Back to Top

  • We are Certified Personal Trainer’s

  • Do Work That Aligns with your Heart

  • A Fresh Approach To Health & Life


  1. Home
  2. Archives forOctober 2021

Fentanyl Citrate: Uses, Dosage, Side Effects

Generic Name
Fentanyl Citrate
Therapeutic Class: Opioid analgesics/Analgesic, Anti Inflammatory

Indications:
Fentanyl is indicated for the management of breakthrough pain in patients with cancer who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain. Patients considered opioid-tolerant are those who are taking at least 60 mg of oral morphine/day, at least 25 mcg of transdermal Fentanyl/hour, at least 30 mg of oxycodone daily, at least 8 mg of oral hydromorphone daily, or an equianalgesic dose of another opioid for a week or longer.

Description:
Fentanyl is an opioid analgesic. Fentanyl interacts predominately with the opioid mu-receptor but also binds to kappa and delta-type opioid receptors. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues. In clinical settings, Fentanyl exerts its principal pharmacologic effects on the central nervous system. Its primary actions of therapeutic value are analgesia and sedation. Fentanyl may increase the patient's tolerance for pain and decrease the perception of suffering, although the presence of the pain itself may still be recognized. In addition to analgesia, alterations in mood, euphoria, and dysphoria, and drowsiness commonly occur. Fentanyl depresses the respiratory centers, depresses the cough reflex, and constricts the pupils.

Dosage & Administration:
Oral-
  • Starting Dose: The initial dose of Fentanyl should be 100 mcg.
  • Re-dosing patients within a single episode: Dosing may be repeated once during a single episode of breakthrough pain if the pain is not adequately relieved by one Fentanyl dose. Re-dosing may occur 30 minutes after the start of administration of Fentanyl and the same dosage strength should be used.
  • Increasing the dose: Titration should be initiated using multiples of the 100 mcg Fentanyl tablet. Patients require to titrate above 100 mcg can be instructed to use two 100 mcg tablets (one on each side of the mouth in the buccal cavity). If this dose is not successful in controlling the breakthrough pain episode, the patient may be instructed to place two 100 mcg tablets on each side of the mouth in the buccal cavity (total of four 100 mcg tablets). Titrate above 400 mcg by 200 mcg increments bearing in mind using more than 4 tablets simultaneously has not been studied and it is important to minimize the number of strengths available to patients at any time to prevent confusion and possible overdose. To reduce the risk of overdose during titration, patients should have only one strength of Fentanyl tablet available at any one time.
  • Dosage Adjustment: Generally, the dose of Fentanyl should be increased when patients require more than one dose per breakthrough pain episode for several consecutive episodes.
Injection-
  • Fentanyl injection can be administered intravenously either as a bolus or by infusion & by intramuscular route also. The dose of fentanyl should be individualized according to age, body weight, physical status, underlying pathological condition, use of other drugs and type of surgery and anesthesia.
  • Doses in excess of 200mcg are for use in anesthesia only. As a premedicant, 1-2 ml fentanyl may be given intramuscularly 45 minutes before induction of anesthesia. After IV administration in unpremedicated adult patients, 2ml fentanyl may be expected to provide sufficient analgesia for 10-20 minutes in surgical procedures involving low pain intensity. 10 ml fentanyl injected as a bolus gives analgesia lasting about one hour. The analgesia produced is sufficient for surgery involving moderately painful procedures. Giving a dose of 50mcglkg fentanyl will provide intense analgesia for some four to six hours, for intensely stimulating surgery.
  • Fentanyl may also be given as an infusion. In ventilated patients, a loading dose of fentanyl may be given as a fast infusion of approximately 1 mcg/kg/min for the first 10 minutes followed by an infusion of approximately 0.1 mcg/kg/min. Alternatively, the loading dose of fentanyl may be given as a bolus. Infusion rates should be titrated to individual patient response; lower infusion rates may be adequate. Unless it is planned to ventilate post-operatively, the infusion should be terminated at about 40 minutes before the end of surgery.
  • Lower infusion rates, e.g. 0.05-0.08 mcg/kg/min. are necessary if spontaneous ventilation.is to be maintained. Higher infusion rates (up to 3 mcg/kg/min) have been used in cardiac surgery. Fentanyl is chemically incompatible with the induction agents thiopentone & methohexitone because of wide differences in pH
  • Use in elderly and debilitated patients: It is wise to reduce the dosage in the elderly and debilitated patients. The effect of the initial dose should be taken into account in determining supplemental doses. 
Transdermal-
Intractable chronic pain:
  • Adult: Patches deliver fentanyl in doses that range from 12-100 mcg/hr. Doses should be individually titrated based on previous use of opioids. Opioid-naive patients: Initially, ≤25 mcg/hr; it is recommended to initially titrate w/ low doses of short-acting opioids before starting fentanyl patches. Patients receiving a strong opioid analgesic: Initial dose should be based on the previous 24-hr opioid requirements. During transfer to fentanyl patches, previous opioid treatment should be phased out gradually. If the patient requires doses >100 mcg/hr, >1 patch may be used; consider alternative or additional therapy if doses >300 mcg/hr are required. Replace the patch every 72 hr and apply the new patch to a different site; avoid using the same area of skin for a few days.
  • Elderly: Dose reduction may be needed.
Administration:
Tablet Administration: Patients should remove the tablet from the blister strip and immediately place the entire tablet in the buccal cavity (above a rear molar, between the upper cheek and gum). Patients should not attempt to split the tablet. The tablet should not be chewed or swallowed, as this will result in lower plasma concentrations than when taken as directed. The tablet should be left between the cheek and gum until it has disintegrated, which usually takes approximately 14-25 minutes. After 30 minutes, if remnants from the tablet remain, they may be swallowed with a glass of water.

Interaction:
Co-administration of different antifungals, macrolide antibiotics, CNS depressant drugs like ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, and nefazodone may enhance or prolong the effects of Fentanyl. The concomitant use of amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, and verapamil with Fentanyl may also result in an increase in Fentanyl plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression.

Contraindications:
Fentanyl is contraindicated in the management of acute or postoperative pain. This product must not be used in opioid non-tolerant patients. Fentanyl is contraindicated in patients with known intolerance or hypersensitivity to any of its components or the drug Fentanyl.

Side Effects:
As with other narcotic analgesics, the most common serious adverse reactions reported to occur with Fentanyl are respiratory depression, apnoea, muscular rigidity, myoclonic movements, and bradycardia. Respiratory depression is more likely to occur with intravenous administration if a dose is given too rapidly and it rarely occurs with intramuscular administration.

Pregnancy & Lactation:
Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Fentanyl should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Fentanyl is excreted in human milk; therefore Fentanyl should not be used in nursing women because of the possibility of sedation and/or respiratory depression in their infants.

Precautions & Warnings:
Opioid analgesics impair the mental and/or physical ability required for the performance of potentially dangerous tasks (e.g. driving a car or operating machinery). Patients taking Fentanyl should be warned of these dangers and should be counseled accordingly. The use of concomitant CNS active drugs requires special patient care and observation.

Chronic pulmonary disease: Fentanyl should be titrated with caution in patients with chronic obstructive pulmonary disease or pre-existing medical conditions predisposing them to respiratory depression.

Head injuries and increased intracranial pressure: Opioids may obscure the clinical course of a patient with a head injury and should be used only if clinically warranted.

Cardiac disease: Intravenous Fentanyl may produce bradycardia. Therefore, Fentanyl should be used with caution in patients with bradyarrhythmias.

Hepatic or renal disease: Fentanyl should be used with caution because of the hepatic metabolism and renal excretion of Fentanyl.

Overdose:
In insufficient overdosage, Fentanyl would produce narcosis, marked skeletal muscle rigidity. Cardio-respiratory depression and cyanosis may also occur. In the presence of hypoventilation or apnoea, oxygen should be administered and respiration should be assisted. A specific narcotic antagonist, such as naloxone, should be available for use as indicated to manage respiratory depression.

Storage:
Store between 20-25°C. Protect from light.

Fenofibrate: Uses, Dosage, Side Effects

Generic Name
Fenofibrate
Therapeutic Class: Cardiovascular / Fibrates

Indications:
Fenofibrate is indicated for hyperlipidemias of type lla, llb, III, IV & V in patients who have not responded adequately to diet & other appropriate measures.

Presentation:
Fenofibrate: Each capsule contains Fenofibrate BP (micronised) 200 mg.

Description:
Fenofibrate is a fibric acid derivative. Fenofibrate is rapidly hydrolyzed after oral ingestion to its pharmacologically active form, fenofibric acid. Fenofibric acid produces reductions in total cholesterol, LDL cholesterol, Apo-lipoprotein B, Total triglycerides and VLDL. In addition, treatment with Fenofibrate results in increases in HDL and apo-proteins apoAI apoAII. Fenofibrate also reduces serum uric acid levels in hyperuricemic and normal individuals by increasing the urinary excretion of uric acid. The micronised form of Nofiate (Fenofibrate) has enhanced absorption over the non-micronized formulation.

