Livro de Fórmulas Farmacêuticas Extemporâneas

A obra apresenta 521 fármacos e mais de 900 fórmulas de medicamentos manipulados, e suas respectivas estabilidades, preparados a partir de matéria-prima, cápsulas, comprimidos, ampolas, solução para nebulização, spray nasal, ou de outras formas farmacêuticas existentes; estabilidade de líquidos orais fracionados e estocados em seringa dosadora oral âmbar.

Todas as informações sobre a estabilidade das fórmulas do livro Fórmulas Farmacêuticas Extemporâneas foram compiladas e harmonizadas através de consultas e pesquisas em mais de 300 referências bibliográficas e seus respectivos artigos científicos publicados na literatura farmacêutica mundial.

Monografia dos seguintes medicamentos: acebutolol, acetato de alumínio, acetato de cálcio, acetato de zinco, acetazolamida, acetilcisteína, aciclovir, ácido acético, ácido ascórbico, ácido bórico, ácido cítrico, ácido clorídrico, ácido dimercaptosuccinico, ácido etacrínico, ácido fólico, ácido folínico, ácido lático, ácido tranexâmico, ácido tricloroacético, ácido ursodesoxicólico, ácido valpróico, água bicarbonatada, água purificada com conservantes, alantoína, álcool etílico, alendronato, alfa-amilase, alimemazina, almitrina + raubasina, alopurinol, alprazolam, ambroxol, amicacina, amilorida, amilorida + hidroclorotiazida, aminofilina, amiodarona, amitriptilina, amoxicilina, amoxicilina + clavulanato de potássio, ampicilina, anfotericina B, anlodipino, aprepitant, atenolol, atorvastatina, atropina, azatioprina, azitromicina, azul de metileno, azul de toluidina, baclofeno, balsamo de Peru, bambuterol, base de Beeler, base de creme emoliente lavável, base de creme emoliente O/A, base de creme evanescente, base de creme Lanette, base de creme para couro cabeludo, base de pomada cetílica, base de pomada simples BP, base de pomada emulsificante O/A, base de pomada hidrofílica, base de pomada oclusiva lavável, base de pomada oftálmica, base de pomada PEG, base de unguento hidrofílico, base de xampu anfótero, base de xampu aniônico anfótero, base emulsificante aquosa, base tópica oleosa e alcoólica, beclometasona, benazepril, bendrofluazida, benzidamina, betametasona, betanecol, bevacizumabe, bosentan, brometo de ipratrópio, bromfeniramina, budenosida, bupivacaína, bupropiona, bussulfano, cafeína, calcitriol, candesartana, capsaicina,captopril, carbamazepina, carbidopa + levodopa, carbomelose, carbonato de cálcio, carisoprodol, carnitina, carvão ativado, carvedilol, cefaclor, cefadroxila, cefalexina, cefatrizina, cefpodoxima, cefuroxima, celecoxibe, cetamina, cetoconazol, cetoprofeno, ciamemazina, cianocobalamina, ciclofosfamida, ciclosporina, cidofovir, cimetidina, ciproeptadina, ciprofloxacino, ciproterona, cisaprida, citalopram, citrato de lítio, citrato de sódio, claritromicina, clindamicina, clobazam, clobetasol, clobetasona, clobutinol, clonazepam, clonidina, clopidogrel, clorambucila, cloreto de potássio, cloreto de sódio, cloreto férrico, clorexidina, clorexidina + mupirocina, clorfeniramina, clormeprazina, cloroquina, clorotiazida, clorpromazina, clotrimazol, clozapina, codeína, codergocrina, coenzima Q10, colchicina, colecalciferol, colesterol, colestiramina, colistina, creme analgésico, creme base aniônico, creme base de cerato simples, creme base de cold cream, creme base de trietanolamina, creme base não-iônico, creme de cetomacrogol, creme de EDTA, cromoglicato de sódio, dantroleno, dapsona, desmopressina, desonida, dexametasona, dexclorfeniramina, diatrizoato de meglumina, diazepam, diazóxido, diclofenaco de sódio, diclofenaco dietilamônio, didanosina, difenidramina, digoxina, diltiazem, dimenidrinato, dimeticona, dinoprostona,dipiridamol, dipirona, dipirona + escopolamina, disopiramida, dissulfiram, dolasetrona, domperidona, donezepil, doxazosina, doxepina, doxiciclina, efavirenz, emulgel com HPMC, emulsão O/A, emulsão O/A de cetomacrogol, enalapril, eosina, epinefrina, ergocalciferol, escitalopram, escopolamina + dipirona, espiramicina, espironolactona, espironolactona + hidroclorotiazida, estavudina, estradiol, etambutol, etinilestradiol, etionamida, etoposido, etosuximida, famotidina, fenazopiridina, fenilbutirato, fenilefrina, fenilpropanolamina, feniramina, fenitoína, fenobarbital, fenofibrato, fenoterol, fenoxibenzamina, fentanila, fexofenadina, fitomenadiona, flecainida, flucitosina, fluconazol, fludrocortisona, flufenazina, flunisolida, fluoresceína, fluoxetina, fosfato