Mellaril online

Drug Approvals

(British Approved Name, US Adopted Name, rINN)

INNs in other languages (French, Latin, and Spanish):

Pharmacopoeias. In Europe and US.

European Pharmacopoeia, 6th ed. (Thioridazine). A white or almost white powder. Practically insoluble in water soluble in alcohol very soluble in dichloromethane freely soluble in methyl alcohol. Protect from light.

The United States Pharmacopeia 31, 2008 (Thioridazine). A white to slightly yellow crystalline or micronised powder odourless or having a faint odour. Practically insoluble in water freely soluble in dehydrated alcohol and in ether very soluble in chloroform. Protect from light.

Drug Approvals

(British Approved Name Modified, rINNM)

International Nonproprietary Names (INNs) in main languages (French, Latin, and Spanish):

Pharmacopoeias. In China, Europe, Japan, and the US.

European Pharmacopoeia, 6th ed. (Thioridazine Hydrochloride). A white or almost white crystalline powder. Freely soluble in water and in methyl alcohol soluble in alcohol. A 1% solution in water has a pH of 4.2 to 5.2. Protect from light.

The United States Pharmacopeia 31, 2008 (Thiondazine Hydrochloride). A white to a slightly yellow granular powder has a slight odor. Freely soluble in water, in chloroform, and in methyl alcohol insoluble in ether. pH of a 1% solution in water is between 4.2 and 5.2. Store in airtight containers. Protect from light.

Incompatibility. This is a warning about the incompatibility between thioridazine hydrochloride solution (Mellaril, Novartis, USA) and carbamazepine suspension (Tegretol, Novartis, USA).

What Is Mellaril?

Mellaril (Thioridazine, Novoridazine, Thioril) is in a class of remedies called phenothiazines. It works by changing the actions of chemicals in the brain.

Thioridazine is taken to heal psychotic disorders, such as schizophrenia. Thioridazine is generally reserved for people who do not respond to other pharmaceuticals or who cannot take other remedies due to side effects.
Thioridazine may also be taken for reasons other than those listed in this medication guide.

What Is the Most Important Information I Should Know About Mellaril?

Do not take thioridazine if you have any of the following conditions or a history of these conditions:

• heart disease;
• an irregular heartbeat or a history of irregular heartbeats;
• a history of prolonged QT intervals;
• a family history of congenital long QT clues;
• or other heartbeat disturbances.

These conditions may increase the risk of irregular heartbeats, heart attack, and death while taking thioridazine.

Do not use thioridazine with any of the following specifics:

• psychiatric pharmaceuticals such as fluoxetine (Prozac), paroxetine (Paxil, Paxil CR), and fluvoxamine (Luvox);
• or blood pressure pills such as pindolol (Visken) or propranolol (Inderal, Inderal LA, others).

Taken with any of these pharmaceuticals, thioridazine may cause irregular heartbeats that could lead to death. This is not a complete list of specifics that may interact with thioridazine and cause heart problems. Talk to your doctor or pharmacist before taking any other prescription or over-the-counter medications. Thioridazine may interact with other specifics that cause drowsiness, including alcohol, antidepressants, antihistamines, pain relievers, anxiety medicines, seizure medicines, and muscle relaxants.

Thioridazine may cause dangerous sedation, dizziness, or drowsiness if it is taken with alcohol or any of these medications. Inform your health care provider before taking thioridazine in combination with alcohol or any other medicine. Take caution when driving, operating machinery, or performing other hazardous activities. If you experience dizziness or drowsiness, avoid these activities.

Dizziness may be more likely to occur when you rise from a sitting or lying position. Rise slowly to prevent dizziness and a possible fall.

Call your health care provider immediately if you have uncontrollable movements of the mouth, tongue, cheeks, jaw, arms, or legs; fever; muscle rigidity; sweating; irregular pulse; or fast or irregular heartbeats.

What Should I Inform My Doctor Before Taking Mellaril?

Before taking thioridazine, report to your pediatrician if you have:

• bone marrow disease;
• glaucoma;
• seizures;
• Parkinson’s sickness;
• enlarged prostate or difficulty urinating;
• liver disease;
• kidney sickness.