Dosage & Administration:
For the treatment of adult patients with hypercholesterolemia or mixed hyperlipidemia, the initial dose of Fenofibrate is 200 mg per day.
For adult patients with hypertriglyceridemia, the initial dose is 67 to 200 mg per day.
The dose should be individualized according to patient response. Fenofibrate should be given with meal thereby, optimizing the bioavailability of the medication. Or, as directed by the registered physician.

Interaction:
Fenofibrate has been reported to potentiate the anticoagulant effects of warfarin. When administered with the antidiabetic drug it may improve glucose tolerance and have an additive effect. Fenofibrate may also increase the nephrotoxicity of cyclosporine. Due to a potential increase in the risk of rhabdomyolysis, caution should be taken against the use of Fenofibrate with HMG-CoA reductase inhibitors. However, the use of low-dose statins with Fenofibrate appears to be well tolerated.

Contraindications:
Fenofibrate is contraindicated in patients with hypersensitivity to Fenofibrate, severe renal or hepatic impairment, existing gall bladder disease, breastfeeding mothers, photosensitivity to ketoprofen.

Side Effects:
Gastrointestinal (e.g. nausea, anorexia, gastric pain), pruritus, urticaria, impotence, also headache, dizziness, vertigo, fatigue, hair loss; myotoxicity.

Pregnancy & Lactation:
Fenofibrate is not recommended for pregnant women.

Precautions & Warnings:
Special care is needed in patients with renal disease, as progressive increases in serum creatinine concentration or failure to follow dosage guidelines may result in myotoxicity; discontinue if myotoxicity is suspected or creatinine kinase concentration increases significantly. Liver function tests are recommended every 3 months for the first year.

Overdose:
There is no specific treatment for overdose with Fenofibrate. General supportive care of the patients is indicated, including monitoring of vital signs and observation of clinical status, should an overdose occur. Because Fenofibrate is highly bound to plasma proteins, hemodialysis should not be considered.

Storage:
Do not store above 30°C. Keep away from light and out of the reach of children.

Febuxostat: Uses, Dosage, Side Effects

Generic Name
Febuxostat
Therapeutic Class: Drugs used in Gout

Indications:
Febuxostat is indicated for the chronic management of hyperuricemia in patients with gout. Febuxostat is not recommended for the treatment of asymptomatic hyperuricemia.

Presentation:
Febuxostat 40 mg tablet: Each tab contains Febuxostat INN 40 mg tablet
Febuxostat 80 mg tablet: Each tab contains Febuxostat INN 80 mg tablet

Description:
Febuxostat is a non-purine, selective xanthine oxidase (XO) inhibitor. It decreases serum uric acid level by inhibiting xanthine oxidase, which is responsible for uric acid production. Xanthine oxidase breaks down hypoxanthine to xanthine and thus to uric acid. Febuxostat is not expected to inhibit other enzymes involved in purine and pyrimidine synthesis and metabolism at therapeutic concentrations.

Dosage & Administration:
Febuxostat is recommended at 40 mg or 80 mg once daily. The recommended starting dose of Febuxostat is 40 mg once daily. For patients who do not achieve a serum uric acid less than 6 mg /dL after 2 weeks with 40 mg, Febuxostat 80 mg is recommended. Febuxostat can be administered without regard to food or antacid use. No dose adjustment is necessary when administering Febuxostat to patients with mild to moderate renal or hepatic impairment.

Interaction:
Concomitant administration of Febuxostat with azathioprine, mercaptopurine or theophylline could increase plasma concentrations of these drugs resulting in severe toxicity.

Contraindications:
Febuxostat is contraindicated in patients being treated with azathioprine, mercaptopurine, or theophylline.

Side Effects:
The most common adverse events associated with the use of Febuxostat may include liver function abnormalities, nausea, arthralgia, and rash.

Pregnancy & Lactation:
Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Febuxostat should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether this drug is excreted in human milk. Caution should be exercised when Febuxostat is administered to a nursing woman.

Precautions & Warnings:
Gout Flare: An increase in gout flares is frequently observed during initiation of anti-hyperuricemic agents, including Febuxostat. If a gout flare occurs during treatment, Febuxostat need not be discontinued. Prophylactic therapy (i.e., non-steroidal anti-inflammatory drug (NSAID) or colchicine upon initiation of treatment) may be beneficial for up to six months.
Cardiovascular Events: A higher rate of cardiovascular thromboembolic events was observed in patients treated with febuxostat than allopurinol in clinical trials. Monitor for signs and symptoms of MI and stroke.
Liver Enzyme Elevation: Transaminase elevations have been observed in febuxostat-treated patients. Monitor liver function tests periodically.

Use in Special Populations:
Pediatric Use: Safety and effectiveness in pediatric patients under 18 years of age have not been established

Overdose:
Febuxostat was studied in healthy subjects in doses up to 300 mg daily for seven days without evidence of dose-limiting toxicities.

Storage:
Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Favipiravir: Uses, Dosage, Side Effects

Generic Name
Favipiravir
Therapeutic Class: Anti-viral drugs

Indications:
Treatment of novel or re-emerging pandemic influenza virus infections (limited to cases in which other influenza antiviral drugs are ineffective or not sufficiently effective).

Description:
Favipiravir is approved for manufacture and sale in Japan as an influenza antiviral. It selectively inhibits the RNA polymerase of the influenza virus, an enzyme required for viral replication once human host cells are infected. COVID-19 also uses this enzyme to replicate and is classified in to the same type of single-stranded RNA virus as influenza; hence, it is believed that Favipiravir may be effective in treating COVID-19.

Favipiravir is only used when there is an outbreak of novel or re-emerging influenza virus infections in which other influenza antiviral drugs are either not effective or insufficiently effective. Its production and distribution is at the discretion of Japan’s Health, Labor, and Welfare Ministry so has never been distributed in the market and is not available at hospitals and pharmacies in Japan or overseas.

Pharmacology:
Favipiravir is a new antiviral drug against influenza. It is metabolized into favipiravir ribosyl triphosphate (favipiravir RTP) by an intracellular enzyme, and favipiravir RTP selectively inhibits RNA polymerase (RNA-dependent RNA polymerase) of the influenza virus, preventing replication of the influenza virus. It is a drug with a mechanism of action different from that of the existing influenza antiviral drugs and effective against all types and sub-types of human influenza A, B, and C viruses in vitro, showing a wide range of anti-viral activity against various influenza virus strains including avian and swine viruses.

Dosage & Administration:
The usual adult dosage is 1600 mg of Favipiravir administered orally twice daily on Day 1, followed by 600 mg orally twice daily from Day 2 to Day 5 or as directed by physicians. The total treatment duration should be 5 days.

Interaction:
In animal studies, decreased RBC production, and increases in liver function parameters such as AST, ALP, ALT, and total bilirubin, and increased vacuolization in hepatocytes. Toxicity information regarding Favipiravir in humans is not readily available.

Contraindications:
Favipiravir is contraindicated for pregnant women and women who may possibly be pregnant.

Side Effects:
The most common side effects are Diarrhea and an increase in blood uric acid levels.

Pregnancy & Lactation:
Favipiravir may cause delayed development or death of embryos during the early stage of pregnancy. Should not be given during pregnancy.

Precautions & Warnings:
Favipiravir should not be given in pregnant women, the requirement of the confirmation of non-pregnancy in women of childbearing potential before use, thorough contraception measures from the start of the treatment to 7 days after the end of the treatment. Caution should be taken for Hepatic and renal impaired patient or use Favipiravir as per the direction of registered Physician

Use in Special Populations:
This drug is only approved as an experimental drug and still, a lot of studies are needed about its efficacy and also toxic reactions and use in children.

Overdose:
In animal studies, decreased RBC production, and increases in liver function parameters such as AST, ALP, ALT, and total bilirubin, and increased vacuolization in hepatocytes. Toxicity information regarding Favipiravir in humans is not readily available.

Storage:
Keep below 30°C temperature, protected from light & moisture. Keep out of the reach of children.

Glycopyrronium Bromide + Formoterol Fumarate: Uses, Dosage, Side Effects

Generic Name
Glycopyrronium Bromide + Formoterol Fumarate
Therapeutic Class: Bronchodilator

Indications:
It is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

Presentation:
Each puff delivers-
Through the actuator: Glycopyrronium Bromide EP 9 mcg and Formoterol Fumarate EP 4.8 mcg &
Through the valve: Glycopyrronium Bromide EP 10.35 mcg and Formoterol Fumarate EP 5.52 mcg.