de sódio, furosemida, gabapentina, galantamina, gel de carbopol, gel de carbopol hidroalcoólico, gel de carboximetilcelulose, gel de metilcelulose, gel hidroalcoólico, gel para ultrassonografia, gentamicina, glibenclamida, gliburida, glicerol, glicina, glicopirrolato, glucobionato de cálcio, gluconato de cálcio, gluconato de magnésio, glutamina, granisterona, griseofulvina, guaifenesina, haloperidol, hidralazina,hidrato de cloral, hidroclorotiazida, hidroclorotiazida + amilorida, hidroclorotiazida + espironolactona, hidrocortisona, hidroxicarbamida, hidroxicloroquina, hidróxido de alumínio, hidróxido de magnésio, hidróxido de sódio, hidroxizina, hipoclorito de sódio, hipromelose, ibuprofeno, imiquimode, indinavir, indometacina, iodeto de potássio, iodofórmio, isoniazida, isotretinoína, isradipino, itraconazol, ivermectina, labetalol, lactobionato de cálcio, lactulona, lamivudina, lamotrigina, lansoprazol, levamisol, levetiracetam, levodopa + carbidopa, levofloxacino, levomepromazina, levotiroxina, lidocaína, lindano, lisina, lisinopril, loção anestésica, loção de base Lanette, loção de calamina, loção de trietanolamina, loção emoliente, loção repelente de insetos, loperamida, lopinavir + ritonavir, lorazepam, losartana, lovastatina, lugol forte, lugol fraco, mandelato de metenamina, melatonina, meloxicam, memantina, menadiona, mercaptopurina, mesna, metadona, metformina, metildopa, metilergometrina, metilfenidato, metilose, metilparabeno, metimazol, metoclopramida, metolazona, metoprolol, metronidazol, mexiletina, mianserina, miconazol, midazolam, minociclina, minoxidil, misoprostol, mofetila, morfina, moxifloxacino, mupirocina + clorexidina, nadolol, naltrexona, naratriptano, neomicina, nevirapina, niaprazina, nifedipino, nimodipino, nistatina, nitrazepam, nitrofurantoína, nitroglicerina, nizatidina,norfloxacino, nortriptilina, olanzapina, oleosorbato 80, olmesartana, omeprazol, ondansetrona, orfenadrina, oseltamivir, oxandrolona, oxibutinina, oxicodona, oxitetraciclina, pantoprazol, papaína, paracetamol, pasta de açúcar, pasta d'água, pasta de Alibour, pasta de dióxido de titânio, pasta de Lassar, pasta de Unna, penicilamina, pentoxifilina, perclorato de potássio, pergolida, periciazina, permanganato de potássio, permetrina, peróxido de uréia, pilocarpina, pimozida, pipamperona, pipotiazina, pirazinamida, piridostigmina, piridoxina, pirilamina, pirimetamina, piroxicam, podofilina, poliestirenossulfonatode sódio, polividona-iodo, pomada de vaselina, pomada emulsificante de cetomacrogol, pravastatina, prednisolona, prednisona, primaquina, procarbazina, proclorperazina, prolina, prometazina, propafenona, propilenoglicol, propilparabeno, propiltiouracila, propranolol, quinapril,quinidina, quinina, rabnitidina, retinol, ribavirina, riboflavina, rifabutina, rifampicina, rifaximina, risperidona, ritonavir, ritonavir + lopinavir, rivastigmina, rufinamida, salbutamol, saliva artificial, saliva artificial com lidocaína, saquinavir, selegilina, sertralina, sevelamer, sildenafil, sirolimo, solução de Carnoy, solução de fosfato, solução de Golitely, solução de Joulie, solução de parabenos, solução de Shohl, solução de Shohl modificada, solução hidroalcoólica, solução sedativa oral, sorbitol, sotalol, sucralfato, sulfadiazina, sulfametoxazol + trimetoprima, sulfassalazina, sulfato de magnésio, sulfato de neomicina, sulfato de zinco, sulfato ferroso, sulpirida, sumatriptano, sunitinibe, tacrolimo, talidomida, tartarato de ergotamina, temozolomida, tenofovir, tenoxicam, teofilina, terbinafina, terbutalina, tetracaína, tetraciclina, tiabendazol, tiagabina, tiamina, timolol, tinidazol, tintura de ópio, tioguanina, tioproperazina, tioridazina, tiossulfato de sódio, tiotixeno, tocoferol, topiramato, tramadol, tramadol + paracetamol, trazodona, triancinolona, trifluoperazina, trifluopromazina, trimebutina, trimetazidina, trimetoprima, trimipramina, uréia, valaciclovir, valganciclovir, valproato de sódio, valsartana, vancomicina, varfarina, vaselina colesterinada, vaselina hidrofílica, vaselina mentolada, vaselina salicilada, vaselina + hidróxido de alumínio, veículo suspensor oral, veículo suspensor oral para drogas amargas, venlafaxina, verapamil, xarope de acácia, xarope de ácido cítrico, xarope de citrato de potássio, xarope de citrao de sódio, xarope de ipeca, zidovudina, zipeprol, ziprasidona, zonisamida, zuclopentixol.

