DRUGS & SUPPLEMENTS

Mindol Forte

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Mindol Forte uses

Mindol Forte consists of Haloperidol, Trihexyphenidyl.

Haloperidol:



SAGENT®

Rx Only

WARNING

Increased Mortality in Elderly Patients with Dementia-Related Psychosis

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Mindol Forte (Haloperidol) injection is not approved for the treatment of patients with dementia-related psychosis.

DESCRIPTION

Mindol Forte (Haloperidol) is the first of the butyrophenone series of major antipsychotics. The chemical designation is 4-[4-(p-chlorophenyl)-4-hydroxypiperidino]-4'-fluorobutyrophenone and it has the following structural formula:

Mindol Forte (Haloperidol) Injection, USP is available as a sterile parenteral form for intramuscular injection in a 1 mL single-dose vial, each mL containing 5 mg Mindol Forte (Haloperidol) (as the lactate) and lactic acid for pH adjustment between 3.0 to 3.8.

Mindol Forte (Haloperidol) Injection, USP is also available as a sterile parenteral form for intramuscular injection in a 10 mL multi-dose vial, each mL containing 5 mg Mindol Forte (Haloperidol) (as the lactate) with 1.8 mg methylparaben and 0.2 mg propylparaben per mL (as preservatives), and lactic acid for pH adjustment between 3.0 to 3.8.

Structural Formula

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ACTIONS

The precise mechanism of action has not been clearly established.

INDICATIONS

Mindol Forte (Haloperidol) Injection, USP is indicated for use in the treatment of schizophrenia.

Mindol Forte (Haloperidol) Injection, USP is indicated for the control of tics and vocal utterances of Tourette's Disorder.

CONTRAINDICATIONS

Mindol Forte (Haloperidol) injection is contraindicated in severe toxic central nervous system depression or comatose states from any cause and in individuals who are hypersensitive to this drug or have Parkinson's disease.

WARNINGS

Increased Mortality in Elderly Patients with Dementia-Related Psychosis

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Mindol Forte injection is not approved for the treatment of patients with dementia-related psychosis.

Cardiovascular Effects

Cases of sudden death, QT-prolongation, and Torsades de Pointes have been reported in patients receiving Mindol Forte (Haloperidol). Higher than recommended doses of any formulation and intravenous administration of Mindol Forte (Haloperidol) appear to be associated with a higher risk of QT-prolongation and Torsades de Pointes. Although cases have been reported even in the absence of predisposing factors, particular caution is advised in treating patients with other QT-prolonging conditions (including electrolyte imbalance [particularly hypokalemia and hypomagnesemia], drugs known to prolong QT, underlying cardiac abnormalities, hypothyroidism, and familial long QT-syndrome). Mindol Forte (Haloperidol) INJECTION IS NOT APPROVED FOR INTRAVENOUS ADMINISTRATION. If Mindol Forte (Haloperidol) injection is administered intravenously, the ECG should be monitored for QT prolongation and arrhythmias.

Tardive Dyskinesia

A syndrome consisting of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.

Both the risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses.

There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment, itself, however, may suppress the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.

Given these considerations, antipsychotic drugs should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that, 1) is known to respond to antipsychotic drugs, and, 2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.

If signs and symptoms of tardive dyskinesia appear in a patient on antipsychotics, drug discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.

(For further information about the description of tardive dyskinesia and its clinical detection, please refer to ADVERSE REACTIONS .)

Neuroleptic Malignant Syndrome (NMS)

A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status (including catatonic signs) and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure.

The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology.

The management of NMS should include 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.

If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.

Hyperpyrexia and heat stroke, not associated with the above symptom complex, have also been reported with Mindol Forte (Haloperidol).

Falls

Motor instability, somnolence, and orthostatic hypotension have been reported with the use of antipsychotics, including Mindol Forte, which may lead to falls and, consequently, fractures or other fall-related injuries. For patients, particularly the elderly, with diseases, conditions, or medications that could exacerbate these effects, assess the risk of falls when initiating antipsychotic treatment and recurrently for patients receiving repeated doses.

