Bifril

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Bifril

Medically reviewed

Laura Arias

Last updated on 22/12/2025

This page provides general, reference-level information compiled from official medical sources. It is not a substitute for professional medical advice, diagnosis, or treatment. For decisions about your health, please consult a qualified healthcare professional.

Overview of Bifril

What is Bifril?

Bifril is a medication belonging to the class of drugs known as angiotensin-converting enzyme (ACE) inhibitors. It contains the active substance zofenopril calcium. This medication is primarily used to manage cardiovascular conditions by affecting the way the body regulates blood pressure and fluid balance.

Mechanism of Action

The active ingredient, zofenopril, works by inhibiting the activity of the ACE enzyme. In the body, this enzyme is responsible for converting angiotensin I into angiotensin II, a potent chemical that causes blood vessels to tighten and narrow. By blocking this conversion, Bifril helps blood vessels relax and widen, which facilitates easier blood flow and reduces the workload on the heart.

Therapeutic Use

Bifril is utilized in the treatment of various cardiovascular states where the regulation of blood pressure or the protection of heart function is necessary:

  • Hypertension: It is used to lower high blood pressure, which helps prevent long-term complications associated with elevated arterial pressure.
  • Acute Myocardial Infarction: It is administered following a heart attack in patients who may or may not show signs of heart failure, to help improve recovery and support cardiac function.

Properties of Zofenopril

Unlike some other medications in the same class, zofenopril is a sulfhydryl-containing ACE inhibitor. It is a prodrug, meaning it is converted into its active form, zofenoprilat, after it is absorbed in the body. This active form is characterized by its high lipophilicity, which allows it to interact effectively with the tissues of the heart and blood vessels.

Regulatory References

  1. EMA - Zofenopril

What side effects are possible with Bifril?

Possible Side Effects and Safety Information

Bifril (Zofenopril calcium), as an Angiotensin-Converting Enzyme (ACE) inhibitor, has a documented safety profile consisting of classified adverse reactions and specific regulatory limitations. All side effects are categorized by frequency based on official government regulatory documents.


Frequency-Classified Adverse Reactions

The most frequent adverse reactions are classified as common (may affect up to 1 in 10 people) and primarily involve symptoms of the respiratory and nervous systems. These common effects include headache, dizziness, and a characteristic, non-productive cough.

Reactions classified as uncommon (may affect up to 1 in 100 people) span several organ systems, including palpitations, insomnia, nausea, and asthenia (general weakness).


Serious Adverse Reactions and Safety Alerts

A key, serious adverse reaction associated with this class of medication is angioedema, which is rapid-onset swelling that requires immediate medical attention. Although uncommon, it is a potentially life-threatening event. Other serious documented risks include severe hypotension (low blood pressure), which is most likely to occur at the start of treatment or following a dose increase, and in rare cases, a syndrome progressing to hepatic failure.


Population-Specific Safety Constraints

Official labeling mandates specific constraints for certain populations. The medicine is strictly contraindicated during the second and third trimesters of pregnancy due to the risk of fetal harm. Use is also contraindicated in patients with a prior history of ACE inhibitor-related angioedema or those with severe hepatic impairment. Furthermore, the regulatory profile notes that ACE inhibitors are associated with a higher incidence of angioedema in Black patients.

Overdose and Emergency Response

Overdose with Zofenopril calcium (Bifril) is characterized by an exaggerated lowering of blood pressure, a condition known as severe hypotension, which is the most prominent documented manifestation. Due to this profound physiological effect, regulatory agencies state that immediate medical attention must be sought for any suspected overdose.

Documented Clinical Manifestations and Outcomes

Manifestation / Outcome Official Regulatory Description
Cardiovascular Effects Severe hypotension, bradycardia (slow heart rate), and syncope (fainting).
Life-Threatening Risks Progression to circulatory shock, or the precipitation of myocardial infarction or cerebrovascular accident (stroke).
Organ System Effects Potential for acute renal failure and documented electrolyte imbalance.

Required Emergency Actions

Patients must contact emergency services immediately if signs of severe hypotension or shock are present. Official labeling confirms that no specific antidote is known for Zofenopril calcium overdose. Consequently, treatment is strictly symptomatic and supportive, often requiring volume expansion through an intravenous infusion of saline solution, patient positioning (supine), and prolonged hospital monitoring until vital signs stabilize. The active metabolite may be subject to removal by certain dialysis procedures.

Therapeutic Uses of Bifril

This medication is commonly used across domains where additional symptomatic support is needed in the management of cardiovascular conditions. The primary therapeutic areas of use for Bifril are for conditions presenting with acute episodes.

The medicine is indicated for two primary purposes: the treatment of mild to moderate essential hypertension (high blood pressure) and for patients with acute myocardial infarction (heart attack).

