Finlepsin, tablets 200 mg 50 pcs

Indications

Mental disorders, Pain in diabetic neuropathy, Pain, Alcoholism, Seizures, Neuralgia, trigeminal neuralgia, Headache, Epilepsy

• Epilepsy:
• complicated or simple partial epileptic seizures (with or without loss of consciousness) with or without secondary generalization;
• generalized tonic-clonic epileptic seizures;
• mixed forms of epileptic seizures.

The drug Finlepsin^® is generally ineffective in absences and myoclonus-epilepsy.

• Acute manic states and maintenance therapy for bipolar affective disorder to prevent exacerbations or to lessen clinical manifestations of exacerbations.
• Alcohol withdrawal syndrome.
• Idiopathic trigeminal neuralgia and trigeminal neuralgia in multiple sclerosis (typical and atypical).
  

Active ingredient

Carbamazepine

Composition

1 tablet contains: active substance carbamazepine 200.00 mg; excipients: microcrystalline cellulose (type 12), gelatin, croscarmellose sodium, magnesium stearate.

How to take, the dosage

Ingestion. The drug may be taken with meals, after meals or between meals. Tablets should be taken with a small amount of liquid. The drug can be used both in monotherapy and in combination therapy.

With regard to drug interactions and pharmacokinetics of antiepileptic drugs, the dose of Finlepsin® should be adjusted with caution in elderly patients.

Epilepsy

The drug should be used in monotherapy whenever possible.

The drug is not used for minor seizures (petit mal, absans) and myoclonic seizures.

The treatment starts with a small daily dose, which is then slowly increased until optimal effect is achieved.

The dose of carbamazepine is adjusted individually to achieve adequate seizure control. To determine the optimal dose of the drug, plasma concentrations of the active ingredient are recommended, which are usually 4-12 µg/mL (17-50 µmol/L).

When Finlepsin^® is added to other antiepileptic drugs being taken, the dose of Finlepsin^® is increased gradually.

If necessary, the doses of the drugs taken are adjusted accordingly. The initial dose of carbamazepine for adults is 100-200 mg once or twice a day.

The dose is then slowly increased until optimal therapeutic effect is achieved; this is usually achieved at a dose of 400 mg 2-3 times daily. Some patients may need to increase the daily dose to 1600 mg or 2000 mg.

Ternal neuralgia

The starting dose for adults is 200-400 mg daily. It is slowly increased until the pain has disappeared (usually to a dose of 200 mg 3-4 times a day). Then the dose is gradually reduced to a minimum maintenance dose.

The maximum recommended dose for adults is 1200 mg/day. When pain resolves, therapy with the drug should be gradually discontinued until the next pain attack occurs.

The recommended starting dose for elderly patients is 100 mg 2 times daily, then the dose is slowly increased until pain resolves, which is usually achieved at a dose of 200 mg 3-4 times daily. Thereafter, the dose should be gradually reduced to the minimum maintenance dose.

In trigeminal neuralgia in this category of patients, the maximum recommended dose is 1200 mg/day. When pain resolves, therapy with the drug should be gradually discontinued until the next pain attack occurs.

Alcohol withdrawal syndrome

The average dose is 200 mg 3 times daily. In severe cases during the first few days the dose may be increased (for example, to a dose of 400 mg 3 times a day). In severe manifestations of alcohol withdrawal, treatment is started with the use of the drug in combination with drugs providing sedative and hypnotic effects (e.g., clomethiazole, chlordiazepoxide). After resolution of the acute phase, treatment with the drug may be continued in monotherapy.

Acute manic states and maintenance treatment of affective (bipolar) disorders

The daily dose is 400-1600 mg. The average daily dose is 400-600 mg (in 2-3 doses). In acute manic states, the dose should be increased rather quickly. In maintenance therapy of bipolar disorders, in order to ensure optimal tolerability, each subsequent dose increase should be small, the daily dose increasing gradually.

Application in children

The main indication for the use of Finlepsin^® in children is epilepsy. This dosage form of the drug should be used to treat the same forms of epilepsy in children over 4 years of age as in adults. Treatment can be started with a dose of 100 mg/day; the dose is increased gradually, by no more than 100 mg per week.

Children 4 years of age and younger are recommended to take carbamazepine in other dosage forms (syrup).

