Artho Artho Composimion: Artho 50 coniains dioferac sodium (enteric coated), BP 50mg misoprostol, USP. 200u9 Artho PLUS conians dicofenac sodium (enteric coated), BP... 759 misoprostol, USP... 200n9 (Manufacturer's Specticatons) DOSAGE AND ADMINISTRATION: For most ofthe indication, one tablets recommended 2-4 times dally swallowed whole, not chewed or use as directed by the physician. Osteoarthritis: The recommended dosage for manimal GI mucosal protection is Artho 50 td. For patients who experience intolerance, Artho PLUS bid of Artho 50 bid can be used, but are less effectve in preventing ulcers, Rheumatoid Ashi: The recommended dosage s Art 50 td or aid. For patients who experiance intolerance, Artno PLUS bid or Atho 50 bid can be used, but are less efece in preventing vices. ‘SPECIAL DOSING CONSIDERATIONS: ‘Artho contains misoprostol, whch rovides protection against gase and duodenal toes. For gatc ulcer preverton the 2003 gi and td regimens are herapeutcally equivalent, but more protective than the bid regimen, For duodenal uler prevention, the oi regimen s more protective than th tid or bd regimens. Honever the gid regimen i less well tolerated than the fd regimen because of usualy sei-imited aes ee te spot doe ad hier may be etre an bd in some patents Dosages may be individualized using the separate products (misoprostol and dofonac Sodium), fle which the patent may be changed to the approprale dose of rth. If clinically naicated, misoprostol cotherapy with Artho, o use othe individual components to optiize the misoprostol dose andlor equeney of administration, may be appropri. The ota dose of misoprostol should not exceed 800 fda, and no more than 20049 of misoprostol shouldbe administered at any one tm. Doses. of dicofenac sodium higher than 160 mlday in ostecarthis or higher than 225 ‘malday in euro aes ara not recommended, PEDIATRIC USE: Safety and efecveness of Arthe in pediatc pation have not been estabished, GERIATRIC USE: ‘AS ih ary NSAIDs, caution should be exercised in eating elderly patents (85 years and oder) with dcofenac sodium Inisoprstol. Of the mare than 2,100 subjects n Clinical studes wih diclofenac sodium imsoprastol, 25% were 65 ad over, whe 6% ere 75 and over. n stuties with diclofenac sodlum, 31% of subjects were 65 and ‘ver. No overall ferences in safety or ffectveness were observed between these ‘sje and younger subjects, and oer reported cncal experience has ntientifed diferences in responses between the elderly and younger patiens, but greater senstvty of some older individuals cannot be ruled out RENAL IMPAIRMENT: Diciofenac sodium is known to be substantially excreted by the Kidney, andthe risk ‘of tori reactions to Artho may be greater in atienis with impaired renal function, Because elt paens are more Ike to have decreased renal function, care should be taken in dose selection, and it may be useful to manilor renal funclon. Based on ‘studies inthe elder, no adjustment ol the dose of Artho is necessary inthe elder for pharmacokinoic reasons, although many eldery may neod to recave a reduced dose because of low body weight or disorders associated with aging CONTRAINDICATIONS: ‘ADMINISTRATION OF MISOPROSTOL TO WOMEN WHO ARE PREGNANT CAN, CAUSE ABORTION, PREMATURE BIRTH OR BIRTH DEFECTS. PATIENTS MUST BE ADVISED OF THE ABORTIFACIENT PROPERTY AND WARNED NOT TO GIVE THE DRUG TO OTHERS, Cardiovascular Ris NSAIDs may cause an increased risk of serious cardiovascular thrombotic rors, mjocatal aren, sa see, wich can be aa kay nase ‘tito oe ™ Tablets vet Gastrointestinal Risk [NSAIDs cause an increased risk f serious gastrointestinal adverse events including ‘leding, ulceration, and perforation ofthe stomach or intestines, whch canbe faa Ue los goss os or parran cod by NSA cca 1% paions teated for 38 months, and in about 24% of patents teste for 1 year. Elderly patients are at greater risk for serious gastrointestinal events. INDICATIONS AND USAGE: Artho i indicated for treatment of the signs and symptoms of osteoarthritis or ‘eumatid arth wit ther complaints, tke polymyesiis,drmatomyosts, dental pain, Temporomancibular joint (TMA), spondvarthis, ankylosing sponds, gout ‘ata, and pain managemen'in cases of kdnay tones and galstones. An adetional Incication i the reatment of acute migraines. Didofenac sodum is used commonly {a teat mid to moderate post-operaive or pos-raumatc pain, patculerly when ‘tammationis aso present, ands elective against menstrual pain and . “Artho should not be taken by pregnant women, ‘Artho is conrandicated in pains wit hypersensivly to dcofenac sodum or {o misoprostol or other prostaglandins. Artho should nt be given to patents who have experienced asthma, uricara or ater alergcype reactons ater taking asprin ‘or oh NSAIDs. Severe, rarely fatlanaphylactcsike reactions to dcofenac sodium hhave been reporied in sch patents. Arth is cntrandicated forthe treatment of er-operative pan inthe seting of coronary airy bypass graft (CABG) surgery. WARNINGS: CARDIOVASCULAR EFFECTS Cardiovascular Thrombotic Events. Cinical tals of several COX.2 selective and nonselective NSAIDs of upto thee years duraton have shoun an inceased rs of sefous cardiovascular (CV) trombotic ‘events, myocaral infarction, and stroke, which canbe fatal Hypertension NSD rceg Artho, can ea tone fnew hypetension or worsening of Dreeiting hypertension, ete of which may connbut tothe Increased Inaderce (fC evens, Pants aig azides oop det may have imped response {ottese therapies when aking NSADs. NSAIDs, including Ath, should be used wih caution in paints wih hypertension, Congestine Hear Fallure and Edema Fluid retention and edema have been observe in some patients taking NSAIDs, ‘Artho shouid be used wit cauton inpatients wih fuldrtenton or heart flu. PREGNANCY: Pregnancy Category X. n late pregnancy, as wih other NSAIDs, Arte shouldbe ‘avoided because it may cause premise closure of the ductus arieiosus, Msoprosiol ‘may cause aborton (sometimes incomplete), premature labor, or bith defecs if ven to pregnant women Nursing mothers Diclofenac sodium has been found inthe mik of nursing mothers. Misoprosto is ‘apldy melaboized in he mother o misoprostol acid, which is biological active and 's excreted in breast mik There steno published repors of adverse effects of ‘misopostl in breast-feeding infants of mothers aking misoprostol. Cauton should be exercised when Artho is administered to @ nursing woman GASTROINTESTINAL EFFECTS: Riskot Ulceration, Bleeding, and Peroraton NSAIDs, incuding Artho, can cause serious gasvoniesinal (3) adverse evens inuding inianmaten, Bleeding, eration, and peroraton ofthe stomacs, smal intestine, orlage intestine, which canbe faa RENAL EFFECTS: Long te administration of NSAIDs has resid in renal pally nexross and other renal inj. HEPATIC EFFECTS: In cinical tals with dlofenac sodium /misoprostol, meaningful elevation of ALT (SGPT, mote than 3 times the ULN ULN = the upper limit ofthe normal rangel) ‘ocurred in 1.6% of 2,184 patients treated with dcofenac sodium imsopostol and in 14% of 1,681 patients teated wth dilofenac sodium. These creases were generally transient, and enzyme eves retumed to witin the normal range upondiscontinuation of therapy with diclofenac sodium /misoprostol. ANAPHYLACTIC REACTIONS: ‘As wih oer NSAIDs, araphylactc reactions may occur in patents without known por exposure to Artho. Artho should not be civen to paints wih the aspirin a, ‘SKIN REACTIONS: NSAIDs, induring Artho, can caus serious skin adverse events such as exoatve Seats, Sens otrsn Syrrae (8), and tac epider noc (TEN), when can, PRECAUTIONS: General: 1.7 to 3.0 mg/dl in men and >1.5 to <2.5 mgidl in women), the dose of Admit (Sitagliptin) is 50mg once daily. For patients with severe renal insufficiency (CiCr<30 milmin,approximately corresponding to serum creatinine levels of >3.0 mg/dl in men and >2.5 mg/dl in women) or with end-stage renal disease (ESRD) requiring haemodialysis or peritoneal dialysis, the dose of Admit (Sitagliptin) is 25mg orice daily. Admit (Sitagiiptin) may be administered without regard to the timing of haemodialysis. ‘CONTRAINDICATIONS: ‘Admit (Sitagliptin) is contraindicated in 1D Patients with known hypersensitivity to sitagliptin or any of the components of the product. 11 Patients with type I diabetes or forthe treatment of diabetic keto-acidosis 1 Children below 18 years of age WARNINGS AND PRECAUTIONS: Pancreatitis Patients should be observed carefully for signs and symptoms of pancreatitis after the initiation of Admit (Sitagliptin) dose. ‘Admit (Sitagliptin) should promptly be discontinued and appropriate management should be initiated if pancreatitis is suspected Hypoglycemia When Admit (Sitagliptin) is used in combination with sulfonylurea or with insulin, medications known to cause hypoglycaemia, the incidence of hypoglycaemia increases ‘when used in combination with a sulfonylurea or with insulin ‘Therefore, a lower dose of sulfonylurea or insulin maybe required to reduce the risk of hypoglycaemia, ADVERSE REACTIONS: Mono-therapy Upper respiratory-tract infection, headache and nasopharyngitis, [Audmit (Sitagliptin) with Metformin HCI Common: Nausea. Uncommon: Somnolence, diarrhoea, upper abdominal pain and decreased blood glucose. Admit Sitagliptin) with Sulfonylurea ‘Common: Hypogiycaermia, ‘Admit (Sitagliptin) with Pioglitazone ‘Common: Hypoglycaemia, flatulence and peripheral oedema ‘Admit Sitagliptin) with Suiphonylurea and Metformin HCI Very common: Hypoglycaemia‘Common: Constipation ‘Admit Sitagliptin) with a Rosiglitazone and Metformin HCI ‘Common: Hypoglycaemia, headache, diarthoea, vomiting and peripheral oedema ‘Admit (Sitagliptin) with Insulin Common: influenza, hypoglycaemia and headache Uncommon: Dry mouth and constipation DRUG INTERACTIONS: ‘Audmit (Sitagliptin) has @ small effect on plasma digoxin concentrations. No dose adjustment of digoxin is recommended. However, patients at risk of digoxin toxicity should be monitored for this when Admit (Sitagliptin) and digoxin are administered concomitantly USE IN SPECIFIC POPULATIONS: Pregnancy The safety of Admit (Sitagliptin) in pregnant women is not known. Admit (Sitagliptin), like other OADs, is not recommended for use in pregnancy. ‘Nursing Mother Itis unknown whether Admit (Sitagliptin) is excreted in human milk or not because many drugs are excreted