Usage in Pregnancy

Rodents given 2 to 20 times the usual maximum human dose of Mindol Forte (Haloperidol) by oral or parenteral routes showed an increase in incidence of resorption, reduced fertility, delayed delivery and pup mortality. No teratogenic effect has been reported in rats, rabbits or dogs at dosages within this range, but cleft palate has been observed in mice given 15 times the usual maximum human dose. Cleft palate in mice appears to be a nonspecific response to stress or nutritional imbalance as well as to a variety of drugs, and there is no evidence to relate this phenomenon to predictable human risk for most of these agents.

There are no well controlled studies with Mindol Forte (Haloperidol) injection in pregnant women. There are reports, however, of cases of limb malformations observed following maternal use of Mindol Forte (Haloperidol) along with other drugs which have suspected teratogenic potential during the first trimester of pregnancy. Causal relationships were not established in these cases. Since such experience does not exclude the possibility of fetal damage due to Mindol Forte (Haloperidol), this drug should be used during pregnancy or in women likely to become pregnant only if the benefit clearly justifies a potential risk to the fetus. Infants should not be nursed during drug treatment.

Non-teratogenic Effects

Neonates exposed to antipsychotic drugs (including Mindol Forte (Haloperidol)) during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization.

Mindol Forte (Haloperidol) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Combined Use of Mindol Forte and Lithium

An encephalopathic syndrome (characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN, and fasting blood sugar) followed by irreversible brain damage has occurred in a few patients treated with lithium plus Mindol Forte (Haloperidol). A causal relationship between these events and the concomitant administration of lithium and Mindol Forte (Haloperidol) has not been established; however, patients receiving such combined therapy should be monitored closely for early evidence of neurological toxicity and treatment discontinued promptly if such signs appear.

General

A number of cases of bronchopneumonia, some fatal, have followed the use of antipsychotic drugs, including Mindol Forte (Haloperidol). It has been postulated that lethargy and decreased sensation of thirst due to central inhibition may lead to dehydration, hemoconcentration and reduced pulmonary ventilation. Therefore, if the above signs and symptoms appear, especially in the elderly, the physician should institute remedial therapy promptly.

Although not reported with Mindol Forte (Haloperidol), decreased serum cholesterol and/or cutaneous and ocular changes have been reported in patients receiving chemically-related drugs.

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PRECAUTIONS

Leukopenia, Neutropenia, and Agranulocytosis

Class Effect: In clinical trial and/or postmarketing experience, events of leukopenia/neutropenia have been reported temporally related to antipsychotic agents, including Mindol Forte. Agranulocytosis has also been reported.

Possible risk factors for leukopenia/neutropenia include pre-existing low white blood cell count (WBC) and history of drug-induced leukopenia/neutropenia. Patients with a history of a clinically significant low WBC or a drug-induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and discontinuation of Mindol Forte (Haloperidol) should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors.

Patients with clinically significant neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count <1000/mm3) should discontinue Mindol Forte (Haloperidol) and have their WBC followed until recovery.

Other

Mindol Forte (Haloperidol) injection should be administered cautiously to patients:

  • with severe cardiovascular disorders, because of the possibility of transient hypotension and/or precipitation of anginal pain. Should hypotension occur and a vasopressor be required, epinephrine should not be used since Mindol Forte (Haloperidol) may block its vasopressor activity and paradoxical further lowering of the blood pressure may occur. Instead, metaraminol, phenylephrine or norepinephrine should be used.
  • receiving anticonvulsant medications, with a history of seizures, or with EEG abnormalities, because Mindol Forte (Haloperidol) may lower the convulsive threshold. If indicated, adequate anticonvulsant therapy should be concomitantly maintained.
  • with known allergies, or with a history of allergic reactions to drugs.
  • receiving anticoagulants, since an isolated instance of interference occurred with the effects of one anticoagulant (phenindione).

When Mindol Forte (Haloperidol) is used to control mania in cyclic disorders, there may be a rapid mood swing to depression.

Severe neurotoxicity (rigidity, inability to walk or talk) may occur in patients with thyrotoxicosis who are also receiving antipsychotic medication, including Mindol Forte (Haloperidol).

Drug Interactions

Drug-drug interactions can be pharmacodynamic or pharmacokinetic (alteration of plasma levels). The risks of using Mindol Forte (Haloperidol) in combination with other drugs have been evaluated as described below.

