Ciprofibrate - Uses, Dosage, Warnings, Side Effects, and Pharmacological Aspects

Overview:

Ciprofibrate is a medication that belongs to a group of drugs known as fibric acid derivatives. It is used to lower high cholesterol and triglyceride levels in the blood and to increase the levels of high-density lipoprotein (HDL), or "good" cholesterol. It is not approved by the FDA (Food and Drug Administration) but has been authorized by various national agencies to treat hyperlipidemia. Ciprofibrate is available as a tablet. Patients are advised to avoid activities requiring mental alertness and coordination until the drug's effects are realized. If symptoms like muscle pain are experienced, report them to a healthcare professional immediately.

For Patients

What Is Hyperlipidemia?

Hyperlipidemia, or high cholesterol, refers to an abnormally high level of cholesterol in the blood, specifically a high level of LDL (low-density lipoprotein) cholesterol, often called "bad" cholesterol. High LDL cholesterol levels can lead to the development of atherosclerosis, a condition in which fatty deposits accumulate in the arteries and increase the risk of stroke, heart attack, and other cardiovascular diseases.

Poor diet, inactivity, obesity, smoking, and heredity are some of the factors that might raise cholesterol levels. High cholesterol levels may frequently be controlled through dietary adjustments, exercise, and other lifestyle alterations.

How Does Ciprofibrate Work?

Ciprofibrate is a medication that belongs to the class of drugs called fibrates, used to decrease blood triglyceride and cholesterol levels. Ciprofibrate's exact mode of action is unknown, although it is believed to function via activating a specific receptor known as peroxisome proliferator-activated receptor alpha (PPARα). PPARα is a nuclear receptor that regulates the expression of lipid metabolism-related genes, such as those responsible for increasing the breakdown of fatty acids in the liver and muscles and decreasing the production of triglycerides.

Activation of PPARα by Ciprofibrate leads to increased expression of enzymes involved in the beta-oxidation of fatty acids and a decrease in the production of very low-density lipoprotein (VLDL), a precursor of LDL cholesterol. Ciprofibrate also increases the activity of lipoprotein lipase (an enzyme that breaks down fats and triglycerides in the blood) and reduces the production of pro-inflammatory molecules, which may aid in reducing the risk of cardiovascular disease.

What Are the Available Doses and Dosage Forms of Ciprofibrate?

Ciprofibrate is available as 100 mg (milligrams) tablets.

Administration:

• The medication is to be administered as instructed by the doctor.

• Swallow the tablets as a whole with a glass of water.

• The physician will determine the frequency and duration of drug therapy based on the patient's age, weight, underlying medical conditions, and medication history.

• Follow the dietary requirements given by the dietician or doctor while taking the medication.

• Adhere to the instructions given by the doctor or healthcare provider. In case of queries, contact the doctor or pharmacist.

How Effective Is Ciprofibrate?

Studies have indicated that Ciprofibrate can effectively reduce triglyceride levels by up to 50 percent and increase HDL cholesterol levels by up to 20 percent. Ciprofibrate has also been shown to reduce the risk of cardiovascular events, like heart attacks and strokes, in some patient populations. It should be noted that Ciprofibrate may not be effective in all patients and may not be appropriate for some individuals with certain medical conditions. Hence, a licensed healthcare professional should only administer the medication as directed.

What Are the Things to Inform the Doctor Before Taking Ciprofibrate?

Avoid administration in the following conditions:

• The patient is allergic or hypersensitive to Ciprofibrate or other ingredients in the medication.

• Signs of an allergic reaction include a rash, difficulty swallowing or breathing, and swelling of the lips, face, throat, or tongue.

• The patient is pregnant, planning to become pregnant, or suspect pregnancy.

• The patient is currently breastfeeding.

• The patient has a history of severe liver or kidney problems

• The patient is taking fibrates, such as Clofibrate, Bezafibrate, Fenofibrate, or Gemfibrozil, used to treat high levels of blood fats.

Inform the doctor if any of the following conditions are present before they prescribe Ciprofibrate:

• If the patient has a history of unexpected muscle pains, tenderness, weakness, liver or kidney problems, under-active thyroid gland, or a family history of muscle problems.

• If the patient is over 70 years of age.

• Taking Ciprofibrate may affect the results of some blood tests, so inform the person taking the test that the patient is taking Ciprofibrate.

• During treatment, the doctor may check how the liver is functioning through blood tests.

• Inform the doctor or pharmacist of all the medications the patient is taking or has recently taken, including alternative or herbal medicines, as Ciprofibrate can affect how some other medicines work and vice versa.