in human milk ‘Admit (Sitagiiptin) should not be administered during nursing OVER DOSAGE: Itis reasonable to employ the usual supportive measurement in the event of an overdose, e.g., remove unabsorbed material from the gastrointestinal tract. Employ clinical monitoring (including obtaining an electrocardiogram),and institute supportive therapy as dictated by the patient's clinical status. Allmit (Sitagliptin) is modestly dialyzable, prolonged haemodialysis may be considered if clinically appropriate, It is not known if Admit (Sitagliptin) is dialyzable by peritoneal dialysis. CLINICAL PHARMACOLOGY: Pharmacodynamics Absorption Following oral administration of a 100mg dose, ‘Admit (Sitagliptin) absorbs rapidly with peak plasma concentration (median Tmax) occurring 1 to 4 hours post-dose, mean plasma AUC of Admit (Sitagliptin) ic 8.52 uumihr, with Cmax 950nm. The absolute bioavailability of Admit (Sitagliptin) is approximately 87%,Plasma AUC of Admit (Sitagliptin) increased in a dose-proportional manner. Distribution The mean volume of distribution at steady state following a single 100mg intravenous dose of Admit (Sitagliptin) is approximately 198 liters. The fraction of Admit (Sitagliptin) SHRIGAN Full prescribing information available on request SHAIGAN Pharmaceuticals (Pvt.) Limited 14Km Adyala Road, Post Office Dahgal, Rawalpindi Pakistan ‘www.shaigan.com reversibly bound to plasma proteins is low (38%). Metabolism & Excretion ‘Admit (Sitagiiptin) is primarily eliminated unchanged in urine (approximately 79%) and metabolism is a minor pathway. Following administration of an oral Admit (Sitagliptin) dose, approximately 100% of the administered radioactivity eliminate in faeces (13%) or urine (87%) within one week of dosing. The apparent terminal t1/2 following a 100mg oral dose of Admit (Sitagliptin) is approximately 12.4 hours and renal clearance is approximately 360ml/min Special Populations Renal Insufficiency Patients with mild renal insufficiency did not have a clinically meaningful increase in the plasma concentration of Admit (Sitagliptin). The plasma AUC of Admit (Sitagliptin) increases approximately two times in patients with moderate renal insufficiency, and an approximately four times in patients with severe renal insufficiency and in patients with ESRD on haemodialysis. Hepatic Insufficiency There is no clinical experience in patients with severe hepatic insufficiency (Child-Pugh score > 9). However, because ‘Admit (Sitagliptin) is primarily renally eliminated, severe hepatic insufficiency is not expected to affect the pharmacokinetics of Ralmit (Sitagliptin). Elderly Elderly subjects (65 to 80 years) had approximately 19% higher plasma concentrations of Ait (Sitagliptin) compared to younger subjects. INSTRUCTIONS: Protect from heat, light & moisture. Store below 30°C. Medicine should be kept out of the reach of children. To be sold on the prescription of a registered medical practitioner only. PRESENTATION: [dmit-25is availabe in alu alu blister pack of 1x14s fim coated tablets. dmit-50 is availabe in au alu blister pack of 1x14's film coated tablets. ‘Aaimit-100 is available in alu alu blister pack of 2x7's fim coated tablets, LS Sr $i be Fuel ave Subeluie Spent Aes is1L tipTe ee a) eee Tablets COMPOSITION: ‘Admit-50/500 Each fim coated tablet contains: ‘Sitaglptin (as Phosphate Monohydrate), BP 50mg Metformin HCl, BP ‘500mg ‘Admit-50/1000 Each fim coated tabiet contains Sitagiptin (as Phosphate Monohydrate) BP. 50mg Metformin HCI, BP ‘000mg (Manufacturer's Specifications) INDICATIONS AND USAGE: ‘Admit (Sitagipin | Metformin) is indicated as: =Intial therapy in patents wit type Il diabetes melitus to improve glycaemic control when det and exercise do nal provide adoquate glycaemic contra AS an adjunct to diet and exercise to improve glycaemic control n patents with typeI cabetes melius inadequately controlled on Metformin or Stagiptin alone on pte areaty berg treated wih the combination of Stagipin and Metformin In gle combination with Peroxisome Proliferator Activated Receptor gamma (PPAR) agonist (Thiazoidinecione) as an adjunct to diet and exercise in patients inadequately controled on ther maximal olerated dose of Metformin and PPAR agonist = In patients with type Il diabetes melitus as an adjunct to diet and exercise to improve glycaemic control in combination with insulin DOSAGE AND ADMINISTRATION: [Admit (Stagiptin Metformin) dose shouldbe individualized onthe basis of patients curent regimen, effectiveness and tolerability while not exceeding the maximum recommended daly dose of 100mg Stag. It should be given twice daily with meals, with gradual dose escalation, 1o reduce the gastrointestinal (GI) side effects associated with Metformin, AS intl therepy for paints with type I ciabetes metus, whose hyper-lycaemiais inadequately controled with diel and exercise alone, the recommended staring dose of ‘Admit (SiagiptinMetfomin) is 50mg of Sitagiptin + 500mg of Metformin twice daly. Patients may be treated upto 50mg Sitaglptin + 1000mg of Metformin twice dally. For patents inadequately controlled on Metfomrin ‘mono-therapy the usual tating dose of Admit (Stagipin/Metformin) should provide Sitaglptin dose as 50mg twice daly (100mg total daly dose), plus Metformin dose already being taken. For patents inadequately controlled on Stagiitin mono-herepy the usual staring dose of allt (StagiptivMetforin) is 50mg Sitalptin+500mg Metformin twice dally, Patient may be treated upto 50mg Sitagiptin+1000mg Metformin twice daily. For patient switching from Sitagliptin co-administered with Metformin (Alone drugs), Admit (SitagptvMetionnin) may be initiated at the dose of Sitaglpin and Metformin alteady being taken, For patents inadequately conroled on dual combination therapy with any two of the folowing three ant-hyperglycaemic agents, ‘Sitaglptin, Metformin or PPAR agonist (thiazolidinadione). The usual starting dose of Amit (Sitagitn’ Metformin) should provide Sitagiptn dose as 50mg twice dally (100mg total day dose). In determining the stating dose of Metformin component, the patient level of glycaemic control and current dose (any) of Metformin should be considered. In determining the staring dose Of Metformin component, the patent level of glycaemic control and curent ose (any) of Metiormin should be considered, SPECIAL POPULATIONS: Renal insufficiency: Sitagiptn: The plasma concentration of Sitaglptn in patients with mild renal insufficiency did not have a dnicaly meaningful ‘norease, In patients with moderate renal insufficiency the plasma AUC of Sitaglpin increases about 2imes, and an about 4times in patents with severe renal insufciency and in patients with ESRD on haemodialysis, Metformin: In patents with decreased renal function (based on measured Creatinine clearance), the plasma and blood hal-ife of Metfomnin is prolonged ‘and the renal clearance is decreased in proportion othe decrease in creatinine dearance, Hepatic Insufficiency: Sitagitin:In patients wih severe hepatic insufficiency (Chiié-Pugh score > 9) there is no clinical experience. However, because Sitagliptin is primarily renally eliminated, severe hepatic insufciency is not ‘expected to affect the pharmacokineic of Sitagiptin. Metformin: Inpatients with hepatic insuficency, no pharmacokinetc studies of Metformin have been conducted Elderly: Sitalptn: Elderly subjects (65 to 80 years) hed approximately 1996 higher plasma concentratons of Sitagipin compared to younger subject, Metformin: n case of elderly patients renal function of Metfomin is impaired, results in decreased total plasma clearance, prolonged t1/2, and increased ‘Cmax. So, itis recommended not to itt Aili (Sitagliptin Metformin) in {geriatric patent 80 years without monitoring renal function. Paediatric: No studies wit Admit (Staglipin/ Metformin) have been performed in paediatric population, CONTRAINDICATIONS: ‘mit (Stagiptn / Metformin is contraindicated in: - Patients with type | diabetes Renal disease or renal dysfunction, e.g. a8 suggested by serum creatinine levels 1 Smgial (males) 1 4mgjdl females), or abnormal creatine Cearance, \which may also resi ftom conditions such as cardiovascular collapse (shock), acute myocardial infarction and septicaemia « Known hypersensitivity to Stagitin, Metformin or any other component of Sitagliptin & Metformin - Act or chronic metabolic acidosis, including keto-acisis, with or without coma WARNINGS AND PRECAUTIONS: ‘Monitoring of renal function: Rumi (Sitagliptin Metformin) are known tobe substantially excreted by the kidney. Metformin HC-elated lactic acidosis increases wit the degree of insufficiency of renal functon, therefore, serum creatinine concentrations should be determined regula. ‘Impaired hepatic function: Since impaired hepatic function has been associated with some cases of lactic acidosis, Admit (SitaglptivMetforrin) ‘Should generally be avoided in patenis with clinical or laboratory evidence of hepatic disease. ‘Hypoglycaemia: Patient receiving Admit (Sitagliptin { Metformin) in combination with suifonyluea orwith insulin may beat risk for hypo-glycaemia. ‘Therefore, a reduction in the dose of the sulfonylurea or insulin may be necessary, Pancreatitis: Sitagliptin: Ate ination of Stagliptin, patients should be cbserved carefully fr signs and symptoms of pancreatitis. If pancreatitis is suspected, Sitagiptin should promptly be discontinued and appropriate management shouldbe inated, Lactic acidosis: Metformin: tis avery rare, but serious, metabolic complication ‘can occur due to Metformin accumulation. The incidence of lacc acidosis can and should be reduced by also assessing other associated risk factors such 28 poorly controlled diabetes, kelosis, prolonged fasting and excessive alcoho intake, hepatic insufficiency and any condtion associated with hypoxia. If metabolic acidosis is suspected, treatment with the medicinal product should be ciscontinued and the patient should be hospitalised immediately ‘Administration of iodinated contrast agent: The inicavascula administration Of iodinated contrast agents in radiological studies can lead to renal failure which has been associated with lactic acidoss inpatients receiving Metformin HCl. Therefore, Admit (Sitagliptin / Netformin) should be ciscontinued priorto, oratthe time ofthe test and not reinsiuted until 48 hours