Colírio de 5-FU

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Fluoruracila 150 mg/mL Injetável..........................20 mL
Água Destilada para Injetáveis............................23 mL
Cloreto de Sódio 0,9% q.s.p..............................100 mL

Calcular a quantidade requerida de cada componente da formulação para o total de material a ser preparado. Este produto deve ser preparado em área com controle ambiental de forma a reduzir a introdução, a geração e a retenção de contaminantes em seu interior. Retirar o volume desejado de fluoruracila, seguindo protocolo para reconstituição de soluções de drogas citostáticas. Adicionar quantidade suficiente de cloreto de sódio e misturar bem, filtrando previamente a solução através de um filtro de membrana esterilizante de 0,22 micra para um frasco plástico âmbar estéril. Estocado em frasco de plástico âmbar na concentração de 1%. Para uso oftálmico. Estabilidade de 180 dias na temperatura ambiente

Referência: Fluorouracil 1% Ophthalmic Solution. IJPC. 2004; 8(3): 217

Pemetrexede: estabilidade das soluções diluídas

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Estabilidade das soluções diluídas:

Diluída em soro fisiológico 0,9% na concentração de 2, 10, 20 e 25 mg/mL é estável para 2 dias em temperatura ambiente e 31 dias sob refrigeração em bolsa plástica de PVC e em seringa de polipropileno.(1)

Diluída em soro fisiológico 0,9% na concentração de 5 mg/mL é estável para 28 dias sob refrigeração em bolsa plástica de PVC.(2)

Diluída em soro fisiológico 0,9% na concentração de 25 mg/mL é estável para 28 dias sob refrigeração em frasco de vidro.(2)

