Irrational Drug Combinations !

When two or more drugs are combined in a fixed dose formulation like tablet, capsule, syrup, powder or injection, then their plasma half-life should approximately be same. The ratio of dose would depend on the volume of distribution and peak plasma concentration. If the combination of drugs is illogical in terms of plasma half-life and pharmacokinetics of the drug, the combination should be termed as irrational drug combination. Large number of such irrational drug combinations are available in the market which unnecessarily increase the cost of medication and add to the side effects of the therapy. Some of these combinations have been discussed below:

1. Ampicillin + Cloxacillin:

Ampicillin is effective against Gram negative bacilli but Cloxacillin is an Anti-staphylococcal penicillin and not effective against Gram negative bacilli. Mixed Gram negative and Staphylococcal (Gram positive) infection rarely coexists. So, in a patient with a single infection, one of the drug of the combination would be useless. In addition to the cost of therapy it would add to adverse side effects and resistance of bacteria to the drug. On the other hand the combination would reduce the dose of effective drug to the half and the patient would need longer course of therapy.

2. Antibacterial + Antiamoebic Combinations:

Ciprofloxacin + Metronidazole, Norfloxacin + Tinidazole and Ofloxacin + Ornidazole are such commonly available fixed dose drug combinations. In bacterial diarrhoea only anti bacterial drug is effective and antiamoebic drug is useless. Similarly, in intestinal amoebiasis only antiamoebic drug is effective while antibacterial drug is useless. Amoebiasis and bacterial diarrhoea rarely coexist. The therapy should be based on the diagnosis to reduce the cost of treatment since in a given case, only one drug of the combination would be effective and the other one would be useless.

3. NSAIDs Combinations

Nimesulide, diclofenec, ibuprofen and paracetamol are some non-steroidal anti-inflammatory drugs (NSAIDs). There is no justification in combining one NSAID (nimesulide, diclofenec, ibuprofen) with another NSAID (paracetamol) having same pharmacological actions. The increased risk of hepatotoxicity has been reported due to the use of combination of nimesulide with paracetamol. There is increased risk of nephrotoxicity with NSAIDs combinations.

4. H₂ Blocker + Domperidone

Ranitidine and Famotidine are H₂ blockers. H₂ blockers reduce gastric acid production in peptic diseases and give symptomatic relief. The combination of these drugs with antiemetic drug (Domperidone) is an irrational drug combination as peptic ulcer is not always associated with vomiting. Even in gastro-esophageal reflux disease (GERD), the domperidone is less effective as compared to metoclopramide, so combining H₂ blockers with domperidone seems to be an irrational choice.

5. Domperidone + Proton Pump Inhibitors

Omeprazole, Pantroprazole and Lansoprazole are proton pump inhibitors. Proton pump inhibitors reduce gastric acid production in peptic diseases and give symptomatic relief. The combination of these drugs with antiemetic drug (Domperidone) is an irrational drug combination as peptic ulcer is not always associated with vomiting. Even in gastro-esophageal reflux disease (GERD), the domperidone is less effective as compared to metoclopramide, so combining proton pump inhibitors with domperidone seems to be an irrational choice.

6. Ondensetron + Proton Pump Inhibitor or H₂ Blocker

Such combination drugs are prescribed for the acid peptic disease, but the disease is not always associated with vomiting. So, the combination of Ondensetron, an antiemetic drug with antisecretary drugs like H₂ blocker (Ranitidine) or proton pump inhibitor (Omeprazole, Pantoprazole or Lansoprazole) seems to be an irrational drug combination.

7. H₂ Blocker (Ranitidine) + Antispasmodic Drug (Dicyclomine)

The pain of peptic ulcer is due to high level of gastric acid but not due to spasm of smooth muscles and will subside only with reduction in gastric acid in stomach by use of H₂ blocker (Ranitidine) or proton pump inhibitor drugs (Omeprazole, Pantoprazole or Lansoprazole). So there is no justification in combining H₂ blocker (Ranitidine) with antispasmodic drug (Dicyclomine).

8. Antacid + Antianxiety Drug

The acid peptic disease is rarely associated with psychosomatic basis. So, there is no justification of combining antianxiety drug like diazepam with antacids. The simultaneous use of antacids with antianxiety drugs should always be avoided as antacids reduce the absorption of antianxiety drugs.

9. Antacid + Antispasmodic Drug (Dicyclomine)

There is no justification in combining antacids with antispasmodic drug like Dicyclomine, because the pain of peptic ulcer is not due to the spasm of the smooth muscles.

10. Mucolytic Agent + Antibacterial

Ambroxol + Ciprofloxacin or Cefadroxil or Roxithromycin. Ambroxol is a mucolytic agent used to liquefy thick respiratory secretions. There is no justification in combining mucolytic agent with antibacterial, as thick secretions in respiratory tract are always not due to respiratory infections. Also the antibacterial therapy always does not require an associated dose of mucolytic agent

11. Mebendazole + Pyrantel-pamoate or Levamisole

Dosages' schedule of both the drugs mismatch so the combination of such two anthelminthic drugs is irrational. The Mebendazole is required to be administered twice a day for three days whereas Pyrantel-pamoate or Levamisole should be administered as a single dose.

12. Leukotrine Antagonist (Montelukast) + Bambuterol or Levocetirizine

Montelukast, the leukotrine antagonist is used as alternative to inhaled steroid in the management of mild persistent asthma. Levocetirizine is an antihistaminic drug and has limited role in the control of asthma as it is not only histamine that triggers the asthma attack. Bambuterol is a long acting beta-2 agonist having role in the management of moderate persistent asthma as well as severe persistent asthma. There is no justification in combining of Montelukast with Bambuterol or Levocetirizine.

13. Metformin + Glimeperide + Pioglitazone

Metformin is indicated drug in obese type -2 diabetes mellitus whereas Sulfonylurea (Glimeperide) is indicated drug in non-obese type-2 diabetes mellitus. As per pharmacological principle, other drug should be added only when monotherapy fails. Metmorfin (biguanide) is to be administered after meal whereas Glimeperide (sulfonylurea) drug is to be administered before meal, therefore even when both the drugs are required, it would be better to administer them separately. Pioglitazone is indicated in suspected cases of insulin resistance. So, the combination of all these drugs in one formulation is an irrational drug combination.