Description:
This preparation contains two bronchodilators: Glycopyrronium is a long-acting muscarinic antagonist (LAMA) and Formoterol is a long-acting β2-adrenergic agonist (LABA) with a rapid onset of action. Glycopyrronium has a similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of the M3 receptor at the smooth muscle leading to bronchodilation. Formoterol causes direct relaxation of airway smooth muscle as a consequence of the increase in cyclic AMP through activation of adenylyl cyclase.

Dosage & Administration:
Adults: Should be administered as 2 puffs twice daily, in the morning and in the evening.
Use in patients with severe renal impairment should be considered if the potential benefit of the treatment outweighs the risk.

Interaction:
  • Other adrenergic drugs may potentiate effect. Use with caution.
  • Xanthine derivatives, steroids, diuretics or non-potassium sparing diuretics may potentiate hypokalemia or EDG changes. Use with caution.
  • Diuretics: Use with caution.
  • Monoamine oxidase inhibitors and tricyclic antidepressants: Use with extreme caution. May potentiate the effect of formoterol fumarate on the cardiovascular system.
  • Beta-Blockers: Use with caution and only when medically necessary.
  • Anticholinergics: May interact additively with concomitantly used anticholinergic medications. Avoid administrations of this combination with other anticholinergic-containing drugs.
Contraindications:
All LABAs are contraindicated in patients with asthma without use of a long-term asthma control medication. This preparation is also contraindicated in patients with hypersensitivity to glycopyrronium bromide, formoterol fumarate or to any component of the product.

Side Effects:
The most common adverse reactions include cough and urinary tract infection. Possible side effects are sudden breathing problems, headache, tremor, nervousness, rash, swelling of the face, mouth and tongue, hives, increase blood pressure, chest pain, irregular heartbeat, muscle spasm, muscle weakness, eye pain or discomfort and urinary retention.

Pregnancy & Lactation:
There are no data on the use of this preparation in pregnant women.

Precautions & Warnings:
  • This combination should not be used with additional medicine containing a LABA because of risk of overdose.
  • Not indicated for the relief of acute bronchospasm
  • Do not initiate in acutely deteriorating COPD or to treat acute symptoms
  • If paradoxical bronchospasm occurs, discontinue this combination and institute alternative therapy
  • Use with caution in patients with cardiovascular disorders
  • Use with patients with convulsive disorders, thyrotoxicosis, diabetes mellitus and ketoacidosis.
  • Be alert to hypokalemia and hyperglycemia
  • Worsening of narrow-angle glaucoma may occur. Use with caution with patients with narrow-angle glaucoma
  • Worsening of urinary retention may occur. Use with caution with patients with prostatic hyperplasia or bladder neck obstruction
Storage:
Do not store above 30°C. Do not expose to temperatures higher than 50°C. Do not pierce the pressurized container. Keep out of the reach of the children.

Glycopyrronium Bromide (Injection): Uses, Dosage, Side Effects

Generic Name
Glycopyrronium Bromide (Injection)
Therapeutic Class: Anticholinergics (antimuscarinics)/ Anti-spasmodics

Indications:
In Anesthesia:
  • As a pre-operative antimuscarinic agent to reduce salivary, tracheobronchial and pharyngeal sections and to reduce the acidity of the gastric contents.
  • As a pre-operative or intra-operative antimuscarinic to attenuate or prevent intra-operative bradycardia with the use of suxamethonium or due to cardiac vagal reflexes.
  • To protect against the peripheral muscarinic actions of anticholinesterases such as neostigmine and pyridostigmine, used to reverse residual neuromuscular blockade produced by non-depolarizing muscle relaxants.
In Peptic Ulcer: For use in adults as adjunctive therapy for the treatment of a peptic ulcer when the rapid anticholinergic effect is desired or when oral medication is not tolerated.

Description:
Glycopyrronium bromide is a quaternary ammonium antimuscarinic with peripheral effects. It is used in anesthetic practice. Given as a premedication before general anesthesia, it diminishes the risk of vagal inhibition of the heart and reduces salivary and bronchial secretions. Intra-operatively, it may be given to reduce bradycardia and hypotension induced by drugs such as suxamethonium, halothane or propofol. Glycopyrronium bromide may be used before or with anticholinesterases such as neostigmine to prevent their muscarinic adverse effects. Antimuscarinic drugs are competitive inhibitors of the actions of acetylcholine at the muscarinic receptors of autonomic effector sites innervated by parasympathetic(cholinergic postganglionic) nerves, as well as being inhibitors of the action of acetylcholine on smooth muscle lacking cholinergic innervation. Peripheral antimuscarinic effects that are produced as the dose increases are: decreased production of secretions from the salivary, bronchial and sweat glands; dilatation of the pupils (mydriasis) and paralysis of accommodation (cyclopegia); increased heart rate; inhibition of micturition and reduction in gastrointestinal tone; inhibition of gastric acid secretion. Quaternary ammonium compounds are sparingly lipid soluble and do not readily pass lipid membranes such as the blood brain barrier. Central effects are negligible.

Dosage & Administration:
Pre-anesthetic Use:
  • Adults: 0.2 mg to 0.4 mg intravenously or intramuscularly before the induction of anesthesia. Alternatively, a dose of 0.004 to 0.005 mg/kg up to a maximum of 0.4 mg may be used. Larger doses may result in profound and prolonged antisialogogue effect, which may be unpleasant for the patient.
  • Children (1 month to 12 years of age): 0.004 to 0.008 mg/kg up to a maximum of 0.2 mg intravenously or intramuscularly before the induction of anesthesia. Larger doses may result in profound and prolonged antisialogogue effect which may be unpleasant for the patient.
Intraoperative Use: When used to treat arrhythmias associated with traction reflexes, the usual attempts should be made to determine the aetiology of the arrhythmia and the surgical or anesthetic manipulations necessary to correct parasympathetic imbalance should be performed.
  • Adults: In those situations where intraoperative use is indicated, a single dose of 0.2 to 0.4 mg (or 0.004 to 0.005 mg/kg up to a maximum of 0.4 mg) by intravenous injection should be used. This dose may be repeated if necessary.
  • Children (1 month to 12 years of age): In those situations where intraoperative use is indicated, a single dose of 0.004 to 0.008 mg/kg or up to a maximum of 0.2 mg by intravenous injection should be used. This dose may be repeated if necessary.
Reversal of Neuromuscular Blockade:
  • Adults: 0.2 mg intravenously per 1 mg neostigmine or the equivalent dose of pyridostigmine. Alternatively, a dose of 0.01-0.015 mg intravenously with 0.05 mg/kg neostigmine or equivalent dose of pyridostigmine. Glycopyrronium may be administered simultaneously from the same syringe with the anticholinesterase; greater cardiovascular stability results from this method of administration.
  • Children (1 month to 12 years of age): 0.01 mg/kg intravenously with 0.05 mg/kg neostigmine or the equivalent dose of pyridostigmine. Glycopyrronium may be administered simultaneously from the same syringe with the anticholinesterase; greater cardiovascular stability results from this method of administration.
Interaction:
Many drugs have antimuscarinic effects; concomitant use of two or more of such drugs can increase side-effects such as dry mouth, urine retention and constipation. Concomitant use can also lead to confusion in the elderly. Anticholinergic agents may delay absorption of other medication given concomitantly. Concurrent administration of anticholingergics and corticosteroids may result in increased intraocular pressure. Concurrent use of anticholinergic agents with slow-dissolving tablets of digoxin may cause increased serum digoxin levels.
  • Ritodrine: tachycardia
  • Increased antimuscarinic side-effects: amantadine; tricyclic antidepressants; antihistamines; clozapine; disopyramaide; MAOIs; nefopam; pethidine; phenothiazines (increased antimuscarinic side effects of phenothiazines but reduced plasma concentrations)
  • Possibly increased antimuscarinic side-effects: tricyclic (related) antidepressants
  • Domperidone/Metoclopramide: antagonism of effect on gastro-intestinal activity
  • Ketoconazole: reduced absorption of ketoconazole
  • Levodopa: absorption of levodopa possibly reduced
  • Memantine: effects possibly enhanced by memantine
  • Nitrates: possibly reduced effect of sublingual nitrates (failure to dissolve under the tongue owing to dry mouth)
  • Parasympathomimetics: antagonism of effect
Side Effects:
Side effects of antimuscarinics such as glycopyrronium bromide are basically extensions of the fundamental pharmacological action. These include constipation, transient bradycardia (followed by tachycardia, palpitations and arrhythmias), reduced bronchial secretions, urinary urgency and retention, dilatation of the pupils with loss of accommodation, photophobia, dry mouth, flushing and dryness of the skin. Side effects that occur occasionally include confusion (particularly in the elderly), nausea, vomiting and giddiness. The following reported adverse reactions are extensions of glycopyrronium bromide’s fundamental pharmacological actions:
  • Cardiovascular: Tachycardia, ventricular fibrillation, bradycardia, palpitation and arrhythmia, hypertension, hypotension, cardiac arrest, heart block, prolonged QTc interval.
  • Dermatological: Flushing and inhibition of sweating, severe allergic reactions or drug idiosyncrasies including urticaria and other dermal manifestations, pruritus, dry skin.
  • Gastrointestinal: Nausea, vomiting, dry mouth, constipation, taste alterations, including loss of taste.
  • Genitourinary: Urinary hesitancy and retention, impotence.
  • Ocular: Blurred vision due to mydriasis, cycloplegia, photophobia, increased ocular tension.
  • Nervous System: Inhibition of transmission at neuromuscular junction, headache, nervousness, drowsiness, dizziness, seizure, insomnia, some degree of mental confusion, especially in the elderly, hyperexcitability in children.
  • Pregnancy and perinatal: Suppression of lactation.
  • Respiratory System: Respiratory arrest.
  • General: Hyperpyrexia bloated feeling, anaphylaxis/anaphylactoid reaction, and hypersensitivity. Injection site reactions including pruritus, oedema, erythema, pain have been reported rarely.
Pregnancy & Lactation:
Data on the use of glycopyrronium bromide in pregnant women, other than on delivery, are not forthcoming, nor is there documentation concerning excretion in breast milk. Although glycopyrronium bromide does not readily cross the placenta, the injection should only be prescribed to pregnant women when clearly necessary. Caution is advised when considering administration to a lactating mother.