Diluída em soro fisiológico 0,9% na concentração de 25 mg/mL é estável para 24 h na temperatura ambiente e sob refrigeração em frasco de vidro.(3)

Referências:
1.Zhang Y, Trissel LA. Physical and Chemical Stability of Premetrexed Solutions in Plastic Syringes. The Annals of Pharmacotherapy. 2005;39(12):2026-2028
2.Rondelot G, Serrurier C, Vigneron J, Zenier H, May I, Demoré, B. Stability of pemetrexed 25 mg/mL in a glass vial and 5 mg/mL stored in a PVC container after storage for one month at 2-8°C. European Journal of Hospital Pharmacy Science 2007;13(1):14-16
3.Alimta. Informativo do produto. Eli Lilly. São Paulo. 2011
4.Interactions and IV Compatibility. Micromedex® Healthcare Series, Thomson Micromedex: USA. 2011
5.West of Scotland Cancer Network. WOSCAN Cancer Nursing and Pharmacy Group. Chemotherapy extravasation guideline. Disponível em: http://www.woscan.scot.nhs.uk. Acesso em 12 de outubro de 2011

STABILITE PHYSICOCHIMIQUE DU BEVACIZUMAB A 25 MG/ML CONSERVE A 4°C EN SERINGUE POLYPROPYLENE

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STABILITE PHYSICOCHIMIQUE DU BEVACIZUMAB A 25 MG/ML CONSERVE A 4°C EN SERINGUE POLYPROPYLENE

V. Vieillard, A. Cauvin, E. Roumi, MC. Despiau, M. Laurent, S. Voytenko, A. Astier, M. Paul

GH Henri Mondor, Service Pharmacie, 51 av du Mal de Lattre de Tassigny, 94010 Créteil; Hôpital de Quinze-Vingts, Service Pharmacie, 28 rue de Charenton, 75012 Paris

Le bevacizumab est un anticorps monoclonal humanisé indiqué dans la prise en charge de nombreux cancers. Son action anti-angiogénique est également intéressante pour la prise en charge de la dégénérescence maculaire liée à l’âge. Dans ce cadre, l’hôpital des Quinze-Vingts prépare des seringues prêtes à l’emploi contenant 150 μl de solution commerciale (25 mg/ml) pour injection intraoculaire. Il nous a été demandé, dans le cadre d’un partenariat, d’effectuer une étude afin de définir une durée de stabilité afin de répondre aux Bonnes Pratiques de Préparation (BPP), s’agissant alors de préparations hospitalières.

Le but de cette étude a donc été d’évaluer la stabilité physicochimique de l’Avastin® conservé en seringue polypropylène à 4°C pendant s ix mois, par des méthodes analytiques appropriées (chromatographiques (CEX, SEC et carte peptidique), spectrométrique UV (dosage, turbidance et agrégation thermique) et diffusion dynamique de la lumière pour la mesure des diamètres). Trois lots de seringues ont été réalisés (2 lots à la lumière, 1 lot abri lumière). Le calendrier de prélèvements a été le suivant (T0, 15, 30, 60, 90 et 180 jours).

Les résultats préliminaires à 3 mois, ont montré que l’avastin conservé à 4°C était parfaitement stable. Aucune agrégation, objectivée par la turbidance à 350 nm (0.0082 +/- 0.0013 (T0) vs 0.009 +/- 0.0004 (T180) et par le rapport des densités optiques (solution centrifugée/ non centrifugée) à 279 nm n’a été observée. Le pourcentage initial d’agrégats (voisin de 2.4%) est resté constant.

Les aires sous courbes et les temps de rétention en chromatographie CEX et SEC sont restés inchangés et aucun nouveau pic n’est apparu attestant ainsi de l’absence de modification de la composition isotypique initiale, de dégradation (desamidation, fragmentation) et d’agrégation. Le poids moléculaire n’a pas été modifié. Les chromatogrammes obtenus en carte peptidique étaient parfaitement superposables. La température moyenne d’agrégation (Tm) est restée identique et voisine de 72.5 °C. Enfin, les diamètres hydrodynamiques sont restés du même ordre (11.57 nm +/- 0.13).

