Lactulose

Lactulose

3.3g/5ml Syrup

Drug Category: Stimulant Laxative / Osmotically acting laxatives.

Brand Name: Duphalac

Pharmaceutical Form and Composition

Lactulose is an oral solution. It is a clear, viscous liquid, colorless to brownish yellow. Lactulose oral solution does not contain any excipients, but may contain small amounts of related sugars (e.g. lactose, galactose, epilactose, and fructose) derived from the route of synthesis.

Pharmacodynamics

In the colon lactulose is broken down by colonic bacteria into low-molecular organic acids. These acids lead to a lowering of pH in the colonic lumen and via an osmotic effect to an increase of the volume of the colonic contents. These effects stimulate the peristalsis of the colon and return consistency of the stools. The constipation is cleared and the physiological rhythm of the colon is reinstated.

In hepatic encephalopathy (HE), the effect has been attributed to suppression of proteolytic bacteria by an increase of acidophilic bacteria (e.g. lactobacillus) trapping of ammonia in the ionic form by acidification of the colonic contents, catharsis due to the low pH in the colon as well as osmotic effect, and alteration of the bacterial nitrogen metabolism by stimulating the bacteria to utilize ammonia for bacterial protein synthesis.

Within this context, however, it should be realized that hyperammonemia alone cannot explain the neuropsychiatric manifestation of HE. The ammonia however might serve as a model compound for other nitrogenous substances.

Lactulose as a prebiotic substance strengthens the growth of health promoting bacteria, like Bifidobacterium and Lactobacillus, whereas potentially pathogenic bacteria, like Clostridium and Escherichia coli may be suppressed. This may lead to a more favorable balance of the intestinal flora.

Pharmacokinetic Properties

Lactulose is poorly absorbed after oral administration and it reaches the colon unchanged. There it is metabolized by the colonic bacterial flora. Metabolism is complete at doses up to 25 – 50g or 40 -75ml; at higher dosages, a proportion may be excreted unchanged.

Preclinical Safety Data

The results of acute, sub-chronic and chronic toxicity studies in various species indicate that the compound has very low toxicity. The effects observed, appear to be more related to the effect of bulk in the gastrointestinal tract than to a more specific toxic activity.

In reproduction and teratology experiments in rabbits, rats or mice no adverse effects were found.

Therapeutic Indications

For Constipation: regulation of the physiological rhythm of the colon. Indicated where a soft stool is considered of medical benefit (hemorrhoids, post colonic/anal surgery). Hepatic Encephalopathy (HE): treatment and prevention of hepatic coma or precoma.

Administration and Dosage

Lactulose solution may be administered diluted or undiluted.

A single dose of lactulose should be swallowed in one and should not be kept in mouth for an extended period of time. The dose should be adjusted according to the individual needs of the patient. In case of single daily dose, this should be taken at the same time, e.g. during breakfast. During the therapy with laxatives it is recommended to drink sufficient amounts of fluids (1.5 – 2 liters, equal to 6 – 8 glasses) during the day. Dosing in constipation or where a soft stool is considered of medical benefit. It may be given as a single daily dose or is two divided doses; in bottles the measuring cup may be used. After a few days the starting dosage may be adjusted to the maintenance dose based upon treatment response. Several days (2 – 3 days) of treatment may be needed before treatment effect occurs.

The following dose is given:

Adult and adolescents: Starting daily dose 15 – 45ml. Maintenance daily dose 15 – 30ml.

Children (7 – 14years): Starting daily dose 15ml. Maintenance daily dose 10 - 15ml.

Children (1 – 6years): Starting daily dose 5 – 10ml. Maintenance daily dose 5 - 10ml.

Infants under 1 year: Starting daily dose up to 5ml. Maintenance daily dose up to 5ml.

Dosing in HE (for adults only)

Starting dose: 3 to 4 times daily 20 – 30g or 30 – 45ml. This dose may be adjusted to the maintenance dose to achieve 2 to 3 soft stools per day.

Pediatric population

The safety and efficacy in children (newborn to 18years of age) with HE have not been established. No data are available.

Elderly patients and patients with renal or hepatic insufficiency

No special dosage recommendations exist, since systemic exposure to lactulose is negligible.

Contraindications

-  Hypersensitivity to the active substance or to any of the ingredients.

- Galactosemia

- Gastrointestinal obstruction, digestive perforation or risk of digestive perforation.

Special Warnings and Precautions for use

Consultation of a physician is advised in case of:

- Painful abdominal symptoms of undetermined cause before the treatment are started.

- Insufficient therapeutic effect after several days.

Lactulose should be administered with care to patients who are intolerant to lactose.

The dose normally used in constipation should not pose a problem for diabetics. The dose used in the treatment of HE is usually much higher and may need to be electrolyte balance.

Chronic use of unadjusted doses and misuse can lead to diarrhea and disturbance of the electrolyte balance.