Maintaining doses: for children set at 10-20 mg/kg body weight per day (in several doses).

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Maximal doses: For children aged <6 years is 35 mg/kg/day, 6-15 years is 1000 mg/day, >15 years is 1200 mg/day.

Since there is insufficient reliable information about its use for other indications in children, it is recommended to choose the dosing regimen according to the age and body weight of the child and not to exceed the doses stated in the table.

Cessation of the drug

The sudden discontinuation of the drug may provoke an epileptic seizure, so carbamazepine should be withdrawn gradually over 6 months or more. If it is necessary to discontinue the drug in a patient with epilepsy, switching to another antiepileptic drug should be done under the cover of the drug indicated in such cases.

Interaction

Carbamazepine is not recommended to be used concomitantly with MAO inhibitors. MAO inhibitors should be discontinued at least 2 weeks before using the drug, or earlier if the clinical situation allows.

Cytochrome P4503A4 (CYP3A4) is the major isoenzyme responsible for the formation of carbamazepine-10,11-epoxide (active metabolite). Concomitant use of CYP3A4 isoenzyme inhibitors with the drug may increase the concentration of carbamazepine in blood plasma, which, in turn, may cause adverse reactions. Concomitant use of CYP3A4 isoenzyme inducers may lead to accelerated metabolism of carbamazepine and thus to a possible decrease in its plasma concentration and, consequently, to a possible reduction in therapeutic effect of the drug. Cancellation of simultaneously taken inducers of CYP3A4 isoenzyme may decrease the rate of biotransformation of carbamazepine, and as a consequence, lead to increased plasma concentrations of carbamazepine.

Carbamazepine is a potent inducer of CYP3A4 isoenzyme and other enzymatic hepatic systems of the first and second phase of drug metabolism, and when used simultaneously with drugs metabolized by CYP3A4 isoenzyme, may cause induction of metabolism and decrease their plasma concentrations.

Because the conversion of carbamazepine-10,11-epoxide to carbamazepine-10,11-transdiol occurs via microsomal epoxide hydrolase, use of carbamazepine concomitantly with microsomal epoxide hydrolase inhibitors may lead to increased plasma concentration of carbamazepine-10,11-epoxide.

Drugs that may increase plasma concentrations of carbamazepine:

• analgesic and nonsteroidal anti-inflammatory drugs: dextropropoxyphene, ibuprofen;
• anti-tumor agents (androgen): danazol;
• antibiotics: macrolide (e.g., erythromycin, troleandomycin, jozamycin, clarithromycin), ciprofloxacin;
• antidepressants: possibly desipramine, fluoxetine, fluvoxamine, nefazodone, paroxetine, trazodone, viloxazine;
• anti-epileptic drugs: styripentol, vigabatrin;
• antifungal agents: azole derivatives (e.g., itraconazole, ketoconazole, fluconazole, voriconazole). Alternative anticonvulsants may be recommended in patients receiving voriconazole or itraconazole;
• histamine H₂-receptor blockers: loratadine, terfenadine;
• antipsychotics (neuroleptics): olanzapine;
• antituberculosis agents: isoniazid;
• antiviral agents: HIV protease inhibitors (e.g., ritonavir);
• antiglaucoma drugs (carboanhydrase inhibitors): acetazolamide;
• hypotensive drugs (slow calcium channel blockers): verapamil, diltiazem;
• anti-ulcer drugs (proton pump inhibitors, histamine H₂-receptor blockers): omeprazole, possibly cimetidine;
• myorelaxants: oxybutynin, dantrolene;
• anti-aggregant agents: ticlopidine;
• other drugs and foods: grapefruit juice, nicotinamide (high doses only).

Because increased plasma concentrations of carbamazepine may lead to BP (e.g., dizziness, somnolence, ataxia, diplopia), in these situations the drug dose should be adjusted and/or plasma concentrations of carbamazepine should be determined regularly.

The drugs that may increase plasma concentrations of carbamazepine-10,11-epoxide are: loxapine, quetiapine, primidone, progabide, valproic acid, valnoktamide, and valpromide.

Because increased plasma concentrations of carbamazepine-10,11-epoxide may lead to adverse reactions (e.g., dizziness, somnolence, ataxia, diplopia), in these situations the drug dose should be adjusted and/or plasma concentrations of carbamazepine-10,11-epoxide should be determined regularly.

