Alextol Suspension
Carbamazepine 100 mg/ 5 ml
Company Name
Alexandria
Therapeutic Group
ANTI-EPILEPTICS
Pharmaceutical form
Suspension
Package
Suspension 100 ml
Indications
"Epilepsy
Alextol is indicated for use as an anticonvulsant drug. Evidence supporting efficacy of Alextol as an anticonvulsant was derived from active drug-controlled studies that enrolled patients with the following seizure types:
1. Partial seizures with complex symptomatology (psychomotor, temporal lobe). Patients with these seizures appear to show greater improvement than those with other types.
2. Generalized tonic-clonic seizures (grand mal).
3. Mixed seizure pattern which include the above, or other partial or generalized seizures. Absence seizures (petit mal) do not appear to be controlled by Alextol.
Trigeminal Neuralgia
Alextol is indicated in the treatment of the pain associated with true trigeminal neuralgia.
Beneficial results have also been reported in glossopharyngeal neuralgia.
This drug is not a simple analgesic and should not be used for the relief of trivial aches or pains."
Warning & Precautions
" Carbamazepine should be prescribed only after a critical benefit–risk appraisal and under close monitoring in patients with a history of cardiac, hepatic or renal damage, adverse haematological reactions to other drugs, or interrupted course of therapy with Carbamazepine. Baseline and periodic complete urinalysis and BUN determinations are recommended Carbamazepine has shown mild anticholinergic activity, patients with increased intraocular pressure should therefore be warned and advised regarding possible hazards. The possibility of activation of a latent psychosis and, in elderly patients, of confusion or agitation should be borne in mind. Effect on ability to drive and use machine: Alextol-induced dizziness or drowsiness may impair the reactions, particularly at the start of treatment or following dose adjustment. Patients should therefore exercise due caution when driving or using machines.
Product Type
Human
Dosage
"General information
Alextol may be taken during, after or between meals with liquid.
The suspension (1 spoonful = 5 ml = 100 mg; ½ spoonful = 2.5 ml = 50 mg) is particularly suitable for patients who have difficulty in swallowing tablets or who require careful initial dose titration.
Dosage in special clinical situation
Elderly patients
Due to possible drug interactions and different antiepileptic drug pharmacokinetics, the dosage of Alextol should be selected with caution in elderly patients.
Epilepsy
Alextol should be prescribed as monotherapy whenever possible.
Treatment should be initiated with a low dosage slowly increasing until an optimum dose.
When Alextol is added to existing antiepileptic therapy this should be done gradually while maintaining or if necessary adapting the dosage of the other drugs.
Adults:
Oral forms: initially 100-200 mg once or twice daily slowly increasing until an optimum response is achieved (generally with 400 mg two or three times daily). In some patients 1600 mg or even 2000 mg daily may be appropriate.
Children:
Oral forms: 10-20 mg/kg/daily in divided dose.
E.g. up to one year of age: 100-200 mg suspension daily (1-2 spoonful)
1-5 years: 200-400 mg suspension daily (2x 1-2 spoonful)
6-10 years: 400-600 mg suspension daily (2-3 x 2 spoonful)
11-15 years: 600-1000 mg suspension daily (3 x 2-3½ spoonful)
A starting dose of 20 -60 mg/day, increasing by 20-60 every second day, is recommended in children 4 years or less. In children aged over 4 years treatment should be started at 100 mg/day, increasing by 100 mg at weekly intervals.
Trigeminal neuralgia:
A starting dose of 200-400 mg /day should be gradually increased until freedom from pain is achieved (normally with 200 mg t.i.d or q.i.d) The dose should be then gradually reduced to the lowest possible maintenance level. A starting dosage of 100 mg b.i.d. is recommended in elderly patients.
Alcohol withdrawal syndrome:
On the first two days of treatment patients should be given 200 mg t.i.d. or q.i.d. in severe cases, the dosage can be increased in the first few days of treatment to a maximum of 1200 mg/day. Dosage should be subsequently be reduced slowly and treatment gradually withdrawn.
Acutemania and maintenance treatment of bipolar effective disorders:
Dosage range approx. 400-600 mg daily dose is 400-600 mg given in 2-3 divided doses.
The dosage should be increased fairly in acute mania, whereas small increments are recommended for maintenance therapy of bipolar disorders to ensure optimal tolerability."
Adverse Reactions
"If adverse reactions are of such severity that the drug must be discontinued, the physician must be aware that abrupt discontinuation of any anticonvulsant drug in a responsive epileptic patient may lead to seizures or even status epilepticus with its life-threatening hazards.