This product contains lactose, galactose and small amounts of fructose. Therefore, patients with the rate hereditary problem of galactose or fructose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Pediatric Population

Use of laxatives in children should be exceptional and under medical supervision. It should be taken into account that the defecation reflex could be disturbed during the treatment.

Pregnancy

No effects during pregnancy are anticipated, since systemic exposure to lactulose is negligible.

Lactation

No effects on the breastfed newborn/infant are anticipated, since the systemic exposure of the breast-feeding woman to lactulose is negligible. Lactulose can be used during breast-feeding.

Fertility

No effects are to be expected, since systemic exposure to lactulose is negligible.

Effects on ability to drive and use machines

Lactulose has no or negligible influence on the ability to drive and use machines.

Undesirable Effects

Flatulence may occur during the first few days of treatment. As a rule it disappears after a few days. Abdominal pain and vomiting may occur, as well as, nausea.

When dosages higher than instructed are used, abdominal pain and diarrhea may occur. In such a case the dosage should be decreased.

If high doses (normally only associated with hepatic encephalopathy, HE) are used for an extended period of time, the patient may experience an electrolyte imbalance due to diarrhea.

Drug Interaction

Do not use with any other gastrokinectic drugs or other laxatives. Concomitant use may lead to severe diarrhea.

Overdose

If the dose is too high, the following may occur:

Symptom: diarrhea and abdominal pain.

Treatment: cessation of treatment or dose reduction. Extensive fluid loss by diarrhea or vomiting may require correction of electrolyte disturbances.

Shelf life

3 years

Storage condition

Store at temperatures not exceeding 25^oC

Clopidogrel

Clopidogrel

75mg Tablet

300mg Tablet

DRUG CATEGORY:

Anti-Thrombotic Agent

PHARMACOLOGY:

Clopidogrel is an inhibitor of ADP-induced platelet aggregation acting direct inhibition of adenosine diphosphate (ADP) binding to its receptor and of the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex.

Clopidogrel is an inhibitor of platelet aggregation. A variety of drugs that inhibit platelet function have been shown to decrease morbid events in people with established atherosclerotic cardiovascular disease as evidence by stroke or transient ischemic attacks, myocardial infarction, or need for bypass or angioplasty. This indicates that platelets participate in the initiation and/or evolution of these events and that inhibiting them can reduce the event rate.

Clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent ADP mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. Biotransformation of Clopidogrel is necessary to produce inhibition of platelet aggregation, but as active metabolite responsible for the activity of the drug has not been isolated. Clopidogrel also inhibits platelet activation by released ADP. Clopidogrel are affected for the remainder of their lifespan. Dose dependent inhibition of platelet aggregation can be seen 2 hours after oral single doses of Clopidogrel. Repeated doses of 75mg Clopidogrel per day inhibit ADP induced platelet aggregation on the first day, and inhibition reaches steady state between Day 3 and Day 7. At steady state, the average inhibition level observed with a dose of 75 mg Clopidogrel per day was between 40% and 60%. Platelet aggregation and bleeding time gradually return to baseline values after treatment is discontinued, generally in about 5 days.

PHARMACOKINETICS:

Absorption and Distribution: Clopidogrel is rapidly absorbed after oral administration of repeated doses 75mg Clopidogrel (base), with peak plasma levels (≡ 3mg/l) of the main circulating metabolite occurring approximately 1 hour after dosing. The pharmacokinetics of the main circulating metabolite are linear (plasma concentrations increased in proportion to dose) in the dose range of 50mg to 150mg of Clopidogrel. Absorption is at least 50% based on urinary excretion of Clopidogrel-related metabolites. Clopidogrel and the main circulating metabolite bind reversibly in vitro to human plasma protein (98% and 94%, respectively). The binding is nonsaturable in vitro up to a concentration of 100mcg/ml.

Metabolism and Elimination: In vitro and in vivo, Clopidogrel undergoes rapid hydrolysis into its carboxylic acid derivative. In plasma and urine, the glucuronide of the carboxylic acid derivative is also observed.

INDICATIONS:

Clopidogrel is indicated for the reduction of atherosclerotic events (myocardial infarction, stroke, and vascular death) in patients with atherosclerosis documented by recent stroke, recent myocardial infarction, or established peripheral arterial disease.

CONTRAINDICATIONS:

• The use of Clopidogrel is contraindicated in the following conditions:
• Hypersensitivity to the drug substance or any component of the product.
• Active pathological bleeding such as peptic ulcer or intracranial hemorrhage.
• Severe liver impairment.
• Pregnancy and Breast Feeding

DOSAGE AND ADMINISTRATION:

For prophylaxis of Thromboembolic events: The usual dose is Clopidogrel 75mg once daily.

For the management of acute coronary syndrome, including unstable angina and non-Q wave myocardial infarction: Clopidogrel is given as single 300mg loading dose, followed by 75mg once daily. Or as prescribed by physician. Drug is not approved for use in children.

No dosage adjustment is necessary for elderly patients or patients with renal disease.

