Extended-release preparation

Any extended release preparation ° CR—controlled-release ° EC—enteric coated ° LA—long-acting ° SR—sustained release 0 TR—time release ° SA—sustained action ° SL—sublingual ° XL—extended length ° XR—extended release... 

Some extended-release preparations are designed with a coating that responds to the acidity of its environment. The polymeric coating of the medicine is formulated for stability during oral delivery and for eventual solubility at the intended organ. The contrasting acidic content of the stomach and the more basic environment of the intestines enable these formulations to function. For example, hydroxypropyl methylcellulose phthalate (HPMCP) (Fig. 14.1.3) is an enteric... 

In nonacute situations, phenytoin may be initiated in adults at oral doses of 5 mg/kg/day and titrated upward. Subsequent dosage adjustments should be done cautiously because of nonlinearity in elimination. Most adult patients can be maintained on a single daily dose, but children often require more frequent administration. Only extended-release preparations should be used for single daily dosing. 

Like bupropion, venlafaxine comes in immediate-release and extended-release preparations. The immediate-release form is taken twice a day starting at 37.5 to 75 mg/day and increased to 75 mg/day after 1 week. The effective dose range is 75-375mg/day. The extended release form is started once daily at 37.5mg/day and is also effective at 75-375 mg/day. The effective dose range is similar to the immediate-release form. 

The recommended dose range is 75-225 mg/day. The extended-release preparation, which allows for once-daily dosing in most pa-... 

Several valproate preparations are available in the United States, including valproic acid, sodium valproate, divalproex sodium, and an extended-release preparation of divalproex sodium. Divalproex sodium is a dimer of sodium valproate and valproic acid with an enteric coating, and it is much better tolerated than other oral valproate preparations. An intravenous preparation also has become available, but it has not been well studied in patients with psychiatric disorders. The half-life of valproate is 9-16 hours. 

Carbamazepine is effective in both acute and prophylactic treatment of mania (Weisler et al. 2005). An extended-release formulation of carbamazepine, available since 1997 for treatment of epilepsy, was approved in 2004 under the brand name Equetro. Extended-release preparations are preferred because simplified dosage schedules facilitate patient adherence. Other extended-release carbamazepine preparations include Tegretol XR and Carbatrol, although neither has been specifically indicated for the treatment of bipolar disorder. The longer-acting preparations are also of benefit because they tend to have fewer gastrointestinal side effects. 

Theophylline Uncertain phosphodiesterase inhibition t adenosine receptor antagonist Bronchodilation, cardiac stimulation, increased skeletal muscle strength (diaphragm) Asthma, COPD Oral duration 8-12 h but extended-release preparations often used Toxicity. Multiple (see text)... 

The sodium salt of valproate is marketed in Europe as a tablet and is quite hygroscopic. In Central and South America, the magnesium salt is available, which is considerably less hygroscopic. The free acid of valproate was first marketed in the USA in a capsule containing corn oil the sodium salt is also available in syrup, primarily for pediatric use. An enteric-coated tablet of divalproex sodium is also marketed in the USA. This improved product, a 1 1 coordination compound of valproic acid and sodium valproate, is as bioavailable as the capsule but is absorbed much more slowly and is preferred by many patients. Peak concentrations following administration of the enteric-coated tablets are seen in 3-4 hours. Various extended-release preparations are available not all are bioequivalent and may require dosage adjustment. 

Acetaminophen, also known as paracetamol in other countries, is available widely without prescription as an analgesic and antipyretic. It is available in various oral dosage forms, including an extended-release preparation. Acetaminophen may be combined with other drugs, such as antihistamines or opioid analgesics, and marketed in cough and cold preparations, menstrual remedies, and allergy products. 

