Description and Composition of Cidophage
Cidophage is a drug used in addition to proper dieting, exercise and at times in combination with other drugs for the treatment of type 2 diabetes. It is an antidiabetic drug in the class of biguanides and contains Metformin hydrochloride as its active pharmaceutical ingredient. It comes in the strength of 500 mg, 850 mg and 1000 mg either as immediate or extended release tablets. It can equally come in oral solution dosage form in the strength of 100 mg, 500 mg and 750 mg.
Pharmacological Actions of Cidophage
What is the mechanism of action of Cidophage or how does it work?
Cidophage is an anti-hyperglycemic agent which improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Its pharmacological mechanism of action are different from other classes of oral anti-hyperglycemic agents.
Metformin controls high blood sugar level because it:
- decreases hepatic glucose production
- decreases intestinal absorption of glucose, and
- improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
Unlike sulfonylureas, Metformin does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects and does not cause hyperinsulinemia. With metformin therapy, insulin secretion remains unchanged while fasting insulin levels and day-long plasma insulin response may actually decrease.
Pharmacokinetics of Cidophage
Food decreases absorption and bioavailability of Metformin. It is therefore better taken at least 30 minutes before meal. This is however not true for extended release Metformin as food increases its absorption to up to 50%.
Metformin has an absolute oral bioavailability of 40 to 60%, and gastrointestinal absorption is apparently complete within 6 hours of ingestion.
Metformin is negligibly bound to plasma proteins, in contrast to sulfonylureas, which are more than 90% protein bound. Metformin partitions into erythrocytes, most likely as a function of time. At usual clinical doses, steady state plasma concentrations of Metformin are reached within 24-48 hours and are generally <1 mg/ml .
Metabolism and Elimination
Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours. In blood, the elimination half life is approximately 17.6 hours, suggesting that the erythrocyte mass may be a compartment of distribution.
Indications and Uses of Cidophage
- The main use for Metformin is in the treatment of type 2 Diabetes Mellitus, especially when this accompanies obesity and insulin resistance.
- Metformin can also be used in the treatment of polycystic ovary syndrome.
- Progressive myoclonus epilepsy type 2 (Lafora disease)
- Type 2 Diabetes Mellitus Prevention (off-label use)
Dosage and Administration of Cidophage
1. Diabetes mellitus
Immediate Release tablet or Solution
Initial dose: 500 mg 12 hourly or 850 mg daily with meals; dose can be increased by 500 mg/week or 850 mg q2Weeks on the basis of glycemic control and tolerability.
Maintenance dose: 1500-2550 mg/day PO in divided doses of 8-12hr with meal.
Extended Release Tablet
500 mg PO qDay with dinner; titrate by 500 mg/day qWeek; not to exceed 2000 mg/day.
2. Polycystic Ovary Syndrome 
Immediate-release tablets (10-16 years)
Initial: 500 mg orally every 12 hours
Maintenance: Titrate once/week by 500 mg; no more than 2000 mg/day in divided doses
Immediate-release tablets (17 years of age and older)
Initial dose: 500 mg orally every 12 hours or 850 mg orally once/daily with meals; increase every two weeks
Maintenance doses: 1500-2550 mg/day orally divided once every 8-12hr with meal.
No more than 2550 mg/day
Extended-release (under 17 years of age)
Safety and efficacy not established
Extended-release (17 years of age and older)
500 mg orally once/daily with dinner; titrate by 500 mg/day once each week; not to exceed 2000 mg/day.
3. Lafora Disease
Titrate Metformin to a mean maintenance dose of 1167 mg/day (range: 500-2000 mg).
4. Type 2 Diabetes Prevention
Initial dose: 850 mg PO qDay.
Target dosing: 850 mg PO q12hr
Contraindications of Cidophage
Renal impairment, ketoacidosis, withdraw if tissue hypoxia likely e.g. sepsis, respiratory failure, recent myocardial infarction, hepatic impairment, use of lodine-containing X-ray contrast media (do not restart Metformin until renal function returns to normal) and use of general anaesthesia (suspend Metformin on the morning of surgery and restart when renal function returns to normal) pregnancy and breast-feeding
Cautions to Observe While Taking Cidophage
- Do not use Cidophage in patients with hepatic disease.
- Before initiating Metformin and at least annually thereafter assess renal function and verity as normal.
- When used with an insulin secretagogue (e.g, sulfonylurea, meglitinide), a lower dose of the insulin secretagogue may be required to reduce the risk of hypoglycemia.
Drug Interactions with Cidophage
- Alcohol: Increased risk of lactic acidosis in acute alcohol intoxication, particularly in case of: fasting or malnutrition, hepatic insufficiency. Avoid consumption of alcohol and alcohol containing medications while taking Metformin.
- Glucocorticoids (systemic and local routes), beta-2-agonists, and diuretics have intrinsic hyperglycamic activity. Inform the patient and perform more frequent blood glucose monitoring, especially at the beginning of treatment. If necessary, adjust the dosage of the antidiabetic drug during therapy with the other drug and upon its discontinuation.
- ACE-inhibitors may decrease the blood glucose levels. If necessary, adjust the dosage of the antidiabetic drug during therapy with the other drug and upon its discontinuation.
Side Effects of Cidophage
- Anorexia, nausea, vomiting, diarrhoea (usually transient)
- Abdominal pain
- Metallic taste
- Rarely lactic acidosis (withdraw treatment)
- Decreased vitamin-B absorption
- Pruritus and Urticaria
- Hepatitis also reported.
Overdosage of Cidophage
An overdose of Cidophage is likely to cause lactic acidosis.
Symptoms of lactic acidosis include a feeling of general discomfort or sickness: weakness, sore or aching muscles; trouble breathing, unusual drowsiness, dizziness or lightheadedness; unusual or unexplained stomach upset (after the initial stomach upset that may occur at the start of therapy with metformin), and the sudden development of a slow or irregular heartbeat.
Treatment of Metformin Overdosage
Treatment of metformin overdose is generally supportive, but may include sodium bicarbonate to address acidosis and standard hemodialysis or continuous veno-venous hemofiltration to rapidly remove metformin and correct acidosis
An overdose of Metformin is likely to cause lactic acidosis
Metformin is known to be substantially excreted by the kidney, and the risk of Metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Thus, patients with serum creatinine levels above the upper limit of normal for their age should not receive Metformin
Metformin should not be used during pregnancy unless clearly needed.
Because of potential for hypoglycemia in nursing infants may exist, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. If Metformin is discontinued, and if diet alone is inadequate for controlling blood glucose, insulin therapy should be considered.
Store in a cool and dry place. Protect from light.