afterwards, and ‘only after renal function has been re-evaluated and found tobe normal ADVERSE REACTIONS: [idm (Sitagiptin’Metformin) Common: nausea, Uncommon: somnolence, Giarmoea, upper abdominal pain and blood hypo-alyczemia {Admit (Stapigtn Metformin) and Suonylurea Very common: hypo-aiycaemia Common: constipation Mimit (Sitagiptin’Metformin) and PPAR agonist Common: hypo-glycaemia, headache, dartoea, voniting, peripheral oedema ‘Admit Stagiptin/ Metformin ard insulin Very common: hypoglycaemia Uncommon: headache, dry mouth DRUG INTERACTIONS: Sitagliptn: Digan: Sitagipn has @ smal effect on plasma digoxin concentrations. No dosage adjustment of digoxin is recommended. However, patents at sk of igorin toxic shou be moritered for hs when Stalin and digoxin ‘are administered concomitant Metformin: Furosemide: Furosemide increased the Mefomin plasma and blood Cmax by 22% and blood AUC by 15%, without any signfcant change in Metformin renal clearance. Medipne: Cc-administaion of Nifedipine increased plasma eon Cmax and AUC by 20% and 9%, respecvly, and increased the amount excreted in the urine. Tmax and hal-ife were unafcted. Nifedipine {appears to enhanoe the absorption of Metformin. Metin had minimal fects conNfedpine, Catone drugs: Catonicdrugs (9, amide, cigoxn, mophine, procainamide quinidine, quinine, raniéne,tiamterene,timethoprim, of ‘vancomycin that ae eliminate by renal tubular secretion theoretically have the polenta for ineracton wih Metformin by competing for common renal ‘ubuar anspor systems. Although suchineractons remain theoretical (xcept for cimetidine), earful pationt monitoring and dose acjstment of Admit (Gtagipin Melton) and” the interfering drugs recommended in paints who are taking catonio medications that are excreted va the proximal real {ubuiar secretory system. Other Certain medicines tend to produce ypergycaomia ard may lead loss of yeaemic contro. These drugs include the thazides and other diuretic, coriosterids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid Sympahomimets, calcum chanel blocking dugs, and sonazid. When sch rugs are adminisiored to a patent receiving Admit (Siagltn/ Metiormin) the patent shouldbe closely observe to maintain adequate glycemic contol USE IN SPECIFIC POPULATIONS: Pregnancy: The safety of Admit (Stagiptn | Metformin) in pregnant women is notknown, So like other ant-hyperglycaemic agent, tis not recommended for use in pregnancy. Nursing Mothers isnot known whether Sitagiotin S| ‘excreted in human milk, because many crugs are excreted in human milk ‘Adalt (Sitagipin Metiomrin) should net be administered during nursing, OVER DOSAGE: Sitagliptin: Inthe event of an overdose, itis reasonable to employ the usual ‘supportive measures, e.., remove unabsorbed materia fom the gastrotestinal trac, employ cinical monitorng (including obtain an electrocardiogram) and Insitute supportive therapy as dictated by the patients clinical slatus, Sitaglpin is modestly dilyzable. Prolonged haemodialysis may be considered icncalyanroptat. ts not known fStagotn s aeablby peroneal dialysis Metformin: In case of Metformin overdose (greater than 50g), hypo-ghycaemia \was reported in approximately 10% of cases, but no causal association with Metformin has bean established. Metftomin is dalyzable wth a clearance of Upto 170milmin under good hemadynamic condtions. Therefore, haemecalysis ‘may be useful foremoval of accumulated drug fom patientsin whom Metformin over-dosage is suspected. gh02-80-16 (LOON 'A8y) ‘SHRIGAN Full prescribing information available on request SHAIGAN Pharmaceuticals (Pvt.) Limited 74Km Adyala Road, Post Office Dahgal, www.shaigan.com CLINICAL PHARMACOLOGY: Pharmacodynamics: “Absorption Sitagliptn: after an oral dose ofa 100mg, Stagiiptin absorbs rapicly with peak plasma concentration (median Tmax) occuring 1 to 4 hours pos-cose, mean plasma AUC of Sitagliptn is 8.52 whr, with Cmax 950nM. The absolute bioavailability of Stagiptin is approximately 87% Plasma AUC of Sitagiptin increased ina dose-proporional manne. Metformin: After an oral dose of Metformin, Tmax is reached in 2.Shrs. The absolute bio-avaliability of a single dose 600mg is reported to be about 50% to 60% given under fasting cordon. Single oral doses of Metformin 500mg +0 1500mg, that there is 2 lack of dose proportional with increasing doses, \wich is due to decreasedin absorption rather than an alteraton in elimination, Food decreases the extent and slightly delays the absorption of Metformin, ‘as shown by about a 40% lower mean peak plasma conceriration (Cmax), a 25% lower area under the plasma concentration versus time curve (AUC), The pharmacokinetics of Metformin absorption is non-linear. Distribution: ‘Sitglptn: Tho mean volume of dstbution at steady sate following a single 10mg IV dose of Siagiptnis approximately 198 litres, The fraction of Staglptn reversibly bound to plasma proteins is low (38%). Metformin: Metformin is negligibly bound to plasma proteins, in contrast to sulfonyiureas, which are more than 90% protein bound, Metformin paritions into erythrocytes, most likely asa function of ime. At usual clinical doses and dosing schedules of Metformin, steady-state plasma concentrations of Metformin ‘are reached within 24-48 hr and are generally <1 mogim. Maximum Metiormin plasma levels do not exceed Smogim, even at maximum doses. Metabolism & Excretion: Siaglpin: Stagitnis psmarly eliminated unchanged in urine (approximately 729%), and metaboism is a minor pathway. After an orl dose of Sitaglptn approximately 100% ofthe administered radioactviy eiminate in faeces (13% ‘and urine (87°) within one week of dosing. The apparent terminal 1/2 folowing 12 100mg oral dose of Sitaglptinis approximately 12.4hrs and renal clearance is approximately 360mm Metformin: Metformin is excreted unchanged inthe urine and does not urdergc hepaticmetabolism (no metabolites have been identified in humans) or bar exoreton, Renal clearance is approximately 35 times greater than creatinine Clearance, which indicates that tubular secretions the majoroute of Meormi elimination, Following oral administration, approximately 20% of the absorbec tug is eliminated via the renal route within the rst 24 hours, wih a plasm clmination hal-ife of approximately 6.2 hrs. n blood, the elimination hal-ie |s approximately 17.6 hrs, suggested thatthe erythrooyte mass may be « ‘compartment of dstibuton. INSTRUCTIONS: Protect from heat, light & moisture. Store below 300C. Medicine should b kept out ofthe reach of children. Tobe sold onthe prescripton of aregistere ‘medical pracitioner only, PRESENTATION: ‘Admit-50/500 is avaiable in alu alu blister pack of 2x7's fm coated tablets. ‘dmit-50/1000 is avaliable in alu alu blister pack of2x7's film coated tablets, LES ret GBs b HAG - Ere Bibel epeNonle aU tes} s1k ion ee ‘awalpindi PakistanTablets Antimin-D L . Gs-gastis| COMPOSITION: Each film coated tablet contains: Desloratadine , BP... ss (Manufacturer's Specifications). DESCRIPTIO! Desloratadine is a non-sedating acting long antihistamine antagonist with selective H1-receptor histamine antagonist activity. It is administered orally The chemical name is 8-chloro-6,11-dihydro-11-(4 piperdinylidene)-5H-benzo[5,6]oycloheptaf1,2-bjpyri- dine and has the following structure: H CLINICAL PHARMACOLOGY INDICATIONS AND USAGE: Seasonal Allergic Rhinitis Antimin-D Tablet is indicated for the relief of the nasal and non-nasal symptoms of seasonal allergic rhinitis in pationts 12 years of age and older. Perennial Allergic Rhinitis Antimin-D Tablet is icated for the relief of the nasal and non-nasal symptoms of perennial allergic rhinitis in patients 12 years of age and older. Chronic Idiopathic Urticaria Antimin-D Tablet is indicated for the symptomatic relief of pruritus, reduction in the number of hives, and size of hives, in Patients with chronic idiopathic urticaria in patients 12 years of age and older. Mechanism of Action: Desloratadine is a long-acting tricyclic histamine antagonist with selective H1-receptor histamine antagonist activity. Desloratadine inhibits histamine release from human mast cells in vitro. Pharmacokinetics: Absorption Following oral administration of a desloratadine Smg tablet once daily for 10 days to normal healthy volunteers, the mean time to maximum plasma concentrations (Tmax) occurred at approximately 3 hours post dose and mean steady state peak plasma concentrations (Cmax) and AUC of 4 ng/mL and 56.9, ng.hrimL. were observed, respectively. Neither food nor grapefruit juice had an effect on the bioavailability (Cmax and AUC) of desloratadine. Metabolism Desioratadine (a major metabolite of loratadine) is extensively metabolized to 3-hydroxydesloratadine, an active metabolite, which is subsequently glucuroni- dated. Distribution Desloratadine and 3-hydroxydesloratadine are approximately 82% to 87% and 85% to 89% bound to plasma proteins, respectively. Elimination The mean plasma elimination halflife of deslorata- dine was approximately 27 hours. Cmax and AUC values increased in a dose proportional manner following single oral doses between 5 and 20 mg. The degree of accumulation after 14 days of dosing was consistent with the halflife and dosing frequency.Analysis of plasma 3 hydroxydesloratadine showed similar Tmax and half-life values compared to desloratadine. USE IN SPECIFIC POPULATIONS: Pregnancy Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, desloratadine should be used during pregnancy only if clearly needed Nursing Mothers Desloratadine passes into breast milk; therefore, a decision should be made whether to discontinue nursing or to discontinue desloratadine, taking into account the benefit of the drug to the nursing mother and the possible risk to the child. Renal Impairment Dosage adjustment for patients with renal impairment is recommended, Desloratadine and 3-hydroxydeslo- ratadine were poorly removed by hemodialysis. Hepatic Impairment Patients with hepatic impairment, regardless of severity, had approximately a 2.4-fold increase in AUC as compared with normal subjects. The apparent oral clearance of desloratadine in patients with mild, moderate, and severe hepatic impairment was 37%, 36%, and 28% of that in normal subjects, respectively. An increase in the mean elimination halflife of desloratadine in patients with hepatic impairment was observed. Dosage