Pharmacodynamic Interactions

Since QT-prolongation has been observed during Mindol Forte (Haloperidol) treatment, caution is advised when prescribing to a patient with QT-prolongation conditions (long QT-syndrome, hypokalemia, electrolyte imbalance) or to patients receiving medications known to prolong the QT-interval or known to cause electrolyte imbalance.

If concomitant antiparkinson medication is required, it may have to be continued after Mindol Forte (Haloperidol) is discontinued because of the difference in excretion rates. If both are discontinued simultaneously, extrapyramidal symptoms may occur. The physician should keep in mind the possible increase in intraocular pressure when anticholinergic drugs, including antiparkinson agents, are administered concomitantly with Mindol Forte (Haloperidol).

As with other antipsychotic agents, it should be noted that Mindol Forte (Haloperidol) may be capable of potentiating CNS depressants such as anesthetics, opiates and alcohol.

Ketoconazole is a potent inhibitor of CYP3A4. Increases in QTc have been observed when Mindol Forte (Haloperidol) was given in combination with the metabolic inhibitors ketoconazole (400 mg/day) and paroxetine (20 mg/day). It may be necessary to reduce the Mindol Forte (Haloperidol) dosage.

Pharmacokinetic Interactions

The Effect of Other Drugs on Mindol Forte

Mindol Forte (Haloperidol) is metabolized by several routes, including the glucuronidation and the cytochrome P450 enzyme system. Inhibition of these routes of metabolism by another drug may result in increased Mindol Forte (Haloperidol) concentrations and potentially increase the risk of certain adverse events, including QT-prolongation.

Drugs Characterized as Substrates, Inhibitors or Inducers of CYP3A4, CYP2D6 or Glucuronidation

In pharmacokinetic studies, mild to moderately increased Mindol Forte concentrations have been reported when Mindol Forte (Haloperidol) was given concomitantly with drugs characterized as substrates or inhibitors of CYP3A4 or CYP2D6 isoenzymes, such as itraconazole, nefazodone, buspirone, venlafaxine, alprazolam, fluvoxamine, quinidine, fluoxetine, sertraline, chlorpromazine, and promethazine.

When prolonged treatment (1 to 2 weeks) with enzyme-inducing drugs such as rifampin or carbamazepine is added to Mindol Forte (Haloperidol) therapy, this results in a significant reduction of Mindol Forte (Haloperidol) plasma levels.

Rifampin

In a study of 12 schizophrenic patients coadministered oral Mindol Forte (Haloperidol) and rifampin, plasma Mindol Forte (Haloperidol) levels were decreased by a mean of 70% and mean scores on the Brief Psychiatric Rating Scale were increased from baseline. In 5 other schizophrenic patients treated with Mindol Forte (Haloperidol) and rifampin, discontinuation of rifampin produced a mean 3.3-fold increase in Mindol Forte (Haloperidol) concentrations.

Carbamazepine

In a study in 11 schizophrenic patients co-administered Mindol Forte and increasing doses of carbamazepine, Mindol Forte (Haloperidol) plasma concentrations decreased linearly with increasing carbamazepine concentrations.

Thus, careful monitoring of clinical status is warranted when enzyme inducing drugs such as rifampin or carbamazepine are administered or discontinued in haloperidol-treated patients. During combination treatment, the Mindol Forte (Haloperidol) dose should be adjusted, when necessary. After discontinuation of such drugs, it may be necessary to reduce the dosage of Mindol Forte (Haloperidol).

Valproate

Sodium valproate, a drug know to inhibit glucuronidation, does not affect Mindol Forte (Haloperidol) plasma concentrations.

Information for Patients

Mindol Forte may impair the mental and/or physical abilities required for the performance of hazardous tasks such as operating machinery or driving a motor vehicle. The ambulatory patient should be warned accordingly.

The use of alcohol with this drug should be avoided due to possible additive effects and hypotension.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

No mutagenic potential of Mindol Forte (Haloperidol) was found in the Ames Salmonella microsomal activation assay. Negative or inconsistent positive findings have been obtained in in vitro and in vivo studies of effects of Mindol Forte (Haloperidol) on chromosome structure and number. The available cytogenetic evidence is considered too inconsistent to be conclusive at this time.