Clopidogrel can be taken with or without the food. If you forget to take a dose of Clopidogrel take it as soon as you remember. If it is almost time for your next dose, skip the forgotten dose and continue with your regular schedule.

PRECAUTION AND WARNING:

Thrombotic Thrombocytopenic Purpura (TTP): TTP has been reported rarely following the use of Clopidogrel, sometimes after a short exposure (<2 weeks). TTP is a serious condition requiring prompt treatment. It is characterized by thrombocytopenia, microangiopathic hemolytic anemia (schistocytes (fragmented RBC) seen on peripheral smear), neurological findings, renal dysfunctions, and fever.

General: As with other antiplatelet agents, Clopidogrel should be used with caution in patients who may be at risk of increased bleeding from trauma, surgery or other pathological conditions. If a patient is to undergo elective surgery and an antiplatelet effect is not desired. Clopidogrel should be discontinued 7 days prior to surgery.

Gastrointestinal Bleeding: Clopidogrel can prolong the bleeding time. In CAPRIE, Clopidogrel was associated with a rate of gastrointestinal bleeding of 2.0% vs 2.7% of aspirin. Clopidogrel should be used with caution in patients who have lesions with a propensity to bleed (such as ulcers). Drugs that might induce such lesions (such as aspirin and other non-steroidal anti-inflammatory (NSAIDs) should be used with caution in patients taking Clopidogrel.

Use in Hepatically Impaired Patients: Experience is limited in patients with severe hepatic disease, who may have bleeding diathesis. Clopidogrel should be used with caution in this population.

Information for Patients: Patients should be told that is may take them longer than usual to stop bleeding when they take Clopidogrel, and that they should report any unusual bleeding to their physician. Patients should inform physicians and dentists that they are taking Clopidogrel before any surgery is scheduled and before any new drug is taken.

Pregnancy: Clopidogrel should be used during pregnancy only if clearly needed.

Nursing Mothers: Studies in rats have shown that Clopidogrel and/or its metabolites are excreted in the milk. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing or to discontinue the drug, taking into account the importance of the drug to the nursing woman.

Pediatric Use: Safety and effectiveness in the pediatric population have not been established.]

SIDE EFFECTS:

The side effects from Clopidogrel are not common but in few cases any of the following symptoms may occur. Upset stomach, fatigue, muscle aches (flu-like symptoms), stomach pain, headaches, diarrhea, constipation, rash or purple areas on skin. If you experience any of the following symptoms, consult physician immediately: i.e. chest pain, unusual bleeding or bruising, bloody vomit, dark urine, bloody diarrhea, tarry stools, fever, constipation, rash or purple areas on skin.

Other side effects, reported rarely, include serum sickness, interstitial pneumonitis, erythema multiforme, Stevens-Johnson syndrome, lichen planus, and myalgia.

DRUG INTERACTION:

1. Aspirin did not modify the Clopidogrel-mediated inhibition of ADP-induced platelet aggregation. Concomitant administration of 500mg of Aspirin twice a day for 1 day did not significantly increase the prolongation of bleeding time induced by Clopidogrel. Clopidogrel potentiated the effect of Aspirin on collagen-induced platelet aggregation. The safety of chronic concomitant administration of Aspirin and Clopidogrel has not been established.
2. In a study in healthy volunteers, Clopidogrel did not necessitate modification of the Heparin dose or alter the effect of heparin on coagulation. Co-administration of heparin had no effect on inhibition of platelet aggregation induced by Clopidogrel. The safety of this combination has not been established, however, concomitant use should be undertaken with caution.
3. In healthy volunteers receiving Naproxen, concomitant administration of Clopidogrel was associated with increased occult gastrointestinal blood loss. Non-steroidal Anti-inflammatory Drugs (NSAIDs) and Clopidogrel should be coadministered with caution.
4. The safety of the coadministration of Clopidogrel with Warfarin has not been established. Consequently concomitant administration of these two agents should be undertaken with caution.
5. No clinically significant pharmacodynamic interactions were observed when Clopidogrel was coadministered with Atenolol, or both Atenolol and Nifedipine. The pharmacodynamic activity of Clopidogrel was also not significantly influenced by the coadministration of phenobarbital, Cimetidine or estrogen. The pharmacokinetics of Digoxin or Theophylline were not modified by the coadministration of Clopidogrel.

STORAGE CONDITION:

Store at a temperatures not exceeding 30^oC.

Protect from light and moisture. Keep out of the reach of children.

Atorvastatin

Atorvastatin

10mg Tablet

20mg Tablet

40mg Tablet

80mg Tablet

DRUG CATEGORY:

Dyslipidemic Agent

MECHANISM OF ACTION:

Atorvastatin is a selective, competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3methyl-glutaryl-coenzyme A to mevalonate, a precursor of steroids, including cholesterol. Cholesterol and triglycerides circulate in the bloodstream (intermediate-density lipoprotein), LDL (low-density lipoprotein), and VLDL (very-low-density lipoprotein) fractions. Triglycerides (TG) and cholesterol in the liver are incorporated into VLDL and released into the plasma for delivery to peripheral tissues. LDL is formed from VLDL and is catabolized primarily through the high-affinity LDL receptor. Clinical and phathologic studies show that elevated plasma levels of total cholesterol (total-C), LDL-cholesterol (LDL-C), and apolipoprotein B (apo B) promote human atherosclerosis and are risk factors for developing cardiovascular disease, while increased levels of HDL-C are associated with a decreased cardiovascular risk.