adjustment for patients with hepatic impairment is recommended. DOSAGE AND ADMINISTRATION: Antimin-D Tablets may be taken without regard to o SHRIGAN B10z-20-16 (L0°ON Ae) Full prescribing information available on request SHAIGAN Pharmaceuticals (Pvt.) Limited 14Km Adyala Road, Post Office Dahgal, Rawalpindi Pakistan www.shaigan.com meals. The recommended dose of Antimin-D Tablets for Adults and Adolescents 12 Years of Age is one 5mg tablet once daily. In adult patients with liver or renal impairment, a starting dose of one 5mg tablet every other day is recommended based on pharma- cokinetic data ADVERSE REACTIONS: The most common adverse reactions were pharyngi- tis, dry mouth, myalgia, fatigue, somnolence, dysmen- orthea. The rare cases of adverse reactions are tachycardia, palpitations, rash, pruritus, urticaria, edema, dyspnea, and anaphylaxis, psychomotor hyperactivity, movement disorders (including dystonia, tics, and extrapyramidal symptoms), seizures, and elevated liver enzymes including bilirubin, and very rarely, hepatitis. CONTRAINDICATIONS: Antimin-D Tablet is contraindicated in patients who are hypersensitive to this medication or to any of its ingredients or to loratadine. INSTRUCTIONS: Protect from heat, light & moisture. Store below 30°C. Medicines should be kept out of the reach of children. To be sold on the prescription of a registered medical practitioner only. PRESENTATION: Antimin-D Tablets are available in blister pack of 1x10's. LIF Sires b Ba sth ete Bret atime BS he tuitaopenion fe Fess AL imipis“Amlopin bons COMPOSITION: Each film coated tablet contains: Amlodipine (as Besylate), U.S.P .eennsnsnnnen SQ (Product Specs.: U.S.P) Amlodipine besylate is slightly soluble in water and sparingly soluble in ethanol and has a molecular weight 567.1 (free base 408.9). Amlodipine besylate is available in tablets containing 5mg of active Amlodipine base. ACTIONS: ‘Amlodipine is a calcium ion influx inhibitor (slow channel blocker or calcium ion antagonist) and inhibits the transmembrane influx of calcium ions into cardiac and smooth muscle. The mechanism of the anti hypertensive action of Amlodipine is due to a direct relaxant effect on vascular smooth muscles. The precise mechanism by which Amlodipine relieves angina has not been fully determined but Amlodipine reduces total ischemic burden by the following two actions: 1. Amlodipine dilates peripheral arterioles thus, reduces the total peripheral resistance (after load) against which the heart works. Since there is no associated reflex tachycardia, this unloading of the heart reduces myocardial energy consumption and oxygen requirements and probably accounts for the effectiveness of Amlodipine in myocardial ischemia, 2. The mechanism of action of Amlodipine probably involves dilatation of the main coronary arteries and coronary arterioles both in normal and ischemic regions. This dilatation increases myocardial oxygen delivery in patients with coronary artery spasm (prinzmetal's or variant angina). After oral administration of therapeutic doses, Amlodipine is well absorbed with peak blood levels between 6-12 hours postdose the volume of distribution is approximately 20 Itr/kg. The terminal plasma elimination half-life is about 35-40 hours and is consistent with once daily dosing. Steady state plasma levels are reached after 7-8 days of consecutive dosing. Amlodipine is extensively metabolized by the liver to inactive metabolites with 10% of the parent compound and 60% of metabolites excreted in the urine. In patients with hypertension once daily dosing provides clinically significant reduction of blood pressure in both the supine and standing positions throughout the 24 hours interval. Due to the slow onset of action, acute hypertension is Not a feature of Amlodipine administration. In patients with angina; once daily administration of Amlodipine increases total exercise time and decreases both angina attack frequency and nitroglycerine tablet consumption. Amlodipine has not been associated with any adverse metabolic effects or changes in plasma lipids and is suitable for use in patients with asthma, diabetes and gout. In vitro studies have shown that approximately 97.5% of circulating Amlodipine is bound to plasma proteins. DRUG INTERACTIONS: Amlodipine has been safely administered with thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, long-acting nitrates, sublingual nitroglycerine, non-steroidal anti-inflammatory drugs, antibiotics and oral hypoglycemic drugs. Special studies have indicated that the co-administration of Amlodipine with digoxin did not change serum digoxin levels or digoxin renal clearance in normal volunteers, and that co-administration of cimetidine did not alter the pharmacokinetics of Amlodipine. In vitro studies with human plasma indicate that Amlodipine has no effect on protein binding of the drugs tested (digoxin, phenytoin, warfarin, orindomethacin.) INDICATIONS: Amlopin (Amlodipine) is indicated for the first line treatment of hypertension and can be used as the sole agent to control blood pressure in the majority of Patients. Patients not adequately controlled ona single antihypertensive agent may benefit from the addition of Amlodipine, which has been used in combination with a thiazide diuretic, beta adrenoceptor blocking agent, or an angiotensin-converting enzyme inhibitor. Amlopin (Amlodipine) is indicated for the first line treatment of myocardial ischemia, whether due to fixed obstruction (stable angina) and/or vasospasm/vasoconstriction (prinzmetal's or variant angina) of coronary vasculature. Amlodipine may beused when the clinical presentation suggests a possible vasospasticivasoconstriction component but where vasospasmivasoconstrictions has not been confirmed. Amlopin (Amlodipine) may be used alone, as monotherapy, or in combination with other antianginal drugs in patients with angina that's refractory to nitrates and/or adequate doses of betablockers. CONTRAINDICATIONS: Amlodipine is contraindicated in patients with a known sensitivity to dihydropyridines. WARNINGS: Use During Pregnancy and Lactation: Safety of Amlodipine in human pregnancy or lactation has not been established. Amlodipine does not demonstrate toxicity in animal reproductive studies other than to delayed parturition and prolonged labor in rats at a dose level fifty times the maximum recommended dose in humans. Accordingly, use in pregnancy is only recommended when there is no safer alternative and when the disease itself carries greater risk for the mother, and child. Use In The Elderly: Although elderly patients may have higher plasma concentrations of Amlodipine than those in the younger ‘subjects, the terminal elimination half-lives were similar. Amlodipine, used at similar doses in elderly or younger patients, is equally well tolerated. Therefore normal dosage regimens are recommended. Use in Renal Failure: Amlodipine is extensively metabolized to inactive metabolites with 10% excreted as unchanged drug in the urine. Changes in Amlodipine plasma concentrations are not correlated with degree of renal impairment. ‘Amlodipine may be used in such patients at normal doses. Amlodipine is not dialyzable. Use in Patients with impaired Hepatic Function: Amlodipine half-life is prolongned in patients with impaired liver function and dosage recommendations have not been established. The drug should, therefore, be administered with cauti in these patients. ADVERSE REACTIONS: ‘Amlodipine is well tolerated. In placebo controlled clinical trials involving patients with hypertension or angina, the gb02-60-02 (oon “nou ‘SHRIGAN | most commonly observed side effects were headache, edema, fatigue, nausea, flushing and dizziness. No pattern of clinically significant laboratory test abnormalities related to Amlodipine has been observed. DOSAGE AND ADMINISTRATION: For both hypertension and angina, the usual initial dose is 5mg Amlodipine once daily, which may be increased toa maximum dose of 10mg depending on the individual patient's response. No dose adjustment of Amlodipine is required upon concomitant administration of thiazide diuretics, beta-blockers and angiotensin-converting enzyme inhibitors. OVERDOSAGE: There is no well-documented experience with Amlodipine over dosage. Since Amlodipine absorption is slow; gastric lavage may be worthwhile in some cases. Available data suggests that gross over dosage could result in excessive peripheral vasodilatation with subsequent marked and probably prolonged systemic hypotension. Clinically significant hypotension due to Amlodipine over dosage calls for active cardiovascular support including monitoring of cardiac and respiratory function, elevation of extremities, and attention to circulating fluid volume and urine output. A vasoconstrictor may be helpful in restoring vascular tone. INSTRUCTIONS: Protect from heat, light & moisture. Store below 30°C. Medicine should be kept out of the reach of children. To be sold on the prescription of a registered medical practitioner only. PRESENTATION: Amlopin is available in alu alu blister pack of 2x10's film coated tablets. LAr GEC be Sued bine SSG Lule epedion ke fet} 310 tips Full prescribing information available on request 9 SHAIGAN Pharmaceuticals (Pvt.) Limited 14Km Adyala Road, Post Office Dahgal, Rawalpindi Pakistan www.shaigan.comHE Acetofen Tablets ...35mg 450mg COMPOSITION: Each tablet contains: Orphenadrine Citrate, BP. Paracetamol, (Manufacturer's Specifications) INDICATIONS: Acute and chronic painful muscular conditions, tension headache, dysmenorrhea, nonarticular rheumatism, lumbago, torticollis, prolapsed intervertebral disc, sprains and strains, pain and spasm due to fractures and surgery. ’ CONTRAINDICATIONS: Glaucoma, pyloric or duodenal obstruction, stenosing peptic ulcer, prostatic hypertrophy or urinary obstruction,cardiospasm, myasthenia gravis, lactation and pregnancy. DOSAGE: 2 Tablets 3 times daily. PRECAUTIONS: Acetofen should be used with caution in patients with cardiac decompensation, tachycardia and cardiacarrhythmias. SIDE EFFECTS: Nausea, vomiting, dry mouth, blurred vision, dizziness, confusion and tremor. INSTRUCTIONS: Protect from heat, light & moisture. Store below 30°C. Medicine should be kept out of the reach of children. To be sold on the prescription of a registered medical