You may not be able to take thioridazine, or you may demand a dosage adjustment or special monitoring during treatment if you have any of the disorders listed above.

It is not known whether thioridazine will harm an unborn baby. Do not use thioridazine without first talking to your doctor if you are pregnant or could become pregnant during medication. It is not known whether thioridazine passes into breast milk. Do not take thioridazine without first talking to your doctor if you are breastfeeding a baby. If you are over 60 years of age, you may be more likely to experience side effects from thioridazine. Your physician may prescribe a lower dose of this cure, or you may demand special monitoring during medication.

What Should I Avoid While Taking Mellaril?

Use caution when driving, operating machinery, or performing other hazardous activities. Thioridazine may cause dizziness or drowsiness. If you experience dizziness or drowsiness, avoid these activities.

Thioridazine may interact with other remedies that cause drowsiness, including alcohol, antidepressants, antihistamines, pain relievers, anxiety medicines, seizure pharmaceuticals, and muscle relaxants.

Adverse Effects and Treatment

As for Chlorpromazine.

Thioridazine has been associated with a higher incidence of antimuscarinic effects but a lower incidence of extrapyramidal effects than chlorpromazine. It may also be less sedating. However, it is more likely to induce hypotension, and there is an increased risk of cardiotoxicity and dose-related prolongation of the QT interval. Because of this and the consequent danger of life-threatening arrhythmias such as torsade de pointes and sudden death, its use has been restricted. Sexual dysfunction also appears to be more frequent with thioridazine.

Pigmentary retinopathy, characterized by reduced visual acuity, the brownish coloring of vision, and impairment of night vision, has been seen particularly in patients taking large doses.

Effects on the Cardiovascular System

Between 1964 and 2001, the UK CSM received 42 reports of suspected heart rate and rhythm disorders associated with thioridazine. There were 21 fatalities reported out of 39 cases where the outcome was known.

See also under Chlorpromazine.

Hypersensitivity

Pruritus and erythematous rash on the genitals of a woman after sexual intercourse were found to be due to thioridazine present in the seminal fluid of her husband, who was taking 100 mg daily at night.

Overdosage

Rhabdomyolysis has been reported in a patient after overdosage with thioridazine. Twenty-four hours after taking 9.4 g of thioridazine, the patient presented with difficulty in moving and speaking. On examination, he had swelling and tenderness over his upper arms, thighs, and calves. Ataxia and transient dysarthria were attributed to generalized muscle weakness. Other effects were consistent with the antimuscarinic effects of thioridazine. He had no signs of neuroleptic malignant syndrome, but his urine contained myoglobin. The patient was treated with gastric lavage, activated charcoal, and rehydration. Serum biochemistry returned to normal over 1 week, and the muscle tenderness and weakness disappeared.

Precautions

As for Chlorpromazine. Thioridazine should not be used in patients with clinically significant cardiac disorders, uncorrected hypokalaemia or other electrolyte imbalance, with known or suspected QT prolongation or a family history of QT prolongation, or with a history of ventricular arrhythmias including torsade de pointes. Use is also contraindicated in patients known to have reduced cytochrome P450 isoenzyme CYP2D6 activity, which is responsible for thioridazine metabolism. Use with drugs liable to interfere with the metabolism of thioridazine, with other drugs known to prolong the QT interval, and with drugs likely to cause electrolyte imbalance should also be avoided (see under Interactions below).

For all patients starting thioridazine, it is recommended that a baseline ECG and electrolyte screening be performed. An ECG should also be repeated before each dose increase, one week after the maximum therapeutic dose has been reached, and at six-monthly intervals in those who continue treatment. Serum electrolyte concentrations should also be monitored periodically during treatment, and any imbalance corrected.

Porphyria

Thioridazine has been associated with acute attacks of porphyria and is considered unsafe in porphyric patients.

Interactions

As for Chlorpromazine. The metabolism of thioridazine is mediated by the cytochrome P450 isoenzyme CYP2D6 thioridazine itself is also an inhibitor of CYP2D6. Therefore, there is the potential for interactions between thioridazine, and other drugs that inhibit or act as a substrate for this enzyme, and such drugs should not be given together with thioridazine. Some examples include antiarrhythmics, certain antidepressants, including SSRIs and tricyclics, certain antipsychotics, beta-blockers, HIV-protease inhibitors, and opioids.

