Carbamazepine administration

Of the various peptides (e.g. the opioids, vasopressin, substance P and somatostatin) thought to be involved in the actions of carbamazepine, there is evidence that the reduction in the CSF concentration of somatostatin might be important in explaining its effects on cognition and also on the hypothalamo-pituitary-adrenal axis somatostatin is a major inhibitory modulator of this axis and h)rpercortisolism frequently occurs in patients following carbamazepine administration. 

Like most of the agents that block sodium channels, side effects associated with carbamazepine administration involve the central nervous system (CNS). Drowsiness is the most common side effect, followed by nausea, headache, dizziness, incoordination, vertigo, and diplopia. These effects occur particularly when the drug is first taken, but tolerance often develops over a few weeks. There appears to be little risk of cognitive impairment with carbamazepine. 

The effect of steady-state carbamazepine administration on the steady-state pharmacokinetics of ziprasidone has been studied in 25 healthy young adults, in a randomized, placebo-controlled study (112). Carbamazepine caused small reductions in ziprasidone AUCo i2 and Cmax (36% and 27% respectively). The authors concluded that carbamazepine had increased ziprasidone clearance by induction of CYP3A4. 

Crosley CJ, Swender PT. Dystonia associated with carbamazepine administration experience in brain-damaged children. Pediatrics 1979 63(4) 612-15. 

History of bone marrow depression hypersensitivity to carbamazepine and tricyclic antidepressants concomitant use of monoamine oxidase (MAO) inhibitors. Discontinue MAO inhibitors for 2 14 days before carbamazepine administration. 

Benitez-Rosario MA, Salinas Ivfertin A, Gom ez-Ontahon E, Feria M. Methadone-induced respiratory depression after discontinuing carbamazepine administration. J Pain Symptom Manage (2006) 32,99-100. 

Mebendazole is contraindicated in patients witii known hypersensitivity. Mebendazole is also contraindicated during pregnancy (Category C). The drug, like albendazole, has exhibited embryotoxic and teratogenic effects in experimental animals. Administration of mebendazole with tiie hydantoins and carbamazepine may reduce plasma levels of mebendazole. 

Pharmacotherapy is the cornerstone of acute and maintenance treatment of bipolar disorder. Mood-stabilizing drugs are the usual first-choice treatments and include lithium, divalproex, carbamazepine, and lamotrigine. Atypical antipsychotics other than clozapine are also approved for treatment of acute mania. Lithium, lamotrigine, olanzapine, and aripiprazole are approved for maintenance therapy. Drugs used with less research support and without Food and Drug Administration (FDA) approval include topiramate and oxcarbazepine. Benzodiazepines are used adjunctively for mania. 

Introduced in clinical practice in the 1960s, lithium was the first mood stabilizer to be used in China. This was followed by carbamazepine and sodium valproate. For many years, these were the only treatment options available as mood stabilizers. Although lamotrigine was approved for maintenance treatment of bipolar I disorder in 2003 by FDA (Food and Drug Administration) in the USA, this indication has not yet been approved by the Chinese authorities. At present, only one atypical antipsychotic drug, risperidone, has been approved for treating acute mania (February 2005 by SFDA [State Food and Drug Administration]) in China (see Table 6.1). 

E. Gavini, A. B. Heqqe, G. Rassu, V. Sanna, C. Testa, G. Pirisino, J. Karlsen, and P. Giunchedi. Nasal administration of carbamazepine using chitosan microspheres in vitro/in vivo studies. Int J Pharm 307 9-15 (2006). 

Anti-epileptic drugs, such as phenytoin, carbamazepine and valproate, may lead to neural tube defects if administered during pregnancy. Concurrent administration of folate supplements, such as folic acid, is recommended. 

Carbamazepine is an anti-epileptic, which may also be used in the treatment of trigeminal neuralgia. Monitoring of carbamazepine plasma concentrations is required if high doses are administered as carbamazepine tends to be an autoinducer, meaning that the half-life is shortened following repeated administration of the drug. 

Theophylline is a narrow therapeutic index drug with significant difference in bioavailability following oral administration. The half-life of the drug is increased by heart failure, cirrhosis and viral infections, in elderly patients, and by certain drugs, such as cimetidine, ciprofloxacin, oral contraceptives and fluvoxamine. The half-life is decreased in smokers, chronic alcoholism, and by certain drugs, such as phenytoin, rifampicin and carbamazepine. 

Q63 When d ispensing carbamazepine tablets it is prudent to avoid changing the formulation. Carbamazepine is absorbed slowly and erratically after oral administration. 

Valproate, carbamazepine, and other anticonvulsants pose teratogenic risks. Despite this, treatment should continue during pregnancy, as the potential threat to the fetus by a seizure is greater However, it is mandatory to administer the lowest dose affording safe and effective prophylaxis. Concurrent high-dose administration of folate may... 

Conversion from conventional tablets to extended-release (ER) tablets ER carbamazepine is for twice daily administration. When converting patients from conventional tablets to ER tablets, administer the same total daily mg dose of ER carbamazepine. Swallow ER tablets whole never crush or chew. Inspect ER tablets... 