• Inform the doctor if the patient is taking statins, Warfarin, insulin, Metformin, contraceptive medicines, or hormone replacement therapy (HRT).

• One of the side effects of Ciprofibrate is muscle pain, and alcohol consumption may increase the chance of muscle problems. Therefore, limit alcohol consumption while taking Ciprofibrate and seek advice from the doctor.

What Are the Side Effects of Ciprofibrate?

The common side effects include:

• Loss of hair or balding.

• Gastrointestinal problems like nausea, vomiting, and diarrhea.

• Indigestion.

• Muscle pain.

• Headaches.

• Issues with balance.

• Dizziness.

• Drowsiness.

The uncommon side effects of the medication include:

• Impotence.

• Easy bruising.

• Inflammation of the muscles.

• Cramping or stiffness of the muscles.

The more serious side effects of Ciprofibrate include:

• Ciprofibrate can cause muscle problems, including cramps, pain, or tenderness, which may result in kidney failure.

• An itchy and lumpy rash, sensitivity to sunlight, and itching can indicate an allergic reaction.

• Inflammation of the lungs leads to breathlessness, coughing, and fever.

• Scarring of the lung tissues leads to shortness of breath.

• Liver problems result in jaundice, characterized by yellowing of the eyes or skin.

• Severe or excruciating pain in the upper right abdomen may extend to the back and be accompanied by fever and vomiting. These symptoms may indicate biliary colic or gallstones.

If any of these symptoms are experienced, report them to a healthcare professional or the emergency department immediately.

What Are the Warnings and Precautions of Ciprofibrate?

• Galactose Intolerance: Ciprofibrate is not advised in patients with a known history of galactose intolerance, Lapp-lactose intolerance, or glucose-galactose malabsorption.

• Liver Diseases: Ciprofibrate may cause adverse effects on the liver. Hence, it is important to notify the doctor of any worsening of liver function (symptoms include vomiting, yellowing of the skin, and severe abdominal pain) at the earliest possible time.

• Muscle Conditions: Some patients have reported muscle problems while taking this medication, which can lead to severe conditions like myopathy and rhabdomyolysis. Patients may be at higher risk if there is a history of kidney problems, low albumin levels, an underactive thyroid, drinking excessively, a family history of muscular disorders, or muscle problems with other medications. Taking higher doses or using this medication with other similar medications can also increase the risk of muscle problems.

What Should Be Done if a Dose Is Missed?

In the case of a missed dose of Ciprofibrate, take the dose as soon as possible to maintain the dosing schedule and avoid any negative effects of a missed dose. However, if the next scheduled dose is near, skipping the missed dose is advisable to ensure the regular dosing schedule is not disrupted. Taking a double dose to compensate for a missed dose is not advisable, as it may increase the risk of side effects and toxicity.

What Should Be Done to Treat a Ciprofibrate Overdose?

If an individual has taken more Ciprofibrate than they should, it is crucial to seek immediate medical attention. They should contact their doctor or go to the hospital right away. It is also recommended that they take the medication pack with them to provide information on the dosage and frequency of administration. This information can be helpful for medical professionals to determine the appropriate course of action.

Stopping the Medication:

It is essential to continue taking Ciprofibrate until a doctor advises stopping, even if the individual starts to feel better. Discontinuing the medication without a doctor's consent can have adverse effects on one's health and lead to the progression of the underlying condition. When taking Ciprofibrate, following the recommended dosing schedule and not altering the dosage without consulting a healthcare professional is important. If there are any questions or concerns regarding using Ciprofibrate, it is advisable to consult with a doctor or pharmacist.

How to Store Ciprofibrate?

• It is important to keep medications out of the sight and reach of children to avoid accidental ingestion or misuse.

• Using Ciprofibrate beyond its expiration date, clearly stated on the carton, is not advisable. The expiration date refers to the last day of the stated month, and after this date, the medication may lose effectiveness or become unsafe for consumption.

• When disposing of unused or expired medications, following proper procedures to protect the environment is important. It is not recommended to dispose of medications via wastewater or household waste. Instead, it is advisable to consult a pharmacist on the appropriate ways to dispose of the medication.

For Doctors:

Indications:

The non-FDA labeled indications include

• Severe hypertriglyceridemia.

• Hyperlipidemia.

Adult Dosing:

For hyperlipidemia: 100 mg tablets once daily.

Dosing Considerations:

• Mild to moderate renal impairment: 100 mg on alternate days.

• Severe renal impairment: Contraindicated.

• Hepatic impairment: Avoid use.