Use with other drugs known to prolong the QT interval, such as class IA and class III antiarrhythmics, tricyclic antidepressants, and some other antipsychotics, should also be avoided, as should use with those drugs known to cause electrolyte imbalance.

Pharmacokinetics

The pharmacokinetics of thioridazine appear to be generally similar to those of chlorpromazine. Thioridazine is metabolized by the cytochrome P450 isoenzyme CYP2D6. Its main active metabolite is mesoridazine (p.1007); another metabolite, sulforidazine, also has some activity. Thioridazine and its active metabolites are reported to be highly bound to plasma proteins (more than 95%). The plasma half-life of thioridazine has been estimated to be about 4 to 10 hours. It also crosses the placenta and is distributed into breast milk.

Metabolism

In 10 psychiatric patients stabilized on thioridazine, therapy was replaced by equipotent doses of the side-chain sulfoxide (mesoridazine) and side-chain sulfone (sulforidazine) metabolites of thioridazine. Both metabolites were shown to have an antipsychotic effect, the dose of each required being about two-thirds that of thioridazine. The serum half-lives were thioridazine 21 hours, mesoridazine 16 hours, and sulforidazine 13 hours. Apathy, depression, and restlessness gradually developed during treatment with the 2 metabolites and they could not be used for any length of time.

Extrapyramidal symptoms, hypersalivation, and drowsiness were more common with the metabolites 2 patients had epileptic seizures, and 1 receiving sulforidazine developed probable cholestatic jaundice. There is some evidence that the thioridazine metabolism is influenced by the debrisoquine hydroxylation phenotype. A single-dose study in 19 healthy male subjects demonstrated slower formation of mesoridazine, and hence higher serum-thioridazine concentrations in poor debrisoquine hydroxylators compared with extensive hydroxylators. Formation of thioridazine ringsulfoxide appeared to be compensatorily increased in slow hydroxylators.

Uses and Administration

Thioridazine is a phenothiazine with general properties similar to those of chlorpromazine. It has a piperidine side-chain and, unlike chlorpromazine, has little antiemetic activity. The use of thioridazine has been restricted to the treatment of schizophrenia in patients who fail to show an adequate response to treatment with other antipsychotics. Its use in other psychiatric disorders was abandoned after it was felt that there was an unacceptable balance of risks and benefits as a result of its cardiotoxic potential; it has been withdrawn in some countries, including the UK.

For all patients starting thioridazine, a baseline ECG and electrolyte screening is recommended. An ECG should also be repeated before each dose increase, 1 week after the maximum therapeutic dose has been reached, and at 6-monthly intervals in those who continue treatment. Serum electrolyte concentrations should also be monitored periodically during treatment, and any imbalance should be corrected. Thioridazine is given orally as the hydrochloride or the base, and doses may be expressed in terms of either. In some countries, doses of oral liquid preparations have been given in terms of the base, whereas those of the tablets have been given as the hydrochloride. In the USA, all doses are given in terms of the hydrochloride. Thioridazine 22.8 mg is equivalent to about 25 mg of thioridazine hydrochloride.

In the treatment of schizophrenia, thioridazine hydrochloride should be started at the usual dose of 50 to 100 mg three times daily and slowly titrated upwards to a maximum of 800 mg daily. If necessary, doses should be reduced once effective control is achieved. The daily dosage range is 200 to 800 mg, which may be given in 2 to 4 divided doses. It has been recommended that increases in doses should be no more than 100 mg weekly. Thioridazine should be given in lower initial doses to patients with a low body mass or those with hepatic or renal impairment. Dosage increases should also be more gradual. In those patients who require withdrawal of thioridazine, the dose should be gradually reduced over 1 to 2 weeks to avoid symptoms such as gastrointestinal disorders, dizziness, anxiety, and insomnia that are sometimes seen after abruptly stopping high-dose or long-term treatment.

Individuals with mental health conditions need to work closely with their healthcare professionals to explore treatment options that offer both efficacy and safety. Mellaril has been a significant medication in the treatment of schizophrenia and other psychiatric disorders. Despite its effectiveness in managing symptoms, there are potential risks associated with Mellaril.