Oral absorption of carbamazepine is quite slow and often erratic. Its half-life is reported to vary from 12 to 60 hours in humans. The development of blood level assays has markedly improved the success of therapy with this drug, since serum concentration is only partially dose related. Carbamazepine is metabolized in the liver, and there is evidence that its continued administration leads to hepatic enzyme induction. Carbamazepine-10,11-epoxide is a pharmacologically active metabolite with significant anticonvulsant effects of its own. 

Most of the drug interactions with carbamazepine are related to its effects on microsomal drug metabolism. Carbamazepine can induce its own metabolism (autoinduction) after prolonged administration, decreasing its clearance rate, half-life, and serum concentrations. The possibility of autoinduction requires the clinician to reevaluate the patient s blood levels after a month of carbamazepine therapy. The autoinduction phenomenon is over in about a month. 

Praziquantel is readily absorbed (80% in 24 hours) after oral administration, with serum concentrations being maximal in 1 to 3 hours the drug has a half-life of 0.8 to 1.5 hours. Its bioavailability is reduced by pheny-toin or carbamazepine and increased by cimetidine. Dexamethasone decreases plasma praziquantel levels by 50%. Praziquantel is excreted by the kidneys. 

Contraindications Co-administration of terfenadine, astemizole, cisapride, pimozide, or carbamazepine hypersensitivity to other phenylpiperazine antidepressants those who were withdrawn from nefazodone due to evidence of hepatic injury use within 14 days of MAOIs... 

Contraindications Concurrent administration of carbamazepine ergot alkaloids pimozide or quinidine( may cause prolonged QT interval or torsades depointes) rifabutin rifampin orsirolimus... 

Baf MH, Subhash MN, Lakshmana KM, et al Alterations in monoamine levels in discrete regions of rat brain after chronic administration of carbamazepine. Neurochem Res 19 1139-1143, 1994... 

Lenox RH, Manji HK Lithium, in The American Psychiatric Press Textbook of Psychopharmacology. Edited by Nemeroff C, Schatzberg A. Washington, DC, American Psychiatric Press, 1995, pp 303-349 Lenox RH, Watson DG Lithium and the brain a psychopharmacological strategy to a molecular basis for manic-depressive illness. Chn Chem 40(2 309-314, 1994 Lenox RH, Watson DG, Patel J, et al Chronic lithium administration alters a prominent PKC substrate in rat hippocampus. Brain Res 570 333-340, 1992 Lenzi A, Lazzerini F, Grossi E, et al Use of carbamazepine in acute psychosis a controlled study. J Int Med Res 14 78-84, 1986 Leonard BE Commentary on the mode of action of benzodiazepines. J Psychiatr Res 27 (suppl 1) 193, 1993... 

Clozapine is contraindicated in patients who have myeloprohf-erative disorders or who are immunocompromised as a result of diseases such as active tuberculosis or human immunodeficiency virus infection because of their increased risk for agranulocytosis. Concomitant administration of medications that are associated with bone marrow suppression, such as carbamazepine, is also contraindicated. 

Quetiapine is metabolized by hepatic CYP 3A3/4. Concurrent administration of cytochrome P450-inducing drugs, such as carbamazepine, decreases blood levels of quetiapine. In such circumstances, increased doses of quetiapine are appropriate. Quetiapine does not appreciably affect the pharmacokinetics of other medications. Pharmacodynamic effects are expected if quetiapine is combined with medications that also have antihistaminic or a-adrenergic side effects. Because of its potential for inducing hypotension, quetiapine also may enhance the effects of certain antihypertensive agents. 

Alcohol, nicotine, and most anticonvulsants induce a number of CYP enzymes (39, 40). This mechanism explains why barbiturates and carbamazepine induce the metabolism of other drugs as well as their own (i.e., autoinduction ). Blood levels obtained 3 or 4 days after starting these drugs reflect the rate of elimination at that time however, levels will subsequently fall on the same dose because autoinduction results in faster elimination (i.e., a shorter half-life) as a function of continued drug administration. Therefore, early TDM of carbamazepine will overestimate the eventual concentration reached after several weeks on the drug (see the section Alternatiye T[eatm in Chapter 10). 

Cyclosporin is metabolised by the hepatic cytochrome P-450 enzyme system, and enzyme induction by phenobarbital, phenytoin, carbamazepine, or rifampicin will drastically increase the clearance of cyclosporin. Concurrent administration of these drugs has caused rejection of transplanted organs. Conversely, the use of enzyme inhibitors, such as erythromycin or the azole antifungal agents, e.g. ketoconazole, will increase the blood concentrations of cyclosporin leading to an increased risk of toxic side effects. 

The rate of absorption of carbamazepine varies widely among patients, although almost complete absorption apparently occurs in all. Peak levels are usually achieved 6-8 hours after administration. Slowing absorption by giving the drug after meals helps the patient tolerate larger total daily doses. 

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