Drugs that may decrease plasma concentrations of carbamazepine:

• anti-epileptic agents: Felbamate, mesuximide, oxcarbazepine, phenobarbital, fensuximide, phenytoin (to avoid phenytoin intoxication and subtherapeutic carbamazepine concentrations, the recommended plasma concentration of phenytoin should be no more than 13 µg/mL before adding carbamazepine to therapy) and fosphenytoin, primidone, and, although data are partially inconsistent, possibly also clonazepam.
• anti-tumor agents: cisplatin or doxorubicin;
• anti-tuberculosis agents: rifampicin;
• bronchodilators: Theophylline, aminophylline;
• acne treatment (retinoids): isotretinoin;
• other drugs and foods: herbal preparations containing St. John’s Wort.

The dose of carbamazepine may need to be adjusted if used concomitantly with the above drugs.

Influence of carbamazepine on plasma concentrations of drugs used as concomitant therapy

Concomitant use with carbamazepine may decrease plasma concentrations, decrease or even completely discontinue the effect of some drugs, and therefore the need to adjust the dose of the following drugs according to clinical guidelines should be considered:

• analgesic and nonsteroidal anti-inflammatory drugs: buprenorphine, methadone, paracetamol (long-term use of carbamazepine and paracetamol (acetaminophen) may lead to hepatotoxic effects), phenazone, tramadol;
• antibiotics of the tetracycline group: doxycycline, rifabutin;
• anticoagulants: oral anticoagulants (e.g., warfarin, phenprocoumon, dicoumarol and acenocoumarol, rivaroxaban, dabigatran, apixaban, edoxaban);
• antidepressants: bupropion, citalopram, mianserine, nefazodone, sertraline, trazodone, tricyclic antidepressants (imipramine, amitriptyline, nortriptyline, clomipramine);
• antipyretics: Aprepitant;
• antiepileptic agents: clobazam, clonazepam, eslicarbazepine, ethosuximide, felbamate, lamotrigine, eslicarbazepine, oxcarbazepine, primidone, tiagabine, topiramate, valproic acid, zonisamide. To avoid phenytoin intoxication and subtherapeutic concentrations of carbamazepine, the recommended plasma concentration of phenytoin should not exceed 13 µg/mL before adding carbamazepine to therapy. There are reports that against the background of carbamazepine administration, plasma concentrations of mefenitoin may increase (in rare cases).
• antifungal agents: itraconazole, voriconazole. Alternative anticonvulsants may be recommended in patients receiving voriconazole or itraconazole;
• anthelminthics: praziquantel, albendazole;
• anti-tumor agents: imatinib, cyclophosphamide, lapatinib, temsirolimus;
• antipsychotics (neuroleptics: clozapine, haloperidol, bromperidol, olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, paliperidone;
• antiviral agents: HIV protease inhibitors (indinavir, ritonavir, saquinavir);
• anxiolytic s agents: alprazolam, midazolam;
• bronchodilators: theophylline;
• contraceptive agents: hormonal contraceptives (alternative methods of contraception must be selected);
• cardiovascular drugs: Slow calcium channel blockers of the dihydropyridine group (felodipine); simvastatin, atorvastatin, lovastatin, cerivastatin, ivabradine;
• cardiac glycosides: digoxin;
• glucocorticosteroids: prednisolone, dexamethasone;
• effective erectile dysfunction agents: tadalafil;
• immunosuppressive agents: cyclosporine, everolimus, tacrolimus, sirolimus;
• thyroid medications: Levothyroxine;
• other drugs and foods: drugs containing estrogens and/or progesterone.

Combinations to consider

In concomitant use of carbamazepine with levetiracetam, an increase in the toxic effects of carbamazepine has been noted in individual cases.

Increased hepatotoxicity caused by isoniazid has been reported in cases where it was used concomitantly with carbamazepine.

The combined use of carbamazepine and lithium or metoclopramide, as well as carbamazepine and neuroleptic agents (haloperidol, thioridazine) may increase the frequency of adverse neurological reactions (in the latter combination – even at therapeutic plasma concentrations of the active substances).

The concomitant use of carbamazepine with some diuretics (hydrochlorothiazide, furosemide) may lead to hyponatremia accompanied by clinical manifestations.