Pharmacology:

Pharmacodynamics:

Clinical trials have demonstrated the efficacy of Ciprofibrate in treating hyperlipidemia caused by high levels of LDL and VLDL in the blood (classified as types IIa, IIb, III, and IV according to Fredrickson's classification). Ciprofibrate is a useful addition to dietary interventions for managing these conditions.

Mechanism of Action:

Ciprofibrate is a derivative of phenoxy-isobutyric acid that can lower lipids and raise HDL levels. It shares a similar structure with other fibric acid derivatives like Clofibrate, Gemfibrozil, Bezafibrate, and Fenofibrate. The primary mechanism by which Ciprofibrate reduces lipids is by increasing the activity of lipoprotein lipase (LPL), which helps break down triglyceride-rich particles such as very low-density lipoproteins (VLDL) and intermediate-density lipoproteins (IDL). Ciprofibrate and other fibric acids may also decrease the production and secretion of VLDL by the liver. Some studies suggest that Ciprofibrate may have a mild inhibitory effect on hydroxy-methylglutaryl CoA (HMG-CoA) reductase, which could be responsible for its stronger low-density lipoprotein (LDL) cholesterol-lowering effects.

Pharmacokinetics:

Absorption:

Ciprofibrate is easily absorbed in the human body, and the highest plasma concentrations are usually observed between one and four hours after oral administration. In healthy volunteers, a single dose of 100mg resulted in maximum plasma concentration levels of 21 to 36 μg/ml (micrograms per milliliter). Higher levels ranging from 53 to 165 μg/ml have been reported in patients undergoing long-term therapy.

Distribution:

Ciprofibrate is highly bound to plasma proteins, with a binding rate of approximately 98 percent within the therapeutic range.

Metabolism:

Ciprofibrate undergoes metabolism in the liver to form two active metabolites. One of the metabolites,1-O-beta-glucuronide, is responsible for most of the hypolipidemic activity. The other metabolite, 1-O-beta-acylglucuronide, is pharmacologically inactive.

Excretion:

Approximately 30 to 75 percent of a single dose of Ciprofibrate administered to healthy volunteers is excreted in the urine within 72 hours, either in its unchanged form (20 to 25 percent of total excreted) or as a conjugate. The terminal elimination half-life of Ciprofibrate varies from 38 to 86 hours in patients receiving long-term therapy.

Toxicity:

The extent of the overdose of Ciprofibrate is not yet known. The management measures are symptomatic and supportive.

Contraindications:

The contraindications of Ciprofibrate are listed below:

• Concomitant administration with other fibrate drugs.

• Pregnancy and lactation.

• Severe renal or hepatic impairment.

Warnings and Precautions:

• Concomitant Administration: If considering use, assess potential risks and benefits and refer to the prescribing information of HMG CoA reductase inhibitors for guidance. Avoid simultaneous use.

• Galactose Intolerance: Do not use it in patients with glucose-galactose malabsorption, Lapp lactose deficiency, or galactose intolerance.

• Hepatic: Patients with impaired liver function should exercise caution as liver injury may occur. Monitoring is recommended for all patients, and discontinuation may be necessary.

• Musculoskeletal: Myopathy has been observed, particularly in patients with renal impairment, hypoalbuminemia, hypothyroidism, alcoholism, age over 70 years, family or personal history of muscular disorders, or prior history of muscular toxicity with another fibrate. Monitoring is recommended, and discontinuation may be required. Rhabdomyolysis has been documented, particularly at higher doses (200 mg or greater) or when combined with other fibrates or HMG-CoA reductase inhibitors. Monitoring is recommended.

Specific Considerations:

• Ciprofibrate in Pregnant and Lactating Women: It is not recommended for use in pregnant women, as there is limited safety data available, and it may cause harm to the developing fetus. Animal studies have shown that Ciprofibrate may cause fetal malformations and impair fetal growth, especially during the first trimester of pregnancy. Additionally, Ciprofibrate is excreted in breast milk, so nursing mothers should not use it.

• Ciprofibrate in Pediatrics: Ciprofibrate has not been extensively studied in children, and its safety and effectiveness in pediatric patients have not been established. Therefore, Ciprofibrate is not recommended for use in children under the age of 12.

• Ciprofibrate in Geriatrics: Careful monitoring of hepatic and renal function is necessary for geriatric patients on therapy with Ciprofibrate. Use with caution in patients over 70 years of age.

• Ciprofibrate in Patients With Renal Impairment: The dosing of Ciprofibrate should be altered to an alternate-day regimen in patients with mild to moderate renal impairment. The use of Ciprofibrate is contraindicated in patients with severe renal impairment.

• Ciprofibrate in Patients With Hepatic Impairment: The use of Ciprofibrate is contraindicated in patients with hepatic impairment.