In hypertension, Bifril is relevant for easing symptoms related to heightened physiological activity by helping to manage blood pressure. This supports the general well-being during symptomatic phases and contributes to easing the overall symptom load related to physiological strain on the cardiovascular system. For acute myocardial infarction, the treatment is applied in addressing conditions associated with acute or disruptive episodes, where the medicine assists with maintaining functional stability in clinical settings that involve acute or unstable symptom patterns.

“The treatment may assist with easing the overall symptom burden during periods of heightened symptoms.”

Quick Fact: May assist with managing Symptoms that create noticeable physiological strain

Regulatory References

  1. National Agency for Food and Drug Administration and Control (NAFDAC) Summary of Product Characteristics

Eligibility and Restrictions for Use

Who Can and Cannot Use Bifril?

Regulatory agencies define specific population criteria that determine eligibility for using Bifril (Zofenopril calcium).

Contraindicated Populations (Must Not Use)

Bifril is contraindicated and must not be used by patients with a history of angioneurotic oedema related to prior ACE inhibitor therapy, or those with hereditary/idiopathic angioneurotic oedema. Use is also prohibited in patients with severe hepatic impairment. Furthermore, it is contraindicated in women during the second and third trimesters of pregnancy.

Age and Condition Restrictions

The safety and efficacy of Bifril have not been established in children and adolescents below 18 years, and its use in this age group is not recommended. For acute myocardial infarction, use is not recommended in patients with pre-existing renal impairment or hepatic impairment. While use is permitted in adults, it requires caution in acute MI patients who are over 75 years of age. Bifril is not recommended during the first trimester of pregnancy or for women who are breastfeeding.

What should I know about interactions with other medicines?

Interactions with other medicines and products

Official regulatory documents define specific combinations and conditions that interact with Bifril (Zofenopril calcium), an ACE inhibitor.

Contraindicated and Time-Separated Combinations

Co-administration with Sacubitril/Valsartan is formally contraindicated due to the significantly increased risk of angioedema. Treatment with Bifril must not be initiated earlier than 36 hours after the last dose of Sacubitril/Valsartan, and vice-versa. The concurrent use of Bifril with aliskiren is contraindicated in patients with diabetes mellitus or moderate-to-severe renal impairment.


Pharmacodynamic and Exposure-Altering Effects

Multiple agents interact by modifying the drug’s effects or concentrations:

  • Hyperkalemia Risk: The risk of elevated serum potassium is increased when Bifril is used with potassium supplements, salt substitutes, potassium-sparing diuretics (e.g., Spironolactone), Heparin, and other potassium-increasing agents.
  • Angioedema Risk: The risk of angioedema is heightened when co-administered with mTOR inhibitors (e.g., Sirolimus), Vildagliptin, and Racecadotril.
  • Exposure Effects: Co-administration with Lithium can result in increased serum concentrations of Lithium and potential toxicity. Antacids may cause a reduction in Zofenopril exposure.

Other Documented Constraints

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) may reduce the antihypertensive effect. The consumption of alcohol is documented to increase the hypotensive effect of the medicine. Furthermore, there is a documented high incidence of anaphylactoid-like reactions in patients undergoing haemodialysis with high-flux polyacrylonitrile membranes.

Mechanism of Action

How Bifril Works

Bifril functions by directly modulating the pro-resorptive NFkappa B signaling pathway within osteoclasts (bone-resorbing cells). This interaction leads to a reduction in the lifespan and activity of the osteoclasts, which slows down the rate of bone degradation.

This mechanism also involves downstream modulation of the RANKL / OPG axis. Specifically, Bifril increases the expression of Osteoprotegerin (OPG), causing a shift in the RANKL to OPG ratio. The consequence of these molecular events is a reduction in the rate of bone resorption, contributing to the maintenance of the physiological balance between bone resorption and bone formation at the tissue level.

Dosage and Administration Information

Official Administration Guidelines for Bifril

Bifril (zofenopril calcium) is administered orally as a film-coated tablet, which may be taken with or without food. The official instructions for use are highly specific and depend directly on the approved indication.


Labeled Dosing Regimens

Condition Starting Dose Frequency & Pattern Official Duration
Essential Hypertension 15 mg once daily (or 7.5 mg for high-risk patients) Once daily, titrating up at four-week intervals based on blood pressure response. Indefinite (long-term plan)
Acute Myocardial Infarction 7.5 mg every 12 hours (first 2 days) Twice daily (every 12 hours), with a step-wise increase to 30 mg every 12 hours by day five. Six weeks total, beginning within the first 24 hours of symptoms.

Dose Modification for Specific Populations

Official prescribing information mandates dose adjustments for certain patient groups to ensure proper use, based on organ function. For patients with moderate-to-severe renal impairment (Creatinine Clearance < 45 mL/min) or mild-to-moderate hepatic impairment, the therapeutic dose should be halved. For patients maintained on dialysis, the starting dose for hypertension should be one-quarter of the dose used for normal function. Use in children and adolescents under 18 years is not recommended.