practitioner only. PRESENTATION: Acetofen Tablets are available in blister pack of 10 X10 tablets. LUIGI L ety SSF AE Are LESS, 5 Ba Gus ey Ea FEES Loe wep fas yak ph pedo ils Full prescribing information available on request: SHAIGAN Pharmaceuticals (Pvt.) Limited 14Km Adyala Road, Post Office Dahgal, Rawalpindi Pakistan ‘SHKIGAN www.shaigan.comBrotin (Bromocriptine) TABLETS ‘Stimulator of dopamine receptors, inhibitor of prolactin secretion, COMPOSITION: Each tablet contains Bromocriptine (as Mosytate), 8.P 25mg (Product Specs.: BP) PROPERTIES: Brotin inhibits the secretion ofthe anterior pituitary hormone prolactin, Without afecing nomal levels of her ptuitary hormones. However Brottin 's capable of reducing elevated levels of growth hormone (GH) inpatients with acromegaly. These effects are due to simulation of dopamine receptors, In the puerperium prolactin is necessary fr the inition and maintenance cf puerperal lactation. Increased prolactin sereton gives ris to pathological lactation (galactorhea) and/or disorders of ovulation and menstuation. ‘As spectic inhibitor of prolactin secretion. Brrotin can be used to prevent ‘or suppress physiological lactation as well as to treat prolacininduced Pathological slates in amenorrhea and J or anovulation of the uterus and ‘does not increase the risk of thrombo-embolism, Brotin has been shown to arrest the growth orto reduce the size of rolactin-secreting pituitary adenomas (prlactinomas), In acromegalc patents-apat from lowering the plasma levels of growth hormone and proiactn Brrottin has a beneficial effect on cinical symptoms and on glucose tolerance. Brotin improves the cinical symptoms ofthe polycystic ovarian syndrome by restoring a normal pattem of LH secretion. Inpatents with benign breast isease. Brotin reduces the size and number of cysts andlor nodules ofthe breast and alleviates the breast pain often associated with such conditions by normalizing the underlying progesteroneloestrogen imbalance. At the same time it reduces prolactin ‘secretion in patients with elevated levels. PHARMACOKINETICS: Following oral administration, Brotin is well absorbed When using tablets in healthy volunteers, the absorption halflife is 0.2-05 h, and peak plasma levels of bromocriptine are reached within 1-3 hours. The prolactinlowering effect sets in within 1-2 aftr ingestion reaches its maximum, ie a reduction of prolactin in the plasma by more than 80%, within 5-10h and remains close tomaximum for 8-12hours. The elimination ofthe parent rug from plasma isbiphasic, wih ateminal hal-ife of about 15 h (range 8-20). Parent drug ‘and melaboites are almost completely excreted via the liver, with only 6% being eliminated via the kidney Plasma protein binding amount is 96%. ‘There iso evidence tha the pharmacokinetic properties and tolerability of Brotiin are directly affected by advanced age. However, in pationts with impared hepatic function, the speed of elimination may be retarded and plasma levels may increase, requiring dose adjustment. INDICATION: Prolactin-dependent menstrual cycle disorders and female infertity: (je. hyperprolactinemic and apparently normoprolactinemic conditions). © Amenortiea (with or without galactorhea), olgomenorthea @ Luteal phase deficiency {@ Drugs induced hyperprotactinemic csorders (e.g. induced by ‘certain psychotropic or antihypertensive agents) PROLACTIN-INDEPENDENT FEMALE INFERTILITY: © Polycystic ovarian synérome © Anowuatory cycles (supplementary to ant-cestrogens, eg. clomiphene) PREMENSTRUAL SYMPTOMS: © Breast tendemess, boating, mood disturbances, HYPERPROLACTINAEMIA IN MEN: © Prolactn-elated hypogonadism (olgosperia, oss of ibid, impotence) PROLACTINOMAS: © Conservative treatment of prolactn-secreting pituitary micro- ‘adenomas or macro-adenomas ‘@ Prior to surgery in order to reduce tumour size and to facilitate removal © After surgery if prolactin levels stil elevated ‘ACROMEGALY: ‘As an adjunct, or in special cases as an alternative, to surgery or raiotherapy. BENIGN BREAST DISEASE: ‘@ Nastaloia isolated or in association with premenstrual syndrome ‘or with benign nodular of cystic alterations) (@ Benign cystic and/or nadular conditions, in particular brocystc breast disease. DOSAGE: Brottin should always be taken with fod. Menstrual cycle disorders, female infertility: 4.25 mg (V2 tablet 2 or 3 times daily: if his roves inadequate, gradually increase to 2.5mg 20r3 tes daly. Continue reatment uni the mensral «yee has retued to ronal andor ovulation restored, trequred,teatment may be continued over several yes to prevent elapse PREMENSTRUAL SYMPTOMS: ‘The treatment begins onthe 1éth day ofthe cycle with 1.25 maj1/2 tablet) dally, the dosage being increased in steps of 1.25 mg dally up to 25 mg twice dally unt menstruation ses in. MALE KYPOGONADISM: 1.25mg (12 tablet) 2or3 times daily, gradually increasing to several tablets daily as required to keep plasma prolactin adequately suppressed. ACROMEGALY: Intl 1.25 mg (1/2 tablet) 2 or 3 times dally, gradualy increasing to 10 to 20 mg daily, depending on clinical response and side effects. PUERPERAL BREAST ENGORGEMENT: Single dose of.§ mg, may be repeated after 6 to 12 hours, without causing inappropriate suppression of lactation,INCIPIENT PUERPERAL MASTITIS: ‘Same dosage a for inhibition of lactation. An antibiotic should be added to the regimen, as required BENIGN BREAST DISEASE: 1.25 meg (12 tablet) 2 or 3 times daly, gradually increasing to § to 7.5 mg per day ‘CONTRAINDICATIONS: Hypersensitvty to bromocriptine or other ergot alkaloids. Toxemia of Pregnancy, hypertension during postpartum and in the puerperium, For procedure during pregnancy, ‘see Use in pregnancy’, PRECAUTIONS: In rare cases (about 1 in 100,000 postpartum women treated with Brotiin forthe prevention oflactaion) serious adverse evens, incuding hypertension, myocardial infarction, seizures, stroke, or psychic disorders have been reported, Insome patents the occurrence of seizures or stroke was preceded by severe headache andlor tansient visual disturbances. Although the causa relationship ofthese events tothe drugis uncertain, Brottin should ‘ot be used in the postpartum and in puerperal women with high blood Pressure, coronaty artery disease of symptoms andlor a history of serious psychic disorders. In postpartum women receiving Brrotin blood pressure should be carefuly monitored, especially during the frst day of therapy Particular caution is required in patients who have recent been treated or ‘are on conconitan therapy with drugs that can alter blood pressure, Although there is no conclusive evidence of an interaction between Brottin and ‘other ergot alkaloids, eg. ergometrine and methylegometne, the onconitant se ofthese medicatons isnot recommended. If hypertension, unremiting headache, or any signs of CNS toxicity develop, treatment should be iscontinued immediately, Fertty maybe restored by treatment wih Brotin. Women of child-bearing age who do not wish to conceive should therefore be advised to practice a relable method of contraception. women wth condons not associated wih hyperprolacinemia are treated with Brrotin the drug should be given nthe lowest elective dose nocossary ‘oreleve the symptoms: this isin order to avoid te possibilty of suppressing plasma prolactin bolow normal level, with a consequentimpairment of luteal function In patients to be treated for mastagia and nodular andlor cystic breast alterations, malignancy must be excluded by appropriate diagnostic procedures, ‘There have been occasional reports of gastro-intestinal bleeding in ‘acromegalic patients, both in those treated with Brottin and those given ‘a different or no medication. Until futher data are available, acromegalc Patients witha history of evidence of peptic ulceration should preferably be siven alternative treatment. f Brottin must be used in such patients, they ‘shouldbe instructed to report promply any gastrointestinal reactions. Caution is required when Bsrottn is being given to patients with a history ‘of psychotic or severe cardiovascular disease. ‘Since hypotensive reactions may be disturbing in some patients, especially uring the fst days of treatment, particular care should be exercised when dbving vehicles or operating machinery. Tolerability Brotin may be reduced by alcohol. (Rev. No.2) 20.09.2018 USE IN PREGNANCY: In patients wishing to conceive, Brottin, lke all other drugs, should be ‘discontinued when pregnancy is confirmed, uniess there is amedical reason {orcontiuing therapy. No increased incidence of abotion has been observed {allowing withdrawal of Brrotin under these conditons. Extensive experience incicates that Brottin, administered during pregnancy does not adversely affect its course or outcome, It pregnancy occurs inthe presence ofa pituitary adenoma and Brotin ‘eeatment has been stopped, close supervision through out pregnancy is essential. In patients who show symptoms of a pronounced enlargement of aprolactinoma, e.g headache & visual field deterioration Brotin treatment may be re-instituted or surgery may be considered appropriate. INTERACTIONS: The conoomitant use of entyomycin or jsamycn may increase bromocriptine piesma levels. ‘SIDE EFFECTS: During theft ow day of treatrent some patents may experience sight nausea and, more rarely, zines, fatigue or vomiting, which ae rt, honever,suffcienty serious to require treatment to be discontinued. If necessary iil nasa aeorvoriing may be inhibted bythe emporary intake ofa suitable ant-emetic hour pro re acinsraton of Brotin. In rare instance Brotin may induce orthostatic hypotension, and itis therefore advisable to check bloodpressure in ambulant patents atintervals during theft days oftreatment. Ohostatc hypotension may be troublesome but can be treated symptomatical, Episodes of reversible pallor ofthe fingers and toes induced by cold have ‘cocasionlly been reported io occur durin prolonged treatment, particulary inpatients previously exhibiing Raynaud's phenomenon, Tose side effects ‘are mosty dose dependent and can usually be contolled by a reduction in dosage. ‘TREATMENT OF OVERDOSAGE: No ife-heatering reactions have been reported ater acute overdosage; the maximum single dose so far ingested by an adit person is 225 mg. The observed symptoms were nausea, vomiting, dizziness, postural hypotension, sweating, drowsiness and halucnatios. The management of acute itoxicaion is sympiomatic. Mtoclopramide may be inciate forthe teatment of emesis or halucinatons INSTRUCTIONS: Protect fom heat, ight and moisture. Store below 30°C Medicine should be kept outofthe reach of children. Tobe sald onthe prescription of aregistered medical practioner ony. PRESENTATION: Brotin is avalabe in bisier pack of x0 tablets EL etn LE Mr bse te roy, “Ane 8bsGoir. Lyoire wp hess stow SHAIGAN Pharmaceuticals (Pvt) Limited ‘V4Kim Adyala Road, Post Ofice Dahgal, Rawalpindi Pakistan ‘vw shaigan.com 9 SHONEYPROST Sterile Ophthalmic Solution COMPOSITION: Each ml contains: Travoprost , U.S.P. (Product Specs. : U.S.P) . 