Precautions & Warnings:
Antimuscarinics should be used with caution (due to increased risk of side effects) in Down’s syndrome, in children and in the elderly. They should also be used with caution in gastro-esophageal reflux disease, diarrhea, ulcerative colitis, acute myocardial infarction, hypertension, conditions characterized by tachycardia (including hyperthyroidism, cardiac insufficiency, cardiac surgery) because of the increase in heart rate produced by their administration, coronary artery disease and cardiac arrhythmias, pyrexia (due to inhibition of sweating), pregnancy and breast feeding. Because of prolongation of renal elimination, repeated or large doses of glycopyrronium bromide should be avoided in patients with uremia. Large doses of quaternary anticholinergic compounds have been shown to block end plate nicotinic receptors. This should be considered before using glycopyrronium bromide in patients with myasthenia gravis. It is known that the administration of anticholinergic agents during inhalation anesthesia can result in ventricular arrhythmias.

Use in Special Populations:
Pediatric Use: Arrhythmias associated with the use of glycopyrronium bromide intravenously as a premedication or during anesthesia appear to be more likely in pediatric patients than in adults. Infants, patients with Down's syndrome and pediatric patients with spastic paralysis or brain damage may experience an increased response to anticholinergics, thus increasing the potential for side effects. A paradoxical reaction characterized by hyperexcitability may occur in pediatric patients taking large doses of anticholinergics including glycopyrronium bromide. Infants and young children are especially susceptible to the toxic effects of anticholinergics. Safety and effectiveness of long-term IV use has not been established in pediatric patients. Long-term use of Glycopyrronium is therefore not recommended in pediatric patients.

Elderly Use: Clinical studies of glycopyrronium bromide did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or drug therapy.

Overdose:
Glycopyrronium bromide is a quaternary ammonium agent and symptoms of overdosage are peripheral rather than central in nature. Excessive peripheral anticholinergic effects may be countermanded by giving intravenously a quaternary ammonium anticholinesterase such as neostigmine methylsulphate in increments of 0.25 mg in adults. The dose may be repeated every 5-10 minutes until anticholinergic over-activity is reversed or up to a maximum of 2.5 mg. Proportionately smaller doses should be used in children.

Storage:
Keep below 25°C temperature, away from light & moisture. Keep out of the reach of children.

Glycopyrronium Bromide (Oral solution): Uses, Dosage, Side Effects

Generic Name
Glycopyrronium Bromide (Oral solution)
Therapeutic Class: Anticholinergics (antimuscarinics)/ Anti-spasmodics

Indications:
Glycopyrronium Bromide is indicated to reduce chronic severe drooling in patients aged 3 to 16 years with neurologic conditions associated with problem drooling (e.g., cerebral palsy).

Description:
Glycopyrrolate is a competitive inhibitor of acetylcholine receptors that are located on certain peripheral tissues, including salivary glands. Glycopyrrolate indirectly reduces the rate of salivation by preventing the stimulation of these receptors. Glycopyrrolate inhibits the action of acetylcholine on salivary glands thereby reducing the extent of salivation.

Dosage & Administration:
Glycopyrronium Bromide oral solution must be measured and administered with an accurate measuring device. Initiate dosing at 0.02 mg/kg orally three times daily and titrate in increments of 0.02 mg/kg every 5-7 days based on therapeutic response and adverse reactions. The maximum recommended dosage is 0.1 mg/kg three times daily not to exceed 1.5-3 mg per dose based upon weight.

During the four-week titration period, dosing can be increased with the recommended dose titration schedule while ensuring that the anticholinergic adverse events are tolerable. Prior to each increase in dose, review the tolerability of the current dose level with the patient’s caregiver.

Glycopyrronium Bromide oral solution should be dosed at least one hour before or two hours after meals. The presence of high-fat food reduces the oral bioavailability of this oral solution if taken shortly after a meal

Interaction:
  • Digoxin tablets: Use with glycopyrrolate can increase digoxin serum levels. Monitor patients and consider use of alternative dosage forms of digoxin.
  • Amantadine: Effects of glycopyrrolate may be increased with concomitant administration of amantadine. Consider decreasing the dose of glycopyrrolate during concomitant use.
  • Atenolol or metformin: Glycopyrrolate may increase serum levels of atenolol or metformin. Consider dose reduction when used with glycopyrrolate.
  • Haloperidol or levodopa: Glycopyrrolate may decrease serum levels of haloperidol or levodopa. Consider a dose increase when used with glycopyrrolate.
Contraindications:
Glycopyrronium Bromide oral solution is contraindicated in:
  • Patients with medical conditions that preclude anticholinergic therapy (e.g., glaucoma, paralytic ileus, unstable cardiovascular status in acute hemorrhage, severe ulcerative colitis, toxic megacolon complicating ulcerative colitis, myasthenia gravis).
  • Patients taking solid oral dosage forms of potassium chloride. The passage of potassium chloride tablets through the gastrointestinal (GI) tract may be arrested or delayed with coadministration of Glycopyrronium Bromide oral solution.
Side Effects:
  • Gastrointestinal: Abdominal distention, abdominal pain, stomach discomfort, chapped lips, flatulence, retching, dry tongue
  • General Disorders: Irritability, pain
  • Infections: Pneumonia, sinusitis, tracheostomy infection, upper respiratory tract infection, urinary tract infection
  • Investigations: Heart rate increase
  • Metabolism and Nutrition: Dehydration
  • Nervous System: Headache, convulsion, dysgeusia, nystagmus
  • Psychiatric: Agitation, restlessness, abnormal behavior, aggression, crying, impulse control disorder, moaning, mood altered
  • Respiratory: Increased viscosity of bronchial secretion, nasal congestion, nasal dryness
  • Skin: Dry skin, pruritus, rash
  • Vascular: Pallor
Pregnancy & Lactation:
There are no available data in pregnant women for Glycopyrronium Bromide to inform decisions concerning any drug-associated risks. There are no data on the presence of glycopyrrolate or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Glycopyrronium Bromide and any potential adverse effects on the breastfed infant from Glycopyrronium Bromide or from the underlying maternal condition.

Precautions & Warnings:
Constipation or Intestinal Pseudo-obstruction: Constipation is a common dose-limiting adverse reaction that sometimes leads to glycopyrrolate discontinuation. Assess patients for constipation, particularly within 4-5 days of initial dosing or after a dose increase. Intestinal pseudo-obstruction has been reported and may present as abdominal distention, pain, nausea or vomiting.