In animal models, Atorvastatin lowers plasma cholesterol and lipoprotein levels by inhibiting HMG-CoA reductase and cholesterol synthesis in the liver and by increasing the number of hepatic LDL receptors on the cell-surface to enhance uptake and catabolism of LDL; Atorvastatin also reduces LDL production and the number of LDL particles. Atorvastatin reduces LDL-C in some patients with homozygous familial hypercholesterolemia (FH), a population that rarely responds to other lipid-lowing medication(s).

A variety of clinical studies have demonstrated those elevated levels of total-C, LDL-C and apo B (a membrane complex for LDL-C) promote human atherosclerosis. Similarly, decreased levels of HDL-C (and its transport complex, apo A) are associated with the development of atherosclerosis.

Epidemiological investigations have established that cardiovascular morbidity and mortality very directly with level of total-C and LDL-C, and inversely with the level of HDL-C. Although frequently found in association with low HDL-C, elevated plasma TG has not been established as an independent risk factor for coronary heart disease. The independent effect of raising HDL-C or lowering TG on the risk for coronary and cardiovascular morbidity and mortality has not been established.

Atorvastatin reduces total-C, and apo B in patients with homozygous and heterozygous FH, Nonfamilial forms of hypercholesterolemia, and mixed Dyslipidemia. Atorvastatin also reduces VLDL-C and TG and produces variable increases in HDL-C and apolipoprotein A-1. This effect of Atorvastatin on cardiovascular morbidity and mortality has not been determined.

PHARMACOKINETICS:

Atorvastatin is rapidly absorbed from the gastrointestinal tract. It has absolute bioavailability of about 12% due to pre-systemic clearance in the gastrointestinal mucosa and/or first-pass metabolism in the liver, its primary site of action. Atorvastatin is metabolized by the cytochrome P450 3A4 to a number of compounds which are also active inhibitors of HMG CoA reductase. The mean plasma elimination half life of Atorvastatin is about 14 hours, although the half-life of inhibitory activity of HMG CoA reductase is approximately 20-30 hours due to the contribution of the active metabolites. It is 98% bound to plasma proteins. Atorvastatin is excreted as metabolites, primarily in the bile.

INDICATIONS:

Atorvastatin is indicated as an adjunct to diet for the reduction of cholesterol, LDL-Cholesterol ApolipoproteinEB and triglycerides and to increase HDL-cholesterol in patients with primary hypecholesterlemia, heterozygous familial and non-familial hypercholesterolemia, and combined (mixed) hyperlipidemia. Atorvastatin is indicated as an adjunct to diet for the treatment of patients with elevated serum triglycerides level, and for the treatment of patients with dysbetalipoproteinemia, who do not respond adequately to the diet. Atorvastatin is also indicated or the reduction of total cholesterol and LDL-cholesterol in patients with homozygous familial hypercholesterolemia when response to diet and other non-pharmacological measures are inadequate.

DOSAGE AND ADMINISTRATIONS:

The patient should be placed on a standard cholesterol-lowering diet before receiving Atorvastatin and should continue on this diet during treatment with Atorvastatin.

Hypercholesterolemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidemia (Frederickson Types IIa and IIb):

The recommended starting dose of Atorvastatin is 10mg once daily. The dosage range is 10 to 80mg once daily. Atorvastatin can be administered as single dose at any time of the day, with or without food. Therapy should be individualized according to goal of therapy and response. After initiation and/or upon titration of Atorvastatin, lipid levels should be analyzed within 2 to 4 weeks and dosage adjusted accordingly. Since the goal of treatment is to lower LDL-C, the NCEP recommends that LDL-C levels be used to initiate and assess treatment response. Only if LDL-C levels are not available, should total-C be used to monitor therapy.

Homozygous Familial Hypercholesterolemia:

The dosage of Atorvastatin in patients with homozygous FH 10 to 80 mg daily. Atorvastatin should be used as an adjunct to other lipid-lowering treatments (eg. LDL apheresis) in these patients or if such treatments are unavailable.

Concomitant Therapy:

Atorvastatin may be used in combination with a bile acid binding resin for additive effect. The combination of HMG-CoA reductase inhibitors and fibrates should generally be avoided

Dosage in Patients with Renal Insufficiency:

Renal disease does not affect the plasma concentrations nor LDL-reduction of Atorvastatin; thus, dosage adjustment in patients with renal dysfunction is not necessary.