Carcinogenicity studies using oral Mindol Forte (Haloperidol) were conducted in Wistar rats (dosed at up to 5 mg/kg daily for 24 months) and in Albino Swiss mice (dosed at up to 5 mg/kg daily for 18 months). In the rat study survival was less than optimal in all dose groups, reducing the number of rats at risk for developing tumors. However, although a relatively greater number of rats survived to the end of the study in high-dose male and female groups, these animals did not have a greater incidence of tumors than control animals. Therefore, although not optimal, this study does suggest the absence of a Mindol Forte (Haloperidol) related increase in the incidence of neoplasia in rats at doses up to 20 times the usual daily human dose for chronic or resistant patients.

In female mice at 5 and 20 times the highest initial daily dose for chronic or resistant patients, there was a statistically significant increase in mammary gland neoplasia and total tumor incidence; at 20 times the same daily dose there was a statistically significant increase in pituitary gland neoplasia. In male mice, no statistically significant differences in incidences of total tumors or specific tumor types were noted.

Antipsychotic drugs elevate prolactin levels; the elevation persists during chronic administration. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro, a factor of potential importance if the prescription of these drugs is contemplated in a patient with a previously detected breast cancer. Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of antipsychotic drugs. Neither clinical studies nor epidemiologic studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis; the available evidence is considered too limited to be conclusive at this time.

There are no well controlled studies with Mindol Forte (Haloperidol) injection in pregnant women. There are reports, however, of cases of limb malformations observed following maternal use of Mindol Forte (Haloperidol) along with other drugs which have suspected teratogenic potential during the first trimester of pregnancy. Causal relationships were not established in these cases. Since such experience does not exclude the possibility of fetal damage due to Mindol Forte (Haloperidol), this drug should be used during pregnancy or in women likely to become pregnant only if the benefit clearly justifies a potential risk to the fetus.

Nursing Mothers

Since Mindol Forte is excreted in human breast milk, infants should not be nursed during drug treatment with Mindol Forte (Haloperidol).

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of Mindol Forte (Haloperidol) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not consistently identified differences in responses between the elderly and younger patients. However, the prevalence of tardive dyskinesia appears to be highest among the elderly, especially elderly women (see WARNINGS, Tardive Dyskinesia ). Also, the pharmacokinetics of Mindol Forte (Haloperidol) in geriatric patients generally warrants the use of lower doses (see DOSAGE AND ADMINISTRATION ).

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ADVERSE REACTIONS

Cardiovascular Effects

Tachycardia, hypotension, and hypertension have been reported. QT prolongation and/or ventricular arrhythmias have also been reported, in addition to ECG pattern changes compatible with the polymorphous configuration of torsade de pointes, and may occur more frequently with high doses and in predisposed patients.

Cases of sudden and unexpected death have been reported in association with the administration of Mindol Forte (Haloperidol). The nature of the evidence makes it impossible to determine definitively what role, if any, Mindol Forte (Haloperidol) played in the outcome of the reported cases. The possibility that Mindol Forte (Haloperidol) caused death cannot, of course, be excluded, but it is to be kept in mind that sudden and unexpected death may occur in psychotic patients when they go untreated or when they are treated with other antipsychotic drugs.

CNS Effects

Extrapyramidal Symptoms

EPS during the administration of Mindol Forte (Haloperidol) injection have been reported frequently, often during the first few days of treatment. EPS can be categorized generally as Parkinson-like symptoms, akathisia, or dystonia (including opisthotonos and oculogyric crisis). While all can occur at relatively low doses, they occur more frequently and with greater severity at higher doses. The symptoms may be controlled with dose reductions or administration of antiparkinson drugs such as benztropine mesylate USP or trihexyphenidyl hydrochloride USP. It should be noted that persistent EPS have been reported; the drug may have to be discontinued in such cases.

Dystonia

Class Effect: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.

Withdrawal Emergent Neurological Signs

Generally, patients receiving short-term therapy experience no problems with abrupt discontinuation of antipsychotic drugs. However, some patients on maintenance treatment experience transient dyskinetic signs after abrupt withdrawal. In certain of these cases the dyskinetic movements are indistinguishable from the syndrome described below under "Tardive Dyskinesia" except for duration. It is not known whether gradual withdrawal of antipsychotic drugs will reduce the rate of occurrence of withdrawal emergent neurological signs but until further evidence becomes available, it seems reasonable to gradually withdraw use of Mindol Forte.

