Mechanism of effect
Troglitazone is a thiazolidinedione antidiabetic agent that lowers blood glucose by improving target cell response to insulin. It has a unique mechanism of action that is dependent on the presence of insulin for activity. Troglitazone decreases hepatic glucose output and increases insulin dependent glucose disposal in skeletal muscle. Its mechanism of action is thought to involve binding to nuclear receptors (PPAR) that regulate the transcription of a number of insulin responsive genes critical for the control of glucose and lipid metabolism. Troglitazone is a ligand to both PPARα and PPARγ, with a highter affinity for PPARγ. The drug also contains an α-tocopheroyl moiety, potentially giving it vitamin E-like activity. Troglitazone has been shown to reduce inflammation, and is associated with a decrase in nuclear factor kappa-B (NF-κB) and a concomitant increase in its inhibitor (IκB). Unlike sulfonylureas, troglitazone is not an insulin secretagogue.
Pharmacodynamic
Troglitazone improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis.
Pharmacokinetics
Absorption: Absorbed rapidly. Food increases the extent of absorption by 30% to 85%.
Protein binding: > 99% (primarily to serum albumin)
Metabolism: A sulfate conjugate metabolite (Metabolite 1) and a quinone metabolite (Metabolite 3) have been detected in the plasma of healthy males. A glucuronide conjugate (Metabolite 2) has been detected in the urine and also in negligible amounts in the plasma. In healthy volunteers and in patients with type 2 diabetes, the steady-state concentration of Metabolite 1 is six to seven times that of troglitazone and Metabolite 3. In in vivo drug interaction studies, troglitazone has been shown to induce cytochrome P450 CYP3A4 at clinically relevant doses.
Half life: 16-34 hoursDosage
Combination Therapy
Sulfonylureas: Troglitazone in combination with a sulfonylurea should be initiated at 200 mg once daily. The
current sulfonylurea dose should be continued upon initiation of Troglitazone therapy. For patients notresponding adequately, the Troglitazone dose should be increased at 2 to 4 weeks. The maximum recommended dose is 600 mg once daily. The dose of sulfonylurea may require lowering to optimize therapy.Metformin: For patients not responding adequately to metformin and sulfonylurea therapy, 400 mg daily
of Troglitazone may be added.Insulin: The current insulin dose should be continued upon initiation of Troglitazone therapy. Troglitazone therapy
should be initiated at 200 mg once daily in patients on insulin therapy. For patients not responding adequately, the dose of Troglitazone should be increased after approximately 2 to 4 weeks. The usual dose of Troglitazone is 400 mg once daily. The maximum recommended daily dose is 600 mg. It is recommended that the insulin dose be decreased by 10% to 25% when fasting plasma glucose concentrations decrease to less than 120 mg/dL in patients receiving concomitant insulin and Troglitazone. Further adjustments should be individualized based on glucose-lowering response.Drug contraindications
excessive sensitivity to the drug or its componentInteractions
Thyrotropin alfa , Ranolazine , Lomitapide , Mipomersen , teriflunomide , Gatifloxacin , levomethadyl acetate , Gefitinib , Alclometasone , flurandrenolideAlerts
In rare cases, troglitazone has caused severe liver damage resulting in death or liver transplant. Notify your doctor immediately if you develop nausea, vomiting, abdominal pain, unusual fatigue, loss of appetite, yellow skin or eyes, itching, clay-colored stools, or dark urine. These symptoms may be early signs of liver damage.
Your doctor will need to monitor your liver function with blood tests before starting treatment with troglitazone, every month for the first year of treatment, and every 3 months (quarterly) thereafter.
Troglitazone usually does not cause hypoglycemia (low blood sugar). However, hypoglycemia may occur as a result of skipped meals, excessive exercise, or alcohol consumption. Know the signs and symptoms of hypoglycemia, which include headache, drowsiness, weakness, dizziness, fast heartbeat, sweating, tremor, and nausea. Carry a piece of hard candy or glucose tablets with you to treat episodes of low blood sugar.
Avoid alcohol. It lowers blood sugar and may interfere with your diabetes treatment.
Troglitazone may decrease the effects of some birth control pills. A higher dose of birth control pills, or another form of birth control, may be necessary while taking troglitazone to prevent pregnancy.
Points of recommendation
Take troglitazone exactly as directed by your doctor. If you do not understand these instructions, ask your pharmacist, nurse, or doctor to explain them to you.
Take each dose with a full glass of water.
Take troglitazone with a meal to help increase the amount of medicine your body absorbs.
Your doctor will need to monitor your liver function with blood tests before starting treatment with troglitazone, every month for the first year of treatment, and every 3 months (quarterly) thereafter.
In rare cases, troglitazone has caused severe liver damage resulting in death or liver transplant. Notify your doctor immediately if you develop nausea, vomiting, abdominal pain, unusual fatigue, loss of appetite, yellow skin or eyes, itching, clay-colored stools, or dark urine. These symptoms may be early signs of liver damage.
Do not take more of this medication than is prescribed for you.
Store troglitazone at room temperature away from moisture and heat.
If you forget to take troglitazone at the usual meal, take it at the next meal that same day. If you completely forget to take it one day, skip the missed dose.Never take more than the usual amount of troglitazone in one day to make up for a missed dose. If you take more than the usual amount, call your doctor right away.
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