The recommended guidelines for baseline and routine laboratory testing for lithium are listed in Table 68-12. The 12-hour postdose lithium serum concentration may be 12% to 33% higher with extended-release preparations and lower with regular-release tablets with divided dosage schedules. The dose should be adjusted based on the steady-state serum concentration drawn 12 hours ( 30 minutes) after the last dose. A therapeutic trial (lithium serum concentrations of 0.6 to 1.2 mEq/L) should last a minimum of 4 to 6 weeks. Acutely manic patients may require serum concentrations of 1 to 1.2 mEq/L, and some need up to 1.5 mEq/L to achieve a therapeutic response. Although serum concentrations less than 0.6 mEq/L are associated with higher rates of relapse, some patients may do well at 0.4 to 0.7 mEq/L. For bipolar prophylaxis in elderly patients, serum concentrations of 0.4 to 0.6 mEq/L are recommended because of increased sensitivity to adverse effects. ... 

Extended-release preparations are becoming available with increased duration of... 

OXYCONTIN is an extended-release preparation containing up to 160 mg of oxycodone per tablet and recommended for use every 12 hours. It has been subject to substantial abuse. 

C. Pharmacokinetics. Carbamazepine is slowly and erratically absorbed from the gastrointestinal tract, and peak levels may be delayed for 6-24 hours, particularly after an overdose (continued absorption for up to 96 hours has been reported with extended-release preparations). It is 75-78% protein bound with a volume of distribution (Vd) of approximately 1.4 LAg (up to 3 Ukg after overdose). Up to 28% of a dose is eliminated in the feces, and there is enterohepatic recycling. The parent drug is metabolized by r ochrome P-450, and 40% is converted to its 10,11-epoxide, which is as active as the parent compound. The elimination half-life is variable and is subject to autoinduction of P-450 enzymes the half-life of carbamazepine is approximately 18-55 hours (initially) to 5-26 hours (with chronic use). The half-life of the epoxide metabolite is approximately 5-10 hours. 

Not understood. It seems possible that verapamil inhibits the metabolism of aleohol by the liver, thereby redueing its loss from the body. Aleohol also appears to inhibit the metabolism of nifedipine, and to inerease the bioavailability of felodipine. Red wine may have eaused dose dumping of felodipine from the extended-release preparation whieh altered its phar-maeokinetie profile, but the reason why the felodipine levels remained low until after a meal is unclear. An in vitro study demonstrated that alcohol inhibited the oxidative metabolism of nifedipine by the cytochrome P450 isoenzyme CYP3A. ... 

In a study, 8 non-smoking, healthy subjects were given a single 10-mg dose of an extended-release preparation of felodipine with 250 mL red wine on an empty stomach and 4 hours before a meal. Plasma felodipine levels were lower for the first 4 hours of the study than when taken with 250 mL water, but rose rapidly at 5 hours after dosing, resulting in a peak level that was higher than when taken with water. ... 

In general the opioid analgesics can enhance the CNS depressant effects of alcohol, which has been fatal in some cases this appears to be a particular problem with dextropropoxyphene. Alcohol has been associated with rapid release of hydromorphone and morphine from extended-release preparations, which could result in potentially fatal doses. Acute administration of alcohol and methadone appears to increase the blood levels of methadone. The bioavailability of dextropropoxyphene is increased by alcohol... 

The bioavailabilities of cefadroxil, cefalexin, cefixime, cefprozil, and cefradine are not affected by food. Cefaclor may be given without regard to food but absorption of an extended-release preparation may be increased by food. The bioavailabilities of cefetamet pivoxii and cefuroxime axetil may be increased by administration with food. 

A 40-year-old man from Ghana presented with 6 months of burning sensation in his penis mostly present during urination and sexual intercourse [23 ]. After careful examination of medications, an extended-release preparation of nifedipine (nifedipine XL) was found to be probably related to the adverse effect. Dysuria disappeared after several days of wash-out from nifedipine, and recurred upon restarting nifedipine XL. The pathophysiology of this drug adverse reaction is unknown and has never been reported with non-XL nifedipine. 

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