Tardive Dyskinesia

As with all antipsychotic agents Mindol Forte (Haloperidol) has been associated with persistent dyskinesias. Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may appear in some patients on long-term therapy or may occur after drug therapy has been discontinued. The risk appears to be greater in elderly patients on high-dose therapy, especially females. The symptoms are persistent and in some patients appear irreversible. The syndrome is characterized by rhythmical involuntary movements of tongue, face, mouth or jaw (e.g., protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements). Sometimes these may be accompanied by involuntary movements of extremities and the trunk.

There is no known effective treatment for tardive dyskinesia; antiparkinson agents usually do not alleviate the symptoms of this syndrome. It is suggested that all antipsychotic agents be discontinued if these symptoms appear. Should it be necessary to reinstitute treatment, or increase the dosage of the agent, or switch to a different antipsychotic agent, this syndrome may be masked.

It has been reported that fine vermicular movement of the tongue may be an early sign of tardive dyskinesia and if the medication is stopped at that time the full syndrome may not develop.

Tardive Dystonia

Tardive dystonia, not associated with the above syndrome, has also been reported. Tardive dystonia is characterized by delayed onset of choreic or dystonic movements, is often persistent, and has the potential of becoming irreversible.

Other CNS Effects

Insomnia, restlessness, anxiety, euphoria, agitation, drowsiness, depression, lethargy, headache, confusion, vertigo, grand mal seizures, exacerbation of psychotic symptoms including hallucinations, and catatonic-like behavioral states which may be responsive to drug withdrawal and/or treatment with anticholinergic drugs.

Body as a Whole

Neuroleptic malignant syndrome, hyperpyrexia and heat stroke have been reported with Mindol Forte (Haloperidol). (See WARNINGS for further information concerning NMS.)

Hematologic Effects

Reports have appeared citing the occurrence of mild and usually transient leukopenia and leukocytosis, minimal decreases in red blood cell counts, anemia, or a tendency toward lymphomonocytosis. Agranulocytosis has rarely been reported to have occurred with the use of Mindol Forte (Haloperidol), and then only in association with other medication. (See PRECAUTIONS: Leukopenia, Neutropenia, and Agranulocytosis .)

Liver Effects

Impaired liver function and/or jaundice have been reported.

Dermatologic Reactions

Maculopapular and acneiform skin reactions and isolated cases of photosensitivity and loss of hair.

Endocrine Disorders

Lactation, breast engorgement, mastalgia, menstrual irregularities, gynecomastia, impotence, increased libido, hyperglycemia, hypoglycemia and hyponatremia.

Gastrointestinal Effects

Anorexia, constipation, diarrhea, hypersalivation, dyspepsia, nausea and vomiting.

Autonomic Reactions

Dry mouth, blurred vision, urinary retention, diaphoresis and priapism.

Respiratory Effects

Laryngospasm, bronchospasm and increased depth of respiration.

Special Senses

Cataracts, retinopathy and visual disturbances.

Postmarketing Events

Hyperammonemia has been reported in a 5½ year old child with citrullinemia, an inherited disorder of ammonia excretion, following treatment with Mindol Forte (Haloperidol).

Rhabdomyolysis has been reported.

To report SUSPECTED ADVERSE REACTIONS, contact Sagent Pharmaceuticals, Inc. at 1-866-625-1618 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

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OVERDOSAGE

Manifestations

In general, the symptoms of overdosage would be an exaggeration of known pharmacologic effects and adverse reactions, the most prominent of which would be: 1) severe extrapyramidal reactions, 2) hypotension, or 3) sedation. The patient would appear comatose with respiratory depression and hypotension which could be severe enough to produce a shock-like state. The extrapyramidal reactions would be manifested by muscular weakness or rigidity and a generalized or localized tremor as demonstrated by the akinetic or agitans types respectively. With accidental overdosage, hypertension rather than hypotension occurred in a two-year old child. The risk of ECG changes associated with torsade de pointes should be considered.