Carbamazepine may antagonize the action of nondepolarizing myorelaxants (e.g., pancuronium bromide). If this combination of drugs is used, it may be necessary to increase the dose of these myorelaxants; patients should be closely monitored, as the effects of myorelaxants may be reversed more rapidly than expected.

There have been reports of bleeding from the vagina between menstruation when concomitant use of the drug with hormonal contraceptives (breakthrough bleeding). The drug may reduce the effect of hormonal contraceptives due to induction of microsomal enzymes.

Carbamazepine, as well as other psychotropic drugs, may decrease the tolerance to alcohol. In this regard, it is recommended that the patient refrain from drinking alcohol.

The concomitant use of carbamazepine and oral direct anticoagulants (e.g., rivaroxaban, dabigatran, apixaban, edoxaban) may lead to decreased plasma concentrations of the oral direct anticoagulant, which leads to a risk of thrombosis. Thus, caution should be exercised for signs and symptoms of thrombosis when concomitant use of these drugs is necessary.

Influence on serologic studies

Carbamazepine may cause false positive results in determining the concentration of perphenazine by high-performance liquid chromatography.

Carbamazepine and 10,11-epoxide carbamazepine may cause false-positive tricyclic antidepressant concentrations by polarization fluorescence immunoassay.

Special Instructions

The drug should only be taken under medical supervision.

Patients with mixed forms of epileptic seizures including absans and myoclonic seizures.

The drug is generally ineffective in absences (petit mal) and myoclonic seizures. In patients with mixed forms of epileptic seizures the drug should be used with caution and only under condition of regular medical supervision (because of possible seizure aggravation). In case of seizures worsening Finlepsin^® should be discontinued.

Decrease in platelet and leukocyte counts

A transient or persistent decrease in platelet or leukocyte counts with varying frequency is noted during carbamazepine use. However, in most cases these phenomena are transient and are not usually precursors to the onset of aplastic anemia or agranulocytosis. Clinical blood counts, including platelet counts and possibly reticulocyte counts, as well as determination of serum iron concentration should be performed before initiating treatment, and periodically during treatment.

The patient should be advised of early signs of toxicity inherent in likely hematologic abnormalities, as well as skin and liver symptoms. Patients should be advised to contact a physician immediately if they experience adverse reactions such as fever, sore throat, rash, oral ulcers, hemorrhages without cause, hemorrhages as petechiae or purpura.

If leukocyte or platelet counts decrease (or tend to decrease) during therapy, the patient should be closely monitored and parameters of a complete clinical blood count should be controlled. If the signs of significant bone marrow depression are found, Finlepsin^® should be discontinued.

Dermatological reactions

Severe dermatological reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell’s syndrome), have been very rarely reported with the use of the drug.

The drug Finlepsin^® should be immediately discontinued and an alternative therapy should be chosen if signs and symptoms are observed suggestive of severe dermatological reactions such as Stevens-Johnson syndrome or Lyell’s syndrome. If severe (in some cases life-threatening) skin reactions develop, the patient must be hospitalized. In most cases, Stevens-Johnson syndrome and Lyell’s syndrome developed in the first months of therapy with the drug. These reactions developed in approximately 1-6 cases per 10,000 first-time users of the drug in countries with predominantly Caucasian populations.

The retrospective analysis in Japanese and Northern European patients demonstrated an association between severe skin lesions (Stevens-Johnson syndrome, Lyell syndrome, DRESS syndrome, acute generalized exanthematous pustulosis, and blotchy-knot rash) in carriers of the HLA-A*3101 human leukocyte antigen (HLA) allele and carbamazepine use.

The frequency of the HLA-A*3101 allele may differ in different ethnic groups: about 2-5% in the European population, about 10% in the Japanese population. The frequency of this allele in the majority of populations in Australia, Asia, Africa and North America is less than 5%, with some exceptions ranging from 5-12%. The frequency of more than 15% is established in some ethnic groups of South America (Argentina and Brazil), in indigenous peoples of North America (Navajo and Sioux tribes, in Mexico – Sanora Ceri), in South India (Tamil Nadu), and 10-15% – among other indigenous peoples of these regions.

When using carbamazepine in possible carriers of the HLA-A*3101 allele (e.g., Japanese, Caucasian, Native American, Hispanic, South Indian, and Arab patients), genotyping for this allele is recommended. Use in carriers of this allele only if the benefit of therapy outweighs the possible risk.