Incomplete Mechanical Intestinal Obstruction: Diarrhea may be an early symptom of incomplete mechanical intestinal obstruction, especially in patients with ileostomy or colostomy. If the incomplete mechanical intestinal obstruction is suspected, discontinue treatment with Glycopyrronium Bromide and evaluate for intestinal obstruction.
High Ambient Temperatures: In the presence of high ambient temperature, heat prostration (fever and heat stroke due to decreased sweating) can occur with the use of anticholinergic drugs such as Glycopyrronium Bromide. Advise patients/caregivers to avoid exposure of the patient to hot or very warm environmental temperatures.
Operating Machinery or an Automobile: Glycopyrronium Bromide may produce drowsiness or blurred vision. As appropriate for a given age, warn the patient not to engage in activities requiring mental alertness such as operating a motor vehicle or other machinery, or performing hazardous work while taking Glycopyrronium Bromide.
Anticholinergic Drug Effects: Use Glycopyrronium Bromide with caution in patients with conditions that are exacerbated by anticholinergic drug effects including:
  • Autonomic neuropathy
  • Renal disease
  • Ulcerative colitis- Large doses may suppress intestinal motility to the point of producing a paralytic ileus and for this reason may precipitate or aggravate "toxic megacolon", a serious complication of the disease
  • Hyperthyroidism
  • Coronary heart disease, congestive heart failure, cardiac tachyarrhythmias, tachycardia, and hypertension
  • Hiatal hernia associated with reflux esophagitis, since anticholinergic drugs may aggravate this condition
Use in Special Populations:
  • Pediatric Use: Glycopyrronium Bromide was evaluated for chronic severe drooling in patients aged 3-16 years with neurologic conditions associated with problem drooling. Glycopyrronium Bromide has not been studied in subjects under the age of 3 years.
  • Geriatric Use: Clinical studies of Glycopyrronium Bromide did not include subjects aged 65 and over.
  • Renal Impairment: Because glycopyrrolate is largely renally eliminated, Glycopyrronium Bromide should be used with caution in patients with renal impairment
Overdose:
Because glycopyrrolate is a quaternary amine that does not easily cross the blood-brain barrier, symptoms of glycopyrrolate overdosage are generally more peripheral in nature rather than central compared to other anticholinergic agents. 
In case of accidental overdose, therapy may include:
  • Maintain an open airway, providing ventilation as necessary.
  • Managing any acute conditions such as hyperthermia, coma and or seizures as applicable, and managing any jerky myoclonic movements or choreoathetosis which may lead to rhabdomyolysis in some cases of anticholinergic overdosage.
  • Administering a quaternary ammonium anticholinesterase such as neostigmine to help alleviate peripheral anticholinergic effects such as anticholinergic induced ileus.
  • Administering activated charcoal orally as appropriate.
Storage:
Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.

Glycopyrronium Bromide (Inhalation capsule): Uses, Dosage, Side Effects

Generic Name
Glycopyrronium Bromide (Inhalation capsule)
Therapeutic Class: Bronchodilator

Indications:
Maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD).

Description:
Glycopyrronium is a long-acting, specific antimuscarinic agent, in clinical medicine often called an anticholinergic. It has a similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, inhibition of M3-receptors at the smooth muscle results in relaxation. The high potency and slow receptor dissociation found its clinical correlate in significant and long-acting bronchodilation in patients with COPD.

Dosage & Administration:
The recommended dosage of Glycopyrronium is the inhalation of the contents of one capsule once daily with the ConviHaler device at the same time of day.

Interaction:
Although no formal drug interaction studies have been performed, Glycopyrronium inhalation powder has been used concomitantly with other drugs, commonly used in the treatment of COPD, including sympathomimetic bronchodilators, methylxanthines, oral and inhaled steroids without clinical evidence of drug interactions.

Contraindications:
Hypersensitivity to the active substance or to any of the excipients.

Side Effects:
Inhaled medicines may cause inhalation-induced bronchospasm, dehydration, dry mouth, constipation, dizziness, insomnia, skin and subcutaneous tissue disorders, immune system disorders.

Pregnancy & Lactation:
There is a limited amount of data from the use of Glycopyrronium in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity at clinically relevant doses. Glycopyrronium should not be used in pregnant or nursing women unless the expected benefit outweighs any possible risk to the unborn child or the infant.

Precautions & Warnings:
Glycopyrronium, as a once-daily maintenance bronchodilator, should not be used for the initial treatment of acute episodes of bronchospasm, i.e. rescue therapy. Immediate hypersensitivity reactions may occur after administration of Glycopyrronium inhalation powder. As with other anticholinergic drugs, Glycopyrronium should be used with caution in patients with narrow-angle glaucoma, prostatic hyperplasia or bladder-neck obstruction.

Overdose:
High doses of Glycopyrronium may lead to anticholinergic signs and symptoms. However, there were no systemic anticholinergic adverse effects following a single inhaled dose of up to 150 micrograms Glycopyrronium in healthy volunteers.

Storage:
Should be stored at temperature not exceeding 25ºC but do not freeze. Should be stored in cool and dry place, protected from light.

Glycerol + Liquid Sugar: Uses, Dosage, Side Effects

Generic Name
Glycerol + Liquid Sugar
Therapeutic Class: Combined cough suppressants

Indications:
Glycerol & Liquid Sugar is indicated in- relief of dry, irritating cough and sore throat. It also assists in relieving productive cough.

Presentation:
Glycerol + Liquid Sugar Syrup: Each 5 ml syrup contains Glycerin BP 0.75ml and Liquid sugar BP 1.93ml (Equivalent to sucrose BP 1.7g)

Description:
Glycerol is an osmotic dehydrating agent that possesses hygroscopic and lubricating properties. It causes plasma osmolality leading to the movement of water into the plasma from the extravascular spaces via osmosis.

Dosage & Administration:
Adults including the elderly and children over 5 years: Two 5 ml spoonful (10 ml)
Children 1 to 5 years: One 5 ml spoonful (5 ml)
Children 3 month to 1 year: ½ to 1 spoonful (2.5 to 5 ml)
The dose should be repeated three or four times a day as required.

Interaction:
No clinically significant interactions known.

Contraindications:
Hypersensitivity or intolerance to any of the ingredients.

Side Effects:
This medicine is unlikely to cause side effects unless the patient is allergic to the ingredients.

Pregnancy & Lactation:
The safety of this medicine during pregnancy and lactation has not been established, but is not considered to constitute a hazard during these periods.

Precautions & Warnings:
Diabetics should take note of the carbohydrate content of this product. Do not give to children under one year. Keep all medicines out of the reach of children.

Overdose:
Over dosage would not be expected to cause any problems and treatment would be merely symptomatic and supportive.

Storage:
Should be stored in a cool and dry place, protected from light.

Glucosamine Sulfate + Chondroitin + Camphor + Peppermint oil

Generic Name
Glucosamine Sulfate + Chondroitin + Camphor + Peppermint oil
Therapeutic Class: Topical Analgesics

Indications:
This pain-relieving cream is applied topically and provides powerful pain relief of osteoarthritis pain, sprains, simple backache, tendonitis, minor arthritis pain.

Presentation:
Each gram cream contains-
  • Glucosamine Sulfate Potassium Chloride USP 20 mg
  • Chondroitin Sulfate Sodium USP 30 mg
  • Camphor USP 31 mg
  • Peppermint oil BP 1.25 mg.
Description:
Glucosamine is sugar protein that is believed to help in developing and renewing cartilage and keep it lubricated for better joint movement and flexibility.

Chondroitin helps to maintain fluid and flexibility in the joints. The combination of chondroitin and glucosamine is widely used to aid in maintaining healthy joints. It is also used as a nutritional supplement in people with osteoarthritis or other inflammatory joint disorders.

Camphor is a strong smelling compound, chemically manufactured from turpentine oil. When applied to the skin, it stimulates nerve endings to relieve pain, itching and to relieve osteoarthritis.

Peppermint Oil is a strong smelling ingredient can be applied to the skin to treat muscle pain, nerve pain and joint pain.

Dosage & Administration:
For the management of osteoarthritis the recommended dose is twice daily into painful muscle and joints for 2-4 week. Apply gently to painful muscles and joints, until this pain relieving cream disappears. Repeat as necessary.

Interaction:
This medicine is not known to interact significantly with other medicines.

Side Effects:
There are no known systemic side effects unless people have an allergy or skin sensitivity to camphor or one of the inactive ingredients.

Pregnancy & Lactation:
It should not be used during pregnancy & lactation.

Precautions & Warnings:
Do not apply on broken or irritated skin or if excessive irritation develops. Do not bandage tightly or use a heating pad. Do not swallow. Avoid eye contact or mucous membranes.

Storage:
Store in a cool and dry place, away from light. keep out of reach of children.

Glucosamine Sulfate + Chondroitin: Uses, Dosage, Side Effects

Generic Name
Glucosamine Sulfate + Chondroitin
Therapeutic Class: Stimulation of Cartilage formation

Indications:
Indicated for the treatment of osteoarthritis of the knee, hip, spine, hand, and other locations as a dietary supplement. It is also beneficial in rheumatoid arthritis, sport injuries, migraine, different skin problems (e.g., psoriasis), vascular complications (e. g., atherosclerosis), kidney stones, and inflammatory bowel disease (e.g., ulcerative colitis, leaky gut syndrome).