Treatment

Since there is no specific antidote, treatment is primarily supportive. A patent airway must be established by use of an oropharyngeal airway or endotracheal tube or, in prolonged cases of coma, by tracheostomy. Respiratory depression may be counteracted by artificial respiration and mechanical respirators. Hypotension and circulatory collapse may be counteracted by use of intravenous fluids, plasma, or concentrated albumin, and vasopressor agents such as metaraminol, phenylephrine and norepinephrine. Epinephrine should not be used. In case of severe extrapyramidal reactions, antiparkinson medication should be administered. ECG and vital signs should be monitored especially for signs of Q-T prolongation or dysrhythmias and monitoring should continue until the ECG is normal. Severe arrhythmias should be treated with appropriate anti-arrhythmic measures.

DOSAGE AND ADMINISTRATION

There is considerable variation from patient to patient in the amount of medication required for treatment. As with all drugs used to treat schizophrenia, dosage should be individualized according to the needs and response of each patient. Dosage adjustments, either upward or downward, should be carried out as rapidly as practicable to achieve optimum therapeutic control.

To determine the initial dosage, consideration should be given to the patient's age, severity of illness, previous response to other antipsychotic drugs, and any concomitant medication or disease state. Debilitated or geriatric patients, as well as those with a history of adverse reactions to antipsychotic drugs, may require less Mindol Forte Injection, USP. The optimal response in such patients is usually obtained with more gradual dosage adjustments and at lower dosage levels.

Parenteral medication, administered intramuscularly in doses of 2 to 5 mg, is utilized for prompt control of the acutely agitated schizophrenic patient with moderately severe to very severe symptoms. Depending on the response of the patient, subsequent doses may be given, administered as often as every hour, although 4 to 8 hour intervals may be satisfactory. The maximum dose is 20 mg per day.

Controlled trials to establish the safety and effectiveness of intramuscular administration in children have not been conducted.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Switchover Procedure

An oral form should supplant the injectable as soon as practicable. In the absence of bioavailability studies establishing bioequivalence between these two dosage forms the following guidelines for dosage are suggested. For an initial approximation of the total daily dose required, the parenteral dose administered in the preceding 24 hours may be used. Since this dose is only an initial estimate, it is recommended that careful monitoring of clinical signs and symptoms, including clinical efficacy, sedation, and adverse effects, be carried out periodically for the first several days following the initiation of switchover. In this way, dosage adjustments, either upward or downward, can be quickly accomplished. Depending on the patient's clinical status, the first oral dose should be given within 12–24 hours following the last parenteral dose.

HOW SUPPLIED

Mindol Forte Injection, USP (For Immediate Release) 5 mg per mL (as the lactate) is supplied in single-dose vials (preservative-free) and multi-dose vials as follows:

NDC Mindol Forte (Haloperidol) Injection, USP (5 mg per mL) Package Factor
25021-806-01 5 mg per mL Single-Dose Vial 10 vials per carton
(Preservative-free)
NDC Mindol Forte (Haloperidol) Injection, USP (5 mg per mL) Package Factor
25021-823-10 50 mg per 10 mL Multi-Dose Vial 1 vial per carton

Storage Conditions

Store at 20° to 25°C (68° to 77°F).

Do not freeze.

Protect from light. Retain in carton until time of use.

Sterile, Nonpyrogenic.

The container closure is not made with natural rubber latex.

SAGENT®

Mfd. for SAGENT Pharmaceuticals

Schaumburg, IL 60195 (USA)

Made in India

©2017 Sagent Pharmaceuticals, Inc.

Revised: March 2017

SAGENT Pharmaceuticals®

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – Vial Label

NDC 25021-806-01

Rx only

Mindol Forte (Haloperidol) Injection, USP

(For Immediate Release)

5 mg per mL

1 mL Single-Dose Vial

For Intramuscular Use Only

PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – Vial Label

NDC 25021-823-10

Rx only

Mindol Forte (Haloperidol) Injection, USP

(For Immediate Release)

50 mg per 10 mL

(5 mg per mL)

10 mL Multi-Dose Vial

For Intramuscular Use Only

Trihexyphenidyl:


INDICATIONS AND USAGE

Mindol Forte (Trihexyphenidyl) HCl tablets are indicated as an adjunct in the treatment of all forms of parkinsonism (postencephalitic, arteriosclerotic, and idiopathic). It is often useful as adjuvant therapy when treating these forms of parkinsonism with levodopa. Additionally, it is indicated for the control of extrapyramidal disorders caused by central nervous system drugs such as the dibenzoxazepines, phenothiazines, thioxanthenes, and butyrophenones.