ADVERSE DRUG REACTIONS:

Body as a Whole: Chest pain, face edema, fever, neck rigidity, malaise, photosensitivity reaction, generalized edema.

Digestive System: Nause, gastroentiritis, liver function tests abnormal, colitis, vomiting, gastritis, dry mouth, rectal hemorrhage, esophagitis, eructation, glossitis, mouth ulceration, anorexia, increased appetite, stomatitis, biliary pain, chellitis, duodenal ulcer, dysphagia, enteritis, melena, gum hemorrhage, stomach ulcer, tenesmus, ulcerative stomatitis, hepatitis, pancreatitis, cholestatic jaudice.

Respiratory System: Bronchitis, rhinitis, pneumonia, dyspnea, asthma and epistaxis.

Nervous System: Insomnia, dizziness, paresthesia, somnolence, amnesia, abnormal dreams, libido decreased, emotional ability, incoordination, peripheral neuropathy, torticollis, facial paralysis, hyperkinesia, depression, hypersthesia, hypertonia.

Musculoskeletal System: Arthritis, leg cramps, bursitis, tenosynovitis, myasthenia, tendinous contracture, myositis.

Skin and Appendages: Pruritus, contact dermatitis, alopecia, dry skin, sweating, acne, urticaria, eczema, seborrhea, skin ulcer.

Urogenital System: Urinary tract infection, urinary frequency, cystitis, hematuria, impotence, dysuria, kidney calculus nocturia, epididymitis, librocystic breast, vaginal hemorrhage, albuminuria, breast enlargment, metorrhagia, nephritis, urinary incontinence, urinary retention, urinary urgency, abnormal ejaculation, uterine hemorrhage.

Special Senses: Amblyopia, tinnitus, dry eyes, refraction disorder, eye hemorrhage, deafness, glaucoma, parosmia, taste loss, taste perversion.

Cardiovascular System: Palpitation, vasodilator, syncope, migraine, postural hypotension, phlebitis, arrhythmia, angina pectoris and hypertension.

Metabolic and Nutritional Disorder: Peripheral edema, hyperglycemia, creatine phosphokinase increased, gout, weight gain, hypoglycemia.

CONTRAINDICATIONS:

Contraindicated in patients who are hypersensitive to any component of this medication, who have active liver disease or persistent elevation of serum transaminase exceeding three times the upper limit of normal, who are pregnant since there is a possibility that it could interfere with fetal sterol synthesis, who are breast feeding, or in women of childbearing potential who are not using adequate contraceptive measures.

PRECAUTIONS:

Before instituting therapy with Atorvastatin, an attempt should be made to control hypercholesterolemia with appropriate diet, exercise, and weight reduction in obese patients, and to treat other underlying medical problems. Patients should be advised to report promptly unexplained muscle pain tenderness, or weakness, particularly if accompanied by malaise or fever.

DRUG INTERACTIONS:

1. When Atorvastatin and antacid suspensions were coadministered, plasma concentrations of Atorvastatin decreased approximately 35%. However, LDL-C reduction was not altered.
2. Because Atorvastatin does not affect the pharmacokinetics of Antipyrine, interactions with other drugs metabolized via the same cytochrome isoenzymes are not expected.
3. Plasma concentrations of Atorvastatin decreased approximately 25% when Colestipol and Atorvastatin were coadministered. However, LDL-C reduction was greater when Atorvastatin and Colestipol were coadminstered than when either drug was given alone.
4. Atorvastatin plasma concentrations and Ldl-C reduction were not altered by coadministration of Cimetidine.
5. When multiple doses of Atorvastatin and Digoxin were coadministered, steady-state plasma Digoxin concentrations increased by approximately 20%. Patients taking Digoxin should be monitored appropriately.
6. In healthy individuals, plasma concentrations of Atorvastatin increased approximately 40% with coadministration of Atorvastatin and Erythromycin, a known inhibitor o cytochrome P450 3A4.
7. Coadministration of Atorvastatin and an oral contraceptive increased AUC values of norethindrone and ethinyl estradiol by approximately 30% and 20%. These increases should be considered when selecting an oral contraceptive for a woman taking Atorvastatin.
8. Atorvastatin had no clinically significant effect of prothrombin time when administered to patients receiving chronic Warfarin treatment.

STORAGE CONDITIONS:

Store ad temperatures not exceeding 30^oC. Protect from light and excessive heat.

Dicyclomine / Dicycloverine

Dicyclomine / Dicycloverine

10mg Tablet

10mg/5ml Syrup

DRUG CATEGORY:

Anticholinergic Drug/ Antispasmodic Drug

BRAND NAME:

Bentyl

PHARMACOLOGICAL ACTION:

Dicycloverine in hydrochloride as its salt, is tertiary amine with antimuscarinic effects similar to but weaker than those atropine. It also has a direct antispasmodic action.

