PharmAssist Notes

Common examples of adverse reactions to excipients

2011-11-01T04:00:00.000-07:00

Excipient: Tartrazine
Function: Colouring agent
Caution in practice: Reported cases of hypersensitivity, and hyperkinetic activity in children

Excipient: Aspartame
Function: Sweetener
Caution in practice: Caution in patients with phenylketonuria

Excipient: Benzalkonium chloride
Function: Preservative
Caution in practice: Bronchoconstriction (nebuliser solutions) and ocular toxicity (soft contact lens solutions)

Excipient: Sodium metabisulphite
Function: Antioxidant
Caution in practice: Hypersensitivity, including bronchospasm and anaphylaxis, are reported for all sulphites

Excipient: Propyl gallate
Function: Antioxidant
Caution in practice: Contact sensitivity and skin reactions

Excipient: Lactose
Function: Tablet filler
Caution in practice: Caution in patients with galactosaemia, glucose-galactose malabsorption syndrome, or lactase deficiency

Excipient: Sesame oil
Function: Oil (injections)
Caution in practice: Hypersensitivity reactions reported

Excipient: Lanolin (wool fat)
Function: Emulsifier (topical products)
Caution in practice: Skin hypersensitivity reactions, caution in patients with known sensitivity

http://www.australianprescriber.com/upload/pdf/articles/1207.pdf

Statins administration

2011-10-27T08:55:00.000-07:00

"... Given that cholesterol is biosynthesized in the early morning hours, the US Food and Drug Administration (FDA) has recommended evening administration for statins with shorter half-lives (lovastatin 2 hours, simvastatin < 5 hours, and fluvastatin < 3 hours). In contrast, the FDA suggested daytime administration for statins with longer half-lives (atorvastatin 14 hours, rosuvastatin 19 hours, and pravastatin 22 hours). Atorvastatin also has active metabolites with half-lives ranging from 20 to 30 hours, which may contribute to the fact that it can be taken at any time."

http://www.medscape.com/viewarticle/552756?src=mp

Aluminum- and magnesium-based antacids

2010-11-05T07:47:00.001-07:00

Aluminum-based antacids cause constipation, and magnesium-based products cause diarrhoea. When combination products are used, diarrhoea tends to predominate as a side effect. Although these are termed 'non-absorbable', a proportion of aluminum and magnesium is absorbed and the potential for toxicity exists, particularly with coexistent renal failure.

__________

Source: Clinical Pharmacy and Therapeutics, 4th ed. by Roger Walker and Cate , p. 164

Drugs causing dyspepsia

2010-10-26T06:57:00.000-07:00

NSAIDs including aspirin

Corticosteroids

Bisphosphonates

Potassium chloride

Iron

Antibiotics

Calcium channel blockers

Nitrates

Theophylline

Drugs with antimuscarinic effects, e.g. tricyclic antidepressants

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Source: Clinical Pharmacy and Therapeutics, 4th ed. by Roger Walker and Cate Whittlesea, p. 152.

Acidosis and dopamine

2010-10-04T07:01:00.000-07:00

"If you're monitoring a patient receiving dopamine (Intropin) and the dopamine isn't raising his blood pressure as expected, check the patient's pH. A pH level below 7.1, which can happen in severe metabolic acidosis, causes resistance to vasopressor therapy. Correct the pH level and the dopamine may be more effective."

_________________
Source: Expert LPN Guides: Fluids & Electrolytes (2007), p.169.

Challenges to raising potassium level

2010-10-02T01:11:00.000-07:00

If you're having difficulty raising a patient's potassium level, reevaluate his fluid and electrolyte status and ask yourself the following questions:

Is the patient still experiencing diuresis or suffering losses from the GI tract or the skin? If so, he's losing fluid and potassium.

Is the patient's magnesium level normal or does he need supplementation? Keep in mind that low magnesium levels make it difficult for the kidneys to conserve potassium.

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Source: Expert LPN Guides: Fluids & Electrolytes (2007), p. 91.