Presentation:
Glucosamine Sulfate + Chondroitin Tablet: Each Tablet contains Glucosamine Sulfate Potassium Chloride USP eq. to Glucosamine Sulfate 750 mg and Chondroitin Sulfate USP 600 mg.

Description:
Glucosamine is a natural amino-sugar, produced by the body and found in certain foods. It is the most fundamental building block required for biosynthesis of glycosaminoglycans (GAGs) like Hyaluronic Acid, Keratan Sulfate, and Chondroitin Sulfate. GAGs binds with protein and form proteoglycans, the essential building block of articular cartilage. When cartilage in a joint deteriorates,Osteoarthritis develops. It also helps to form ligaments, tendon, nails, and various other connective tissues.When we take artificially synthesized Glucosamine Sulfate supplement, it increases Glucosamine level in the body, thus facilitates production and repair of cartilage. Glucosamine also activates chondrocytes in the cartilage which help produce GAGs and proteoglycans.

Chondroitin Sulfate is a glycosaminoglycan (acid muco polysaccharide) found in connective tissue, especially in the articular cartilage of all mammals. Chondroitin Sulfate supplement acts similarly as Glucosamine Sulfate, since it also provide substrate for proteoglycans. Chondroitin also protects existing healthy cartilage from premature decline by preventing the MMP (Matrix metalloproteinase) enzyme that breakdowns the proteoglycans.

Combining Glucosamine with Chondroitin Sulfate shows synergistic effect. Data supports that this combination has been shown to be very much effective in severe cases of Osteoarthritis that treats both sign and symptoms of Osteoarthritis & modifies disease progression. It prevents Osteoarthritis in case of normal adults. In Osteoarthritic pain it is as effective as NSAIDs with significantly better tolerability and clinical compliance. It is also helpful during the repair phase of musculoskeletal soft tissue injuries such as tendon or ligament strains

Dosage & Administration:
250/200 mg tablet: 1 to 2 tablets, three times daily. The dose may be adjusted according to the response of the drug and body weight. Doses can be tapered after 60 days as per the requirement of the individual and for cost convenience. Typical dosage recommendation, based on body weight is as follows-

Under 54 Kg: 1000 mg Glucosamine Sulfate & 800 mg Chondroitin Sulfate per day
54 Kg to 91 Kg: 1500 mg Glucosamine Sulfate & 1200 mg Chondroitin Sulfate per day
Over 91 Kg: 2000 mg Glucosamine Sulfate & 1600 mg Chondroitin Sulfate per day.750/600 mg tablet: 1 tablet two times daily or as directed by the physician.

Interaction:
There have been no reports of significant drug interactions of Glucosamine and Chondroitin with Antibiotics/ Antidepressants/ Antihypertensives/ Nitrates/ Antiarrythmics/ Anxiolytics/ Hypoglycemic agents/ Antisecretives/ Antiasthmatics. Chondroitin may enhance the blood-thinning effects of anticoagulants like Warfarin, Heparin.

Contraindications:
There are no known contraindications for Glucosamine and Chondroitin. But proven hypersensitivity (e. g. allergic to shellfish or sulfur) to Glucosamine and Chondroitin is a contraindication.

Side Effects:
Safety studies with Glucosamine Sulfate & Chondroitin Sulfate show no demonstrable side effects. Rarely occurring side effects (such as mild & reversible intestinal flatulence) are almost like a placebo.

Pregnancy & Lactation:
Women who are pregnant or who could become pregnant should not supplement with Glucosamine Sulfate or Chondroitin Sulfate. Glucosamine and Chondroitin have not been studied enough to determine their effects on a developing fetus. No studies have evaluated the use of Glucosamine and Chondroitin during pregnancy or lactation. It should be taken with caution and medical advice during pregnancy and lactation.

Precautions & Warnings:
Patients with Diabetes Mellitus are advised to monitor blood glucose levels regularly when taking Glucosamine. No special studies were formed in patients with renal or hepatic insufficiency. The toxicological and pharmacokinetic profile of Glucosamine and Chondroitin does not indicate limitations for these patients. However, administration to patients with severe hepatic or renal insufficiency should be under appropriate medical supervision. Children should not be supplemented with Glucosamine and Chondroitin.

Storage:
Store in a cool and dry place, protected from light.

Glucosamine Sulfate + Diacerein: Uses, Dosage, Side Effects

Generic Name
Glucosamine Sulfate + Diacerein
Therapeutic Class: Stimulation of Cartilage formation

Indications:
This tablet is indicated in-
  • Osteoarthritis
  • Rheumatoid arthritis
  • Bone and Joint injuries
Presentation:
Glucosamine Sulfate + Diacerein Tablet: Each tablet contains Glucosamine Sulfate Potassium Chloride USP equivalent to Glucosamine Sulfate USP 750 mg and Diacerein INN 50 mg.

Description:
Glucosamine: Glucosamine (2-amino-2-deoxy-alpha-D-glucose) is a natural amino sugar, produced by the body and found in certain foods. It is the most fundamental building block required for biosynthesis of glycosaminoglycans (GAGs) like Hyaluronic Acid, Keratan Sulfate and Chondroitin Sulfate. GAGs binds with protein and form proteoglycans, the essential building block of articular cartilage. When cartilage in a joint deteriorates, Osteoarthritis develops. It also helps to form ligaments, tendon, nails and various other connective tissues. When we take artificially synthesized Glucosamine Sulfate supplement, it increases Glucosamine level in the body, thus facilitates production and repair of cartilage. Glucosamine also activates chondrocytes in the cartilage which help produce GAGs and proteoglycans.

In humans, about 90 percent of glucosamine, administered as an oral dose of glucosamine sulfate, is absorbed from the digestive tract. Predominantly metabolized by liver & excreted through urine.

Diacerein: This is used for the treatment of Osteoarthritis. It has also analgesic, antipyretic and anti-inflammatory activity. It's released in vitro and directly inhibits InterLeukin-1(IL-1) synthesis, which is the main cytokine involved in cartilage destruction. Due to specific mode of action, it have been shown to have a disease-modifying effect in experimental models of osteoarthritis and in human subjects with finger joint and knee osteoarthritis.

The oral bioavailability of Diacerein is 56%. Concurrent intake of food delays the time to peak concentration but associated with a 25% increase in absorption. Therefore, diacerein is best given with food. Mainly binds with protein albumin. Diacerein is metabolized extensively (100%) in liver following oral dosing. Urinary excretion of diacerein in the form of its metabolites has ranged between 35% and 60%.

Dosage & Administration:
Use in adults: One tablet twice daily with food.

Use in children and adolescents: The safety and effectiveness of children and adolescents under the age of 18 years have not been established.

Interaction:
Decrease absorption of Diacerein with aluminium and/ or magnesium hydroxide antacids. Increase risk of diarrhea with laxatives or antibiotics.

Contraindications:
Contraindicated for those who show hypersensitivity to Glucosamine or Diacerein.

Side Effects:
No serious adverse effect has been reported. Nausea, vomiting, diarrhea, epigastria pain, headache, skin rashes & intense yellow coloring of urine may have occurred.

Pregnancy & Lactation:
This tablet is contraindicated during pregnancy and breastfeeding.

Precautions & Warnings:
Caution should be practised when administering this tablet in the case of patients who are allergic to Glucosamine or Diacerein.

Overdose:
There is no data available regarding the overdose of this combination.

Storage:
Store in a cool & dry place below 30ºC, protect from light & moisture. Keep out of reach of children.

Glucosamine Hydrochloride: Uses, Dosage, Side Effects

Generic Name
Glucosamine Hydrochloride
Therapeutic Class: Stimulation of Cartilage formation

Indications:
Indicated for the treatment of osteoarthritis of the knee, hip, spine, and other locations. Also indicated as a dietary supplement.

Presentation:
Glucosamine Tablet: Each film-coated tablet contains Glucosamine Hydrochloride USP 500 mg.

Description:
Glucosamine is a naturally occurring compound for the body's production of joint lubricants and shock absorbers necessary to maintain healthy cartilage and joint function. Glucosamine hydrochloride is a prodrug for glucosamine that is well absorbed after oral administration and diffuses into several tissues, including bones and articular cartilages. The active ingredient in the treatment of osteoarthritis is glucosamine. The hydrochloride acid salt is the delivery vehicle. Once it has entered the stomach, after oral administration the salt's job is done and it is the glucosamine that is released to perform its function.

Data supports Glucosamine as the first anti-osteoarthritic drug that treats both signs and symptoms of osteoarthritis & modifies disease progression. It is as effective as NSAIDs with significantly better tolerability and clinical compliances.

Dosage & Administration:
500 mg tablet three times daily or as directed by the physician. A single dose of 1500 mg daily may also be effective. Obese individuals may need higher doses, based on body weight.

