The present invention relates to
solid pharmaceutical combinations for
oral administration comprising nicotinic acid or a nicotinic acid compound or mixtures thereof in an
extended release form and an HMG-CoA
reductase inhibitor, which are useful for altering lipid levels in subjects suffering from, for example,
hyperlipidemia and atherosclerosis, without causing
drug-induced hepatotoxicity,
myopathy or rhabdomyolysis. The present invention also relates to methods of altering serum lipids in subjects to treat, for example,
hyperlipidemia in hyperlipidemics, lipidemia in normolipidemics diagnosed with or predisposed to cardiovascular
disease, and atherosclerosis, by administering such oral
solid pharmaceutical combinations once per day as a single
dose during the
evening hours, without causing
drug-induced hepatotoxicity,
myopathy or rhabdomyolysis, or without causing in at least an appreciable number of individuals
drug-induced hepatotoxicity,
myopathy or rhabdomyolysis to such a level that
discontinuation of such therapy would be required. More particularly, the present invention concerns oral
solid pharmaceutical combinations comprised of, for example, (1) an HMG-CoA
reductase inhibitor for immediate or
extended release, (2) nicotinic acid, a nicotinic acid compound or mixtures thereof, and (3) a swelling agent to form a sustained release composition for
extended release of the nicotinic acid or nicotinic acid compound or mixtures thereof for nocturnal or
evening dosing for reducing serum lipids and increasing HDL-
cholesterol. In accordance with the present invention, and by way of example, a composition for
oral administration during the
evening hours to alter serum lipids comprised of nicotinic acid and hydroxypropyl methylcellulose in the form of an extended or
sustained release tablet or caplet coated with a
coating comprising an HMG-CoA
reductase inhibitor in
immediate release form is disclosed. Also in accordance with the present invention, the pharmaceutical combinations may include a
nonsteroidal anti-inflammatory agent for reducing the capacity of nicotinic acid or nicotinic acid compounds to provoke flushing reactions in individuals.