Causes of hypokalemia

2010-10-02T00:10:00.000-07:00

Shift of potassium to the intracellular compartment

Acute alkalosis

Following correction of metabolic acidosis (e.g., diabetic acidosis)

Hypokalemic periodic paralysis

Insulin administration

Administration of beta 2-agonists

Conditions of catecholamine excess

Cardiac surgery
Myocardial infarction
Delerium tremens

Barbiturate intoxication

Vitamin B12 therapy

Thyrotoxicosis (rare)

Inadequate potassium intake (uncommon because of renal conservation of potassium)

Starvation

Postoperative state without replenishment

Gastrointestinal potassium loss

Diarrhea

Laxative abuse

Villous adenoma of rectum

Vomiting

Fistulas

Renal potassium loss (renal cause of hypokalemia should be sought if the urinary loss of potassium exceeds 20mEq/day)

Osmotic diuresis

Magnesium depletion

Acute leukemia

Antimicrobial agents (such as carbenicillin, gentamicin, amphotericin B)

Cisplatin administration

Renal conditions with metabolic acidosis

Distal renal tubular acidosis
Proximal renal tubular acidosis
Ureterosigmoidostomy
Administration of acetazolamide

Conditions with metabolic acidosis

Cushing's syndrome
Exogenous corticosteriod administration
Primary aldosteronism
Licorice usage
Renovascular hypertension
Malignant hypertension
Renin-producing renal tumor
Diuretics (thiazides, furosemide)
Liddle's sydrome
Bartter's sydrome

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Source: the portable internist by Anthony J. Zollo Jr., MD (1995), p. 328-329.

Metoclopramide and paracetamol

2010-09-29T06:22:00.000-07:00

"Metoclopramide increases gastric emptying and increases the absorption rate of paracetamol, an effect which is used to therapeutic advantage in the treatment of migraine."

Source: Clinical Pharmacy and Therapeutics, 4th ed. by Roger Walker and Cate Whittlesea

Digoxin and drugs that inhibit P-glycoprotein

2010-09-29T06:14:00.000-07:00

"Digoxin is a substrate of P-glycoprotein and drugs that inhibit P-glycoprotein, such as verapamil, may increase digoxin bioavailability with the potential for digoxin toxicity (DuBuske 2005)."

Source:Clinical Pharmacy and Therapeutics, 4th ed. by Roger Walker and Cate Whittlesea

Bisphosphonates and calcium supplements

2010-09-29T06:08:00.000-07:00

"Bisphosphonates are often co-prescribed with calcium supplements in the treatment of osteoporosis. If these are taken concomitantly, however, the bioavailability of both is significantly reduced, with the possibility of therapeutic failure."

Source: Clinical Pharmacy and Therapeutics, 4th ed. by Roger Walker and Cate Whittlesea, p. 42.

Simvastatin and grapefruit juice

2010-09-29T05:57:00.000-07:00

"...[Patients] prescribed simvastatin should be advised not to drink grapefruit juice due to the increased risk of statin-induced adverse effects such as myopathy. Grapefruit juice inhibits cytochrome P450 3A4, which is involved in simvastatin's metabolism."

Source: Clinical Pharmacy and Therapeutics, 4th ed. by Roger Walker and Cate Whittlesea, p.40.

Weight gain and drugs for diabetes mellitus

2010-09-26T02:48:00.000-07:00

"Unlike the sulfonylureas, insulin, and the thiazolidinediones, [alpha]-glucosidase inhibitors do not cause weight gain."

Source: Modern Pharmacology with Clinical Applications, 5th ed. by Charles R. Craig and Robert E. Stitzel, p. 775.

Mixing Insulin Glargine with other form of insulin

2010-09-26T02:32:00.000-07:00

"Because it is necessary to maintain its acidic pH prior to injection, insulin glargine must not be mixed with any other form of insulin during injection."

Source: Modern Pharmacology with Clinical Applications, 5th ed. by Charles R. Craig and Robert E. Stitzel, p. 770.

Metformin and lactic acidosis

2010-09-26T02:18:00.000-07:00

"Metformin can cause lactic acidosis, but its occurrence is rare except when renal failure, hypoxemia, or severe congestive heart failure is present or when coadministered with alcohol."

Source: Modern Pharmacology with Clinical Applications, 5th ed. by Charles R. Craig and Robert E. Stitzel, p. 773.

Modified-release drug products

2007-07-12T21:04:00.000-07:00

"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

2007-07-07T19:13:00.000-07:00

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."

____________

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.

___________

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

2007-07-07T00:27:00.000-07:00

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.

Aspartame-Containing Drug Products

2007-06-29T02:20:00.000-07:00

Acetylcysteine (Fluimucil) 100 mg and 200 mg granulates (Zambon Switzerland Ltd./The Cathay Drug Co., Inc.)