Patients considered high-risk for severe acute hypotension, such as those who are volume-depleted, must have their first dose administered under close monitoring, preferably in a hospital setting, as part of the procedural conditions of use.

Recent Clinical Evidence

Research Evidence Overview

This section summarizes the formal clinical research, primarily from regulatory-level Randomized Controlled Trials (RCTs) and systematic reviews, that was evaluated for the approved uses of Zofenopril (Bifril) for cardiovascular conditions. The information presented is strictly descriptive, focusing on the study designs, the patient groups examined, and the outcomes that researchers measured. The findings describe group patterns and research context, not individual predictions.


Evidence for Use in Managing High Blood Pressure (Essential Hypertension)

Research examining Zofenopril for the management of high blood pressure relies primarily on short-term to intermediate-term Randomized Controlled Trials. The main goal of these studies was to measure the change in systolic and diastolic blood pressure (BP) in adult patients. Studies consistently reported measurements indicating a change in both systolic and diastolic blood pressure across the observed populations. Trials that explored the fixed-dose combination product described different patterns of measured BP change compared to measurements in patients receiving monotherapy.

However, the majority of the core regulatory trials focused on measuring blood pressure change over relatively short periods, typically up to 12 weeks. This means there is limited information for long-term outcomes that specifically track the long-term occurrence of major cardiovascular events in the isolated hypertension population is not well characterized by these studies.


Evidence for Use Following Acute Myocardial Infarction (Heart Attack)

The research that examined the use of Zofenopril following an acute heart attack is centered on a coordinated program of large-scale, international Randomized Controlled Trials known as the SMILE studies. These studies explored the response to treatment initiated in adult patients generally within the first 24 hours of symptom onset.

The key studies monitored outcomes describing episodic or acute changes related to cardiovascular events using a composite measure, which tracked the occurrence of death, non-fatal re-infarction, and hospitalization due to severe congestive heart failure. Researchers observed differences in the patterns related to this primary composite endpoint at 6 weeks and 1 year for patients receiving Zofenopril compared to those receiving placebo.


Key Limitations and Areas of Uncertainty in the Research

For the heart attack indication, a substantial portion of the patient population enrolled in the early definitive trials had not received thrombolytic therapy at the time the study was initiated. This is an important contextual factor because current treatment settings may differ from the patient care environment at the time of the studies. For both approved indications, long-term effects are not fully established beyond the 5-year period for the original trial cohorts, and comparative evidence is lacking against many newer therapies that have since been developed. Data for certain groups, such as children, also remain insufficient.

Key Studies & References SUMMARY OF PRODUCT CHARACTERISTICS Bifril Plus 30 mg/12.5 mg film-coated tablets (Regulatory source on indications and limitations in specific populations)

Frequently Asked Questions (FAQ)

Common questions about Bifril (FAQ)


Q: What is the main difference between Bifril and other similar drugs I see advertised?

A: Official regulatory documents classify Bifril as belonging to a group of medicines called Angiotensin Converting Enzyme (ACE) inhibitors. This classification describes the specific way the medicine acts in the body compared to other therapeutic classes that treat similar health issues.

Q: Do you have to take Bifril every day, or only as needed?

A: According to official product information, Bifril is intended to be taken on a scheduled regimen, not just as needed. Depending on the condition being addressed, the official instructions describe administration either once or twice daily as part of a continuous course of treatment.

Q: What happens when you stop taking Bifril after using it for a while?

A: Official documentation for its use in acute myocardial infarction indicates a prescribed treatment duration of six weeks. After this period, a patient's need for continued treatment is subject to re-evaluation, and if certain signs are present, the treatment might be continued long term.

Q: What if a person feels like Bifril is not helping them after several weeks?

A: The official schedule for hypertension involves evaluation based on blood pressure response at four-week intervals. This suggests that several weeks may be needed before the medication’s full therapeutic effect can be assessed, according to prescribing guidelines.

Q: What is the typical duration of treatment described for Bifril?

A: The required duration of treatment depends on the condition. For essential hypertension, the treatment plan is officially described as indefinite (long-term plan). For acute myocardial infarction, the prescribed treatment duration is six weeks.

Q: Are there specific food items that must be avoided entirely with Bifril?

A: Official documents state that Bifril may be taken with or without food (the timing is not critical). The product information does not generally list specific food items that must be completely avoided.

Q: Is it normal to feel a change in energy level when first starting Bifril?

A: Regulatory documents list common adverse effects that may be experienced when starting this medication, including dizziness and fatigue. These may be perceived as a change in energy level.

Q: What should be avoided in terms of food or drink while taking Bifril?