40ug DESCRIPTION: EYPROST contains Travoprost, one of a group of medicines called prostaglandin analogues. It works by reducing the pressure in the eye. It may be used on its own or with other drops e.g. Beta-blockers, which also reduce pressure. INDICATIONS AND USAGE: EYPROST is used to reduce high pressure in the eye in adults, adolescents and children from 2 months old onward. This pressure can lead to an itiness called glaucoma. DOSAGE AND ADMINISTRATION: One drop in the affected eye or eyes, once a day - in the evening. OVERDOSAGE: No cases of over dosage have been reported. A topical overdose is not likely to occur to be associated with toxicity. A topical overdose of travoprost eye drops may be flushed from the eye with lukewarm water. DRUG INTERACTION: No interaction studies have been performed. CONTRAINDIGATIONS: Hypersensitivity to the active substance or any of the excipients. WARNING AND PRECAUTIONS: EYPROST may increase the length, thickness, color and/or number of your eyelashes. Changes in the eyelids including unusual hair growth or in the tissues around the eye have also been observed. EYPROST may change the color of your iris (the colored part of your eye). This changemay be permanent. A change in the colour of the skin around the eye may also occur. Ifyou had cataract surgery, talk to your doctor before you use EYPROST. If you have current or previous history of an eye inflammation (iritis and uveitis), talk to your doctor before you use EYPROST. PREGNANCY: Pregnancy Category C Travoprost has harmful pharmacological effects on pregnancy andior the fetus/new bom child. Travoprost should not be used during pregnancy unless clearly necessary. BREAST FEEDING Do not use Travoprost if you are breast feeding. SIDE EFFECTS: Eye redness, changes in the color of the iris (colored part of the eye), eye pain, eye discomfort, dry eye, itchy eye, eye irritation. INSTRUCTIONS: Protect from heat, light & moisture. Store at 2°C-25°C. To be used within 30 days after opening. Medicine should be kept out of the reach of children. To be sold on the prescription of a registered medical practitioner only. PRESENTATION: EYPROST ophthalmic solution is supplied as 2.5m! sterile ophthalmic solution in a plastic dropper bottle. HII L oth SH Sap LAK, Sro rib Bisset Gricty Pp Foe BS ubebipp La JPi ec ostent a feti}z VL pis ——iut SHAIGAN Pharmacet (Pvt.) Limited ‘ékm Adyala Road, Pot Ofce Dahgal, Rawalpnd Pakistan ‘www shaigan.comCeftazidime 250, 500, 1000 For I.M / 1.V INJECTION COMPOSITION Each vial dry substance contains: Ceftazidime (as Ceftazidime Pentahydrate), USP ... 250 or 500 or 100mg (Product Specs.: U.S.P) DESCRIPTION Cet or inecton is supped asa wh fat yellow pond vials containing 250mg, 500mg and 1g ceftazidime (as pentahydrate). On the addition of water for injections, Cefiz dissolves with effervescence to produce a solution for inject Ceftz for injection contains 116mg ceftazidime pentahydrate which is equivalent to 100mg ceftazidime free acid. INDICATIONS Treatment of single or multiple infections caused by susceptible organisms. May be used alone as first choice drug before the results of sensitivity tests are a May be used ic against anaerobes when presence of Bacteriodes fragilis is suspected. Indications Include: Severe infections e. g. septicaemia, bacteraemia, ‘meningitis, infection in immunosuppressed patients, infection Urinary tract infections, fections and abdominal infections ‘continuous amb Prophylaxis: pros! ) BACTERIOLOGY Ceftazidime is highly stable to most produced by both Gram-positive and itis active against many ampi Ceftazidime has high intrn MIC range for most genera with minimal changes in MIC at varied inoculum levels. In vitro the activities of ceftazidime and aminoglycosides in combination are additive There is evidence of synergy in some s Ceftazidime is active in Gram-negative: E col Klebsiel including KI pneumoniae) Proteus mirabilis Proteus vulgaris Morganella morgani (formerly Proteus morganil) Proteus rettger Pseudomonas spp (including Ps. aeruginosa) 1e following organisms: Providencia spp Enterobacter spp Citrobacter spp Serratia spp Salmonella spp Yersinia enterocolitica Pasteurella multocida Acinetobacter spp Neisseria gonorthoeae (Group A beta-haemolytic streptococci) rept, agalactiae) Streptococcus pneumoniae Streptococcus ‘Streptococcus (excluding Enterococcus, Streptococcus faecalis) ‘Anaerobic Strai Peptococcus sp Peptostreptococcus spp Streptococcus spp Propionibacterium spp Clostridium peringens Fusobacterium spp Bacteroides spp (many resistant staphylococci Streptococcus faecalis and many other Enterococci Clostridium dificile Listeria monocytogenes Campylobacter spp DOSAGE : Dosage depends on severity, sensitivity site and type of infection and ‘age and renal function of the patient. 6g / day in 2 of 3 divided doses by IV or IM fact and less severe infections: 500mg or 1g every 8 hours or 2g every 12 hours. in Immunocompromised patients jection Including ystic adults vided doses When used as a prophylactic agent in prostatic surgery 1g should be given at the induction of anesthesia. A second dose should be considered atthe time of catheter removal ia: 2g every 8 or 12 :seudomonal lung infections: 100-150mg/kg/day In sits with nora renal incon Side has been used without il effect. Infants and children (>2 months): 30-100mgikg/day in 2 or 3 divided doses. Doses upto 150mg/kg/day (maximum 6g/day) in three be given to infected immunocompromised or fbrocystic children or children with meningitis Neonates (0- the serum rly patients, the daily dosage should nat normally exceed in those over 80 years of age. pai Ceftazidime is excreted unchanged by the kidneys. Therefore in with impaired renal function the dosage should be reduced. Ar loading dose of 1g should be given. Maintenance doses should be based on Gi Recommended maintenance doses of ceftazidime in renal insufficiency: ‘Approx. Serum | Recommended | Frequency creatinl unit dose of | of dosing (memovl)(mg/dl) | ceftazidime (g) | (hourly) <150 : Normal dosage 150-200 (1.7-2.3)| 1.0 12 200-350 (2.3-4.0)| 1.0 24 ‘350-500 (4.0-5.6)| 0.5 24 >500 (>5.6) 05 48 In patients with severe infections the unit dose should be increased by 50% or the dosing frequency sed. In such patients the ceftazidime tera levee shou bo m itored and trough levels should not exceed 40mag/ In children the creatinine clearance should be adjusted for body surface area or lean body mass. to 5 hours. Following each haemodialysis period the mé of ceftazidime recommended in the above table should be repeated. a single dose or in di : dosage recommended under impaired renal function. ADMINISTRATION Use intravenously or by deep intramuscular injection. Recommended IM gluteus maximus oF igh. jons: When the product dissolves, carbon dioxide ‘and a posiive pressure develops. ‘Small bubbles of carbon dioxide in the constituted solution may be ignored. Vial Size | Route of a Approx Administration. | Di Concentration A ‘mgiml 250mg | Intramuscular | 1.0m! 210 2.5m 90 500mg 1.5ml 280 Intravenous 5.0m 90 19 Intramuscular _| 3.0mi 260 Intravenous 100m! 90 Ceftazidime solutions may be given directly into the vein or introduced 3 patient is receiving parenteral fis. ly used intravenous fluids. ge needle through the vial closure and inject the recommended volume of dient. ‘2.Withdraw the needle and shake vial to give a clear solution.3. Inver the vial. With the syringe piston fully depressed insert the needle into the solution. Withdraw the total volume of solution into the syringe ‘ensuring that the needle remains inthe solution, Small bubbles of carbon dioxide may be disregarded. CONTRA-INDICATIONS > Patients with known hypersensitivity to cephalosporin antibiotics. WARNINGS Before beginning treatment establish whether the patient has of hypersensitivity reactions to ceftazidime, cephalosporins, per or other drugs. Special caution is necessary when giving ceftazidime to patients who have previously shown type 1 orimmediate hypersensitivity reactions to penicilin. if an allergic reaction to ceftazidime ocours discontinue the drug. Serious 18 may require epinephrine (adrenaline), ‘amine or other emergency measures. PRECAUTIONS Concurrent treatment with high doses of cephalosporins and nephrotoxic drugs such as aminoglycosides or potent diuretics (e.g. frusemide) may adversely affect renal function. Clinical experience has shown that this is ne 10 evidence that ceftazidime adversely affects renal function at rapeutc doses. Ceftazidime is eliminated via the kidneys; during the early ‘months of pregnancy and early infancy. Ceftazidime is excreted in human milk in small quantities and should be used with caution in nursing mothers. Ceftazidime does not interfere with enzyme-based tests for glycosuria ith copper reduction methods Ceftazidime does not interfere in the ine. in about 5% of patients and may interfere prolonged use may result in Candida, Enterocoosi), the overgrowth of non-susceptile ‘appropriate measures, which may require interruption repeated evaluation ofthe patient is essential. Chloramphenicol is antagonistic in vitro wth ceftazidime and other cephalosporins. The dlnical relevance ofthis finding is unknown, but concurent adminstraton of ceftazidime with chloramphenicol is proposed, the possibility of antagonism should be considered. SIDE-EFFECTS Ceftazidime is generally well tolerated. Adverse reactions are infrequent ‘ombophlebits with IV administration, pain and/or injection. Hypersensitivity: Maculopapular or urticarial rash, fever, pruritus, and very rarely angioedema and anaphylaxis incuding bronchospasm andlor hypotension) et