WARNINGS

Patients to be treated with Mindol Forte (Trihexyphenidyl) HCl should have a gonioscope evaluation and close monitoring of intraocular pressures at regular periodic intervals.

PRECAUTIONS

Although Mindol Forte (Trihexyphenidyl) HCl is not contraindicated for patients with cardiac, liver, or kidney disorders, or with hypertension, such patients should be maintained under close observation.

Since the use of Mindol Forte (Trihexyphenidyl) HCl may, in some cases, continue indefinitely and since it has atropine-like properties, patients should be subjected to constant and careful long-term observation to avoid allergic and other untoward reactions. Inasmuch as Mindol Forte (Trihexyphenidyl) HCl possesses some parasympatholytic activity, it should be used with caution in patients with glaucoma, obstructive disease of the gastrointestinal or genitourinary tracts, and in elderly males with possible prostatic hypertrophy. Geriatric patients, particularly over the age of 60, frequently develop increased sensitivity to the actions of drugs of this type, and hence, require strict dosage regulation. Incipient glaucoma may be precipitated by parasympatholytic drugs such as Mindol Forte (Trihexyphenidyl) HCl.

Tardive dyskinesia may appear in some patients on long-term therapy with antipsychotic drugs or may occur after therapy with these drugs has been discontinued. Antiparkinsonism agents do not alleviate the symptoms of tardive dyskinesia and, in some instances, may aggravate them. However, parkinsonism and tardive dyskinesia often coexist in patients receiving chronic neuroleptic treatment, and anticholinergic therapy with Mindol Forte (Trihexyphenidyl) HCl may relieve some of these parkinsonism symptoms.

ADVERSE REACTIONS

Minor side effects, such as dryness of the mouth, blurring of vision, dizziness, mild nausea or nervousness, will be experienced by 30 to 50 percent of all patients. These sensations, however, are much less troublesome with Mindol Forte (Trihexyphenidyl) HCl than with belladonna alkaloids and are usually less disturbing than unalleviated parkinsonism. Such reactions tend to become less pronounced, and even to disappear, as treatment continues. Even before these reactions have remitted spontaneously, they may often be controlled by careful adjustment of dosage form, amount of drug, or interval between doses.

Isolated instances of suppurative parotitis secondary to excessive dryness at the mouth, skin rashes, dilatation of the colon, paralytic ileus, and certain psychiatric manifestations such as delusions and hallucinations, plus one doubtful case of paranoia all of which may occur with any of the atropine-like drugs, have been reported rarely with Mindol Forte (Trihexyphenidyl) hydrochloride.

Patients with arteriosclerosis or with a history of idiosyncrasy to other drugs may exhibit reactions of mental confusion, agitation, disturbed behavior, or nausea and vomiting. Such patients should be allowed to develop a tolerance through the initial administration of a small dose and gradual increase in dose until an effective level is reached. If a severe reaction should occur, administration of the drug should be discontinued for a few days and then resumed at a lower dosage. Psychiatric disturbances can result from indiscriminate use (leading to overdosage) to sustain continued euphoria.

Potential side effects associated with the use of any atropine-like drugs include constipation, drowsiness, urinary hesitancy or retention, tachycardia, dilation of the pupil, increased intraocular tension, weakness, vomiting, and headache.

The occurrence of angle-closure glaucoma due to long-term treatment with Mindol Forte (Trihexyphenidyl) has been reported.

DOSAGE AND ADMINISTRATION

Dosage should be individualized. The initial dose should be low and then increased gradually, especially in patients over 60 years of age. Whether Mindol Forte HCl may best be given before or after meals should be determined by the way the patient reacts. Postencephalitic patients, who are usually more prone to excessive salivation, may prefer to take it after meals and may, in addition, require small amounts of atropine which, under such circumstances, is sometimes an effective adjuvant. If Mindol Forte (Trihexyphenidyl) HCl tends to dry the mouth excessively, it may be better to take it before meals, unless it causes nausea. If taken after meals, the thirst sometimes induced can be allayed by mint candies, chewing gum or water.