Acetylcysteine (Fluimucil) 600 mg effervescent tablets (Zambon Switzerland Ltd./The Cathay Drug Co., Inc)

CalciumCarbonate (Calsan) 1.25 g (500 mg elemental calcium) chewable tablet (Interphil Laboratories/Diethelm Phils. Inc)

Ranitidine (Zantac FR) 150 mg effervescent tablet (GlaxoSmithKline) - contains 30 mg aspartame

Ranitidine (Zantac FR) 300 mg effervescent tablet (GlaxoSmithKline) - contains 45 mg aspartame

Sodium-Containing Drug Products

2007-06-29T01:58:00.000-07:00

Calcium Carbonate (Calsan) 1.25 g (500 mg elemental Calcium) chewable tablet (Interphil Laboratories, Inc./Diethelm Phils., Inc.) - contains 4.29 mg (0.18 mmol) of Sodium

Piperacillin Sodium/Tazobactam Sodium (Tazocin) 2g/250 mg vial (Wyeth) - contains 4.69 mEq (108 mg) of Sodium

Piperacillin Sodium/Tazobactam Sodium (Tazocin) 4g/500 mg vial (Wyeth) - contains 9.39 mEq (216 mg) of sodium

Ranitidine (Zantac FR) 150 mg effervescent tablet (GlaxoSmithKline) - contains 14.3 mEq (328 mg) of sodium

Ranitidine (Zantac FR) 300 mg effervescent tablet (GlaxoSmithKline) - contains 20.8 mEq (479 mg) of sodium

Iberet FT and Iberet Active

2007-03-19T06:16:00.000-07:00

...IBERET FT and IBERET ACTIVE are one and the same. There has been no reformulation whatsoever, simply a change in packaging and name. Just like Iberet FT, Iberet Active contains:

525 mg Ferrous Sulfate (elemental iron, 105 mg)
6 mg Thiamine (Vitamin B1)
6 mg Riboflavin (Vitamin B2)
30 mg Nicotinamide
5 mg Pyridoxine (vitamin B6)
25 mcg Cyanocobalamin (Vitamin B12)
10 mg Calcium Pantothenate
500 mg Ascorbic Acid (Vitamin C)

_______________

Source: Letter of Mr. Bernardo L. Pacheco of Abbott Laboratories addressed to the pharmacists of the the Philippine General Hospital dated March 1, 2007.

Tartrazine-containing drug products

2007-03-07T00:21:00.000-08:00

Patients who are sensitive to aspirin may also be sensitive to tartrazine, a yellow dye used in medicines and foods. Symptoms of an allergic reaction (urticaria, rhinitis, or asthma) may occur after exposure to many chemicals used to colour, flavour, or preserve food and drugs, but tartrazine (FD & C yellow No. 5) is the colour most frequently incriminated. Intolerance to tartrazine was first reported in 1959, and its part in induction of intractable urticaria has been recognised since 1975. Non-thrombocytopenic purpura is also reported to be due to hypersensitivity to tartrazine---which suggests the possibility that tartrazine may act as a hapten bound to the endothelial cells of small blood vessels.

Source: "Sensitivity to tartrazine" at
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1500754&blobtype=pdf

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Tartrazine-containing Drug Products Available in the Philippines*

Metronidazole (Pharex Metronidazole) 250 mg and 500 mg tablet

Mfr/Dist..: Pascual Lab., Inc./Pharex HealthCorp

________________

* If you know of a drug product containing tartrazine available in the Philippines, kindly inform the pinoypharmacist through your comment or by e-mail (pinoypharmacist@yahoo.com)

All about drug-induced hyponatraemia

2007-03-01T00:49:00.000-08:00

Articles about drug-induced hyponatraemia:

"Managing drug-induced hyponatraemia in adults"
at http://www.australianprescriber.com/magazine/26/5/114/7/

"Drug-induced hyponatraemia" (Letters) at http://www.australianprescriber.com/magazine/27/2/28/33/

Drugs that can cause hyponatraemia:*

"Tramadol and hyponatraemia" (Medicinal mishap) at http://www.australianprescriber.com/magazine/27/4/artid/495/

"Severe hyponatraemia associated with omeprazole" (Medicinal mishap) at
http://www.australianprescriber.com/magazine/28/2/48/9/

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* Not a complete list.