The most severe adverse reactions have been observed in the hemopoietic system and skin, liver, and the cardiovascular system.
The most frequently observed adverse reactions, particularly during the initial phases of therapy, are dizziness, drowsiness, unsteadiness, and vomiting. To minimize the possibility of such reactions, therapy should be initiated at the low dosage recommended.
The following additional adverse reactions have been reported:
Hemopoietic system: Aplastic anemia, agranulocytosis, pancytopenia, bone marrow depression, thrombocytopenia, leucopenia, leucopenia, leukocytosis, eosinophilia, acute intermittent porphyria.
Skin: Toxic epidermal necrolysis (TEN) and stevens-johnson syndrome (SJS), Pruritic and erythmatous rashes, urtecaria, photosensitivity reactions, alternations in skin pigmentation, exfoliative dermatitis, erythema multiforme and nodosum, purpura, aggravation of disseminated lupus erythematous, alopecia, and diaphoresis. In certain cases, discontinuation of therapy may be necessary. Isolated cases of hirsutism have been reported, but a causal relationship is not clear.
Cardiovascular System: Congestive heart failure, edema, aggravation of hypertension, hypotension, syncope and collapse, aggravation of coronary artery disease, arrhythmias and AV block, thrombophlebitis, thromboembolism, and adenopathy or lymphadenopathy.
Some of these cardiovascular complications have resulted in fatalities. Myocardial infraction has been associated with other tricyclic compounds.
Liver: Abnormalities in liver function tests, cholestatic and hepatocellular jaundice, hepatitis, very rare cases of hepatic failure.
Pancreatic: Pancreatitis
Respiratory system: Pulmonary hypersensitivity characterized by fever, dyspnea, pneumonitis, or pneumonia.
Genitourinary System: Urinary frequency, acute urinary retention, oliguria with elevated blood pressure, azotemia, renal failure, and impotence. Albuminuria, glycosuria, elevated BUN, and microscopic deposits in the urine have also been reported.
Nervous system: Dizziness, drowsiness, disturbances of coordination, confusion, headache, fatigue, blurred vision, visual hallucinations, transient diplopia, oculomotor disturbances, nystagmus, speech disturbances, abnormal involuntary movements, peripheral neuritis and paresthesias, depression with agitation, talkativeness, tinnitus and hyperacusis.
There have been reports of associated paralysis and other symptoms of cerebral arterial insufficiency, but the exact relationship of these reactions to the drug has not been established.
Isolated cases of neuroleptic malignant syndrome have been reported with concomitant use of psychotropic drugs.
Digestive system: Nausea, vomiting, gastric distress and abdominal pain, diarrhea, constipation, anorexia, and dryness of the mouth and pharynx, including glossitis and stomatitis.
Eyes: Scatered punctuate cortical lens opacities, as well as conjunctivitis, have been reported. Although a direct casual relationship has not been established, many phenothiazines and related drugs have been shown to cause eye changes.
Musculoskeletal system: Aching joints and muscles, and leg cramps.
Metabolism: Fever and chills. Inappropiate antidiuretic hormone (ADH) secretion syndrome has been reported. Cases of frank water intoxication, with decreased serum sodium (hyponatremia) and confusion have been reported in association with Carbamazepine use. Decreased levels of plasma calcium have been reported.
Other: Multiorgan hypersensitivity reactions occurring days to weeks or months after initiating treatment have been reported in rare cases. Signs or symptoms may include, but are not limited to fever, skin rashes, vasculitis, lymphadenopathy, disorders mimicking lymphoma, arthralgia, leucopenia, eosinophilia, hepatosplenomegaly and abnormal liver function tests. Isolated cases of a lupus erythematous-like syndrome have been reported. There have been occasional reports of elevated levels of cholesterol, HDL cholesterol, and triglycerides in patients taking anticonvulsants.
A case of aseptic meningitis, accompanied by myoclonus and peripheral eosinophilia, has been reported in a patient taking carbamazepine in combination with other medications. The patient was successfully dechallenged, and the meningitis reappeared upon rechallenge with carbamazepine."
Contra Indications
"Alextol should not be used in patients with a history of previous bone depression, hypersensitivity to the drug, or known sensitivity to any of the tricyclic compounds, such as amitriptyline, desipramine, imipramine, protriptyline, nortriptyline, etc.
Likewise, on theoretical grounds its use with monoamine oxidase inhibitors is not recommended.
