Fixed Dose Combination (FDC) Drugs Characteristics

1. Introduction

Fixed Dose Combination (FDC) drug products are widely used across various therapeutic areas. A survey of oral FDC products shows that the five leading therapeutic areas with approved FDCs include infectious diseases, cardiovascular diseases, hormonal disorders, allergies, and pain management. Some notable statistics include:

• • In the cardiovascular segment, nearly 80% of FDCs are used for hypertension treatment
  • In infectious disease treatment, FDCs for HIV/AIDS rank the highest
  • In metabolic disorder management, most FDCs are used for diabetes treatment.
  • Among disease groups, hypertension and type II diabetes are the two key areas attracting FDC development.
  • In terms of dosage forms, oral FDCs account for the highest proportion, followed by inhalation formulations.

2. Advantages of FDCs

2.1 Therapeutic Benefits

2.1.1. Combining Drugs with Different Pharmacological Mechanisms .

This is particularly valuable in therapeutic areas such as hypertension, antiviral therapy, blood glucose control, and cholesterol management, where multiple drugs are required to achieve optimal efficacy. For example, Aggrenox®—a combination of two oral antiplatelet agents, dipyridamole and aspirin—demonstrates superior efficacy compared to the individual drugs taken separately.

2.1.2. Reducing the Risk of Microbial Resistance

This is especially crucial for antiviral drugs and tuberculosis (TB) treatment. For instance, the FDC of amoxicillin and potassium clavulanate enhances amoxicillin’s effectiveness because potassium clavulanate inhibits β-lactamase, protecting amoxicillin from degradation by β-lactamase-producing microorganisms. This combination effectively broadens amoxicillin’s antibacterial spectrum. In HIV treatment, the combination of efavirenz, emtricitabine, and tenofovir in Atripla® improves therapeutic outcomes.

2.1.3. Enhancing Treatment Adherence

By reducing the number of pills taken daily, FDCs improve patient compliance. For example, the “cocktail” therapy for HIV/AIDS patients combines multiple active ingredients to suppress viral replication and prevent drug resistance. Adherence to therapy is critical to avoiding resistance development.

The table below compares the number of tablets required for separate drugs versus FDCs in the initial phase of tuberculosis (TB) treatment for patients over 8 years old weighing 50–70 kg:

2.1.4. Improving Safety and Tolerability

For example, in Arthrotec® tablets, misoprostol—a prostaglandin analog—is combined with diclofenac, a nonsteroidal anti-inflammatory drug (NSAID). Misoprostol provides gastric protection, reducing the risk of gastrointestinal irritation and ulcers caused by diclofenac.

2.2. Cost Benefits:

2.2.1. Reducing Healthcare Costs

Surveys show that the cost of an FDC formulation is often comparable to or lower than the total cost of individual drug components.

2.2.2. Providing Opportunities for Pharmaceutical Companies to Maintain Product Lines

FDCs allow pharmaceutical companies to develop new product lines when patented single-entity drugs are nearing patent expiration.

3. Disadvantages of FDCs

3.1. Reduced Dosing Flexibility

FDCs make it difficult to adjust the dosage of individual components to meet specific patient needs or minimize side effects. To compensate for this limitation, multiple strength combinations have been developed to cover commonly used doses of each component. However, for patients requiring frequent dose adjustments, FDCs may be less suitable.

3.2. Difficulty in Identifying Adverse Drug Reactions .

Because FDCs contain multiple drugs in a single dosage form, determining which drug is responsible for an adverse reaction can be challenging.

3.3. Pharmacists and physicians can easily overlook the limits of some drugs in the FDC.

For instance, acetaminophen has a maximum daily dose limit of 4 g/day. Many patients may take acetaminophen concurrently with multiple FDCs containing acetaminophen and other analgesics such as codeine, oxycodone, or hydrocodone, leading to unintentional overdose. Similarly, metformin is contraindicated in men and women with serum creatinine levels of 1.5 mg/dL and 1.4 mg/dL, respectively. This contraindication may be overlooked when prescribing FDCs containing metformin.

3.4. Large Tablet Size

Since FDCs combine multiple drugs in a single tablet, the size may be too large for pediatric and elderly patients. For example, in type 2 diabetes treatment, metformin is a primary therapy with doses ranging from 500 mg to 2000 mg. When combined with another antidiabetic agent, the tablet size may become too large for easy swallowing.

3.5. Presence of Irrational FDCs .

Studies from Asia, India, and Latin America indicate that many FDCs lack a scientific rationale, leading some governments to ban certain FDCs due to insufficient efficacy evidence.

4. Common FDCs by Therapeutic Class

4.1. Antibiotics

4.2. Anti-Tuberculosis Drugs

4.3. Hypertension and Cardiovascular Drugs

In conclusion, FDCs offer numerous benefits for patients, healthcare providers, and pharmaceutical manufacturers, contributing to improved treatment outcomes and healthcare system efficiency.

References

Fixed-Dose Combination Formulations in Solid Oral Drug Therapy: Advantages, Limitations, and Design Features

Formulation design, challenges, and development considerations for fixed dose combination (FDC) of oral solid dosage forms