Prescriptions for intravenous potassium chloride

2007-02-28T01:27:00.002-08:00

"The pharmacist who receives a prescription for intravenous potassium chloride must be careful and check the amount of potassium chloride in the prescription and the infusion rate at which the drug is to be administered to the patient. The usual additive dilution of potassium chloride is 40 mEq/liter of intravenous fluid. The maximum desirable concentration is 80 mEq/liter of potassium chloride, although severe emergencies may dictate greater concentrations. The maximum infusion rate should not exceed 40 mEq per hour with a maximum24-hour dose not exceeding 400 mEq of potassium chloride. Because of its potent ECG effects, when infused it is wise to monitor the patient's ECG, and to check the patient's serum potassium level after the first 50 to 100 mEq of potassium chloride are administered."

Source: Pharmaceutical Dosage Forms and Drug Delivery Systems, 6th ed. by Ansel, Howrd C., et. al., page 325.

"The risks associated with intravenous potassium chloride are well known. If it is injected too rapidly or in too high a dose, it may cause cardiac arrest within minutes. The effect of hyperkalaemia on the heart is complex - virtually any arrhythmia may be observed."

Source: "High-risk medication alert: intravenous potassium chloride" at http://www.australianprescriber.com/magazine/28/1/14/6/

Example of prescriptions for intravenous potassium chloride we encountered:

Potassium Chloride 120 mEq in PNSS 1L x 12 H
Potassium Chloride 200 mEq in PNSS 200 cc x 16 H

Lactose-containing drug products

2007-02-23T01:36:00.000-08:00

"We should remember that we are NOT just prescribing the active ingredient when we prescribe. There is the issue of varying particle size and varying excipients that may make a difference. For example, I once had a psychotic patient with lactose intolerance and I had to work to identify which brands (or even which strengths of the same brand) of antipsychotics were lactose free..." -- R.J. Taylor, Psychiatrist

Source: http://www.australianprescriber.com/magazine/28/4/84/7/

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LACTOSE-CONTAINING DRUG PRODUCTS AVAILABLE IN THE PHILIPPINES*

Amphotericin B USP, 5% (w/w) (Amphocil) 50 mg (50,000 I.U.); 100 mg (100,000 I.U. vial

Mfr./Dist.: Ben Venue Laboratories Inc./Mayne Pharma Pty. Ltd.

Celecoxib (Coxid) 100 or 200 mg capsule

Mfr./Dist.: Searle Ltd./Biomedis

Clarithromycin (Klaricid O.D.) 500 mg Modified Release tablet

Mfr.: Abbott

Domperidone (Motilium) 10 mg film-coated tablet

Mfr./Distributor: Interphil Laboratories, Inc./JANSSEN PHARMACEUTICA

Gabapentin (Neurontin) 100 mg, 300 mg or 400 mg capsule

Mfr.:Pfizer

Lactulose (Duphalac) 3.3 g/5 mL Syrup (Contains , 0.9 g of lactose per 15 mL)

Mfr./Interphil Laboratories, Inc./Solvay Pharma, Inc., Phils

Methylergometrine hydrogen maleate (Methergin) 0.125 mg sugar-coated tablet

Mfr.: Novartis

Moxifloxacin (Avelox) 400 mg film-coated tablet

Mfr.: Bayer

Nifedipine (Calcibloc OD) 30 mg coated tablet

Mfr./Dist.: Bayer/Therapharma

Risperidone (Risperdal) 1 mg, 2 mg, 3 mg or 4 mg tablet

Mfr./Dist.: JANSSEN-CILAG SpA/Zuellig Pharma Corp.

Tramadol HCl (Tramundin IR) 50 mg immediate-release tablet

Mfr./Dist.: Mundipharma GmgH/Zuellig

_______________________

*Note: The above list is incomplete. If you know of a lactose-containing drug product, feel free to inform me through your comments or by writing me through my e-mail address at pinoypharmacist@yahoo.com. Your contributions will be highly appreciated.

Chlorhexidine-toothpaste interaction

2007-02-17T18:12:00.000-08:00

"... The efficacy of chlorhexidine may be reduced by toothbrushing and rinsing because of a chemical interaction. The interval between toothbrushing and rinsing should therefore be at least 30 minutes."

___________________
Source: "Management of drug-induced gingival enlargement" at http://www.australianprescriber.com/magazine/26/1/11/3/

Epinephrine products expressed as ratio strengths

2007-02-17T00:50:00.000-08:00

Medication errors have occurred due to confusion with epinephrine products expressed as ratio strengths (eg 1:1000 vs 1:10,000.

