets after meals.

How many time can I take Setil daily?

You can usually take Setil when you need it, up to 3 times a day.

How long does Setil take to work?

Setil starts to work in around 30 to 60 minutes.

How long does Setil stay in my system?

The elimination half-life is approximately 24 hours, presumably due to its enterohepatic circulation.

Can I take Setil for a long time?

Setil should be used for the shortest possible time and at the lowest dose that works for you. If you take it for a long time and stop suddenly, it can cause withdrawal symptoms such as feeling or being sick and problems sleeping.

Who should not take Setil?

You should not use Setil if you have recently used alcohol, sedatives, tranquilizers, or narcotic medications. Setil is not approved for use by anyone younger than 2 years old or weighing less than 20 pounds. Do not give prochlorperazine to a child before or after a surgery. Do not use Setil if you have recently used large amounts of alcohol or medicine that makes you sleepy.

What happens if I miss a dose?

Use the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not use two doses at one time.

What happens if I overdose?

Seek emergency medical attention. Overdose can cause severe drowsiness, irregular heartbeats, agitation, seizure, or fainting.

What happen If I stop taking Setil?

Setil should be used for the shortest possible time and at the lowest dose that works for you. If you take it for a long time and stop suddenly, it can cause withdrawal symptoms such as feeling or being sick and problems sleeping.

Will Setil affect my fertility?

Setil can increase levels of a hormone called prolactin. If levels of prolactin become high enough this can cause periods to stop in women and impotence in men.

Does Setil affect blood pressure?

skin rash, headache, and. low blood pressure (hypotension).

Can Setil affects my liver?

Setil is extensively metabolized by the liver via sulfoxidation and oxidation, and some instances of serum aminotransferase elevations as well as more clinically apparent liver injury may be caused by production of a toxic intermediate of its metabolism.

Does Setil cause weight gain?

Setil can causes weight gain also with other side effect.

Does Setil help with anxiety?

Setil is also used to treat anxiety, and to control severe nausea and vomiting.

Can Setil make me depressed?

Setil may cause depression or make the symptoms of depression worse.

*** Taking medicines without doctor's advice can cause long-term problems.
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