Mindol Forte (Trihexyphenidyl) HCl in Idiopathic Parkinsonism

As initial therapy for parkinsonism, 1 mg of Mindol Forte (Trihexyphenidyl) in tablet form may be administered the first day. The dose may then be increased by 2 mg increments at intervals of three to five days, until a total of 6 to 10 mg is given daily. The total daily dose will depend upon what is found to be the optimal level. Many patients derive maximum benefit from this daily total of 6 to 10 mg, but some patients, chiefly those in the postencephalitic group, may require a total daily dose of 12 to 15 mg.

Mindol Forte HCl in Drug-Induced Parkinsonism

The size and frequency of dose of Mindol Forte (Trihexyphenidyl) HCl needed to control extrapyramidal reactions to commonly employed tranquilizers, notably the phenothiazines, thioxanthenes, and butyrophenones, must be determined empirically. The total daily dosage usually ranges between 5 and 15 mg, although, in some cases, these reactions have been satisfactorily controlled on as little as 1 mg daily. It may be advisable to commence therapy with a single 1 mg dose. If the extrapyramidal manifestations are not controlled in a few hours, the subsequent doses may be progressively increased until satisfactory control is achieved. Satisfactory control may sometimes be more rapidly achieved by temporarily reducing the dosage of the tranquilizer on instituting Mindol Forte (Trihexyphenidyl) HCl therapy and then adjusting dosage of both drugs until the desired ataractic effect is retained without onset of extrapyramidal reactions.

It is sometimes possible to maintain the patient on a reduced Mindol Forte (Trihexyphenidyl) HCl dosage after the reactions have remained under control for several days. Instances have been reported in which these reactions have remained in remission for long periods after Mindol Forte (Trihexyphenidyl) HCl therapy was discontinued.

Concomitant Use of Mindol Forte HCl with Levodopa

When Mindol Forte (Trihexyphenidyl) HCl is used concomitantly with levodopa, the usual dose of each may need to be reduced. Careful adjustment is necessary, depending on side effects and degree of symptom control. Mindol Forte (Trihexyphenidyl) HCl dosage of 3 to 6 mg daily, in divided doses, is usually adequate.

Concomitant Use of Mindol Forte HCl with Other Parasympathetic Inhibitors

Mindol Forte (Trihexyphenidyl) HCl may be substituted, in whole or in part, for other parasympathetic inhibitors. The usual technique is partial substitution initially, with progressive reduction in the other medication as the dose of Mindol Forte (Trihexyphenidyl) HCl is increased.

The total daily intake of Mindol Forte (Trihexyphenidyl) HCl tablets is tolerated best if divided into 3 doses and taken at mealtimes. High doses (>10 mg daily) may be divided into 4 parts, with 3 doses administered at mealtimes and the fourth at bedtime.

HOW SUPPLIED

Mindol Forte (Trihexyphenidyl) HCl tablets are available as follows:

2 mg – round, flat, scored, white tablets; debossed "5971" above the score and "V" below the score. Available in bottles of 100, 500 and 1000.

5 mg – round, flat, scored, white tablets; debossed "5972" above the score and "V" below the score. Available in bottles of 100, 500, and 1000.

Dispense in a tight, light-resistant container as defined in the USP.

Store at 20° to 25°C (68° to 77°F).

Manufactured for:

QUALITEST PHARMACEUTICALS

Huntsville, AL 35811

8181446

Rev 2/08

R2

Mindol Forte pharmaceutical active ingredients containing related brand and generic drugs:

infoActive ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Mindol Forte available forms, composition, doses:

infoForm of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Mindol Forte destination | category:

infoDestination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Mindol Forte Anatomical Therapeutic Chemical codes:

infoA medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Mindol Forte pharmaceutical companies:

infoPharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."HALOPERIDOL SOLUTION [SILARX PHARMACEUTICALS, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."HALOPERIDOL: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. "trihexyphenidyl". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Mindol Forte?

Depending on the reaction of the Mindol Forte after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Mindol Forte not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Mindol Forte addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sDrugs.com conducted a study on Mindol Forte, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Mindol Forte consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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