cephalosporins, there have been rare reports of toxic nausea, vomiting, abdominal pain and very Genito-urinary: Candidiasis, vaginitis Central Nervous System: Headache, dizziness, parasthesia and bad taste. There have been repors of neurological sequelae including tremor, myocolonia, convulsions and encephalopathy in patients with renal impairment. In whom the dose of ceftazidime has not been appropriately have been observed penia, agranulocytosis, thrombocytopenia and lymphocytosis have been reported. ‘OVERDOSAGE Overdosage can lead to neurological sequelae including encephalopathy, convulsions and coma. Serum levels of ceftazidime can be reduced by haemodialysis or peritoneal dialysis. PHARMACEUTICAL PRECAUTIONS Vials of Ceftiz for injection should be stored at a temperature below 25°C. Occasional st ‘temperatures not higher than 30°C for up to 2 months is not detrimental to the product. Protect unconstituted vials from li lutions of ceftazidime in Water for injections or compatible fluids retain sfactory potency for 18 hours at a temperature below 25°C or 7 days eftazidime is compatible with most commonly used Js. Ceftazidime is less stable in Sodium Bicarbonate Js. Its not recommended as a should not be mixed in the same giving set or syringe. Pre n has been reported when vancomycin has been added to ceftazidime in solution. Therefore it would be prudent tofush giving sets and intravenous lines between administration of these two agents. Solutions range from lght yellow to amber depending on concentration, diluent and storage conditions used. Within the stated recommendations, product potency is not adversely affected by such colour variations. Cetaze at concenteons between Iginla Omg compel 0.9% Sodium Chloride injection MI6 Sodium Lactate Injection Compound Sodium Lactate Injection (Hartmann’s Solution) 5% Dextrose Injection 0.225% Sodium Chloride and 5% Dextrose Inj 0.45% Sodium Chloride and 5% Dextrose Inj 0.9% Sodium Chloride and 5% Dextrose injection 0.18% Sodium Chloride and 4% Dextrose Injection 10% Destro Dextran 40 Ceftazidime at concentrations between 0.05mg/ml and 0.25mgiml is compatible with intraperitoneal Dialysis Fluid (Lactate), Geftazidime may be constituted for intramuscular use with 0.5% or 1% Lignocaine Hydrochloride Injection Both components retain satisfactory potency when ceftazidime at 4mgiml is admixed with Hydrocortisone (hydrocortisone sodium phosphate) mg/m in 0.9% Sodium Chloride Injection or 5% Dextrose Injection. Cefuroxime (cefroximesocum) mg n0.% Sodium Chore inject Cloxacilin (cloxacilin sodium) 4mg/ml in 0.9% Sodium Chloride Heparin 101U/mi_ in 0.9% Sodium Chloride Injection Potassium Chloride mg or mE nO. Saum Close injection The contents of a 500mg val of Ceftizfor Injection, constituted with 1.5m ections, may be added to metronidazole injection (500mg in 100m)) and both retain their activity. PHARMACOKINETICS Parenteral administration produces high and prolonged serum levels, which decrease with a halt-ife of about 2 hours. After IM administration ‘of 500mg and 1g, peak levels of 18 and 37mgll respectively are rapidly achieved, and minutes afer IV bolus injection of 800ma, 19 oF 2, serum levels are respectively 46, 87 and 1 Therapeutically effective concentrations are ‘12 hours after either IV or IM administration. ‘Sorum protain bind Ceftazidime is not metabolized in the body and is excreted unchanged, imately 80- ‘resentin the serum &- in active from into the urine by glomerul of the dose is recovered in Elimination of ceftazidime is decreased in patients with function and the dose should be reduced. See section on rene Less than 1% is excreted via the bile, which limits the amount entering in excess of the MIC for common pathogens the intact blood-brain barrier is poor resulting in in CSF in the absence of inflammation, However therapeutic levels of 4- 2Omgll or more are achieved inthe CSF when the meninges ae inflamed. 3: Use only freshly prepared solution. Protect from heat, re. Store below 25°C, Medicine should be kept out of the practitioner only. PRESENTATION Box containing 1 vial of 250mg, 500mg or 1000mg ceftazidime (as pentahydrate) + solvent ampoule (water fr injection 5m) for intramuscular or intravenous use. LA Serb Lethe bipeiterle SE Sites $B St Hes hess A fis 5p i5 oe GS ubetuit ——— Full prescriing information av SHAIGAN Pharmaceuticals (Pvt. 44km Adyala Road, Post Office Dahgal, Rawalpindi Pakistan SHAICAN www-shaigan.comCeftriaxone 250 & 500 For 1.M INJECTION Long-acting, broad-spectrum cephalosporin antbitc for parenteral use Composition (GELTIS LM 250: Each vial of dry substance contains: Ceftriaxone sodium, USP og. to ceftiaxone 250mg (CELTIS LM'S00: Each va of dry substance contains: Cettaxone sodium, USP eq, to ceftiaxone. 500mg (Product Specs: USP) Properties, Effects Microbiology ‘The bactericidal att of ceftiaxone resus from inhiton of cll wal synthess Ceftriaxone exerts in-vivo actvty agains a wide range of gram-negative and gyam-gosiive mérorganisns, Cefrixone highly sable to most acatamases, both penictinases and cephalospornases, of gram-positive and gram-negative bacteria. Cefriaxone is usualy active agains the folowing microorganisms in vito and in cinical infections (see Indications} Gram-positive aerobes: ‘Staphylococcus aureus (nclding peniiinase-producng strains), Staphylococcus ‘epidermidis, Sreptococcus pneumoniae, Sreptococcus group A (St. pyogenes), ‘Steptacoccus group B (St. agalactiae), Streptococcus viridans, Streptococcus bovis Noe: Methilinesistant Stahylococcus spp. are resistant fo cephalosporin, including cetriaxone. Most strains of Enterococci (e.g. Sreptococcus faecalis) are resistant. Gram-negative aerobes: Aeromonas spp, Alcaligenes spp, Branhamelia catahalis (tactamase negative and postive), Citrobacter spp, Enterobacter spp. (some sans are resistant, Escherichia coli Haemophilus ducreyi, Haemophilus infuenzae (including penicilinase-producing strains) Haemophilus parainfuenzae, Klebsiella spp. (including Ki. pneumoniae), Moraxella spp. Morganella morgani, Neisseria ‘gonoroeae (inudingpeniiinase-producing stains) Neissaa meningits, Pesiomonas shgeoides, Proteus mab, Proteus vugaris Provdencia sp, Pseudomonas aeruginosa (some stains ae resistant), Salmonela spp. (including. typhi), Serratia spp. (incuding S. marcescens), Shigella spp, Vibrio spp. (including V.choleree), Yersinia spp (including Yenterocotca) "Note: Many stains ofthe above microorganisms that are mutiple resistant other antbotes, eg penis, oder copalospoins and aminoacids, are suscepble toceftiaxone. Treponema palium s sensive nitro and in animal experments, nical invesigations inate tat primary and secondary syphilis respond wel ceftianone therapy Anaerobic organisms, Bacteroides spp (including some stains of 8 fags), Clostridium spp (Cl. dle), Fusobacterium spp. (except F. moriferum and F. varium), Peptococcas spp. Peptosterplozoccus spp. Note: Many stains of pactamase-producing Bacteroides spp (notably Brags) ‘at resistant Pharmacokinetics Cefriasones characterized by an unusual long einaon hale of approximately ght hours in healthy adults. The area unde the plasma concentration time curve ‘means bioavaiabity of CHTIS (Ceftiaxone) administered is 100%. Elimination The elimination hain heathy adits is abou eight hous. In iefents aged iss than eight days andin person over75 years of ge, the average eiinaion halite is about twice as ong, In adits, 50-60% ofcetraxoneis excreted unchanged by the kidneys, while 40-50% is excreted unchanged in tho bil. The intestinal fora transforms ceftiaxone into inactive metaboles. In neonates, renal elminalon account for about 70% ofthe dose. In patos wit ronal impairment or hepatic ‘dystuncton the pharmacokinetics of ceftiaxone ae only minimal altered andthe elimination halite is only sight increased. kidney funtion alone is impaired, bilaryeinatin of cetiaxone is inreased iver funcion lone iimpared, renal elimination i increase. Protein binding Ceftriaxone is reversibly bound to albumin, and the binding decreases with the increase in the concentration, e.g om 95% nding at plasma concentration of < 100 mal to 85% binding at 300 maf. Owing to the lower albumin content the proportion of ree cefiaxone in intersital uid is correspondingly higher than in plasma, Penetration into the cerebrospinal fluid Ceftriaxone penetrates te iffamed meninges of infants and cilden. The average extent of dui in he cerebrospinal fd in bacterial meningitis 17% othe plasma concentration, ie. aprosimately four times that in aseptic meningitis Cefriaxone concentaions of>1 4m have been found inthe CSF 24 hours after injection of CELTS in doses of $0-100 mfg. In adult meningitis paint, administration of 50 meg leas within 2-26 hours to CSF concentrations several times higher than the minimum inhibitory concentrations required forthe most common causatve organisms of meningits Indications Infections caused by pathogens sensitive fo CTS (Ceftriaxone), eg © sepsis; mening abdominal fectons (pent, infection ofthe biary and gastointsina ac); infecon ofthe bones, joints, sof tissue, sin and of wounds, infects in ations with impaired defence mechanisms; tora and nary tact infobons: respiratory tract infections, particule pemonia, car, 050 and teat infections: genialnfectons, incuting gororea, peropeative prophylaxis of infections Standard dosage ‘Adults and chidren over twelve years: The usual dosage is 1-2 g of GELTIS (Cettiaxone) administered once daly every 24 hours). In severe cases or in infectons caused by moderately sensitive organisms, the dosage may be raised to4, administered once day Neonates, infants and children up to twelve years: The following dosage ‘schedules are recommended for once daly administration: "Neonates (up to two weeks): A daly dose of 20-50 mglkg bodyweight, not to ‘exceed 50 mag, on account ofthe immaturity of the infant's enzyme systems. 