Conclusion: L’ensemble de ces résultats justifie la mise en oeuvre de préparations hospitalières dans le respect des BPP, garantit une qualité optimale et permet d’optimiser le travail dans l’unité de préparation.

Reference: Société Française de Pharmacie Oncologique. Congress 2011

Muscular toxicity from docetaxel in HIV-patient treated by ritonavir

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Muscular toxicity from docetaxel in HIV-patient treated by ritonavir

C. Pichard, J. Jezequel, A. Pont, M. Bascoulergue, A. Oufella, V. Duperrin, A. Fabreguettes

CH Robert Ballanger, Seine-Saint-Denis, Aulnay sous Bois, France

Background: In hospital patients are treated in different care units for their cancer
and for their chronicles diseases. Interactions between their treatments can lead to iatrogenic consequences.

Purpose: To report a case of a docetaxel-ritonavir interaction in a HIV-patient with breast cancer

Material and Methods: Informations including HIV treatment have been obtained from patient clinical history. Chemotherapy treatments were obtained from CHIMIO.

Results: A 36-year-old HIV-positive woman was diagnosed with breast cancer in February 2010. The HIV-infection was diagnosed in 1996. Since 2007 eighth line treatment contains atazanavir (boosted with ritonavir), tenofovir and emtricitabine.
Neoadjuvant chemotherapy contains four cycles of Epirubicine-Cyclophosphamide followed by four cycles of docetaxel. Patient received four cycles of EC without important side effects. Three days after her first docetaxel cycle she was admitted to emergencies for muscular pains interesting her legs. Docetaxel-ritonavir interaction was supposed because docetaxel was metabolized by CYP450-3A4 and ritonavir inhibited CYP450-3A4.HIV treatment couldn’t be changed because infection was well controlled with viral load below the limit of detection. So docetaxel dose was reduced from 100mg/m² to 65mg/m². However seven days after the second cycle patient was again admitted for muscular pains. Docetaxel was definitely stopped. another possiblechoice was to use vinorelbine but review of literature has showed
vinorelbine is also metabolized by CYP450-3A4. Thereby patient received two more cycles of Epirubicine-Cyclophosphamide beforemastectomy.

Conclusion: This case report highlights severity of potential interaction between docetaxel and ritonavir. Concomitant administration of these medications may increase docetaxel blood concentration probably due to the inhibition of CYP450 by ritonavir. So docetaxel must be avoided in HIV-patient treated by ritonavir. While these interactions are well known to clinicians treating HIV, they are probably less obvious to the clinician prescribing chemotherapy. The optimal care for cancers requires that practitioners attend multidisciplinary meeting around the file of the
patient

Reference: 16th Congress of EAHP. 30 March - 01 April 2011. Viena. Austria

Imagine One World

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Feliz Natal.

Cyclophosphamide 10-mg/mL Oral Liquid

Cyclophosphamide 10-mg/mL Oral Liquid

Loyd V. Allen, Jr, PhD
Professor Emeritus
College of Pharmacy, University of Oklahoma
Oklahoma City, Oklahoma

US Pharm. 2010;35(3):42-43.

Method of Preparation: Calculate the quantity of each ingredient for the amount to be prepared. Accurately weigh or measure each ingredient. Reconstitute the cyclophosphamide for injection with the 0.9% Sodium Chloride Injection. Place the mixture in an appropriate graduate, add sufficient Ora-Plus or simple syrup to final volume, and mix well.

Use: Cyclophosphamide oral liquid is used in the treatment of many adult and pediatric malignancies.

Packaging: Package in tight, light-resistant containers.

Labeling: Keep out of the reach of children. Shake well. Store in a refrigerator. Discard after 56 days.1,2

Stability: A beyond-use date of 56 days can be used for this preparation only when it is stored in a refrigerator.1,2 The reported stability study used the injection as the source of the drug.