Epinephrine 1:000 = 1mg/mL and is most commonly used SubQ.

Epinephrine 1:10,000 = 0.1 mg/mL and is used I. V.

____________________
Source: Lexi-Comp's Pediatric Dosage Handbook, 12th ed. by Carol K. Taketomo, PharmD, et al. 2005, p. 486.

Bioavalability problems with some drug products

2006-06-06T23:13:00.000-07:00

It should not be assumed that every generic drug product is as satisfactory as the trade-named product, though most generics are satisfactory. Bioavailability - the effective absorption of the drug product - varies between manufacturers and sometimes between different lots of a drug produced by the same manufacturer. In the case of a very small number of drugs, which usually have a low therapeutic index,poor solubility, or a high ratio of inert ingredients to active drug content, a specific manufacturer's product may give more consistent results. In the case of life-threatening diseases, the advantages of generic substitution are probably outweighed by the clinical urgency so that the prescription should be filled as written.

Source: Basic and Clinical Pharmacology, 8th ed. Bertram G. Katzung, ed. 2001 McGraw-Hill p. 1112 New York.

Related References:

"Generics - equal or not?" at http://www.australianprescriber.com/magazine/26/4/85/7/

"Quality use of generic medicines" at http://www.australianprescriber.com/magazine/27/4/80/1/

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DRUGS REQUIRING STRICT PRECAUTION IN PRESCRIBING, DISPENSING AND USE BECAUSE OF BIOAVAILABILITY PROBLEM AND AVAILABILITY IN PHILIPPINE MARKET IN SEVERAL BRANDS/MANUFACTURERS; PRESCRIPTION MUST BE FILLED ACCORDING TO THE SPECIFIED INTERNATIONAL NON-PROPRIETARY NAME (INN) AND BRAND NAME (B)

Total no. of drugs = 24

Core List = 16

Complementary List = 8

A. Core List

Atenolol

Carbamazepine

Dexamethasone

Diltiazem

Esmolol

Gliclazide

Haloperidol

Levothyroxine

Lithium Carbonate

Metformin

Metoprolol

Phenytoin

Propranolol

Rifampicin

Valproate disodium/Valproic Acid

Warfarin

B. Complementary List

Bromocriptine

Busulfan

Diltiazem

Felodipine

Gemfibrozil

Theophylline (anhydrous)

Valproate disodium/Valproic Acid

Verapamil

Source: Philippine National Drug Formulary Vol I 6th ed 2005 p. DOH Manila 2005 p. Appendix T p. 167

Sulfite-containing drug products

2006-06-04T15:51:00.000-07:00

In June 1987, [the U.S.] FDA labeling regulations went into effect requiring a warning about possible allergic-type reactions, including anaphylaxis in the package insert for prescription drugs to which sulfites have been added to the final dosage form. Sulfites are used as preservatives in many injectable drugs, such as antibiotics and local anesthetics. Some inhalants and ophthalmic preparations also contain sulfites, but relatively few oral drugs contain these chemicals. The purpose of the regulation is to protect the estimated 0.2% of the population who suffer allergic reactions from the chemicals. Many of the sulfite-sensitive persons suffer from asthma or other allergic conditions. Previous to the regulations dealing with prescription medication, the FDA issued regulations for the use of sulfites in food. Asthmatics and other patients who may be sulfite-sensitive should be reminded to read the labels of packaged foods and medications to check for the presence of these agents.

The most frequent symptom of a sulfite reaction is difficulty breathing. Other symptoms include diarrhea, nausea and vomiting, abdominal pain and cramps, dizziness, wheezing, hives, itching, local swelling, rash, difficulty swallowing, headache, fainting, change in body temperature, chest pain, change in heart rate, unconsciousness and coma. Symptoms usually occur within minutes of ingesting or taking sulfited foods or drug products.

Sulfiting agents covered by the regulations are potassium bisulfite, potassium metabisulfite, sodium bisulfite, sodium metabisulfite, sodium sulfite and sulfur dioxide.

The labeling of drugs to which sulfites have been added to the final dosage form must contain the following statement in the "Warnings" section of the labeling:
"Contains (name of sulfite), a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than nonasthmatic people."