Interaction:
There have been no reports of significant drug interactions of Glucosamine with antibiotics, antidepressants, antihypertensives, nitrates, antiarrhythmics, anxiolytic, hypoglycaemic agents, anti-secretive.

Contraindications:
There are no known contraindications for Glucosamine. But proven hypersensitivity to Glucosamine is a contraindication.

Side Effects:
Safety studies with Glucosamine show no demonstrable toxicity. Rarely occurring side effects like mild & reversible intestinal flatulence are almost like a placebo.

Pregnancy & Lactation:
Women who are pregnant or who could become pregnant should not supplement with glucosamine. Glucosamine has not been studied enough to determine its effects on a developing fetus. And no studies have evaluated the use of Glucosamine during pregnancy or lactation. It should be taken with caution and medical advice during pregnancy and lactation.

Precautions & Warnings:
Diabetics are advised to monitor blood glucose levels regularly while taking Glucosamine. No special studies were formed in patients with renal and/or hepatic insufficiency. The toxicological and pharmacokinetic profile of the product does not indicate limitations for these patients. However, administration to these patients with severe hepatic or renal insufficiency should be under appropriate medical supervision.

Storage:
Should be stored in a cool and dry place.

Glimepiride + Metformin HCL: Uses, Dosage, Side Effects

Generic Name
Glimepiride + Metformin
Therapeutic Class:  Anti Diabetic / Combination Oral hypoglycemic preparations

Indications:
This tablet is indicated as an adjunct to diet and exercise in type 2 diabetes mellitus patients-
  • In case that the monotherapy with glimepiride or metformin does not result in adequate glycemic control.
  • Replacement of combination therapy of glimepiride and metformin.
Presentation:
 1/500 SR: Each sustained release tablet contains Glimepiride BP 1 mg and Metformin HCl BP 500 mg
 2/500 SR: Each sustained release tablet contains Glimepiride BP 2 mg and Metformin HCl BP 500 mg

Description:
Glimepiride is a sulfonylurea antidiabetic agent which decreases blood glucose concentration. The primary mechanism of action of Glimepiride appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells. Glimepiride acts in concert with glucose by improving the sensitivity of beta cells to physiological glucose stimulus, resulting in insulin secretion. In addition, extrapancreatic effects like reduction of basal hepatic glucose production, increased peripheral tissue sensitivity to insulin and glucose uptake may also play role in the activity of Glimepiride. In non-fasting diabetic patients, the hypoglycaemic action of a single dose of Glimepiride persists for 24 hours.

Metformin Hydrochloride is a biguanide type oral antihyperglycemic drug used in the management of type 2 diabetes. It lowers both basal and postprandial plasma glucose. Its mechanism of action is different from those of sulfonylureas and it does not produce hypoglycemia. Metformin Hydrochloride decreases hepatic glucose production, decreases intestinal absorption of glucose and improves insulin sensitivity by an increase in peripheral glucose uptake and utilization.

Dosage & Administration:
  • The dosage of this tablet is governed by the desired blood glucose level. The dosage of this tablet must be the lowest which is sufficient to achieve the desired metabolic control. During treatment with this tablet glucose levels in blood and urine must be measured regularly.
  • Mistakes, e.g. forgetting to take a dose, must never be corrected by subsequently taking a larger dose.
  • As an improvement in control of diabetes is, in itself, associated with higher insulin sensitivity, glimepiride requirements may fall as treatment proceeds. To avoid hypoglycaemia timely dose reduction or cessation of this tablet therapy must therefore be considered.
  • The highest recommended dose per day should be 8 mg of glimepiride and 2000 mg of metformin.
  • In order to avoid hypoglycaemia the starting dose of this tablet should not exceed the daily doses of glimepiride or metformin already being taken.
  • When switching from combination therapy of glimepiride plus metformin as separate tablets, this combination should be administered on the basis of dosage currently being taken.
Administration
This tablet must be swallowed whole and not crushed or chewed.

Interaction:
For Glimepiride:
  • Glimepiride is metabolized by cytochrome P450 2C9 (CYP2C9). This should be taken into account when glimepiride is coadministered with inducers (e.g. rifampicin) or inhibitors (e.g. fuconazole) of CYP 2C9.
  • Potentiation of the blood-glucose-lowering efect and, thus, in some instances hypoglycaemia may occur when one of the following drugs is taken, for example: insulin and other, oral antidiabetics; ACE inhibitors; anabolic steroids and male sex hormones; chloramphenicol; coumarin derivatives; cyclophosphamide; disopyramide; fenfuramine; fenyramidol; fbrates; fuoxetine; guanethidine; ifosfamide; MAO inhibitors; miconazole; fuconazole; para-aminosalicylic acid; pentoxifylline (high dose parenteral); phenylbutazone; azapropazone; oxyphenbutazone; probenecid; quinolones; salicylates; sulfnpyrazone; clarithromycin; sulfonamide antibiotics; tetracyclines; tritoqualine; trofosfamide.
  • Weakening of the blood-glucose-lowering efect and, thus raised blood glucose levels may occur when one of the following drugs is taken, for example: acetazolamide; barbiturates; corticosteroids; diazoxide; diuretics; epinephrine (adrenaline) and other sympathomimetic agents; glucagon; laxatives (after protracted use); nicotinic acid (in high doses); oestrogens and progestogens; phenothiazines; phenytoin; rifampicin; thyroid hormones.
  • H2 receptor antagonists, beta-blockers, clonidine and reserpine may lead to either potentiation or weakening of the blood-glucose-lowering efect. Under the infuence of sympatholytic drugs such as beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation to hypoglycaemia may be reduced or absent.
  • Both acute and chronic alcohol intake may potentiate or weaken the blood-glucose-lowering action of glimepiride in an unpredictable fashion.
  • The efect of coumarin derivatives may be potentiated or weakened.
  • Bile acid sequestrant: Colesevelam binds to glimepiride and reduces glimepiride absorption from the gastrointestinal tract. Glimepiride should be administered at least 4 hours prior to colesevelam.
For Metformin: Concomitant use not recommended:
  • Alcohol: Alcohol intoxication is associated with an increased risk of lactic acidosis, particularly in case of fasting, malnutrition or hepatic insufciency. Avoid consumption of alcohol and alcohol-containing medications
  • Iodinated contrast agents: Metformin must be discontinued prior to, or at the time of the imaging procedure and not restarted until at least 48 hours after, provided that renal function has been re-evaluated and found to be stable.
  • Combinations requiring precautions for use: Some medicinal products can adversely afect renal function which may increase the risk of lactic Acidosis. When starting or using such products in combination with metformin, close monitoring of renal function is necessary. Glucocorticoids, beta-2-agonists, and diuretics have intrinsic hyperglycemic activity. Inform the patient and perform more frequent blood glucose monitoring. ACE-inhibitors may decrease the blood glucose levels. Metformin may decrease the anticoagulant efect of phenprocoumon. Therefore, a close monitoring of the INR is recommended. Levothyroxine can reduce the hypoglycemic efect of metformin. Monitoring of blood glucose levels is recommended, especially when thyroid hormone therapy is initiated or stopped, and the dosage of metformin must be adjusted if necessary.
Organic cation transporters (OCT): Metformin is a substrate of both transporters OCT1 and OCT2. Co-administration of metformin with:
  • Inhibitors of OCT1 (such as verapamil) may reduce efcacy of metformin.
  • Inducers of OCT1 (such as rifampicin) may increase gastrointestinal absorption and efcacy of metformin.
  • Inhibitors of OCT2 (such as cimetidine, dolutegravir, ranolazine, trimethoprime, vandetanib, isavuconazole) may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration.
  • Inhibitors of both OCT1 and OCT2 (such as crizotinib, olaparib) may alter efcacy and renal elimination of metformin.Caution is therefore advised, especially in patients with renal impairment, when these drugs are coadministered with metformin, as metformin plasma concentration may increase. If needed, dose adjustment of metformin may be considered as OCT inhibitors/inducers may alter the efcacy of metformin.
Contraindications:
For Glimepiride-
  • In patients hypersensitive to glimepiride, metformin, other sulfonylureas, other sulfonamides, or any of the excipients of Amaryl M.
  • In pregnant women.
  • In breastfeeding women.
No experience has been gained concerning the use of glimepiride in patients with severe impairment of liver function and in dialysis patients. In patients with severe impairment of hepatic function, change-over to insulin is indicated, not least to achieve optimal metabolic control.
For Metformin-
  • Hypersensitivity to metformin or any of the excipients.
  • Any type of acute metabolic acidosis such as lactic acidosis Diabetic ketoacidosis, diabetic pre-coma.
  • Severe Renal failure or renal disfunction (e.g., serum creatine levels >135 μmol/L in males and >110 μmol/L in females), GFR < 30 mL/min.
  • Acute conditions with the potential to alter renal function such as Dehydration, severe infection, intravascular administration of iodinated contrast agents etc.
  • Acute or chronic disease which may cause tissue hypoxia such as cardiac or respiratory failure, recent myocardial infarction, shock
  • Hepatic insufciency.
  • Acute alcohol intoxication, alcoholism.
  • Lactation.
Side Effects:
For Glimepiride:
Metabolism and nutrition disorders-
  • As a result of the blood-glucose-lowering action of glimepiride, Hypoglycaemia which may also be prolonged.
  • The clinical picture of a severe hypoglycaemic attack may resemble that of a stroke.
Eye disorders: Especially at the start of treatment, there may be temporary visual impairment due to the change in blood glucose levels. The cause is a temporary alteration in the turgidity and hence the refractive index of the lens, this being dependent on blood glucose level.