's not necessary fo differentiate between premature and infants bom at erm, Infants and children (three weoks to twelve years}: Adal dose of 20-80 mgika, For children with body weights of §0 kg or mare, te usual adult dosage should be sed, Intevenous doses of £0 mg of more per kg should be given by infusion over at least 30 minutes, Elderly patients: The dosages recommended ‘or adults require no modification in the case of geriatric patents. Duration of therapy ‘The duraton of therapy varies according to the course of the disease. As with antibiotic therapy in general, administration of GELTIS (Ceftiaxone) should be continued for a minimum of 48-72 hours ater the patient has become afebrile or evidence of bacterial eradication has been obtained, Combination therapy Sypergy between GEIIS (Ceftiaxone) and arnogyeosies hasbeen demonstrated with many gram-negative bac under experimental condor. Although enhancedactivity of such combinations is no avaysprediabe it should be considered in Severe, e-hreatning infecons de to microorganisms suchas Pseudomonas ders, Brae ops mcangabaly he Wo cs muse adntred separa atthe recommended dosages. Special dosage instructions Meningiés Inbacteral mein ininfants and chien, treatment bgins with doses of 100 ‘gh (otto exceed 4g) once dally. As soon asthe causative organism hasbeen, idee an is sensi, determined, the dosage canbe reduced accordingly ‘The best resus Rave ben fund with the folowing duration of therapy [Neisseria meningitis 4 days, Haemophilus inluenase 6days ‘Streptococcus pneumonias days Suscaptd Entorbactriaceae 10-14 days Gonorrhea For the treatment of gonorrhea (penicilinase-producing and ‘onpeniclinaseprodusing stains), a single doce of GEITIS (cofriaxone) 250!q (L.M)is recommended. Perioperative prophyfaxis ‘To prevent postoperative infection in contaminated or potentially contaminated surgery he recommerded approach depending on the sk of infections single dose of 1-2 g GETS (Cetraxone) administered 30-90 minutes prior to surge in ‘orci surgery, concurent (bu separate) administration of CEITS Ceftiaxone) anda S-ittomidazole, e.g. omidazle, has proven efecive Impaired renal an hepatic tuncton In patients wth impaied renal function, there is no need to reduce the dosage of [BIS (Cefriaxone) provides epatichunctio ntact. Oy in cases of pretemial renal fave (creatinine clearance <10 mini) should the GEITS (Cefriaxone) dosage not exceed 2g daly. in patents wt iver damage, thereis no need forthe dosage tobe reduced provided renal function is intact. In cass of concomitant severe renal andhepatcdystureton, he plasma concetaton of cefraxcne shoud be determined at regular intervals. In patiens undergong dialysis no addtional supplementary dosing is required folowing te dalsis. Serum concentrations should be monitored, however, to ‘determine whether dosage adjustments are necessary, since the elimination rate in hese patients may be reduced. Directions for use Reconstitited solution retain ther physical and chemical stabi for sic hours at ‘oom temperature (or 4 hours a 5°), Asa general ru, however te soluions should be sed immediately, ar preparation. Thy range in color from pale yellow to amber, depending on the concentration and the length of storage. This characteristic he acve ingens fn significance forthe eficacy ortlrance oe drug. Intramuscular injection For im. injector, CELTS (Cettiaxone) 250 or 00 gram is dissolved in lof 1% lidocaine and administered by deep itraglutea injection. Its recommended that ‘ot more than 1g be injected on ether side. The lidocaine soluton must never be administered intravenously Restrictions on use [GEIS (Cetriaxone) is contraindicated in pation wth known hypersensitivity to the cephalosporn class of antbiotcs. In pens hypersensitive fo peniclin, the possibilty of allergic coss-eactons should be bome in mind. ‘Although the relevant precinical investigations revealed nether mutagenic nor teratogenic effects. (Cefriaxone) should not be used in pregnancy (particulary in the fst trimester unless absolutely indicated. Precautions AS with other cephalosporins, anaphyactic shock cannot be ruled out even if a ‘thorough patient histor is taken Anaphylactc shock requies immediate counter measures such a intravenous epinephrine flowed by a glucocorticoid In tar cases, shadows suggesting sudge have been detected by sonograms of ‘he galbladder. Tis conion was reversible on discontinuation or completion of [CELTS (Cofriaxono) therapy. Even if such findings are associated with pain, conservative, nan surgical management is recommended, Inevito studies have shown tat ceftiaxone, ike some other cephalosporins, can 1.4 mglhave been foundin the CSF 24 hours after i injection of BEITIS in doses of 50-100 mg/kg. In adit meningits patients, ‘administration of 50 mg/kg leads within 2-26 hour to CSF concentrations several times higher than the minimum inhibitory concentrations required for the most ‘common causative organisms of mening. Indications: Infections caused by pathogens sensitive to CELTS, e.9, Sepsis; meningitis IE abdominal infections (penis, infections ofthe biliary and gastrointestinal act), infecions ofthe bones ons, soft tssue, skin and of wounds, infecSons in patents wid impaired defence mechanisms; renal and urinary tract infections, respiratory tract infections, particulaty pneumonia, and ear, nose and throat infections; 1 genital infections, including gonorrhea. 1 perioperative prophylaxis of infections Standard dosage: ‘Adults and children over twelve years: The usual dosage is 1-2 ¢ of CANIS ‘administered once daly (every 24 hours) In severe cases orn infections caused by moderately sensitve wganiss, the dosage may be raised og, administered onoe daly "Neonates infants and children upto twelve years: Te olovng dosage schedules ‘are recommended for once dally administration: "Neonates (upto two weeks). A daly dose of 20-50 mag bodyweight, not to exceed 50 mgkg, on aocourt ofthe immaturity ofthe infants enzyme systems, tis not ‘necessary to dferentate between premature and infants bom at tm. Infants and children (three weeks to twelve years): Adaly dose of 20-80 mglkg For chien wih body weights of50 kg or move, the usual adult dosage should be used Inravenous doses of 50 mg or more per kg shouldbe given by infsion over at ast 30 minutes, Eiderty patients: The dosages recommended for adits require no modification in the case of geriabc patents. Duration of thorapy: The duration of therapy varies according to the course of the dsease. As with anibitic therapy in general, administration of BELTS should be continued fr & minimum of 48-72 hours afer the patent has become afebrile or evidence of bacterial eradication has been obtained. Combination therapy: Syeray between GEIS and aminoglycosides has been demonsvated wth many ‘grar-negative baci under experimental condions, Although enhanced actly ‘of such combinations isnot always predictable, i shouldbe consideredin severe,liesteateninginfectons de omicorgniss suchas Psewdomenas aeruginosa, Because of physical incompatibility the two dugs must be adminstere separately al the recommended dosages, Special dosage instructions: Meningitis Im bacterial meringts in infants and children, treatment begins with doses of 100, "Malka (not to exceed 4g) once daily. As soon asthe causative erganism has been ‘dotied and is sensitvty, determined the dosage can be reduced accordingly ‘The best results have been found with the folowing duration of therapy: Neisseria meningitidis days Stretococcus pneumonias 7 days Gonorrhea: For the treatment of gonorhea (penicilinase-producing and onpencilinase-producing strains), GEIISis recommended, Perioperative prophylaxis: To prevent postoperative infecion in contaminated or potentially contaminated surgery the recommended approach depending on the risk af infectonsa single dose of 1-2 g GEITIS administered 30-90 minutes prior to surgeny In colorectal Surgery concurent (ut separate) administration of GBITIS and aS-nitemidazole, 29, omidazol, has proven effective. ‘Impaired renai and hepatic function: Inpatens wih imped real uncon, thor is no needa reduce he dosage of BETIS Provided hepatic function is ifac. Oy in cases of pretorminal renal fare (reaine Cearance <10 mlm) should the CIS dosage not exceed 2 g dal. Ingtiens with Iver damage, there no ned forthe dosage io be reduced provided renal uncon is intact. In cases of concomitant severe renal and hepatic dysfunction, the psa ‘oncerraton of oetiaxone should be determined at regular iervas, In patents undergoing dialysis no addtional supplementary dosing required ‘olowing the dialysis. Serum concentrations should be monitored, however, 10 {determine whether dosage adjustments are necessary since the elimination fate in these patients may be reduced. Directions for use Reconsituted solutions retain ther physical and chemical stabilty for sixhours at ‘oom temperature (or 24 hours at 5°C). As general rule, however the solutions shouldbe used immediatly afte preparation. They range in color from pale yelow to amber, depending on the concentration and the length of storage. This ‘characteristic of th active ingen sof 0 signiicance forte eflcacy orerance of the ug, Intravenous injection: For. njetion, BETTS 250, 500 or 1000 dissolved in Sm, of stele water for injections, and then administered by iv injection. lasting two to four minutes Haemophiusinfiuenzae ‘Says ‘Suscepibe Enerobactoracoae 10-16 days Restrictions on use: [CIM scontacate in gates with known hypersonsviyt the cephalosporin dass of anton patients hypersensitive fo pencil, the possibly of allergic ‘Goss-reactions should be bome in mind. ‘Although the relevant preclinical investigations revealed nether mutagenic nor teratogenic elec, should not be used in pregnancy (pariculary inte ist trimester) unless absolutely indicated, Precautions: ‘swith other cephalosporin, anaphylactic shock cannot be ruled out even if a thorough patient history is taken. Anaphyjactc shock requires immeciate counter measures such as intravenous epineptvine folowed by a glucooortcoid. In rare cases, shadows suggesting sludge have been detected by sonograms of ‘ho galladder. Tis conditon was reversible on discontinuation or completion of [CELTS terapy. Even if suc ndings are associated with pan, conservative, non surgical management is recommended. In-io studies nave shown that cetiaxone, tke some other cephalosporins, can displace bilirubin from serum albumin. Caution should be exercised when Considering GELS for hyperbirubinemic neonates, especialy prematures During prolonged treatment the biod picture shouldbe checked at regular interval, Undesirable effects: GELTIS is generally well tolerated. During the use of GEIIS, the folowing side

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