1. Clinical Overview
Vitamin K is a fat-soluble vitamin essential for the synthesis of functional prothrombin and other clotting factors (II, VII, IX, X) and proteins involved in bone metabolism (osteocalcin, matrix Gla protein). The 1mg formulation typically contains Vitamin K1 (Phytonadione), the plant-derived form, which is the preferred therapeutic agent for the management and prophylaxis of hypoprothrombinemia due to vitamin K deficiency or antagonism (e.g., by warfarin).
| Onset | Duration | Bioavailability |
|---|---|---|
| Prothrombin Time (PT) begins to shorten within 1-2 hours of intravenous administration; significant effect is seen within 3-6 hours. Oral administration has a slower onset, typically 6-10 hours. | The effect on coagulation factors lasts approximately 24 hours after a single dose, but full synthesis of new clotting factors takes up to 24-48 hours. The duration depends on hepatic function and the underlying cause of deficiency. | Oral: Approximately 80% when administered with a fatty meal (requires bile for absorption). Intramuscular (IM): 70-85%. Subcutaneous (SC): Variable, 20-60%. Intravenous (IV): 100%. |
2. Mechanism of Action
Vitamin K acts as an essential cofactor for the hepatic microsomal enzyme gamma-glutamyl carboxylase. This enzyme catalyzes the post-translational carboxylation of specific glutamic acid (Glu) residues to gamma-carboxyglutamic acid (Gla) residues on the precursor proteins of coagulation factors II, VII, IX, and X, as well as anticoagulant proteins C and S, and bone proteins like osteocalcin. The carboxylation reaction requires reduced vitamin K (vitamin K hydroquinone), which gets oxidized to vitamin K epoxide in the process. The enzyme vitamin K epoxide reductase (VKOR) recycles the epoxide back to the active hydroquinone form, completing the vitamin K cycle. Warfarin inhibits VKOR, disrupting this cycle.
3. Indications & Uses
- Prophylaxis and treatment of hypoprothrombinemia (vitamin K deficiency) causing bleeding or elevated INR.
- Reversal of excessive anticoagulation induced by vitamin K antagonists (e.g., Warfarin, Acenocoumarol).
- Prevention of Vitamin K Deficiency Bleeding (VKDB, formerly Hemorrhagic Disease of the Newborn) in neonates.
4. Dosage & Administration
Adult Dosage: **Deficiency:** 1-10 mg orally or 1-10 mg by SC/IM injection. **Warfarin Overdose (no bleeding, high INR):** 1-2.5 mg orally; may repeat in 24h based on INR. **Warfarin Overdose (serious bleeding):** 5-10 mg by slow IV infusion (not bolus) supplemented with Fresh Frozen Plasma (FFP) or Prothrombin Complex Concentrate (PCC).
Administration: **Oral:** Administer with food (preferably containing fat) to enhance absorption. **Injectable (IM/SC):** Preferred over IV to avoid anaphylactoid reactions. Inject deeply into muscle (gluteus maximus or vastus lateralis) or subcutaneously. **IV:** ONLY if other routes not feasible. Dilute in 50 mL of 5% Dextrose or Normal Saline and infuse slowly over 15-30 minutes. Monitor for anaphylaxis. Do not give as IV bolus.
5. Side Effects
Common side effects may include:
- Pain, swelling, or erythema at injection site (IM/SC).
- Transient flushing sensation, taste alterations (especially with IV).
- Mild gastrointestinal upset with oral dose.
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Warfarin / Acenocoumarol | Antagonizes anticoagulant effect. Can cause resistance. | Major |
| Broad-spectrum Antibiotics (e.g., Cephalosporins like Cefoperazone) | May enhance hypoprothrombinemia by killing gut flora that produce vitamin K; may increase requirement for vitamin K. | Moderate |
| Orlistat, Mineral Oil | Reduces absorption of fat-soluble vitamins including Vitamin K. | Moderate |
| Bile Acid Sequestrants (Cholestyramine, Colestipol) | Bind to vitamin K in GI tract, reducing its absorption. Administer vitamins at least 4 hours apart. | Moderate |
| Salicylates (High Dose) | May potentiate hypoprothrombinemia. | Moderate |
7. Patient Counselling
- **DO** take oral vitamin K with a meal containing some fat (e.g., milk, yogurt).
- **DO** inform all your doctors and dentists that you are taking vitamin K, especially if you are on blood thinners like warfarin.
- **DO** keep follow-up appointments for INR testing if prescribed for warfarin reversal.
- **DON'T** suddenly change your intake of vitamin K-rich foods (leafy greens) if you are on warfarin. Maintain a consistent diet.
- **DON'T** take other vitamins, herbal supplements (like ginkgo, coenzyme Q10), or over-the-counter medications without consulting your doctor.
8. Toxicology & Storage
Overdose: Vitamin K1 has very low acute toxicity. Symptoms are related to over-correction of coagulation: risk of thrombosis (especially in patients with prior thromboembolic disease). With massive IV overdose in neonates: hemolytic anemia, hyperbilirubinemia, kernicterus.
Storage: Store in original packaging below 25°C. Protect from light. Do not freeze. Keep oral tablets in a dry place. Injectable solutions should be inspected visually for particulate matter and discoloration before use. Follow manufacturer's expiry date.