Modified-release drug products

"Many terms are used to describe modified-release products including extended-release, prolonged-release, controlled-delivery, slow-release and sustained-release. These preparations, by definition, have a reduced rate of release of active substance. In general, these terms are interchangeable.



Delayed-release products are modified-release, but by definition are not extended-release. They involve the release of discrete amount(s) of drug some time after drug administration, e.g. enteric-coated products, and exhibit a lag time during which little or no absorption occurs...



Extended-release products contain a higher drug load and thus any loss of integrity of the release characteristics fo the dosage form has potential problems. While some extended-release products can be divided to provide half-d0ses..., others should only be taken whole... Modified-release products should never be crushed or chewed as the slow-release characteristics may be lost and toxicity may result. This is particularly important in patients unable to swallow whole tablets, a problem commonly affecting the elderly. The larger size of extended-release products may cause difficulties in ingestion or transit through the gut. These problems may result in some drugs... causing local tissue damage in patients who have a pathological or drug-induced reduction in gut motility."



Source: Oral extended-release products by Lloyd N. Sansom, Head, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide

(http://www.australianprescriber.com/magazine/22/4/88/90/)

Drug products that should not be broken, divided, chewed or crushed

Bisacodyl (Dulcolax) 5 mg Enteric Coated Tablet

Mfr./Dist: Interphil Labs., Inc.

Butamirate Citrate (Sinecod Forte) 50 mg Sustained-release Tablet

Mfr./Dist.: Interphil Labs., Inc./Novartis

Felodipine (Versant-XR) 5 mg Extended Release Tablet

Mfr./Distr.: Standard Chem.& Pharm.Co., Ltd./United Labs., Inc./L.R. Imperial, Inc.

Ferrous Sulfate (Sorbifer Durules) 500 mg Sustained Release Tablet

Mfr.: AstraZeneca

Furosemide 40 mg/Potassium Chloride 600 mg (Diumide-K) Continus Tablet (Controlled-Release)

Mfr./Dist: NAPP Lab., Inc/Pascual/Mundipharma

Gliclazide (Glubitor-OD) 30 mg Modified-Release Tablet

Mfr./United Lab., Inc./L.R Imperial, Inc.)

Nifedipine (Adalat GITS 30) 30 mg Extended Release Tablet

Mfr.: Bayer AG/Bayer Phils., Inc.

Nifedipine (Calcibloc OD) 30 mg Coated Tablet

Mfr.: Bayer AG/Bayer Phils., Inc./Therapharma

Oxycodone HCl (Oxycontin) 10 mg, 20 mg, 40 mg, 80 mg Controlled-Release Tablets

Mfr./Dist: Bard Pharmaceuticals, Ltd.Mundipharma/Pascual/Zuellig Pharma Corp.

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Drug products that may be divided (split) but should not be chewed or crushed

Isosorbide-5-Mononitrate (Imdur Durules) 30 mg and 60 mg Sustained Release Tablets

Mfr.: AstraZeneca

Theophylline (Theo-Dur) 200mg and 300 mg Sustained-Release Tablets

Mfr./Dist.: Valpharma S.A./AstraZeneca

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Note: The above list is incomplete.

Benzyl alcohol as preservative in drug products

Benzyl alcohol, another preservative, has been linked to "a number of neonatal deaths and severe respiratory and metabolic complications in low-birth-weight premature infants." Most drugs have very low levels of benzyl alcohol and are not suspected of causing infant complications, although the [American Academy of Pediatrics] note that "the effects of lower amounts... have not been adequately studied."

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Source: http://www.personalmd.com/news/a1997021009.shtml

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Benzyl alcohol gasping syndrome may occur due to a decrease in glycine conjugation seen in neonates and accumulation of benzoic acid.
Remember from class: Glycine conjugation is decreased in neonates and reaches adult levels at approximately 8 weeks of age. Because of decreased glycine conjugation, benzoic acid can accumulate in newborns given excess benzyl alcohol or benzoic acid.
Benzyl alcohol--> benzoic acid ----> glycine conjugation-----> hippuric acid.
This accumulation of benzoic acid results in the "benzyl alcohol gasping syndrome" with deterioration of multiple organ systems, severe metabolic acidosis and gasping respirations. This is a dose related syndrome and has been reported with doses of benzyl alcohol greater than 99 mg/kg. Because of this syndrome, the FDA now recommends that drugs containing benzyl alcohol or benzoic acid as preservatives should NOT be used in neonatal nurseries.
Therefore, one should USE PRESERVATIVE FREE MEDICATIONS FOR NEONATES.

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Source: http://www.uic.edu/classes/pmpr/pmpr652/Final/krauss/pedsdevcase.html

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Drug products containing benzyl alcohol as preservative:

Heparin Sodium (Heparin Leo Injection) 1,000 i.u., 5,000 i.u., 25,000 i.u.

Mfr./Distr.: Leo Pharmaceutical Products/Zuellig Pharma. Corp.

Polyethoxylated castor oil in Vitamin K products

Studies in animals given polyethoxylated castor oil have shown a severe anaphylactic reaction associated with histamine release. Strong circumstantial evidence implicates polyethoxylated castor oil in similar reactions in humans. Polyethoxylated castor oil, when given to patients over a period of several days, can also produce abnormal lipoprotein electrophoretic patterns, alterations in blood viscosity and erythrocyte aggregation (red blood cell clumping).

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Source: Vitamin K: A literature review by Karin Rothville DipCBEd (http://www.whale.to/a/rothville.html

Vitamin K product containing polyethoxylated castor oil as non-ionic surfactant:

Phytomenadione (Cycomin) 10 mg/mL Injection

Mfr./Distr.:Rotexmedica, GmbH/Duopharma Trade Phils., Inc.

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Note: If you know of any drug product containing polyethoxylated castor oil that is available in the Philippines, kindly e-mail at pinoypharmacist@yahoo.com. Your contribution will be highly appreciated.