Sulfite-containing epinephrine for injection for use in allergic emergencies must contain the following statement:

"Epinephrine is the preferred treatment for serious allergic or emergency situations even though this product contains (name of sulfite), a sulfite that may in other products cause allergic-type reactions including anaphylactic symptoms or life-threatening or less severe asthmatic episodes in certain susceptible persons. The alternatives to using epinephrine in a life-threatening situation may not be satisfactory. The presence of a sulfite(s) in this product should not deter the administration of the drug for treatment of serious allergic or other emergency situations."

The FDA permits the use of sulfites in prescription products, with the proper labeling, because there are no generally suitable substitutes for sulfites to maintain potency in certain medications.

Source: Pharmaceutical Dosage Forms and Drug Delivery Systems, 6th ed. p. 117-118.

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The Bureau of Food and Drugs issued B.O. 67-B s. 1996, dated June 5 1996 "Requiring the Inclusion of Warning Statement for Products Containing Sodium Metabisulfite and other Derivatives of this Sodium Salt." This, however, is currently not available for viewing in the BFAD web site.

Source: http://www.bfad.gov.ph/

Sulfite-Containing Drug Products Available in the Philippines:*

Contains Sodium metabisulfite:

Amikacin Sulfate (Amikacide) 125 mg/mL Injection; 250 mg/mL Injection

Mfr.: SVP Phils., Inc.

Dexamethasone sodium phosphate (Penodex) 4 mg/ml solution for injection

Mfr./Dist.: ROTEXMEDICA/Duopharma

Epinephrine (Hizon Epinephrine) 1 mg/mL Sterile Solution for Injection

Mfr.: Hizon Laboratories, Inc.

Gentamicin Sulfate (Orimed) 40 mg/ml solution for injection

Mfr./Dist.: Oriental Chemical Works, Inc./Medicamenta, Inc.

Gentamicin Sulfate (Topigen) 40 mg/mL Solution for Injection

Mfr./Dist.: Ashford Pharmaceutical Laboratories, Inc./Vendiz Pharmaceuticals, Inc.

Metoclopramide (Plasil) 5 mg/mL ampule

Mfr./Dist.: Gruppo Lepetit SpA/GSK

Metoclopramide (Pharex Metoclopramide) 10 mg/2ml Injection

Mfr./Dist.: Pascual Laboratories, Inc./Pharex Healthcorp

Noradrenaline (Levophed) 1 mg/mL concentrate solution for Injection

Mfr.: Abbott

Paracetamol (Naprex) 150 mg/mL Solution for Injection (IM/IV) (300 mg/2mL)

Mfr.Dist.: SVP Phils., Inc./Pediatrica, Inc.

Contains Sodium Sulfite:

Paracetamol (Aeknil) 150 mg/mL Solution for Injection IM/IV

Mfr./Dist.: Therapeutic Pharmaceuticals/Medicamenta, Inc.

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* This list is incomplete. If you know a sulfite-containing drug product not included in the above list, kindly inform the pinoypharmacist through your comments or through his e-mail address.

Breaking nifedipine capsules

2006-06-03T16:16:00.000-07:00

"Because nifedipine acts rapidly, especially when given as liquid-containing capsules, symptomatic hypotension and/or orthostatic hypotension can occur and can be associated with rapid heart rate. The practice of breaking nifedipine capsules to speed drug delivery may exacerbate these adverse effects. Indeed, there is no evidence that this approach to administering nifedipine has efficacy in preventing clinically significant endpoints but may increase the risks of adverse events and unpredictable reductions in blood pressure, especially in patients with severe hypertension or coronary artery disease...

Broken capsules of nifedipine administered sublingually (actually swallowing the contents works faster) has been very extensively used in the treatment of hypertensive urgencies. However, this approach leads to particularly unpredictable large falls in blood pressure that may have severe adverse consequences in terms of tissue ischemia. These include stroke or acute myocardial infarction."

Source: Melmon and Morrelli's Clinical Pharmacology, 4th ed. 2000, p. 83, 90.

Learning with pleasure

2006-06-03T16:04:00.000-07:00

"What we learn with pleasure we never forget."
These are the words of Alfred Mercier and I would like to believe that learning is fun, too.

But although I am almost in my 15 years of being a pharmacist, I still have difficulty in some aspects of my profession. So, I tried to help myself by writing some notes which I intend to share with fellow pharmacists, pharmacy students and interns...

It is my hope that by sharing these notes we could help more patients with the proper use of their medications, prevent medication errors and effectively work with doctors, nurses and other health professionals.

It is my pleasure to welcome you to PharmAssist Notes!!!