PHARMACOKINETICS:

Dicycloverine is readily absorbed from the gastrointestinal tract; it is also absorbed from mucous membranes, the eye, and to some extent through intact skin. It is rapidly cleared from the blood and is distributed throughout the body. It crosses the blood-brain barrier. It is incompletely metabolized in the liver and is excreted in the urine as unchanged drug and metabolites. A half-life of about 4 hours has been reported. It crosses the placenta and traces appear in breast milk.

INDICATIONS:

For the treatment of functional gastrointestinal conditions including smooth muscle spasms, e.g. irritable colon (mucous colitis, spastic colon, irritable bowel syndrome) and spastic constipation. Adjunctive therapy in organic gastrointestinal conditions to relieve associated smooth muscle spasms (e.g. diverticulitis, regional enteritis, gastric, and peptic ulcers).

DOSAGE AND ADMINISTRATION:

Adults: 10mg to 20mg 3 to 4 times a day.

Children: 6 mos to 2 years – 5mg to 10mg 3 to 4 times daily. Dose does not exceed 40mg. 2yrs to 12 years – 10mg 3 times a day.

Elderly: older adults should begin with the lowest possible dose and increase their dosage only as needed.

Child (under 6 months): not recommended

Or as prescribed by a physician.

Dose is usually given 15 minutes before meals. If you forget to take a dose of Dicycloverine (Dicyclomine, in USA), take it as soon as you remember. If it is almost time for your nest dose, skip the forgotten dose and continue with your regular schedule.

CONTRAINDICATIONS:

It is contraindicated in patients with prostatic enlargement in whom it may lead to urinary retention, and in those with paralytic ileus or pyloric stenosis. In patients with ulcerative colitis its use may lead to ileus or megacolon, and its effects on the lower esophageal sphincter may exacerbate reflux. Caution is generally advisable in any patient with diarrhea. Its should not be given to patients with myasthenia gravis except to reduce adverse muscarinic effects of an anticholinesterase.

Antimuscarinic should not be given to patients with angle-closure glaucoma or with a narrow angle between the it is and the cornea, since it may raise intra-ocular pressure and precipitate an acute attack. Acute angle-closure glaucoma has been reported in patients receiving nebulized atropine. Some recommend that atropine eye drops should not be used in infants aged less than 3 months due to the possible association between the induced cycloplegia and the development of amblyopia. Systemic reactions have followed the absorption of atropine from eyes drops; overdosage is less likely if the eye ointment is used. In the event of blurred vision following topical administration of atropine to the eye patients should not drive or operate machinery. Systemic administration of antimuscarinics may also cause blurred vision, dizziness, and other effects that may impair a patients ability to perform skilled tasks such as driving.

Because of the risk of provoking hyperthermia, antimuscarinic should not be given to patients, especially children, when the ambient temperature is high. It should also be used cautiously in patients with fever.

Antimuscarinics need to be used with caution in conditions characterized by tachycardia such as thyrotoxicosis, heart failure, and in cardiac surgery, where they may further accelerate the heart rate. Care is required in patients with acute myocardial infarction, as ischemia and infarction may be made worse, and in patients with hypertension.

Antimuscarinics may cause confusion, especially in the elderly, Reduced bronchial secretion caused by systemic administration of antimuscarinic may be associated with the formation of mucous plugs.

In the treatment of parkinsonism, increases in dosage and transfer to other forms of treatment should be gradual and antimuscarinic should not be withdrawn abruptly. Minor reactions may be controlled by reducing the dose until tolerance has developed.

Persons with Down's syndrome appear to have an increased susceptibility to some of the actions of antimuscarinic, whereas those with albinism may have reduced susceptibility.

ADVERSE DRUG REACTIONS:

The pattern of adverse effects seen with atropine and other antimuscarinics can mostly be related to their pharmacological actions at muscarinic and, at high doses, nicotinic receptors. These effects are dose-related and are usually reversible when therapy is discontinued. The peripheral side-effects of antimuscarinic are a consequence of their inhibitory effects include dryness of the mouth with difficulty in swallowing and talking, thirst, reduced bronchial secretions, dilatation of the pupils (mydriasis) with loss of accommodation (cyclopegia) and photophobia, flushing and dryness of the skin, transient bradycardia followed by tachycardia, with palpitation and arrhythmias, and difficulty in micturition, as well as reduction in the tone and motility of the gastrointestinal tract leading to constipation.

PRECAUTIONS AND WARNINGS:

It should be given with caution to children and geriatric patients, who may be more susceptible to its adverse effects. It is contraindicated in patients, who may be more susceptible to its adverse effects. It is contraindicated in patients with prostatic enlargement and in those with paralytic ileus or pyloric stenosis. In patients with ulcerative colitis, myasthenia gravis, and closed-angle glaucoma and in patients taking antimuscarinic agents in conditions characterized by tachycardia such as thyrotoxcosis, cardiac insufficiency, or failure and in cardiac surgery.

Pregnancy and Lactation:

A few cases of human malformation were linked to Dicycloverine, but studies have shown that the drug has not effect on the developing baby. As with all other drug products, Dicycloverine should be used during pregnancy only when absolutely necessary.