Quality Control: Quality-control assessment can include weight/volume, pH, specific gravity, active drug assay, color, rheologic properties/pourability, physical observation, and physical stability (discoloration, foreign materials, gas formation, mold growth).3

Discussion: Cyclophosphamide is a widely used chemotherapeutic drug for treating a broad range of malignancies. It is used in the treatment of Hodgkin’s disease, non-Hodgkin’s lymphoma, multiple myeloma, leukemias, cutaneous T-cell lymphoma, neuroblastoma, ovarian cancer, retinoblastoma, breast cancer, small-cell lung cancer, sarcomas, and other diseases. A former method of preparing an oral liquid involved the use of Aromatic Elixir USP and had a reported stability of 14 days. However, Aromatic Elixir USP is no longer commercially available and takes time to prepare, so the current formula is presented with a beyond-use date of 56 days when it is stored in a refrigerator.1

It should be noted that storage at room temperature resulted in 10% degradation of the drug in 10.6 days in simple syrup and in 6.0 days in Ora-Plus. Therefore, this preparation must be refrigerated.

Cyclophosphamide (C7H15Cl2N2O2P.H2O, MW 279.10) is a nitrogen mustard derivative that is used as an antineoplastic and immunosuppressant. It occurs as a white, crystalline powder that liquefies upon the loss of its water of crystallization. Cyclophosphamide is soluble in water and in alcohol.1

0.9% Sodium Chloride Injection contains not less than 95.0% and not more than 105.0% of the labeled amount of sodium chloride in water for injection. It has a pH between 4.5 and 7.0, and it contains no added antimicrobial agents. Sodium chloride solutions are chemically and physically stable. They can be sterilized by filtration or autoclaving. Aqueous sodium chloride solutions will react to form precipitates with silver, lead, and mercury salts. When acidified sodium chloride solutions are mixed with strong oxidizing agents, chlorine can be liberated. Sodium chloride will decrease the solubility of some organic compounds; methylparaben is not as soluble in sodium chloride solutions as it is in water. Sodium chloride is soluble in water to the extent of 1 g in 2.8 mL water, and it is slightly soluble in alcohol (1 g in 250 mL of 95% ethanol).4

Ora-Plus is an oral suspending vehicle that accepts dilution of up to 50% or more with water, flavoring agents, or syrups and still retains its suspending properties. It has a pH of approximately 4.2 and an osmolality of about 230 mOsm/kg. Ora-Plus is a thixotropic vehicle with a viscosity of approximately 1,000 cps at 25˚C. It contains purified water, microcrystalline cellulose, sodium carboxymethylcellulose, xanthan gum, carrageenan, sodium phosphate, and citric acid as buffering agents; simethicone as an antifoaming agent; and potassium sorbate and methylparaben as preservatives.5

Syrup (simple syrup) is a clear, sweet vehicle used as a sweetening agent and as the base for many flavored and medicated syrups. It contains 85% w/v sucrose in water and has a specific gravity of not less than 1.30. Simple syrup is generally self-preserving as long as the sucrose concentration is maintained sufficiently high. Preferably, it is prepared without the use of heat, but it can be prepared by the use of boiling water. Simple syrup should be stored in tight containers, preferably in a cool place.1
REFERENCES

1. USP Pharmacists’ Pharmacopeia. Rockville, MD: US Pharmacopeial Convention, Inc; 2005:388,775-779,1433.
2. Kennedy R, Groepper D, Tagen M, et al. Stability of cyclophosphamide in extemporaneous oral suspensions. Ann Pharmacother. 2010;44:295-301.
3. Allen LV Jr. Standard operating procedure for performing physical quality assessment of oral and topical liquids. IJPC. 1999;3:146-147.
4. Maximilien JS. Sodium chloride. In: Rowe RC, Sheskey PJ, Quinn ME, eds. Handbook of Pharmaceutical Excipients. 6th ed. London, England: Pharmaceutical Press; 2009:637-640.
5. Ora-Plus (product information). Minneapolis, MN: Paddock Laboratories, Inc; 1992.

To comment on this article, contact rdavidson@uspharmacist.com.