Before administration of Alextol, MAO inhibitors should be discontinued for a minimum of 14 days, or longer if the clinical situation permits.
Co administration of carbamazepine and nefazodone may result in insufficient plasma concentrations of nefazodone and its active metabolite to achieve a therapeutic effect. Co administration of carbamazepine with nefazodone contraindicated.
Drug Interactions
"Cytochrome P450 3A4 (CYP3A4) is the main enzyme catalyzing the formation of Carbamazepine -10,11 epoxide. Co-administration of CYP3A4 inhibitors may result in increased plasma level of carbamazepine, which could induce adverse reactions. Co-administration of CYP3A4 inducer might increase the rate of carbamazepine metabolism, leading to a decrease in serum carbamazepine metabolism, leading to a decrease in serum carbamazepine and, possibly a reduction in therapeutic effect. Similarly discontinuation of CYP 3A4 inducer may decrease the rate of metabolism of carbamazepine serum levels.
Substances that may increase plasma concentration of Alextol:
Isoniazid, verapamil, diltiazem, dextropropoxyphene, viloxazine, fluoxetine, fluvoxamine, possibly cimetidine, acetazolamide, danazole, desipramine (possibly), nicotinamide (in adult only in high dose),
, macrolide antibiotic, (e.g. erythromycin, trolindomycin, josamycin, clarithromycin), derivatives (e.g. itraconazole, ketoconazole, fluconazole), terfenadine, loratadine, grapefruit juice, protease inhibitors for HIV therapy (e.g. retonavir). Since raised plasma carbamazepine concentration may result in adverse effect(dizziness, drowsiness, ataxia, diplopia) the dosage of Alextol should be adjusted accordingly and/or plasma concentrations monitored.
Substances that may decrease plasma concentration of Alextol:
Phenobarbital, primidone, progabide, theophylline, methsuximide, rifampicin, cisplatin or doxorubicin, and although the data are partly contradirectory, possibly also clonazepam, valproic acid orvalpromide.
Oxacarbamazepine, herbal preparations containing St John,s wort (hypericum perforatum).
Plasma phenytion levels have been reported to be both raised and lowered by carbamazepine. On the other hand, valproic acid, valbromide and primidone have been reported to raise the plasma levels of the pharmacologically active metabolite, carbamazepine-10,11 epoxide. Alextol dosage should be adjusted when necessary.
Co-administration of felbamate may decrease the serum carbamazepine -10,11 epoxide plasma carbamazepine concentration should be monitored.
Effect of carbamazepine on plasma level of concomitantly administered substance:
Carbamazepine may lower the plasma concentration, or diminish or even abolish the activity of certain drugs. The dosage of the following drugs may have to be adjusted to clinical requirements, clobazam, clonazepam, ethosuximide, primidone, valproic acid, alprazolam, corticosteroids, (e.g. prednisolone, dexamethazone, ciclosporin, digoxin, doxycycline, felodipine, haloperidol, imipramine, methadone, oral contraceptives (alternative contraceptive method should be used), theophylline, oral anticoagulants, (warfarin, phenprocoumon), felbamate, lamotrigine, zonisamide, tiagabine, topiramate, oxcarbazepine, protease inhibitor for HIV therapy, e.g. indinavir, ritonavir, saquinqvir, calcium channel blockers (dihydropyridine group), e.g. felodipine, itraconazole, levothyroxine, midazolam, olanzapine, products containing estrogens, and /or progestron praziquantil, risperidone, tramadol, ziprasidone.
Combination to be taken into consideration:
Concomitant administration of carbamazepine and paracetamol may reduce the bioavailability of paracetamol.
Concomitant administration of carbamazepine and isoniazid has been reported to result increased hepatotoxicity of isoniazid.
Combined use of carbamazepine and lithium or metoclopramide on the one hand and of carbamazepine and neuroleptics (haloperidol, thioridazine) on the other may lead to an increase in neurological adverse effects (with the latter combination even in the presence of therapeutic plasma concentration).
Concomitant administration of Alextol and some diuretic (hydrochlorothiazide, furosemide) may leadto symptomatic hyponatraemia.
Carbamazepine may antagonize the effects of non-depolarizing muscle relaxants (e.g.pancuranium), the dosage of which may therefore need to be raised. Patients should be monitored closely for unexpected rapid recovery from neuromuscular blockade.
Like other psychoactive drugs, Alextol may reduce alcohol tolerance and abstention from alcohol is therefore advised.
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