Dicycloverine or Dicyclomine should not be used by nursing mothers because like other drugs in is group, it may reduce the amount of milk produced. Also, a few infants less than 3 months o age who were given Dicycloverine drops developed breathing difficulty that went away on its own after 20 to 30 minutes.

Use in Elderly:

Older adults may be more susceptible to the side effects of the drug, especially memory loss, mental changes, and glaucoma, and may need less medicine to get a beneficial effect than a younger adult. Report any problems to your doctor at once.

Effects on ability to drive and operate machinery:

Oral administration of antimuscarinics such as Dicycloverine may cause blurred vision, dizziness, and other effects that may impair a patients ability to perform skilled tasks such as driving and operating machinery.

DRUG INTERACTIONS:

1. Never mix Dicycloverine with other anticholinergic drugs, including Atropine, Belladonna, Clidinium, Glycopyrrolate, Hyoscyamine, Isopropamide, Propantheline, Scopolamine, and others because of the possibility of intensifying drug adverse effects.
2. Dicycloverine can reduce stomach acidity and reduce the amount of Ketoconazole absorbed into the blood after it is taken by mouth.
3. Antacids containing calcium and/or magnesium citrates, sodium bicarbonate, and carbonic anhydrase inhibitor drugs may slow the rate at which Dicycloverine is released from the blood, increasing its therapeutic effect and possible side-effects.
4. Taking Dicycloverine may counteract the effect of Metoclopramide in reducing nausea and vomiting when taken together.
5. Dicycloverine together with narcotic pain reliever can increase the chances of severe constipation.
6. Taking this drug or any other drug that slows the movement of stomach and intestinal muscles together with a potassium chloride supplement (especially one that comes in wax-matrix tablet form) can lead to excessive irritation of the stomach.

OVERDOSAGE:

The principal signs of overdose are blurred vision; clumsiness; confusion; difficulty breathing; dizziness; drowsiness; dry mouth, nose, or throat; rapid heartbeat; fever; hallucinations; weakness; slurred speech; excitement, restlessness, or irritability; warmth; and dry or flushed skin. Overdose victims should be taken to a hospital emergency room at once for treatment. Always bring the medicine with you.

STORAGE CONDITIONS:

Store at temperatures not exceeding 30^oC. Protect from light.

Erythromycin

Erythromycin

100mg/ml Suspension Oral Drops

125mg/5ml Suspension

200mg/5ml Suspension

250mg/5ml Suspension

250mg Tablet

500mg Tablet

DRUG CATEGORY:

Macrolide Antibacterial Drug

MECHANISM OF ACTION:

Erythromycin and other macrolides bind reversibly to the 50s sub units of the ribosome, resulting in blockage of the transpeptidation or translocation reactions in inhibition of protein synthesis, and hence inhibition of cell growth. Its action is predominantly bactericidal against the more sensitive strains.

PHARMACOKINETICS:

Erythromycin base is destroyed by stomach acid and must be administered with enteric coating. Stearates and esters are fairly acid-resistant and relatively well absorbed. The lauryl salt of propionyl ester of Erythromycin (Erythromycin estolate) is among the best-absorbed oral preparations. Oral doses of 2 g/d result in serum levels of up to 2μg/ml. Large amounts are lost in feces. Absorbed drug is distributed widely except to the brain and cerebrospinal fluid. It traverses the placenta and reaches the fetus.

Erythromycins are excreted largely in the bile, where levels may be 50 times higher than in the blood. A portion of the drug excreted into bile is reabsorbed from the intestines. Only 5% of the administered dose is excreted in the urine.

INDICATIONS:

Streptococcus pyogenes: Upper and lower respiratory tract, skin, and soft-tissue infections of mild to moderate severity.

Staphylococcus aureus: Acute infections of skin and soft tissue that are mild to moderately severe. Resistant organisms may emerge during treatment.

Streptococcus pneumoniae: Infections of the upper respiratory tract (e.g. otitis media, pharyngitis) and lower respiratory tract (e.g. pneumonia) of mild to moderate severity.

Mycoplasma pneumoniae: In the treatment of respiratory tract infections due to this organism.

Hemophilus influenzae: For upper respiratory tract infections of mild to moderate severity when used concomitantly with adequate doses of sulfonamides. The concomitant use of sulfonamides is necessary since not all strains of Hemophilus influenzae are susceptible to Erythromycin at the concentrations of the antibiotic achieved with usual therapeutic doses.

Chlamydia trachomatis: Erythromycin is indicated for treatment of the following infections caused by Chlamydia trachomatis: conjunctivitis of the new born, pneumonia of infancy and urogenital infections during pregnancy. When tetracyclines are contraindicated or not tolerated, Erythromycin is indicated for the treatment of uncomplicated urethral, endocervical, or rectal infections in adults due to Chlamydia trichomatis.

Treponema pallidum: Erythromycin is an alternate choice o treatment for primary syphilis in penicillin-allergic patients. In treatment of primary syphilis, spinal fluid examinations should be done before treatment and as part of follow-up after therapy.