A: Regarding beverages, official documentation describes that ACE inhibitors in general may lead to enhanced effects of alcohol. This is an important consideration during treatment.

Q: Can Bifril affect sleep patterns, like causing insomnia or making you drowsy?

A: Official product information lists sleep disorders as a rare adverse reaction. Any change in sleep patterns is considered an effect that has been noted.

Q: What kinds of non-prescription supplements are commonly described as interacting with Bifril?

A: Regulatory warnings indicate a potential for interaction with non-prescription supplements that contain high levels of potassium. This includes certain potassium supplements and salt substitutes that contain potassium.

Q: Is there any data on how Bifril affects cognitive functions or memory?

A: Official regulatory documents list confusional state as a rare adverse reaction. This is one example of a cognitive effect that has been noted in patients using the medicine.

Q: Can Bifril be taken with common over-the-counter pain relievers?

A: Official documentation notes that Nonsteroidal Anti-inflammatory Drugs (NSAIDs), which include many common pain relievers, may reduce the intended blood pressure-lowering effect of Bifril. They also may be associated with an increased risk of kidney problems, according to regulatory sources.

Q: Are there different strengths of Bifril tablets available?

A: Yes, official product information describes that Bifril is available in multiple strengths to allow for titration. These include 7.5 mg, 15 mg, 30 mg, and 60 mg film-coated tablets.

Q: Does Bifril require special storage conditions, like refrigeration?

A: Official storage information recommends keeping the medicine out of the sight and reach of children. It also specifies a temperature limit, advising against storing it above 30 C.

Q: Do studies suggest Bifril is effective across different age groups?

A: Official prescribing information notes that use is not recommended in children and adolescents under the age of 18. Furthermore, special care is described as being required when treating patients over 75 years of age who have had a heart attack.

Q: Can Bifril affect the results of standard lab tests (e.g., blood work)?

A: Regulatory information for a related product that contains zofenopril notes that it could cause a positive anti-dope test. This indicates a potential impact on that specific type of laboratory result.

Q: Is Bifril safe to take while drinking alcohol?

A: Official documentation describes that the ACE inhibitor class of medicine, to which Bifril belongs, may lead to enhanced effects of alcohol.

Q: How is Bifril officially described as interacting with medicines for high blood pressure?

A: Official documents warn against the concomitant use of Bifril with Angiotensin II Receptor Blockers (ARBs) and aliskiren. This is a specific warning, particularly for patients with diabetes-related kidney problems.

Q: What is the purpose of the 'inactive ingredients' listed in Bifril?

A: Inactive ingredients are listed for safety reasons. For example, official documents list the inactive ingredient lactose monohydrate and include a warning that patients with certain rare hereditary problems of sugar intolerance should not take the medicine.

Q: Are there any official recommendations about driving while taking Bifril?

A: Official documents state that the medicine may cause dizziness or tiredness. If this occurs, patients are described as advised not to drive or operate machinery where impairment could be a risk.

Q: Why is Bifril sometimes described as a 'starter' drug before trying other options?

A: For the related combination product (Bifril Plus), dose titration with the individual components is often recommended before switching to the fixed dose combination. This established approach is a typical method for initiating and adjusting therapy.

Q: Does Bifril carry any specific 'Black Box Warnings' from regulatory agencies?

A: All drugs in the Angiotensin Converting Enzyme (ACE) inhibitor class carry a warning that use during the second and third trimesters of pregnancy can cause injury and death to the developing fetus. This is a critical safety classification required by regulatory bodies like the FDA.

Q: Are there known cross-sensitivities between Bifril and other drug ingredients?

A: Official documentation states that Bifril is contraindicated (a reason not to use the drug) in those with a history of severe swelling (angioneurotic oedema) associated with previous ACE inhibitor therapy.

Q: How does a person get a prescription for Bifril?

A: Bifril is classified as a prescription-only medicine. It is not available for purchase over the counter.

Q: Is it possible to be allergic to Bifril?

A: Yes, official documentation lists hypersensitivity (allergy) to zofenopril or any other ACE inhibitor as a contraindication (a reason why the drug should not be used).

How should Bifril be stored and disposed of?

The official regulatory requirements for Bifril (Zofenopril calcium) establish specific conditions for its storage, stability, and eventual disposal.

Storage Requirements

Condition Requirement (Official Labeling)
Temperature Does not require special storage conditions (e.g., refrigeration).
Child Safety Must be kept out of the sight and reach of children.
Stability Do not use the medicine after the expiry date printed on the box and the blister pack.

Disposal Instructions

To discard unused or expired Bifril tablets, the regulatory instruction is to ask your pharmacist how to throw away the medicine. This ensures protection of the environment.

  • Prohibition: Do not dispose of this medicine via wastewater or household waste.

Attention! Always consult to a doctor or pharmacist before using pills or medicines.

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