Patients already receiving carbamazepine should not be genotyped for this allele because severe skin reactions were seen in most cases in the first months of use (regardless of the presence of HLA-A*3101).

A retrospective analysis of carbamazepine use in Chinese and Thai patients showed a correlation between the incidence of Stevens-Johnson syndrome and Lyell syndrome and the presence of the HLA-B*1502 allele in the patient’s genome. The frequency of this allele in patients of Chinese ethnicity is 2-12% and in patients of Thai ethnicity about 8%.

The use of carbamazepine in patients in countries in the Asian region (Taiwan, Malaysia, Philippines), where there is a high prevalence of the HLA-B*1502 allele, has been found to increase the frequency of development (grading from “very rare” to “rare”) of Stevens-Johnson syndrome. The frequency of HLA-B*1502 allele prevalence is: in the Philippines and among some populations in Malaysia – more than 15%. The prevalence of the HLA-B*1502 allele in Korea and India is 2% and 6%, respectively. The prevalence of this allele in persons of Caucasoid, Negroid, Hispanic, Native American and Japanese races is insignificant (< 1%).

The frequencies of these alleles represent the percentage of chromosomes in certain populations that carry the allele. This means that the percentage of patients carrying a copy of the allele in at least one of their two chromosomes is almost twice the frequency of the allele. Thus, the percentage of patients who might be at risk is almost twice the frequency of the allele.

When using carbamazepine in possible carriers of the HLA-B*1502 allele, genotyping for this allele is recommended. The drug should be used in carriers of this allele only if the benefit of therapy outweighs the possible risk. Genotyping is not recommended in ethnic groups with a low incidence of this allele in their populations.

Patients already receiving carbamazepine should not be genotyped for this allele because severe skin reactions were observed in most cases in the first months of use (regardless of the presence of HLA-B*1502).

The identification of patients with the HLA-B*1502 allele and not using carbamazepine in these patients has been shown to reduce the incidence of carbamazepine-induced Stevens-Johnson syndrome or Lyell syndrome.

However, the results of genotyping should not affect the degree to which the patient is monitored and the physician’s alertness to severe skin reactions. The development of severe skin lesions is possible in patients negative for these alleles. Also, in many cases, patients who are positive for HLA-B*1502 or HLA-A*3101 alleles have not developed severe skin syndromes when using carbamazepine.

The effect of other factors, such as anticonvulsant medication dose, patient compliance, concurrent therapy with other drugs, comorbidities, or level of dermatologic reaction control, on the incidence and prevalence of severe skin reactions has not been established.

Mild skin reactions, such as isolated maculopapular or maculopapular exanthema, are in most cases transient and not severe, usually resolving within a few days or weeks with continued treatment or after reduction of the drug dose. However, since differential diagnosis between early manifestations of severe skin reactions and mild transient skin rashes may be difficult, the patient should be kept under medical supervision if any skin reactions develop (with the goal of discontinuing therapy in a timely fashion if the patient’s condition worsens).

There is an association between the HLA-A*3101 allele in the genome and the development of less severe skin reactions (such as hypersensitivity to anticonvulsants or non-serious maculopapular exanthema); this relationship has not been established for the HLA-B*1502 allele.

Hypersensitivity reactions

. When patients develop hypersensitivity to carbamazepine, various reactions may occur, including DRESS syndrome, delayed multi-organ manifestations of hypersensitivity with the development of fever, skin rash, vasculitis, lymphadenopathy, pseudolymphoma, arthralgia, leukopenia, eosinophilia, hepatosplenomegaly, changes in liver function parameters and bile duct destruction syndrome with decreased number, which may occur in any combination. Other internal organs (including lungs, kidneys, pancreas, myocardium, colon) may also be affected.

In case of signs and symptoms of hypersensitivity, the drug should be stopped immediately.

Patients with known hypersensitivity to carbamazepine should be informed of the possibility of 25-30% of cases of hypersensitivity reactions to oxcarbazepine.

The development of cross-sensitivity reactions between carbamazepine and aromatic antiepileptic drugs (e.g., phenytoin, pyrimidone and phenobarbital) is possible.