Corynebacterium diphtheriae: As an adjunct to antitoxin, to prevent establishment of carriers, and to eradicate the organisms in carriers.

Corynebacterium minutissimum: In the treatment of erythema.

Estamoeba histolytica: in the treatment of intestinal amoebiasis only. Extra-enteric amoebiasis requires treatment with other agents.

Listeria monocytogenes: Infections due to this organism.

Bordetella pertussis: Erythromycin is effective in eliminating the organisms from the nasopharynx of infected individuals.

DOSAGE AND ADMINISTRATION:

Erythromycin may be given as the base or its salts or esters; doses are expressed in terms of the base. The usual oral dose is the equivalent of Erythromycin 1 to 2 g daily in 2 to 4 divided doses; for severe infections, this may be increased to up to 4g daily in divided doses. For children the dose is usually about 30 to 50mg per Kg body-weight daily although it may be doubled in severe infections; a recommended dose for children aged 2 to 8 years 1g daily in divided doses, and for infants and children up to 2 years of age, 500mg daily in divided doses.

In the patient who is unable to take Erythromycin by mouth and in severely ill patients in whom it is necessary to attain an immediate high blood concentration, Erythromycin maybe given intravenously in the form of one its more soluble salts such as gluceptate or the lactobionate, in doses equivalent to those by mouth.

CONTRAINDICATION:

Erythromycin is contraindicated in patients with known hypersensitivity to this antibiotic and in those with liver disorders.

PRECAUTION AND WARNING:

There have been a few reports of hepatic dysfunction, with or without jaundice, occurring in patients receiving oral Erythromycin products. All forms of Erythromycin should be used with care in patients with existing liver disease or hepatic impairment.

DRUG INTERACTION:

1. Erythromycin use in patients who are receiving high doses of Theophylline may be associated with an increase in serum Theophylline levels and potential Theophylline toxicity. In case of Theophylline toxicity and/or elevated serum Theophylline levels, the dose of Theophylline should be reduced while the patient is receiving concomitant Erythromycin therapy.
2. Concomitant administration of Erythromycin and Digoxin has been reported to result in elevated Digoxin serum levels.
3. There have been reports of increased anticoagulant effects when Erythromycin and oral anticoagulant were used concomitantly.
4. Concurrent use of Erythromycin and Ergotamine or dihydroergotamine has been associated in some patients with acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia.
5. Erythromycin has been reported to decrease the clearance of triazolam and thus may increase the pharmacologic effect of triazolam.
6. The use of Erythromycin in patients concurrently taking drugs metabolized by the cytochrome P450 system may be associated with elevations in serum Erythromycin with carbamazepine, cycloporine, hexobarbital and phenytoin.
7. Serum concentrations of drugs metabolized by the cytochrome P450 system should be monitored closely in patients concurrently receiving Erythromycin.
8. Troleandomycin significantly alters the metabolism of terfenadine when taken concomitantly; therefore, observe caution when Erythromycin and terfenadine are used concurrently.
9. Patients receiving concomitant Lovastatin and Erythromycin should be carefully monitored: cases of rhabdomyolysis have been reported in seriously ill patients.
10. Concomitant use of CYP3A inhibitors like nitroimidazole antifungals can cause increased serum levels of Erythromcyin and probably increase the risk of cardiac arrhythmia.
11. Concurrent use of diltiazem or verapamil with Erythromycin should be avoided by persons at risk for heart irregularities or those with long QT manifestations.
12. Erythromycin may interfere with some diagnostic tests including measurement of urinary catecholamines and 17 – hydroxycorticosteroids.

ADVERSE DRUG REACTION:

The most frequent side effects of oral Erythromycin preparations are gastrointestinal and are dose-related. They include nausea, vomiting, abdominal pain, diarrhea and anorexia. Symptoms of hepatic dysfunction and/or abnormal liver function test results may occur. Pseudomembranous colitis has been rarely reported in association with Erythromycin therapy. There have been isolated reports of transient central nervous system side effects including confusion, hallucinations, seizures, and vertigo; however, a cause and effect relationship has not been established.

Occasional case reports of cardiac arrhythmias such as ventricular tachycardia have been documented in patients receiving Erythromycin therapy. There have been isolated reports of other cardiovascular symptoms such as chest pain, dizziness, and palpitations; however, a cause and effect relationship has not been established.

Allergic reactions ranging from urticaria and mild skin eruptions to anaphylaxis have occurred.

There have been isolated reports of reversible hearing loss occurring chiefly in patients with renal insufficiency and in patients receiving high doses of Erythromycin.

OVERDOSAGE:

In case of overdosage, Erythromycin should be discontinued. Overdosage should be handled with the prompt elimination of unabsorbed drug and all other appropriate measures. Erythromycin is not removed by peritoneal dialysis or hemodialysis.

STORAGE CONDITION:

Store at a temperatures not exceeding 30^oC.