Gastrointestinal disorders-
  • Occasionally, Gastrointestinal symptoms such as nausea, vomiting, sensations of pressure or fulness in the epigastrium, abdominal pain and diarrhea may occur.
  • In isolated cases, there may be hepatitis, elevation of liver enzyme levels and/or cholestasis and jaundice, which may progress to life-threatening liver failure.
  • Dysgeusia (frequency not known)
Blood and lymphatic system disorders-
  • Changes in the blood picture may occur: Rarely, thrombocytopenia and, in isolated cases, leucopenia, hemolytic anemia, erythrocytopenia, granulocytopenia, agranulocytosis or pancytopenia may develop. Cases of severe thrombocytopenia with platelet count less than 10,000/μl and thrombocytopenic purpura have been reported in post-marketing experience (frequency not known).
Skin and subcutaneous tissue disorders: Alopecia (frequency not known)

General disorders-
  • Occasionally, Allergic or pseudo allergic reactions may occur, e.g. in the form of itching, urticaria or rashes. Such mild reactions may develop into serious reactions with dyspnoea and a fall in blood pressure, sometimes progressing to shock.
  • In isolated cases, a decrease in serum sodium concentration and allergic vasculitis or hypersensitivity of the skin to light may occur.
Investigations: Glimepiride, like all sulfonylureas, can cause weight gain (frequency not known)

For Metformin:
  • Gastrointestinal symptoms such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite (>10%) are very common. These occur most frequently during initiation of therapy and resolve spontaneously in most cases.
  • Metallic taste (3%) is common
  • Decrease of vitamin B12 absorption with decrease of serum levels has been observed in patients treated long-term with metformin and appears generally to be without clinical signifcance (<0.01%). However, Cases of peripheral neuropathy in patients with vitamin B12 defciency have been reported in post-marketing experience (frequency not known). (frequency unknown)
  • Lactic acidosis (0.03 cases/1000 patient-years) is very rare
  • Hemolytic anemia (frequency unknown)
  • Reduction of thyrotropin level in patients with hypothyroidism (frequency unknown)
  • Hypomagnesemia in the context of diarrhea (frequency unknown)
  • Encephalopathy (frequency unknown)
  • Photosensitivity (frequency unknown)
  • Hepatobiliary disorders: Reports of liver function tests abnormalities and hepatitis resolving upon metformin discontinuation.
Pregnancy & Lactation:
Pregnancy-
For Glimepiride: Glimepiride must not be taken during pregnancy. Otherwise, there is risk of harm to the child. The patient must change over to insulin during pregnancy. Patients planning a pregnancy must inform their physician. It is recommended that such patients change over to insulin.
For Metformin: When the patient plans to become pregnant and during pregnancy, diabetes should not be treated with metformin but insulin should be used to maintain blood glucose levels as close to normal as possible in order to lower the risk of fetal malformations associated with abnormal blood glucose levels.

Lactation-
For Glimepiride: To prevent possible ingestion with the breast milk and possible harm to the child, glimepiride must not be taken by breast-feeding women. If necessary the patient must change over to insulin, or must stop breastfeeding.
For Metformin: Metformin is excreted into milk in lactating rats. Similar data is not available in humans and a decision should be made whether to discontinue nursing or to discontinue metformin, taking into account the importance of the compound to the mother.

Precautions & Warnings:
For Glimepiride: In the initial weeks of treatment, the risk of hypoglycemia may be increased and necessitates especially careful monitoring. If risk factors for hypoglycemia are present, it may be necessary to adjust the dosage of glimepiride or the entire therapy. This also applies whenever illness occurs during therapy or the patient's life-style changes. It is known from other sulfonylureas that, despite initially successful countermeasures, hypoglycaemia may recur. Patients must, therefore, remain under close observation. Severe hypoglycaemia further requires immediate treatment and follow-up by a physician and, in some circumstances, in-patient hospital care. Treatment of patients with G6PD-defciency with sulfonylurea agents can lead to hemolytic anaemia. Since glimepiride belongs to the class of sulfonylurea agents, caution should be used in patients with G6PD-defciency and a non-sulfonylurea alternative should be considered.

For Metformin: Regular monitoring of thyroid-stimulating hormone (TSH) levels is recommended in patients withhypothyroidism. Long-term treatment with metformin has been associated with a decrease in vitamin B12 serumlevels which may cause peripheral neuropathy. Monitoring of the vitamin B12 level is recommended.

Use in Special Populations:
Children: Data is insufficient to recommend pediatric use of this tablet.

Renal impairment: A GFR should be assessed before initiation of treatment with metformin-containing products and at least annually thereafter. In patients at increased risk of further progression of renal impairment and in the elderly, renal function should be assessed more frequently, e.g. every 3-6 months. The maximum daily dose of metformin should preferably be divided into 2-3 daily doses. Factors that may increase the risk of lactic acidosis should be reviewed before considering the initiation of metformin in patients with GFR<60 mL/min. If no adequate strength of this tablet is available, individual monocomponents should be used instead of the fixed dose combination.

GFR 60-89 ml/min:
  • Metformin: Maximum daily dose is 3000 mg. Dose reduction may be considered in relation to declining renal function.
  • Glimepiride: The highest recommended dose per day should be 8 mg of glimepiride.
GFR 45-59 ml/min:
  • Metformin: Maximum daily dose is 2000 mg. The starting dose is at most half of the maximum dose.
GFR 30-44 ml/min:
  • Metformin: Maximum daily dose is 1000 mg. The starting dose is at most half of the maximum dose.
GFR <30 ml/min:
  • Metformin: Metformin is contraindicated
  • Glimepiride: Change-over to insulin is indicated, not least to achieve optimal metabolic control.
Overdose:
For Glimepiride: Acute overdosage, as well as long-term treatment with too high a dose of glimepiride, may lead to severe life-threatening hypoglycaemia. As soon as an overdose of glimepiride has been discovered, a physician must be notifed without delay. The patient must immediately take sugar, if possible in the form of glucose unless a physician has already undertaken responsibility for treating the overdose. Careful monitoring is essential until the physician is confdent that the patient is out of danger. It must be remembered that hypoglycaemia may recur after initial recovery. Admission to hospital may sometimes be necessary even as a precautionary measure. In particular, signifcant overdoses and severe reactions with signs such as loss of consciousness or other serious neurological disorders are medical emergencies and require immediate treatment and admission to hospital. If, for example, the patient is unconscious, an intravenous injection of concentrated glucose solution is indicated (for adults starting with 40 ml of 20% solution, for example). Alternatively in adults, administration of glucagon, e.g. in doses of 0.5 to 1 mg i.v., s.c. or i.m., may be considered. In particular when treating hypoglycaemia due to accidental intake of glimepiride in infants and young children, the dose of glucose given must be very carefully adjusted in view of the possibility of producing dangerous hyperglycaemia, and must be controlled by close monitoring of blood glucose. Patients who have ingested life-threatening amounts of glimepiride require detoxifcation (e.g. by gastric lavage and medicinal charcoal). After acute glucose replacement has been completed it is usually necessary to give an intravenous glucose infusion in lower concentration so as to ensure that the hypoglycaemia does not recur. The patient's blood glucose level should be carefully monitored for at least 24 hours. In severe cases with a protracted course, hypoglycaemia, or the danger of slipping back into hypoglycaemia, may persist for several days.

For Metformin: Hypoglycaemia has not been seen with metformin doses of up to 85 g, although Lactic acidosis has occurred in such circumstances. High overdose or concomitant risks of metformin may lead to lactic acidosis Lactic acidosis is a medical emergency and must be treated in hospital. The most efective method to remove lactate and metformin is haemodialysis. Pancreatitis may occur in the context of a metformin overdose.

Storage:
Store in a cool (not exceeding 25°C) and dry place, protected from light.