Hyponatremia

The development of hyponatremia is associated with the use of carbamazepine. In patients with pre-existing renal impairment connected with low sodium content in serum or in patients receiving concomitant medicines, which reduce sodium content (e.g. diuretics, medicines which influence on antidiuretic hormone secretion), serum sodium content should be determined before starting carbamazepine therapy. Thereafter, sodium content should be determined after about two weeks and then monthly for the first three months of therapy, or as clinically necessary. These risk factors are particularly common in elderly patients. If hyponatremia is present, fluid restriction is important to determine the condition if clinically indicated.

Hypothyroidism

Carbamazepine may decrease serum thyroid hormone concentrations by enzyme induction, which requires increasing the dose of replacement therapy drugs in patients with hypothyroidism. In this category of patients, monitoring of thyroid function is necessary to select the dose of drugs of substitution therapy.

Hepatic disorders

Hepatic function tests should be performed before and during the use of Finlepsin^®, especially in patients with a history of liver disease and in elderly patients. Finlepsin® should be discontinued immediately if pre-existing liver function abnormalities worsen or if active liver disease develops.

Renal dysfunction

Before starting treatment with the drug and periodically during therapy, urinalysis and determination of blood urea concentration are recommended.

M-cholinoblocking activity

The drug has weak m-cholinoblocking activity. Therefore, patients with elevated intraocular pressure, prostatic hyperplasia, and urinary retention should be closely monitored when the above drugs are used concomitantly.

Mental disorders

As latent mental disorders may worsen with the use of the drug, elderly patients should be monitored for symptoms such as confusion and psychomotor agitation.

Suicidal behavior or intentions

Suicidal behavior or intentions have been reported in patients treated with anticonvulsants for several indications. Results of a meta-analysis of randomized placebo-controlled trials showed a small increase in the risk of suicidal behavior in patients receiving anticonvulsants. The mechanism of increased suicidal behavior in this patient population has not been established. Therefore, careful monitoring of suicidal behavior and intentional symptoms and decision making about appropriate treatment is necessary. Patients (and their caregivers) should be strongly encouraged to seek medical attention if symptoms of suicidal behavior or intentions occur.

Endocrinological disorders

Because of enzyme induction, carbamazepine may impair the therapeutic effect of oral contraceptives containing estrogens and/or progesterone. Patients with preserved reproductive potential should be advised to use alternative methods of contraception during therapy with the drug. Bleeding from the vagina between menstruations has been reported with concomitant use of the drug with hormonal contraceptives (breakthrough bleeding).

Pregnancy and patients with preserved reproductive potential

The use of the drug during pregnancy may be associated with a risk to the fetus (see section “Pregnancy and breastfeeding“). The use of the drug in pregnancy is possible only if the expected benefits justify the potential risks.

Pregnant patients and patients with preserved reproductive potential should be fully informed about the risks to the fetus associated with the potential teratogenic effects of carbamazepine (see section “Pregnancy and Breastfeeding“).

Patients with preserved reproductive potential should use reliable contraception during therapy and for 2 weeks after the last dose of the drug (see Endocrinologic Disorders, as well as the sections on Interaction with Other Drugs and Pregnancy and Breastfeeding.)

Determination of plasma carbamazepine concentration

While there is little relationship between drug dose, plasma carbamazepine concentration, clinical efficacy or tolerability, regular determination of carbamazepine concentration may nevertheless be appropriate in the following situations if there is a sudden increase in seizure frequency, to see if the patient is taking the drug properly; during pregnancy; when treating children or adolescents; if carbamazepine absorption disorders are suspected; if toxic reactions are suspected if the patient is taking multiple medications.

Falls

The drug therapy was accompanied by ataxia, dizziness, somnolence, hypotension, confusion, sedation (see Side effects), which may lead to falls and, consequently, to fractures or other injuries. In patients with concomitant diseases, conditions, or receiving concomitant drug therapy with drugs that may exacerbate the above effects, the risk of falls during long-term therapy with the drug should be regularly evaluated.

Influence on driving, operating machinery

The ability of a patient taking Finlepsin^®

The ability to respond quickly, especially at the beginning of therapy or during dose adjustment, may be impaired by the disease itself (e.g., seizures) as well as by adverse events such as dizziness, drowsiness, ataxia, diplopia, accommodation disorder, and visual impairment. Patients should be advised of the possible dangers of driving and operating machinery.